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ISSN  2364-2351 | A  60711 |

Life Sciences and Industry Magazine Winter Edition 2018 | Volume  17 | 20 €

Interview Serial founder Andreas Bergmann explains how his companies will extend personalised medicine beyond oncology.

High Potential

Ruling under fire

Artificial Intelligence


Biofairs Compass

Scientists press EU Commission to modernise GMO legislation

How the new paradigm of AI is disrupting drug development

Biotech leaders and climate experts call for a carbon tax

The ultimate guide to relevant life sciences events in H1/2019

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Shimadzu_Euro-Bio-Tech_2018:00 09.05.18 10:14 Seite 1

Don´t prepare. Just be ready. C2MAP-2000 – 1 method, 17 mins, 95 media components The new 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


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C2MAP-2000 – Complete LCMS solution

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European Biotechnology | Winter Edition | Vol. 17 | 2018



More money needed to drive the bioeconomy Bioeconomy comprises the Bio-Based Industries (BBIs) and the Blue Economy of the sea. Investments into the Bioeconomy help reduce Europe’s dependence on non-renewable natural resources, transform the production of food and manufacturing of biomaterials, and promote sustainable and resource-efficient production. This sounds like a very attractive field for investors. However, an analysis of the European Investment Bank (EIB) revealed that funding of BBI projects is not as high as it should be. Companies suffering from this lack of funding are mainly those with successfully tested products and where small-scale pilot production had been demonstrated. Further up-scaling and market development require much more capital, often well above available funding levels. For demonstration plants, typical investment volumes range from €10m to €100m; for commercial scale plants these figures are much higher. The capital demand varies depending on technology and product type. Investors favour projects with lower capital needs in order to limit a too high exposure to single investments, but also to minimise financing risks of individual investments. Those BBI companies that manage to receive funding still face significant challenges, such as technological risks when up-scaling, regulatory uncertainties, as well as business risks arising from volatility of market demand and input factors. Investing in this field therefore requires specific knowledge about technologies and markets. As a result, only a handful of specialised financial investors and a few corporate venture capitalists are investing in BBIs. This is in line with EIB’s finding that 77% of bioeconomy projects in Europe are facing issues in raising investments when scaling up technologies to demonstration or even to industrial scale. To address the funding gap, the EIB has just recently announced the launch of a Circular Bioeconomy Investment Platform (CBIP). An initial €100m will be made available from EIB on very favorable terms, clearly with the intention to mobilise additional public and private capital. The vehicle itself is conceived as a specialist fund which should help to crowd in more investors by removing barriers resulting from limited understanding of the sector. For BBI projects seeking funding this would be a great step forward.

Picture: BASF SE

Michael Nettersheim joined BASF Venture Capital in 2011 from High-Tech Gruenderfonds, Germany. Prior to this, he was responsible for corporate finance and IR at a publicly listed biotech company in Munich. Within the Bio-based Industries, he is currently serving on the Boards of Directors of Advanced BioNutrition Corp., P2 Science Inc., and Renmatix Inc. (all US). Nettersheim studied chemistry at the University of Bonn, where he was awarded a doctorate in biochemistry. He holds a MBA from the Kellogg-WHU Executive MBA Program.

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Specialist Investors have learned to manage technological, up-scaling and market development risks. This, however, is different for regulations affecting individual investment cases, sometimes literally overnight. The most prominent example is the recent classification of CRISPR-Cas9 technology as genetic engineering by the European Court of Justice. For investors those kinds of risks are hardly assessable and manageable, thereby creating a significant investment barrier for specialist and generalist investors alike. In addition to launching the CBIP, reliable and efficient frameworks are important drivers to increase investor commitment to the European Bioeconomy. These frameworks should cover innovation and technology utilisation, labeling, and classification of prodL ucts as well as environmental, sustainability, and societal aspects.

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Cover Story

Insight Europe

Regional News


74 Northern Europe: Sweden, Denmark, Norway and Finland

CJEU ruling triggers exodus of EU plant research

10 AMR still growing; EESC urges EC to boost investments to fight global warming

Economy 20 Investments in novel antibiotics surge 22 A poor climate for Austrian IPOs

76 Western Europe: France, Belgium, The Netherlands and the UK 78 Central Europe: Germany, Switzerland and Austria 80 Southern Europe: Italy, Spain and Greece

23 Update on clinical trials 26 BIO-Europe focuses on advanced therapies


Cannabis and the great green rush Marijuana is the most cultivated, trafficked and abused illicit drug worldwide. But the list of European countries that see clear medical benefits from the plant and want to legalise cannabis for medical purposes has grown long. Canadian manufacturers in particular have been signing export deals with European governments to get a foot in the door in the billion­ dollar business. Gold fever is growing in the industry, but doctors urge caution on the path to improving care for patients.

82 Eastern Europe: Poland and Czech Republic

29 Analyst commentary

Science & Technology

30 Euro Biotech Stocks

89 Zeroing in specifically on HER2 limits side effects

32 Interview: Andreas Bergmann, Founder, CSO Adrenomed AG; Founder, CEO Sphingotec GmbH

90 Killing the metastasis switch

36 EMA News

91 Sugar replacement hits tumour energy metabolism; Shaping the tumour niche

37 Focus Pharmapack: Blockchain for serialisation 40 Interview: Philip Falkenstein, Bähren Druck 42 Highest manufacturing standard 71 Rentschler Fill Solutions starts new facility 72 Metabolic control of CHOBC for production of biologics

Service 83 Biopeople 92 News from partner associations: Swiss Biotech Association and Europa­Bio 95 Events 96 Company index 97 New products 98 Encore

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), Dr. Martin Laqua, Sandra Wirsching, Helene Märzhäuser; Advertising: Oliver Schnell, +49-30-2649-2145, Christian Böhm, +49-30-2649-2149, Andreas Macht, +49-30-2649-2154; Distribution: Marcus Laschke, +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. Cover Photo: AlenKadr/stock.adobe.com (leaf), mishaabesadze/stock.adobe.com (stamp); Supplement: BIOCOM AG; ® BIOCOM is a registered trademark of BIOCOM AG, Berlin, Germany.

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Artificial Intelligence



The tightrope

Drug discovery and AI The time it takes to bring a drug to market hasn’t improved significantly for 40 years now, and productivity in terms of return on investment is even dropping in the pharmaceutical industry. Will powerful new algorithms help usher in a new age of drug development? We talked with CEOs from companies confident that AI is going to make all the difference. But will it really?


Picture: AlenKadr/stock.adobe.com (leaf), mishaabesadze/stock.adobe.com (stamp) (left), WWF (top), foxaon1987/shutterstock.com (middle), doomu/stock.adobe.com (bottom)

Need for incentives

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S ix years ago the European Commission launched its Bioeconomy Strategy, but since then investment in biotech has actually dropped. Faced with climate change and other global threats, the EC now wants to go green through funding. Industry leaders and experts recommend ramping up innovation – and paying for it with taxes on CO2.

SPECIAL EU Event Compass 45 46 48 50 52 54 56 58 60 62 64

Update on EU Events in H1/19 DIA Europe, Vienna Pharmapack, Paris HIC/DSP Conference, Interlaken European Chemistry Partnering, Frankfurt/Main Berlin Conference on Life Sciences, Berlin BIO-Europe Spring, Vienna Annual meeting DGPharMed, Berlin Swiss Biotech Day, Basel International Conference on Bio-based Materials, Cologne Amgen Scholars Europe

For regulators, CRISPR-Cas9 genome editing is a tough topic to legislate. It can bring huge benefits, or wreak irreversible damage on humankind and the environment. The claimed birth in China of genome­-edited HIV-resistant twins in November rightly provoked an international outcry, as it both violated Chinese law and crossed accepted ethical and moral lines. Control of research is crucial to prevent the misuse of this powerful technology by renegade researchers. At the same time, plant researchers in Europe are suffering under over­ regulation in the field of genome editing (see p. 6), which blocks them from commercialising crops that can be adapted within a generation to withstand the impacts of climate change. All because the plants have been declared GMOs. Meanwhile, killing mosquitos with gene traps as they head to the Northern hemisphere carrying malaria and dengue might morph into an uncontrolled field release experiment. What to do with the many different applications of one technique? Interest and advisory groups have called for a staggered approach to regulation and control of genome editing that looks at the very different risks and potentials posed by CRISPR-Cas9 technology in various applications. In light of the global challenges, it’s high time regulators forget dogmas and do more to balance science with ethics.

Thomas Gabrielczyk Editor-in-Chief

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Insight Europe

European Biotechnology | Winter Edition | Vol. 17 | 2018

CJEU ruling triggers exodus of EU plant research Targeted Breeding  According to a brand-new EU-wide survey, European plant researchers

are concerned about the European Court of Justice‘s (CJEU) interpretation that targeted mutation methods aimed at improving crop yield and resistance to climate change yield GMOs. In an open letter, they call for political action and a modernisation of the EU Directive 2001/18/EC because a lack in tech-transfer would put Europe at the bottom of the pile in the upcoming bioeconomy.

According to Staffan Eklöf (Swedish Board of Agriculture) and Sonny Purdue, the US Secretary of Agriculture, it’s simple to explain what a GMO is: “If there is foreign DNA in the plants in question, they are regulated. If not, they are not regulated.” The different thinking of the CJEU (see European Biotechnology, Autumn 2018), however, could trigger another exodus of European R&D in the field of targeted mutation/genome editing. EU plant researchers face a significant drop in R&D funding for genome-edited crops after the CJEU has ruled that genetic methods that use the cell’s DNA repair system to induce targeted point mutations in the crop genome cannot be exempted from the bloc’s GMO Directive

2001/18/EC. Nearly 74% of 197 EU researchers surveyed by German pro-agribiotech information platform WGG (Wissenschaftlerkreis Grüne Gentechnik) said they expect the ruling to have a negative impact on public and private funding in the field of new breeding methods (see figure below). As GMO safety assessment and market approval cost 5 to 20 times more than deregulated marketing of genome-edited crops, which were greenlighted in March 2018 in the US, innovative seed developers are turning away product development from Europe. “We respect the ruling of the CJEU and won’t be making use of CRISPR-Cas in the development of our vegetable varieties,” a spokesman for Dutch vegetable seed sup-

plier Rijk Zwaan said, “though we do use CRISPR-Cas in our research.” Also, other European companies follow the paradigm of “research can be done anywhere; development is going outside the EU.” ›› Einbeck/St. Louis-based KWS Saat SE, the world’s largest supplier of sugar beet seeds, said that it saw “great potential in the new breeding methods” and will refocus product development of genome-edited crops to more innovation-friendly non-EU markets. ›› Dutch HZPR NV, the largest trader in seed potatoes, announced it will relocate its R&D on CRISPR-Cas outside the EU. The Dutch potato sector accounts for 60% of global exports inseed potato.

What German and EU researchers think about the CJEU ruling on mutagenesis (in %) GER EU











75 77 62

30 14*

40 11



9 3

not applicable


9 30


28 28



28 13

74 52

4 9




92 2 2 16

12 2 4


no answer

9 17 30 2 57 2 49 2

*including “yes, but only when we would have guarded fields” Source: WGG


1 Does the CJEU judgement or its consequences affect you and the freedom of research? 2 Will the CJEU ruling or its legal implementation have an impact on your research? 3 Are you worried that the CJEU ruling or its implementation will have a negative impact on public/private funding? 4 Do you expect the CJEU ruling or its implementation to trigger funding for environmental safety research of genome-edited organisms? 5 Did you intend to carry out field trails with genome-edited organism before the CJEU ruling? 6 (only for Germany) Would you even carry out field trials in Germany?

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Pictures: Ernesto del Aguila III, NHGRI


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Insight Europe

European Biotechnology | Winter Edition | Vol. 17 | 2018

ceeded for the first time in improving a wild tomato variety in just one generation. While conserving all of its natural pest resistance and good taste, which has been lost in conventionally bred tomatoes, they significantly improved the yield (see boxed report).

SMEs at disadvantage?

Targeted Mutation German plant researcher Jörg Kudla (University of Münster) has created a high-yield, high-lycopene level tomato that carries all beneficial taste and resistance genes from the pea-sized ancestor of today's tomato plants. Using CRISPR-Cas9 genome editing technology, they eliminated loss-of-function mutations that cause increased disease susceptibility, lack of taste, and reduced vitamin and nutrient content in today's high-perfomance tomatoes. “The new method allows us to start from zero and restart a domestication process,” commented Kudla (Nature Biotechnology, doi: 10.1038/nbt.4272).

However, the brand-new EU survey conducted by WGG clearly shows that researchers are not willing to conduct field trials with genome-edited crops labeled as GMOs because they fear field destructions by anti-GM activists. “We wanted to know how researchers think about the CJEU ruling. Thus, we conducted the very first surveys ever on the topic; one in Germany and one in the EU member states,” WGG Board member Klaus-Dieter Jany told European Biot­ echnology. “Our results indicate that research and value creation in the internationally competitive field of genome editing will be blocked in Europe by the application of the EU rules for GMO field trials and market autorisation.” For Jany, it‘s a loss in competitiveness in a field that Europe pioneered six years ago: the bioeconomy (see p. 8). “Targeted

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mutagenesis methods can contribute to ultra-rapid breeding of crops needed, in light of climate change and a growing world population, to meet the UN sustainability development goals and to provide healthy food for all, i.e. through backcrossing of ancient natural varieties but with high yields.” The German Bioeconomy Council supports Jany‘s notion to partially exempt genome-edited crops from EU GMO rules, particularly when it comes to mutagenesis. “Crops that have been mutated with biological methods and that are imported from countries where those are deregulated can‘t be analytically distinguished from crops that have undergone classical chemical or radiation-induced mutagenesis,“ adds Jany. Using CRISPR-directed mutagenesis, German researchers this October suc-

Lobby gridlock As of November 2018, 88 EU research institutions supported a position paper launched by CropDesign co-founder Dirk Inzé, currently professor at VIB in Ghent. In brief, it calls upon European decision-makers to respond to the CJEU ruling by altering Directive 2001/18/1C to also exempt crops containing small gene edits and instead let them fall under the regulatory regime that applies to classically mutated crops. However, only 53% of the responders to Jany's survey support a legal change while 25% are opposed to it, as they fear another 20year roadblock for innovative breeding technologies. European GM opponents see the CJEU ruling as a means to strengthen consumer safety and transparency in Europe but

Picture: FIBL

Breeding back to the future

A spin-out company at Belgian VIB that used targeted mutation technology to fight two fungal pathogens that cause Panama disease and black Sigatoka in Africa lost funding after the CJEU ruling. According to Roel Sterken, who leads the business, a €1m venture capital financing “blew up” and a commercialisation partner quit the project because African farmers involved export most of their harvest to Europe where the bananas must go through the costly GMO approval process, according to the CJEU. This would add at least €20m in extra cost to the project. Stakeholders at MusaRadix BV and its partner KeyGene N.V. said they will continue developing bananas resistant to banana pests, but “feel that the ruling is a lost opportunity as targeted mutation methods can make a huge difference in the development of disease resistant banana varieties.”

