European Biotechnology Magazine Spring 2020 by BIOCOM Interrelations GmbH

ISSN 2364-2351 | A 60711 |

Life Sciences and Industry Magazine First Edition 2020 | Volume 19 | 20 €

Interview Immatics Biotechnologies CEO Harpreet Singh explains how TCR-T cell therapy can combat cancer.

Biomolecular Condensates

Droplets & Disease COVID-19

Novel Food

Biofairs Compass

Industry struggles to overcome paralysis caused by SARS-CoV-2

Emerging sustainable solutions for protein production

The ultimate guide to leading Life Sciences Events in H2/2020

Don t prepare. Just be ready. C2MAP-2000 â&#x20AC;&#x201C; 1 method, 17 mins, 95 media components The C2MAP-2000 automates all steps from pretreatment to measurement without any human intervention. It simplifies the workflow for optimizing cell culture conditions. There is no need to prepare. Just be ready. Complete LCMS solution for cell culture analysis combining the C2MAP-2000 pretreatment module with ultra-fast LCMS-8060

Monitoring of up to 95 components including amino acids, metabolites, sugars, vitamins and organic acids Changes at a glance with C2MAP-TRENDS viewer software visualizing temporal changes of components

Highly efficient through cutting culture media analysis time by 80 percent

www.shimadzu.eu/c2map

C2MAP-2000 â&#x20AC;&#x201C; Complete LCMS solution

Intro

European Biotechnology | Spring Edition | Vol. 19 | 2020

Support the Year of Investors in Antimicrobial Resistance We call on investors to include antimicrobial resistance (AMR) in your Environmental, Social, and Governance (ESG) frameworks. ESG is already driving market outlooks and investor portfolios. Sustainable investments are building resilient supply chains, meeting increasing and evolving global consumer demand, and creating brand and asset value. You, as investors, will shape ESG practices throughout 2020 and beyond. Effective antibiotics are critical for each of the E, S, and G pillars, and for the 2030 Sustainable Development Goals (SDGs) agreed upon by all nations at the UN. In a world with antibiotics, modern medicine thrives, and investments in healthcare, water, and food production profit. But, effective antibiotics are rendered ineffective by over-consumption around the world, leading to AMR. It follows, therefore, that in a world without effective Professor Dame Sally Davies antibiotics, food, pharma, healthcare, and insurance sectors, is the UK Government’s Special for a start, risk disruption and devaluation. Envoy on Antimicrobial Resistance (AMR). Dame Sally was the Chief Medical Officer for England and Senior Medical Advisor to the UK Government from 2011–2019. She is a leading figure in global health, serving as a member of the World Health Organisation (WHO) Executive Board and as co-convener of the United Nations Inter-Agency Coordination Group on AMR. She has championed the need to address AMR across human and animal health, agriculture, and environment within the UN family and globally.

In our globalised world, antibiotics are used and misused by humans in all sectors, including human health, animal health, and agriculture. Intensive livestock farming and poor animal husbandry currently over-rely on antibiotics to prevent diseases, and, outside the EU, to promote growth, to meet consumer demand, and to generate quicker, larger profits. Farming and food production can both cause and spread AMR, which means sick patients and animals can die. This hits investors’ bottom lines and will continue to do so unless we take sufficient action.

Picture: WHO

Drug-resistant infections are already reducing labour productivity and economic output, presenting ongoing risks to investors. Without urgent action, AMR will cause 10 million deaths per year by 2050 and cost the global economy in excess of US$100 trillion. On micro-levels, production costs will increase, and consumer purchasing will move away from livestock farmed with high levels of antibiotics. Yet, this is not a problem for the future. Canada estimated that drugresistant infections cost their economy an additional CA$1.4 billion in 2018.

Governments, investors, and industry all have roles to play in reducing risks of AMR for patients, animals, and crops, and lessening the impact on our global economy. Reducing antibiotic usage in humans and livestock farming, practicing good hygiene and husbandry, and supplying appropriate vaccines will maintain our ability to treat human and animal infections. Building end-to-end sustainable supply chains will develop our health and environmental systems and support the delivery of the UN’s SDGs. If we act at global, national, and individual levels to contain AMR, then investors stand to make long-term, sustainable returns on their investments. L

Contents

European Biotechnology | Spring Edition | Vol. 19 | 2020

Cover Story

Insight Europe

Regional News

COVID-19: Diagnostics and biopharma developers join forces to fight the global pandemic

72 Northern Europe: Sweden, Denmark and Finland

Commission plans information campaign to break resistance to new breeding technologies

12 Agriculture Ministers commit to global trade rules

Economy 22 Interview: Harpreet Singh, CEO and founder of Immatics Biotechnologies 24 Market commentary

74 Western Europe: France, Belgium, NL and the UK 76 Central Europe: Germany, Switzerland and Austria 78 Southern Europe: Italy, Spain, Portugal and Slovenia 80 Eastern Europe: Czech Republic and Poland

Science & Technology 82 Medicinal cannabis market needs clear rules

26 Euro Biotech Stocks

84 German medical cannabis market 28 Covid-19 spread: is AMR next?

The promise of condensate medicine

29 Update on clinical trials

In January, Dewpoint Therapeutics garnered US$60m in financing. Then Bayer signed a US$100m licensing contract with the US-German company, which is taking a completely new approach to drug development. Is it science fiction, or will we soon be able to restore ‘healthy’ gene expression in patients suffering from cancer, Alzheimer’s or MS? The company's founders say it's possible – if we solve the metabolic mysteries found in constantly changing cellular droplets.

34 Focus on bioprocessing: vector supply for gene and cell therapies

32 IP: product hopping – boon or bane?

88 Digitally supported production of medical cannabis 89 Cancer killer 90 Clinical trial validates utility of septic shock biomarkers 91 New approach to treating diabetes

36 Viral vector one-stop-shopping 38 Radiant Precision

Service

40 Phages as drugs

44 New products 93 News from SBA & MedTec Europe 97 Events 96 Company index 98 Encore

42 Sustainable packaging 81 EMA News

IMPRINT European Biotechnology (ISSN 2364-2351) is published quarterly by: BIOCOM AG, Lützowstr. 33–36, D-10785 Berlin, Germany, Tel.: +49-30-264921-0, Fax: +49-30-264921-11, Email: service@european-biotechnology.com, Internet: www.european-biotechnology.com; Publisher: Andreas Mietzsch; Editorial Team: Thomas Gabrielczyk (Editor in Chief), Derrick Williams (Co-editor), Sandra Wirsching, Uta Mommert; Advertising: Oliver Schnell, +49-30-2649-2145, Christian Böhm, +49-30-2649-2149, Andreas Macht, +49-30-2649-2154; Distribution: Lukas Bannert, +49-30-2649-2148; Graphic Design: Michaela Reblin; Production editor: Benjamin Röbig; Printed at: Königsdruck, Berlin; European Biotechnology Life Sciences & Industry Magazine is only regularly available through subscription at BIOCOM AG. Annual subscription fees: € 80.00, Students € 40.00 (subject to proof of enrolment). Prices include VAT, postage & packaging. Ordered subscriptions can be cancelled within two weeks directly at BIOCOM AG. The subscription is initially valid for one year. Subscriptions will be renewed automatically for one more year, respectively, unless they are cancelled at least six weeks before the date of expiry. Failures of delivery, which BIOCOM AG is not responsible for, do not entitle the subscriber to delivery or reimbursement of pre-paid fees. Seat of court is Berlin, Germany. As regards contents: individually named articles are published within the sole responsibility of their respective authors. All material published is protected by copyright. No article or part thereof may be reproduced in any way or processed, copied and proliferated by electronic means without the prior written consent of the publisher. Insert: EuroJobsites Ltd. Cover Photo: freepik.com©picoftasty; ® BIOCOM is a registered trademark of BIOCOM AG, Berlin, Germany.

Contents

European Biotechnology | Spring Edition | Vol. 19 | 2020

Bioeconomy

Editorial

COVid-19

Brexiting science

Lab-grown food

SPECIAL EU Event Compass

Post-Brexit, the European Commission and Member States have to cope with a €75bn reduction in the EU’s next seven-year budget. At the end of February, EU leader negotiations to fill the hole left by the UK’s departure from the bloc failed. The Netherlands, Austria, Denmark and Sweden refused to increase their contributions to boost the Cohesion Funds and the Common Agriculture Policy (CAP) by €4.4bn – including project funding of €2bn to help support future technologies driving a sustainable bio-econonomy. COVID-19 has made the situation even worse. In the end, what would a reduced budget mean for European research and innovation? Like the four countries mentioned above, Luxembourg is a net contributor. Its Prime Minister Xavier Bettel says: “I see the EU as a chance, and not as a bill”. EC President Ursula von der Leyen has warned that “we will have no budget, we will have no Erasmus Programme, no resources for research, no resources for regional development or border protection” if there is not a solution by December. The current EC proposal foresees budget cuts of about €10bn per year compared to the original proposal that resulted in a Horizon Europe budget, and 27% instead of 30% more money for climate reduction. That money is desperately needed to drive innovation. Researchers need to speak out!

55 56 58 60 62 64 66 68 70

Thomas Gabrielczyk Editor-in-Chief

Cultured meat alternatives are gaining momentum. Start-ups in the field are attracting millions in financing, and are also teaming up with biopharma companies and manufacturers to move forward industrial scale-up processes. A first wave of companies is entering the home stretch, among them European firms like Mosa Meat and Peace of Meat.

6/55/70

Viral pandemics

Pictures: Microone/freepik.com (below), Mosa Meat (upper left), CDC (middle), BIOCOM AG (right)

The COVID-19 crisis has clearly shown how vulnerable our populations, economies, political and healthcare systems are when dangerous and highly contagious pathogens emerge and begin spreading rapidly. Despite a number of efforts to improve diagnostics, as well as develop vaccines and new treatments or repurpose existing ones, it will take time before we have a widely applicable therapy. An overview of a planet in the midst of a pandemic.

Update on EU Events in H2/20 AMR Conference, Basel, Switzerland Swiss Biotech Day 2020, Basel, CH EFIB 2020, Frankfurt/Main BIO Japan 2020, Yokohama, Japan Pharmalab 2020, Neuss, Germany Chemspec 2020, Cologne, Germany Biofit 2020, Strasbourg, France 1st virtual BIO-Europe Spring, Paris

Insight Europe

European Biotechnology | Spring Edition | Vol. 19 | 2020

EU industry seeking solution for coronavirus crisis SARS-CoV-2 According to the World Health Organisation, over 468 trials addressing the globally

spreading coronavirus SARS-CoV-2 had been started by the end of March. While the diagnostic industry increased capacities, drug developers, governments, and regulators pooled resources to rapidly identify, test, and approve safe and effective repurposed drug combinations using machine learning algorithms.

Four months after the new Coronavirus SARS-CoV-2 emerged for the first time in the Chinese megacity Wuhan, social distancing was the only available measure to limit the spread of the new virus – cutting international travel, business, global GDP, and fundamental democratic rights. After researchers at Berlin-based Charité deciphered the genomic sequence in January, and it turned out later that all sequenced SARS-CoV-2 genomes available shared 99% sequence similarity, diagnostic companies as well as vaccine and drug developers entered into development or expansion of diagnostic PCR testing capacities for identification, isolation, and disease management of infected people. From February to the end of March, EU central labs ramped up their capacities from 8,275 to over 7 million diagnos-

3D animation of the virus shell of the single-strand, RNA COVID-19 virus

tic PCR tests per day, with Roche providing more than 1 million dual target tests per 24 hours running on its fully automated, cobas high-throughput instruments.

Facts on COVID-19 Coronaviruses are rapidly changing +ssRNA viruses (mutation rate (1 x 10 –4 10 –5) that cause respiratory or intestinal infections in humans and animals. Coronaviruses are classified into four groups, two of which (α and b) are known to cause infection in humans. They contain four major structural proteins: the spike (S) protein (which mediates attachment to the ACE 2 receptor on host cells and fusion of the virus and cell membrane, the nucleocapsid (N) protein, the

membrane (M) protein, and the envelope (E) protein. Currently, seven CoV strains are known to infect humans, four of which cause self-resolving infections. Only SARS-CoV, MERS-CoV, and SARSCoV-2, can cause lethal respiratory infections. Human coronaviruses enter cells via two distinct pathways: the endosomal pathway using cathepsins to activate spike protein and the cell-surface or early endosome pathway using extracellular proteases, such as TMPRSS2.

Smaller providers, such as Bruker-Hain Diagnostics, which inked a global distribution agreement with Novacyte’s British PCR testing arm, Primerdesign Ltd, at the end of March, immediately initiated shipments to Spain, France, Germany, and the UK. Most of the 96 manual and 30 automated PCR assays commercialised by the end of March – at least 20 more were in development – however, still required lab processing. Roche CEO Severin Schwan concluded in early March that “diagnostic testing will remain a bottleneck for the next weeks.” Abbott Inc. provided a sequencebased, five-minute PCR-like test at the end of March, which might boost capacities.

Bottleneck diagnostics Only a fraction of automated assays were near point of care (POC), thus easing testing logistics at the 50% of EU hospitals, that do not own a central lab. For example, the COVID-19-POC rapid test Vivalytic-VRI, marketed worldwide by Bosch Healthcare and Randox Laboratories Ltd from April, distinguishes ten respiratory pathogens simultaneously but with low throughput. Besides the PCR testing gold standard, 70 antibody-based COVID-19 diagnostic tests were available at the end of March. While entailing long processing times, having different specificities/ sensitivities and requiring lab personel, these tests may provide additional data on the true number of people infected with SARS-CoV2-, thus feeding future projections of epidemiologists, predicting when social distancing could be ended.

Picture: ECDC

JUST RELEASED: SPECIAL REPORT ON COVID-19

CONTAINING CORONAVIRUS THROUGH INNOVATION AND INVESTMENT AN

SPECIAL REPORT

Based on pertinent news and analysis as well as discussion from industry experts during the Combatting Coronavirus live panel at BIO-Europe Spring®, this report brings you the latest coronavirus news from the frontlines as top biotech and investment players offer their best plans and current progress in stemming and ultimately defeating the current worldwide pandemic.

THE SPECIAL REPORT INCLUDES: • Regeneron, Moderna, J&J and the Ongoing Battle Against COVID-19 • Funding Coronavirus R&D Efforts: Governments and the Private Sector Will Step Up • Getting Back to Business: Lessons from China Two Months On • Rapid Response Vaccine Capacity Vital for Pandemics, Say Experts • Investors Shaken by Coronavirus Sow Seeds of M&A, Financing Slowdown • One Billion Doses: CureVac Gains $88m to Support Capacity for COVID-19 mRNA Vaccine

FREE DOWNLOAD AT XCONOMY.COM

Insight Europe

European Biotechnology | Spring Edition | Vol. 19 | 2020

Like the original SARS virus, the new corona virus, SARS-CoV2, uses the angio tensin 2 receptor (ACE2) to infect lung cells (left). A good part of the experimental antiviral drug candidates in clinical development are designed to block or prevent the interaction between the viral spike (S-)protein with ACE2 on human cells, such as Viennese Apeiron Biologics AG’s Phase II candidate APN01, a recombinant ACE2, which masks the virus (right) by competitive binding to the viral S-protein.

As of the end of March, there was no approved vaccine or drug against SARSCoV-2, but 35 drug candidates were in development. WHO officials clearly prioritised rapid repurposing of existing drugs over the development of vaccines and new drugs, as this would only take only months instead of years to approve. In contrast, development of preventive vaccines, such as survivor-serum derived antibodies, protein, DNA (i.e. Sanofi) or mRNA vaccines (i.e. CureVac, BioNtech, J&J, etc.) would need at least 18 months for mass vaccination. Development of completely new drugs is expected to take much longer, even if virtual screening, artificial intelligence-directed docking, and interaction analyses, as well as accelerated clinical testing schemes (i.e. EU PRIME status) will be used.

Collaboration with fixed combos Five to-be repurposed drug candidates that zero in on different human or viral targets have been included in combination studies coordinated by the WHO

(SOLIDARITY), the EU (Discovery), and the UK (recovery), following an appeal from the EMA to companies and researchers to organise joint, multi-national, multi-arm, controlled, and randomised patient studies for their medicines. Under the different schemes, promising repurposed candidates will be systematically tested in defined combinations:

›› Basic treatment (BT) monotherapy ›› BT + Remdesivir ›› BT + Ritonavir/Lopinavir ›› BT + Ritonavir/Lopinavir + b-Interferon/ immunosuppressant

›› Basic treatment + hydroxy/chloroquine Clinical development of the potential SARS-Cov-2 RNA polymerase blocker Remdesivir from Gilead Sciences restarted in early April. The nucleotid analogon killed MERS viruses in lab tests but, in combination with corticosteroids, was 20% less effective in reducing Ebola mortality than an antibody cocktail developed by Regeneron. In March, Italy approved

Favipiravir (Toyoma Chemical), another promising RNA polymerase blocker that reduced viral clearance time from 11 to 4 days in pilot trials. AbbVie’s C30 endopeptidase blocker of coronaviruses, Lopinavir/Ritonavir, neither accelerated the elimination of the viruses nor reduced the morbidity and mortality of patients. However, lab results published in the NEJM (doi: 10.1056/NEJMoa2001282) suggest that usage may not be entirely hopeless. Following mixed results from clinical studies conducted in China, Belgium, and France, EU drug developers Bayer and Sanofi reactivated production of their old malaria drugs chloroquine and hydroxychloroquine, which have numerous side effects. Malaria pathogens, which have a mutation rate 1000 – 100 times lower than SARS-CoV-2, are now often resistant to chloroquine/hydroxychloroquine.

Quick action needed Immunosuppressants, such as Roche’s IL-6 antagonist tocilizumab or interferon beta-1a, are not antiviral medicines. While tocilizumab dampens the hefty immune reaction leading to sepsis-like organ failure in later disease stages, interferons stopped the multiplication of SARS-related viruses in lab tests. German Merck supplies Rebif to the French INSERM, where it is tested on COVID-19 patients. Many European biotechs, such as Spanish PharmaMar (EF1A inhibitor plitidepsin), German Atriva Therapeutics (ATR-002 human MEK blocker), Austrian APEIRON Biologics AG (APN01, Vienna), and the German Primate Centre in Göttingen (Camostat mesilate, Ono Pharmaceuticals), contributed to the global effort to find new uses for old drugs with antiviral activity, while vaccine developers focussed on finding the most effective jab. In contrast to Apeiron’s approach, Camostat mesilate (see page 100) targets the serine protease TMPRSS2, which is essential to activate the S-protein for binding to ACE2. L t.gabrielczyk@biocom.eu

Picture: Apeiron Biologics AG

European Biotechnology | Spring Edition | Vol. 19 | 2020

Insight Europe

Study might prepare for rapid revision of EU GMO law Modern Breeding methods The European Commission has taken up the European Council’s

demand for deregulation of new plant breeding techniques (NBT). A new study is being conducted to form the basis for a campaign from the Commission to inform the public about the benefits of targeted mutation technologies and to break the resistance to genetically engineered crops.

The new European Commission (EC), headed by Christian Democrat Ursula von der Leyen, is taking action to overhaul the current EU GMO legislation in order to exempt new breeding technologies (NBT) from the current testing, labelling, and approval requirements. The industry-friendly move to overcome European consumer rejection of food products made by genetic engineering techniques was prepared long beforehand by the former Agriculture Commissioner Phil Hogan. Following the European Court of Justice’s 2018 ruling (C-528/16) that all crops, which were modified by biotechnological, targeted mutagenesis techniques, fall under the strict legal regulations for genetically modified organisms (GMOs), Hogan requested a new study on NBTs to prove the benefits of NBTs versus classical breeding. The study is

now underway, confirmed Health Commissioner Stella Kyriakides in December. Previously, the European Council, under leadership of the Netherlands, demanded that such a study be carried out (see European Biotechnology, Winter edition 2019). Kyriakides said its results will be published by Spring 2021 under Portuguese EC presidency and will form the basis for a political solution. However, Kyriakides left open why the Commission does not want to utilise the results from an already existing study published by the EU Joint Research Centre (JRC) in Ispra in 2011 and ordered by the EC to lay the scientific foundation for a political decision on NBTs. Insiders told European Biotechnology that a study published after the ECJ ruling would be more convincing. Greens party representatives, however, fuelled rumours that the Commission in-

tends to follow a lobbying push by agribiotech proponents – EU researchers, who depend on funds for their agri-biotech research and multinational ag-companies – to remove the process-orientated, precautionary labelling and testing regime applied to GMOs when it comes to products obtained by new, mutational techniques.

Greens mounting the barricades Martin Häusling, agricultural policy spokesman for the Green Group in the European Parliament called for EU-wide, strict regulation of breeding technologies using targeted mutagenesis. “The organic sector must become unmistakably loud here, because if we don’t have very clear regulation, we will be at the mercy of the industry,” suggested Häusling at BioFach

Insight Europe

European Biotechnology | Spring Edition | Vol. 19 | 2020

(17 – 20 February 2020), the world’s leading trade fair for organic food in Nuremberg, Germany. He warned against replacing the precautionary principle with the innovation principle in Brussels. Risk assessment, traceability, labelling, and safety monitoring must be guaranteed, because the new genetic engineering comes with risks, he claimed. For the organic sector, a dilution of the strict labelling and traceability requirements currently applied under EU rules to NBTs would put their holistic “100% natural and GMO-free” approach at risk, as producers wouldn’t be able to track if a field planted with NBT-modified crops neighbours a field with organically produced products. According to Häussling, the organic sector would be faced with an enormous task, if this happened. “We are the form of agriculture that has a future,” claimed Häussling, pointing to the sustainability ambitions of the EU’s bioeconomy strategy.

communication, whose financial promises haves come under doubt after failed EU budget negotiations (see page 5) between the European Council and the Commission. “I have always made clear that we need to have a broad and open debate whether and, if so, how biotechnologies could help make our food system more sustainable, both for citizens and the environment,” she added. What can be expected specifically from this latest approach of the Commission to overcome public resistance against genetic engineering in food production is written down in a position paper (translated from German: “Genome Modification in Plants: Opportunities for Sustainable and Resource-Conserving Agriculture”) published by von der Leyen’s Christian Democratic party last December.

EU on the path to innovation

In the paper, experts from the Federal Expert Committee on Education, Research, and Innovation of the Christian Democratic Party conclude:

Kyriakides said innovation, in all its forms, is essential “particularly if we want to reduce the current dependence on chemical pesticides,” as announced in the Commission’s recent green deal

Creating public acceptance?

›› that the ECJ judgement makes the application of the new breeding methods

New view on genome editing According to a position paper published by von der Leyen’s party (CDU/ CSU) in December, genome editing is a collective term for various new methods (including CRISPR/Cas, TALEN, or oligonucleotide-directed mutagenesis, ODM) that allow targeted interventions in the genetic material. Two components are required for this: a protein (nuclease, i.e. Cas9) that cuts the DNA of the target organism and a guide DNA strand that directs this nuclease to the desired location on the DNA. The guide recognises the desired location in the genome of the target organism. The nuclease can either be introduced into the cell from outside (CRISPR/Cas,

TALEN) or be naturally present in the cell (ODM). In contrast to conventional mutagenesis, genome editing has many advantages, suggests the paper: “While molecular breeding methods are simple, fast, precise, flexible, and inexpensive, conventional breeding using ionising radiation and chemicals produces thousands of random mutations in the genome. Time-consuming backcrossing is then necessary to isolate a desired new trait and delete the interfering mutations. Conventional breeding also costs a lot of space and resources. Depending on the type of crop, molecular breeding can save 6 to 50 years compared to conventional methods.” L

in the EU practically impossible and, thus, prevents their beneficial use for biodiversity and sustainable agriculture; ›› that the judgement is based on the Directive 2001/18/EG from 2001, the scientific basis of which, in turn, dates back to the 1980s and which has, so far, been exclusively focused on the regulation of classical genetic engineering, namely the introduction of foreign, transgenic DNA into organisms, which can be easily detected. In contrast, the genetic changes introduced into crops by NBT are often “no longer distinguishable from changes in plants obtained by conventional breeding or mutagenesis”; ›› that this would mean “that organisms carrying one and the same genetic modification are regulated completely differently in the EU, depending on how the modification was produced”; ›› that in this way, European genetic engineering law would not only inhibit research, development, and application of urgently needed improved crops to support sustainable agriculture. On the contrary, the time-consuming and cost-intensive approval procedure, which applies equally to classical, genetically modified organisms and genome-modified organisms, would also promote further monopolisation in the already highly concentrated seed and plant breeding markets. At the same time, European genetic engineering law threatens to uncouple the EU from international biotechnological and bioeconomic developments. According to the paper, technologies improving food and feed quality and reducing the use of fertilisers and crop protection products could help support global problems, such as hunger, climate change, and supply of bio-based resources for industrial production within the framework of a bio-economy. As this progress could not be achieved in the short term with conventional breeding, “the procedural regulatory approach is not scientifically justifiable,” and updated EU GMO rules should allow deregu-

European Biotechnology | Spring Edition | Vol. 19 | 2020

Insight Europe

lation of products generated using NBTs. For example, research on more resistant crops – part of the US$55.4bn global seed market – must be intensified, says the paper – particularly with field trials. At the heart of this U-turn in GMO regulation is a campaign to build consumer acceptance for genome-edited crops and products. This drive’s aim is “to drop positive labelling specific to genetic engineering” for all products that do not contain genes from alien organisms.

Picture: Cibus

Silent start of campaigning In contrast, researchers attached to the green lobby, such as Michael Antiniou from Kings College London, warn that existing on-target and off-target effects of NBTs, particularly those triggered by uncontrollable cellular DNA repair mechanisms, would be downplayed. However, as the Commission wants to actively implement consumers in the decision process to improve acceptance, consumers may have options to create a solution that goes beyond economic interests. Furthermore, figures published by the ag-industry information broker and consultancy Phillips McDougal demystifies the claim that the “unduly slow and expensive EU-GMO rules” would present an important barrier for biotech SMEs to apply for EU product approval. According to the study, only 25% of the average $136m cost of bringing a GM trait to market between 2008 and 2012 is related to regulatory issues. The remaining 75% went towards research and development and licencing costs. By mid-February, the “EU information campaign for consumers” took off with an announcement from Italy. Italian Agriculture Minister Teresa Bellanova said that Italy will continue to keep GMOs from the market while launching a collaboration that is set to foster next-gen biotech in Italy’s farming, namely “sustainable biotechnologies, such as cisgenesis and genome editing.” The deal between the farmer association Coldiretti and the Italian Society of Agricultural Genetics (SIGA) will focus on the application of latest-generation biotech to typical Italian

NBTs such as oligonucleotide-directed mutagenesis change gene activity without inserting foreign DNA.

varieties, representing a turning point in the troubled relationship between antiGM farmers and pro-GM scientists. SIGA member Mario Pezzotti from the University of Verona announced that development of climate-change- and pathogenresistant grape varieties with conserved oenological profile will be one goal of the collaboration, which would need a change in the current EU GMO law. At the end of February, Sweden, which criticised the ECJ ruling, joined the PR club publishing a press release for Mistra Biotech, a research programme focusing on the use of biotechnology in crop and livestock breeding for sustainable and competitive agriculture led by Lund University. In a series of articles, agriresearchers discuss options for reforming EU GMO rules in order “to make

risk assessments and decision-making more compatible with scientific principles, and to lay the foundations for international harmonization, which is a prerequisite for the feed and food chain to function globally.”

Opposition from France At the beginning of February, France’s highest court, the Conseil d’Etat, ruled that organisms obtained by biotechnological mutagenesis techniques should be identified within six months and become subject to GMO rules. A big challenge for policymakers in their information campaign will be to differentiate between interest-group-led PR and serious scientific input. L t.gabrielczyk@biocom.eu

Insight Europe

News Promoting circularity In mid-March, the European Commission relaunched its circular economy action plan to prepare the ground for a sustainable bio-economy. The new action plan aims to strengthen the EU’s competitiveness, while protecting natural resources. As resources are limited, the action plan is aimed at restricting single-use products, tackling premature obsolescence, and banning the destruction of unsold, durable goods. However, the plan will be developed with “the close involvement of the business and stakeholder community,” the Commission said. ”Today, our economy is still mostly linear, with only 12% of secondary materials and resources being brought back into the economy,” said Executive Vice-President for the European Green Deal, Frans Timmermans. The Commission will plans to start a “Circular Electronics Initiative,” to have longer product lifetimes and to improve the collection and treatment of electronic waste. It aims at enhancing the sustainability and boosting the circular potential of batteries, packaging, plastics, and textiles, as well as sustainable construction and buildings, and avoid EU exports of waste and tackle illegal shipments.

European Biotechnology | Spring Edition | Vol. 19 | 2020

Agriculture ministers commit to global trade rules GFFA Agriculture Ministers from 72

countries want to support rule-based free trade to withstand global challenges, such as hunger and climate change. In January, at the twelfth Minister Conference within the Global Forum for Food and Agriculture (GFFA), participants adopted a joint communiqué on global trade supporting:

›› global rules for international markets, strengthening of the WTO, bilateral, free trade agreements as a contribution to the opening up of markets, and reduction of market-distorting support measures; ›› strengthening of local, regional, and global value chains and promotion of agricultural trade; equitable distribution of welfare gains across all countries and social strata; ›› promotion of technical and organisational innovations, e.g. in the field of digitalisation, to increase efficiency and to make the food and agricultural sectors attractive to a new generation of farmers; ›› support for smallholders in the form of micro-credits and facilitation of

their engagement in cooperatives in order to better integrate them into markets; ›› granting of increased rights to women and facilitation of their access to markets in order to effectively lift numerous families out of poverty; ›› continuation of environmental measures and compliance with international climate agreements; and ›› introduction of global standards for sustainable agriculture. The joint communiqué was presented to Aidarbek Saparov, Vice-Minister of Kazakhstan, who will be hosting the next World Trade Organisation’s Ministerial Conference, Alan Wolff, Deputy Director-General of the WTO and Dr Qu Dongyu, Director-General of the FAO. During the event, the concept of an International Digital Council was also discussed. The FAO has been called upon to implement this concept. The aim is for the Digital Council to advise states on issues of digitalisation and to drive the exchange of ideas and experiences. L

Emergency fund In March, the IMI launched a €45m call for the development of therapeutics and diagnostics to tackle coronavirus outbreaks. While treatments to respond rapidly to the current Sars-CoV-2 outbreak and development of fast diagnostic tests to identify people infected with the coronavirus will be funded, vaccine development will not be included in the funding.

Agriculture Ministers from 72 countries met at the Global Forum for Food and Agriculture (GFFA).

Picture: By Dr Graham Beards at en.wikipedia, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=25206097

No scrabbling needed â&#x20AC;&#x201C; all solutions in one hand P B M C

N T R

O M

M U L

MLM Medical Labs is one of the leading central labs for clinical trials in Europe. For over 25 years we have been supporting clinical studies phase I-IV with full laboratory services, kit building and logistics. For further information please contact Dr. Katja Neuer at kneuer@mlm-labs.com or visit us at mlm-labs.com. MLM Medical Labs GmbH Dohrweg 63 41066 MĂśnchengladbach Germany

Cover Story

European Biotechnology | Spring Edition | Vol. 19 | 2020

Pictures: xxx

Cover Story

European Biotechnology | Spring Edition | Vol. 19 | 2020

Life in a bubble – droplet science research advances It’s a discovery that revolutionises our fundamental understanding

of cells. Tiny droplets called condensates that form through weak interactions between proteins and RNA are at the heart of many key biological processes. Dewpoint Therapeutics – the first start-up to harness the basic research for a new therapeutic platform technology – is now opening a facility in the German capital Berlin.

Pictures: Freepik (left), Christian Hoege/MPI-CBG (right)

hillip Sharp almost gave up. For practically his entire career, the Nobel-prizewinning biochemistry researcher at the Massachusetts Institute of Technology struggled to clarify one of the fundamental unsolved riddles of biology. How do the millions of tiny molecules within a cell come together at exactly the right time and the right place at the right concentration to perform all the necessary chemical reactions that are the beating heart of life itself? The transcription process, for instance, which is at the center of genetic information and its transmission? That’s Sharp’s specialty. “We’ve been thinking about gene expression for decades, and we were all still saying: ‘Transcription factors come to the DNA somehow, and then they perform the transcription and terminate it, somehow.’” But how exactly? “We didn’t know how to think about it,“ says the 75-year-old, who still works in his lab at MIT’s Koch Institute for Integrative Cancer Research. “I basically turned my back on the subject, because I couldn’t figure out how to do anything about it.” But then, in 2012, a British cell biologist came to the rescue. While study ing structures called P granules in stem cells, he stumbled on a phenomenon that fundamentally changed how molecular biologists think about how chemical reactions are processed in living beings. It would prove a breakthrough.

Sharp thinks “it’s at the heart of basically every biological process.” Almost every task a cell has to perform involves dozens to thousands of different proteins or other chemical molecules, all interacting like workers and machines in a factory. But where production steps in a factory follow strict plans in terms of time and place, biologists had no clue how all the different molecules drifting through a cell’s cytoplasm are able to come together to form the complexes that perform basic living processes – and then dissolve again afterwards.

“If there is a disease pathway that involves a condensate, then we can take advantage of that and can modulate that activity.” What signals call them to duty? Biology textbooks don’t hold the answer, although it’s an essential one. After all, if team play isn’t working at the molecular level, it results in diseases like Alzheimer’s, Parkinson’s and cancer. So knowing the answer to that question would potentially open up ways to tackle these devastating illnesses. “Tony Hyman made the essential discovery,“ Sharp says. A stroke of luck, as Hyman nearly didn’t become a scientist in the first place.

Unlike others, Hyman says he wasn’t drawn to the natural sciences from a young age. He didn’t perform extremely well in high school either, and was unsure afterwards which direction to pursue professionally. So he took a temporary job at University College in London paying £30 a week tending to stem cell culture media and preforming other background lab-tech work.

Densely packed with colloids One of the scientists there convinced him that life under the microscope was fascinating, made him start an experiment, and encouraged his curiosity. One Friday evening, when the technicians and researchers had disappeared for the usual pub-crawl, he decided to spend the evening over his microscope instead. Since then, says Hyman, a fascination

P granules (red), like in a one-cell-stage nematode embryo, are condensates necessary for germ line development.

Cover Story

European Biotechnology | Spring Edition | Vol. 19 | 2020

Special fluorescent imaging microscopy technologies are needed to observe the appearance and dispersion of condensates (the tiny greenish dots) in living cells.

with what makes cells ‘alive’ never left him. He went on to study biology and pursue a career in the field that eventually landed him a job in Dresden as Director of the Max Planck Institute of Molecular Cell Biology and Genetics. That’s where he made the discovery that thrilled Sharp and many other scientists. Just as water molecules distributed throughout the air condense as dewdrops on a leaf or cold windowpane in the early morning, protein molecules are able to come together to form tiny droplets. Like drops of vinegar in oil, they build separate fluid phases. This is essential for cell function, because in these droplets the proteins reach concentrations a hundred to a thousand times higher than in the cytoplasm circulating outside the droplets. Those concentrations are necessary for enabling chemical processes – like transcription – that are essential to life. In an oft-cited paper published in Science in 2012,Hyman wrote that the question of exactly how biological macro molecules form organised assemblies was first posed when the field of biochemistry was born in the early 20th century. At that time, he says, “biologists considered the cytoplasm to be densely packed with liquid colloid particles that constituted a separate phase, distinct from the surrounding aqueous environment.“ Some of these droplets – called ‘stress granules’ – appear when the cell is exposed to harsh condi-

tions. Others, like the P granules found in germ cells, are associated with the development of oocytes and sperm. Yet other very tiny granules that are only revealed by modern imaging technologies are involved in transcribing, splicing and other processes in the cell nucleus. Although cell biologists already began describing some of these droplets a century ago, they didn’t know enough about the biology of macromolecules to make any sense of what they saw. Only today has it grown possible to watch proteins come together

in living cells, forming and dissolving the condensate droplets. After endless hours of observations and experiments aimed at altering the structure of these proteins, Hyman and his colleagues in Dresden slowly began to understand the mechanism of action at work – how the proteins go through a phase separation process to form the condensate drops. The key is a protein region with a name that highlights the misunderstandings the domain provokes. Molecular biologists call regions within proteins that are so fuzzy we have no clue what they do ‘Intrinsically Disorganised Regions’ (IDRs). In fact, most of the time, structural biologists trying to crystallise transcription factors in important proteins try to simply cut such regions off. “They were seeing them, but they just didn’t think about what they could mean,” Sharp says. It turns out that, like misnamed ‘junk’ DNA, or small RNA sequences – which turned out not to be chopped up rubbish from essential longer RNAs – the IDR tails of proteins are an important feature. “The function of low-complexity sequence domains, which are abundant in the protein universe, have long puzzled biologists, but these experiments support the idea that they may have evolved to mediate such liquid-liquid demixing,“

Biomolecular condensates Biomolecular condensates are like cell organelles that aren’t screened from the cytoplasm by membranes. They compartmentalise certain biochemical processes and macromolecules simply through phase transfer. Dewpoint Therapeutics co-founders Anthony Hyman (MPI of Molecular Cell Biology and Genetics) and Richard Young (Whitehead Institute, MIT) have discovered that the previously under explored activation domains of transcription factors are brought into proximity by phase transfer in aqueous cell compartments, thereby initiating and maintaining the transcription of specific

genes. A handful of activation domains like ‘mediator’ or ‘p300’ can regulate the transcription of hundreds of different transcription factors. The researchers want to take advantage of this to specifically influence disturbed transcription in cancer, neurological diseases, cardiovascular diseases and other medical fields. It’s an approach that doesn’t target those conditions at the genetic level, but instead aims to correct disturbed biological functions. Fields of application for addressing molecular condensates with drugs are found in almost all important indication areas.

Picture: Dewpoint Therapeutics

Picture: Sascha Karberg

European Biotechnology | Spring Edition | Vol. 19 | 2020

Hyman wrote in his 2012 study. His work helped show that IDR tails in proteins are able to form very low affinity bindings with one another. Under certain physical conditions, like high or low salt concentrations, hundreds or even thousands of IDRs can come together. Although the binding properties of individual IDRs are weak, the arranged mass of them enables a phase switch – a separation of the proteins into a fluid droplet suspended within the cytoplasm. Hyman calls them ‘condensates’. “We see this condensate biology all over the cell,“ says Sharp. “In signalling in the cell membrane (…) and we see condensate biology in synapses … in DNA replication and splicing.“ According to him, it’s a fundamental physical fact of biological systems that is quite widely utilised in human cells. It’s also one that “we haven’t been thinking about.” As experts gradually accept that condensates are a necessary prerequisite

in the complex protein machinery essential to processes like transcription, Sharp is already thinking about using this knowledge for drug discovery. The serial founder of successful biotech companies that include Biogen and Alnylam believes that through understanding “what initiates condensates and dissolves condensates, we can think about how to use drugs to inhibit or stimulate that process.”

Is cancer a disease of condensate dysfunction? If condensates are fundamental for cells, then it’s clear that condensate dysfunction could be involved in the onset of disease. One hypothesis several groups of scientists are currently pursuing is that some condensates might actually undergo a further phase shift – changing from a fluid to a solid state like that seen in the beta-amyloid-plaques that accumulate in

Science for a better tomorrow July 13–15, 2020 Darmstadt, Germany www.curious2020.com

Cover Story

Dewpoint named meeting rooms after known condensate organelles, like the “stress granule”.

the nerve cells of Alzheimer’s patients. “If those factors are concentrated and then undergo a morphological change, they can form amyloids – they can form pathogenic material,“ Sharp believes. “So we’re likely looking at a set of processes that also explain a lot of amyloid toxicity in different genetic diseases.“ That means cancer – by definition a genetic disease – might also be a target for condensate-

Cover Story

led drug discovery. Recent research has shown that cancer cells, which depend to a great extent on the transcription of oncogenes, need to form large transcriptional condensates around the genes they rely on for their abnormal growth and cancerous division cycles. The search is therefore on for drug candidates able to change condensate biology, hence potentially making a difference in diseases like Alzheimer’s or cancer. Sharp has joined the scientific advisory board of Dewpoint along with other wellknown scientists like Bob Langer, Rudolf Jaenisch, Richard Young and Tony Hyman himself. It’s the first company seeking to harness the potential of condensate biology. Based in Dresden, Boston and now Berlin, the firm is currently screening small molecule libraries. And they seem confident they’ll find drugs able to influence condensates in ways relevant to the pathogenesis of neurodegenerative diseases and cancer – even though other library screens have been performed many times before by other companies and scientists (see interview p. 19).

RNA is an important component of condensates “I would argue that few of those screens – maybe none of them – have been done in a situation where you’re monitoring the behavior of these droplets,” argues Whitehead Institute Director Richard Young. He’s convinced libraries will be “extraordinarily rich” in compounds that could alter droplet behavior. “Condensates are regulated in really fascinating and complex ways by many of the classical regulators of biological function like kinases, phosphatases and ubiquitases,” he says. “All of these enzymes that have for the last half century been described as playing important regulatory roles in diverse biology.” When they act, he thinks, they’re modifying proteins in a way that can change the partitioning of those proteins both in and out of the droplets. “In other words, they are actually controlling the component levels in the droplets where these functions are occurring.” If Dewpoint screens a library and finds

European Biotechnology | Spring Edition | Vol. 19 | 2020

Watching condensates’ life cycle in cells is one way to study their biology, the other is to catalog their parts list.

a compound that changes the partitioning behaviour – for instance, the preference of a kinase substrate for a particular droplet – then “that’s a very interesting concept, because we already have drugs against kinases and against all these different enzymes.”

“Regarding neurodegeneration, there’s a lot published about condensates being involved in diseases such as ALS and dementia. But there’s also quite a lot of evidence of the roles condensates play in Huntington’s, Parkinson’s and Alzheimer’s.” But even if you find a drug that influences a certain condensate in a profound and therapeutically relevant way, how do you manage to direct it to a specific condensate – and away from others? Can you be specific enough to not have a lot of side effects? “If you would have asked me this question say, 20 months ago – before I was aware of Tony’s work – I would have said: That’s going to be very hard,” Young admits. But he’s changed his opinion after seeing “empirical data that you can get very selective effects.” One approach is

for instance to alter the partitioning property of a protein that’s drawn to the droplet by altering phosphorylation. Another way to increase specificity might be to use RNA molecules to alter condensate biology. “If you look hard at the components of condensates, they always have RNA components,” Young says. “These play pretty important roles in condensate behavior.” Any approach that modulates levels of these condensate-related RNA molecules could represent “a very reasonable path to a therapeutic,” Young believes. “There are many ways to modulate RNA levels, and to do it quite specifically.”

A field that’s still in its infancy The goal now is to turn up or down 50% of given proteins that play roles in suspected Alzheimer’s or Parkinson’s pathways. “That’s an ideal scenario for a delivery of a small RNA,” says Young. “Particularly when you can deliver that small RNA once every six months or a year“. Sharp agrees that “RNA is heavily involved in these condensate processes.” He thinks biologists will use RNA-technologies to therapeutically modulate condensates, but also to better understand the function of these mysterious droplets within cells. “Condensate biology isn’t mature,” Sharp says. “Not even close.” L Sascha Karberg

Picture: Dewpoint Therapeutics

Cover Story

European Biotechnology | Spring Edition | Vol. 19 | 2020

“We have enough evidence” Drug Discovery By the end of January, Dewpoint Therapeutics had attracted investor

interest with a completely new approach to therapies for a wide range of devasting diseases. European Biotechnology spoke with Stephen Hale, the company’s Senior Vice President of Discovery Biology, and Chief Scientific Officer and board member Mark Murcko about the start-up’s US$60m Series A round and perspectives.

EuroBiotech_Dewpoint Therapeutics was founded in Dresden and Boston. Recently you decided to open a third base in Berlin, at the Bayer site near the river Spree. Why? Hale_We moved into Berlin for a couple

Picture: Dewpoint Therapeutics

of reasons. One is the talent pool. In Dresden, we have the Max Planck Institute for Cell Biology and Genetics, and that’s a great recruiting tool. But it’s limited from an industrial perspective in terms of the sort of people we can hire. We want to have a diverse, inclusive society within the company, because that gives us advantages scientifically and intellectually. We have not had a hard time so far hiring a diverse group in Dresden. Half are German citizens and half are not. It’s been a good mix, quite diverse, from different countries, different ethnicities. But Berlin has a broader population and it may be easier to actually recruit people from outside of Berlin that would want to work in a biotech. Berlin is a city that people want to go to. It’s up and coming, it’s growing, it’s vibrant. And there is also the Bayer connection… EuroBiotech_Bayer announced a US$100m cooperation with Dewpoint Therapeutics in November … Hale_Bayer has a big site in Berlin, and

as we’re going to move that relationship with them forward, a Berlin base makes it easier.

Stephen Hale is a biochemist who worked as a consultant and entrepreneur before joining Dewpoint. He was CSO of Ensemble Therapeutics, and worked for Praecis Pharmaceuticals as well as Phylos, a therapeutics discovery and development company he co-founded.

EuroBiotech_Why do you think that condensate biology could develop into a platform technology? Hale_In biology, to have function, you

need a certain activity at a certain location at the right time. So the easiest way to think about condensates is that they are a method that the cell uses to compartmentalize the right things at the right time, but in a very dynamic fashion. A nucleus or a mitochondrium is more stable. Conden-

sates are called on at a need-be-basis – sometimes hundreds of things are needed at the right place at the right time to do some simple functions. So they’re like a minifactories that assemble, do what they need to do, and then dissolve again. The advantage is that a condensate takes very little energy to form. They can be very dynamic, and can be built in milliseconds or seconds, depending on what their function is. But they can form and go away in a regulated process to perform very specific functions – for instance transcription or splicing – and many more cellular functions. So if condensates have such a broad biological impact, you can imagine that when any of these things get dysfunctional, you could develop a disease. And if there is a disease pathway that involves a condensate then we can take advantage of that and can modulate that activity. So it could be a signaling pathway, it could be a transcription event, it could be a splicing event, it could be T-cell signaling – there’s a lot of biology that takes advantage of condensates. So with something that has such a broad impact it can be therapeutically agnostic and across all therapeutic areas or indications. EuroBiotech_What are the tools you use or develop to study condensates? Hale_Very important for us is to build the

tool set that we need to be able to figure out what is the best opportunity, and then figure out how to make drugs out of that

Cover Story

European Biotechnology | Spring Edition | Vol. 19 | 2020

opportunity. For instance, we have a tool called “D.Map” that is able to say what components are in a condensate. Based on that, we can figure out what they’re doing, and which components might be missing or are enhanced in a disease state, so that we can say which one is drugable. Murcko_People have already done this kind of condensate mapping, building the parts list of a condensate. But it’s a ton of work. For us, it’s important to have a much faster and more reliable way to do the mapping experiment. So we spend a lot of time developing the appropriate tools. EuroBiotech_Dewpoint is focusing on cancer and neurodegeneration. Why? Murcko_Regarding neurodegeneration,

there’s a lot published about condensates being involved in diseases such as ALS and dementia, but there’s also quite a lot of evidence for the roles of condensates in Huntington’s, Parkinson’s and Alzheimer’s. One of the things that makes this field so exciting is that we can all see many possibilities. What will make a company like this successful is to really be looking very systematically at where the evidence is the strongest. We’re looking pretty carefully at all of these different neuro degenerative diseases to try to understand where the evidence is the strongest.

Picture: xxx

EuroBiotech_The theory is that these fluid- or gel-like condensates build through a phase separation event. But for some reason, perhaps in a pathogenic setting, this liquid state could transform into a solid condensate, for instance the betaamyloid-plaques seen in Alzheimer’s disease. If Dewpoint targets this process, what is your strategy? Do you search for small molecules that reverse this process, or do you look for drugs to prevent or stop this solidification? Which approach might cure Alzheimer’s? Murcko_This is one of the challenges that

we have. The honest answer is that the best strategy is not yet clear. Just to pick a simple example: There are some people, who would argue that the early formation of fibrils is actually a protective mechanism. I’m not saying that’s true. I don’t know. But that’s the challenge we face. So one hy-

right time to build a company out of such interesting research? Do you know enough already? Murcko_I think that condensates and liquid

Mark Murcko Before joining Dewpoint, the organic chemist worked as CSO for Relay Therapeutics and Vertex Pharmaceuticals, specialising in structure-based drug design. He’s directly contributed to seven marketed drugs spanning HIV, cystic fibrosis and glaucoma.

pothesis could be exactly what you said: find a cell in which the condensate has hardened and then screen small molecules to see if you can dissolve those hardened condensates. That’s a perfectly reasonable strategy. And we’re doing that. Whether that will ultimately be the thing that cures the disease, no one knows. It could be. But there are many different mechanisms. It could also be that mutations in certain proteins cause them to change their location in the cell. If a mutation in their IDR-domains, their ‘intrinsic disordered regions’, forces those proteins to show up in condensates in the cytosol, you would fix that by changing the shape of the mutant protein. So the question is a very deep question. The reality is, that we don’t quite know yet. And so that’s why collaborating with leading labs is a central part of Dewpoint’s activities. And that’s why our partnership with Bayer is so important, because we need access to really smart disease area biologists and clinicians. EuroBiotech_This is a totally new field. We only started to realise what condensates are five or six years ago. So when is the

face separation are now unquestionably real. But two years ago, people were still debating that. I think at this point, pretty much everybody acknowledges that this is a fundamental part of how cells function. So we’re past that debate phase. But how do you make a drug out of this? Or is it too early to even try? My conclusion, a year and a half ago, when we were setting this up, was: It’s not too early for two reasons. The first is that there’s already a great deal of evidence that links clinically observed mutations in neurodegenerative diseases and cancers with aberrant condensate function. That was starting to become clear 20 months ago. So you can show mutations in certain proteins, and you can visually see that the condensates in those mutated stem cells from those patients behave very badly. The second line was work coming out of Rick Young’s lab at the White head Institute in Cambridge, one of our founders, showing that quite a few known cancer drugs go into condensates and work inside of condensates and some of them interact with IDRs in those proteins. And then a third line of evidence was more and more of an understanding of how those IDRs interact with each other. Some people call that the grammar, the rules by which these IDRs find each other. So the third point of the evidence...the understanding of how these disordered domains interact with each other. All three of those things were starting to become clear about 20 months ago. And we felt like there was enough evidence. Plus, the number of labs around the world working on quantities was zooming upwards. The number of papers was doubling every few months. EuroBiotech_You screen small molecule libraries like Bayer’s to find drug candidates that interact with condensates. Such libraries have been screened a thousand times before. Why do you think you might now find a new therapeutic? Murcko_There are two parts to the an-

swer. The first is that we already know examples of existing marketed drugs that

Pictures: Relay Therapeutics

European Biotechnology | Srpng Edition | Vol. 19 | 2020

work in condensates. Second: Often in drug discovery, when someone runs a phenotypic screen in cells, they find hits but they don’t know how those compounds work. They then try to figure out the mechanism. Often that’s done biochemically, or it’s done in other traditional ways. But if the way that compound had worked in the phenotypic assay was because of something it was doing in a condensate, all of those traditional ways of trying to figure out the target to deconvolute the target fail. They all fail and get dropped. So my personal belief is that in fact many, many drugs work inside of condensates. EuroBiotech_How do these small molecules interact with condensates? Murcko_It depends. In some projects it is

pretty clear, in some projects we simply have the observation of a phenotype that we’re excited about, and we’re currently trying to figure that out. That was another reason why we thought it was okay to start now, because we thought there was enough meat on the bones to get going. And since we’ve started the company, quite a few additional targets have come up. EuroBiotech_In the end, these should be targets with a market … Murcko_We think there are enough exam-

ples already where there’s a significant medical need. All of the diseases that

we’re working on so far are many thousands of patients. EuroBiotech_Small molecules are one way to go. But is there also a more direct way to address these condensates? For example, with RNA approaches? Murcko_A lot of the proteins in conden-

sates have RNA binding domains. If you look at the proteins that are found in condensates, there’s a lot of intrinsic disordered regions, and there are a lot of RNA binding domains. So there are many strategies that you can follow. Small molecules is only one of them. And there’s nothing that says we couldn’t, in principle, apply a number of other strategies as well – like RNA therapeutics. EuroBiotech_With RNA, you could address certain molecules and functions of condensates more specifically … Murcko_What you really want to do is to

pull a single component out of the condensate. Or you want to slightly change the shape of a single component so that it no longer functions in the same way in the condensate. So depending on the link between the condensate and the disease phenotype, that will lead you to think about different drug discovery strategies. EuroBiotech How about delivery? That’s been a huge problem for gene therapy. Or do you face other challenges?

Cover Story

Murcko_That’s not an issue for us. If we’re

talking about small molecules, we have one hundred years of pharmaceutical history to build on. We know how to make molecules that can get into different compartments in the body. I think the challenges are fairly clear: to understand in detail the linkage between the condensate behavior and the disease behavior. We need to find those kinds of very clear connections between the genetics, the condensate and the disease phenotype. That’s a challenge. Another one is the tools. It’s difficult to study condensates. They’re very dynamic. You can’t freeze a cell, because the condensates won’t hang around. The lab technique to study condensates is really quite challenging. So very high resolution imaging, for example, is an important thing. Which is why we have a number of advisers who are world experts at that. EuroBiotech So, what’s the read-out of your assay? Do you test for how these small molecules change the condensates, or do you look for changes in the disease? Murcko_We have a lot of debates about

this, as you can imagine...about the screening strategy. But because condensates are so new, we need to have flexibility about how to try to answer that question. The future will tell us. L Sascha Karberg

The New Definition of Simplicity for Cell Culture Monitoring and Optimization 9 Test Stat Menu

pH, PCO2, PO2, Na+, K+, Cl-, Ca++, Gluc, Lac

Maintenance-free MicroSensor Card Technology 16 day use life and replacement in half the time needed by other analyzers

novabiomedical.com

High Throughput Low Sample Volume

Up to 45 samples per hour Sample volume: 100µL

Maximum Analyzer Readiness Calibration and QC are performed automatically to maintain constant readiness

Interview

European Biotechnology | Spring Edition | Vol. 19 | 2020

Expansion through partnerships TCR-T Immatics Biotechnologies has landed a potential US$1.1bn deal with GlaxoSmithKline

(GSK) to find novel cancer targets on solid tumours and to direct TCR-T cell therapies against them. European Biotechnology spoke with Dr Harpreet Singh, CEO of Immatics Biotechnologies.

EuroBiotech_What are the most important elements of this new partnership for Immatics? Singh_GSK is a leading pharmaceutical

player truly committed to T-cell receptor technology therapies (shortened TCR-T), with a clear strategy to build next-generation, commercial manufacturing platforms and next-generation, engineering technologies to enhance the efficacy and safety of drugs based on this treatment modality. Combining GSK’s capabilities with our highly differentiated discovery platform that identifies true targets and the right T-cell receptors could unlock new treatment opportunities that would benefit cancer patients, particularly patients with solid cancers that currently have little to no therapeutic options. EuroBiotech_How does the cooperation with GSK advance Immatics’ business development? Singh_The collaboration with GSK will

allow us to further expand our activities in the T-cell receptor therapy field, particularly for the treatment of solid tumours. Together with GSK, we will combine existing resources and expertise in the development, validation, and manufacturing of T-cell receptor therapeutics to rapidly and successfully advance Immatics’ novel TCR candidates. Furthermore, our collaboration with a major pharmaceutical partner like GSK serves as an additional validation of the potential of our unique technology platforms.

EuroBiotech_What distinguishes and qualifies Immatics’ XPRESIDENT® platform for target identification and validation from competitors’ cancer antigen discovery platforms? Singh_ XPRESIDENT® is the most sensi-

harpreet Singh is CEO of Immatics Biotechnologies. He cofounded Immatics GmbH/Tübingen, Germany in 2000 to translate pioneering scientific discoveries in immunology into cancer immunotherapies as Managing Director and Chief Scientific Officer. In 2015, Dr Singh became President & CEO of Immatics US, overseeing all operations of Immatics in Houston, Texas, to develop next-generation Adoptive Cell Therapies (ACT). He led the team that achieved a US$20m CPRIT grant from the State of Texas. In 2019, Harpreet became CEO of Immatics Biotechnologies. A scholar under Prof. HansGeorg Rammensee, Singh completed his academic studies by earning a PhD in immunology at the University of Tübingen, Germany.

tive, accurate, and highest-throughput technology capable of identifying targets in virtually any type of cancer. Immatics’ innovative TCR platform, XCEPTOR™, enables the rapid and efficient identification and characterization of a large number of high-affinity and highly specific T-cell receptors, which, in turn, can be used for the modification of T cells in adoptive cell therapies. The key differentiators of our platform are: ›› XPRESIDENT® is the leading mass spectrometry-based platform used to identify pHLA target structures. ›› XPRESIDENT® is ultra-sensitive (in the attomolar range) and enables a quantitative analysis of target structures per tumour cell. XPRESIDENT® is able to detect the most relevant and naturally-occurring cancer target structures. ›› XPRESIDENT® uses an extremely comprehensive data set comprised not only of tumour tissues but also of normal tissue. This data enables the selection of the T-cell receptors with the highest specificity through analysis of on- and off-target toxicity. EuroBiotech_CAR-T therapies are currently only approved for leukaemia and lymphoma. From the partners’ point of view, why are TCR-Ts also effective against solid tumours?

Picture: Immatics Biotechnologies

European Biotechnology | Spring Edition | Vol. 19 | 2020

Singh_Although no approved TCR-T ther-

apies for solid tumours currently exist, promising results have been shown from clinical studies examining the TCR-T approach (including those from GSK, among others). Indeed, solid cancers are harder “nuts” to crack, as they develop various mechanisms to protect themselves against T cells. A large number of effective and specific T cells, such as TCRs, are, thus, needed to infiltrate and attack the tumour. Solid tumours are most often heterogenous, not only between different cancer types but also between different patients suffering from the same type of tumour. Therefore, choosing the right targets for the TCR therapy is critical. We and our partners believe that having the ability to apply our screening platform, XPRESIDENT®, to discover and validate therapeutic targets, gives us a significant advantage for developing efficient TCR-T therapeutics. The heterogeneity of solid tumours and the self-defence mechanisms that they devel-

op to evade the immune system could be tackled by attacking the tumour on multiple targets simultaneously using a premanufactured “warehouse” of targets and TCRs. We have successfully shown the feasibility of this warehouse concept with our ACTolog® pilot trial. Our vision is to apply this concept to TCR-T therapies, too. In the short term, we hope to treat patients with multiple TCRs simultaneously, selected from a large TCR warehouse covering multiple types of targets and multiple HLA phenotypes.

Interview

EuroBiotech_Which developmental stage have the TCR-T programs licensed by GSK reached? Singh_Through our collaboration, Glaxo-

SmithKline will gain access to two of Immatics’ TCR-T programs. The next generation T-cell receptor therapeutics that will be developed as a result of this collaboration are directed against two proprietary targets that were discovered and valid ated by Immatics’ XPRESIDENT® technology.

EuroBiotech_How big would the market potential be in comparison to blood cancer? Singh_Blood cancer encompasses vari-

EuroBiotech_Will there be an additional target screening as part of the collaboration in order to agree on further potential drug targets? Singh_Under the terms of the agreement,

ous malignancies in the haematopoietic and lymphatic systems. At 10%, these cancers represent a minority, especially in terms of mortality rates. Therefore, the market potential and developmental potential for patients with solid tumours is a lot higher than in blood cancers.

GlaxoSmithKline has the option to select additional target programs for further milestone and royalty payments. Proprietary targets for each additional program will be selected and validated using Immatics’ XPRESIDENT® platform.  t.gabrielczyk@biocom.eu

DŽƌĞ ƚŚĂŶ ϭϬ ǇĞĂƌƐ experience in 'DWͲŵĂŶƵĨĂĐƚƵƌŝŶŐ ŽĨ ĐĞůů ĂŶĚ ŐĞŶĞ ƚŚĞƌĂƉŝĞƐ WŝŽŶĞĞƌ ŝŶ ŐĞŶĞƟĐĂůůǇ ŵŽĚŝĮĞĚ ĐĞůů ƉƌŽĚƵĐƚƐ tĞ ĞǆĐĞů ŝŶ ƋƵĂůŝƚǇ ĂŶĚ ƐĂĨĞƚǇ

We are hiring! contact@apceth.com www.apceth.com

Financial Markets

European Biotechnology | Spring Edition | Vol. 19 | 2020

European assets ahead despite virus panic Frederic Gomez, PhD Equity Research Analyst Biotech, Pharmium Securities_Every year,

it’s the same: in January, investors are scratching their heads, searching to find investment ideas that could ensure the greatest return/performance. Given the current valuation, can 2020 deliver windfall surprises for European names?

Predicting on the first of January which way financial markets will go is never easy, and the feeling that prevailed at the return of a famous HC Conference in January was “wait-and-see” or “wait-andsell.” The usual frenzy in the corridors and the lobby of the hotel had subsided to a strange feeling of calm. Generally rich in M&A announcements, the month had been quiet, and many investors saw the US presidential election as one of the potential threats for 2020. The jolt finally came from China, where, ironically, it was a very simple infectious agent (genome, capsid, and envelope) that caused the indices to fall, also taking away most of the European biotechs. Yet, in this tsunami, Acceleron’s

performance (up 76.9% since 01/01) following Reblozyl’s US approval ahead of schedule and the announcement of positive Phase II data in PAH reminds us that this industry has unique and specific characteristics. Any clinical, regulatory, and/ or commercial success/action is on the rise. In a bear market, corrections inevitably create great buying opportunities. So, what can we expect for the European biotech sector in 2020, and can some of them be big winners? First, among our four locomotives (market cap >€3bn), Galapagos, Genmab, and Morphosys are all waiting for an approval in the US. On this regula-

tory front, Pharmamar, Cassiopea, and DBV also hope to attain the holy grail with the FDA. EMA will also play a crucial role with MAA currently under review for Advicenne, Orchard Therapeutics, and Hansa Biopharma. On the clinical front, Argenx’s Phase III results in myasthenia gravis will be scrutinised, as will those of several NASH players (Genfit, Poxel, Inventiva) or Erytech’s Phase III data in pancreatic cancer and Zealand Pharma with dasiglucagon for congenital hyperinsulinism. The ability of the European sector to convince US and generalists’ investors to return and, thus, enable us to compete with US peers will rely on the outcome of these events. Then, it will be always be time to see if a virus is panicking the markets, because that is another story. L

News from the floor Qiagen NV Berenberg analyst Scott

Bardo downgraded Qiagen from “buy” to “hold” after Thermo Fisher Scientific announced plans to take over the company. Calling Thermo Fisher a “good new home” for Qiagen, Berenberg raised its price target from €37 to €39. Genmab A/S Following inflow from in-

stitutional investors in Q3 and Q4/2019, Morgan Stanley raised their target price on shares of Genmab A/S from $30.00

to $31.00 and gave the stock an “overweight” rating.

8800 systems. Roche Holdings AG Basel has an average rating of “buy” and an average target price of $42.50.

Roche Holdings AG Roche Hold-

ings AG Basel (RHHBY) was upgraded by equities researchers at Goldman Sachs Group from a “buy” rating to a “conviction-buy” rating in March, after having received the FDA approval for a dualtarget PCR test for a fully automated, highthroughput COVID-19 diagnosis running on Roche Diagnostics cobas 6800 and

Valneva SE First Berlin Equity Re-

search analyst Simon Scholes reiterated his “buy” rating and maintained his €6 price target following a 25.2% jump in 2019 product sales to €129.5m, mainly attributable to sales growth (+60%) of the Japanese encephalitis vaccine, Ixiaro, to the U.S. military. L

Picture: Pharmium Securities

NEW: Bioprocess control station

One for All SciVario® twin – Innovative, Intuitive, Intelligent It does not matter with which organism you are working with now, or in the future. SciVario twin is our intelligent solution for your changing needs. The innovative bay-drawer system allows for the ﬂexible adaption to your needs. The integrated, improved TMFCs and pumps allow the individual or parallel control of up to two vessels in a range of 0.7 L up to 3.8 L.

> Innovative: Personalize your SciVario twin according to your needs with the ﬂexible bay-drawer system. > Intuitive: Easily set-up your process with the integrated VisioNize® onboard software. > Intelligent: Automated detection and recognition of plugged-in devices.

www.eppendorf.com/scivario Eppendorf®, the Eppendorf %UDQG 'HVLJQ, BioBLU®, SciVario® and VisioNize® are registered trademarks of Eppendorf AG, Germany. All rights reserved, including graphics and images. Copyright © 2020 by Eppendorf AG.

financial markets

COMPANY 4D Pharma plc 4SC AG A1M Pharma AS AB Science SA Abcam plc Abionix Pharma SA Abivax SA Acacia Pharma plc Active Biotech AB Addex Therapeutics Ltd ADL Bionatur Solutions SA

QUOTE 0.30 1.56 0.07 6.71 12.61 0.55 15.70 2.12 0.24 1.08 1.35

M-CAP 32,500k 73,600k 11,400k 298,700k 2,594,400k 11,800k 194,100k 121,400k 34,100k 35,500k 49,800k

European Biotechnology | Spring Edition | Vol. 19 | 2020

52 weeks indicator low high

COMPANY Brain AG C4X Discovery Holdings plc Calliditas Therapeutics AB Cantargia AB Carbios SAS Cassiopea SpA Cellectis SA Cellink AB Celon Pharma SA Celyad SA Circassia Pharmaceuticals plc Co.don AG Cosmo Pharmaceuticals NV Curetis AG Cytotools AG Cyxone AB DBV Technologies SA

European Biotech Stocks The unique and most complete list of share price developments of biotech companies listed in Europe – exclusively in European Biotechnology Magazine.

Deinove SA Destiny Pharma plc Diamyd Medical AB Diasorin SpA Elanix Technologies AG e-Therapeutics plc Ellen AB Enzymatica AB Epigenomics AG Erytech Pharma SA Esperite NV

Adocia SAS Advicenne SACA ALK-Abelló A/S Allergy Therapeutics plc Alligator Bioscience AB Annexin Pharmaceuticals AB Aqua Bio Technology ASA Argenx SE Arocell AB Asit Biotech SA Avacta Group plc Avantium Holding NV Bachem Holding AG Basilea Pharmaceutica AG Bavarian Nordic A/S Bergenbio ASA Bioarctic AB Bio-On SpA Biocartis NV Biofrontera AG Biogaia AB Bioinvent International AB Biomed-Lublin SA Biomérieux SA Biophytis Bioporto Diagnostics A/S Biosearch Life SA Biotec Pharmacon ASA Bioventix plc Biovica International AB Bone Therapeutics SA

7.01 7.40 193.57 0.10 0.56 0.07 0.17 118.50 0.08 0.21 0.25 3.70 177.36 37.11 14.97 1.17 5.31 10.12 3.60 2.79 34.31 0.09 0.29 100.0 0.19 0.28 0.81 0.64 36.80 1.08 2.80

47,300k 60,600k 2,113,400k 60,800k 39,100k 5,200k 2,600k 5,080,000k 5,800k 4,600k 44,000k 96,000k 2,426,400k 441,500k 862,800k 86,700k 450,300k 19,051,000k 203,000k 123,100k 577,600k 45,200k 14,900k 1,629,000k 7,300k 48,500k 46,200k 31,000k 191,000k 27,700k 32,700k

Eurobio Scientific SA Eurofins Scientific SE Evgen Pharma plc Evolva SA Evotec SE Expedeon AG Expres2ion Biotech Holding AB Faron Pharmaceuticals Oy Fermentalg SA Formycon AG Fusion Antibodies Ltd. Gabather AB Galapagos NV Genedrive plc Geneuro SA Genfit SA Genmab A/S Genomed SA Genomic Vision SA Genovis AB Genoway SA Gensight Biologics SA Genkyotex SA Genus plc Global Bioenergies SA Hansa Biopharma AB Heidelberg Pharma AG Herantis Pharma Oyj Hofseth Biocare ASA Horizon Discovery Group plc Hybrigenics SA

QUOTE 6.37 6.37 0.14 7.20 1.40 7.04 26.32 7.91 7.22 7.04 6.48 0.19 1.82 60.28 1.0 8.20 0.27 7.32 0.66 0.37 1.33 111.0 0.25 0.09 0.01 0.71 1.22 4.62 0.04 8.98 434.60 0.04 0.17 20.06 1.51 0.61 5.51 0.98 20.20 0.96 0.35 168.0 0.22 2.15 13.30 24.73 6.05 0.27 1.61 1.49 1.87 1.82 35.21 6.65 6.14 6.65 0.60 1.30 0.07

M-CAP 109,600k 109,600k 15,200k 269,400k 97,800k 48,600k 259,400k 339,700k 303,500k 316,300k 93,300k 67,900k 47,700k 879,600k 26,800k 22,100k 13,500k 402,100k 12,900k 16,500k 92,000k 6,070,000k 2,000k 27,900k 3,000k 98,100k 46,800k 84,000k 1,800k 101,200k 7,556,000k 4,800k 135,200k 3,013,000k 83,300k 8,200k 233,500k 17,500k 197,000k 25,200k 4,700k 10,617,000k 11,000k 44,300k 505,300k 1,577,000k 8,000k 9,800k 109,000k 11,100k 58,500k 20,300k 2,231,500k 266,500k 172,100k 47,100k 189,900k 183,200k 16,800k

52 weeks indicator low high

financial markets

European Biotechnology | Spring Edition | Vol. 19 | 2020

COMPANY Idorsia Ltd. Immunicum AB Immunodiagnostic Systems plc Immunovia AB Immupharma plc Index Pharm. Holding AB Infant Bacterial Therapeutics AB Innate Pharma SA Integragen SA Intervacc AB Inventiva SA Isofol Medical AB ISR Holding AB Kancera AB Karo Pharma AB Kiadis Pharma BV Kuros Biosciences AG LIDDS AB Lysogene SA Marinomed Biotech AG MDxHealth SA Medigene AG Medivir AB Mereo Biopharma Group plc Metabolic Explorer SA Midatech Pharma plc Molecular Partners AG Molecular Medicine SpA Mologen AG Morphosys AG Motif Bio plc Nanobiotix SA Neurosearch A/S Neurovive Pharmaceutical AB Newron Pharmaceuticals SpA Nicox SA Nordic Nanovector ASA Novozymes Biopharma DK A/S Noxxon Pharma NV Oncimmune Holdings plc Oncoarendi Therapeutics SA Oncodesign Biotechnology SA Oncology Venture A/S Oncopeptides AB Onxeo SA Optibiotix Health plc Orphazyme A/S Oryzon Genomics SA OSE Pharma SA Oxford Biodynamics plc Oxford Biomedica plc Oxurion NV Paion AG PCI Biotech Holding ASA Pharma Mar SA Pharming Group NV Pharnext SA Photocure ASA Physiomics plc

QUOTE 22.92 0.61 2.11 9.55 0.12 0.49 6.91 5.10 1.45 1.54 3.40 0.77 0.36 0.03 3.90 1.34 1.98 1.34 2.57 92.0 0.65 4.40 1.15 0.21 1.19 0.26 15.0 0.47 0.08 91.0 0.0 5.96 1.62 0.06 4.34 3.50 1.11 41.67 0.36 0.55 2.18 7.22 0.13 9.22 0.43 0.34 11.35 2.39 3.37 0.64 6.35 2.44 1.76 3.13 4.20 0.93 4.50 4.42 0.02

M-CAP 2,996,200k 56,600k 62,100k 187,700k 20,100k 43,300k 76,700k 377,000k 9,500k 65,600k 107,400k 21,800k 8,500k 7,000k 875,300k 39,000k 46,000k 32,500k 42,600k 135,200k 45,400k 104,400k 27,700k 26,600k 32,800k 6,200k 316,400k 219,000k 994,900k 2,932,000k 300k 134,800k 36,200k 11,800k 76,600k 115,300k 73,200k 11,866,000k 4,700k 35,000k 29,900k 50,500k 16,400k 515,600k 25,500k 33,100k 307,600k 106,000k 51,600k 59,300k 475,100k 94,900k 114,500k 126,700k 929,800k 584,000k 72,800k 101,000k 1,300k

52 weeks indicator low high

COMPANY Plant Advanced Technologies SA Polyphor AG Poxel SA Probi AB Probiodrug AG Promore Pharma AB Proteome Sciences plc Qiagen NV Q-Linea AB Quantum Genomics SAS Relief Therapeutics Holding AG Reneuron Group plc Saniona AB Santhera Pharmaceuticals AG Sareum Holdings plc Scancell Holdings plc Selvita SA Sensorion SA Shield Therapeutics plc Silence Therapeutics plc Simris Alg AB Skinbiotherapeutics plc Swedish Orphan Biovitrum AB Synairgen Research Ltd Targovax ASA Theradiag SA Theranexus SADIR Tissue Regenix Group plc Tiziana Life Sciences plc Transgene SA Valirx plc Valneva SE Vectura Group plc Verona Pharma plc Virogates A/S Vita 34 AG Xbrane Biopharma AB Xintela AB Yourgene Health plc Zealand Pharmaceuticals A/S

QUOTE 14.80 5.09 5.86 13.51 4.12 0.27 0.04 36.67 4.34 2.06 0.02 1.18 1.72 6.42 0.0 0.06 9.41 0.58 1.0 5.39 0.09 0.06 14.55 0.56 0.39 1.31 2.50 0.01 0.39 1.22 0.0 2.30 0.98 0.48 6.18 10.35 2.80 0.30 0.16 26.39

M-CAP 13,000k 54,800k 145,100k 156,700k 82,200k 9,700k 10,400k 8,320,000k 105,100k 35,100k 51,100k 34,500k 49,800k 75,000k 12,600k 26,700k 136,600k 33,800k 119,800k 428,000k 1,900k 9,700k 4,461,700k 70,300k 31,300k 11,300k 9,000k 5,600k 60,300k 98,500k 603,600k 207,800k 604,300k 50,700k 18,800k 42,900k 43,900k 12,400k 102,200k 948,500k

52 weeks indicator low high

All quotes are listed in euro. All data is provided without guarantee. The effective date is 31 March 2020 These dedicated biotech companies are listed on European stock markets.