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European Biotechnology | Winter Edition | Vol. 17 | 2018

not as a roadblock to address challenges such as climate change and agricultural productivity. “It‘s not too clever to speed up development of breakthrough innovations by a taxpaid European Council for Innovation (EIC) and at the same moment stick to a policy that blocks them to come to the European market place,” comments Jany.

The Best Antibody Discovery Technology Is Now at Your Fingertips

EC: Move or move not?

However, pressure on the Commission as of November is growing: 28 nations led by Argentina (including Australia, Brazil, Canada, Colombia, Dominican Republic, Guatemala, Honduras, Jordan, Paraguay, the United States, Uruguay, and Vietnam, as well as the Secretariat of the Economic Community of West African States (ECOWAS), submitted a position paper to the World Trade Organisation (WTO) in which the alliance supports science-based consideration of agricultural innovations, encouraging regulatory compatibility among countries aimed at minimising potential disruptions to trade. It warns that potential trade issues may arise as a result of differences in the regulatory oversight of precision biotechnology products. According to US Secretary Sonny Purdue, “Unfortunately, such technologies too often face regulatory roadblocks that are based on misinformation and political posturing.“ Global players support that stance: “The CJEU ruling shows that the existing GMO directive no longer reflects current knowledge and scientific evidence,” said Dr. Elke Duwenig, Senior Expert Global Regulatory/Public & Government Affairs Biotechnology, Nutrition & Health at BASF SE, “ and with that jeopardises food security in Europe by creating a massive non-tariff-trade barrier by putting on importers and processors a responsibility that cannot be managed for the volumes that L are needed to meet the demand of the EU.”   t.gabrielczyk@biocom.eu

The Trianni MouseTM platform is the only transgenic antibody discovery platform ever developed that offers the entirety of human antibody variable gene diversity in a single organism. The V-gene segments in The Trianni Mouse are chimeric, but the variable domains of antibodies made by the mouse are entirely human. The result is human antibody leads generated from antibody genes optimized for function in the mouse. Or, in the simplest terms, The Trianni Mouse is a more human mouse. To learn more about this innovative platform and how it can help you leave your mark on therapeutic antibody discovery and development, visit Trianni.com. HUMAN Amino Acid frequency

Creating barriers

Trianni Mouse Antibodies are a Match for Humans

Amino Acid position

TRIANNI Amino Acid frequency

In November, the Commission’s seven chief scientific advisors (SAM) published a statement providing “a scientific perspective on the regulatory status of products derived from gene editing, and the implications for the GMO Directive,” calling for a revision of Directive 2001/18/EC to reflect current knowledge and scientific evidence. “Gene-editing is a critical technology with an enormous potential to improve human health and preserve the environment,” commented Research Commissioner Carlos Moedas. “I therefore welcome the statement from our Chief Scientific Advisors, which provides a valuable input into our reflections on future proofing regulation so that our laws can keep up with our labs.” As Health Commissioner Vytenis Andriukaitis, however, suggested to start a broad public discussion on gene editing before taking any measures, the Commission seems not to be hasty in setting up a stable regulatory framework needed by the industry to invest into the technology (see p. 3).

Amino Acid position

CDR-H3 residue utilization in antibodies derived from human samples and the Trianni transgenic Ig Mouse. In the naive Trianni Mouse, heavy chain CDR3 (CDR-H3) aa utilization frequency is effectively the same in humans and in The Trianni Mouse.

Exceptional Human Antibody Discovery 06-10_EB_Winter_2018_Insight_tg.indd 9

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insight europe

News Deplastify the globe Plastics never decompose, they kill animals, and their additives pollute our oceans. Three organisations have declared war on marine littering. Together, the European Investement bank (EIB), German Kreditanstalt für Wiederaufbau, and the Agence Française de Développement will invest €2bn with their initiative “Clean Oceans” over the next five years. Current estimates say that 8 million tons of plastics annually enter the sea, about 90% coming stemming from Asia, Africa, and the Middle East. The goal of the initiative is to fund means to reduce the plastic intake into the oceans.

Money boost   Brussels-based EU‘s European Economic and Social Committee (EESC) has called on the European Commission to earmark 40% of the next EU multiannual financial framework (2021-2027) to fight climate change and its effects in order to meet the 2030 climate targets. The proposal, drafted by Rudy De Leeuw, is significantly above the proposals of the European Commission (25%) and the European Parliament (30%) for the low-carbon transition. “We have to give Europe a new purpose, a new hope, especially to young people,” De Leeuw said. The EU should mobilise €1,115bn in order to put the bloc on a low-carbon economy pathway, he added. Putting a price on carbon emissions is gaining momentum worldwide to incentivise the industry to decarbonise its production. However, just 42 countries worldwide put a price on carbon emissions, with taxes seeming to be the most efficient way.

European Biotechnology | Winter Edition | Vol. 17 | 2018

AMR still growing ECDC  Antimicrobial resistance (AMR)

has increased by 32% since 2007 in Europe. According to a brand new Lancet report based on data the EARS-Net provided in 2015, 33,000 deaths could be attributed to AMR, 39% thereof caused by infections with bacteria resistant to last-line antibiotics such as carbapenems and colistin. Estimates by the European Centers for Disease Control and Prevention (ECDC) in 2007 reported that there were just 25,100 AMR-related deaths 11 years ago. The burden of AMR-associated infections is comparable to that of influenza, tuberculosis, and HIV/AIDS combined. However, the contribution of various antibiotic-resistant bacteria to the overall burden – 75% thereof attributable to healthcare-associated infections – varies greatly between countries (see graphic).

Resistant bugs love supermarkets AMR, however, no longer seem to be limited to hospitals. Researchers at the Julius Kühn Institute, Germany, reported in November that fruits and vegetables are a reservoir for transferable antibiotic resistance genes that often escape tradi-

tional molecular detection methods such as PCR but could still be transferred to human pathogens or commensals. Analysing 24 samples of salad, arugula, and cilantro purchased from supermarkets in Germany by cultivation and DNA-based methods, the researchers found low-abundant tetracyclin-resistant E. coli in all purchased produce samples after nonselective enrichment. Multidrug resistance plasmids were transferable to sensitive E. coli recipients, a process that could occur in the human gut. Almost all E. coli isolates were resistant to antibiotics from at least one class and two isolates were resistant to eight classes. The researchers said such bacteria should be considered an important route of disseminating transferable antibiotic resistances, which might be relevant for patients under antibiotic treatment. To date, no real-time PCR systems can detect or quantify these plasmids in total community DNA. Progress in the field and latest developments in AMR diagnostics and therapeutics will be highlighted by developers, policymakers, regulators and IP experts at the 12th Berlin Conference on L Life Sciences. 

The abundance of multiresistant bugs greatly varies in EU countries.

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Picture: Lancet 0.1016/S1473-3099(18)30605-4/ECDC


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cover story

European Biotechnology | Winter Edition | Vol. 17 | 2018


The great green rush Cannabis  It’s the most commonly cultivated, trafficked and abused illicit drug worldwide, and

there’s still a lot of social stigma attached to the recreational use of pot. But it’s slowly dawning on regulators in countries from Canada to the US to South Africa that by ignoring the clear medical benefits of marijuana, they may have thrown the baby out with the bathwater. Countries across Europe are now also opening their minds, laws and wallets to cannabis.

Pictures: PixelCatchers/istockphoto.com (left), Walter Breitinger (right)


hen every other method fails to control a patient’s pain, a low-dose cannabinoid treatment can be a highly effective approach, says Dr. Marc Seibolt. He works at the Munich­- based Algesiologikum MVZ GmbH, one of Germany’s largest pain therapy clinics. Since 2013, Seibolt has been prescribing medical cannabis as an additional therapy if various other treatment methods prove ineffective or are simply not providing sufficient relief. “Cannabis-based drugs have huge potential for patients with chronic – especially neuropathic – pain, spasticity in multiple sclerosis, and loss of appetite, nausea and vomiting,” the pain expert says. The German government now also recognises that potential, and legalised the medical use of the Cannabis sativa plant in March 2017. Around 147 million people – or nearly 2.5% of the global population – consume cannabis regularly. The World Health Organisation (WHO) says that makes marijuana and the family of other products derived from the plant the most commonly cultivated, trafficked, and abused illicit drug worldwide. But more and more, its bad reputation is improving. Cannabis no longer provides just a way for people to get high, but is increasingly recognised for its proven pharmaceutical benefits in fields like pain management. “The newly enacted cannabis legislation has led to a much wider acceptance of cannabinoids as a drug in the population than was previously the case,” says Prof. Dr. Sven Gottschling,

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in cancer therapy as a good way to stimulate appetite and at the same time relieve nausea. “In the past, I had to convince and persuade sceptical patients. But today, many patients approach us proactively with the desire for a cannabinoid therapy. In particular, the demand for flowers has certainly risen”.

Prof. Dr. Sven Gottschling Chief Physician, Center for Palliative Medicine and Child Pain Therapy, Saarland University Hospital

? !

When do you prescribe cannabis as a therapy?

Cannabinoid-based drugs are not a first-line therapy. They’re usually an additional therapy if various other treatment methods have not been effective or not sufficiently effective. I see a wide range of indications here – from chronic pain and nerve pain to lack of appetite, nausea relief, treatment of refractory seizures in children, and severe restlessness in the palliative situation.

Chief Physician at the Center for Palliative Medicine and Child Pain Therapy at Saarland University Hospital. He began working with cannabis products as a pediatric oncologist, where he treated children with cannabinoids who had massive appetite disorders and weight loss. Before long, it gained acceptance

Health insurance companies hesitant about paying for it Before the law was liberalised in Germany, patients who suffered from diseases like multiple sclerosis, chronic pain or cancer could only use cannabis if they had applied for a specific exemption at the country’s Federal Institute for Drugs and Medical Devices (BfArM). As regulations were extremely strict, that effectively meant only a few hundred patients with specific indications were granted permission to use the plant for medicinal purposes. But numbers are now rising steadily. Figures from market research institute IQvia reveal that there were around 3,500 prescriptions issued directly in March last year. By October, that number had more than doubled to around 7,300 prescriptions. Overall, physicians in Germany like Seibolt and Gottschling are now able to treat significantly more patients with cannabin­ oids because the legalisation has made it possible for patients to apply via an application procedure without any indication restrictions. That said, only around 60% of all applications submitted are currently approved by health insurance companies. In addition to the bureaucracy, a lack of

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European Biotechnology | Winter Edition | Vol. 17 | 2018

The human endocannabinoid system CB1

Receptors are mostly found in the nervous system and brain


Source: SatiMedUSA; © BIOCOM, Original illustration: Normaals/stock.adobe.com

Receptors mostly found in peripheral organs, as well as in immune cells

-Liver-CB1+ CB2-

-Brain-CB1+ CB2-

-Gall bladder-CB1+ CB2-

-Thyroid gland-CB1-

-Stomach-CB1+ CB2-


-Vascular system-CB1-

-Large intestine-CB1+ CB2-

-Pancreas-CB1+ CB2-Heart-CB1+ CB2-

-Small intestine-CB1+ CB2-

-Immune system-CB1-Male reproductive organs-CB1-

C a n n a b in o i d r e c e p t o r p h a r m a cology began in the late 1960s when ∆9-THC was isolated, synthesised and found to be the primary psychoactive constituent of the ancient medicinal plant Cannabis sativa (marijuana). The discovery in the early 1990s of specific membrane receptors for ∆9-THC led to the identification of the endogenous signaling system now known as the endocannabinoid system (ECS). It is mediated by two members of the Gprotein-coupled receptor family – cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Both are found throughout the body on the surfaces of cells in the brain, organs, tissues and glands. CB1 receptors are primarily found in the brain and central nervous system. CB2 receptors are mostly in the

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-Female reproductive organs-CB1-

peripheral organs, especially in cells associated with the immune system. The ECS essentially regulates most of the basic functions and patterns found in the human body and psychology, including mood, appetite, pain, immune function, sleep, metabolism, inflammation, digestion and memory. It’s also known to influence neuroplasticity, apoptosis, excito toxicity, neuroinflammation and cerebrovascular breakdown associated with stroke and trauma. That’s why it has become a prominent target in treating neurodegenerative diseases, cancer, epilepsy and traumatic brain injury. Marijuana contains large amounts of tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the most widely studied cannabinoid. It’s known for its

psychoactive effects, and is the reason humans get high when they use cannabis. Unlike THC, CBD does not produce a high, and even counteracts THC effects. That’s why many cannabinoidbased medications contain high-CBD, low-THC formulations. The therapeutic effects of CBD are more pronounced when combined with other cannabinoids and compounds in what is coined the ‘entourage effect’. It states that the synergy of different compounds produces effects that would not be felt when taking the individual compounds alone. The plant also includes more than 100 other trace cannabinoids, including cannabigerol (CBG), cannabinol (CBN) and cannabichromene (CBC), which also seem to have an effect on the endocannabinoid system.

12.12.2018 13:38:27 Uhr

European Biotechnology | Winter Edition | Vol. 17 | 2018

solid studies still leads to high rejection rates by health insurers when it comes to reimbursing patients for the drug. “70% of my patients respond to cannabinoid therapy,” says Seibolt. “I believe the intensive studies and research that are now being carried out will enable us to better identify the indications for which cannabinoids offer a real benefit.”