Insight Europe

European Biotechnology | Spring Edition | Vol. 19 | 2020

Is AMR following COVID-19 as the next, but hidden, crisis? Antibiotic resistance With the coronavirus pandemic mounting, experts are already warn-

ing of antimicrobial resistance as being the next, hidden crisis. The AMR community still urgently waits for substantial pull incentives. While the US DISARM act was pulled at the last minute from the country’s corona stimulus package, the UK’s NHS has started stakeholder engagement for its flat-rate model. Meanwhile, Forge Therapeutics has closed a €170m deal with Roche.

New treatments against resistant Gram-negative bacteria, such as Pseudomonas aeruginosa, are the focus of a deal that Swiss pharma company Roche signed with USbased biotech company Forge Therapeutics in March.

Typically, antibiotic work has not been seen as a high priority for big pharma in the past years, but with COVID-19, this may change. At the end of March, Swiss pharma company Roche announced a deal worth up to €170m with US-based Forge Therapeutics to work on a therapy for antibiotic-resistant Gram-negative bacteria, including Pseudomonas aeruginosa, which can cause lung infections. This deal adds up to the $5.7m CARB-X grant awarded to Forge in 2019. “We look forward to combining our novel approach with Roche’s proven drug development and commercialization expertise to provide a truly new class of antibiotics,” says Forge CEO Zachary Zimmerman. Additional good news was provided by US-based Paratek at the end of 2019. The company received a five-years contract from Biomedical Advanced Research and Development Authority (BARDA), with an option to extend to 10 years. Under

the agreement, the development of Paratek’s Nuzyra® for the treatment of pulmonary anthrax is supported, as well as FDA post-marketing requirements associated with the initial Nuzyra approval, and the option to procure up to 10,000 treatment courses of the drug for the Strategic National Stockpile. “We are honoured that BARDA has selected us. This provides us with enough capital through the end of 2023,” CEO Evan Loh told European Biotechnology. However, in light of other companies going bankrupt (Archaogen, Melinta) or facing an acquisition (Tetraphase), Loh points out that “one company doesn’t make a sector successful.” He and many other experts in the field are emphasising, that antimicrobial resistance might be the next global, but silent, pandemic crisis. “As we come together to fight today’s COVID-19 crisis, we must also look ahead to the next one. We cannot be short-sighted, and we can-

not be complacent, especially about antibiotic resistance,” urges Julie Gerberding, Chief Patient Officer at MSD. In addition, there is growing concern about how COVID-19 deaths are linked to AMR (BMJ 2020;368:m1091). “Secondary infections are often way more deadly than the original infection. We need an armamentarium of functioning anti-infectives,” comments Aleks Engel, investor from the REPAIR Impact Fund. Effective pull incentives are in high demand, but countries are still moving slowly. In March, the UK Government, along with NICE and the NHS England, started a stakeholder dialogue around the details of their pilot approach. Thus, the NHS England proposes to pay a subscription fee of up to £10m/year for a decade for each of two new antibiotics covering WHO priority pathogens, whether the antibiotic is used or not. According to AMR expert John Rex, ”the analysis suggests that they are proposing – if the rest of the G20 pays their fair share – a global pull incentive of up to $4bn.” And, what are other countries doing? In the US, there was some hope that the DISARM Act could be included in the COVID-19 stimulus package, but that did not happen so far. According to Evan Loh, another emphasis should be to join forces across Europe. “Neither the country-by-country pricing system nor EMA’s need for extra data compared to FDA requirements makes it easy for antibiotic SMEs to survive postapproval,” he says. “It’s time for everyone to work together.” L s.wirsching@biocom.de

Picture: CDC/Janice Haney Carr

Regulatory Affairs

European Biotechnology | Spring Edition | Vol. 19 | 2020

Updates on clinical trials Septic shock

German Adrenomed AG’s antibody candidate adrecizumab has met the primary endpoint of the Phase II AdrenOSS-2 study of 301 patients with early septic shock. The antibody is designed to target patients with early septic shock who suffer from endothelial dysfunction. Adrecizumab binds to the C-terminus of the vasoactive peptide hormone adrenomedullin (bio-ADM®), concentrating it in its active form in the vessel lumen, restoring the barrier function of the leaky endothelium. The disturbed barrier function of the blood vessels in this patient group, which was stratified using a proprietary bio-ADM assay developed by Sphingotec GmbH (see report, page 90, leads to oedema, a steep drop in blood pressure that ends up in organ malperfusion and dysfunction, shock, and finally, death. Adrenomed said that the result of the proof-of-concept study in the medically underserved indication was very promising. The company’s vaso-stabilising, bio-ADM-binding antibody treatment reached the primary study endpoint of safety and tolerability. Pointing to a treatment-related reduction in mortality, Adrenomed’s CMO Jens Zimmermann said that “patients with septic shock could benefit from adrecizumab.”

In the study, adrecizumab reduced the 28 day-mortality in the treatment group versus patients receiving standard critical care treatment. Adrenomed CEO Jens Schneider-Mergener said: “We look forward to discussing the further development of adrecizumab with the relevant authorities and partners. Based on the proof-of-concept now available, we believe that adrecizumab has great potential, not only for treating septic shock, but also in other life-threatening diseases associated with increased vascular permeability.” At the time of the release of its ad-hoc news, Adrenomed AG was, however, not able to provide more details regarding the efficacy of adrecizumab, specifically, to what degree did the antibody reduce the 28 day-mortality rate compared with that of patients receiving standard critical care treatment. Its high-ranking academic partners have plans to submit the data for publication to a peer-reviewed scientific journal as soon as possible. GVHD

DISCOVER UNLOCK PICHIA Productivity through Diversity

Broadest Pichia protein production toolbox Record breaking productivities MeOH-induced & MeOH-free processes Tailor-made glycoproteins UNLOCK PICHIA boosting Pichia GlycoSwitch®

www.validogen.com www.unlockpichia.com

Xenikos BV (Nijmegen, The Netherlands) has started a US pivotal study (NCT04128319) to evaluate the safety and efficacy of its T-Guard ® therapy in 47 patients with steroid-refractory

acute Graft-versus-Host disease (SRaGVHD), following allogeneic stem cell transplantation. T-Guard consists of antibody toxin conjugates that home in on T cells and natural killer (NK) cells carrying the CD3 and/or CD7 surface antigen. In the single-arm, multicentre Phase III study, patients will receive four infusions of T-Guard within one week, which is thought to decrease the probability for opportunistic infections. The primary endpoint of the study is a complete response rate on day 28; secondary endpoints include duration of complete response rate, overall response rate, and overall survival six months after treatment. Lung cancer

In February, PharmaMar SA (Madrid, Spain) and its new licence partner Jazz Pharmaceuticals plc (Dublin, Ireland) received an FDA Priority Review for a new drug application (NDA) for lurbinectedin as a second-line treatment for patients with SCLC (Small Cell Lung Cancer), who relapsed following platinum-based chemotherapy. The PDUFA date was set for August 16, 2020. This synthetic drug works by blocking RNA polymerase II-dependent oncogenic transcription programmes and modulating the activity of tumour-associated macrophages. The NDA is based on data from a Phase II monotherapy basket

Regulatory Affairs

European Biotechnology | Spring Edition | Vol. 19 | 2020

News Targeted drug delivery At the end of February, French Transgene SA (Strasbourg) dosed the first colorectal cancer patient with unresectable liver metastases in a Phase I/IIa trial with its oncolytic virus TG 6002. In the single-arm, openlabel study, the company will assess the safety, pharmacokinetics, biodistribution, and efficacy of intrahepatic artery (IHA) infusion as a novel route of administration of repeated and ascending doses of TG6002 and the nontoxic prodrug flucytosine (5-FC). TG6002 is a next generation oncolytic immunotherapy that allows for the conversion of 5-FC into the chemotherapeutic 5-Fluorouracil (5-FU) directly in the tumour.

Parkinson’s progress Herantis Pharma plc (Helsinki, Finland) announced “encouraging biological responses” from a Phase I/II study on the safety of its neuroprotective factor candidate CDNF in advanced-stage Parkinson’s disease patients. Results from the Phase II part of trial, in which all patients will receive CDNF for an additional six months, are expected in Q3/2020. In animal models, CDNF has been shown to protect neurons from degeneration and to restore the function of already degenerating neurons. Patients were dosed with a surgically implanted delivery system provided by Renishaw plc (Wottonunder-Edge, UK). The secondary and exploratory endpoints of the study evaluate initial signs of efficacy, including assessments based on the Unified Parkinson’s Disease Rating Scale (UPDRS), dopamine transporter PET imaging, actigraphy measurements, and alpha-synuclein levels.

Affinity-matured CD19 binding site  Direct tumour cell killing

Tafasitamab (MOR208) Engineered Fc portion  Enhanced ADCC  Enhanced ADCP

Mode of action of tafasitamab (MOR208), a CD19-specific monoclonal antibody that was licenced from Xencor Inc.: The therapeutic FDA-approved antibody directly and indirectly kills tumour cells.

trial (NCT02454972), which included an evaluation of lurbinectedin for the treatment of relapsed SCLC. A total of 105 patients from 39 centres were recruited in Europe and the US. The trial met its primary endpoint of Objective Response Rate (ORR), which was 35.2%. Median duration of response was 5.3 months, while progression-free survival was 3.9 months, and overall survival was 9.3 months. Lurbinectedin (PM1183), a DNA minor groove binder analogue of trabectedin, inhibits oncogenic transcription in tumourassociated macrophages, downregulating the production of cytokines that are essential for the growth of the tumour. Transcriptional addiction is an acknowledged target in those diseases, many of them lacking other actionable targets. However, lurbinectedin failed to outperform progression-free survival vs chemotherapy in ovarian cancer patients and, thus, must be evaluated on a case-by-case basis. Lymphoma

ADC Therapeutics SA has met the primary endpoint of a pivotal, unblinded, control arm-free Phase II study of its second-line treatment Loncastuximab tesirin (ADCT-402) for the treatment of dif fuse, large B - cell lymphoma (DLBCL). The response rate in 66 (45.5%) of 145 refractory patients, 20% of whom had a complete response, is in line with

the Lausanne-based company’s expectation to submit a marketing application to the US Food and Drug Administration (FDA) in Q3/2020. The results also confirm data obtained in a previous Phase II study with 70 patients, in which the antibody drug conjugate (ADC) was observed to be effective in 41.4% of 70 patients. In 21.4% of the patients enrolled, ADCT-402 led to the complete clearance of the degenerated blood cells. Loncastuximab tesirin consists of a pyrrolobenzodiazepine toxin chemically linked to a CD19-targeting antibody. Af ter licencing it s anti- CD19 antibody tafasitamab to Inc y te Corp. (Wilmington, USA) in a US$2bn deal, MorphoSys AG (Martinsried, Germany) enrolled the first patients with diffuse, large B-cell lymphoma (DLBCL) in a Phase Ib study with the company’s tafasitamab as first-line therapy. An EU registration dossier for market approval as a second-line treatment will be submitted to the European Medicines Agency (EMA) by mid-2020. In early March, the US Food & Drug Administration (FDA) granted Priority Review for tafasitamab. Roche AG’s bispecific CD20/CD3 antibody mosunetuzumab has led to complete remissions in patients with nonHodgkin lymphoma (NHL), who did not

Picture: MorphoSys AG

Regulatory Affairs

European Biotechnology | Spring Edition | Vol. 19 | 2020

respond to the company’s proprietary blockbuster rituximab, which has come under pressure from biosimilars. The engineered antibody also produced a lasting, therapeutic response in the 10% of nonresponders to highly effective CAR-T cell therapy. The Basel-based pharmaceutical developer had already presented its first data at the American Society of Haematology (ASH) meeting. In the expanded Phase I/IIb study involving 270 patients, mosunetuzumab was shown to be effective in patients with both slow-evolving non-Hodgkin lymphoma (NHL) and aggressive NHL. In the first group, 43.3% of the patients in the study experienced complete remission (objective response 62.7%), which lasted for 26 months in 80% of all patients. In patients with aggressive NHL, the response rate was still 37.1%, and for complete remission, 19.4%. In 71% of patients, the therapy success lasted at least 16 months. However, the risk of a cytokine storm was relatively high, at 30%. Myeloid leukaemia

Shares of Medigene AG (Martinsried, Germany) rose 30% in January upon the announcement of positive Phase I/II data for the company’s autologous DC vaccine in 20 patients with acute myeloid leukaemia (AML). After 24 months, both the primary endpoints (safety/tolerability) of the study were met, and the feasibility of manufacture/administration was demon-

strated. Secondary endpoints to evaluate the key clinical parameters of the patients showed that the overall survival rate (OS) was 80% (16 of 20 patients), and the progression-free survival rate (PFS) was 55% (11 of 20 patients). Even in the 50% of patients over 60 years of age who are not eligible for haematopoietic stem cell transplantation under current AML treatment standards and, thus, had a bad prognosis, the overall survival rate after 24 months’ follow-up was 80% (8 of 10 patients), and PFS was 50% (5 of 10 patients), like the population under 60 years of age. In the group of patients younger than 60 years of age, the PFS was slightly higher, at 60% (6 of 10 patients).

-2). BOSTON-3 is an open-label, Phase III extension study of the two pivotal trials, in which eligible participants will receive LCsA-i, Zambon’s inhalable cyclosporine. The primary endpoint is change in forced expiratory volume (FEV1) (mL) from baseline to week 24. BOSTON-4 is a safety and tolerability Phase II study of L‑CsA‑i in adults with BOS following alloHSCT. L‑CsA‑i is administered via a drug-specific, Investigational eFlow ® Technology nebuliser system (PARI Pharma GmbH, Gräfelfing, Germany). The investigational drug-device combination is designed to deliver L‑CsA‑i to the site of disease in the lung. Retinitis pigmentosa

BOS

Breath Therapeutics GmbH (Munich, Germany, which was taken over in July 2019 by Milan-based Zambon SpA, initiated two additional studies (BOSTON-3 and BOSTON-4) in February to evaluate its liposomal, inhalable immunosuppressant cyclosporine A as a treatment of bronchiolitis obliterans syndrome (BOS). BOS is caused by T‑cell mediated inflammation that leads to blockage of bronchioles. This devastating, rare lung disease is associated with high mortality, particularly among recipients of lung and allogeneic haematopoietic stem cell transplants (alloHSCT). Both studies complement two ongoing pivotal Phase III studies (BOSTON-1 and

ReNeuron Group plc has reported positive, 12-month follow-up data from patients with retinitis pigmentosa treated with the company’s hRPC stem cell therapy candidate in an ongoing Phase IIa study. Retinitis pigmentosa is a group of hereditary diseases of the eye that lead to progressive loss of sight and blindness. The company also submitted a protocol amendment to the US FDA to expand the Phase I/IIa study to treat up to a further nine patients in the Phase IIa part of the study with a dose of two million hRPC cells. The company said it expects to present further data from the expanded trial this year and to commence a pivotal clinical study in H1/2021. L

Economy

European Biotechnology | Spring Edition | Vol. 19 | 2020

Product hopping – Boon or Bane? Intellectual Property Providing access to medicines at affordable prices while

maintaining incentives for the originators to invest into significant innovations is a balance that's hard to find. Product hopping is a strategy for originators to minimise the erosion of their sales that has caught the attention of regulators and courts. › Dr Ute Kilger, Boehmert & Boehmert, Berlin, Germany

“Product hopping,” is a term used to describe a concerted patent, regulatory, and marketing strategy employed by pharmaceutical originators to protect sales of a successful drug. For example, a pharmaceutical company might introduce a new formulation of a drug that is patent protected before it faces significant price erosion due to generic entry. The marketing authorization for the old formulation is eventually deregistered and the originator may engage in a marketing campaign to disparage the old formulation. Hence, patients are switched to the new patent-protected formulation before generic entry. There is a growing number of case laws in the US and Europe that illustrate the competition law risks involved with such product hopping. It is not the introduction of a novel product alone that has caught the attention of the courts and regulators: it has been the combination of different patent, regulatory, and marketing strategies that was eventually found to be abusive. The new drug formulation may or may not be truly innovative. Critics say that such new drugs are the result of marginal innovation and incremental patenting of existing products. This would allegedly allow originators to preserve market exclusivity, but without significantly improving the standard of care. In addition, the pharmaceutical company has patented numerous improvements, including medical devices that may provide for a more convenient or safer application of

Dr. UTE KILGER (German Patent Attorney and European Patent and Trademark Attorney, Partner at Boehmert & Boehmert) specialises in all kinds of patent-related issues concerning the obtaining and enforcement of property rights, due diligence, mergers and acquisitions, contract negotiations, and licensing agreements.

this new formulation. This may lead to numerous patents covering said improvements, and may eventually lead to a patent thicket. These patents are also called “evergreening patents,” if they meet the definition as “artificially extending the protection cliff.” For instance, AbbVie was accused of evergreening its blockbuster Humira with an extremely thick patent thicket. The drug has more than 100 patents. Humira is already the bestselling drug in the world. Amgen and Boehringer Ingelheim have had FDA-approved biosimilars

to Humira but couldn’t launch them for quite some time, due to AbbVie’s patent shield. This led to patent disputes being litigated all over the world. What was the subject of AbbVie’s thicket patents? At first, Humira was marketed in a formulation comprised of a citrate buffer that caused pain immediately following injection. In the improved formulation, sodium citrate, known to cause pain, was removed. Other improvements concerned the application device, a pen. The injection volume was reduced by 50%, and the needle was thinner. If one looked closely at the Humira portfolio, less than 10 patents constituted an obstacle to generic entry, because the patented improvement could not be applied to the generic product, and thus, the generic had a competitive disadvantage, as the generics could only market the sodium citrate formulation that caused pain. This made the generics cry out loudly and complain about the “unfair patent thicket,” though it could be argued that 100 patents did not constitute an obstacle, and the said 10 patents that covered later, valuable improvements were rightly granted. Thus, it could be questioned whether the patent thicket debate is a clever marketing campaign of the generics. Remarkably, politicians have jumped on the bandwagon. US Senators Corbyn and Blumenthal introduced a bill called “Affordable Prescriptions for Patients.” This would empower the Federal Trade Commission (FTC) to challenge the originator as being anti-competitive and

Pictures: Boehmert & Boehmert

Economy

enable the FTC to bring antitrust suits against originator companies who build up secondary patent protection. However, the European Court of Justice has recognized that it is legitimate for pharmaceutical companies to adopt strategies seeking to minimize the erosion of their sales when faced with competition from generic products. [AstraZeneca v Commission, Case C-457/10 P, at 129]. According to this view, there is nothing inherently wrong with product hopping. In addition, the development of a new and improved formulation of a drug can be extremely beneficial, both to the patients that might find it more effective, safer, or more convenient, and to society, for the jobs created in researching, manufacturing, and marketing the new product. The question remains: where is the line between providing incentives for innovations, even for improving â&#x20AC;&#x153;old drugs,â&#x20AC;? and abusive â&#x20AC;&#x153;evergreeningâ&#x20AC;? strategies that â&#x20AC;&#x153;artificiallyâ&#x20AC;? extend protection. There is a call for the pharmaceutical originators not to abuse the patent system with anti-trust behaviour. But, there is also a call to politicians not to throw out the baby with the bath water. We do need patent protection for later improvements of already-marketed drugs; otherwise, no one would provide them, which would be detrimental to the patients. Yet, we also need to secure generic entry at a certain point of time, in order to have a balanced ecosystem that provides access to affordable medicines. The decision on how to secure such a balanced system should be determined according to competition law on a case-by-case basis. L

Asier_Relampagoestudio - Freepik.com

European Biotechnology | Spring Edition | Vol. 19 | 2020

The shortage of skilled labour is a serious obstacle to growth for businesses in many European countries. At the same time, in many places well-qualified people are looking for a job â&#x20AC;&#x201C; they might even want to work in another European country. Unfortunately, the labour markets in Europe are very diverse. How do I find a new job or a new employee? Now, there is an easy solution: eurobiotechjobs.net, the new, Europe-wide job market for biotechnology and the life sciences. Presented by the European Biotechnology Network.

Some selected case examples of product hopping

Company

Drug/Case

Year

Subject

â&#x20AC;ş Indivior Inc

Suboxane/ Case 2:16-cv05073

9/2017

Anti-competitive behaviour. Indivior simultaneously introduced a Suboxone film, removed its tablets from the market, and engaged in a marketing campaign to disparage Suboxone tablets in order to prevent competition from generic tablets.

â&#x20AC;ş Actavis plc

Namenda/ Case 14-4624

2015

In 2013, Actavis switched the marketing of its Alzheimerâ&#x20AC;&#x2122;s drug Namenda IR with high rebates to a new patent-protected formulation Namenda XR (soft switch). Briefly before it was due to lose patent protection, Actavis discontinued Namenda IR (hard switch), preventing patients from having another choice, rather than switching to Namenda XR.

â&#x20AC;ş AstraZeneca plc

Losec/ Case C-457/10 P

12/2012

Withdrawing Losec capsules in favour of new Losec tablets, AstraZeneca deregistered its marketing authorisation for Losec capsules in several EU Member States, excluding generic competition.

WĆ&#x152;Ĺ˝Ä?Ä&#x17E;Ć?Ć? ZÄ&#x17E;Ä&#x201A;Ä?Ć&#x161;Ĺ˝Ć&#x152;Ć? Ä¨Ĺ˝Ć&#x152; Ĺ&#x161;Ä&#x17E;ĹľĹ?Ć?Ć&#x161;Ć&#x152;Ç&#x2021;

ZÄ&#x17E;Ä&#x201A;Ä&#x161;Ç&#x2021;Í˛Ć&#x161;Ĺ˝Í˛ĆľĆ?Ä&#x17E; ZÄ&#x17E;Ä&#x201A;Ä?Ć&#x161;Ĺ˝Ć&#x152; ^Ç&#x2021;Ć?Ć&#x161;Ä&#x17E;ĹľĆ? Ä&#x201A;ĹśÄ&#x161; Ä?ĆľĆ?Ć&#x161;Ĺ˝ĹľĹ?Ç&#x152;Ä&#x17E;Ä&#x161; WĆ&#x152;Ĺ˝Ä?Ä&#x17E;Ć?Ć? ZÄ&#x17E;Ä&#x201A;Ä?Ć&#x161;Ĺ˝Ć&#x152;Ć? ÍžĎŻĎŹĎŹ ĹľĹŻ Ć&#x161;Ĺ˝ ĎĎŹĎŹ ĹŻÍż Ç&#x20AC;Ä&#x201A;Ĺ?ĹŻÄ&#x201A;Ä?ĹŻÄ&#x17E; Ä¨Ć&#x152;Ĺ˝Ĺľ ĆľĹśĹś >Ä&#x201A;Ä?Ĺ˝Ć&#x152;Ć&#x161;Ä&#x17E;Ä?Ĺ&#x161;ĹśĹ?ĹŹÍ&#x2014; Â&#x2021; :Ä&#x201A;Ä?ĹŹÄ&#x17E;Ć&#x161;Ä&#x17E;Ä&#x161; Ĺ˝Ć&#x152; ĆľĹśĹŠÄ&#x201A;Ä?ĹŹÄ&#x17E;Ć&#x161;Ä&#x17E;Ä&#x161; 'ĹŻÄ&#x201A;Ć?Ć? ZÄ&#x17E;Ä&#x201A;Ä?Ć&#x161;Ĺ?Ĺ˝Ĺś sÄ&#x17E;Ć?Ć?Ä&#x17E;ĹŻĆ?Í&#x2022; Ĺ?Ć&#x152;Ä?ĆľĹŻÄ&#x201A;Ć&#x161;Ĺ˝Ć&#x152;Ć? Ä&#x201A;ĹśÄ&#x161; ,Ä&#x17E;Ä&#x201A;Ć&#x161;Ĺ?ĹśĹ? DÄ&#x201A;ĹśĆ&#x161;ĹŻÄ&#x17E;Ć? Â&#x2021; &Ĺ?ĹŻĆ&#x161;Ä&#x17E;Ć&#x152; ZÄ&#x17E;Ä&#x201A;Ä?Ć&#x161;Ĺ˝Ć&#x152;Ć? Ä&#x201A;ĹśÄ&#x161; 'Ä&#x201A;Ć? ^Ä?Ć&#x152;ĆľÄ?Ä?Ä&#x17E;Ć&#x152;Ć? Â&#x2021; Ä?Ä?Ä&#x17E;Ć?Ć?Ĺ˝Ć&#x152;Ĺ?Ä&#x17E;Ć?Í&#x2014; Ä&#x17E;Ć?Ć&#x161;Ĺ?ĹŻĹŻÄ&#x201A;Ć&#x161;Ĺ?Ĺ˝Ĺś Ć&#x2030;Ć&#x2030;Ä&#x201A;Ć&#x152;Ä&#x201A;Ć&#x161;ĆľĆ?Í&#x2022; &ĆľĹśĹśÄ&#x17E;ĹŻĆ?Í&#x2022; Ä&#x161;Ä&#x201A;Ć&#x2030;Ć&#x161;Ä&#x17E;Ć&#x152;Ć?Í&#x2022; Wd& Ä&#x201A;ĹśÄ&#x161; 'ĹŻÄ&#x201A;Ć?Ć? ^Ć&#x161;Ĺ?Ć&#x152;Ć&#x152;Ä&#x17E;Ć&#x152;Í&#x2022; dÄ&#x17E;ĹľĆ&#x2030;Ä&#x17E;Ć&#x152;Ä&#x201A;Ć&#x161;ĆľĆ&#x152;Ä&#x17E; ^Ä&#x17E;ĹśĆ?Ĺ˝Ć&#x152;Ć? Ä&#x201A;ĹśÄ&#x161; DĹ˝ĹśĹ?Ć&#x161;Ĺ˝Ć&#x152;Ć? Â&#x2021; 'ĹŻÄ&#x201A;Ć?Ć? ZÄ&#x17E;Ä&#x201A;Ä?Ć&#x161;Ĺ˝Ć&#x152;Ć? Ç Ĺ?Ć&#x161;Ĺ&#x161; ^Ć&#x161;Ä&#x201A;Ĺ?ĹśĹŻÄ&#x17E;Ć?Ć? ^Ć&#x161;Ä&#x17E;Ä&#x17E;ĹŻ Ä?Ä?Ä&#x17E;Ć?Ć?Ĺ˝Ć&#x152;Ĺ?Ä&#x17E;Ć?

'XQQ /DERUWHFKQLN *PE+

7KHOHQEHUJ Ä ' $VEDFK 7HO LQIR#GXQQODE GH Ä ZZZ GXQQODE GH

9LVLW XV DW WKH &KHPVSHF (XURSH

Focus on Bioprocessing

European Biotechnology | Spring Edition | Vol. 19 | 2020

Growing market for viral vector biomanufacturing Antibiotic resistance With the coronavirus pandemic mounting, experts are already warning

of antimicrobial resistance as being the next, hidden crisis. The AMR community still urgently waits for substantial pull incentives. While the US DISARM act was pulled at the last minute from the country’s corona stimulus package, the UK’s NHS has started stakeholder engagement for its flat-rate model. Meanwhile, Forge Therapeutics has closed a €170m deal with Roche.

The market size for originator biologics, biosimilars, and cell and gene therapies in 2019 of about US$262bn is projected to grow $133bn until 2023 (CAGR of 9.1%), to $371bn. Accordingly, the market share of biologics to the total pharmaceutical market is expected to grow from currently 20% to more than 25% by 2023, a new report from London-based Results Healthcare states. The market for gene and cell therapies is small, and thus, the share of the viral vectors and plasmid DNA manufacturing market size stood at US$368.3m in revenues last year. However, by 2025, it is predicted to grow with a CAGR of 14.5% per year. Driven by market approval of ultra-expensive, advanced therapies, particularly gene and cell-based therapies, such as

Novartis’ US$2.1m per patient SMA gene therapy Zolgensma, new lucrative markets might materialise. Thus, contract manufacturing organisations, pharma developers, and service providers producing the required DNA plasmids, viral vectors, and transposons, are expanding their capabilities to benefit from this potential, additional business arm. Currently, around two-thirds of the research in gene therapy is focused on oncology. Furthermore, 350 million patients are diagnosed globally with a rare disease, another key area of interest in gene therapy.

Need for cost-efficienc While RNAi therapeutics delivery is currently the largest market segment

Global viral vectors & plasmid DNA manufacturing market share by disease in 2019 Others

Cancer

Infectious diseases

Genetic disorders

Source: www.grandviewresearch.com

Disease areas mostly affected by the current hype around gene and cell therapies

for viral vector producers, the approval of gene therapy products in US is fuelling the necessity for completely scalable, clinical-grade Good Manufacturing Practice (GMP) solutions to develop gene therapies for large patient groups who need high vector doses. In Q1/2019, 372 clinical trials were registered that involved vector-mediated gene therapy production. In 2019, the FDA announced the drafting of guidelines to facilitate clinical testing and market approval of ATMPs, as many gene therapies provide solutions for ultra-rare genetic diseases and help establish highly personalised treatments for stratified cancer patient populations. Vector manufacturers, such Belgian Univercells SA, know how complex and resource-intensive processes can be, which are needed for GMP-compliant ATMP-manufacturing. In mid-February, the company received a US$50m financing from KKR-subsidiary Gamma Biosciences for a highly-automated, virus production platform with a footprint of only 10 m2. According to the FDA, further progress is needed to improve batch reproducibility and quality assurance for vector production. While it’s not clear if gene therapies are a business case, in the future, gene and cell therapies might become a significant part of the current US$11.7bn contract development and manufacturing market for biologics, which is expected to grow with a CAGR of 13% by 2023. L t.gabrielczyk@biocom.eu

PASSION FOR PERFORMANCE

YOUR�WORLD-CLASS BIOPHARMACEUTICAL�CDMO •��Experts�in�cell�culture�bioprocess�development� and�manufacturing •��Family-owned�company,�globally�thinking�and� focusing�exclusively�on�our�clients‘�projects •��Biopharma� pioneer� with� commitment� to advanced�technology�and�innovation�leadership� •��E� xtensive�track�record,�40�years�of�experience� and�quality�made�in�Germany

YOUR�TRUSTED�PARTNER FROM�CONCEPT�TO�MARKET

INCREASED PRODUCT�VALUE •� Tailored�algorithm-based and� database-driven formulation�development •� Superior� stability� and� quality

Rentschler Biopharma SE Erwin-Rentschler-Str.�21�·�88471�Laupheim�·�Germany info@rentschler-biopharma.com�·�www.rentschler-biopharma.com

Focus on Bioprocessing

European Biotechnology | Spring Edition | Vol. 19 | 2020

Viral vector one-stop-shop for gene and cell therapy viral vectors Many CDMOs have taken actions to meet the growing demand of viral vector

development and manufacturing services for clinical trials, as well as for commercial scale production. While capacity is important, there are only a few companies who provide services across the entire supply and value chain. So, what should you expect when choosing a true one-stop-shop as a CDMO partner in the gene therapy space? › Dr. Knut Ringbom, CEO, Biovian Oy, Turku, Finland

Currently, global biopharmaceutical companies are facing increasing pressure to develop innovative drugs in faster time and at lower cost. Thus, partnering with a CDMO that offers a comprehensive range of services can be the best policy for the drug developers seeking increased efficiency. Many manufacturing organisations have adopted a phrase “one-stop-shop” to define their way to operate. However, a deeper look at the processes and operations may bring up some substantial differences between service providers, despite supposedly similar positioning. While there is no one-size-fits-all answer for gene therapy developers, a reflective, mutually transparent gap analysis is an important exercise between any developer

and manufacturer when looking for the right CDMO for their specific needs.

to clinical, to commercial GMP supply of plasmid DNA and viral vectors. Our new GMP production area includes 200 L scale, single-use bioreactors, which enable efficient manufacturing of viral vectors at a sufficiently large scale for more advanced clinical trials and support of commercial strategies. With this current facility extension, we will more than double our capacity in the production of adenovirus, AAV, and lentivirus, building on over a decade of experience in the viral vector field. A key part of the value chain is, of course, quality and regulatory support from expert teams. We are very proud to have four qualified persons who ensure that clients’ investigational, medicinal products are released smoothly for clinical trial use or for sale.

Benefits of a true one-stop-shop

Keeping an eye on the future

Biovian’s definition of a one-stop-shop, is to provide clients with services across the supply and value chain. This is facilitated by Biovian’s fully integrated infrastructure of resources and capabilities. Within the supply chain, we cover services all the way from GMP cell bank manufacture to aseptic fill and finish for final products. Further, labelling and warehousing of the drug products at −80°C can be provided within the comfort of our EMAcertified, FDA-inspected facility. When it comes to the value chain, Biovian fully covers the life cycle from pre-clinical,

To summarise, it is important to keep an eye on the future of the product from the very beginning of the project. When partnering with a qualified, dynamic one-stop-shop CDMO, like Biovian, that accompanies the entire supply chain and value chain, there is no need to change providers, which is often a time-consuming and costly hurdle. We eagerly look forward to Viral Vector-based gene therapy to step out of its niche, and we are ready to serve our new, current, and returning clients with Nordic consistency, reliability, and efficiency. L

Pictures: Biovian Oy

BROCHURE | ECHOÂŽ LIQUID HANDLERS

EchoÂŽ Liquid Handlers

www.la

THE FUTURE OF SCIENCE IS SOUND

In 2004, Labcyte revolutionized liquid handling by introducing the

Handler. Unlike traditional liquid handlers, the Echo system uses so

precisely transfer liquid without contact or using pipette tips, noz

Designed for diverse application in scientiďŹ c research, the EchoÂŽ L

combines the innovative technologies of Dynamic Fluid Analysisâ&#x201E;˘

Droplet Ejection to accurately and reliably transfer a wide range o

many scientiďŹ c disciplines including drug discovery, genomics, syn

and personalized medicine, Echo systems provide the following b

Improved data quality with lower risk of cross-contaminatio leachates when compared to use of pipette tips

Precise, low-volume liquid transfers to miniaturize assays, re costs, and conserve precious samples

High-throughput â&#x20AC;&#x153;any-well to any-wellâ&#x20AC;? transfers to rapidly highly complex, multi-component assays and experiments

EchoÂŽ 650 Series Liquid Handlers

Meet Today's Needs and Tomorrow's Vi EchoÂŽ 650 Series Liquid Handlers represent our most ďŹ&#x201A;exible line for high-throughput, acoustic transfer of samples and reagents in

low as 2.5 nanoliters (nL). EchoÂŽ 655T and 650T Liquid Handlers o

Echo 650 Series Acoustic Liquid Handlers Acoustic Sample Tubes

IMPACTING SCIENCE WITH SOUND

The Brooks Life Sciences FluidXâ&#x201E;˘ AcoustiXâ&#x201E;˘ Sample Tube transforms workďŹ&#x201A;ows by enabling acoustic dispensing directly from tubes. The AcoustiXâ&#x201E;˘ Tube

to transfer from acoustic sample tubes and process microplates a

throughput. EchoÂŽ 650 and 655 Liquid Handlers transfer from Ech

Microplates and can be upgraded to transfer from acoustic sampl

improved ďŹ&#x201A;uidics handling for simpler maintenance, better robotic

support for transfer from sample tubes, and quieter operation, the

Series builds on the long and successful history of Echo acoustic l technology.

MODEL

TRANSFER THROUGHPUT

SOURCE

EchoÂŽ 655T

High throughput

EchoÂŽ QualiďŹ ed Sample Tubes

EchoÂŽ 650T

Medium throughput

EchoÂŽ QualiďŹ ed Sample Tubes

EchoÂŽ 655

High throughput

EchoÂŽ QualiďŹ ed Microplates

EchoÂŽ 650

Medium throughput

EchoÂŽ QualiďŹ ed Microplates

preserves sample integrity by allowing samples to be accessed individually â&#x20AC;&#x201C; ideal for applications that require

&RQWDFW IUHH FRVW HIÂ´ FLHQW OLTXLG WUDQVIHUV DW QDQROLWHU UHVROXWLRQ subsets of large libraries to be accessed frequently.

IMPACTING SCIENCE WITH SOUND Â&#x2021; (OLPLQDWLRQ RI FRPSRXQG ORVV FURVV FRQWDPLQDWLRQ FDUU\RYHU RU OHDFKDWHV WKURXJK Contact-free, cost-efficient liquid transfers at nanoliter resolution non-contact transfer Â&#x2021; (QDEOHV WUDQVIHUV DV ORZ DV Q/ IURP ZHOO DQG ZHOO PLFURSODWHV Acoustic dispensing technology has revolutionized the transfer of liquids, enabling highÂ&#x2021; )OH[LELOLW\ WR WUDQVIHU DQ\ YROXPH RI OLTXLG IURP DQ\ VRXUFH ZHOO WR DQ\ GHVWLQDWLRQ ZHOO precision and contact-free liquid handling at nanoliter range for high throughput Â&#x2021; 7UDQVIHU IURP (FKR TXDOLÂ´ HG VDPSOH WXEHV DQG PLFURSODWHV applications. Due to tiny dispensing volumes (from 2.5 nl), assays can be miniaturized and thus reagent costs can be saved. The completely contact-free transfer of liquids 7KH (FKR SURYLGHV DFFXUDWH DQG SUHFLVH WUDQVIHU RI QDQROLWHU VFDOH TXDQWLWLHV HQDEOLQJ DVVD\ utilizing sound energy virtually eliminates F GLVFLSOLQHV LQFOXGLQJ GUXJ the risk of cross-contamination and thus PLQLDWXUL]DWLRQ IXUWKHU UHGXFLQJ FRVWV DFURVV PDQ\ VFLHQWLÂ´ improves the data quality of scientific results. Fast "any-well to any-well" transfers allow GLVFRYHU\ FRPSRXQG PDQDJHPHQW JHQRPLFV V\QWKHWLF ELRORJ\ SURWHRPLFV DQG PRUH highly complex, multi-component assays and experiments to be performed. For multidevice workflows, the Echo Liquid Handlers can be seamlessly integrated with Biomek Learn more: pipetting robots or Access robotic systems. Whether in drug discovery, compound beckman.com/liquid-handlers/echo-650-series management, genomics, synthetic biology, proteomics, functional screening or other * Available for tube-enabled models research applications, reliable scientific results can be achieved with Echo Acoustic Liquid (FKR 6HULHV $FRXVWLF /LTXLG +DQGOHUV DUH QRW LQWHQGHG IRU XVH LQ WKH GLDJQRVLV RI GLVHDVH RU RWKHU FRQGLWLRQV Handlers. Â&#x2039; %HFNPDQ &RXOWHU ,QF $OO ULJKWV UHVHUYHG %HFNPDQ &RXOWHU WKH VW\OL]HG ORJR DQG WKH %HFNPDQ &RXOWHU SURGXFW DQG VHUYLFH PDUNV PHQWLRQHG KHUHLQ DUH WUDGHPDUNV RU UHJLVWHUHG WUDGHPDUNV RI %HFNPDQ &RXOWHU ,QF LQ WKH 8QLWHG 6WDWHV DQG Learn more: https://www.beckman.com/liquid-handlers/echo-650-series RWKHU FRXQWULHV

)RU %HFNPDQ &RXOWHUÂV ZRUOGZLGH RIÂ´ FH ORFDWLRQV DQG SKRQH QXPEHUV SOHDVH YLVLW ÂŞ&RQWDFW 8VÂŤ DW beckman.com

Focus on Bioprocessing

European Biotechnology | Spring Edition | Vol. 19 | 2020

Radiant Precision Radionuclides High-Precision Radionuclide Therapy is a promising, new generation of

targeted molecular therapy in which the smallest amounts of medical radioactivity find their way through the bloodstream specifically to the tumour cells for diagnosis and treatment of cancer. › Dr Tamara Ćiković, ITM Isotopen Technologien München AG Since the time of Marie Curie, radiation research has been fundamental for the development of nuclear medicine. Furthermore, biomedical investigations on various tumour markers have contributed to the evolution of precision oncology, paving the way for Targeted Radionuclide Therapy. In contrast to radiotherapy, where radiation is applied from outside the body, Targeted Radionuclide Therapy is defined by the injection of a radiopharmaceutical, which precisely recognizes tumour cells. Radiopharmaceuticals consist of a medical radioisotope conjugated to a tumour-specific targeting molecule that binds specifically to a tumour antigen according to the lock-and-key principle. A very small amount of medical radiation is sufficient for this therapeutic approach.

Tumour

Due to the efficacy and specificity of Targeted Radionuclide Therapy, healthy tissue is minimally affected, and side effects are maximally reduced. In many cases, the targeting molecule can be used for both diagnosis and therapy, the only difference being their conjugated radioisotope. Radioisotopes with shorter half-lives are used for diagnosis, while therapeutic ones have slightly longer half-lives. The biotechnology and radiopharmaceutical group of companies ITM Isotopen Technologien München AG (ITM) develops, produces, and globally distributes a new generation of radio pharmaceuticals for Targeted Radionuclide Therapy. They have established a method to produce a highly pure, nocarrier-added (n.c.a.) Lutetium-177,

Targeting Molecule

Tumour Specific Receptor Radioisotope

Targeted Radionuclide Therapy uses radiopharmaceuticals, which are conjugates of a medical radioisotope and a tumour-specific targeting molecule, recognizing the tumour cell precisely according to the lock-and-key principle.

which does not contain impurities, with metas table, long-lived Lutetium-177m. This ensures economical waste management and environmental sustainability. Recently, ITM received the “German Medical Award” for their dedicated work in this field and the prestigious support of the European Investment Bank. ITM’s goal is to achieve a sustainable medical benefit with their therapeutic approach and to significantly improve the quality of life for cancer patients.

How to improve outcomes? “We are currently conducting the clinical phase III trial COMPETE, which is investigating the efficacy and safety of the radiopharmaceutical Solucin®,” says ITM’s CEO Steffen Schuster. Solucin® is comprised of a somatostatin analogue as the targeting molecule and ITM’s highly pure n.c.a. Lutetium-177 and is used for the treatment of somatostatin-positive neuroendocrine tumours (NET) of gastroenteropancreatic origin. NETs are rare diseases, thus exacting a high demand for effective therapies. “We are confident that COMPETE will confirm the promising results of our Phase II study and will give many NET patients the opportunity to benefit from this new generation of Targeted Radionuclide Therapy,” added Mr. Schuster. In addition to Solucin®, ITM is working on further product candidates for the diagnosis and therapy of bone metastases and other cancer indications, thereby actively shaping the progress of radiopharmaceutical research and development – a “radiant” contribution to treating cancer. L

Picture: ITM Isotopen Technologien München AG

Contract Development and Manufacturing of Biopharmaceuticals

Biovian has 17 years of experience in biopharmaceutical GMP-production and a solid track record in tailored services from early development to finished vial.

ONE-STOP-SHOP Virus production for gene therapy and vaccines Microbial production of recombinant proteins and plasmid DNA Process development Formulation Fill & Finish Analytical quality control Cell and virus bank preparation

www.biovian.com

Focus on Bioprocessing

European Biotechnology | Spring Edition | Vol. 19 | 2020

Phages as a promising alternative to antibiotics Phagomed The Vienna-based biotech company Phagomed wants to establish therapies with

phages – viruses that infect bacteria – as an alternative to antibiotics. For 2020, a Series A financing round is planned to proceed with the three drug programs. Currently, the start-up is focusing particularly on advancing a new treatment for Bacterial Vaginosis (BV), based on phage lysins. The highlight of this approach: They target the pathogenic bacteria without harming the rest of the microbiome.

Since its foundation in November 2017, Austrian Phagomed has specialised in developing phage-based drug candidates for the treatment of severe bacterial infections in humans. “Phages and endolysins offer effective alternatives to antibiotics blunted by bacterial resistance, and they work very precisely without destroying the natural microbiome. What’s more, they can combat bacteria in impenetrable biofilms, where antibiotics are ineffective independent of resistances,” explains PhagoMed’s co-founder and co-CEO, Lorenzo Corsini. Currently, the company has three active development programs in the fields of implant associated infections, urinary tract infections, and Bacterial Vaginosis (BV). In Autumn 2019, the BV candidate was added to the pipeline. PhagoMed

has isolated Gardnerella-specific phage lysins based on the company’s phage biology platform, optimised them by genetic engineering, and filed a patent application for this class of recombinant endolysins.

More precise BV treatments are urgently needed For Corsini, BV is an attractive indication, because it affects between 10% and 30% of women worldwide, making it not only the most frequent vaginal infection with a more than 50% recurrence rate, but also one of the top reasons for antibiotic prescriptions and antibiotic resistance. Werner Mendling, a professor and gynaecologist at the German Center for Infections in Gynecology and Obstetrics in Wuppertal, Ger-

Phagomed has a team of 15 scientists focusing on its three programs, 11 of which work at the Campus Vienna Biocenter in Vienna, Austria.

many, is convinced that new treatments are urgently needed. “Millions of women suffer from recurrent BV – despite the widespread use of antibiotics. We need to find more precise solutions for combating the biofilm that forms on the vaginal epithelial cells,” he says. To advance the program, in late 2019, Phagomed received a €1m grant from the Austrian Research Promotion Agency. In addition, the company has set up a new development team for BV, which is cooperating with vaginal microbiome specialists at Ghent University, and has recruited the previous Head of Pre-Clinical development at Austrian Affiris AG, Christine Landlinger-Schubert, as the director of the lysin program. According to Corsini, “phage lysins are able to specifically target Gardnerella without harming the microbiome, and they are able to attack resistant bacteria, making them prime candidates to treat BV.“ Mendling also believes that such a strategy could be a promising approach: “Next generation BV therapies should combine precision with efficacy. Killing facultatively pathogenic bacteria, such as Gardnerella spp., while preserving the vaginal microbiome could become the new gold standard for BV therapy.” For 2020, the company seeks further capital to proceed into the clinical phase over the next two years in its lead programs. So far, Phagomed has raised more than €6.5m in private funding and public grants. “Now, we are raising a larger Series A,” says Corsini. L s.wirsching@biocom.eu

Picture: Phagomed

PRECISELY FOR ME. Dedicated to giving cancer patients better answers than “maybe”.

Developing Targeted Radionuclide Therapies in Precision Oncology. www.itm.ag

Focus on Bioprocessing

European Biotechnology | Spring Edition | Vol. 19 | 2020

Corporations are boosting packaging innovation Sustainable innovation In March, food and beverage companies signed on to the European

Plastic Pact and pledged to increased support for innovation. Earlier this year, food giant Nestlé announced that it will invest up to two billion CHF to lead the shift from virgin plastics to foodgrade, recycled plastics and to accelerate the development of innovative, sustainable packaging solutions. French water brand Perrier, part of Nestlé, announced the support of three start-ups within the Next Packaging Movement.

The European Plastics Pact is a publicprivate coalition that aims to accelerate the move towards a circular economy for plastic packaging in Europe. Launched in March in Brussels, 15 governments and 66 companies have signed on to the pact, including large food and beverage companies such as Unilever and Nestlé. This is also the first regional pact to join the Ellen MacArthur Foundation’s global Plastics Pact network. The pact was initiated by the French Ministry of the Ecological and Solidarity Transition, the Dutch Ministry of Infrastructure and Water Management, and the Danish Ministry of Environment and Food, in consultation with more than 80 organisations from across Europe. Its members will cooperate across the value chain on a Eu-

ropean scale to boost the development of smarter techniques and approaches, harmonise guidelines, standards, and national supporting frameworks, and connect to share best practices and lessons learned across Europe.

Sustainable packaging fund will invest CHF 250 million In addition, many food companies that have signed the pact have set themselves further sustainability commitments. Many of these goals include increased availability of products that come in sustainable packaging. Marco Settembri, Nestlé CEO for Europe, Middle East, and North Africa said: “We are pleased to sign the European Pact. One of our joint objec-

tives is to create a circular economy by improving collection, sorting, and recycling schemes across Europe.” Building on its 2018 commitment to make 100% of its packaging recyclable or reusable by 2025, Nestlé already announced in January its aim to reduce its use of virgin plastics by one third in the same period. Thus, to create a market, Nestlé is committed to sourcing up to two million metric tons of food-grade recycled plastics, allocating more than CHF1.5bn to pay a premium for these materials between now and 2025. In addition to its in-house research through the Nestlé Institute of Packaging Sciences, the company launched a CHF250m sustainable packaging venture fund to invest in startup companies that focus on these areas. Some brands within the Nestlé group also launched their own initiatives, such as Perrier with its Next Packaging Movement. Through this programme, Perrier will invest in three startups: Biotic, Flexikeg, and PlastiSkul. The startups were selected from among 90 submissions, following an application process launched in April 2019, which evaluated key factors, such as the breakthrough dimension of the proposed solutions, potential environmental and social benefits, and the ability to scale across the sparkling water market and the broader beverage industry. The three winning startups will receive technical, operational, and financial support to help bring their solutions to market by 2025. L s.wirsching@biocom.de

Picture: Nestlé

Advertorial

European Biotechnology | Spring Edition | Vol. 19 | 2020

Human iPSC-derived glutamatergic neurons Cell production Widespread use of human-induced, pluripotent stem cell (hiPSC)-derived,

mature cell types is restricted by complex differentiation protocols and inefficient reprogramming methods. By applying a novel gene engineering approach, opti-ox™, to cellular reprogramming, these restrictions have been largely overcome. This proprietary technology enables precise reprogramming and homogeneous differentiation of entire stem cell cultures into any desired cell type.

Opti-ox1 (optimised inducible overexpression) cellular reprogramming enables tightly controlled and homogenous expression of selected transcription factors. The result is the consistent manufacturing of homogenous and mature hiPSC-derived functional cells within days, offering access to the highest quality of cellular models with simple protocols. Glutamatergic neurons (ioNEURONS/glut) are derived from hiPSCs through Neurogenin-2 (NGN2)driven opti-ox reprogramming. Human stem cells rapidly convert into functional neurons, providing a reliable model for the study of neurologi-

cal activity and a robust platform to advance CNS drug discovery programs in a relevant human cell type.

are compatible with plates ranging from 6 to 384 wells and validated for HTRF® and CellTiter-Glo® assays.

Reliability

Ease of Use

IoNEURONS/glut are well characterized and defined, consisting mainly of glutamatergic neurons (more than 80%). The minor remaining fraction of neuronal cells express marker genes of cholinergic neurons. Cells have a rostral CNS (central nervous system) identity and express the classic cortical marker genes FOXG1 and TBR1. These cells form functional neural networks, and spontaneous activity is observed after three weeks of differentiation when cultured in BrainPhys™ neuronal medium.

Speed and Scalability

Cells arrive programmed to rapidly mature upon revival with only one medium required in a two-step protocol. Employing a combination of screening and machine learning, Bit Bio has developed a high-throughput discovery platform to identify optimal transcription factor combinations for the direct reprogramming of target cell types. By applying opti-ox, Bit Bio achieves controlled and unprecedented homogenous expression of identified transcription factors in all stem cells. Bit Bio aims to solve some of the most pressing challenges facing medicine through democratising access to consistent and functional human cells. This will improve research and drug discovery, as well as lower the cost and extend the application of cell therapies. Our range is constantly expanding, and human induced skeletal myocytes, the ioMYOCYTES/ skeletal, will launch in Q2/2020.

The cells are ready for experimentation as early as two days post revival and form functional neuronal networks at 17 days. Industrial-scale quantities allow the cells to be utilised in a range of applications, from research to screening purposes. Cells

Contact Bit Bio Discovery Drive Cambridge Biomedical Campus Cambridge | CB2 0AX | UK info@bit.bio www.bit.bio

Consistency

Picture: Bit Bio

Batch-to-batch reproducibility and homogeneity create a stable, human model for excitatory neuronal activity and disease.

Immunofluorescent staining on post-revival day 11 demonstrates homogenous expression of panneuronal proteins (MAP2 and TUBB3) and glutamatergic neuron-specific transporters (VGLUT1 and VGLUT2). Cells exhibit neurite outgrowth.

World class services from target ID

ŕ¤°

European Biotechnology | Spring Edition | Vol. 19 | 2020

Monitoring of cell culture

Nanolitre dispensing

Process control Nova Biomedical’s

Pictures: Nova Biomedical Switzerland/Beckman Coulter

BioProfile® Prime analyser provides simplicity in cell culture monitoring. BioProfile Prime features maintenance-free M icroSensor Card technology, Snapin cartridge system, and automated, onboard, liquid QC. This design optimises cartridge life, improves analyser uptime, and eliminates the waste, downtime, and higher costs of older, combined calibrator/ sensor cartridge systems – providing exceptional value in a cell culture analyser. BioProfile Prime delivers a nine-test profile of key gases and chemistries in only 60 seconds. The test menu includes pH, pCO2, pO2, Na+, K+, Cl-, Ca++, glucose, and lactate. Onboard QC cartridges perform quality control automatically, saving time and labour. For more demanding applications, our full-featured BioProfile FLEX2 analyser provides 16 key cell culture parameters, including chemistries and gases, cell density, cell viability, cell diameter, and osmolality.

The The Host HostCell CellProtein Protein Specialist Specialist Track TrackYour YourProcessProcessRelated RelatedImpurities Impurities •• Generic GenericHCP HCPELISA ELISAkits kits

(CHO (CHOand andE.coli) E.coli) •• Custom CustomHCP HCPAssays Assays Liquid Handler The acoustic dispens-

ing technology of the Echo-Series Liquid Handlers has revolutionised the transfer of liquids. It enables high-precision and contact-free liquid handling at nanolitre range for high throughput applications (sample processing in 384, 1,536, or 3,456 well plates). Due to tiny dispensing volumes (from 2.5 nl), assays can be miniaturised, and thus, reagent costs can be saved. The completely contact-free transfer of liquids utilising sound energy virtually eliminates the risk of cross-contamination and, thus, improves the data quality of scientific results. Fast “any-well to any-well” transfers allow highly complex, multi-component assays and experiments to be performed. For multi-device workflows, the Echo Liquid Handlers can be seamlessly integrated with Biomek pipetting robots or Access robotic systems. Whether in drug discovery, compound management, genomics, synthetic biology, proteomics, functional screening, or other research applications, reliable scientific results can be achieved with Echo Acoustic Liquid Handlers.

(specific (specificororplatform) platform) •• 2D 2DWestern WesternBlot Blot&&

Coverage CoverageAnalysis Analysis •• 2D 2DDIGE DIGEAnalysis Analysis&&IAC IAC

Also Alsoavailable: available:PerforPerformance manceStudy Studytotoidentify identify the themost mostsuitable suitablekitkit

Contact

Nova Biomedical Switzerland GmbH Turmstraße 18 CH-6312 Steinhausen Phone: +41 41 521 66 55 ch-info@novabio.com www.novabiomedical.com

Contact

Beckman Coulter Eurocentre S.A. 22, rue Juste-Olivier CH-1260 Nyon lsreurope@beckman.com www.beckman.com/liquid-handlers

BioGenes BioGenesGmbH GmbH· ·www.biogenes.de www.biogenes.de

Mosa Meat hamburgers are made with cultured cells.

Food

European Biotechnology | Spring Edition | Vol. 19 | 2020

Upscaling in the race to culture meat Novel Foods The concept of meat grown in the lab is gaining momentum. Firms in the field

attract financing rounds worth millions, and are also teaming up with biopharma companies and manufacturers to accelerate industrial scale-up. A first wave of companies is pushing the envelope, with US-based Memphis Meat among the leaders. European start-ups like Mosa Meat or Peace of Meat are farther back in the pack. They aim to have production up and running by 2022.

Pictures: Mosa Meat

he goals are ambitious. “The vision we want to offer is delicious meat with a global impact on sustainability at a very competitive price for mass consumers,” Maarten Bosch says. He’s the CEO of Mosa Meat, one of the frontrunners in the cultured meat space. When the Dutch company presented the world’s first hamburger made from cultured cells back in 2013, the scientists were taking the first steps on a long journey filled with technological challenges to cultivate meat from a biopsy. Back then, the hamburger that made headlines cost €250,000. Most of the work was financed by Google co-founder Sergey Brin. Since then, the Netherlands-based company has grown. It now employs over 40 staff, and is in the process of moving into a new facility outside the university labs it has occupied until now. In late December, the company reached another major milestone when it published a new method for creating serum-free media for the growth of primary bovine myoblasts. “Instead of using pricy fetal bovine serum, which is actually drawn from fetal calves, we have developed a plant-based replacement that performs as well as serum-derived medium to grow the meat cells,” Bosch told European Biotechnology. Currently the company is preparing to transform its lab-proven process of cell differentiation

and tissue formation into large-scale settings. “Some parts of the process have been done already at a large scale, some haven’t. We’re able to make a few hamburgers, but we need to make millions or billions of hamburgers,” Bosch says. “It’s now about producing large volumes and bringing down costs. We can

Maarten Bosch CEO of Mosa Meat (Maastricht, The Netherlands)

? !

ould you briefly explain your C current action plans and your next steps and goals?

It’s now about producing large volumes and bringing down costs. We can do it, but we have to prove it. The ambitious goal is to have our pilot plant operational in 2021, and to start the first industrial production line in 2022.

do it, but we have to prove it. And we will need to create a complete new value chain and ecosystem.” The CEO knows his firm will need strong partners to be as quick as possible. Merck’s investment arm, M Ventures, is already supporting Mosa Meat, as is Swiss meat producer Bell Food Group. In a next step, the company is focusing on setting up a first pilot plant, and is pursuing a new major financing round. “The goal is to have the pilot plant operational in 2021, and to start the first industrial production line in 2022,” outlines Bosch. In January, the company announced a new strategic partnership with animal nutrition company Nutreco, which will help provide a large-scale version of the nutrient-filled medium used to grow the meat. Nutreco also pledged an undisclosed amount of funding to Mosa Meat, as did climate-minded investment firm Lowercarbon Capital. During the course of the year, Bosch hopes to attract further partners able to provide support with capital and/or strategic knowledge. “We see a lot of interest in this space, but we will be selectively looking for those who provide a strategic fit to our plans,” the CEO explains. One aspect of the firm’s strategy is to remain as European as possible, and initially launch in the EU, although Bosch is aware that regions like the US and Asia may have more potent investors and promise as a growing market for alternative meat in the long run. “In the

Food

European Biotechnology | Spring Edition | Vol. 19 | 2020

Global meat consumption is on the rise overall, but by 2040, the consumption of conventional meat should actually fall considerably

+3%

in bn USD 1,400 1,200 1 10%

90%

2025

10% 18%

72%

2030

Growth rate per year 2025–2040

1,800 1,600 22% 23%

55%

2035

35%

cultured meat

25%

vegan meat alternatives

+9%

40%

conventional meat

–3%

+41%

2040

Numbers are rounded to $100 billion Sources: United Nations, World Bank, Expert interviews, A.T. Kearney Analysis 1

end, we want to make a global impact,” he says. Competitors in the field are on track as well, particularly in the US. In January, Silicon Valley start-up Memphis Meat announced the close of a US$161m Series B funding round – the largest ever in a cell-based meat company. It was led by SoftBank Group, Norwest and Temasek. Also joining the round are new and existing investors, including billionaires Bill Gates and Richard Branson, celebrities like Kimbal Musk, and conventional meat producers Cargill andTyson Foods. Memphis Meats wants to use the new funds to build a pilot production facility, continue to grow its team, and launch new products. Three years have passed since the firm served its first lab-grown breaded chicken strips to eager tastetesters in San Francisco. Even though the California-based company hasn’t made many headlines since then, a lot has been happening behind the scenes. The five-year-old high-tech meat-maker also claims to have developed a production method that doesn’t require fetal bovine serum. It has yet to announce a date to launch a product commercially, but has confirmed it’s working with regulatory agencies to ensure timely and safe market entries. Last August, Memphis Meat was among a group of other start-ups like JUST Inc., Finless Foods, BlueNalu, and Fork & Goode that announced the formation of the Alliance

for Meat, Poultry & Seafood Innovation (AMPS Innovation), a coalition seeking to work with government regulators to create a pathway to market for cultured meat and seafood. “We are committed to an open and science-based dialogue with all stakeholders, including industry partners, policymakers, advocates and consumers,” the CEOs of all five startups stated in a press release. “As we look ahead to the imminent challenges of feeding a growing population, AMPS Innovation is dedicated to working together, in partnership with the broader agricultural community, to advance solutions to address these needs.”

Still not a clear regulatory pathway in the US At the moment, regulatory guidelines for cell-based manufactured animal products are still pretty fuzzy. Last year, the FDA and USDA agreed to regulate cultured meat jointly, with the FDA overseeing animal cell collection and initial cell growth and the USDA in charge of largescale production labeling. But it’s still unclear at exactly what point in the process that handoff will take place, and there’s no timeline about when the governmental bodies will actually approve cultured meat for sale. AMPS Innovation clearly understands that to gain regulatory approval, they’ll have to fight not just sceptical regulatory bodies, but also tradition-

al animal agriculture companies that have large amounts of cash and governmental support. The AMPS webpage says terms like “meat / poultry / seafood” or “meat / poultry / seafood products” are also applicable to cell-based equivalents to traditional sources, since they are derived from animals and real animal tissue.

The discussion on labeling has only just begun One of the biggest open questions is not related to science or manufacturing processes, but to another important aspect involving market access. What do you name products to allay consumer fear or confusion? ‘Cultured meat’ may sound fine to the ears of people who speak English as their native language, but the high diversity of national markets and languages in Europe make naming products problematic. “We will analyse different types of labelings, and have not yet found the ideal description,” says Mosa Meat CEO Bosch. That’s why one of the biggest challenges facing upcoming market entries is educating consumers on the processes behind the products, and finding labels for them that are suitable and also sound good. From an EU regulatory perspective, any food that was not consumed to a significant extent in the bloc before 1997 is a so-called ‘novel food’, and hence falls under the Novel Food Regulation. Valid since the beginning of 2018, the regulation’s approval process is complex and expensive. Another challenge is requirements that will be tough for cell-based companies to meet. “For instance, you need to have your product tested in labs in a thorough process to prove it’s safe and healthy. But this is accompanied by a request that the company provide 10kg of material, which is to date very expensive if you don’t have large-scale production ready,” Bosch explains. “It’s obvious, that if this (rule) is applied to the cellbased meat space as well, all approval-related processes would be extremely delayed.” But according to Bosch, European regulators are open to thinking about a more feasible approach. Be-

European Biotechnology | Spring Edition | Vol. 19 | 2020

cause the whole process is new, however, nothing happens fast. Another hurdle in Europe is that you can only start the approvals process with EFSA if your product is completely defined with regard to production processes. “This puts us in a challenging position, as we know already that our manufacturing process will still change in some details over the upcoming two years. We are currently figuring out how this can work to not delay everything too long,” Bosch explains. Could a European coalition of cell-based companies help advocate jointly, as AMPS is doing with the FDA in the US? Maybe, says Bosch, but so far no such alliance is on the horizon, as most companies are focused narrrowly on their individual dossiers. “In the end, we all have

our own and different way of producing meat in the lab, which results in individual discussions at the regulatory level,” he says. When it comes to public awareness, on the other hand, linking up with others appears more likely to happen in 2020 and the immediate future. In January, Mosa Meat partnered with German manufacturing company Merck to hold an event in Berlin near the German Parliament. It’s aim was to get the topic of cell-based meat on the radar of German delegates and ministry employees, and push the message that Europe should not lag behind by instituting approval processes that are too lengthy or complicated. “We are committed to our roots. That’s why we are focus-

Food

ing on Europe to enter the market first. But our goal is to be a global player,” says Bosch. The decision on where exactly to launch products will then also be partly driven by the question of who is investing, and in which areas a product could reach first market entries. Although companies are investigating how to bring down manufacturing costs, it’s very clear that – at the beginning at least – cultured meat will be pretty pricy. But Bosch and his peers are confident scaling up will lower costsin the long-term. “We will be comparable with conventional meat, and then even significantly cheaper, because we are more efficient than a cow. It will all depend on manufacturing and efficient bioreactor design. That’s why we’re keen to build our

Accelerate food transformation New Food conference ProVeg International promotes alternative pro-

tein solutions and supports start-ups. European Biotechnology spoke with its head Albrecht Wolfmeyer about current activities and the next event. EuroBiotech_ProVeg’s history dates back to the 19 th century, and it’s become an international food awareness organisation that is active globally. How do you perceive the state of the alternative protein market today? Wolfmeyer_The trend is strong and sus-

Picture: Proveg International

tainable. Today it’s easier than ever for consumers to choose delicious plantbased products. It’s not only young visionaries creating innovative and novel foods. We keep seeing well-established brands expanding their portfolios towards more plant-based options. Whether it’s producers, retailers or food services, all stakeholders along the value chain have recognised a change in consumer preferences, and investments have seen a steep rise. The race is on. EuroBiotech_What are your next steps and goals with regard to supporting startups in this field? Wolfmeyer_ Since the launch of our Incu-

bator in 2018, we have supported more than 30 start-ups from over 15 countries. In April, we will onboard our fourth cohort of start-ups. Due to the corona crisis, we will offer a full-fledged remote programme, with modules like fundraising, branding and product development. For the first time, all accepted start-ups will receive a €20,000 grant to boost their business, with the potential for a further €30,000–€180,000 in investment after completing the programme. Guests at the New Food Conference in Berlin can get to know our most promising start-ups. EuroBiotech_What is the aim of the New Food Conference that’s slated to be held from 5–6 August in Berlin? Wolfmeyer_The conference will focus on

the latest developments in the plantbased and cultivated protein sector. It brings together scientists, start-ups, investors, entrepreneurs and companies working in the field. They will present the lat-

Albrecht Wolfmeyer heads the ProVeg Incubator that was launched in Berlin in 2018. It’s the first global incubator to exclusively support start-ups that are replacing animal-based foods.

est cutting-edge cell-based meat research, best practices, and expertise from the plant-based sector. The conference has a highly interactive atmosphere that allows participants to connect with leading stakeholders. There is a huge demand for that kind of event. Its first edition in 2019 was sold out rapidly, that’s why we have expanded its format. We’re expecting 400 attendees this year. L

Food

own process know-how and techniques, starting with a pilot plant and then scaling up,” Bosch says. He and many other stakeholders in the field believe this is now only a matter of time. And unlike other sectors where reaching markets first can really matter, speed seems less relevant for cultured meat, as market shares and consumer demand are expected to be high enough for some time to come to allow for a range of producers. “The reality is that conventional production methods for meat can’t keep up with global demand, which is expected to double by 2050. Cell-based meat addresses this issue while offering enormous potential to improve the environment and have a positive impact on food safety and animal welfare,” comments Priti Youssef Choksi, a partner at Norwest Venture Partners, one of Memphis Meat’s backers. After all, there is also growing interest among companies with production expertise to get involved in the market. Merck, Novozymes, DSM and others are expressing a lot of interest. At events such as the yearly “European Forum on Industrial Biotechnology and Bioeconomy (EFIB) which took place in Brussels in 2019 and will this year be held in Frankfurt (see p. 62), it’s clear that a lot of participants want to secure a piece of the pie in the attractive market.

“There is growing interest among biomanufacturers such as DSM, Novozymes or Merck to get involved in the market.” Food experts from the Startlife Incubator at the University of Wageningen and the Berlin-based food organisation ProVeg International recommended cooperating strategically with manufacturers. “It will be possible to reduce the consumption of animal meat by 50% by 2040 through attractive biotechnical innovations, but then scaling up production is crucial,” ProVeg Incubator head Albrecht Wolfmeyer said in Brussels. However, as Cornelia Habacher from Rebel Meat

European Biotechnology | Spring Edition | Vol. 19 | 2020

GmbH stated at the event, companies will have to find their own individual strategies. The Austrian start-up is betting on hybrid technology and the right mix of meat and plant products. It already supplies a dozen restaurants in Vienna. “We only want to work with natural ingredients, not use any additives, and establish ourselves in the market as quickly as possible,” Habacher says. “The right mix is our secret.” The Rebel Meat patty is still made from 50% organic beef sourced in Austria. But the company is planning to replace that with cultured meat as soon as larger-scale cell culture technologies are in place. “We wanted to get established in the market, and not have to wait so long for all the scaling problems to be solved by cultured meat.”