A hundred active ingredrients ‘Cannabinoids’ is a collective term for the substances present in the resin of the hemp plant. The female plant produces over 100 phytocannabinoids. From among them, the most intensively studied so far are the psychotropic tetra­hydrocannabinol (THC) and the primarily anti-inflammatory compound cannabidiol (CBD). Both bind to receptors in the body’s endocannabinoid system (ECS – see opposite page). Medicinal cannabis is usually given to patients in the form of buds from the hemp plant. Whether the patient then prepares it as tea, smokes it in a joint, nebulises it or cooks it in biscuits is up to him or her. The type of administration can have a considerable influence on the absorption of the active ingredient. There are also state-approved cannabis-based pharmaceuticals that have undergone approval procedures and clinical studies. These drugs have a standardised compo-

12-18_EB_Coverstory_Cannabis_2018_hm.indd 15

sition, and their effects and side effects are well known. The first approved medicine to target the endocannabinoid system was Marinol. That’s the brand name for a synthetic form of THC called dronabinol that was originally introduced in the early 1980s to treat symptoms caused by AIDS. Two other preparations have since been given the go-ahead: Nabiximol Spray, a high-alcohol solution that’s approved for therapy refractory spasticity in multiple sclerosis, and the synthetic cannabinoid Nabilone for the treatment of therapy refractory nausea under chemotherapy. Since its legalisation for medical uses, German physicians have also been allowed to prescribe cannabis extracts and cannabis blossoms for their patients (see Table 2, p. 18).

The domino effect in Europe In the last few years, there has been a major shift in Europe’s understanding of cannabis. Countries across the continent are cautiously opening up to the idea of more normalised use in society. While the legal status of cannabis varies from country to country in the EU, many governments now take a more progressive approach. The dominoes began to fall in 2003 with the legalisation of medical cannabis in the Netherlands, and the effect soon reached other nations – including Germany, which

Cover story


has some of the strictest anti­-narcotics laws in Europe. Today, the list of countries in Europe that have legalised or are considering the legalisation of cannabis for medical purposes is long. It includes Germany, Denmark, Macedonia, Malta, Italy, Belgium, the Netherlands, Portugal,

“Tilray was the first company that legally exported medical cannabis products from North America to Europe.” the Czech Republic, Luxembourg, Croatia, Estonia, Finland, Poland, Greece, Norway, Ireland, the UK and Lithuania. The European Industrial Hemp Association (EIHA), nova-Institute and HempConsult estimate that the European market for CBD as a pharmaceutical product is already worth €2bn. According to the 3rd edition of The European Cannabis Report that’s published by market intelligence firm Prohibition Partners, Europe’s medical cannabis market could be worth €55bn once all member states have implemented legislation and market infrastructure. With a market of over 742 million people, and healthcare spending that totals €2.3tn, Europe is potentially the largest medical cannabis market in the world,

07.12.2018 12:45:19 Uhr

cover story

which is making it attractive for global cannabis producers. Canadian manufacturers in particular have been signing export deals with European governments, and also buying local companies and opening production facilities in the region. Prohibition Partners says Canadian firms account for the majority of operating licenses in Europe along with around 70% of all European cannabis imports. A major player in medical cannabis research, cultivation, processing, distribution and export of cannabis-based products is Canadian company Tilray Inc. “In 2016, we were the first company that legally exported medical cannabis products from North America to Europe,“ says Marla Luther, Director of Business Development Europe at Tilray Inc.

European Biotechnology | Winter Edition | Vol. 17 | 2018

The situation right now in many European countries is similar to that in Canada back in 2014, when the Canadian government decided that patients should only purchase cannabis products from licensed providers.

From start-up to global company “At that time there were a lot of hempgrowers with huge knowledge about the plant, but they barely had enough capital to produce pharmaceutical-grade cannabis,” says Luther, who has been working for Tilray since it was founded. “So the Canadian Department of Health approached today’s Tilray executive Brendan Kennedy to invest in one of the companies that applied for a license.“

High time to protect cannabis IP commentary  Aspiring biotech businesses looking to gain a foothold

in the fledgling European medical cannabis industry should take a leaf from their Canadian counterparts on intellectual property, say specialist life sciences patent attorneys Micheline Gravelle and Jane Wainwright.

After decades of global prohibition, cannabis in 2018 is rapidly going mainstream. Medical access has existed across Canada and swathes of the US for some time, with the former fully legalising adult recreational usage just this October. Europe too is embracing regulatory change, albeit more slowly, with the Netherlands, Germany and – most recently – the UK all permitting medical usage. Indeed, the potential of the wider European market is huge, with projections from market intelligence firm Prohibition Partners estimating a fully legal industry being worth €115.7bn by 2028. Given the international competition in this hugely dynamic and commoditized industry, robust intellectual property protection will be absolutely crucial for European businesses looking to make their mark.

12-18_EB_Coverstory_Cannabis_2018_hm.indd 16

Micheline Gravelle is managing partner and co-leader of the cannabis group at Canadian IP firm Bereskin & Parr

As the market evolved in Canada during the 1990s, it was truly eye-opening to see such a patchy understanding of the basics of IP. Typically, bigger biotech players with budgets to match are well-versed in the art of protecting their innovations, but in the rush to bring products to market, smaller start-ups often found themselves falling short on the fundamentals. So where are the opportunities?

Kennedy owns private equity firm Privateer Holdings, which has been investing in the legal cannabis industry since 2011. “After a lot of discussion and research, the executives didn’t find a suitable company that knew the cultivation as well as they did themselves – so they decided to found Tilray,“ explains Luther. Five years on, the medicinal cannabis company sells its products to patients, researchers and pharmacies all over the world, and was the first such company to conduct an IPO in the US in 2017. In the process it raised US$153m in capital. Then in early October, Tilray announced the closing of an additional US$435m in net financing, on top of the cash it received from its IPO. That mon-

Harnessing the IP toolbox Obtaining a patent is often the strongest protection available for cannabis products and processes, providing a monopoly to the owner to exclude others from making, using or selling the invention for 20 years from the filing date once the patent has issued. There are many patentable products and processes in the cannabis industry, such as novel or modified active ingredients extracted from the cannabis plant or chemically synthesized. This includes the isolation of novel cannabinoids as well as specific combinations of cannabinoids and/or terpenes. Patents can also be obtained for novel formulations comprising cannabis active agents or new combinations of active agents. New uses of cannabis or cannabis actives, such as new indications that were not previously treated with cannabis products, may also be patented. In temperate climates, the specialised growing conditions for cannabis may yield new equipment or novel arrangements of equipment, for which patents may also be obtainable. Novel cannabis plant varieties may also be protected in certain countries under various regimes. In Europe, plant va-

Pictures:EMBO Picture: Pictures: Suited Fotolia.com/crevis Comms. Mol Med. 2017 Sep; 9(9)- 1183–1197. Published online 2017 Aug 1. doi- 10.15252:emmm.201607485


06.12.2018 14:16:41 Uhr

Cover story

European Biotechnology | Winter Edition | Vol. 17 | 2018

ey can now be used to explore market possibilities in Europe.

Portugal – the right place to be

Pictures:Suited Picture: xxx Comms.

Last year Tilray announced the investment of €20m through its affiliate Tilray Portugal Unipessoal Lda to build an EU Campus located in the Biocant Research Park in the Portuguese city of Cantanhede. It will in future cultivate, process, package, and distribute GMP-grade medical cannabis products to qualified patients, pharmacies, and researchers throughout the European common market. “For two years, we have been searching intensively for a suitable location in Europe from which to serve the rapidly growing European market for high-quality, rigorously tested med-

rieties can be protected by Community Plant Variety Rights (CPVR) or through national protection systems. The variety must be proven to be new, distinct, uniform and stable. Once the PVR is granted, the cannabis breeder gets exclusive rights to the propagating material of their variety for a period of 20 years, covering the right to sell, produce, reproduce, import and export propagating material of the variety. When the time comes for developing and protecting their all-important brands, companies should also consider conducting clearance searches and file for trademark protection. Generally, trademarks can be obtained for words, slogans and designs that function to distinguish a company’s goods and services from others. It is currently difficult to obtain trademarks in the European Community, as a whole, for cannabis products due to the prohibition of trademarks for products considered “immoral”. However, it may be possible to obtain trademark protection directly in certain European countries. Trade secrets can also be a useful tool for cannabis companies looking to keep their IP confidential. These generally apply to methods or formulas that cannot be easily reverse-engineered by competi-

12-18_EB_Coverstory_Cannabis_2018_hm.indd 17

ical cannabis products,” says Tilray CEO Brendan Kennedy, “and Portugal has an ideal climate for growing cannabis, a large number of qualified professionals and a large scientific community.” The EU campus will be home to both indoor and outdoor facilities, along with greenhouses. In addition, facilities for the processing, packaging and distribution of medical cannabis products are to be built. The first live cannabis samples were exported from Canada to Portugal last year. “As we are working with natural plants you still need some time for the growing process. Right now we are finishing the last construction and regulatory requirements, and will be exporting from the facility in 2019,“ says Luther. With its two new greenhouses covering 30,0000 m2,

Jane Wainwright is a partner specialising in life sciences at European IP firm Potter Clarkson

tors. Here, companies may want to keep their method for producing cannabis or their formulations as trade secrets if it provides more economic value than disclosing the information in a patent.

Diligence pays Vibrant M&A activity is a feature of any rapidly developing industry, and a further area where robust IP protection is key. The stakes are indeed high. According to figures from PwC, Canadian cannabis M&A activity hit CA$93bn in the first quarter of 2018. While those numbers are some way off in Europe, assessing the existing IP provisions of acquisition targets is an integral part of the due diligence process for buyers, often meaning the difference between making or breaking a deal.


Tilray’s cannabis production should rise to 62 tonnes per year. The first legal medicinal product grown in the EU will then be available for patients next year.

It remains a plant “We know a lot about cultivation, harvesting, and the different batches of the cannabis plant, but it still remains a plant and you can’t say that every batch has exactly identical levels of active ingredients”, explains Luther. According to her, active ingredient content in plants can vary from harvest to harvest by 15% or more. Tilray has developed cannabis fullspectrum extracts which, in addition to the main active ingredients THC and

European companies also need to be especially mindful of the international nature of the industry. While there are now 90 publicly listed cannabis-related companies in Canada with a market value of about CA$31bn, the top three filers of patents there are actually Swiss, US and British businesses. While more established businesses naturally have the systems, procedures and capabilities to quickly enter markets across the globe, the Canadian experience has shown that start-ups can be responsible for a great number of market-shaping innovations – but only when their IP is protected.

Tracking growth Although the Canadian industry is already maturing, it remains uncertain just how swiftly the European market will follow suit. That said, developments from November alone, when healthcare provider Columbia Care became the first US business given a license to operate in the EU and Greece issued its first licences to companies for growing medical cannabis, underline the imperative for European businesses to safeguard their innovations before the green rush L here hits full swing.

06.12.2018 14:16:46 Uhr


Cover story

CBD, contain the other compounds found in cannabis flowers like terpenes. Both extracts are refined in grape seed oil, and remain natural products that smell like cannabis and have a yellowgreen colour.

European Biotechnology | Winter Edition | Vol. 17 | 2018

Market value of canadian cannabis suppliers

Clinical research important “It’s an unprecedented situation in the therapy of patients,” exclaims Luther. “All over the world, public health systems are providing access to products for which there are hardly any approved products.” To promote clinical research, Tilray founded a German subsidiary in Berlin last year. “Germany is of course particularly interesting due to the rich research landscape and excellent university hospitals. And the infrastructure in the healthcare market is so advanced there that we not only see opportunities to sell our products commercially, but above all to drive our research and development forward,” says Luther. “As public interest in cannabisderived medicines continues to grow, we need objective, valid data about the potential risks and benefits of medical cannabis gathered through clinical trials and the scientific methods. Tilray is currently developing specific cannabinoid and terpene profiles for study drugs based on preclinical and clinical data, generating relevant pharmaco­kinetic parameters of study drugs and establishing and maintaining a pharmacovigilance database.” Tilray isn’t the only company to sense a big opportunity with medical cannabis in the EU. Aiming to pursue the


Founded in

Market value (US$)*

› Tilray Inc.



› Canopy Growth Corp. Inc



› Aurora Inc.



› Aphria Inc.



› Cronos Group Inc.



* tracked by the Bloomberg Intelligence Global Cannabis Competitive Peers Index

cultivation and worldwide distribution of organic, EU GMP-certified medical cannabis, in September Aphria Inc. announced a strategic partnership with Danish Schroll Medical, a subsidiary of prominent European flower producer Schroll Flowers.

Who’s in the race? The company has already received its license for the cultivation of medical cannabis from the Danish Medicines Agency, and currently owns property where production has started in a retrofit greenhouse. Its first products are expected by early 2019. To strengthen its end-to-end operations and infrastructure in Germany, Aphria also announced the €24.5m acquisition of CC Pharma GmbH in November. Earlier this year, through its wholly­ owned subsidiary Aphria Deutschland, the firm acquired a 25.1% interest in Berlin-based Schöneberg Hospital. That move was made to provide access to support education for both doctors and

patients on the benefits of medical cannabinoids. It was also the first step in Aphria Deutschland’s plans to build and operate pain treatment centres throughout the country. Tilray and Aphria are just two companies in what’s become a crowded field. However, doctors like German palliative physician Gottschling say we should be careful not be too precipitous. “An almost unmanageable number of cannabis suppliers are now entering the market. Should this competition serve to encourage different companies to support urgently needed research projects, among other things, I see this as a positive development,” Gottschling says. “However, you now notice a certain gold-rush atmosphere. Many companies simply want to grab a piece of the tempting pie, but that won’t actually change or improve care for patients. We doctors are also caught in a maze of different providers, so due to the sometimes rather aggressive marketing strategies, we need to be careful to keep our bearings.” h.maerzhaeuser@biocom.eu

Approved cannabis-based products in Germany and how they are administered


Pharmaceutical properties



› Dronabinol

Pure THC that can be used for the preparation of prescription drugs

Oily drops, capsules or ethanolic solution for inhalation

Predominantly mediated by cannabinoid receptors

› Nabilon

THC analog that doesn’t occur naturally; 1mg has the same effect as 7-8mg THC

Capsules contain 1mg active ingredient

Similar to THC

› Nabiximols

Mixture of two cannabis extracts, normalised to a specific THC and CBD content

Ethanolic mouth spray (1.7 mg THC + 2.5 mg CBD)

Similar to THC, possible additional effects due to low-dose CBD / other ingredients unclear

› Cannabis extracts

Standardised multi-component mixtures from cannabis flowers

Recipe ingredients for the production of oily drops

Mostly dominated by THC, additional effects of low-dose CBD / other ingredients so far not clear; no study evidence

› Cannabis flowers

Female blossoms of various hemp varieties; cannabinoid composition and other ingredients differ depending on variety

Uncrushed, crushed, sifted or granulated for evaporation, smoking, baking or tea preparation

Depends on THC:CBD ratio; no study evidence on specific varieties of flowers

12-18_EB_Coverstory_Cannabis_2018_hm.indd 18

06.12.2018 14:16:50 Uhr

25 Years of Success > 50 Countries > 1000 Trials > 1.380.000 Samples > 8.500.000 Analytical Results MLM Medical Labs is one of the leading central labs for clinical trials in Europe. For 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 www.mlm-labs.com. MLM Medical Labs GmbH Dohrweg 63, 41066 Mรถnchengladbach/Germany