Chinese investors actively investing in the space Many experts who presented at the EFIB 2019 were convinced that biotechnology would be part of the solution. “Without upstream innovations, we cannot expect products at the end of the value chain. Biotechnology is an essential driver in which we want to invest,” said EFIB panelist Joseph Zhou from Chinese food tech investor Bits x Bites. In Brussels, he provided his insights on what’s happening

in Asia: “China is facing a major upheaval in the food sector, and we will actively invest in technologies that we consider promising for the Chinese market.” For Zhou, the EFIB was a good scouting platform for new technologies. Chinese investors have already sunk funding into some companies – among them British genome editing specialist Tropic Biosciences Ltd. and Israel’s cell-based meat company Future Meat Technologies. Incubators like that organised by ProVeg International are also now moving beyond just advising companies and into investing in them and holding their own conferences on the topic. “New technologies can go a long way towards addressing the urgent challenges of the global food system in terms of climate change, environmental destruction, antibiotic resistance and public health. The future of protein is plantbased and – in the longer run – cultivated,” comments Wolfmeyer. (see interview p. 49) Large financing rounds like those seen in the US, along with growing investment commitments from accelerators all over the globe, are also making cultured meat producers confident that the capital needed to finance costly large-scale production facilities will be available in the coming years. In Europe, apart from Mosa Meat, many other companies are also working

Regulatory pathway still open As of now, the regulatory pathway for cell-based animal products is still pretty open in several regions of the world. Last year, the FDA and USDA agreed that they would jointly regulate cultured meat for the US market. The FDA will oversee animal cell collection and initial cell growth, while the USDA will be in charge of large-scale production and labeling. However, it’s still unclear at exactly what point that handoff will take place, and there’s no timeline about when the governmental bodies will actually approve cultured meat for sale. In Europe, cell-based meat is covered by

the Novel Food Regulation, which involves a pre-market approval process in which the EFSA body is participating as acting regulatory body. Companies have criticised that some requirements should be adapted to the specifics of cultured meat. In addition, labeling questions still need to be discussed. Some Asian jurisdictions, among them Hong Kong, Singapore and Japan, also offer promising pathways to market. Singapore, for instance, is currently looking into developing a comprehensive regulatory framework to govern novel food production for human consumption in the country.

BIO 2020, SAN DIEGO Panel: Product Hopping, Evergreening, Patent Thickets â&#x20AC;&#x201C; A story of Sharply Diverging Views â&#x2020;&#x2019; June 8th, 2:30 PM | Moderated by Ute Kilger

SCIENTIST & LAWYER

Food

European Biotechnology | Spring Edition | Vol. 19 | 2020

In early March, Peace of Meat founders Dirk von Heinrichshorst, Eva Sommer and David Brandes together with cook Christian Heinenbruch invited journalists and food experts to try out chicken nuggets made with cultured fat at a tasting event in Berlin.

hard to bring cultured meat into this next phase. Headed by CEO Krijn de Nood, Dutch company Meatable reported in September 2018 that it had succeeded in culturing beef from pluripotent stem cells taken from the animals’ umbilical cords. Other companies have relied on fetal bovine serum or Chinese hamster ovaries to stimulate cell division and production, but Meatable says it has developed a process where it can sample tissue from an animal, revert that tissue to a pluripotent stem cell, then culture that cell sample into muscle and fat to produce meat products. In December 2019, the firm announced a US$10m financing round to help it pivot from beef to pork production as the African swine fever epidemic ravaged a quarter of the world’s herds. A quite similar but GMO-free technological approach is being taken by Peace of Meat. The Belgian company was founded in 2019 by German biologist and former McKinsey Manager and MigrosManager David Brandes, Belgian partner Dirk von Heinrichshorst and Austrian biotechnologist Eva Sommer, who previously worked with Israel-based Super Meat. Compared to competitiors, Peace of Meat is pursuing a much stronger B2B approach. Its aim is to establish itself as a

provider of cultured fat made from duck embryonic stem cells: “We can generate as much fat as we want out of one cell line.” Brandes explained the advantages of the firm’s approach at a Berlin event in early March, when the company publicly presented its first proof-of-concept in Europe – three chicken nuggets containing 20% cultivated fat and 80% plant-based ingredients (see image above).

Peace of Meat with B2B approach as a new provider of cultured fat With support from several partners, the biotech start-up is now focusing on designing the optimal cell line and production process. The partners include – among others – the KU Leuven, the Bio Base Europe Pilot Plant in Ghent and Flanders Food, the Flemish food industry’s innovation center. The project’s experts include not just researchers and technicians in bioprocessing and food technology, but also ones from the field of medical tissue engineering. In December, the company and its partners also received a €3.6m research grant from the Flemish Innovation Ministry to develop an animal-free foie gras in the Foieture project. The long-term aim is to develop proprietary bioreactor hardware.

“We have to reach high-volume production at an affordable price to produce cultivated fat and serve B2B customers in the food market,” says Brandes. His business plans call for building up to a minimum 100,000 tons in production volume annually over the next ten years. According to Brandes, the fat market could be worth up to €9bn a year, and working in it opens up many cooperation opportunities with a wide range of customers. They could be other companies culturing meat, but also firms that make plant-based alternatives that want to add cultured fat as an ingredient for taste reasons. “There’s a lot of interest in the food sector from meat producers,” Brandes reports, “but also from those with vegan products.” He says cultured meat and plant-based approaches aren’t really in direct competition with one another. “To the contrary, we believe the future could see them merging more.” If it does, his company will be in a good position to profit. It wants to start selling B2B clients cultivated fat in 2021. The next aim would then be 2023 regulatory approval of largescale sale of Peace of Meat cultured fat at under €5.5/kg. To meet that goal fundraising has started now. L s.wirsching@biocom.de

Pictures: BIOCOM

Euroâ&#x20AC;&#x2030;BioFairs Compass 1 st Edition 2020

II G uide to Life Sciences Events

SPECIAL

European Biotechnology | Spring Edition | Vol. 19 | 2020

Euro Biofairs Compass

Delays across Europe EuroBiofairs Compass The COVID-19 pandemic has particularly challenged the event sector. Personal

Picture: ASCO; viperagp/stock.adobe.com (page 35)

networking in times of high infection risk seemed impossible for managers, scientists, and business developers. While some must-attend events were cancelled, other faced delays, but some chose a new way: digital partnering. Euro Biofair’s Compass will help you navigate the EU meeting jungle in H2/2020.

Financially, the COVID-19 outbreak and the resulting limitations in international travel seemed catastrophic for the organisers of life sciences events. At the time when COVID-19 began to expand globally and political preparedness was low, even established partnering meetings such as euroPLX 72 (9 – 10 March, 2020, Berlin) were not just postponed but cancelled. “The COVID-19 situation is far from conclusive, and ministries and health authorities are no big help with vague and contradictor y recommendations. It has been really a tough choice to cancel euroPLX 72 Berlin, but the wellbeing of our customers outweighs everything else, and this is our measure,” said Dr Norbert Rau, Managing Director of the organising RauCon GmbH & Co. KG. The meeting’s 400+ registrants, however, were offered a transfer of their registration to a forthcoming euroPLX or asiaPLX conference.

Meetings scheduled for early summer, such as Chemspec Europe (see page 66), the AMR Conference – Novel Antimicrobials & AMR Diagnostics (see page 56), BIOspain 2020, or the Swiss Biotech Day (see page 58) were postponed, to take place after the predicted peak of the global pandemic in early summer.

Wait or go digital Global biopharma meetings, such as the BIO International Convention 2020 (8 – 11 June, San Diego) but also important events scheduled for autumn 2020, were still in a waiting position as this issue went to press, including the EFIB 2020 (5 – 6 October, Frankfurt/M., page 60), CPhI Worldwide 2020 (13 – 15 October, Milan), BioJapan 2020 (14 – 16 October, page 62), and BioFit 2020 (1 – 2 December, Strasbourg, page 68).At the end

of March, however, the EBD Group pioneered a completely new approach to partnering: instead of postponing its BIO-Europe Spring 2020, originally scheduled to take place from 23 – 26 March in COVID-19 hard-hit Paris, they offered their event in a digital format (see exclusive report on p. 70). CEOs who were annoyed by travelling around the globe welcomed the digital format, which could become a pilot for the 26th edition of BIO Europe 2020 in November, which might connect over 4,000 executives from over 60 countries for high-level networking, partnering meetings, strategic panel discussions, and world-class workshops. High ranking meetings, as the ASCO meeting with 40,000 participants followed, suit the new age of digital conferences. Just turn the page to learn everything you need to know about Europe’s must-do events in the biotech industry. L

Euro Biofairs Compass

European Biotechnology | Spring Edition | Vol. 19 | 2020

4th AMR Conference Novel Antimicrobials & AMR Diagnostics

24 – 25 August 2020 Congress Centre Basel, Switzerland

Why AMR matters AMR Conference 2020 The conference convenes 400 international at-

tendees active in the field of Antimicrobial Resistance (AMR), offering a platform for all stakeholders to discuss the latest challenges. In view of the coronavirus pandemic, experts urge that there is a higher need than ever before to establish a sustainable pipeline of new antibiotics. Why has antimicrobial resistance not yet received the same attention that SARS-CoV2 has? This is most probably due to its slow and somehow hidden progression. However, AMR experts across the globe are warning that treatment of COVID-19 patients is get-

› Quick facts Satellite meeting Promoting Innovative Antibiotic R&D in Switzerland, 25 August 2020 Pre-conference workshop “Top 10 Mistakes in Antibacterial Drug Preclinical Development,” 24 August 2020; by Novo REPAIR Impact Fund, CARB-X, GARDP, and Wellcome Trust www.amr-conference.com

ting harder if secondary infections are caused by antibiotic-resistant bacteria. “It’s a one-two punch: A virus can weaken the body, making it easier for complex, hard-to-treat bacteria to take hold,” Julie Gerberding, M.D., Chief Patient Officer of MSD, recently explained in a statement highlighting the need to fill up the antibiotics pipeline to combat AMR. Manica Balasegaram, a medical doctor who heads the Geneva-based Global Antibiotic Research and Development Partnership (GARDP) also urges that while antibiotics won’t treat viruses directly, they are an important line of defence against secondary bacterial infections, like ventilator-associated pneumonia, urinary tract infections, and sepsis, which are more common with prolonged stays in intensive care units, particularly among people with weak immune systems. “We don’t have a line of sight into the supply and demand of

antibiotics right now. But, in outbreaks, you still need essential medicines like antibiotics,” says Balasegaram. This is underlined by first studies from Chinese COVID-19 patients, which showed that those who recovered from severe cases mostly received antibiotics. This wouldn’t be a major concern if it weren’t that the antibiotics market is already suffering from years of neglect, resulting in a dry pipeline of novel antibiotics and a broken business model, which is only slowly tackled by novel initiatives, such as the novel reimbursement model piloted by the NHS England or new cooperations amongst big pharma and antibiotic innovators (see page 28). “Neglecting for years the investment in the prevention, treatment, and control of infectious disease has now led to a predictable global crisis,” Marc Gitzinger, Vice President of the BEAM Alliance and CEO of Swiss BioVersys stressed. “While we now have to focus on the emergency measures, I hope that we learn some lessons. Society should value again the R&D of vaccines, antibiotics, and diagnostics for infectious disease.” Being a platform to connect relevant AMR stakeholders from industry, SMEs, finance, hospitals, science, and policy, the fourth AMR Conference will offer the opportunity to discuss solutions for solving the long-term AMR challenge and, thus, being better prepared for future pandemics. L

Picture: BIOCOM AG

Aug 24|25

New date!

2020 Congress Center Basel | Switzerland

4th AMR Conference

Novel Antimicrobials & AMR Diagnostics MSQHDR VNQKCVHCD DWODQSR #NMS@BS TR DLADQ NQF@MHR@SHNMR 6HRHS DDM DB DTQNO@ DT SN EHMC

ÂŠSebastian Kaulitzki/stock.adobe.com

%MSDQOQHRD %TQNOD .DSVNQJ %%. Sponsors & Partners: OR ATRHMDRRDR HMMNU@SD @MC FQNV @M HMSDQM@SHNM@K RB@KD )S HR SGD KCdR K@QFDRS RTOONQS MDSVNQJ ENQ RL@KK LDCHTL RHYDC DMSDQOQHRDR 3-%R G HMSDQM@SHNM@K @LAHSHNMR

!CUHBD

0@QSMDQRGHOR

A joint DNDi / WHO initiative

Supporting Partners:

(NV B@M VD GDKO XNTQ ATRHMDRR

... ONE BIOTECH CLUSTER

â&#x20AC;&#x153;WHITE BIOTECHNOLOGYâ&#x20AC;? WORKING GROUP

Local Host:

)MMNU@SHNM

@ .DSVNQJ DWODQS MD@Q XNT

Leading chemical companies are exploring the opportunities that have been opened up by modern biotechnology, especially in the field of â&#x20AC;&#x153;whiteâ&#x20AC;? or industrial biotechnology. And they are also applying these technologies, wherever it makes sense. The SBA takes such initiatives seriously and has formed a working group specifically dedicated to white biotechnology. The Swiss Industrial Biocatalysis Consortium is an important partner in this effort. The group includes leading multinational companies that support white biotechnology as a pillar of economic growth. The planned activities are in agreement with OECD strategies. In partnership with the Swiss Biotechnet (see pages 14/15) the SBA develops training programmes and useful support tools for the industry. It is of importance that the industry specifies its training needs so that the academic side can create tailor-made education. This strategy ensures that the industry gets the right workforce with the right education. The SBA profits from the marketing alliance â&#x20AC;&#x153;Swiss Biotechâ&#x20AC;? (see box) in a multiplied form. Thanks to Swiss Biotech, the

sector is internationally visible. The project-specific participating companies (most of them young and internationally less savvy) find a comprehensive partner which is helping to put them in the public window. The participating Life Science Regions are important internal carriers of the dynamics in the Biotech sector, thus enhancing the common understanding of the industry. This and more knowledge is brought into Europa Bio, the European Biotech Association, where the SBA is an active member.

Media Partners:

European Biotechnology NET WORK

amr-conference.com #AMRconference We are part of the #GlobalAMRChallenge Organisation: BIOCOM AG I LĂźtzowstraĂ&#x;e 33â&#x20AC;&#x201C;36 I 10785 Berlin I Germany amr@biocom.de I Tel. +49 (0)30 264921-38 I Fax +49 (0)30 264921-66

Domenico Alexakis is Executive Director of the Swiss Biotech Association.

SWISS BIOTECH...

...is an alliance of four leading Biotech regions of Switzerland (Bio Alps, BioPolo Ticino, Basel Area and Greater Zurich Area). They have combined efforts to streamline interests of the national biotech sector. The SWX Swiss Exchange holds a leading position in terms of lifescience listings and offers companies from that industry â&#x20AC;&#x201C; be they located in Switzerland or abroad â&#x20AC;&#x201C; access to an internationally recognised financial marketplace. The initiative was co-founded by the SBA which also manages the executive office of Swiss Biotech.

For further information please visit www.swissbiotechassociation.ch www.swissbiotech.org

Euro Biofairs Compass

European Biotechnology | Spring Edition | Vol. 19 | 2020

15 September 2020 Congress Centre Basel Basel, Switzerland

Facets of biotech Swiss Biotech Day In May of 2019, more visitors than ever before

came together at the leading biotech conference in Switzerland. In 2020, the Swiss Biotech Day will offer networking opportunities and an inspiring programme.

With 850 visitors from 25 countries, last year’s event easily filled the additional space provided by the new venue in Basel. The record-breaking attendance confirmed the leading role of the Swiss Biotech Day as an industry networking platform. Few regions can compete with the density and variety of biotech stakeholders and their international partners gathered in Basel. Highlights of this year's conference included the keynotes by Jean-Paul Clozel (CEO of Idorsia) and

Patrick Aebischer (former EPFL president), the second edition of the Swiss Biotech Success Stories for remarkable industry achievements, and the presentation of the Swiss Biotech Report.

A key event

decision-makers, and industry stakeholders in Switzerland over the years, we decided to postpone it to autumn and give you the opportunity to meet and network as you are used to. We would be very happy to welcome you in Basel in order to maintain contacts and, above all, to make new ones. Join us in Basel for an intense and stimulating exchange!

GREETINGS Due to the current coronavirus situation, the Swiss Biotech Day cannot take place in Spring at its usual time of the y e ar. Bu t , a s the event became the key networking platform for biotech entrepreneurs, investors, researchers, analysts, political

Proud tradition The 2020 event is shaping up to follow in this tradition. The event covers the entire value chain, from world-leading research groups, to investors, biotech

Michael Altorfer CEO, Swiss Biotech Association

entrepreneurs, start-ups, and patent specialists. The Swiss Biotech Day will present an inspiring programme with plenty of time for networking. An emphasis will lie on opportunities and synergies offered by the close collaboration of pharma and biotech. Platforms will be provided to discuss new threats in research and development, production, data management, artificial intelligence, and innovative financing. The celebration of the Swiss Biotech Success Stories’ laureates of 2020 will also be on the agenda. With partnering talks, discussions with experts on financing, and presentations of emerging companies, the Swiss Biotech Day will be as multifaceted as the life sciences industry itself. L

› Quick facts REGISTRATION www.swissbiotechday.ch Phone: +41-43-508-11 21 register@swissbiotechday.ch Highlights ›› 700+ participants ›› 50+ exhibitors ›› Swiss Biotech Success Stories Awards ›› Presentation of innovative bio tech start-ups and mediumsized biotech companies ›› Thematically focussed panel discussions ›› One-on-one partnering

Pictures: SBA/Deirdre O’Keeffe

New Date! © Sahachatz/shutterstock.com

SWISS BIOTECH DAY 2020

15 Sept 2020 Congress Center Basel

What you can expect in 2020: › Around 700+ senior life science experts from 25+ countries › 50+ exhibitors and international delegations › Presentation of the Swiss Biotech Report › Swiss Biotech Success Stories Awards › Innovative biotech start-ups and medium-sized biotech companies › Thematically focused panel discussions › Pre-scheduled one-to-one partnering meetings › High-trafic exhibition with ongoing catering

Wir wollen die bestmögliche Krebstherapie.

Find out more on the program and register at www.swissbiotechday.ch

Sponsors:

Die Schweizerische Arbeitsgemeinschaft für Klinische

Krebsforschung führt klinische Studien durch, um weitere Fortschritte gegen Krebs zu ermöglichen. Mit dem Ziel, die Lebensqualität von Patienten zu erhöhen und die Zahl der Krebskranken weiter zu senken. Unterstützen Sie unsere Forschung gegen Krebs. PC 60-295422-0, sakk.ch

SAKK_AZ_Fueller_210x297mm_8.2016.indd 1

... ONE BIOTECH CLUSTER

BRAND INSTITUTE Where Great Brands Begin!

08.08.16 15:29

“WHITE BIOTECHNOLOGY” WORKING GROUP

Leading chemical companies are exploring the opportunities that have been opened up by modern biotechnology, especially in the field of “white” or indusSupporting partners: trial biotechnology. And they are also applying these technologies, wherever it makes sense. The SBA takes such initiatives seriously and has formed a working group specifically dedicated to white biotechnology. The Swiss Industrial Biocatalysis Consortium is an important partner in this effort. The group includes leading multinational companies that support white biotechnology as a pillar of economic growth. The planned activities are in agreement with OECD strategies. European In partnership with the Swiss Biotechnet (see pages 14/15) the SBA develops training programmes and useBiotechnology NET WORK ful support tools for the industry. It is of importance that the industry specifies its training needs so that the academic side can create tailor-made education. This strategy ensures that the industry gets the right

Domenico Alexakis

SWISS BIOTECH...

...is an alliance of four leading Biotech regions of Switzerland (Bio Alps, BioPolo Ticino, Basel Area and Greater Zurich Area). They have combined efMedia partners: interests of the national biotech forts to streamline sector. The SWX Swiss Exchange holds a leading position in terms of lifescience listings and offers companies from that industry – be they located in Switzerland or abroad – access to an internationally recognised financial marketplace. The initiative was co-founded by the SBA which also manages the executiveby: office of Swiss Biotech. Organized

Euro Biofairs Compass

Materials & Packaging

Technologies & Processes

European Biotechnology | Spring Edition | Vol. 19 | 2020

Food & Nutrition

Fashion & Textiles

Green & Circular EFIB 2020 500 attendees are expected to join the 13th edition of the

“European Forum for Industrial Biotechnology and the Bioeconomy” (EFIB) in Frankfurt, Germany. The two-day event provides a platform to showcase industrial contributions towards a green and circular economy and to discuss sustainability challenges in the food, packaging, and textile sectors. With the Green Deal announced by the European Commission in December 2019, Europe has reaffirmed its goal to be among the global leaders of sustainable innovation. It includes a “Farm to Fork” strategy that aims at developing an environmentally friendly food system and will proceed with a Circular Economy Action Plan, among others. With the 13th edition of EFIB, EuropaBio will showcase corporate strategies in the Green Econ-

omy and provide a platform to discuss how industry is contributing to sustainable innovation in key consumer sectors, such as food, packaging, and fashion. By highlighting product examples, business strategies and alliances, large corporations as well as small and medium sized companies (SMEs), investors, start-ups, and policymakers will share insights on how to advance innovation within publicprivate coalitions, such as the European

People & Planet

bioeconomy to implement SDGs. The #EFIB2020 congress is hosted in Frankfurt, and will gather policymakers, industry, academics, young innovators, as well as SMEs and other stakeholders, to discuss the current state of green economy. We look forward to inspiring presentations, partnering and networking, a dynamic exhibition, a third edition of our Start-up Village, and much more. We hope that you will join us in Frankfurt.

GREETINGS With the Green Deal launched by the European Commission in 2019, sustainable innovation has gained momentum more than ever. The 13th edition of Europa- Bio’s annual EFIB congress will shed light on the role of industrial biotech and

Agnes Borg, Industrial Biotech, Director, EuropaBio

5 – 6 October, 2020 Frankfurt, Germany

Plastic Pact, how to organise legal frameworks for sustainable processes, how to scale up new means for food production, and how to best implement market access for start-ups in the fields of plantbased and cultured meat alternatives. In addition, discussions will include the potential of groundbreaking technologies, such as synthetic biology and genome editing, or how to deal with plastic waste and its huge impact on reaching the Sustainable Development Goals. Further tracks will cover CO2 as a resource, as well as the sustainability challenge in the textile business. Sustainable financing and how banks are reacting towards the Green Economy will also be addressed.

Special invitation to start-ups EFIB offers SMEs as well as academics a reduced fee. Start-ups are invited to apply for free booth space in the Startup Village until 15 June. L

› Quick facts Highlights ›› 80+ speakers ›› Various tracks on plastics, packaging, food, synthetic biology, green economy, and fashion ›› Inspiring “Get a Taste of the Future” tour as part of the evening reception in the exhibition ›› Reduced fees for SMEs, academics, start-ups, and 1-on-1 partnering ›› www.efibforum.com

Pictures: BIOCOM AG (top); EuropaBio (bottom)

Organised by

Picture: rh2010/stock.adobe.com

EUROPE’S LEADING EVENT ON INDUSTRIAL BIOTECHNOLOGY AND THE BIOECONOMY 5 – 6 October 2020 · Frankfurt/Main · Germany Network with your peers and gain insight into the sustainability challenges and opportunities in the food, packaging and textile sector:

› Around 500 delegates from 30+ countries › Topics: Food, Feed & Nutrition | Materials & Packaging | Fashion & Textiles | Industrial Processes & Synthetic Biology | › ›

Genome Editing | CO2 | SDGs | Financing | Policy and Industry Perspectives Start-up village & Innovation pitches on novel technologies and trends Green and circular economy innovation showcases

Contribute with your sustainable innovation to EFIB 2020! Submit a scientific poster abstract or apply for a free space in the Start-up Village. Deadline: 15 June 2020

www.eﬁbforum.com | #EFIB2020 Supporting Partner

Local Partner

Euro Biofairs Compass

European Biotechnology | Spring Edition | Vol. 19 | 2020

14 – 16 October 2020 Pacifico, Yokohama Japan

Partnering in Asia BioJapan/Regenerative Medicine Japan/healthTECH JAPAN 2020 The 22nd

iteration of Asia’s premier partnering event for the global biotech industry will take place 14 – 16 October 2020 in Yokohama, Japan. Over 1,000 organisations from industry and academia around the world are expected to take part in this year’s partnering, for over 12,000 meetings in total. Interest in pursuing partnerships with Europe and ASEAN organisations are on the rise at BioJapan. As a result, the presence of national and regional Europe and ASEAN delegations are increasingly apparent, and these organisations comprised approximately one third of participants in the 2019 partnering event. The high number of expected returns in 2020 stands as a testament to their success.

Besides the partnering and exhibition, the three-day event (14 – 16 October) will be host to a jam-packed seminar and presentation track, including both Japanese and English sessions from pharma, academia, biotechs, ventures, and other organisations. The full schedule will be available online in August, and new sessions will be announced right up to the start of the event.

Come to Japan

tells us that this interest is mutual! What’s more, with the 2020 Tokyo Olympics happening this year, Japan is strengthening its efforts to develop a more globally-focused infrastructure, so this is the perfect time to visit and build relationships with Japanese companies. We hope you’ll join us in Yokohama and look forward to welcoming old friends and new to Japan to make this year’s event even more successful than ever.

GREETING The growing number of European participants at BioJapan in recent years is an encouraging sign of the increasing internationalisation of the Japanese biotechnology industry. We’ve experienced a lot more interest among Japanese organisations in working with teams from overseas, and the number of returning international companies and associations

Keiko Abe Chairman, BioJapan Organising Committee

In anticipation of rapid growth in the healthcare industry, great attention has been brought to the Digital Medicine, Digital Therapeutics (DTx), Healthcare, and Wellness products using digital technologies. Thus, the new event healthTECH JAPAN is now launching to provide a total solutions and wider business platform for all the healthcare industry players. Since BioJapan and Regenerative Medicine JAPAN are now known as an Asian exhibition hub and partnering event facilitating interaction between Japanese and global companies/organisations, the addition of new event healthTECH JAPAN will increase synergy for all the attendees in Yokohama this October. Since the partnering system is fully shared between the three co-located exhibitions, BioJapan, Regenerative Medicine JAPAN, and healthTECH JAPAN, the potential for cross-field collaboration is greater than ever. L

› Quick facts Contact & Registration biojapan@jtbcom.co.jp saisei@jtbcom.co.jp healthtech@jtbcom.co.jp (+81) 3 5657 0758 www.ics-expo.jp/biojapan Highlights

›› 950+ Exhibitors from 30 countries ›› 17,000+ Visitors ›› 12,000+ Meetings ››Partnering opens in July

Pictures: BioJapan

Euro Biofairs Compass

European Biotechnology | Spring Edition | Vol. 19 | 2020

9 – 11 November 2020 Crowne Plaza Düsseldorf – Neuss Congress Centrum Düsseldorf/Neuss

QC/QA lab challenges PHARMALAB In November, it’s time again: the eighth edition of PharmaLab

will offer information on the latest regulatory and scientific developments in the field of pharmaceutical quality control (QC) and quality assurance (QA) – from 9 to 11 November, with five conference tracks and a workshop.

The fields of analytics, bioanalytics, and microbiology continue to be characterised by important developments. Regulatory changes and innovations will either have a direct impact – as with ICH Q14 “Development of Analytical Procedures” or Q2(R1) “Analytical Validation” – or an indirect impact, as with ICH Q12 “Life Cycle Management” or Annex 1 of the GMP Guide. The requirements for data integrity also represent a challenge in the laboratory sector. For cell- and tissuebased products and gene therapeutics,

› Quick facts Contact & Registration www.pharmalab-congress.com/2020 Highlights

›› Key speakers from the US, the UK, Denmark, Italy, Spain, the Netherlands, Germany, and others ›› Ten conferences with over 60 lectures in English or German ›› Networking options and social events

the number of relevant guidelines and guides is also continuously increasing. So far this year, the FDA alone has published six final guidelines and one draft guideline for gene therapeutics. Yet, in the field of microbiology, developments are also continuing to move forward, as, for example, in the pyrogen test with monocyte activation tests (MAT), instead of rabbit tests, or in the field of low endotoxin recovery. Also, many companies are advancing the establishment of alternative microbiological test methods for monitoring, in-process controls, and release tests. This is especially true with regards to the development and production of modern active ingredients and therapeutics on a biological basis. They also provide the foundation for laboratory optimisation, for which the congress will also offer a track. Together with an exhibition of around 40 suppliers and service providers, PharmaLab offers the unique opportunity to learn about the latest developments, to discuss them with experienced colleagues, and to benefit from the experience of some 60 speakers. L

Lab professionals GREETING Become par t of the PharmaLab community and benefit from the leading meeting of experts from regulator y authorities, industries, contract laboratories, and laboratory suppliers. Whether analytics, bioanalytics, or microbiology – the relevant topics will be discussed. This ranges from the pre-conference workshop on 9 November on mycoplasma detection to the four international and one national conference tracks during the two-day congress on 10 and 11 November. Almost 60 speakers from authorities, industries, and laboratories will present the latest regulatory developments, new methods, and their practical experience. The planned presentations will cover various topics, such as the detection of mycoplasmas or viruses, testing for endotoxins and pyrogens, validation of analytical methods, and laboratory optimisation. You can further take advantage of the exhibition with about 40 exhibitors to get to know the latest laboratory technology and the possibilities of external laboratory services. We look forward to meeting you in Neuss. Axel H. Schroeder Concept Heidelberg Operations Director

Pictures: Concept Heidelberg; Rizwan Chaudhrey – RSK Solutions

Congress & Exhibition for Analytics, Bioanalytics and Microbiology

Düsseldorf/Neuss Germany 10/11 November 2020 The PharmaLab is the ideal forum to discuss current trends, developments and applications in the pharmaceutical lab. As a delegate, you can choose between the following conferences Laboratory Optimization and Automation Endotoxin/Pyrogen - Routine Testing, LER and Alternative Methods like MAT and rFC Challenges in Bioanalytics and Bioassays Qualitätskontrolle – Aktuelle Trends im pharmazeutischen Labor* (Conference in German)

Challenges in Analytical QC Virus Safety and Next Generation Sequencing Testing and Analytics of Cells, Tissues and ATMPs Rapid Microbiological Methods and Real Time Testing

Be part of the PharmaLab 2020 as an exhibitor For you, as a solutions provider, the PharmaLab exhibition is the right platform to present your latest technologies and services for the modern lab. All information can be found at: www.pharmalab-congress.com/congress-2020

Official Media Partners 2020:

Euro Biofairs Compass

European Biotechnology | Spring edition | Vol. 19 | 2020

11 – 12 November 2020 Kölnmesse Cologne, Germany

The place to be chemspec europe This fine and speciality chemicals exhibition is a key

event for the industry. Purchasers and agents will have the opportunity to meet with manufacturers, suppliers, and distributors of fine and speciality chemicals to source bespoke solutions and innovative substances.

Covid-19, sustainability, new trends, such as power foods and bio-based cosmetics, and digitalisation, are not just buzzwords. In fact, these aspects, as well as ongoing demand for innovations, determine the industry. The choice of the right suppliers and the exchange of knowledge within international industry networks is more important than ever. With a highly specialised exhibition profile, Chemspec Europe is the place to be for buyers, traders, and agents in search of bespoke solutions and innovative substances.

› Quick facts Venue information Chemspec Europe 2020 11 – 12 November 2020 Koelnmesse, Messeplatz 1 50679 Cologne, Germany Contact Phone: +44 (0) 1727 814 400 Email: info@chemspeceurope.com Web: www.chemspeceurope.com

Chemspec Europe 2020 features the full spectrum of fine and speciality chemicals for various applications and industries, including pharmaceuticals, agrochemicals, polymers, green chemicals, food and feed ingredients, flavours and fragrances, bio-based chemicals, pigments and dyes, paints and coatings, household and cleaning chemicals, adhesives and sealants, petrochemicals, electronic chemicals, and many others. Amongst the exhibiting companies are Albemarle, Arkema France, CABB AG, Chevron Phillips Chemicals International N.V., Johnson Matthey, Kemira Oyj, Lonza Ltd, Solvay, Sumitomo Chemical Europe SA/NV, Tosoh Europe B.V, Vertellus, WeylChem International GmbH and many more. An outstanding, two-day conference programme will provide further knowledge and insights into major industry developments, as well as key strategies adopted by industry leaders to succeed and grow. All visitors at Chemspec Europe 2020 are invited to attend, free of charge. L

Chemicals finest GREETINGS On behalf of the organisers of Chemspec Europe 2020, I welcome you to Europe’s No 1 tr ade fair for the fine and specialit y chemicals industry. As you know, we’ve decided to postpone the exhibition to 11 – 12 November 2020 following the escalation of COVID-19. We trust that the decision will enable the show to continue to serve as primary specialised trading and networking event in the secure and safe conditions needed. The exhibition covers the most comprehensive range of fine and speciality chemicals, including bio-based chemicals and biocatalysts. Visitors will have the opportunity to meet with international suppliers and explore the latest technical advancements, specific ingredients, and custom-made solutions. With its audience, Chemspec Europe reflects the global scale and complex structure of the fine and speciality chemicals industry. The trade show provides excellent sourcing and trading opportunities, as well as a place to network and keep up to date with the latest developments. Nicola Hamann Managing Director Mack Brooks Exhibitions Ltd

Pictures: Mack Brooks Exhibitions Ltd

ciality e p s d n a e Fin for chemicals stries u d n i s u o i var 35th International Exhibition for Fine and Speciality Chemicals Koelnmesse, Cologne, Germany

11 – 12 November 2020

Europe’s No 1 trade fair for the fine and speciality chemicals industry Chemspec Europe 2020 is the place to be: Find bespoke solutions & innovative substances for your enterprise and take your networking to the next level • custom synthesis

• colourants & dyestuffs

• plastics additives

• pharmaceuticals

• ﬂavours & fragrances

• cosmetics

• ﬁne chemicals

• green chemicals

• polymers

• chemical intermediates

• surfactants

• agrochemicals

• household & industrial cleaning

• petrochemicals

Agrochemical Lecture Theatre

• adhesives & sealants

• biocatalysts

• electronic chemicals

Chemspec Careers Clinic

• paints & coatings

• bio-based chemicals

• and much more

Pharma Lecture Theatre

Top conferences and workshops offer valuable insights into ongoing R&D projects!

Regulatory Services Lecture Theatre RSC Lecture Theatre Innovative Start-ups

Get your ticket now:

www.chemspeceurope.com

Organisers:

Euro Biofairs Compass

European Biotechnology | Spring Edition | Vol. 19 | 2020

1 – 2 December 2020 Palais de la Musique et des Congrès Strasbourg, France

Sourcing innovation BioFIT Gathering 1,300 delegates from 35+ countries, BioFIT has

taken on a whole new dimension, becoming the meeting point in Europe for tech transfer, early-stage innovation deals and pre-seed/seed/ Series A investment rounds in the Life Sciences.