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07.08.18 19:20 06.12.2018 14:17:09 Uhr



European Biotechnology | Winter Edition | Vol. 17 | 2018

Are novel antibiotics worth investing in? Antimicrobial resistance  In autumn, stakeholders across the globe pledged to take more

action in the fight against antimicrobial resistance (AMR). Whereas from the “push” side new public and private initiatives appeared on the screen, discussion about which “pull” mechanism should be started first is in full swing. Meanwhile, small and medium-sized companies combine forces aiming to propel preclinical and early clinical R&D.

at the United Nations General Assembly and bundling together the commitment of over 100 organisations in the fight against AMR. “It is important to pursue new policies and reimbursement approaches now, to shift the investment landscape right away. One constructive way would be to develop innovative payment mechanisms that allow companies to capture a greater upfront share of the social value of antibiotic drug development,” FDA commissioner Scott Gottlieb said during the kick-off event

New reimbursement models

G20 leaders urge for action Only two days later, G20 leaders in Argentina released their final declaration, underlining the need for urgent action: “We note the work done by the Global AMR R&D Hub and, drawing on this, we look forward to further examining practical market incentives.” In the AMR community, this message was well-appreciated; however, rather than examining the options, the implementation of pilot measures would be preferred by most stakeholders. Particularly because there is, in principle, no lack of ideas about how to spur up the antibiotics market with market incentives. In mid-September, the US-regulatory body FDA unveiled its “2019 Strategic Approach for Combating AMR” under the umbrella of the “Global AMR Challenge” initiative, launched

20-21_EB_Winter_2018_AMR_sw.indd 20

co-hosted by the Bill & Melinda Gates Foundation, the Pew Charitable Trusts, the United Nations Foundation, Wellcome Trust, and the CDC Foundation. Although Gottlieb lauded the accomplishments of existing “push”-style incentive programmes, such as the Generating New Antibiotics Now (GAIN) Act and the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD), in generating new drug R&D, he noted that in spite of these efforts only 11 antibiotic products that are designed to address the most-threatening pathogens, as identified by the World Health Organization (WHO), are currently in clinical trials.

Christian Riemann  CEO of Bacteriobator, and Global Investment Bridge Capital AG, Munich

? !

Which investment focus in AMR does Bacteriobator have?

We look into new therapeutic, diagnostic, as well as hygienic approaches, such as antiseptic agents and materials in Europe and the US. This allows us to balance our risk-return profile, over a medium-term time frame of 4–6 years.

He thus advocated for stronger “pull” incentives, including new reimbursement models that would provide milestone payments and subscription fees for new FDAapproved antibiotics with demonstrable clinical and social values. Pilot projects based on new market incentive models are also prepared at NICE in the United Kingdom, as AMR experts told European Biotechnology, but currently financing is still under discussion. In most other European countries, however, government‘s priority action goes into push funding.

Germany officially joins CARB-X During the Antibiotic Awareness Week in November, for instance, the French government committed €40m to academic research, and Denmark announced they

Pictures: Christian Riemann (private)

The news spread like wildfire in the AMR community: Exactly one year after USbased Melinta Therapeutics executed a US-$270m pact to buy out the Medicines Co’s infectious disease group – one in a string of pipeline expansion deals – the Connecticut-based drugmaker reported it had reduced headcount at its headquarters, laying off 22 out of 25 staff members and spinning out research projects. “Sad, but not unexpected news,” commented Kevin Outterson, head of US-based financing vehicle CARB-X, on Twitter and added: “Does anyone need more proof that the way we pay for antibiotics is thoroughly broken and we need delinked reimbursement reform immediately?”

07.12.2018 12:46:59 Uhr


European Biotechnology | Winter Edition | Vol. 17 | 2018

Basic Science

Preclinical research and development

Phase I

Phase II

Phase III



JPI AMR GAIN: Generating Antibiotic Incentives Now Act, e.g. QIDP designation

Horizon 2020 and IMI/ND4BB BARDA

READI: Tax credit for Phase III costs

NIH/NIAID Wellcome Trust

REVAMP: Transferable exclusivity award

National Science Research Agencies CARB-X

DISARM: Reimburses antimicrobials outside of DRG coding

GARDP EIB’s InnovFin

FDA Subscription Model: Fixed amounts of payments per hospital

UK/China Global Innovation Fund Novo REPAIR Impact Fund

Market Entry Award: US$1bn cash award

Bacteriobator Accelerator PUSH INCENTIVES Existed prior to 2016  

Recently launched  

would host a new international research centre for global solutions on AMR. A month earlier, Germany earmarked €500m for global AMR activities, of which about €40m will flow into CARB-X to build up a European office in Germany. Swiss regional agency Baselarea.Swiss also joined this initiative as a new European hub. How this kind of non-profit public-private financing could also be used to leverage private investments was discussed during a workshop at the World Investment Forum in September, organised by the United Nations Conferences on International Trade (UNCTAD) together with the WHO. Experts explored major gaps in AMR financing and how to bring in new investors. During the Novel Antimicrobials & AMR Diagnostics conference, held from 14– 15 March 2019 in Berlin, UNCTAD and WHO will host a session to determine requirements for structuring a new global AMR fund (see p. 54). Meanwhile, another European investment initiative called Bacteriobator Accelerator popped up in Germany. “We

20-21_EB_Winter_2018_AMR_sw.indd 21

PULL INCENTIVES Currently discussed

already have €50m pre-negotiated, available from private investors and are now in the process of structuring it for investments. Our aim is to incubate or accelerate the most promising academic and post-academic projects until clinically relevant stages so that further capital may step in,” Christian Riemann, from Munich-based Global Investment Bridge Capital AG, who runs Bacteriobator Accelerator, told European Biotechnology. The money will target the whole range of AMR innovation.

How to reduce R&D costs One of the biggest challenges for most of the existing AMR-active smaller companies, however, is to reduce R&D costs. A new solution could be provided very soon by three companies, BioSystems Technology (UK), BioVersys (CH) and Voxcan (FR). Under the umbrella of the EUfunded IMPACT2 consortium they joined forces to establish a novel translational AMR platform. “With respect to AMR


R&D, the basis on which new antibiotics are discovered and tested uses old standard methods to characterise novel compounds, and they do not suit all types of approaches, such as anti-virulence compounds,” explains Jonathan Butcher, Head of Business Development at BioVersys. The new platform is combining BioVersys‘ capability to genetically manipulate multi-drug and even PAN-resistant clinical isolates, Biosystems Technology’s moth larvae model and Voxcan’s imaging technologies for generating real-time animal model infection data with up to date clinical isolates. It provides services for discovery and preclinical stage projects – target validation and confirmation, compound screening in larvae, toxicity and in vivo efficacy testing, covering Gram-negative pathogens like A. baumannii and K. pneumoniae. “Our combined technologies will allow for a faster, cost-effective and ethical development of novel AMR compounds, both traditional and non-traL ditional,” Butcher says. s.wirsching@biocom.eu

07.12.2018 12:47:05 Uhr


FinanciAL markets

European Biotechnology | Winter Edition | Vol. 17 | 2018

Two surrenders to the adverse market Austria  The race was on this fall: Marinomed Biotech AG and Themis Bioscience NV were head-

A bell rings the trading day on and off again. But you still have to wait for trading in the shares of Marinomed AG on the Vienna Stock Exchange.

While formulation expert Marinomed had staged its IPO carefully in regional and in­ ternational media, fellow Austrian vac­ cine and cancer immunotherapy specialist Themis took the fast lane – in November, it announced the terms of its initial public offering (IPO) and listing on Euronext Am­ sterdam (Netherlands), beating Marino­ med by a couple days. Themis planned to offer up to a total of 3,600,000 ordinary shares within a price range of €9.70–€11.60 per share totaling €55.3m in the best case scenario, includ­ ing a fully exercised 15% overallotment option. The expected market capitalisa­ tion would have been between €120.4m and €157.5m. The IPO was announced as a public offering to retail investors in the Netherlands and private placements to institutional and eligible investors in other countries. Existing shareholders Global Health Investment Fund I, Wel­ lington Partners, aws Gründerfonds

22_EB_Winter_2018_FinanceThemisMarinomed_ml.indd 22

Beteiligungs GmbH & Co KG, FPCI Ven­ tech Capital III, and Evotec CEO Wern­ er Lanthaler had pledged to subscribe for shares for an aggregate amount of €8.6m. After postponing its IPO, citing adverse market conditions, Themis said that it now will investigate other strategic options, including financings, for the de­ velopment of its programmes.

Dry spell continues Marinomed also announced its plans for entering the public market at the stock exchange in Vienna in November. It would have been the first IPO there for more than a year. The company intended to float around 43% of the family busi­ ness by issuing 400,000 shares. With a price range of €75–€90, Marinomed wanted to net around €30m–€36m. The IPO comprised a public offering to retail and institutional investors in Austria, and

a private placement outside Austria to selected institutional investors. The run-up to their planned IPOs was picture-perfect. Themis’ news flow, for instance, included a PRIority MEdicines (PRIME) designation by the European Medicines Agency for its marketing au­ thorization application for the Chikungun­ ya fever vaccine MV-CHIK. Following the successful completion of a Phase II study this year, work is currently underway on the design of the pivotal Phase III study for the prophylactic vaccine. A big fraction of the money of the proposed offering – about €30m – would have been spent to carry out that study, including production of the measles-virus-based vaccine. To widen the scope beyond infectious diseases, Themis also had ventured into oncology in October by securing a world­ wide exclusive license for the deve­lopment, production, and marketing of (again mea­ sles-virus-based) oncolytic virotherapies – but as it turned out, to no avail. After string of successful IPOs through late summer, the IPO window seems to be closing. Besides Themis and Marinomed, Danish pharma company Abacus Medicine (on the Frankfurt stock exchange), Euronextlisted French biotech Nicox, and US-pain specialist Centrexion Therapeutics (both on Nasdaq New York), have also pulled out of their planned listings, pointing to the cur­ rent volatility of the financial markets. On the other hand, British gene therapy com­ pany Orchard Therapeutics managed to go public on Nasdaq in early November, rak­ ing in US$225.5m. Just a small bump or turning tides? The verdict about investor in­ L terest in biotech is still out. m.laqua@biocom.eu

Picture: Wiener Börse

to-head on their way from a private to a public company. So far, there’s no winner – both had to give up their plans of going public in the final stretch, when investor sentiment turned wary.

06.12.2018 14:18:24 Uhr

Update on clinical trials Lymphoma


Genentech’s new partner Affimed NV has halted two Phase I studies assessing the safety of its tetravalent bispecific T cell engager AFM11 after a death and two cases of severe neurotoxicity occurred. The company’s shares, which skyrocketed after Genentech licenced the company’s ROCK platform for $5bn, dropped by 30%. The death and two severe neurotoxicities occurred at the highest dose of AFM11 (2CD19 x 2CD3) in two Phase I dose escalation trials enroling 33 patients with ALL (acute lymphoblastic leukemia) and NHL (Non-Hodgkin Lymphoma). Although the company didn’t publish any details describing what exactly happened, it’s no secret that modalities that link effector T cells to the Bcell target CD19 can trigger neurotoxic SAEs: Amgen’s bispecific T cell engager blinatumomab has a black box warning both for cytokine release syndrome (CRS) and neurotoxicity. Furthermore, approved CAR-T cell therapies from Gilead Sciences and Novartis targeting the CD19 antigen on B cells induce CRS and show 15–30% neurotoxic SAEs. Most recently, Spanish researchers proved that IL-1 blocker anakinra (SOBI AB) can help manage neurotoxicities, while IL-6 receptor blocker tocolizumab (Roche) has been FDA-approved to manage CRS. MorphoSys AG reported a 58% overall response rate for the CD19 antibody MOR208 plus lenalidomide in 81 patients with treatment-refractive diffuse large B cell lymphoma (DLBCL). Twenty-seven patients had a complete response and 20 a partial response. Median progression-free survival (PFS) was 16.2 months. At the end of October, Genmab A/S announced a combo of its CD38-targeting antibody daratumumab with lenalidomide and dexamethasone has met the primary endpoint of progression-free survival (PFS) in an interim analysis of its pivotal Phase III MAIA study in patients with mul-

23-25_EB_Winter_2018_Trial_tg.indd 23

tiple myeloma (MM). The antibody was licenced from Janssen Biotech. alzheimer's Disease


Spanish Grifols SA reported a 61% reduction in the progression of moderate Alzheimer’s disease using a combination of plasmapheresis with a 20% albumin solution (AlbuteinŽ 20%). In patients with mild disease, there was no significant difference observable between the treatment and the placebo arm using the AMBAR treatment protocol. Wet AMD


Roche AG has reported superiority of its bispecific antibody faricimab (RG7716) in wet age-related macular degeneration (AMD), when dosed every four months, compared to monthly administration of its VEGF-A inhibitor ranibizumab. People treated with the Ang2 x VEGF-A antibody dosed every 16 weeks experienced a mean improvement of 11.4 letters from baseline, compared to 10.1 letters in patients treated with faricimab dosed every 12 weeks, and 9.6 letters in patients treated with 0.5 mg ranibizumab dosed every four weeks. LHON


Gene therapy specialist GenSight Biologics SA has reported 72-week efficacy data from its REVERSE Phase III clinical trial of GS010 (rAAV2/2-ND4) in 37 patients with Leber Hereditary Optic Neuropathy (LHON). According to the company, a clinically meaningful improvement of +15 ETDRS letters in visual acuity of treated eyes were observed, with concomitant contralateral improvement of +12 letters in sham-treated eyes. Continued improvement was also observed in contrast sensitivity as determined by Pelli-Robson low-contrast testing. At 72 weeks, GS010-treated eyes and sham-treated eyes gained on average +0.21 LogCS and +0.15 LogCS versus baseline, respectively. The proportion of treated eyes that achieved a clinically meaningful improvement of at least


European Biotechnology | Winter Edition | Vol. 17 | 2018



06.12.2018 14:19:34 Uhr


Regulatory Affairs

European Biotechnology | Winter Edition | Vol. 17 | 2018

News Drug beats arrythmia

Let it flow Genkyotex SA has met interim efficacy endpoints in the ongoing Phase II study of the NOX1/4 blocker GKT831 in 92 patients with primary biliary cholangitis. PBC is an orphan chronic autoimmune disease resulting in the progressive destruction of bile ducts. NADPH oxidases (NOX) are believed to be essential for the generation of reactive oxygen species that activate hepatic myofibroblasts that produce extracellular matrix proteins triggering fibrosis. After six weeks of treatment with 400mg GKT831 twice daily, GGT values dropped by 23% and alkaline phosphatase levels were 17% lower than at baseline. Final study results after 24 weeks of treatment in 111 PBC patients are expected in spring 2019.