With more than 1,300 international actors from tech transfer offices (TTOs), research institutes, and academia, together with big pharma, emerging and small biotech, diagnostic companies, veterinary firms, and pre-seed/seed/ Series A investors, BioFIT has become the leading partnering event in Europe for technology transfer, academia-industry collaborations, early-stage innovation deals, and the European marketplace for early-stage financing rounds in the Life Sciences field. The event is,

above all, an optimal business convention with prequalified one-on-one meetings. Its online platform allows participants to identify potential partners, to pre-schedule meetings with them, and to meet them during the event, in order to build partnerships. During the last edition, over 13,000 meetings had been generated through the partnering system. In addition to the one-on-one meetings, BioFIT offers pitch sessions that give the opportunity to detect the most

Welcome to BioFIT Greetings Since its first edition, in 2010, BioFIT has become the leading European partnering event for early-stage deals and investment rounds in the Life Sciences field. We would be very pleased to welcome you to Strasbourg on 1 and 2 December 2020 for the 9th edition

innovative start-ups and promising collaborative and licensing opportunities, in order to foster partnerships and business development in the Life Sciences field. It is also a great opportunity for bioentrepreneurs to showcase in front of potential partners. The session entitled “Start-up Slams” are dedicated to startups seeking to raise a seed or Series A financing round, whereas the “Collaborative and Licensing Opportunity Presentations” are devoted to TTOs, universities, research institutes, and companies willing to promote an early-stage asset. Furthermore, BioFIT offers its participants a “Would-Be CEO” session. This session aims to bring together startups, incubators, TTOs, scientific founders, and would-be CEOs, and allows bioentrepreneurs seeking a project to lead, to find new companies or those in process of being created, or to become involved as a CEO. This Would-Be CEO session also allows projects in need of CEOs to find their future leaders. L

› Quick facts of BioFIT, which provides the ideal environment for academia and industry actors to build partnerships, to source innovative and competitive early-stage R&D projects, to facilitate the emergence of collaborative projects, to increase licensing opportunities, to obtain funding, and to facilitate market access. Etienne Vervaecke, General Manager of Eurasanté & Clubster NHL

2020 Key figures: 1,300 delegates, 35+ countries represented, 35+ one-to-one meetings per participant, 17 conferences, 80 speakers, 110 exhibitors More Information www.biofit-event.com

Pictures: Vincent Eschmann (above); Maxime Dufour (below)

advertorial

European Biotechnology | Spring Edition | Vol. 19 | 2020

Fully digital partnering at BIO-Europe Spring 2020 BIO-Europe Spring Leading life sciences partnering event pivots to deliver dealmaking

opportunities in a new format during very unusual times. With just 16 days to plan, EBD Group transformed BIO-Europe Spring from a physical event held in Paris to a fully digital solution where 1,700 delegates around the world participated in virtual partnering meetings and panels.

Things were changing fast, very fast in the first two weeks of March 2020. Before the last sentence of an online article about the rapidly spreading coronavirus was written, new data popped up with even more frightening statistics. The number of people infected with the coronavirus was climbing, and governments around the world were anxious for solutions to stop its spread. Limiting the number of people gathered in one location was one of the first steps France adopted. France was also where EBD Group’s highly anticipated fourteenth annual BIO-Europe Spring® international partnering conference was scheduled to take place 23 – 25 March in Paris. The City of Light was to host delegates from around the world, as they met and connected with potential biopharma partners, attended in-

sightful panel discussions, and listened to company presentations. “Our reason for being is to serve the global biotech community and help biotech and pharma companies connect, do business, and find investment opportunities,” explains Anna Chrisman, Group Managing Director, EBD Group. “The meetings that take place at BIOEurope Spring drive valuable dealmaking for the rest of the year.” The state-of-the-art partnering software, partneringONE®, which enables delegates at BIO-Europe Spring to efficiently identify and engage with new opportunities via one-to-one meetings, had already received 30,000 requests for meetings before it became apparent that a large in-person conference wouldn’t be possible. With the event just 16 days away, Chrisman and

her team began reaching out to event partners and delegates. “The consensus from big and small companies was that they wanted to find a way to make par tnering happen despite restrictions on travel,” explains Chrisman.

Creating a digital event in record time How to make this happen was something no one at EBD Group had a manual for. They would have to figure this out on their own and in just two weeks. The solution they came up with was to take this popular face-to-face event and turn it into a fully digital experience for nearly two thousand attendees. With that, BIO-Europe Spring “digitally delivered” was born. Most delegates and companies appreciated the quick pivot EBD Group made and quickly showed their support and enthusiasm for the digital event when the announcement was made on 5 March. “With the uncertainties of the coronavirus outbreak, we fully support EBD’s decision to transform the BIO-Europe Spring conference into an entirely digital edition. Merck looks forward to contributing to the digital panels and the presentations in March, and meeting face-to-face at BIO-Europe in October in Munich,” said Philippe Lopes-Fernandes, Senior VP, Global Head, Business Development and Alliance Management, Merck KGaA, Darmstadt, Germany.

Picture: EBD Group

European Biotechnology | Spring Edition | Vol. 19 | 2020

“We welcome the effort to do a digital partnering conference! You bridge the gap between ‘We’ll meet in Paris’ and ‘We do no business at all.’ BIO-Europe Spring is an important conference in the spring season, and Bayer doesn’t want to miss it. We will participate with all registered colleagues and look forward to our virtual meetings,” said Dr. Martin Beuck, VP, Head of BD&L Radiology & Operations, Bayer AG.

Business almost as usual Working literally around the clock, EBD Group was able to build a digital exhibit portal filled with company presentations and downloadable content. BIOEurope Spring delegates could watch live or prerecorded panel discussions. Investors got the opportunity to listen to company presentations at their convenience. The event was extended to March 27, enabling partnering meetings to occur more easily across time zones. Potential partners couldn’t shake hands, but they could still meet via secure video. Business could still take place as usual during these very unusual times. When the idea to transform BIO-Europe Spring came about during the first week in March, many people were still working from their offices, visiting friends, and going about their normal, daily lives. By 23 March, the first day of BIO-Europe Spring digitally delivered, people all over the world had been ordered to stay home.

Picture: EBD Group

New perspectives The reality that connecting with someone via their computer’s camera was the only way to meet someone new, pitch their company or participate in a panel convinced skeptics to embrace the opportunity to participate in the first large scale partnering event done digitally. “We are very pleased that we were able to offer BIO-Europe Spring delivered digitally over a five-day span to help the global biotech community keep in

touch during this critical time, connecting, dealmaking, and finding investment opportunities,” says Chrisman. “Usually, our attendees often have to choose between attending presentations or panel discussions and conducting partnering meetings. In this format, they could do it all on their own schedule.”

Statistics: Good acceptance By the close of the digital event, BIOEurope Spring had welcomed over 1,700 delegates from 986 companies for nearly 6,000 vir tual par tnering meetings, hosted 12 recorded panels featuring industry experts, 45 recorded company presentations, and a virtual exhibit (open to all until 30 April) with recorded and downloadable information about companies. “Some people were skeptical of the virtual format at first. But in the end, the main value is in partnering, and the sentiment has shifted very quickly, as we are all coming to terms with the fact that most of our interactions are going to be virtual for a while. This week, we have received overwhelmingly positive feedback for keeping communication in this community afloat,“ says Chrisman. The response has been overwhelmingly positive. “#BIOEuropeSpring looks a little different this year, but it’s great to connect with companies (and see a few familiar

advertorial

@IAmBiotech faces virtually as well!). The Combating #Coronavirus plenary was a fantastic start, looking forward to a productive week,” posted Elizabeth Gaskins @LizatBIO on Twitter. “The current situation of remote working is something we already do on a daily basis at AIPEX B.V. – Europe connected. Today, I'm enjoying the fully digital conference BIO-Europe Spring with Luc Smeets!” posted Marc den Hoed on LinkedIn. Two of the panels, available online here, were pulled together in the days leading up to the event to update delegates regarding the biopharma community’s response to the global pandemic. They focused on the COVID-19 solutions currently being researched and tested, with panellists from Moderna, Johnson & Johnson, CEPI, Regeneron, Omega Funds, and Biotechnology Innovation Organization (BIO), as well as the road to recovery in China, with Novartis China, Johnson & Johnson Innovation, the Shanghai Delta Hospital Co., Ark Biosciences, Pharma Intelligence, ChinaBio® Group, and the American Chamber Shanghai participating. The learnings and insights that arose from these panels contributed to Xconomy’s new e-book, Containing Coronavirus Through Innovation and Investment: An Xconomy Special Report, now available for free download. Several more panels from the BIO-Europe Spring program will be made available in the coming weeks. The next BIO-Europe Spring event will be held for the fourth time in Barcelona, Spain, 22 – 24 March 2021. “We look forward to returning to Barcelona in 2021 for what we hope will be a long-awaited, face-to-face BIO-Europe Spring event,” says Chrisman. Contact EBD Group Deborah Gravelle Marketing Manager Carlsbad, CA DGravelle@ebd-group.com www.ebdgroup.com/

Northern EUROPE

European Biotechnology | Spring Edition | Vol. 19 | 2020

Biorefinery boost

Novo investing AMR Novo Holdings has add-

ed an additional investment of US$12m in companies developing novel compounds breaking antimicrobial resistance (AMR). French Mutabilis SA and Integrated Biotherapeutics, Inc.’s subsidiary IBT Vaccines successfully acquired US$12m from the REPAIR Impact Fund, which has invested US$48m since its launch in 2018. Paris-based Mutabilis SA will receive €7m to push lead optimisation of its GDabocins programme that blocks beta lactamases of multi-drug resistant Gramnegative P. aeruginosa and A. baumannii. This programme is currently undergoing lead optimisation. Maryland-based IBT Vaccines Inc. will receive an investment of US$3.9m to advance the development of IBT-V02, a vaccine preventing recurrent skin and skin structure infections (SSSI) caused by S. aureus. IBT-V02, which also gets funding from CARB-X and the NIAID, is currently in the late-preclinical development stage. The jab has a novel mode of action and consists of five toxoids that elicit protective responses to 12 to 15 S. aureus toxins. Given the difficult funding environment for anti-infectives, the REPAIR Impact Fund will keep some capital in reserve to support funding of Phase II studies of its portfolio companies. The Fund will continue to initially invest only in projects that are between lead optimisation and Phase I clinical trials; however, this change in strategy will allow the REPAIR Impact Fund to continue to support its portfolio companies as they advance. 

UPM Finnish UPM will invest €550m to build a wood biorefinery in Leuna, Germany. According to the Finnish pulp and paper producer, the new, industrial-scale biorefinery will produce renewable glycols and lignin to replace fossilbased ingredients in a wide variety of industrial applications. “Once operational in 2022, the UPM Leuna Biorefinery will mark the beginning of a new, more sustainable era for the entire chemical industry,” the company announced in February. Insiders told European Biotechnology that Frankfurt/Germany had also applied to become UPM’s European biorefinery site but did not succeed, because Leuna gets special subsidies to modernize the former Eastern German chemistry hub. There, green chemicals will be produced from wood in Q4/ 2022. Saxony-Anhalt’s Economics Minister Armin Willingmann announced that InfraLeuna GmbH, which manages the former chemistry park, will contribute with an additional investment to the infrastructure of about €100m.

New jobs to be created The biorefinery will have an annual production capacity of 220,000 tons of biobased monoethylene glycol for textiles, non-degradable PET bottles, packaging and de-icing agents, monopropylene glycol for composites, drugs, cosmetics, and detergents, as well as fillers to replace industrial soot and silicates and industrial

sugar. UPM said it intends to use sawmill residues as raw materials and certified hardwood from the region. “Sustainable chemicals from biomass are one of the three strategic growth areas for our company and central to our efforts to create innovations for a future without fossil fuels,” said Jussi Pesonen, CEO of UPM. “Currently, the supply of biochemicals from renewable resources is very limited. This is another reason why the market for sustainable alternatives is very lucrative.”

Carbon footprint in focus UPM said it will save transport cost for raw materials sourcing wooden waste on a regional basis: “It is important for us to have a purely European value chain,” stressed Juuso Konttinen, VP at UPM Biochemicals. Furthermore, the products could easily be used in customers’ existing production processes and integrated into existing recycling infrastructures. The Finnish group emphasised Germany’s importance as a European centre of the chemical industry, its proximity to key customers, and its offering of sustainable forest management. The Fraunhofer Centre for Chemical-Biotechnological Processes (CBP), a biorefinery research centre, is also located in the neighbourhood. UPM announced that it will immediately start tendering for the plant, the personnel expansion, and the approval process. 

New industrial applications established at UPM

Picture: UPM

European Biotechnology | Spring Edition | Vol. 19 | 2020

Northern EUROPE

News Cell therapy deal

Next-gen antibody cleavers IgG-mediated Diseases In January, Hansa Biopharma AB (Lund) completed enrollment of 15 patients with the ultra-rare autoimmune disease Anti-GBM into an investigator-initiated Phase II study. According to the company, a first read-out on safety, tolerability, and efficacy data for its lead candidate imlifidase will be announced in Q3/2020. Anti-GBM is characterised by the presence of anti-GBM antibodies that attack capillaries in the kidneys (glomerulus) and lungs, manifesting as anti-GBM nephritis or as pulmonary-renal syndrome with severe lung haemorrhage. Imlifidase, which is also developed by Hansa

Biopharma to eliminate hazardous preformed donor-specific antibodies (DSA) causing organ rejection, cleaves antiGBM antibodies (IgGs). GBM is the first IgG-mediated disease outside transplantation. The orphan disease affects roughly one patient in a million annually. A different approach to desensitize patients with the orphan disease is being performed at the University Hospital of Marseille: doctors, headed by Emilie Garrido, compared 40 patients’ reduction rates in anti-GBM IgGs achieved through plasma exchange and extracorporal immunoadsorption. Primary results are expected in Q1/2022. L

Don’t write off IDO blockers

Picture: Hansa Biopharma AB

NSCLC At the end of Febru-

ary, Danish IO Biotech A/S and its partner Merck Sharp & Dohme Corp (MSD) announced the futility of their Phase I/II combination study in first-line metastatic, nonsmall cell lung cancer (NSCLC), following an interim analysis of an independent data monitoring board. In the non-blinded study, the companies investigate the safety and efficacy of MSD’s PD1-checkpoint blocker pembrolizumab with IO Biotech’s cancer immune escape blocker IO 102 vs chemotherapy with carboplatin and pemetrexed. The primary endpoint is improvement in objective response rate (ORR) in 108 metastatic NSCLC patients who either receive chemotherapy or do not. IO 102 is a therapeutic cancer vaccine blocking overexpression of the tryptophan (TRP)-degrading

enzyme indoleamine-pyrrole 2,3-dioxygenase (IDO), which was suggested to create a tumour microenvironment supporting cancer growth. Particularly, IDO was expected to support suppression of activated T and NK cells, generation of active Tregs and myeloid-derived suppressor cells, and also to boost angiogenesis. IDO also directly kills cancer cells by the formation of kynurenins, which are enzymatic degradation products of tryptophan. Some studies with TRP-related IDO inhibitors, such as BMS-986205 (Bristol Myers-Squibb), are ongoing, while studies with Epacadostat (Merck/ Incyte) and Navoximod (Roche/NewLink) have been terminated because of a lack of efficacy and off-target effects (Nature, doi:10.1038/d41586-018-07445-3. L

In February, InDex Pharmaceuticals Holding AB announced the publication of data supporting the mode of action of it TLR9 agonist cobitolimod for the treatment of ulcerative colitis (JCC, doi: 10.1093/eccojcc/jjz170). The DNA oligonucleotide markedly suppressed experimental colitis activity, and microarray analyses demonstrated TLR-9-dependent mucosal IL10 upregulation and suppression of IL17 signalling pathways. Cobitolimod treatment was associated with significant induction of mucosal IL10+Tr1 and Treg cells and suppression of pro-inflammatory Th17 cells. According to study leader Markus Neurath from the University of Erlangen, Germany, “the fact that cobitolimod was able to balance the Th17/Treg cell response both in a mouse model, in vitro, in cells from UC patients, and in patients demonstrates the robustness of the results.”

Migraine ahead In February, Danish bio pharma giant Lundbeck A /S was granted approval by the US drug authority FDA for its intravenously administered CGRP-blocking migraine antibody eptinezumab. While there is only one CGRP inhibitor marketed (fremanezumab; Teva Pharmaceutical) with comparable efficacy in preventing episodic and chronic migraines that is also administered quarterly, all competitor products are administered subcutaneously and could be self-administered on a monthly basis. Other products on the US and EU market include CGRP receptor inhibitors, such as erenumab from Amgen Inc. or galcanezumab from Eli Lilly & Co.

WESTERN EUROPE

European Biotechnology | Spring Edition | Vol. 19 | 2020

Allogeneic CAR-T expansion

Microbial drugs Live Microbials A new com-

pany for microbiome-based treatments for metabolic diseases has entered into an industry collaboration with nutrition giant DuPont Nutrition & Biosciences. MRM Health NV (Ghent, Belgium), a spin-out company from VIB, KU Leuven, and UGent, raised €14m in a Series A financing round led by Ackermans & van Haaren with coinvestments by DuPont Nutrition & Biosciences, MRM Technologies, Qbic II, and VIBDupont. MRM Health and DuPont Nutrition & Biosciences said they will combine selected DuPont strains under MRM Health’s platform to design novel, live microbial therapeutics that tackle a range of metabolic diseases. “Microbiomebased therapeutics are a great combination in the quest to deliver a novel class of natural and efficacious solutions for millions of patients worldwide,” said Sam Possemiers, CEO and co-founder of MRM Health. Through a strategic research partnership with VIB, MRM Health will leverage the extensive complementary microbiome and bioinformatics capabilities of the lab of Jeroen Raes (VIB/KU Leuven) and the know-how in arthritis and inflammatory diseases of Dirk Elewaut (VIB/UGent) and his team. The investment provides MRM Health with the financing resources to advance its preclinical lead program in inflammatory bowel disease (IBD) and to progress its discovery programs to deliver treatments in spondyloarthritis and other indications. L

Cell therapy As the market for adoptive cellular immunotherapies, particularly CAR-Ts, is projected to grow from roughly US$0.6bn in 2019 to US$3.8bn in 2027, companies are expanding their portfolios and manufacturing capacities. In February, two French companies dove in as well. CAR-T cell therapy developer Cellectis SA and France’s pharma giant Servier expanded their 2014/15 co-licensing deal on UCART19 currently in Phase I dose expansion testing and ended the inclusion of cell therapies directed against five targets on solid tumours. Cellectis’ allogeneic CAR T- cell product homes in on the CD19 protein on the surface of lymphomas.

Focus on blood cancer Under the terms of an expanded binding term sheet, Servier acquires additional, exclusive global commercialisation rights, including all next generation, gene-edited, allogeneic CAR T-cell products targeting CD19. ALLO-501A, the most advanced candidate, is currently undergoing Phase I dose-finding tests. In ALLO-501A, the rituximab recognition domains have been removed, either directly or through Cellectis’ US sublicensee Allogene Therapeutics. According to the amended contract, financial terms will be improved to include an additional

€25m upfront payment, as well as up to €370m in milestones. The royalty rate will be increased from tiered, high single-digit royalties to flat, low double-digit royalties, based on net sales of products. According to the amendment, Cellectis will regain control over the five undisclosed allogeneic CAR T-cell targets on solid tumours that were the subject of the initial agreement. Currently, experts from Big pharma appear to be split regarding the prospects of success when it comes to adoptive cell therapies directed against solid tumours, which make up 90% of the cancer drug market. One day after Cellectis got back its five cell therapy candidates against solid tumours, GlaxoSmithKline signed a potential US$1.1bn deal with German immatics biotechnologies GmbH for two TCR-T cell therapies to treat certain solid cancer indications. Currently, only CAR-T cell therapies against leukaemia and lymphomas have reached the market. According to André Choulika, CEO of Cellectis, the contract allows his company “to enrich its proprietary portfolio of targets,” adding “we are committed to positioning Servier and Allogene for streamlined success, so the CD19-directed products have the potential to reach patients faster, while also providing Cellectis with the means to expand our proprietary product pipeline.” L

1 Start from healthy, unmodified donor T-Cells Tumour cell

2 Insertion of single-chain CAR construct and suicide gene 3 Gene-knockout of TCR Alpha to avoid GvHD and CD52 to resist Alemtuzumab TCR

TCR

CD52

Suicie Gene

TCR CD52 CAR

T-Cell

Genomic DNA

Normal T-cell

T-Cell Gene addition

Gene Insertion

Suicie Gene

CD19 CAR

T-Cell

Suicie Gene

CAR

T-Cell

Gene inactivation

Gene Knockout (KO)

UCART19

Last year, Cellectis SA reported on an engineered CAR-T cell that secretes the proinflammatory cytokine IL-12 upon contact with tumour cells.

Picture: Cellectis

European Biotechnology | Spring Edition | Vol. 19 | 2020

Struggling for market shares

WESTERN EUROPE

News Miniaturised endoscope Leuven-based nanoelectronics provider imec NV has presented the first-ever millimetre-scale wireless transceiver for smart, insertable pills. The ingestible sensor allows for real-time monitoring and transmission of intestinal health parameters. The transceiver occupies an area only of up to 15mm2.

Picture: Glycom A/S

Glycom’s €50m HMO manufacturing site in Esbjerg, Denmark Infant Formula Royal DSM NV has entered the growing market of human milk oligosaccharides (HMO), taking over the producer of recombinant 2’-fucosyl lactose, Danish Glycom A/S. The Dutch industry giant for nutrition, health, and sustainable products paid €765m for Glycom A/S, which made €74m in sales of human milk oligosaccharides (HMO) in 2019, mainly from a collaboration with Nestlé, which markets the Danish company’s recombinantly produced infant formula supplement 2’-fucosyl lactate (2-FL). This HMO, which can be produced much more cheaply in E. coli than by the classical chemico-enzymatic route, is the second largest component of human breast milk, and is not only attributed to be crucial for the development of a health-promoting gut microbiota, but is also said to be essential for the development of the brain and immune system in infants. “We are excited to join DSM,” said Odd Hansen, CEO of Glycom. “This not only enables us to accelerate the growth of Glycom by adding our HMO products to DSM’s broad global customer base and integrating it in the company’s full solutions offering for infant nutrition customers, it also creates leverage with DSM’s strong R&D platform and clinical competencies to support the development of Glycom’s next generation HMOs. DSM is a really great home for Glycom to reach its full potential.” Royal DSM said it expects Nestlé to continue to be an important

customer in the future. Specifically, the Nestlé collaboration was cited as “a mutually beneficial, long-term contract with firmly committed volumes also covering the mid-term horizon.” However, a patent dispute pending between Glycom and German Jennewein Biotechnologie GmbH might challenge the collaboration. According to Nestlé spokesman Tobias Henritzi, Glycom assured that its recombinantly produced 2-FL was not infringing on other companies’ patents, upon signing the contract with the Swiss nutrition giant, which made an equity investment of €200m representing a 36.3% share in 2011. However, Jennewein Biotechnologie, which was the first company to receive a market approval for E. coli-made 2’-FL under the EU Novel Food Regulation in 2017, says Glycom is infringing on two of its patents, which allowed the company to make the purification process for recombinantly produced 2-FL significantly cheaper. According to the EU Novel Food Catalogue, which was introduced in late 2017, Glycom A/S submitted its Novel Food application for a recombinantly produced 2-FL just at the end of 2018. However, an FDA document indicates that Glycom had its recombinant process as early as of 2016 in place. Since 2017, a huge array of infant formula suppliers, which collaborate with biotech partners, entered the market of recombinant 2’-FL production, which contributes to the US$14bn human infant formula supplement world market. L

Adding compounds Using single-cell RNA-sequencing, research teams from Cambridge London, Newcastle (UK), and Leuven (Belgium) have drawn the first cellular atlas of human thymic development, the site of the establishment of adaptive immunity. The results may accelerate the development of in vitro culture systems that generate T cells and T-cell therapeutic strategies. Autologous CD8+-T killer cells have shown huge potential in immuno-oncology, while a new generation of FOXP3+ regulatory T cells are expected to offer huge benefits to patients with autoimmune diseases. Headed by Jong-Eun Park, the team, performed whole-genome analyses on 25 fetal and postnatal thymi and examined the changes that occur over the course of a human life. Using the data, the authors were able to develop models for how T-cells with different and specific immune functions develop (Science, doi: 10.1126/science.aay3224).

Production getting viral In mid February, Univercells SA cashed in €50m from KKR subsidiary Gamma Bioscience to advance its virus manufacturing platforms for gene and cell therapy.

Centr al EUROPE

European Biotechnology | Spring Edition | Vol. 19 | 2020

German bioindustry in turmoil

Virtual Flow COVID-19 Some two billion pos-

sible agents are going to be tested during the world’s largest computer-aided screening project: Austrian researchers are working on possible SARS-CoV-2 drugs, together with Harvard University scientists and Google. Project partners include the biotech start-up Innophore GmbH, the University of Graz, and acib, the Austrian Centre of Industrial Biotechnology. The Google parent company, Alphabet, contributes unlimited Google Cloud computing power to allow the simulation of such a vast number of agents for the first time in history. Vienna Scientific Cluster, a collaboration between several Austrian universities, also provides the resources of its supercomputers. “In virtual drug discovery at this scale, the biggest challenge is not only to obtain the data for these billions of compounds, but computing power. At the moment, we assume that we have to perform more than 100 billion individual computations, as every potential compound is being screened individually,” says Christian Gruber, CEO of Innophore. The novelty in this project’s approach is in the computer-aided method used to screen all the individual agents. “Virtual Flow” was developed at the Harvard Medical School. Currently, Innophore supports Harvard’s Virtual Flow process by simulating countless potential starting points of druggable targets using its patented 3D point cloud technology. The results are filtered by artificial intelligence before feeding them into the Virtual Flow pipeline. 

Qiagen’s headquarters in Hilden, Germany Turbulence Stormy times for the biotech sector in Germany. On the one hand, its expertise in the corona crisis is in highest demand; on the other hand, there is a lot of unrest, which shows how fragile the sector appears in comparison to the boom regions of the biotech world. Prior to the COVID-19 crisis paralysing Europe, it became known that Germany’s probably most successful biotechnology company was to be swallowed up: The US giant Thermo Fisher Scientific Inc. is offering around €10bn in cash for the Dutch holding company Qiagen N.V., whose management has already agreed to the bid. The company, which was founded in the mid-1980s under the name Diagen, was last seen as a source of hope with the ramp-up of test production for SARSCoV-2. But apparently, the managers and strong shareholders still prefer to cash in, after the company found itself in troubled waters last year with the abandonment of its own next-generation sequencers, problems in China, and the demission of longtime boss Peer Schatz. The Americans have deep pockets: With a surcharge of 23% on the closing price of the ordinary shares in the Frankfurt Prime Standard on 2 March, the approximately 66% free float needs to be convinced of the deal. Although the share price increased by around 15% after the takeover bid was announced, it was quoted above the offered price of 39€ per share at the time of going to press. Thermo Fisher itself lost 20% of market capitalisation during the crisis. If the minimum acceptance rate of 75% is reached, and the antitrust authorities

agree, Germany would lose its showpiece company in biotechnology. The 5,100 employees in 26 countries generated sales of almost €1.5bn last year. Qiagen is regarded as a global leader in molecular diagnostics and sample preparation technologies. Thermo Fisher will, according to all experience, know how to cleverly integrate market shares and knowledge; Qiagen is likely to disappear from the stock market.

America first? Another strange case was about a company which is one of the most promising developers of a vaccine in the corona crisis: Tübingen-based biotech company Curevac AG. SAP co-founder Dietmar Hopp, who is the majority shareholder of with a stake of around 80%, has clearly spoken out against granting the US pre- or exclusive licensing rights for the mRNA vaccine against the SARS-CoV2 virus developed by the Tübingen-based company. “Hopefully, if we soon succeed in developing an effective vaccine against the corona virus, it will be possible to reach, protect, and help people not only on a regional level, but in a spirit of solidarity, all over the world,” explained Hopp. It had been circulated several times among German government insiders that US President Donald Trump had offered CEO Daniel Menichella, who was later surprisingly replaced by Curevac founder Ingmar Hoerr, a large sum of money at a meeting of the US coronavirus task force with COVID-19 vaccine developers at the beginning of March to entice Curevac away from Germany and into the US. 

Picture: Qiagen

European Biotechnology | Spring Edition | Vol. 19 | 2020

Immatics goes public creatively IP O Through a merger with the listed US company Arya Sciences Acquisition Corp. and a simultaneous equity investment, the German T-cell therapy specialist Immatics Biotechnologies GmbH is aiming for NASDAQ listing. Financially, the manoeuvre is interesting: Arya Sciences Acquisition Corp. (Houston) is an empty shell, a Special Purpose Acquisition Company (SPAC). The new Immatics N.V. (IMTX), which will be created by the merger in the future, will initially receive US-$148m in cash – the money from Arya, it is parked in an escrow account. In addition, Immatics will receive a further US-$104m through a private investment in public equity (PIPE) by several US institutional investors led by Perceptive Advisors – a total of US-$252m. The transaction is expected to be completed in the second quarter of 2020 following shareholder approval. In addition to Perceptive Advisors, the PIPE investors include Redmile Group, Federated Hermes Kaufmann Funds, RTW Investments, Sphera Funds, an-

other unnamed healthcare investor, as well as the previous Immatics investors Dievini Hopp BioTech, AT Impf, and Wellington Partners. The German Immatics GmbH is contributing US-$350m equity to the business combination. In exchange, its shareholders will receive 35 million shares in the new Immatics N.V. The shareholders of Arya will exchange old shares for the new ones at a ratio of one to one. If all shareholders participated in the transaction, the current Immatics owners would hold approximately 61% of the shares of the new Immatics NV. The combined market capitalisation could amount to approximately US-$634m. According to Adam Stone, Chief Investment Officer at Perceptive Advisors and CEO of Arya, Immatics is a leader in the fast-growing TCR-T cell therapy segment. The old and new CEO of Immatics, Harpreet Singh, said he sees the transaction as a unique opportunity to make Immatics a global cancer specialist (see also page 22). Immatics recently attracted attention with a billion-euro deal with GSK. 

Picture: pixabay/kalhh

Big milestone for AC Immune

Alzheimer’s AC Immune SA has received a milestone payment of CHF10m from US giant Eli Lilly and Company. In only 15 months’ time, the Swiss biotech has been progressing its small-molecule, Morphomer™ Tau aggregation inhibitor candidate ACI-3024 into Phase I testing. The collaboration between Lilly and AC Immune focussing on the broad development of Morphomer™ Tau aggregation in-

hibitors for Alzheimer’s disease (AD) and other neurodegenerative diseases started in December 2018 with a CHF80m milestone payment and CHF50m equity investment by Lilly. Lilly made a first milestone payment of CHF30m in September 2019. Under the original deal, AC Immune received CHF 130m in upfront cash and convertible equity. The company is now eligible for a new, additional milestone payment of CHF60m. The change increases the total deal potential value to CHF1.86bn No changes were made to other later-stage milestones or royalty terms. AC Immune will conduct a Phase I trial of ACI-3024 initiated in July, while Lilly will fund and conduct further clinical development and commercialisation. 

Centr al EUROPE

News Investment from China Chinese Fosun Pharmaceutical Group (Shanghai) will pay up to US$135m (€120m) upfront and in milestones, including an equity investment of US$50m (€40m) for 1,580,777 ordinary shares in German BioNTech SE (Mainz) to get the commercialisation rights in China for BioNTech’s preventive mRNA vaccine candidate BNT162.

Corona postponements The 4th AMR Conference – Novel Antimicrobials & AMR Diagnostics – has been postponed and will now take place on August 24 and 25 in Basel/Switzerland. +++ The Swiss Biotech Day also has a new date: The SBD will now take place on 15 September at the Congresss Centre Basel. +++ The date for EFIB 2020, the European Forum for Industrial Biotechnology and Bioeconomy, is currently still being held: 5 and 6 October in Frankfurt/ Main.

Collagen animal-free Up until recently, virtually all collagen for medical or pharmaceutical applications was animal-derived, because efforts to produce functional, collagen-like molecules in bacteria, yeast, or insect cells in industrial scale were less effective. German fine chemical specialist Evonik Industries AG (Essen) announced recently that it was the first company worldwide that has set up an industrial, biotech process for the manufacture of recombinantly produced human collagen – a US$3.5bn market growing at 5.3% annually.

SOUTHERN EUROPE

Vector alliance Virus purification BIA Sep-

arations (Ajdovšcina, Slovenia) and the University of Zagreb (Croatia) signed a license contract to commercialise the very first native elution method affinity chromatographic purification of viral vectors for gene therapy. The scalable method, which works at a pH of 6 – 8 and was developed by Marija Brgles and coworkers at the Institute of Immunology, University of Zagreb, helps preserve the integrity, infectivity, and potency of viral vaccines, oncolytic virotherapeutics, and gene therapy vectors. Usually, viral particles are partially degraded, due to the low pH during the elution from affinity columns. The novel, patented technology (WO 2017/129450A1) circumvents this by using a concentrated solution of amino acids and their salts, maintaining a neutral pH (6 – 8). Under the contract, monolith column provider BIA Separations will gain global marketing rights for directly licencing the technology to life sciences companies and researchers, and for providing elution media for its monolith affinity columns. As part of the agreement, research teams from both organisations will collaborate to develop follow-on technologies to support the purification of viruses and viral vectors for research and clinical use. According to Aleš Štrancar, CEO of BIA Separations, his company wants to “provide customers with a one-stop-shop for the manufacture of gene therapy vectors, vaccines, exosomes, DNA/RNA, and any novel, complex biopharma product.” L

European Biotechnology | Spring Edition | Vol. 19 | 2020

End of the line

Ready for EMA

Bankruptcy Beleaguered Bio-On SpA, charged with market manipulation and false accounting as part of the Guardia di Finanza operation aptly named “Plastic Bubbles,” is bankrupt. The court of Bologna declared the bankruptcy in December, simultaneously authorising the temporary continuation of the bioplastics company, in order to maintain business continuity and prevent the company’s dissolution. In November, the company had announced it was suspending any type of payment, including to employees, suppliers, and credit institutions. 

m anufac turing Together with the Swedish biotech Intervacc AB and LIOF-Pharma, CDMO 3P Bio pharmaceuticals has completed the manufacturing process for Strangvac, a vaccine against equine strangles. The compound is now ready for the EMA registration application. The vaccine has been developed with a technology based on recombinant proteins that reduces the risk of serious side effects. Intervacc CEO Andreas Andersson celebrated the “very important milestone towards an approved vaccine against strangles.” 

Hat trick for skin health Dermatology Barcelona-based pharma company Almirall has hit the ground running in 2020: in January alone, the company clinched three deals. First up, Almirall strengthened its medical dermatology pipeline by acquiring Bioniz Therapeutics. With the acquisition, the company will have access to BNZ1, a novel multicytokine inhibitor in development for cutaneous T-cell Lymphoma, an orphan disease with high unmet medical need, and alopecia areata, an autoimmune hair disorder with no approved treatments. The very next day, Almirall signed a strategic agreement with Californian consumer genetics and research company 23andMe, giving Almirall the rights to develop and commercialise 23andMe’s

bispecific monoclonal antibody that blocks all three isoforms of IL-36 cytokine. IL-36 is a part of the IL-1 cytokine family, which is associated with a number of inflammatory diseases, including various dermatological conditions. The same day, the skin-health-focused pharmaceutical company announced a strategic collaboration agreement with WuXi Biologics, gaining Almirall access to WuXi Biologics’ proprietary antibody platforms, including WuXiBody™, to discover multiple, novel bio-specific antibodies. “With these new agreements, Almirall expands its innovative options in medical dermatology, including therapeutic bio-specific antibodies,” commented CEO Peter Guenter. L

Pictures: Tarkan K/Pixabay

European Biotechnology | Spring Edition | Vol. 19 | 2020

SOUTHERN EUROPE

Shortcut to market for SCLC drug News Market approval Pharma Mar‘s lung cancer drug is taking the quick route to the US market. In February, the FDA granted Priority Review of the NDA for lurbinectedin in relapsed Small Cell Lung Cancer (SCLC). PharmaMar had submitted the NDA based on Phase II multicentre basket trial, in which the compound achieved its primary endpoint of Overall Response Rate. “The application for registration under accelerated approval regulations gives us the possibility that the FDA could approve lurbinectedin in the US for treatment of small cell lung cancer in 2020, and that, if approval is obtained, could begin to be marketed in the second half

of 2020 in the United States,” explains Luis Mora, general manager of PharmaMar’s Oncology Business Unit. The synthetic drug developed by Madrid-based PharmaMar SA was exclusively licenced by Jazz Pharmaceuticals plc (Dublin, Ireland) in December 2019. PharmaMar collected an upfront payment of US$200m and is also eligible to receive US$800m in milestone payments, in addition to royalties on net sales. Lurbinectedin, a DNA minor groove binder analogue of trabectedin, works by blocking RNA Polymerase II-dependent, oncogenic transcription programmes and by modulating the activity of tumour-associated macrophages. L

Immune push

Vaccine deal

Combo Therapy Bioncotech Therapeutics has found a major collaborator with Merck Sharpe & Dohme. In December, the Madrid-based RNA specialist entered into a Phase II clinical trial collaboration with an MSD subsidiary. The two companies plan to evaluate if Bioncotech’s synthetic dsRNA complex BO-112 can improve the efficacy of MSD’s PD1 checkpoint inhibitor pembrolizumab in patients with advanced-stage, solid tumours with liver metastases. MO-112 is a stimulator of the innate immune system when administered intra-tumourally. “Early clinical data suggest that BO112 induces immunological changes in the tumour microenvironment and beyond, which may render previously anti-PD1 refractory tumours susceptible to checkpoint inhibition,” said Dominique Tersago, CMO of Bioncotech. “By targeting the metastatic liver lesions as the site for intra-tumoural injection, we aim to reduce organ-related variability of the injection site, and also to evaluate if BO112 has the potential to break through the generally immune-tolerant hepatic environment and trigger or improve responsiveness to anti-PD1 therapy.” L

Collaboration After working together since 2015, Algenex and FATRO are once again collaborating on the development of a vaccine. Privately owned biotech Algenex (Madrid) specialises in disruptive technologies for recombinant biologics production and has developed a baculovirus, vector-mediated expression platform that uses insects as natural, single-use bioreactors. This platform, CrisBio, will be used by Bologna-based animal health specialist FATRO SpA to develop a vaccine for a major swine indication. The CrisBio technology was also involved in the recombinant VLP vaccine jointly developed by the two companies, which was submitted for EU marketing authorisation in October. “For FATRO, CrisBio technology represents an important opportunity to expand its portfolio of vaccines for veterinary use with a series of highly innovative products,” said FATRO VP Francesco Meliota. “The excellent results obtained during the development of the first product further reinforced our belief in its practical potentialities.” Commercial and financial terms of the agreement were not disclosed. 

Beneficial microbes Researchers have discovered a bacterium that can reduce the risk of acquiring infections. The scientists, led by Karina Xavier from Instituto Gulbenkian de Ciência in Oeiras, Portugal, published their findings in N ature M icrobiology (doi: 10.1038/s41564-019-0658-4). They revealed that when the bacterium Klebsiella michiganensis was present, it could resist the invasion by other bacteria like E. coli or Salmonella, because it can metabolise nutrients available in the intestine more efficiently, competing against potential invaders and preventing the entry of other bacteria that can harm the host.

Pooling strengths Milan-based drug discovery company Axxam has formed a strategic alliance with Dutch CRO ZoBio. The goal is to offer an integrated toolbox of protein production and engineering technologies and screening methods using cellular, biochemical, high content, and biophysical assays.

COVID-19 vaccine Advent Srl, an IRBM company, is collaborating with the Jenner Institute to develop a coronavirus vaccine for clinical testing. The “seed stock” of the novel coronavirus vaccine ChAdOx1 nCoV-19 is currently being produced at Oxford University’s Clinical Biomanufacturing Facility. This will be transferred to Advent, which will initially produce 1,000 doses for the first clinical trials of this vaccine.

EASTERN EUROPE

European Biotechnology | Spring Edition | Vol. 19 | 2020

Western expansion

Wind of change EMA Following receipt

of a Questions & Answers document from the European Medicines Agency (EMA) in December 2019, Polish biosimilar developer Mabion SA said it is considering filing two registrations for its lead product MabionCD20, with both resulting in a possible market launch in Q1/2022. The company’s current MAA is for production of the biosimilar version to Roche’s blockbuster rituximab at 250l scale at its Lódz site. According to Anna Małecka, regulatory specialist at Mabion, the company originally planned to apply for post-registration approval of a commercial 2,500 litre scale. However, the Agency, which hasn’t yet submitted an opinion to Mabion’s MAA filed in 2018, seems “to have more comfort” in a single registration, including “a large, target scale of production” process. As a consequence, Mabion is now considering two scenarios for registration – the first being the original two-stage MAA, and the second, a one-stage scenario, including the withdrawal of the current application for a small scale and the inclusion of an already targeted product in the new registration application. A possible resubmission of such a large-scale application could take place in Q4/2020. Mabion’s Board expects the EMA to publish its opinion in Q4/2020. The EMA has already approved CD20 biosimilars from Sandoz AG (Rixathon, Riximyo) in 2017, Celltrion Hungary (Ritemvia, Truxima, and Blitzima, 2017), and Pfizer Europe (Ruxience 2020). L

Cancer Pipeline In January, Prague-based SOTIO a.s. opened a subsidiary in the midst of global biopharma hub Basel, Switzerland. SOTIO Biotech AG will accelerate the company’s pivotal clinical trials, EU market approval, and commercialisation of its oncological pipeline. Czech investor PPF Group holds a majority share in the developer of chemo-immunotherapies, ADCs, cancer cell therapies, and chemotherapeutics. The new entity will be located within Technology Park Basel. “The opening of offices in Switzerland is part of our strategy of expanding our pipeline of new immuno-oncological products and strengthening our presence in globally-recognised biotech hubs,”

says Dr. Radek Spisek, CEO of SOTIO. “We are growing internationally and running and preparing multiple clinical trials with various oncology treatments. Basel complements our R&D activities in other European countries, the US, and China.“ SOTIO and PPF, which acquired a 19.2% stake in British T cell specialist Autolus Therapeutics plc last September (see European Biotechnology, Winter 2019 edition), have built a biotechnology portfolio through in-house research and development, investments, acquisitions, and in licensing of innovative products with companies like NBE-Therapeutics, Cellestia Biotech (both CH), Cytune Pharma (F), Autolus Therapeutics (UK), MaveriX (US), and Lead Discovery Centre (GER). L

Sotio headquarters

Mediterranean food is good Microbiome An EU-funded consortium has discovered that a 12-month switch to a Mediterranean (NU-AGE) diet alters the gut microbiota and can reduce frailty. The team from Finland, the Netherlands, France, the UK, Ireland, Italy, Russia, and Poland profiled the gut microbiota in 612 nonfrail or pre-frail subjects across five EU countries before and after the Mediterranean diet. Certain enriched microbiome

taxa were linked to markers of lower frailty and improved cognitive function, and showed less inflammatory markers, such as CRP and IL-17. At the same time, short/branch-chained fatty acid production increased, while secondary bile acids, p-cresols, ethanol, and carbon dioxide decreased. The researchers conclude their results may lead to the development of prebiotics, which may support healthy aging. L

Picture: Sotio

Regulatory Affairs

European Biotechnology | Spring Edition | Vol. 19 | 2020

Use of real world data Real World Data The European Med-

icines Agency EMA explained at the beginning of February how it intends to take real-world data into account in the future for European drug approval. DARWIN (Data Analysis and Real World Interrogation Network), a central database system that is intended to bring together the data collected within the various EU healthcare systems on a single platform by 2023 and, thus, counteract the fragmentation

of data, is to serve as an interface for the data collected from patients in hospitals. Since clinical studies are conducted under very artificial conditions, they only represent the daily treatment routine quite partially, it is argued, to justify interference with personal data sovereignty. For companies, the inclusion of real-world data would reduce development costs and significantly increase the speed of development, since the importance of time-con-

www.ema.europa.eu

suming clinical studies will decline in the long term. The EMA estimates that the development of DARWIN will cost €30m to €50m, and the annual maintenance costs €10m to €20m. L

Recommendations from the EMA: MA (market authorisation); cond MA (conditional MA); ODD (orphan drug designation)

Drug name

Indication

Company

Status

› Givlaari (givosiran)

Treatment for acute hepatic porphyria in humans aged 12 years and older

Alnylam Netherlands BV

MA rec/ PRIME

› Rybelsus (semaglutide)

Treatment of adults with insufficiently controlled type 2 diabetes to improve glycaemic control

Novo Nordisk A/S

MA rec

› Vaxchora (recombinant oral live Cholera vaccine)

Prophylaxis against cholera

Emergent Netherlands BV

MA rec

› Liumjev (insulin lispro)

Treatment of diabetes mellitus in adults

Eli Lilly Nederland BV

MA rec

› Nilemdo (bempedoic acid), Nustendi (bempedoic acid / ezetimibe)

Treatment of primary hypercholesterolaemia and mixed dyslipidaemia

FGK Representative Service GmbH

MA rec

› Nubeqa (darolutamide)

Treatment of prostate cancer

Bayer AG

MA rec

› S taquis (crisaborole)

Treatment of atopic dermatitis

Pfizer Europe MA EEIG

MA rec

› Ruxience (biosimilar rituximab)

Treatment of non-Hodgkin lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis, and Pemphigus vulgaris

Pfizer Europe MA EEIG

MA rec

› Budesonide/Formoterol Teva Pharma BV (budesonide/formoterol fumarate dihydrate)

Treatment of asthma and chronic obstructive pulmonary disease

Teva Pharma BV

MA rec

› Trepulmix (treprostinil sodium)

Treatment of chronic thromboembolic pulmonary hypertension

SciPharm Sarl

MA rec

› Idhifa (enasidenib)

Treatment of adults with acute myeloid leukaemia (AML)

Celgene Europe BV

MA withdrawn

› Fetcroja (cefiderocol)

Treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options

Shionogi BV

MA rec

› Zolgensma (onasemnogene abeparvovec)

Treatment of spinal muscular atrophy in infants with functional mutations in the SMN1 gene or with SMN2 trisomy

Novartis AG

cond. MA rec

› Pretomanid FGK

Treatment of tuberculosis, in combination with bedaquiline and linezolid

FGK Representative Service GmbH

cond. MA rec

› Zeposia (ozanimod)

Treatment of adult patients with relapsing remitting multiple sclerosis.

Celgene Europe BV

MA rec

› S utimlimab

Treatment of immune thrombocytopenia

Celerion Austria GmbH

ODD

Medical Cannabis

European Biotechnology | Spring Edition | Vol. 19 | 2020

Medical cannabis needs a clinical and regulatory path CBD Medical or low-THC cannabis or cannabinoids, such as CBD, have been predicted to create

new treatment options in medically underserved areas such as neurology and pain relief. Figures from the IMARC Group valued the global cannabis market at US$11bn in 2017, with the Canadian and US markets leading, and predict it to reach about US$37bn by 2023. However, companies that aim to develop CBD-derived treatments face prejudices and adverse acceptance of their products.

vomiting in patients undergoing cancer chemotherapy. Furthermore, dronabinol is given to HIV patients who suffer from weight and appetite loss.

Turning point

For the public, cannabis is still mostly perceived as an addictive drug, whose psychoactive effect is due to the action of tetrahydrocannabinol (THC), an activator of the CB1 receptor protein in the human brain. Medical applications, however, often make use of dried cannabis, hemp flowers, and their extracts, low in THC and rich in cannabidiol (CBD), which restrains CB1 signalling and prevents the adverse effects of THC, such as psychosis, etc. In 2011, British GW Pharmaceuticals plc pioneered the use of Sativex, a mouth spray given to treat multiple sclerosis-associated spasticity. Though Sativex was the first EU-approved botanical drug con-

taining THC and CBD, it had to be prescribed under the narcotics act and, thus, did not change the perception of medical cannabis. As the exact mode of action of Sativex and of Canemes ® – a synthetic THC derivative originally developed by Eli Lilly and re-introduced to the market in 2017 by AOP Orphan Pharmaceuticals AG – remained elusive, researchers who wanted to conduct clinical trials or to publish research results faced regulatory hurdles and rejections. Canemes (nabilone) and the synthetic THC derivative dronabinol are tranquillizers prescribed as second-line therapeutics under the narcotics act to treat nausea and

While there is little data available from clinical studies suggesting that CBD preparations are helpful in neuropathic pain relief, there are many claims for potential medical cannabis benefits, namely as a new treatment option for ADHS, Alzheimer’s, etc. Furthermore, many companies sell CBDcontaining oils and formulations that are not quality-controlled in markets, such as those in Canada and many US states, which have approved medical cannabis use but neglected to implement an appropriate regulatory framework to ensure a reproducible composition and quality of products. The year 2018 probably marked a tipping point for researchers and developers of CBD-derived drugs, because that period saw the regulatory approval of a CBD oil product with a defined composition: GW Pharmaceuticals received FDA approval of the cannabinoid Epidiolex (in sesame oil), which, as adjunctive therapy to clobazam, significantly reduced the frequency of seizures in two rare forms of paediatric epilepsy, Lennox-Gastaut syndrome (LGS) and Dravet syndrome (by 27 – 28% vs placebo).

Creating confidence The approval shows what is lacking to instill confidence concerning composition

Picture: Canopy Growth Corp

Medical Cannabis

European Biotechnology | Spring Edition | Vol. 19 | 2020

3A4 substrates

2D6 substrates

1A4 substrates

Cyclosporine Fentanyl Dexamethasone Amiodarone

Amitriptyline Carvedilol Duloxetine Haloperidol Tolterodine

Clozapine Propranolol Amitriptyline Oxycodone Venlafaxine

bioavailability CYP 3A4/2D6 inhibitor

CYP 1A2 inducer bioavailability

2C19 Inhibitors Clopidogrel Omeprazole Fluoxetine Voriconazole

2C9 Inhibitors CYP 2C19 Cannabinol

Tetrahydrocannabinol

CYP 2C9

metabolite

CYP 3A4 metabolite

Amiodarone Clopidogrel Fluconazole Phenytoin Metronidazole 3A4 Inhibitors Clarithromycin Ketoconazole Itraconazole Protease-Inhibitors

Ibeas Bih C, Chem T, Nunn AV, Bazelot M, Dallas M, Whalley BJ. Molecular Targets of Cannabidiol in Neurological Disorders. Neurotherapeutics, 2015; 12(4), 699–730.

 @CulshawReed

CBD and THC interactions through the cytochrome P450 system

and quality of CBD products for consumers: a regulatory path that does not block trials, which could provide clinical evidence for new medical uses of CBD products, through six months of paperwork. In contrast, guidelines are urgently needed, which define quality and GMP rules for

all manufacturers, to ensure access for patients to cannabinoids that have been reproducibly shown to be beneficial for good health. A recent scientific report on cannabis as medicine, commissioned by German health insurance company TK, defines the medical indications in which

CBD-based products have been proven to be beneficial for patients:

›› neuropathic pain ›› spasticity in multiple sclerosis ›› epilepsy ›› nausea/vomiting after chemotherapy ›› appetite increase with HIV/AIDS. Furthermore, possible indications for medical cannabis are: ›› anxiety disorders ›› insomnia ›› Tourette syndrome ›› ADHD. Cannabis, however, has not been shown to be effective for the following indications:

›› depression ›› psychoses ›› dementia ›› glaucoma ›› bowel disease.

t.gabrielczyk@biocom.eu

AIRGENEX® MedCann

Controlled Drying of Medical Cannabis efficient, safe, GMP ready for high quality Results and constant Processes Visit us at ICBC Berlin // 1-3 April 2020 // Hall Potsdam 1 / Stand 12

www.harter-gmbh.de

Medical Cannabis

European Biotechnology | Spring Edition | Vol. 19 | 2020

An Outline of the German Medical Cannabis Market Medicinal Cannabis The medical cannabis market has grown significantly in recent years.

In Germany, the quantity of imported cannabis products has increased dramatically. In comparison to only 1.2 tons in 2017, German medical cannabis distributors imported about 3.13 metric tons of cannabis flowers for direct medical care of patients in 2018, while around 120 kg have been re-exported. In 2019, this amount doubled to around 6.7 tons. › Peter Homberg, Dentons, Berlin, Germany

According to statistics from the International Narcotics Control Board (INCB), which is the independent, expert body that was established by the member states of the 1961 UN Single Convention on Narcotic Drugs, Germany has imported in total around 7.6 tons of all kind of cannabis products, namely the sum of cannabis flowers, extracts, preparations, and finished medicinal products in 2018, compared to around 4.5 tons in 2017. In Germany, the gross turnover for unprocessed cannabis flowers in the statutory health insurance for 2018 amounted to about €33m, and about €26m for cannabis-containing preparations. Moreover, the INCB has estimated that the demand for medical cannabis in Germany may further grow to a maximum of 16 tons in 2020. This, in comparison to 6.7 tons to 8.8 tons in 2019, is a significant increase, which is expected, due to rising patient numbers in 2020. It is, however, interesting to note that the INCB’s estimated figure for 2019 has been briefly raised to 21 tons in November 2019 and immediately corrected to 16 tons for 2020. The expected increase in demand has, therefore, apparently not occurred as quickly as expected. In order to meet the steady increase in patient demand, the cultivation of medical cannabis in Germany was approved on the basis of a tender for a total of 10.4 tons for four years. The first harvest is only to be expected at the end of this year. A public invitation to tender is cur-

rently pending for the provision of logistics, distribution, and services required for the federal, wholesale trade in cannabis flowers. Additionally, imports from other countries will continue to be possible in future.

Requirements for the import of medical cannabis to Germany

Peter Homberg is a partner in the Dentons Berlin office. He focuses on life sciences, IP, corporate law, and M&A transactions in the life sciences and high-tech sectors, as well as in R&D and cooperation agreements, cross-border IP licensing, and IP strategies. Furthermore, he has extensive experience providing legal advice on compliance issues. Additionally, he is the head of the European Cannabis sector group. Peter advises inter alia companies in the pharmaceutical, diagnostics, biotechnology, medical device, and medical cannabis industries— from startups to large, publicly listed companies. Furthermore, he has broad transactional experience in Southeast Asia. Peter is a member of several societies and associations, such as the LES, the GRUR, the DIS, as well as the Pharma-Lizenz-Club Deutschland e.V.

Requirements for the distribution of medical cannabis have not yet been harmonized in the European Union and are, thus, still governed by the applicable national law. Under Annex III of the Narcotics Law (Betäubungsmittelgesetz – BtMG), only cannabis coming from cultivation for medical purposes under state control in accordance with Articles 23 and 28, Paragraph 1 of the 1961 Single Convention on Narcotic Drugs may be marketed and prescribed in Germany. This means that, in addition to finished pharmaceuticals, only cannabis flowers and extracts which have a recognized medical purpose in the country of origin and are subject to control there, in accordance with the aforementioned requirements of international law, can be imported into Germany on the basis of a general narcotics license granted by the Federal Institute of Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte – BfArM) under Section 3 Paragraph 1 of the BtMG and individual import licenses pursuant to Section 11 Paragraph 1 of the BtMG.

Picture: Dentons

MEDICINAL CANNABIS Patient safety made by GMP-compliance

Keeping GACP-/GMP-compliance in mind PRODUCT sets the frame for PROCESS sets the frame for FACILITY

Production of medicinal cannabis means more than growing healthy plants

Cloud based technology Together with a large German corporation, we are developing a blockchain-based softwareas-a-service (SaaS), offering the management of data in the value chain of medicinal cannabis and the storage of critical data in a tamper-proof manner. Please contact us for further information and participation.

Your reliable way to a safe and consistent production of medicinal cannabis J&K CONSULTING KirchstraĂ&#x;e 11, 41569 Rommerskirchen | Germany T. +49 2183 41 894-0 | www.j-k-consulting.de

Medical Cannabis

The BfArM issues the permits and authorizations applied for by the market participants if the legal requirements are met. In addition, the qualitative requirements for medicinal cannabis are regulated by drug law and pharmacy law. The state authorities involved in drug monitoring and testing are responsible for checking, determining, and complying with the regulations of drug law with regard to the import of medical cannabis. The authorities check, for example, if cannabis is cultivated under EU Good Agricultural and Collection Practice (GACP), and if the exporting company follows the EU Good Manufacturing Practice (GMP) requirements. On top of that, itâ&#x20AC;&#x2122;s not only a question of the exporter being EU GMP compliant, but there is also the question of whether the exporter has the respective export licenses in his jurisdiction. When importing from non-EU countries, additional permits are usually required. According to the most recently written statement of

European Biotechnology | Spring Edition | Vol. 19 | 2020

the Federal Opium Agency (Bundesopiumstelle), Canada, the Netherlands, and Portugal are the only countries currently exporting cannabis products under the 1961 UN Single Convention to Germany. General narcotic permits in accordance with Section 3 BtMG for the import of medical cannabis have already been granted for the Netherlands, Canada, Portugal, Spain, and Denmark. With the exception of Spain, corresponding import licenses have been issued in accordance with Section 11 Paragraph 1 BtMG. For the import of cannabis for medical purposes from Uruguay, Colombia, Israel, and Australia, no permission according to Section 3 BtMG and no import permit according to Section 11 Paragraph 1 BtMG has been granted so far. The fact that Canada has legalized the use of cannabis is viewed by the Federal Government of Germany as unproblematic. To the knowledge of the Federal Government, the existing Canadian legal

framework for the cultivation and distribution of cannabis for medical purposes, under which the export to Germany occurs, will also be continued under the new Canadian legislation. In the view of the German Federal Government, there are no consequences for the import of medical cannabis to Germany.

Unresolved problems and hurdles Recent problems for cannabis distributors include the application of the permit requirement for irradiation with ionizing radiation to cannabis. In order to improve the microbiology, cannabis flowers are frequently irradiated with ionizing radiation. This means that often radiation is used to kill-off microbial contaminants. Manufacturers and distributors selling cannabis using such technique are obliged to hold a respective license under the act for the treatment of pharmaceuticals with radioactive or ionizing radiation (AMRadV), which is the applicable law for the irradiation of pharmaceuticals. The Canadian cannabis producer Aurora was forced, for example, to take its cannabis products off the German market, because they had been irradiated, and the company didnâ&#x20AC;&#x2122;t hold the respective license. Meanwhile, Aurora has actually received the necessary irradiation licenses and is now back in business. Problems and hurdles for patients are still posed, above all, by the excessively high prices caused by costly, time-consuming quality inspections of the products in the pharmacies and protracted approval and reimbursement procedures of health insurance funds. Finally, the commercialization of CBD products opens up another important market and offers, on the other hand, some more uncertainties. In this respect, the marketability of CBD products under the Narcotics Act and their classification as novel food is still a major issue. Another problem is the marketability of CBD in cosmetics. Here, opinions still differ widely. It remains to be seen whether there will be a uniform, EU-wide approach in the future. L

Picture: Jcomp - Freepik.com

When a cookie cutter response just won’t cut it talk to the people with a focus on ﬂexibility, talk to Luina Bio. When it comes to biomanufacturing GMP materials for use in clinical trials, many production facilities lack the ﬂexibility needed to create bespoke solutions in a timely, scaled and cost effective manner. At Luina Bio we do things a little differently.

Products: • Recombinant proteins • Live Biotherapeutics • Bacterial vaccines • Plasmid DNA

With over 20 years experience in the pharmaceutical, biotechnology and veterinary industries we know the more we focus on each client’s speciﬁc needs and goals, the clearer their vision for the future will become. Looking for an early phase clinical biomanufacturing partner? Talk to Luina Bio to see how we can bring your drug to life.

Services: • Bacterial / Yeast Fermentation • Cell Banking • Process Development/Scale-up • cGMP Manufacture of biopharmaceutical APIs • Stability Testing

Luina Bio: your vision is our focus.

Contact: visit: luinabio.com.au

call: +61 (7) 3273 9176

email: enquiries@luinabio.com.au

Medical Cannabis

European Biotechnology | Spring Edition | Vol. 19 | 2020

Digitally supported production of medical cannabis Intellectual Propertyâ&#x20AC;&#x192; A challenge whose success lies in efficient process management

and digital development! The times of digitalisation and Industry 4.0 do not stop at the production of medical cannabis for the pharmaceutical industry. The combination of IT systems and blockchain-based processes allows the value-added chain to be automated and the data generated to be mapped in a tamper-proof manner. â&#x20AC;ş Hannah Maria Lambertz, Consultant and Quality Manager at J&K Group

Filling and packaging are just as relevant as components of pharmaceutical production as all preceding process steps in the value-added chain. Therefore, an intensive and effective risk assessment is required to ensure patient safety regarding medical cannabis. This is due to the fact that upstream, finishing processes result in an open pharmaceutical product whose composition can be affected or contaminated by external influences. Furthermore, in the course of the process, the risk of contamination cannot be excluded, even when cannabis products are packaged. The greatest risk to patients is with the immediate packaging, as here, the packaging is in direct contact with the medicinal product, and therefore, the highest risk of exposure to the medicinal product exists. In the case of secondary and tertiary packaging, the greatest risk lies in the unambiguous traceability of batches.

ess. Since patient safety is the top priority in the production of drugs, switching to fully-automated systems at this point will greatly increase patient safety.

Digital change

Hannah Maria Lambertz Master of Agricultural Sciences, Consultant and Quality Manager at J&K Group

Within the value chain, all data that have a quality-relevant influence must be recorded and processed to ensure clear batch traceability. In order to maintain data integrity, various companies are working on electronic data management systems that, in combination with cloud-based block chain solutions, digitally map parts of or even the entire value chain and store and distribute relevant information in a tamperproof manner. While manual work steps related to the product, like packaging, are still the order of the day, in many places in the medical cannabis industry, the pharmaceutical industry is currently rethinking this proc-

Since a digital solution is available for almost every procedure step, GMP processes must be designed in accordance with the latest state of the art in science and technology, because only the continuous development of processes can keep up with the global market. Furthermore, it is recommended that all manufacturing processes are based on digital concepts, the projects are planned and implemented digitally, and the production is managed digitally. In this way, all process-relevant information can be stored and utilized in a single, digital solution in a tamper-proof manner, so that in this system, from sowing to growing, processing, packaging, and storage to distribution, all data can be made available remotely for the various stakeholders. A cannabis agency, for example, can retrieve the quantity reports from the cloud, instead of these having to be reported by the company, as was previously the case, offering a whole new level of data integrity. This is essential in order to be able to implement upcoming, regulatory requirements in a timely and cost-effective manner and, thus, to be able to survive in the constantly growing market. L

Pictures: Mareike Daennart; stock.adobe.com/creativefamily

European Biotechnology |Spring Edition | Vol. 19 | 2020

Science & Technology

Cancer triggers Double impact Colorectal Cancer Intestinal bacte-

Bone loss Although JAK inhibitors

ria can trigger the development of colorectal cancer. For the first time, Dutch researchers headed by Hans Clevers proved that pks+ E. coli strains expressing DNA-damaging colibactin induced specific mutations in human intestinal organoids. Using whole-genome sequencing of the organoids before and after injections over five months revealed a distinct mutational signature that was absent from organoids injected with a control E. coli strain that cannot produce active colibactin. The mutational signature was also present in a subset of 5,876 human cancer genomes – mostly genomes of colorectal cancer – from two independent cohorts. The authors conclude that their data suggest a discrete mutational signature in colorectal cancer and imply that the underlying mutational process directly results from past exposure to pks+ E. coli. They note that pks+ E. coli is present in around 20% of healthy individuals and suggest that removing the strains could decrease the risk of developing colorectal cancer – although further research is needed to confirm these findings L

are mainly known for their anti-inflammatory effects, particularly in approved drugs for rheumatoid arthritis, some research suggests that they may also counteract the pathways that contribute to bone loss, which frequently appears in arthritis patients. Seeking insight, Susanne Adam and co-workers gave tofacitinib and baricitinib (another JAK inhibitor) to both healthy mice and mice with either inflammatory or noninflammatory bone loss. The drugs increased bone mass in the rodent models and guarded against further bone erosion. When given to isolated cells, the JAK inhibitors supported the function of bone-building osteoblasts by increasing the activity of the Wnt signalling pathway. Adam et al. then performed CT scans on two patients who received tofacitinib for their rheumatoid arthritis and observed that the treatment repaired a substantial part of the eroded bone in their knuckle joints. Although the findings in patients are preliminary, the researchers say they support further testing of JAK inhibitors as treatments for bone loss in larger groups of patients down the road. L

Regmed progress

Picture: MPI Münster, Hubrecht Institute

Molecular Medicine Researchers at

the Hubrecht Institute (Utrecht) and the Max Planck Institute for Molecular Biomedine (Münster) have revealed how the transcription factor Oct4 opens the chromatin to reset the DNA transcription of regular adult human cells into stem cells (Biophysical J., doi: 10.1016/j. bpj.2019.12.038). The researchers revealed for the first time which DNA and Oct4-binding domains in nucleosomes support DNA transcription. The ultimate plan of the researchers headed by Vlad Cojocaru is to engineer transcription factors for efficient and reliable production of stem cells and other cells needed in regenerative medicine. L

News Resistance breaker E x t racor p oreal UV ac tivation of a subset of NK cells (extracorporeal photopheresis) helped a patient with melanoma to recover from three grade II/III episodes of glucocorticoid-resistant autoimmune colitis induced by a cancer immune therapy by the PD1 blocker nivolumab and the CTLA4 inhibitor ipilimumab (NEJM, doi: 10.1056/ NEJMc1912274). The team, headed by Robert Zeiser from the University Medical Centre, Freiburg, was able to show that photopheresis quadruplicated the number of an immunosuppressive NK cell population that mostly expressed the surface marker CD16, but also CD57 as well as CD56, and expressed less proinflammatory cytokines 53 and 75 weeks after photopheresis than healthy controls. When transplanted to mice triggered with anti-PD1 antibodies and T-cells, these human NK cells in a dose-dependent manner prevented immune-related adverse effects. Thus, ECP may be effective in treating the 10% of patients who develop checkpoint inhibitor-induced autoimmune colitis.

Bacterial LEDs

Schematic image showing the pioneer transcription factor Oct4 (blue) binding to the nucleosome

Within the FET Open Horizon 2020 project ENABLED, engineers from Austria, Italy, and Spain are working to make sustainable light emitting diodes (LEDs) from bacteria-made proteins coupled to artificial amino acid-encoded dyes with sufficient luminosity. The sustainable, low-cost LEDs are to be built on a stable, organic coating, replacing rare earth minerals, a matrix of organic polymers, and the embedded proteinous dyes.

Science & Technology

European Biotechnology | Spring Edition | Vol. 19 | 2020

Trial validates clinical utility of septic shock biomarker bio-Adrenomedullin For decades, there hasn’t been a diagnostic option for critical care

experts to identify patients at high risk for the development of organ dysfunction and lifethreatening septic shock. Outcomes from a Phase II trial, in which risk patients were stratified by high bio-ADM plasma levels, suggest the marker may add significant benefit to patients. This supports personalised sepsis care driven by biomarkers that identify disease mechanisms.

Every 3.5 seconds, one in the 30.7 million patients annually diagnosed with sepsis, dies. But for decades, the causes of high sepsis mortality have remained obscure, blocking the development of disease-modifying treatments. Now, novel biomarkers are set to close the existing diagnostic gap, allowing identification of the cause of sepsis-related organ dysfunction in patients upon admission to the intensive care unit (ICU). This is significantly faster than the current standard of care and could form the basis of a personalised sepsis care, according to Andreas Bergmann, who led the development of procalcitonin (PCT) as a sepsis marker at BRAHMS AG, which he (and cofounders) sold to ThermoFisher Scientific. Under the Medicines4Future initiative, Bergmann subsequently cofounded three companies – Sphingotec GmbH (diagnostic biomarker tests), Adrenomed AG, and 4Teen4 GmbH (therapeutic antibodies) – following the vision of a targeted, and particularly more successful sepsis diagnosis and therapy.

Sphingotec GmbH currently has three sepsis biomarkers in its published diagnostic portfolio: bio-ADM as a marker reflecting endothelial function; DPP3 as a marker for cell necrosis-induced heart depression and kidney dysfunction, which identifies the sepsis patient population that could benefit from treatment by the MA-approved antiotensin II Giapreza. The Medicines4Future company 4TEEN4 is in preclinical development of the antibody procizumab, which targets DPP3, and penKid, which seem to allow a more rapid and specific monitoring of kidney function in patients admitted to the ICU than the current standard of care. About 700,000 of the 6 million sepsis deaths per year come from worsening of the kidney function, namely acute kidney injury.

Definitive proof-of-utility In February, the first proprietary biomarker – bioactive Adrenomedullin (bioADM®) – of Sphingotec, was validated through the results of the AdrenOSS-2 Phase II as a stratification and monitoring marker for patients with impaired endothelial barrier function. An elevated blood level of bioADM had previously been demonstrated to predict blood pressure break down via blood vessel leakage, resulting in oede-

ma, organ failure, and mortality in approximately 60% of sepsis patients and, thus, was chosen as an inclusion criterion for 301 patients enrolled into the trial. Modulating the adrenomedullin plasma level with the help of Adrenomed’s antibody adrecizumab clearly improved the survival rate for the preselected patient population vs patients obtaining standard treatment (see page 29). “From multiple prospective studies, we know that

bio-ADM alters endothelial permeability and predicts outcomes in patients admitted with sepsis to the ICU and ED,” said Prof. Dr Pierre-François Laterre from St Luc Hospital in Brussels, the principal investigator for the AdrenOSS-2 study, who spoke at a December meeting of 30 leading sepsis experts in Berlin. “However, when we announce the results of the AdrenOSS-2 study, we will have the proof that there is more than a correla-

Picture: Adrenomed. AG

Science & Technology

European Biotechnology | Spring Edition | Vol. 19 | 2020

tion between bio-ADM on endothelial function and outcomes,” Laterre then told European Biotechnology. At the end of February, his prediction came true: “In this case, I presume, we will see bioADM become the diagnostic standard-of-care within only a few years of time because, as with PCT, physicians will be able to stratify patients according to the need for early, aggressive intervention at admission to the intensive care unit or emergency department.” According to Laterre, early risk stratification “would [also] save significant amounts in cost.” Sphingotec GmbH, the developer of the bio-ADM and other sepsisrelated biomarker tests (see figures), said it will launch a rapid POC test called IB10 sphingotest ® bio-ADM ® by mid2020. The test is especially designed for ICUs and runs on its Nexus IB10 pointof-care platform. According to Laterre, “to evaluate if IB10 POC testing of bioADM is cost-effective compared to the extremely cheap diagnostic standard lactate, one must know the price per assay.”

endothelial function biomarker whose detection in the blood provides dynamic information on the patients’ progression in sepsis. High or rising blood levels of bio-ADM indicated an imbalance in the endothelial barrier function leading to oedema and shock, while decreasing levels demonstrated improved patient outcomes. Thus, bio-ADM represents not only a valid biomarker for endothelial function but also qualified as a biotarget and led to the subsequent development of adrecizumab by Adrenomed AG, a therapeutic antibody to treat septic shock. The lower, all-cause mortality for adrecizumab-treated patients in AdrenOSS-2 compared to placebo “allowed us to select the patients who have endothelial dysfunction” said Laterre, adding that “we saw that bio-ADM gave information on top of clinical standard parameters to assess patients’ severity. We will now go ahead to further investigate use-cases of bioactive Adrenomedullin as a biomarker in the clinical routine.” According to Bergmann, AdrenOSS-2 “indicates that using bioactive adrenomedullin as a biomarker can help identify those patients who could benefit in the future from adrecizumab. The utility of this biomarker expands far beyond this and already supports today the early clinical decision-making and monitoring of treatment success in sepsis.” L t.gabrielczyk@biocom.eu

Broad range of applications The amidated bio- or vasoactive form of adrenomedullin (bio-ADM), which makes up 5% to 20% of total adrenomedullin in the blood, has been previously validated in more than 22,000 patients as an

Infection PCT Systemic Inflammation Aministration of Chemicals (Antibiotics, Vasopressors) penKid®

Worsening of Kidney Function

Picture: Sphingotec GmbH

10%

Endothelial Dysfunction

DPP3 Release DPP3

bioADM®

Shock

Loss of Hearth and Kidney Function

Loss of Organ Perfusion 60%

20%

Multi Organ Failure Death

Clinical significance of bio-ADM; penKid and DPP3

News T cell factory thymus Italian and US doctors have found a therapy for severe combined immunodeficiency (SCID) forms that are not caused by mutation of bone marrow cells but by thymus cells, such as DiGeorge syndrome, CHARGE syndrome, FOXN1 deficiency, and otofaciocervical syndrome type 2 (doi: 10.1126/sciimmunol.aax1036). SCID causes an increased susceptibility to viral, bacterial, and fungal infections. When Luigi Notarangelo and colleagues from Meyer Children’s Hospital in Florence examined the mutation pattern in thymus cells of children with otofaciocervical syndrome type 2, they found biallelic and full loss-offunction PAX1 mutations that contribute to the disorder, which is characterized by deafness, facial and skeletal anomalies, and mild intellectual disability. In cell cultures, they found that PAX1-mutant cells have an altered gene expression profile for genes involved in thymic develop. They propose thymus transplantation as an appropriate treatment.