Bacteria vs diabetes Immatics Biotechnologies GmbH has kicked off a Phase I study with its adoptive T cell therapy IMA202 in hepatocellular and advanced non-small cell lung cancer. Twelve patients will be enrolled at the MD Anderson Cancer Center in Houston.

23-25_EB_Winter_2018_Trial_tg.indd 24

Mode of action of UCB’s IL-17A x IL-17F bispecific antibody bimekizumab.

0.3 LogCS (45.9%) was statistically significantly higher than that of sham-treated eyes (24.3%; p=0.0047). The visual function outcomes were accompanied by evidence that GS010 was engaging its anatomic targets, the ganglion cells. At 72 weeks, high-resolution SpectralDomain Optical Coherence Tomography (SD-OCT) objectively demonstrated sustained preservation of the retina anatomy relevant to LHON in GS010-treated eyes. The ganglion cell layer macular volume was preserved (+0.000 mm3) in treated eyes, while sham-treated eyes deteriorated from baseline (-0.044 mm3). The difference was statistically significant (p=0.0060). Drug-treated eyes also showed a limited loss in thickness of the temporal quadrant of the retinal fiber layer of -1.6 µm, compared to a loss of -3.6 µm in sham-treated eyes (p=0.0521). Psoriatric arthritis


Belgian UCB SA’s anti-IL17 antibody bimekizumab showed promising response rates in 206 patients with psoriatic arthritis enrolled in the Phase IIb BE ACTIVE study. The results presented at the ACR/ARHP Annual Meeting were the first long-term results reported for the IL-17A and IL-17F-specific bimekizumab. The study achieved its primary endpoint, with 46% of PsA patients who received bimekizumab experiencing at least 50% improvement in psoriatic arthritis signs and symptoms (ACR50), versus 7% with placebo, at Week 12. These results were generally consistent regardless of prior exposure to an antiTNF and were maintained to Week 48

across doses. At Week 48, ACR20/50/70 response rates were 70%/55%/43% for the 160 mg dose; 73%/57%/46% for the 160 mg dose with a loading dose; and 76%/63%/39% for the 320 mg dose. In addition, Psoriasis Area and Severity Index (PASI90) response rates at Week 48 were 70% for the 160mg dose with and without a loading dose, and 85% for the 320mg dose. The study also evaluated several other endpoints, including the number of patients who achieved minimal disease activity (MDA), which continued to increase from Week 12 (2946%) to Week 24 (37–60%) across dose ranges (160mg to 320mg). Response rates were then maintained through Week 48 (46 – 60%) across the same dose ranges. Serious adverse events were reported in 4.4% of patients at all doses at Week 48. Nasopharyngitis was the most frequently reported adverse event (12.1%). Oral candidiasis was reported by 4.9% of patients and did not lead to discontinuations. Systemic Lupus erythematosus ˆ

J&J subsidiary Janssen-Cilag AG has reported 12 months results from a Phase II study with ustekinumab as treatment of active systemic lupus erythematosus (SLE). Compared to placebo (33%), 62% of patients treated with ustekinumab met the primary endpoint of SRI-4 response at week 24. After the 24-week placebocontrolled period of the study, patients receiving placebo crossed over to receive ustekinumab (90 mg SC every 8 weeks), while patients receiving ustekinumab continued to receive ustekinu-

Picture: © W.D. Shipman

Cardiac arrhythmia specialist Acesion Pharma ApS is heading to Phase II testing of its lead compound in cardioversion, the SK channel blocker AP30663. Results of a Phase I dose finding study enroling 43 volunteers in the Netherlands pointed to a good safety profile. According to the company “no significant adverse events” occurred.

06.12.2018 14:19:39 Uhr

European Biotechnology | Winter Edition | Vol. 17 | 2018

mab at the same dose (90 mg SC every 8 weeks). Following approximately one year of treatment, rates of changes from baseline in SLE Disease Activity-2K (SLEDAI-2K) were sustained from week 24 (65%) through one year (67%). Based on the results of the Phase II study, Janssen has initiated the Phase I I I LOT US s t u d y (N C T03517 72 2 / EudraCT2017-001489-53). Solid Tumours


Roche AG has reported hints of efficacy of its anti-FAP/interleukin-2 fusion protein RO6874281 in metastatic cancers. Out of 30 patients with solid tumours enrolled in a Phase I study, two melanoma patients showed a partial clinical response, and one patient with head and neck cancer showed a complete response. The monoclonal antibody moiety of RO6874281 recognises and binds to FAP, thereby concentrating IL-2 in FAPexpressing tumour tissue. The IL-2 moiety can activate natural killer (NK) cells and T killer cells but not regulatory T cells. Diabetes


Intrexion subsidiary ActoBio Therapeutics Inc. and Intrexon T1D Partners LLC have dosed the first patient with engineered Lactococcus lactis bacteria in a Phase Ib/ IIa clinical trial for the treatment of early onset type 1 diabetes (T1D). ActoBiotics AG019 is designed to induce immune tolerance in T1D by expressing proinsulin and the immune-dampening cytokine IL10. The idea of this novel approach is to deliver human proinsulin and IL-10 to the mucosal lining of digestive tract. While patients will receive AG019 monotherapy in the PhaseIb part of the study, patients will get an add on therapy with the antiCD3-antibody teplizumab in the Phase IIa part of the study. Preclinically, the combo induced reversion to normal blood sugar levels in 60% of diabetic mice, and effectively reversed the disease in 89% of mice treated at early stage. Results are expected by Q1/2020. HAemophilia


UniQure NV’s hemophilia B gene therapy AMT-061 has led to Factor IX activity

23-25_EB_Winter_2018_Trial_tg.indd 25

between 23% and 37% over six weeks in patients with severe disease who received a single infusion of 2x1013 vc/kg of the AAV5-based therapeutic. None of the three patients enrolled in the open label Phase IIb dose confirmation study required immunosuppression or further factor IX infusions. No bleeding events were reported over 24 weeks. Patients in the study will be followed for 52 weeks to assess factor IX activity – measured via an activated partial thromboplastin time (aPTT) assay – bleeding rates, and usage of factor IX replacement therapy. They will be monitored for five years to evaluate the safety of AMT-061. AMT-061 has been granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) and Priority Medicine (PRIME) status by the European Medicines Agency (EMA). UniQure expects to submit data from the Phase IIb study to the FDA and EMA this year. Uniqure’s plan is to initiate Phase III testing in 50 patients with severe hemophilia B in Q1/ 2019. S a n g a m o T h e r a p e u t i c s I n c . lo s t US$250m in market capitalisation in November, following the announcement that Phase I/II results of its hemophilia A therapy SB-525 will be reported with delay and won’t be presented at the American Society of Hematology (ASH) meeting. SB-525 is an adeno-associated virus-based gene therapy expressing factor VIII gene under control of a liver-specific promoter. SB-525 has been exclusively licenced by Pfizer. Prostate Cancer

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Darolutamide (ODM-201), a novel oral androgen receptor antagonist co-developed by Orion Corp and Bayer SE under a 2014 agreement, has met the primary endpoint of a pivotal Phase III study in patients with castration-resistant prostate cancer. The drug significantly extended metastasis-free survival compared to placebo. Under the agreement, Bayer has global commercialisation rights, but Orion may co-promote ODM-201 in Europe and is eligible to receive substantial L royalties on the product sales.



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European Biotechnology | Winter Edition | Vol. 17 | 2018

How to make better drugs and bring them to patients BIO Europe  A frothy market, gene and cell therapies, and birth control for women –

there were topics galore to discuss at coffee breaks and evening receptions at this year’s BIO-Europe held in the Danish capital Copenhagen. In between, everyone was busy doing business, as indicated by a record number of B2B meetings.

tion with DKK392m (€52.5m) – presented eight local start-ups at BIO-Europe that take part in BII’s Business Acceleration Academy programme. Among them, Circle Biomedical attracted most of the attention with their on-demand birth control technology that puts women in charge of contraception. The hormone-free approach leverages the barrier function of the cervical mucus. No wonder that Circle Biomedical also won the inaugural accelerator programme in late November.

The auditorium was packed at BIO-Europe’s opening plenary session on November 5.

“I’m not interested in how frothy the market is right now. What interests me is if the whole ecosystem is about to change. Can we make better drugs cheaper and faster by setting up the industry in an alternative way?” While this could have easily been the boiled-down message of this year’s partnering conference BIOEurope, Ruth McKernan was referring to the Dementia Discovery Fund (DDF) she works for as a Senior Advisor. The world’s largest venture fund is focused entirely on discovering and developing novel therapies for dementia, including Alzheimer’s disease, has £250m under management. Several patient and academic organisations and six pharma companies are part of the syndicate. According to McKernan, the DDF is a prime example for new collaboration models that have begun to emerge: “With a diversity of views from nonprofits, government as well as phar-

26-28_EB_Winter_2018_BIO-Europe_ml.indd 26

ma, we believe we have a knack to tackle a major global health issue that has seen many setbacks in the past.”

Spotlight on Denmark and Sweden Maybe it is this spirit of cooperation that drives the success of the event. Event organiser EBD Group counted new record numbers concerning both attendees (4,350) and partnering meetings (26,100) for the first BIO-Europe event organised outside German-language territory. Local co-producers in Denmark and Southern Sweden included Copenhagen Capacity, Invest in Skåne, LEO Pharma, Lundbeck Fonden, Novo Holdings, Novo Nordisk, and Novozymes. Showcasing the region’s strengths, the Bio­innovation Institute (BII) – a three-year project funded by Novo Nordisk Founda-

Another topic with a potentially huge impact was brought up later on. Experts on health technology assessment (HTA) discussed the current state of harmonisation of HTA programmes across Europe. The idea dates back to a project started in 2006 when one of the driving forces, the European network for health technology assessment (EUnetHTA), was initiated. The concept gained traction in 2017, when the European Commission (EC) had been consulting on multiple scenarios for HTA harmonisation. EUnetHTA Senior Technical Advisor Zoe Garrett told the audience in Copenhagen that a Europewide HTA could become mandatory in 2026 in a best-case scenario: “Legislation is likely to go through the European Parliament in 2019 with expected adaptation of regulation in 2020. Next follows a three-year development and adoption period between 2020 and 2022, followed by a transition period where a limited number of assessments will be complet-

Picture: Schedl/EBD Group

HTA on a European level

06.12.2018 14:21:25 Uhr

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Financial Markets

ed, and participation will be voluntary for member states. Mandatory participation could begin as early as 2026.” From an industry perspective, an EUlevel HTA could speed up and simplify a process that has to be done on a country by country level at the moment. The industry largely backed the European Commission’s proposal published this spring. However, the European Parliament has since stated it wants Europe’s numerous national and regional HTA bodies – the EUnetHTA has 81 partners – to retain the right to run some of their own checks, in parallel to a joint HTA. Bertram Häussler, Chairman of IGES Institute (Germany), pointed out one of the problems that has to be addressed: “What if a centralised assessment for an expensive drug is positive? Certainly, rich countries will provide the drugs. But what about countries that can’t effort them?” Here, voluntary cooperations regarding a pricing system are the way to go, Häussler and Garrett agreed.

Pharma remains reluctant Garrett also gave insight about her ongoing work of developing practical tools to provide reliable, timely, transparent and transferable information for HTA. Within the third EUnetHTA Joint Action programme, the goal is to implement a sus-

European Biotechnology | Winter Edition | Vol. 17 | 2018

tainable model for the scientific and technical cooperation on HTA in Europe. “As working on this topic is completely voluntary, it has been incredibly difficult to convince the pharma industry to share data – for example in the field of clinical assessments – with us. This problem needs to be overcome if we want to succeed in creating a straightforward unified HTA in Europe.”

partnerships, corporate innovation needs to use more of the many available tools to translate these new scientific advances into profitable products.”

Innovation in BD needed

Lanthaler was a panelist at BIO-Europe’s opening session “Europe: The Global Innovation Trailblazer.” Questioning the panel’s title, Onno van de Stolpe, CEO of the listed Belgian drug developer Galapagos, said that the European biotech ecosystem still misses big independent biotech companies like Gilead or Regeneron in the US. In terms of commercialising its products, small and midsize European drug developers are far too dependent on Big Pharma. “I wish European entrepreneurs the stamina to fight hostile takeover bids. Hopefully, such big biotech companies will exist in ten years from now,” van de Stolpe said. Harpal Kumar, Head of Johnson & Johnson Innovation EMEA, reflected on the reasons for this. It’s all about the money, he concluded: “In Europe, cash is distributed in smaller packages and for smaller time frames than in the US – both for VC-backed and listed companies. Hence, CEOs are busy with raising money, with no time left for building the company.” Concerning the quality of European science, Kumar made a less dismal diagnosis: “There is enough going on to be optimistic. A third of our 400plus collaborations come from Europe, including first-in-class and best-in-class programmes.” Besides cell and gene therapies, formulation was a major topic at the conference. In the pediatrics workshop, Hubert Birner of investor TVM Capital Life Science, suggested starting a European “Genzyme in the pediatrics space.” Neglected by the biotech industry, some markets are as attractive as certain orphan disease markets, he suggested. The low-hanging fruits in this space are “just” reformulations of established drugs. L m.laqua@biocom.eu

After the recent EU approval of the first bunch of CAR-T cell therapies, the mostvisited conference track of the three-day event was about the lucrative field of cell and gene therapies. Developers moaned about the lack of manufacturing capacities at contract manufacturing organisation (CMOs). The CMOs, however, have to deal with a plethora of new different formats such as bispecific antibodies, ADCs etc., and expertise in the complex field of autologous cell therapies is still limited to specialists. While it is commonplace that manufacturing complexity and capacity of an asset can make or break a deal, Werner Lanthaler of German Evotec AG painted a picture of even more complexity: “In terms of innovation, business development lags behind research and development,” he said. “In establishing

Partnering talks and company exhibitions were located at Bella Center Copenhagen.

26-28_EB_Winter_2018_BIO-Europe_ml.indd 28

“I wish European entrepreneurs the stamina to fight hostile takeover bids.”