Nanoparticles vs disease It’s just a preclinical proofof-principle; however, German and Finnish researchers report that nanoparticles coated with the protein gliadin can rebalance a failure of the regulation of gliadin-specific Tcells that might trigger celiac disease (doi: 10.1053/j.gastro.2020.01.045). Uptake of such nanoparticles by antigen-presenting cells induced immune tolerance in models of autoimmune disease and reduced markers of inflammation and enteropathy. Takeda has licenced the programme from the Finnish company Cour Pharmaceutical Development.

Science & Technology

European Biotechnology | Spring Edition | Vol. 19 | 2020

Reversing the loss of insulin-secreting cells Diabetes In mid-February, two research teams independently claimed to be the first to

reverse the loss of insulin-producing beta cells using combinations of existing diabetes drugs. The earlier the cell loss is prevented, the less detrimental the symptoms of diabetes will be.

Up until this February, it was not clear if the 422 million patients worldwide suffering from diabetes could go into remission if only the function and number of insulinproducing beta cells in the pancreas were restored. At the end of the month, a team from the Munich-based Helmholtz Centre Munich and the Danish diabetes drug giant Novo Nordisk A/S demonstrated how to induce redifferentiation and restore the function of beta cells in mice pharmacologically. According to the research team headed by Heiko Lickert, Director of the Institute for Diabetes and Regeneration Research, “this opens up new avenues for a possible diabetes remission.”

Beta cell redifferentiation Single-cell RNA sequencing of surviving beta cells from mice with streptozotocin-induced diabetes revealed that these cells actually lost their cell identity following even low-dose streptozotocin treatment. Treating these mice with certain marketed diabetes meds and experimental treatments, the researchers looked for drug combinations that would restore beta cell function. They found that a stable conjugate of glucagonlike peptide-1 (GLP-1) and oestrogen developed by Novo Nordisk normalised blood glucose levels and glucose tolerance, as well as the number of beta cells and the amount of insulin produced by them in the pancreas. Further testing in human 3D cell models provided by the German cell culture specialist InSphero GmbH revealed that only the conjugate but not GLP-1 or oestrogen monotherapy improved beta cell function under cytokine stress, which occurs physiologically in diabetics. “This is

Langerhans islets of the pancreas of a diabetic mouse: nuclei in white, beta cells and insulin in green, alpha cells that produce glucagon in red, and delta cells, which make omatostatin, in magenta.

the first study to demonstrate beta cell redifferentiation through targeted pharmacological intervention,” stressed Lickert.

Swiss-US redifferentiation Previously, a team of Swiss and US researchers reported in Science Translational Medicine that they have found a way to support the regeneration of insulin-secreting cells in the pancreas. The new strategy “offers a scalable and rapid approach to overcome the current obstacles in the treatment of diabetes, thus addressing an unmet therapeutic need,” commented Marissa Scavuzzo and Malgorzata Borowiak, two key opinion leaders in the field of diabetes. The scientists demonstrated that the combining of drug classes that increase insulin-secretion and, at the same time, reduce caloric intake – so called Glucagonlike peptide-1 receptor (GLP1R) agonists

and dipeptidyl peptidase 4 (DPP4) inhibitors – with inhibitors of a drug class (dual-specificity tyrosine-regulated kinase 1A, DYRK1A) that can unspecifically increase adult human beta cell proliferation, increased regeneration. Specifically, the combo led to an increase in human beta cell replication (5 to 6%) and an actual increase of 40% in the numbers of human beta cells, which secrete insulin. Furthermore, diabetic mice transplanted with human pancreatic islets that received the combination of drugs secreted more insulin and displayed improved blood sugar control compared with mice that received either drug alone. Scavuzzo and Borowiak note that many patients with type 2 diabetes already take GLP1R agonists, suggesting that simply adding low doses of a safe DYRK1A inhibitor could feasibly improve clinical outcomes. L t.gabrielczyk@biocom.eu

Picture: Helmholtz Zentrum München/Aimée Bastidas-Ponce

associations

European Biotechnology | Spring Edition | Vol. 19 | 2020

Biomanifesto EFPIA Infections with COVID-19 are

spreading worldwide, and, according to experts, will continue to do so. The European Federation of Pharmaceutical Industries and Associations (EFPIA) is already responding to the viral threat. “Many EFPIA members have R&D efforts under way or are providing donations of medicines and critical medical supplies as well as financial support to first responders in addressing this evolving crisis,” EFPIA said in a statement. Many EFPIA members are taking measures to fast track collaborative research, identifying suitable assets in their libraries that could be utilised to develop diagnostics or treatments for COVID-19. Members have been donating investigational compounds that may have potential to treat COVID-19, while others are researching vaccine candidates. The industry is providing financial support to organisations on the ground. Many are working with European, Chinese, and global health authorities. 

European Biotechnology is published in co-operation with the following organisations: European Biotechnology NET WORK

Europe: european-biotechnology.net

Europe: medtecheurope.org

Austria: lifescienceaustria.at

Spain: asebio.com

Switzerland: swissbiotech.org

Promoting R&I France BIOTech French life science

association France Biotech is joining forces with Leem, the French industry association which represents drug companies operating in France, to boost the development of the research and innovation ecosystem in France. The two associations plan to strengthen the attractiveness of the sector and to help promote faster access to innovation for patients. Goals include: ›› supporting medical research ›› accelerating patient access ›› developing partnerships between drug and healthtech companies ›› developing expertise in the field of health innovation. In order to facilitate the cooperation, Franck Mouthon, president of France Biotech, is to join the LEEM Board of Directors. 

Europe: medicinesforeurope.com

Ireland: ibec.ie/ibia

Denmark: danskbiotek.dk

The Netherlands: hollandbio.nl

Germany: biodeutschland.org

Portugal: www.p-bio.org

UK: biopartner.co.uk

France: france-biotech.org

Council of European BioRegions

CMYK

Italy: assobiotec.it

Sweden: swedenbio.com

Hungary: hungarianbiotech.org

Europe: cebr.net

Europe: ebe-biopharma.org

Norway: biotekforum.no

Finland: finbio.net

Belgium: bio.be

Blue: 100/15/0/35 Orange: 0/75/90/0

European Biotechnology covers the biotechnology sector of the current 27 EU member states, Norway, Switzerland, and UK. If you would like to subscribe, please refer to european-biotechnology.com.

EBE

White Paper on Personalised

associations

European Biotechnology | Spring Edition | Vol. 19 | 2020

Procurement for better healthcare outcomes Procurement In healthcare, the traditional role of procurement was

to secure the availability of goods and services needed to deliver care. Once this was achieved, procurement moved one step up the “pyramid of procurement activities”: negotiating on product prices and discounts, in order to reduce spending on medical devices and consumables.

In recent years, things have moved on. Procurers have engaged with internal multi-stakeholder interests when tendering for new contracts. This has helped to make procurement, in itself, an important business function. Looking back at how things have evolved, I think we have already come a long way. In fact, it has been quite some time now since purchasing decisions for medical devices were made only by doctors.

effectiveness (bundling of purchasing volumes and obtaining better purchasing conditions). We have even seen the first examples of cross-border cooperation: German Group Purchasing Organisations (GPOs) entering the Dutch market; EHPPA, a partnership Hans Bax of several European GPOs; Senior Adviser and private clinics organising MEAT Value-Based their procurement activities Procurement from a central hub, to name just a few. Despite this dramatic change for the Cross-border cooperation better, I believe the ultimate objective for procurement (“the top of the pyraThese days, healthcare institutions coopmid”) should be to take a strategic role: erate at a national level in the area of procontributing to patient-centric, sustainacurement in order to achieve greater efble healthcare across Europe. However, ficiency (distribution of activities) and when pooling of activities, knowledge,

Upcoming Events › 25 May 2020 Berlin MedTech Forum German Day › 25 – 27 May 2020 Berlin MedTech Forum 2020 › 25 – 27 May 2020 Berlin Global MedTech Compliance Conference

and volume is narrowly applied only to lowering product prices, procurement misses out on achieving its full potential. Procurement cooperation offers a unique opportunity to adopt innovative procurement approaches much faster and with greater impact compared to single healthcare providers. Furthermore, by including (patient) outcome criteria in tenders, procurement can have a major impact on both the improvement of healthcare outcomes and the total cost of delivery – not just the price of products.

Advantages on both sides Another interesting example of cross-European collaboration is the Value-Based Procurement Community of Practise. This collaborative initiative offers opportunities for both European procurement authorities and the medtech industry to cooperate on the development and adoption of value-based procurement in order to partner for patient-centric, sustainable healthcare. As we work together to embrace this new paradigm in healthcare, it is important that we come together to discuss how we can accelerate the necessary shift in procurement practice. For more information, visit medtecheurope.org

Pictures: medtech europe (top), ar130405 via Pixabay (bottom)

Leading chemical companies are exploring the opportunities that have been opened up by modern biotechnology, especially in the field of “white” or industrial biotechnology. And they are also applying these | Spring | Vol. | 2020 European Biotechnology Edition 19SBA technologies, wherever it makes sense. The takes such initiatives seriously and has formed a working group specifically dedicated to white biotechnology. The Swiss Industrial Biocatalysis Consortium is an important partner in this effort. The group includes leading multinational companies that support white biotechnology as a pillar of economic growth. The planned activities are in agreement with OECD strategies. In partnership with the Swiss Biotechnet (see pages 14/15) the SBA develops training programmes and useful support tools for the industry. It is of importance that the industry specifies its training needs so that the academic side can create tailor-made education. This strategy ensures that the industry gets the right workforce with the right education. The SBA profits from the marketing alliance “Swiss Biotech” (see box) in a multiplied form. Thanks to Swiss Biotech, the

ternationally less savvy) find a comprehensive partner which is helping to put them in the public window. The participating Life Science Regions are important internal carriers of the dynamics in the Biotech sector, thus enhancing the common understanding of the industry. This and more knowledge is brought into Europa Bio, the European Biotech Association, where the SBA is an active member.

Domenico Alexakis is Executive Director of the Swiss Biotech Association.

Awards The Swiss Biotech Success Stories Awards recognize valuable

accomplishments and honour those who have made important and sustainable contributions to the biotech industry in Switzerland. The next awards are presented at the Swiss Biotech Day on 15 September.

Pictures: Swiss Biotech Association

associations

Logo des Verbands

Swiss Biotech Success Stories

Switzerland is one of the world’s leading biotech hubs and attracts many foreign companies, specialists, and investors. The sector provides over 50,000 jobs and, together with the pharmaceutical and chemical industries, accounts for almost half of all Swiss exports. To make the industry’s impact more visible, the Swiss Biotech Success Stories initiative was launched in 2018 by the Swiss Biotech Association. Selected success stories are showcased to illustrate how Swiss biotech companies help patients, improve health care worldwide, and make a valuable and significant contribution to the Swiss and global economy. Laureates are individuals or groups who have earned extraordinary merits. Success is broadly defined as scientific, translational, medical, or commercial, together with other aspects that have a positive impact on the biotech and life science industry and society in Switzerland. The Swiss Biotech Association nominated five laureates for the Swiss Biotech Success Stories Awards 2020: Headquartered in Allschwil, Actelion is part of the Johnson & Johnson Family of Companies. Its ground-breaking research

...is an alliance of four leading Biotech regions of Switzerland (Bio Alps, BioPolo Ticino, Basel Area and Greater Zurich Area). They have combined efforts to streamline interests of the national biotech sector. The SWX Swiss Exchange holds a leading position in terms of lifescience listings and offers companies from that industry – be they located in Switzerland or abroad – access to an internationally recognised financial marketplace. The initiative was co-founded by the SBA which also manages the executive office of Swiss Biotech.

and medicines have been a key contributor to improve the lives of people affected by pulmonary hypertension and made Actelion an industry leader in this area. Lausanne’s family-owned Debiopharm identifies high-potential compounds in the oncology field and for the treatment of bacterial infections. They are tested in clinical development and licensed to business partners globally. Over a million patients benefit from their therapies every year.

Upcoming Forevents further information please visit www.swissbiotechassociation.ch www.swissbiotech.org

› 15 September 2020, Basel Swiss Biotech Day & Swiss Biotech Success Stories Awards swissbiotechday.ch

Helsinn, an important employer in Ticino, has a broad portfolio of marketed cancer care products and a deep development pipeline. It has built significant R&D and manufacturing capacities and also advances patient care and supports healthcare innovation with its investment fund. The three startup supporters Venture, Venturelab, and Venture Kick have been helping young biotech companies with great success for more than 10 years, thereby making a significant contribution to the growth of the Swiss biotech industry. They share the nomination for the Swiss Biotech Success Stories Award. Prof. Dr Werner Arber, a Swiss microbiologist and geneticist, won the 1978 Nobel Prize in Physiology or Medicine for his discovery of restriction endonucleases. His groundbreaking research in the field of molecular genetics was instrumental in the development of bio technology. L

Company Index

23andme (USA) . . . . . . . . . . . . . . . . . . . . 78 3P Biopharmaceuticals S.L. (ES). . . . . . . . 78 4Teen4 GmbH (DE) . . . . . . . . . . . . . . . . . 90 A Abbott Inc. (USA). . . . . . . . . . . . . . . . . . . . 6 AbbVie Inc. (USA) . . . . . . . . . . . . . . . . . . . 8 AC Immune SA (CH). . . . . . . . . . . . . . . . . 77 Ackermans & von Haaren (B). . . . . . . . . . 74 ADC Therapeutics SA (CH). . . . . . . . . . . . 30 AdrenoMed AG (DE). . . . . . . . . . . . . . 29, 90 Advent Srl (IT). . . . . . . . . . . . . . . . . . . . . . 79 Advicenne SA (F) . . . . . . . . . . . . . . . . . . . 24 Almirall S. A. (ES). . . . . . . . . . . . . . . . . . . 78 Alnylam Pharmaceuticals Inc. (USA) . . . . 17 Alphabet (USA). . . . . . . . . . . . . . . . . . . . . 76 Amgen Inc. (USA). . . . . . . . . . . . . . . . . . . 73 apceth Biopharma GmbH (DE). . . . . . . . . 23 Apeiron Biologics AG (AT) . . . . . . . . . . . . . 8 arGEN-X BV (NL/B) . . . . . . . . . . . . . . . . . 24 Arya Sciences Acquisition. (USA). . . . . . . 77 Atriva Therapeutics (DE). . . . . . . . . . . . . . . 8 Aurora Biosciences Corp. (CDN) . . . . . . . 86 Autolus Therapeutics Ltd. (UK). . . . . . . . . 80 Axxam SpA (IT). . . . . . . . . . . . . . . . . . . . . 79 B Beckman Coulter LS (CH). . . . . . . . . . 37, 45 Bell Food Group (CH). . . . . . . . . . . . . . . . 47 Bio-On S.p.a. (IT). . . . . . . . . . . . . . . . . . . 78 BIOCOM AG (DE) . . . . . . . . . . . . 33, 56, 57 BioFIT 2020 (F). . . . . . . . . . . . . . . . . . 68, 69 Biogen Idec (USA) . . . . . . . . . . . . . . 17, 100 BioGenes GmbH (DE) . . . . . . . . . . . . . . . 45 BioJapan 2020 (JP). . . . . . . . . . . . . . . 62, 63 Bioncotech Therapeutics S.L. (ES). . . . . . . 79 Bioniz Therapeutics (ES). . . . . . . . . . . . . . 78 BioNTech AG (DE). . . . . . . . . . . . . . . . 8, 77 BIOVIAN Oy (FIN). . . . . . . . . . . . . . . 36, 39 Bit Bio ltd (UK). . . . . . . . . . . . . . . . . . . . . 43 Bits x Bites (CN). . . . . . . . . . . . . . . . . . . . 50 BlueNalu Inc. (USA). . . . . . . . . . . . . . . . . 48 Boehmert & Boehmert (DE) . . . . . . . . 32, 51 Bosch Healthcare (DE). . . . . . . . . . . . . . . . 6 Brahms AG (DE). . . . . . . . . . . . . . . . . . . . 90 Breath Therapeutics GmbH (DE). . . . . . . . 31 Bristol Laboratories Ltd. (UK) . . . . . . . . . . 73 Bruker-Hain Diagnostics (DE). . . . . . . . . . . 6 C Cassiopea SPA (IT) . . . . . . . . . . . . . . . . . . 24 Cellectis (F). . . . . . . . . . . . . . . . . . . . . . . . 74 Cellestia Biotech AG (CH). . . . . . . . . . . . . 80 Celltrion Healthcare Hungary Kft.. . . . . . . 80 Chemspec Europe 2020 (UK). . . . . . . 66, 67 CONCEPT HEIDELBERG (DE). . . . . . . 64, 65 Cour Pharmaceutical Dev. (FIN). . . . . . . . 91 CureVAC AG (DE). . . . . . . . . . . . . . . . . 8, 76 Cytune Pharma SAS (F). . . . . . . . . . . . . . . 80 D Dentons (DE) . . . . . . . . . . . . . . . . . . . . . . 84 Dewpoint Therapeutics (USA). . . . . . . 16–21 DSM (NL). . . . . . . . . . . . . . . . . . . . . . 50, 75 Dunn Labortechnik GmbH (DE). . . . . . . . 33 DuPont Nutrition & Biosciences. . . . . . . . 74 E EBD Group (CH). . . . . . . . . . . . . . . 7, 70, 71 Eli Lilly (USA). . . . . . . . . . . . . . . . . . . 73, 77 Enterprise Lithuania . . . . . . . . . . . . . . . . . 54 Eppendorf – Bioprocess Center (DE). . . . . 25

European Biotechnology | Spring Edition | Vol. 19 | 2020

Erytech Pharma (F). . . . . . . . . . . . . . . . . . 24 EuroJobsites Ltd (UK) . . . . . . . . . Supplement EuropaBio (B). . . . . . . . . . . . . . . . . . . 60, 61 European Biotechnology Network (B). . . . 33 Evonik Industries AG (DE). . . . . . . . . . . . . 77 F FGK Clinical Research (DE) . . . . . . . . . 9, 31 Finless Foods (USA) . . . . . . . . . . . . . . . . . 48 Flexikeg (F). . . . . . . . . . . . . . . . . . . . . . . . 42 Fördergesellschaft IZB (DE). . . . . . . . . . . CP3 Forge Therapeutics (USA). . . . . . . . . . . . . 28 Fosun Pharma (CN). . . . . . . . . . . . . . . . . . 77 Fujifilm Toyoma Chemicals (JP). . . . . . . . . . 8 Future Meat Technologies (IL). . . . . . . . . . 50 G Galapagos NV (B). . . . . . . . . . . . . . . . . . . 24 Genmab A/S (DK). . . . . . . . . . . . . . . . . . . 24 Gilead Sciences Limited (USA). . . . . . . . . . 8 GlaxoSmithKline (UK) . . . . . . 22, 23, 74, 77 Glycom A/S (DK) . . . . . . . . . . . . . . . . . . . 75 H Hansa Biopharma AB (SE). . . . . . . . . . 24, 73 Harter GmbH (DE). . . . . . . . . . . . . . . . . . 83 Herantis Pharma plc (FIN) . . . . . . . . . . . . 30 I IBT Vaccines (USA). . . . . . . . . . . . . . . . . . 72 imec NV (B). . . . . . . . . . . . . . . . . . . . . . . 75 immatics biotech (DE) . . . . . . 22, 23, 74, 77 Incyte Corporation (USA). . . . . . . . . . . . . 30 Index Pharmaceuticals AB (SE). . . . . . . . . 73 InfraLeuna GmbH (DE). . . . . . . . . . . . . . . 72 Innophore GmbH (AT). . . . . . . . . . . . . . . 76 InSphero AG (CH). . . . . . . . . . . . . . . . . . . 89 Integrated Biotherapeutics, Inc. (USA) . . . 72 Intervac AB (SE) . . . . . . . . . . . . . . . . . . . . 78 IO Biotech A/S (DK). . . . . . . . . . . . . . . . . 73 ITM Isotopen Techn. Munich (DE). . . . 38, 41 J J&J (UK) . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 J+K Group (DE). . . . . . . . . . . . . . . . . . 85, 88 Jazz Pharmaceuticals plc (IRL) . . . . . . 29, 79 Jennewein Biotech GmbH (DE) . . . . . . . . 75 JUST Inc. (USA) . . . . . . . . . . . . . . . . . . . . 48 L Lead-Discovery Center GmbH (DE) . . . . . 80 Liof Pharma (ES). . . . . . . . . . . . . . . . . . . . 78 LuinaBio (AUS). . . . . . . . . . . . . . . . . . . . . 87 Lundbeck A/S (DK). . . . . . . . . . . . . . . . . . 73 M Mabion S.A. (PL). . . . . . . . . . . . . . . . . . . . 80 MaveriX (USA). . . . . . . . . . . . . . . . . . . . . 80 Meatable (NL). . . . . . . . . . . . . . . . . . . . . . 50 MediGene AG (DE). . . . . . . . . . . . . . . . . . 31 Memphis Meat (USA). . . . . . . . . . . . . 47, 48 Merck & Co (USA). . . . . . . . . . . . . . . . . . 50 Merck KGaA (DE). . . . . . . . . . . . . . . . . . . 17 MLM Medical Labs GmbH (DE). . . . . . . . 13 MorphoSys AG (DE). . . . . . . . . . . . . . 24, 30 Mosa Meat (NL). . . . . . . . . . . . . . 47, 48, 49 MRM Health NV (B). . . . . . . . . . . . . . . . . 74 MSD (USA). . . . . . . . . . . . . . . . . . 28, 73, 79 Mutabilis SA (F) . . . . . . . . . . . . . . . . . . . . 72 N NBE Therapeutics AG (CH). . . . . . . . . . . . 80

Nestle S.A. (CH). . . . . . . . . . . . . . . . . 42, 75 NewLink Genetics (USA) . . . . . . . . . . . . . 73 Norwest Venture Partners (USA). . . . . 48, 50 Nova Biomedical Switzerland . . . . . . 21, 45 Novartis AG (CH). . . . . . . . . . . . . . . 34, 100 Novo Holdings (DK). . . . . . . . . . . . . . 89, 72 Novozymes A/S (DK) . . . . . . . . . . . . . . . . 50 O Orchard Therapeutics (UK/USA). . . . . . . . 24 P Paratek (USA). . . . . . . . . . . . . . . . . . . . . . 28 Pari Pharma GmbH (DE). . . . . . . . . . . . . . 31 Peace of Meat (B). . . . . . . . . . . . . . . . . . . 47 Pfizer Deutschland GmbH. . . . . . . . . . . . 80 PhagoMed Biopharma GmbH (AT). . . . . . 40 PharmaMar (ES) . . . . . . . . . . . . 8, 25, 29, 79 Polpharma Biologics S.A. (PL). . . . . . . . . CP4 PPF Group (CR). . . . . . . . . . . . . . . . . . . . 80 PrimerDesign Ltd (UK). . . . . . . . . . . . . . . . 6 Q Qiagen NV (DE/NL). . . . . . . . . . . . . . 24, 76 R Randox Life Sciences (UK). . . . . . . . . . . . . 6 Rebel Meat GmbH (AT) . . . . . . . . . . . . . . 50 Regeneron Pharmaceuticals Inc. (USA). . . . 8 Renishaw plc (UK). . . . . . . . . . . . . . . . . . 30 Rentschler Biopharma SE (DE) . . . . . . . . . 35 Roche AG (CH). . . . . . . 6, 24, 28, 30, 73, 80 Roche Diagnostics GmbH (DE). . . . . . . . 100 S Sandoz AG (CH). . . . . . . . . . . . . . . . . . . . 80 Sanofi SA (F) . . . . . . . . . . . . . . . . . . . . . . . 8 Servier (F). . . . . . . . . . . . . . . . . . . . . . . . . 74 Shimadzu Deutschland GmbH. . . . . . . . CP2 SoftBank Group (JP) . . . . . . . . . . . . . . . . . 48 Sotio a.s. (CR). . . . . . . . . . . . . . . . . . . . . . 80 Sotio Biotech AG (CH) . . . . . . . . . . . . . . . 80 SphingoTec GmbH (DE). . . . . . . . . . . 29, 90 Super Meat (IL). . . . . . . . . . . . . . . . . . . . . 50 Swiss Biotech Association. . . . . . . . . . 58, 59 T Takeda Pharma GmbH (DE). . . . . . . . . . . 91 Teva Pharma (IL). . . . . . . . . . . . . . . . . . . . 73 ThermoFisher Scientific (USA) . . . . . . 76, 90 TrakCel Europe Ltd (UK). . . . . . . . . . . . . 100 Transgene SA (F). . . . . . . . . . . . . . . . . . . . 30 Tropic Biosciences Ltd. (UK). . . . . . . . . . . 50 U Univercells SA (B). . . . . . . . . . . . . . . . 34, 75 UPM (FIN) . . . . . . . . . . . . . . . . . . . . . . . . 72 V Validogen GmbH (AT) . . . . . . . . . . . . . . . 29 Valneva SA (F) . . . . . . . . . . . . . . . . . . . . . 24 W WuXi Biologics (CN) . . . . . . . . . . . . . . . . 78 WuxiApptec (USA). . . . . . . . . . . . . . . . . . 44 X Xenikos BV (NL). . . . . . . . . . . . . . . . . . . . 29 Z ZAMBON Company S.p.A. (IT). . . . . . . . . 31 Zealand Pharmaceuticals A/S (DK). . . . . . 24

EVents

European Biotechnology | Spring Edition | Vol. 19 | 2020

euroPLX 73 15.–16.6.2020 Vienna EuroPLX is

an international platform for pharmaceutical and biopharmaceutical companies to initiate cooperations. Information exchange on new business opportunities and interaction start right after registration, concluding with the two-days conference. www.europlx.com

30.6.–2.7.20

BIOKET 2020, Lille (F) Info: Annabelle Heyvaert, IAR – The French Biotech Cluster, www.bioket.eu

24.–25.8.20

4th AMR Conference on Novel Antimicrobials and AMR Diagnostics, Basel (CH) Info: BIOCOM AG, https://amr-conference.com

30.8.–3.9.20

10 th International Congress on Biocatalysis – biocat 2020, Hamburg (DE) Info: Hamburg University of Technology/Conventus, www.biocat-conference.de

8.–10.9.20

Nordic Life Science Days 2020, Malmö (SE) Info: Olivier Duchamp, SwedenBio, www.nlsdays.com

13.–15.10.20

CPhI Worldwide 2020, Milan (IT) Info: CPhI Global Office, www.cphi.com

19.–22.10.20

Analytica 2020, Munich (DE) Info: Messe München GmbH, www.analytica.de

25.10.20

Europe CEO, Munich (DE) Info: Informa, https://informaconnect.com/europe-ceo/

26.–28.10.20

BIO-Europe 2020, Munich (DE) Info: Informa, https://informaconnect.com/bioeurope

Life Sciences Baltics 30.9.–1.10.2020 Vilnius The interna-

15.9.20

Swiss Biotech Day, Basel (CH) Info: SBA/BIOCOM AG www.swissbiotechday.ch

18.–22.9.20 12.–13.5.20

13th International Conference on Bio-based Materials, online Info: nova institute, www.bio-based.eu/conference

ESMO Congress 2020, Madrid (ES) Info: ESMO – European Society for Medical Oncology, www.esmo.org

tional forum in the Baltics for biotechnology, pharmaceutical and medical devices experts from all around the world, provides a unique opportunity to explore the new horizons of partnerships, exchange ideas and seek progress through networking. www.lifesciencesbaltics.com

29.9.–1.10.20

BioSpain 2020, Pamplona (ES) Info: Asebio, https://biospain2018.org/

6.–9.6.20

European Human Genetics Conference, Berlin (DE) Info: Vienna Medical Academy https://2020.eshg.org/

8.–11.6.20

BIO International Convention, San Diego (USA) Info: Biotechnology Innovation Organization, https://convention.bio.org/2020

Pictures: andreas N (l.)/Werner März (M.)/ Peggy und Marco Lachmann-Anke (r.) – all at Pixabay

16.–17.6.20

17th International Conference of the European Industrial Hemp Association - EIHA, Cologne (DE) Info: Dominik Vogt, nova institute, www.eiha-conference.org

17.–18.6.20

Future of Biofuels – European Conference, Copenhagen (DK) Info: FORTES, https://fortesmedia.com

18.6.20

Swiss Symposium of Lab Automation 2020, Rapperswil (CH) Info: Institute for Lab Automation und Mechatronics (ILT), www.ilt.hsr.ch

28.6.–1.7.20

European Congress on Biotechnology – ECB2020, Maastricht (NL) Info: European Federation of Biotechnology EFB, www.efbiotechnology.org/ECB2020

5.–6.10.20

EFIB 2020, Frankfurt am Main (DE) Info: EuropaBio, www.efibforum.com

New Food Conference 5.–6.8.2020 Berlin The 2nd New

Food Conference will present newprotein solutions, valuable networks, and the latest on cuttingedge novel-food innovation and development, investment strategies, plant-based best practices, and latest news on advancements in the cultured‑meat sector. www.new-food-conference.com

2.–4.11.20

World Bio Markets/SynBio Markets,Amsterdam (NL) Info: https://worldbiomarket.com/

11.–12.11.20

Chemspec Europe 2020, Cologne (DE) Info: Mac Brooks Exhibitions, www.chemspeceurope.com

11.–13.11.20

Global Congress on Plant Biology and Biotechnology 2020, Valencia (E) Info: Grace Angel, Magnus Group, https://plantbiologyconference.com

19.–20.11.20

Global Bioeconomy Summit 2020, Berlin (GER) Info: Conference office c/o BIOCOM AG, https://gbs2020.net/home/

1.–2.12.20

BioFIT 2020, Strasbourg (F) Info: Eurosanté, www.biofit-event.com

Encore

No entry!

I’m in biotechnology because ...

Swiss-Style PCR In

SARs-CoV-2 virus In March, German infection biologists found a human target and potential medicine inhibiting the new coronavirus SARS-CoV-2 from entering lung cells of infected people. In Cell (doi: 10.1016/j.cell.2020.02.052), the group, headed by Stefan Pöhlmann, head of the Infection Biology Unit at the German Primate Centre, reported that SARS-CoV-2 requires interaction of the viral spike protein ACE2 with the human serine protease TMPRSS2 to enter cells. As Ono Pharmaceutical has developed an approved drug for pancreatitis called camostat mesilate, which inhibits TMPRSS2, they propose to initiate clinical trials with humans that have been diagnosed with COVID-19 to see if the drug can be repurposed to limit virus spread. 

Dr FIONA Withey, CEO, TrakCel Europe Ltd, Cardiff, UK

Swiss Lottery Novartis AG started a lot-

tery for 100 free shots of its US$2.1m SMA gene therapy Zolgensma. The move triggered criticism from doctors, because it appeared as a hidden marketing campaign against the competitor drug Spinraza from Biogen. 

“… my passion is inspiring teams as well as working with companies to reach potential, making a difference to patients’ lives. TrakCel’s strapline is ‘there is a patient at the end of everything we do’.”

Precision med growing In the precision medicine model, diagnostic testing is utilised for choosing apt or alternate medical treatment mode, depending on patients’ genetic make-up or structure, as well as cellular analysis. Biopharma market experts expect precision medicine to improve health outcomes, to reduce toxicity, to boost cost-efficiency, and to optimise disease management. A recent study published by FNF Research predicts the European precision medicine market to grow from approximately US$17.132bn in 2018 to around US$40.487bn by 2025. 

FNF Research estimates for the growth of personalised medicine 45 US$40.49bn

40 CGAR = 13.1%

35 30 25

US$17.49bn

20 15 10 2017

2018

#COVID19 collaboration efforts Collaboration is key in fighting the #COVID19 pandemic. We’re excited to have @ChanZuckerberg join the COVID-19 Therapeutics Accelerator along with @wellcometrust & @Mastercard: shorturl.at/vBUXZ @gatesfoundation We have published a new backgrounder on the different types of #diagnostics for #COVID19 as well as #SARSCoV2 #diagnostic use cases: shorturl.at/dmEK0 @FindDx

EMA has published guidance on the actions that sponsors of #ClinicalTrials affected by #COVID19 should take to help

Please follow us @EuroBiotechNews ensure the integrity of their studies and interpretation of study results: shorturl.at/ coACR @EMA_News

2019

2020

2021

2022

2023

2024

2025

2026

Next issue Second edition Outsourcing biomanu

facturing and clinical testing is a huge growth opportunity with numerous players, pushing proprietary cell lines and processes The CRO/CMO special in European Biotechnology’s Autumn Edition will be distributed widely. If you want to participate, please contact Andreas Macht (+49-30-264921-54), Oliver Schnell (-45), or drop us an email: marketing@biocom. de. Publishing date is 11 September 2020; deadline for ads is 24 September 2020. 

Pictures: Start Codon Ltd, TrakCel (top), www.fnfresearch.com (bottom)

mid-March, Roche Diagnostics got an FDA Emergency Use Authorization for its dual-target SARS-CoV-2 PCR test for the 695 cobas 6800 and 132 cobas 8800 systems, which can measure 1,440 and 4,128 tests per day, respectively. This boosted the capacity of worldwide COVID-19 PCR testing by 1,027,921 tests per day.

Source: www.fnfresearch.com

Winners & losers

European Biotechnology | Spring Edition | Vol. 19 | 2020

Precision medicine world market

YOU HAVE THE IDEA— WE HAVE THE LOCATION Æ Site: 26,000 m2, S1 laboratories Æ Real estate and facility management on site Fördergesellschaft IZB mbH Am Klopferspitz 19 82152 Planegg/Martinsried Tel. + 49 (0)89.55 279 48-0 Fax + 49 (0)89.55 279 48-29 info@izb-online.de www.izb-online.de

Æ Faculty Club and conference rooms for up to 100 people Æ Kindergarden (Bio Kids), Chemistry School Elhardt Æ Hotel CAMPUS AT HOME Æ Restaurant SEVEN AND MORE, Café Freshmaker Æ On the Martinsried Campus: over 50 start-ups in the IZB, two Max Planck Institutes, ten faculties of the LMU, Clinic of the University Munich

WHERE THE FUTURE BECOMES REALITY