Picture: Schedl/EBD Group


06.12.2018 14:21:31 Uhr

European Biotechnology | Winter Edition | Vol. 17 | 2018

financial markets


The Netherlands and Belgium – a safe haven for investors? Frédéric Gomez  Analyst, Pharmium Securities_ Belgian and Dutch biotech companies have

higher market capitalisations, turnovers, and R&D expenditures than similar-sized businesses from most parts of Europe. They even seem to be immune to the prevailing adverse public market.

Even if they didn’t win the World Cup this summer, there is an area where the Belgians and the Dutch can take pride in being the strongest in 2018 – in bio­t ech. Judge instead: with two biotech companies bought by Big Pharma for a total amount of €4.4bn (Ablynx by Sanofi and Tigenix by Takeda) and the giant US public offerings of Galapagos (US$345m) and argenx (US$301m following the US$266m raised in December 2017), no other country has done better in Europe! On top come the following offerings: €31.2m, €36m, €77.5m and US$147.5m raised respectively by Kia­d is, MDX Health, Mithra, and uniQure. Looking at the performance of the share price (as of mid-November), again, overall

2018 has been a great year for Belgian and Dutch biotech companies with gains observed for Mithra (+125.1%), uniQure (+57.9%), argenx (+55.4%), Oxurion (+29.5%), Galapagos (+14.4%), and Kiadis (+6%). Although some companies (Celyad, Pharming, ASIT, Biocartis and MDX Health) have indeed seen a negative share price development, in neighbouring France almost all listed biotech companies performed poorly. Even though its a much bigger economy, France does not harbour a biotech company with a market capitalisation greater than €1bn. In comparison, both Galapagos and argenx are worth more than €2.5bn each. Why do Belgian and Dutch companies outperform the market? What is their magic formula? Under bad market condi-

tions, such as the market slump seen over the past couple weeks, investors believe it is important to have a technology platform validated by industrial partnerships with Big Pharma. This decreases the binary risk linked to one or two proprietary products. Companies showing up among the best performers this year align with this profile – as do tier-one EU biotech companies like Genmab (Denmark) and Morphosys (Germany). I believe that this feature is appealing for many reasons but investors should not forget that at the end, it boils down to the clinical data validating the platform. Finally, in approaching small-mid cap development stage companies, especially in tough market conditions, I would advise even greater stock selectivity with a strong focus on fundamentals (clinical data and/or partnerships) and rates of enterprise value (EV) to cash lower than three. L

News from the floor

Picture: Mirabaud Securities

Gal apagos NV   Trading around €90 per share, Raymond James started coverage on shares of Galapagos (NA:GLPG) in a research note to investors issued in mid-November. The brokerage issued a strong Buy rating and a €139 target price on the biotechnology company’s stock. Novo Nordisk A/S  JPMorgan Chase

& Co. upgraded shares of Novo Nordisk A/S (DC:NOVOB) from a neutral rating

29_EB_Autumn_2018_market-sentiment_ml.indd 29

to an overweight rating in a research report released in November. Morphosys AG  Analyst Sven Diermei-

er of Independent Research downgraded the €105 target price on Morphosys’ stock slightly to €104 at the end of November. Genmab A/S  Jefferies Financial Group reduced the 2018 earnings per share estimate for shares of Genmab (DC:GEN) in a report issued in mid-November. Analyst

Peter Welford now anticipates that the company will post 2018 earnings 17% lower and 2021 earnings 6% higher than their prior estimate. Uniqure NV  After a “compelling clin-

ical update,” H.C. Wainwright analyst Debjit Chattopadhyay maintained a Buy rating on uniQure NV (Nasdaq:QURE) and increased the price target from US$48 to US$60. The stock stood at US$30 at the end of November. 

06.12.2018 14:23:06 Uhr


financial markets



4D Pharma plc

European Biotechnology | Winter Edition | Vol. 17 | 2018


52 weeks indicator low high






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European Biotechnology | Winter Edition | Vol. 17 | 2018




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European Biotechnology | Winter Edition | Vol. 17 | 2018

Reading in the blood Biomarkers  Robust biomarkers predicting critical health states can be valuable as both targets

and diagnostics. Two companies outside oncology, the classical field of precision medicine, raised €44m in growth financing this autumn to develop both precision biomarkers and corresponding antibody therapeutics. Speaking about his business strategy, Dr. Andreas Bergmann, who founded Sphingotec and Adrenomed, explains what drives him to run multiple companies in parallel.

test some of the hypotheses I already had in mind at BRAHMS. That freedom is invaluable because it allows me to check if I am on right track to success – if not, I would simply quit the project. And of course I knew that it needed a business to bring an invention to the patient.

EuroBiotech_ Dr Bergmann, 2018 has turned out to be an exciting year for two companies you ’ve founded. In October, blood diagnostics company Sphingotec raised €20m in growth financing. In November, antibody developer Adreno­med followed suit with a €24m financing. Is it by chance that the funds came from the same investors, HBM BioCapital and Wellington Partners? Bergmann_That’s a long story. So let’s first

EuroBiotech_A brief question: I guess you had enough money in the bank after that deal. What made you continue to work and lead the development of two companies at the same time? Bergmann_I think I am not a person who

needs to think a lot about work-life balance. I need to do something, dive into data and find novel medical applications. Even before that deal, my work as Chief Research Officer for BRAHMS was more triggered by interest than by money. The deal assets gave me scientific freedom to

32_34_EB_Winter_2018_Interview_Bergmann_tg.indd 32

are set to reach significant milestones, which may require major investments. For that reason we sought external investment.

Andreas Bergmann, PhD, is not a serial but a parallel entrepreneur in the field of blood biomarkers/targets for the prediction, prevention, and early intervention for diseases with unmet medical need such as cancer, cardiovascular diseases, and acute kidney injury. With a 25-year track record in the life science sector, the biochemist has founded more than a dozen of companies. After he and co-founders sold BRAHMS AG – where he developed, for example, the sepsis gold standard marker Procalcitonin – for €330m to Thermo Fisher Scientific in 2009, he turned to develop Sphingotec GmbH, AdrenoMed AG, and Deutsche Biotech Innovativ AG, for all of which he’s on the Executive Board. Bergmann holds more than 120 patents and has authored over 150 peer-reviewed scientific papers.

EuroBiotech_Could you tell a bit more about that and the value proposition and market, please? Bergmann_Let’s start with Sphingotec. I

founded the company in 2002 with the goal to identify and validate first-in-class peptide biomarkers, whose concentration in the blood of patients indicate the outcome and allows us to monitor whether the patient responds to a given therapeutic intervention. Since then, we have identified and validated a series of first-in-class diagnostic blood biomarkers. Two of them are set to reduce the high mortality from acute congestive heart failure, which affects 26 million patients globally, and from sepsis, which causes 8 million deaths annually, 700,000 thereof by acute kidney injury (AKI). Bio-ADM, the amidated biologically active part of the vasoactive blood peptide hormone adrenomedullin, is the very first diagnostic that indicates endothelial dysfunction, that is when blood vessels become leaky. Based on the data of 30,000 patients, we demonstrated

Picture:Sphingotec/Oliver Ziebe

take a look at what investors are looking for, more generally: a good track record of management, a clear value proposition in an attractive market, and a short time to exit providing a multiple of their investment. I already knew HBM from a diagnostics company I’d previously cofounded: BRAHMS AG, where I led the development of procalcitonin, the current gold standard for monitoring of antibiotics therapy in sepsis, and other innovative blood biomarkers. When we sold BRAHMS to Thermo Fisher Scientific in 2009 for €330m, HBM exited with more than a 11.5 multiple. I think our investors now expect something similar to happen with Adrenomed and Sphingotec.

EuroBiotech_So why didn’t you continue to finance Adrenomed and Sphingotec with private money? Bergmann _Next year, both companies

06.12.2018 14:24:12 Uhr

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06.12.2018 14:25:20 Uhr


European Biotechnology | Winter Edition | Vol. 17 | 2018

Nexus IB10 system is a CD player-like microfluidic POC testing device. After a drop of blood has been added, plasma is separated by the rotating testing disc and channeled into up to five lateral flow tests. Results are available within 20 minutes.

that blood levels of bio-ADM predict septic shock and allow therapy monitoring of critically ill patients in intensive care units (ICUs) and emergency departments. BioADM is also capable of diagnosing residual congestion in heart failure patients. Residual congestion is the leading cause of death after discharge of heart failure patients who appeared to be successfully treated with diuretics. Secondly, we have identified and validated the very first blood biomarker that allows monitoring of acute kidney function: penKid has been clinically shown to diagnose and monitor acute kidney injury (AKI) in earliest stages of congestion in acute heart failure. If you think of a bio­marker-assisted diuretics therapy in patients with congestive heart failure or cardio-renal syndrome, a combination of bio-ADM and penKid is set to lead to lower re-hospitalisation and mortality rates. So, why did we acquire external capital? We are in the midst of the endeavour to create a market monopoly for point-of-care (POC) acute biomarker blood tests. This May, we acquired Nexus, a Samsung subsidiary that runs its fully automated Nexus IB10 point-of-care (POC) platform in more than 1,000 ICUs and emergency departments in Europe and Middle East. We will complement the standard acute biomarker diagnostics run-

32_34_EB_Winter_2018_Interview_Bergmann_tg.indd 34

ning on the desktop system with bio-ADM and penKid starting next year. Why do we believe that hospitals will embrace our offer? Seventy percent of hospitals have no central laboratory and will have interest in buying the low-priced CD player-like IB10 that processes up to five different tests at a time from one blood drop: it provides threefold faster time-to-result than central labs can provide, it offers access to biomarker tests able to reduce mortality, and it allows direct invoicing of diagnostic testing for the hospital. Those small hospitals we target with the IB10 make up 50% of the market for acute biomarker tests. In this market segment there is no competition for Sphingotec. Of course we will continue to licence our innovative tests to licensees that want to run them in a central lab. I think we will need 3-5 years from now to provide proof-of-concept for this business approach. EuroBiotech_Let’s talk about Adreno­ med … Bergmann_It’s important to understand

that Adrenomed has a thematic overlap with Sphingotec. Adrenomed is in clinical Phase II tests of Adrecizumab, a therapeutic antibody targeting bio-ADM, the biologically active moiety of the vasoactive peptide hormone adrenomedullin.

Simply spoken, adrecizumab repairs vascular dysfunction. Data suggest that the antibody acts like a hoover for bio-ADM, which concentrates the vasoactive peptide in blood vessels, which ends vascular leakage. By H2/ 2019, we will have the readout on adrecizumab’s efficacy as measured as reduction in mortality in 300 sepsis patients. Then we will decide whether to use the proceeds to seek conditional approval and head for Phase III and marketing on our own or with a licence partner. I am happy that we have taken the classical way to conduct our proof-of-concept study because it will provide solid data. We are planning also to go the classical way in the second indication in which Adrecizumab is being clinically tested: prevention of congestion in heart failure, which will be advanced to Phase II testing next year. There are many additional potential therapeutic fields in which endothelial disintegrity may play an important role. If data indicate a major benefit in other indications we will validate them and expand the label of adrecizumab. In the end, I must be sure that our assumptions prove true and that our approach works. EuroBiotech_Rumors say you are already working on the next project with a new company … Bergmann _I never comment on ideas

that have not been sufficiently validated but we have enough projects with solid data in our portfolio to be able to quit projects that don’t work. Our simple strategy is: Never copy an idea; generate and analyse observational data from disease-relevant sources such as human blood; develop a model based on the pattern observed and validate strictly data-based if it is diagnostically or therapeutically relevant. Hopefully, bio-ADM is just the first in a series of companion diagnostics to be developed. My personal goal is to develop blood-based companion diagnostics along with therapeutics antibodies that add value to many patients. That’s much better than making a lot of money with meds for L just a few. t.gabrielczyk@biocom.eu

Picture: EIB


06.12.2018 14:25:05 Uhr

Regulatory Affairs

European Biotechnology | Winter Edition | Vol. 17 | 2018


EMA scales back activities Brexit As long as it remained unclear

which relationship British regulatory agency MHRA and the EMA would have after the transition period assured in the preliminary Brexit deal, drug developers prepared for the worst. In autumn, Pharma heavyweights Novartis, AstraZeneca and Sanofi said they have started stockpiling medicines in Britain. AZ announced it will replicate critical production processes, both in the UK and in Sweden. According to a November agreement, however, MHRA and EMA will share MAA dossiers and honor IP protections through the end of 2020. Shortly before the vote on Theresa May’s Brexit deal, members of the UK Health and Social Care Select Committee pushed the Prime Minister for guarantees that the UK will be able to closely cooperate with EMA following the UK’s EU exit in March.

Meanwhile, the EMA announced it would have to suspend non-essential activities in order to safeguard core activities related to the evaluation and supervision of medicines. Due to the move of the agency to Amsterdam in March of 2019, it will have to cope with a loss of at least a third of its staff. “EMA has put in place supporting measures to facilitate the relocation of staff to Amsterdam and additional support is provided by the Dutch government. Other mitigating actions, such as a comprehensive staff recruitment programme, are underway. However, in the short- to mid-term, EMA will have to reprioritise its resources to fully maintain its core activities,” the agency said a statement. One of the activities scaled back is clinical data publication, for which the launch of new procedures will be temporarily suspended as of 1 August 2018.

www.ema.europa.eu Measures included scaling back guideline development and revision and putting on hold non-product related working parties. The EMA has drawn up priority lists of what will be continued: Work on seven guidelines, which address either an urgent public/animal health need, or are necessary to support preparations for Brexit or the implementation of new or revised legislation, will continue beyond 1 November 2018; meetings of product-related working parties will continue as scheduled. All meetings of non-product-related working parties have been temporarily put on hold in line with the reduction in the number of L guidelines to be processed.

Recommendations from the EMA: MA (market authorisation); cond. MA (conditional MA); e.c. MA (MA under exceptional circumstances); OD (orphan drug).

Drug name




› Cablivi (caplacizumab)

Treatment of acquired thrombotic thrombocytopenic purpura

Ablynx NV (now Sanofi)

MA rec.

› Dengvaxia (tetravalent Dengue vaccine)

Prevention of infection with dengue virus serotypes 1-4 in people between 9 and 45 years old who live in endemic regions and had prior dengue infections

Sanofi Pasteur

MA rec.

› Kymriah (tisagenlecleucel)

Treatment of acute lymphoblastic leukaemia (ALL) and diffuse large B-cell lymphoma (DLBCL)

Novartis Europharm Ltd

MA rec.

› Yescarta (axicabtagene ciloleucel)

Treatment of diffuse large cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL)

Kite Pharma EU BV (now Gilead Sciences)

MA rec.

› Mepsevii (vestronidase alfa)

Treatment of mucopolysaccharidosis type VII

Ultragenyx Germany GmbH

MA rec.

› Veyvondi (vonicog alfa)

Treatment of von Willebrand disease

Baxalta Innovations GmbH

MA rec.

› Vyxeos (daunorubicin / cytarabine)

Treatment of acute myeloid leukaemia

Jazz Pharmaceuticals Ireland Ltd

MA rec.

› Nerlynx (neratinib)

Adjuvant treatment of adults with breast cancer

Puma Biotechnology Ltd

MA rec.

› Ogivri (biosimilar to trastuzumab)

Treatment of breast and gastric cancer

Mylan SAS

MA rec.

› Braftovi (encorafenib) + Mektovi (binimetinib)

Treatment of BRAF V600 unresectable or metastatic melanoma

Pierre Fabre Medicament

MA rec.

› Ilumetri (tildrakizumab)

Treatment of moderate to severe plaque psoriasis

Almirall SA

MA rec.

› Imfinzi (durvalumab)

Treatment of non-small-cell lung cancer

AstraZeneca AB

MA rec.

› Takhzyro (lanadelumab)

Prevention of HAE attacks

Shire Pharmaceuticals

MA rec.

› Hulio (biosimilar to adalimumab)

Treatment of inflammatory and autoimmune disorders

Mylan SAS

MA rec.

35_EB_Winter_2018_EMA_tg.indd 35


06.12.2018 14:26:09 Uhr


IP Flash

By Dr. Ute Kilger, Partner, Boehmert & Boehmert, Berlin, Germany Market Access  German case law has

disadvantage. In the case of “Abdichtsysa quite broad concept of liability for pat- tem”, the FCJ, however, reduced the reent infringement. The jurisprudence dis- quirements for the liability of the defendtinguishes between “near” and “distant” ant located abroad. It emphasized that if acts of patent infringement. The “near” specific indications suggest that pro­ducts patent infringer is the one who actually sold abroad may end up distributed in commits the infringement and is therefore Germany, the supplier has to ask its cusliable. Such “near” patent infringement tomer, warn against patent infringement acts are ruled in § and stop the sup139 (1) of the Gerply if its concerns Who is liable for patent man Patent Law. are not addressed. The “distant” inSuch a specific ininfringement? fringer may be the dication that sugChief Executive gests a distribution Officer (Geschäftsführer) of an infringing in Germany and, consequently, patent incompany (Federal Court of Justice, FCJ, fringement could be the value of the units decision “Glasfasern II”). A “distant” in- purchased. Let’s take, for instance, a diagfringer may be also a company that is lo- nostic kit with a market volume of €100m cated abroad and sells the patent-infring- in its main market, Germany, where the ing products to another company abroad patent has also been gran­ted. Other EU if the patent-infringing goods are ultimate- markets account for €10m in combined ly shipped to Germany (FCJ decisions revenues. If an abroad producer supplies “Audiosignalcodierung” & “Abdichtsys- an abroad distributor for Europe with its tem”). A hauler or an exhibitor may be kits worth €50m, this producer must susa “distant” infringer (FCJ decisions “MP3- pect that patent infringement in Germany Player-Import” & “Larynxmaske”). occurs because of market volume. This means that any third party conThe open question, however, remains tributing to, or enabling infringing acts what measures can be taken by the “dismay be liable for patent infringement, ac- tant” infringer that would be considered cording to German case law. In the case as being “enough” not to be liable for of “Audiosignalcodierung”, the defend- subsequent patent infringement in Gerant, located abroad, did not deliver the many. This question remains to be aninfringing goods to Germany but did ad- swered by legal practice. In any case, mit knowledge of potential delivery to companies should take into consideraGermany, thus, the FCJ in its decision as- tion the broad concept of liability in Gersumed actual know­ledge of delivery to many and consult with their attorney the German market to the defendant’s when making business decisions. 

36_EB_Winter_2018_IPFlash_ml.indd 36

European Biotechnology | Winter Edition | Vol. 17 | 2018

Twin-win Antib o di e s   Two pieces of good news from Dutch-Belgian antibody drug developer Argenx NV (Euronext & Nasdaq: ARGX) sent its stock price skywards in early December. The first one was about the Phase II trial of efgartigimod in immune thrombocytopenia (ITP), a rare blood disorder. The preliminary results of efgartigimod were received not so well a few weeks ago. The stock crashed by almost 30% and the company’s market capitalisation was down €0.7bn. However, detailed data presented at the 60th Annual Meeting of the American Society of Hematology (ASH) in San Diego (US) unequivocally documented a clinically meaningful rise in platelet counts. “With these results and the drug candidate’s continued favourable tolerability, we look forward to advancing into a potential pivotal trial next year,” commented Nicolas Leupin, Chief Medical Officer of Argenx.

J&J strikes deal The second stock booster was news centering around Argenx’ candidate cusa­ tuzumab. The therapeutic antibody is currently in a Phase I/II study in patients with acute myeloid leukaemia and high-risk myelodysplastic syndrome who are unfit for chemotherapy. Giving an update on the Phase I part of the study, Leupin not only reported a good tolerability but also a high patient response rate. The two firstin-class candidates raised interest among peer companies, resulting in a US$1.6bn licensing deal with J&J affiliate Janssen Cilag GmbH for for the global commercialisation rights of cusatuzumab. Janssen will pay US$300m in cash upfront and potentially up to US$1.3bn in milestone payments plus tiered, double-digit royalties. Furthermore, Johnson & Johnson Innovation Inc. acquired a US$200m stake in Argenx. Fueling the long-term prospects of the Dutch drug developer, Argenx will cocommercialise cusatuzumab in the US. All in all, Argenx’ market capitalisation was pushed beyond the €3bn mark – about 20% more than back in September.  

Picture: Boehmert&Boehmert


06.12.2018 14:26:37 Uhr

European Biotechnology | Winter Edition | Vol. 17 | 2018

Pharma Pack aging


Digital solutions to serialisation Blockchain Technology  It‘s only been nine years since the first blockchain technology

applications in finance were introduced. Big players are now working to use distributed computing to protect pharma logistics from counterfeit drugs. Unlike current Internet-based solutions, the decentralised blockchain network is immune to manipulation or hacks, as transactions can be verified, recorded, and coordinated autonomously without third-party involvement. Though blockchain technology is still far from maturity and mainstream adoption, 22% of life sciences companies surveyed by Health IT Analytics in 2017 said they would experiment with the technology. Four years from now, 80% of them believe, blockchain usage will be widespread. In contrast to current centralised data hubs that store 2D barcodes, including the serial number, batch/lot number, ex-

piry date, and global trade item number printed on medicine packs, blockchain technology is not centralised but works with a distributed database network (Fig. 1). Within the network, every change or manipulation can be seen in real-time by every stakeholder who has the permission to participate in the network. This allows forgery-proof, tamperevident tracking of a (pharmaceutical)

product‘s lifecycle, even as it changes hands between the manufacturer (pharma company), logistics service provider, wholesaler (distributor), retailer (pharmacy), and consumer (patient). Every single action (i.e. sending or repackaging a vial from a certain lot to a distributor) is signed with a digital fingerprint and time stamp and broadcasted to the trusted members of the private network. Simply spoken, blockchain is a data format that uses previous entries in a sequence as part of the current entry: an algorithm attributes a unique “block“ to every single action, which is calculated from the chain of existing blocks and then added to the growing chain, creating a unique data set that can’t be altered by single parties.

Picture: Savi Technology

Prototypes launched

Figure 1: How blockchain technology may be useful in serialisation efforts.

37-38_EB_Winter_2018_Pharmapack_Intro_tg.indd 37

A key challenge in pharmaceutical serialisation that can be solved by blockchain technology is maintaining traceability when units are repackaged or aggregated from unit to case to pallet for logistics purposes and then disaggregated back down to unit level for consumption. A few solutions are in the advanced stage: In March, DHL and Accenture established a blockchain-based track-andtrace serialisation prototype. In a simulation, the system was able to track more than 7 billion unique pharmaceutical serial numbers and over 1,500 transactions per second in a global network of “nodes” across six countries. Accord-

06.12.2018 15:21:58 Uhr


Pharma Pack aging

European Biotechnology | Winter Edition | Vol. 17 | 2018

ing to Keith Turner, CIO at DHL Supply Chain, “we are refining the solution … with key industry stakeholders to operationalise the concept.”

Nascent market

Figure 2: The logistics of pharmaceuticals is complex.

carried out with SAP customers Genentech, AmerisourceBergen, McKesson, and Pfizer) and was fully compliant with the DSCSA. According to speakers at TraceLink‘s Futurelink conference in Munich this spring, blockchain technology is private by nature, as it runs decentrally and thus does not attribute accountability to a legal entity, such as the US Food and Drug Administration (FDA) or European Medicines Agency (EMA).

Figure 3: Model of a blockchain-based track-and-trace system to monitor prescription meds.

37-38_EB_Winter_2018_Pharmapack_Intro_tg.indd 38

Futhermore, blockchain is not compatible with the EU general data protection regulation (GDPR), because it does not allow users “to revoke the use of personal data at any time.” For the moment, blockchain has had a long run in terms of industry-wide adoption for serialisation. Other applications, such as the management of real world data with predefined data protection settings, may drive adoption in the future.  t.gabrielczyk@biocom.eu

Pictures: DHL/Accenture (below), U.S. Department of Health and Human Services (tabove)

Database giant SAP, along with 15 Big Pharma companies, is working on a prototype solution that uses the MultiChain protocol, an early blockchain based on Bitcoin’s technology. According to Raimond Gross, Chief Blockchain Strategist at SAP, it provides the “only production grade infrastructure available,” it‘s “easy to use,” and “everyone knows its founder Gideon Greenspan.” As the US Drug Supply Chain Security Act (DSCSA) requires the pharma industry to adopt an “interoperable system” to manage records of ownership and transfers of prescription drugs in the United States, San Francisco-based startup Chronicled, Inc. announced last March its MediLedger project with data privacy and business intelligence would meet the requirements of the pharma industry (a proof-of-concept study was

06.12.2018 15:22:05 Uhr


SERIALIZATION USING LABELS Upgrade your serialization project with flexibility. Bähren Druck supports the implementation of the Falsified Medicines Directive 2011/62 with pre-serialized labels. Order product samples and receive the key-facts poster on EU serialisation at www.your-special-case.com



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European Biotechnology | Winter Edition | Vol. 17 | 2018

Serialisation using labels Pharma Packaging  According to the FMD 2011/62, serialisation of all prescription drug packs in

Europe will inevitably become a daily routine for the pharmaceutical industry from 2019. European Biotechnology spoke with Philip Falkenstein, Product Manager at Bähren Druck, about the use of pre-serialised labels as solution for special implementation areas and the current legal framework.

much room for interpretation. Alternatively, member states should decide in a given case if labels are an appropriate solution, the Commission suggested.

EuroBiotech_Usually, a pharmaceutical company buys equipment to serialise pharmaceutical packaging in its production line. When should serialised labels be considered? Falkenstein _Correct, the majority of

EuroBiotech_Has there been a reaction yet? Falkenstein_In Germany, the authorities

packages are serialised inline. However, there are plenty of areas in which standardised systems and processes – technically, economically, or organisationally – reach their limits. In these situations, the use of pre-serialised labels comes into play.

have recently officially accepted the use of labels. We assume that this is the beginning and that other national authorities will follow. EuroBiotech_Do you think that safety concerns about using labels are justified? Falkenstein_No. Security labels were ap-

such as: bundle or so called clinical packs, oversized packaging dimensions, overweight packs, small and medium quantities, manual packaging, backup or even as a standard solution to avoid high technical investment. Our page www.yourspecial-case.com provides further details. EuroBiotech_As serialisation data need to be exchanged, how is this handled? Falkenstein_The use of pre-serialised labels

requires a clear agreement between the pharma company and us. Defining the main questions relating to the serial numbers, data interfaces, and reporting is an important task, and will be addressed during our onboarding process. EuroBiotech_Regarding compliance: is the use of labels generally accepted? Falkenstein_All pre-serialized labels are

produced under GMP conditions. Internal as well as customer audits verified the process. Furthermore, each label is controlled by a camera system in order to verify the barcode grading and the serial number documentation. From an or-

40_EB_Winter_2018_Interview_Baehrendruck_tg.indd 40

Philip Falkenstein joined Bähren Druck in 2016. In his newly created role of product manager, he is responsible for developing and executing an portfolio of security label solutions for the implementation of the Falsified Medicines Directive. Before joining Bähren Druck, he finished his Master’s Degree at the University of Wuppertal where he focussed on the FMD 2011/62.

ganisational and technical point of view, we´re ready to onboard further customers. Unfortunately, there were inconsistencies about the general use of pre-serialized labels. Directive 2001/83 Article 56 allows the labelling of the security feature. However, a Q&A paper on safety features, which is continuously updated by the European Commission, has caused confusion. It states the use of labels will be acceptable when “no technically feasible alternative” exists, which leaves

proved as an anti-tampering device according to the EN 16679. Only safety labels with special material properties, which are irreversibly damaged upon manipulations, are used for serialisation. The Commission recommends this tamper-evident function in its Q&As, so it seems to be regarded as safe. EuroBiotech_What would you recommend in the current situation? Falkenstein_The situation has changed in

a very positive way, since pre-serialized labels are officially released for all use cases for the German market now. Furthermore, all other EU-markets should go ahead with pre-serialized label where technically necessary, as the Commission said. Basically, the focus should be on the obligation to serialise. In other words, the pragmatic and risk-based approach should be chosen to ensure that products can continue to be market, if necessary with a pre-serialised label. At the same time, we should wait and see how further authorities will finally decide on this. L t.gabrielczyk@biocom.eu

Picture: Wilhelm Bähren GmbH & Co. KG

EuroBiotech_What areas and situations? Falkenstein _Special serialisation cases

06.12.2018 14:30:33 Uhr


IMPROVING PATIENTS‘ LIVES THROUGH OUR INNOVATIVE HEALTH CARE SOLUTIONS IS THE CORE OF OUR BUSINESS. BECAUSE WE CARE. Datwyler Sealing Solutions is a leading industrial supplier and a key player in the health care world. Our state-the-art solutions for drug packaging and medical devices are built on over 100 years of experience.

We provide a unique range of products and services including the most advanced elastomer formulations, coatings, aluminum seals, and processing technologies. Partnering up with the world’s top pharmaceutical and medical companies, we stand by our mission to improve patients’ lives.


41_EB_Winter_2018_Daetwyler.indd 1

07.12.2018 13:48:09 Uhr


Pharma Pack aging

European Biotechnology | Winter Edition | Vol. 17 | 2018

Highest manufacturing standard: First Line CDMO  Datwyler Sealing Solutions is a leading industrial supplier and a key player in the

global health care world. Our unique product range includes the most advanced elastomer formulations, coatings, aluminum seals, and processing technologies. These are based on a broad spectrum of experience in the healthcare industry. To ensure the highest quality in our broad product portfolio, we have implemented the most advanced manufacturing standard. › by Massimo Mainetti, Head of Strategic Marketing, Datwyler Sealing Solutions

Ongoing commitment to quality Datwyler offers best-in-class packaging solutions for the pharmaceutical and biotech markets. To ensure patient safety, our priority is to deliver safe and effective sealing solutions for drug packaging to our customers. Our most advanced manufacturing standard, First Line, is specially designed to manufacture pharmaceutical rubber components for high-end pharmaceutical and biotech markets in a fully integrated cleanroom environment conforming to the highest industry standards. The First Line manufacturing concept is based on ultra-modern cleanroom technology, automated production cells, fully automated cam-

42_EB_Winter_2018_Dätwyler_tg.indd 42

The state-of-the-art cleanroom environment contributes to producing components with the lowest endotoxin, bioburden, particulate, and defect levels in the industry.

era inspection, and a unique validated washing process. All facilities aligned with the First Line manufacturing standard are specially designed and operated under a zero-defect philosophy.

Ultra-modern zoning concept Each zone has been accurately designed and constructed in order to prevent biocontamination and is equipped with material airlocks. State-of-the-art pass-through washing equipment has its automatic loading side in one zone and its automatic unloading side in a zone of even higher cleanliness. The process flow, gowning protocols, personnel and material flow, as well as state-of-the-art automation proc-

esses all result in the lowest endotoxin, bioburden, particulate, and defect levels available in the industry – both visible and subvisible. This innovative approach to manufacturing exceeds the most stringent quality standards of the European and US regulatory authorities and is certified to ISO 15378. The health care industry benefits from the high-quality standards, especially regarding rational test and lean production flows, which are uniform in all First Line facilities. In addition, every element, such as particle measurement, air temperature and moisture levels, is independently monitored. In this way, Datwyler is shaping the future of the global health care industry and stays by its vision L to improve patients’ lives.

Pictures: Dätwyler

Datwyler’s state-of-the-art solutions for drug packaging and medical devices are built on over 100 years of knowledge. Our experts are constantly researching and developing the most advanced standards to ensure the highest available purity and compatibility of our products. A global strategic approach with a local presence is a key success factor in the pharmaceutical market. Datwyler’s manufacturing set-up guarantees identical quality standards on a global level. Due to the most advanced quality standard identically produced in three different continents, we can provide our customers with flexible supply chains to improve time-to-market risk mitigation plans to ensure business continuity.

06.12.2018 14:33:36 Uhr

Euro BioFairs Compass Q1 / Q2 Edition 2019

II Guide to Life Sciences Events

SPECIAL 43_EB_Winter_2018_Compass_Title.indd 43

06.12.2018 14:34:05 Uhr

Š Rawpixel/Fotolia.com

Join the European Biotechnology Network!

The European Biotechnology Network is dedicated to facilitating co-operation between professionals in biotechnology and the life sciences all over Europe. This non-profit organisation brings research groups, universities, SMEs, large companies and indeed all actors in biotechnology together to build and deliver partnerships. Do you want to know more about the advantages of a (free) membership? Just have a look at our website.

C O R P O R AT E M E M B E R S 12 /18

European Biotechnology

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European Biotechnology Network AISBL Rue de la Science 14b | 1040 Brussels, Belgium Tel: +32 (0)2 588 70 71 info@european-biotechnology.net


06.12.2018 14:35:59 Uhr

European Biotechnology | Winter Edition | Vol. 17 | 2018

Euro Biofairs Compass


European event update EuroBiofairs Compass  Every manager, scientist, and business developer has their own individual,

Picture: UBM

specific network – and so, too, their must-attend events vary significantly. Where to meet potential new partners and how to widen one’s scope beyond well-known terrain can be quite difficult to determine. Euro Biofairs Compass will help you navigate the European meeting jungle in H1/2019.

Pharmapack 2019 (6–7 February 2019) is a must-go for experts in pharma packaging, serialisation hardware and equipment, who will gather in Expo Paris. The 11th HIC/DSP Bioseparation Conference (February 18–21, 2019, Interlaken, Switzerland) is a must-attend for experts in the field of chromatographic isolation and purification of biological targets. Bioeconomy is set to revolutionise chemical production. In Frankfurt, more than 1,000 bioeconomy industry decision-makers will meet with investors in 20-minute partnering meetings at European Chemistry Partnering (26 February 2019). The worldwide threat of antimicrobial resistance in medicine will be the focus of the 12th edition of the Berlin Conference in Life Sciences (14–15 March 2019, Berlin, Germany). Decision-makers from Big Pharma, and biotech SMEs, policy

45_EB_Winter_2018_Compass_intro_tg.indd 45

makers, regulators, payors, business developers, and investors will meet in Berlin to explore how to incentivise companies to develop novel antibiotics that can break drug resistance and diagnostics. The sister meeting to biotech industry’s largest partnering event, EBD’s Bio-Europe Spring 2019 (25–27 March 2019), on the other hand, will provide the perfect partnering point for biotechs, investors, and pharma executives in Vienna. The 35th Annual Congress on Pharmacuetical Medicine “Access to New Therapies: from Challenge to Solution!“ (28–29 March, 2019, Berlin) will give the latest insights into drug safety and new concepts in drug development. A meeting with major impact kicks off on 7 May 2019 at Congress Centre Basel, which will host what has become the nation’s most important biotech event, the Swiss Biotech Day. As in previous years,

the new Swiss biotech report will shine a light on the industry’s status in the country. Due to the growing number of visitors (500+), the Swiss Biotech Day moved to Basel Congress Centre in 2017. For the 12 th time the International Conference on Bio-based Materials will present the technology leaders in the fields of bio-based chemistry and materials (15–16 May 2019). In Cologne, technology leaders will present and discuss their latest innovations with about 200 international participants, primarily from industry. Until 1 February 2019, undergraduate students can apply to participate in Amgen Scholars Europe (June24 – September 4, 2019) to engage in hands-on research at five of Europe’s premier educational institutions Just turn the page to learn everything you need to know about Europe’s mustattend events in the biotech industry. L

07.12.2018 12:51:12 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

5 –7 February 2019 Austria Center Vienna Vienna, Austria

DIA Europe 2019  "Join Us at the Crossroads of Healthcare" emphasiz-

es the multi-stakeholder, outcome-driven dialogue that fuels collaborative solutions for those who join the DIA Europe annual meeting.

The topics of the 2019 programme reflect the meeting‘s mission to ensure industry, payers, patients, and regulators all have an equal voice in the debates advancing regulatory science and access to healthcare. Cross-functional dialogues will address important topics such as the Evolution of

› Quick facts Quick Facts

›› 2000+ attendees including 300+ speakers

›› Daily Keynote Presentations! Dave deBronkart; Hans Lehrach, Director at   Max Planck Institute for   Molecular Genetics;   Kristel Van der Elst, CEO,   The Global Foresight Group

›› Follow Us on Twitter @DIA_Europe Registration DIAglobal.org/EuroBiotech

46_EB_Winter_2018_Compass_DIA_tg.indd 46

Science and Policy, Modern Clinical Research, Access to Medicines, and Digital Disruptors. It is critically important for all development and access stakeholders to understand current policies, as well as future pathways for regulatory science. DIA Europe 2019 uniquely brings together representatives from over 35 regulatory, HTA, and patient advocacy organisations, including EMA, MHRA, BfArM, PMDA, and AGES, to name a few. Despite the Agency’s business continuity strategy and the impact on its external engagement approach, a number of EMA representatives will be present to cover important areas, including a first European public update on the Agency's draft Regulatory Science Strategy 2020-2025. New learning and discussion formats, such as Content Hubs, will facilitate more informal conversations and targeted networking on the nuances and solutions within specific fields of expertise. As our members say, “there is something special about DIA Europe.” It's a chance to learn, engage, and grow as a healthcare L professional.

Come to Vienna GREETING  Not in the least because of Brexit, 2018 proved to be a pivotal year. International best practice sharing and collaborative partnerships continue to gain traction. Our regulatory agencies are working to embrace the emerging situation in Europe, while also preparing for the arrival of new therapies and technologies. We see progress in removing roadblocks to patient access while ensuring the highest standards of safety are met. Throughout Europe, the everchanging political parameters surrounding the Brexit agreement have kept us on our toes. With all of these developments, I’m excited to kick-off 2019 by bringing together key players from around the globe to discuss the developments impacting access to therapies for patients. While DIA’s history is rooted in regulatory focused discussions, we’ve evolved to address the interconnectedness of all functions and facilitate conversations across the entire drug development spectrum – from discovery to access. In 2019 we will continue to emphasize these collaborations and recognize that each of you is central to paving the road that lies ahead. Thomas Bols SVP and Managing Director DIA EMEA

Pictures: DIA

At the Crossroads

11.12.2018 9:44:38 Uhr


Director, Regulatory Policy & Intelligence

Founder, CEO, Speaker in Pharmacovigilance International Clinical Trial Project Manager Head of Data Management

Global Medical Affairs Lead

Director, Market Access


EUROPE 2019 5-7 February | Vienna

What will YOU bring to the debates? Register today to join the medicines development and access dialogue in February. Learn more at DIAglobal.org/EuroBiotech

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06.12.2018 14:36:53 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

6 –7 February 2019 Paris Expo Porte de Versailles, France

Pharmapack Europe  Pharmapack is Europe’s largest event dedicated

to the pharmaceutical packaging and drug delivery industries. In addition to an extensive conference programme, it also provides invaluable   opportunities for networking and showcasing innovations.

Pharmapack 2019 will bring together over 400 exhibitors from 37 countries and 5,290 attendees to network, innovate, and learn about the latest advancements and trends in the pharmaceutical packaging and drug-delivery industries. Beyond the exhibition floor, 40 sessions, delivered by industry experts, will take place over the two-day event to discuss the very latest market trends and provide an analysis of regulatory changes in the EU and US markets. Session topics will

include: Patient Adherence; Challenges in Usability and Regulatory Update; New in Packaging Materials and Drug Delivery Systems; New in Biologicals and Biosimilar Drug Delivery Devices; and Sustainability and Pharmaceutical Packaging and Devices. Running alongside these sessions will be the Technical Symposium, which will provide insight from exhibiting industry leaders on overcoming challenges. A Start-up Hub will provide a platform for young companies to exhibit their in-

Join the pack

exploring patient-friendly and ecological solutions. During this hugely dynamic time, our Start-up Hub has been specifically designed as a low-cost solution to introduce these breakthrough companies to a wider audience. This will be our most exciting edition to date. We invite you to join us at Pharmapack 2019 to see the future of pharmaceuticals.

› Quick facts

Silvia Forroova Brand Director Pharmapack

More Information www.pharmapackeurope.com

GREETING   In the last year we have seen a tremendous proliferation of industry innovation: not only have FDA market approvals increased rapidly, but at our event we are now seeing the launch of increasing novel technologies and newer market entrants

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Highlights Over 400 exhibitors in Hall 7.2 Over 5,200 professional visitors Conference with 40 sessions Technical Symposium Startup Hub Pharmapack Awards Pictures: UBMi

Wave of Innovation

novations, providing them with valuable brand visibility. Companies will also be able to pitch their concepts to a panel of experts and an audience of industry professionals, and provide them with valuable networking and learning opportunities. Finally, the Pharmapack Awards will be hosted on the first evening of the event and will celebrate the best pharmaceutical packaging and drug delivery products from 2018 in the categories of Exhibitor Innovation and Health Products. All Exhibitor Innovations finalists will be showcased in the Innovation Gallery, which will give a comprehensive overview of recently developed products. The Health Products category will include two winners: one for Patient-Centric Design, launched in partnership with HCPC Europe; and a second, introduced alongside Adelphe, for Eco-design in health packaging and drug delivery devices. Attendees will also be able to explore this year’s Exhibitor Innovation finalists via expert guided Innovation Tours. L

06.12.2018 14:37:44 Uhr

Pharmapack Visitor Ad 2019 210x275 191018 v1.pdf





• Innovation Gallery • Pharmapack Awards • Innovation Tours • Pharmapack Start-up Hub

• Networking Areas & Events

• International Meetings Programme

• Conference • Symposium • Workshops • Learning Lab


49_EB_Winter_2018_UBMi.indd 1







te E nd !










Pharma’s dedicated packaging & drug delivery event

Follo the l w ink bit.ly /2q1 : MiA 2


06.12.2018 14:37:57 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

18 –21 February 2019 Hotel Royal-St Georges  Interlaken, Switzerland

HIC/DSP conference  The HIC/DSP conference provides a platform to better

understand the chromatographic isolation and purification of biological targets. Professionals will share their expertise and experiences on all aspects of chromatographic separation and process design for biomolecules.

The HIC/DSP conference (formerly known as HIC/RPC) builds upon on a strong foundation of successful events focused on Hydrophobic Interaction Chromatography (HIC) and Reversed Phase Chromatography. The upcoming conference will keep an eye on the HIC fundamentals while expanding its scope to all modes of chromatography, focusing more on the output of separation techniques in downstream processing (DSP): the efficient purification of biomolecules. Today’s most challenging elements of modern downstream processing are the continuous increase in expression levels in fermentation and cell culture, the stringent demands for purity and recovery of biopharmaceuticals, and the high-

› Quick facts Registration http://www.hic-dsp.org Contact Romain.Dabre@tosoh.com Phone: +49-6155-704 37 11

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ly competitive environment. The conference will discuss potential solutions for these problems using new chromatography media and innovative processes. The practical elements of chromatographic development and implementation will be balanced by discussions about novel approaches and theories. Examples of the areas that will be covered in more than 40 lectures and posters:

›› Mechanisms of biomolecule-surface interaction

›› DSP method development and mechanistic understanding of bioprocesses ›› DSP case studies ›› Trends in Process Chromatography and Integrated Manufacturing The event takes place in Interlaken, Switzerland. Interlaken can easily be reached by car or train. Direct rail links exist from Zurich and Geneva airports with trains leaving every hour. The registration fee is all-inclusive, covering the conference, hotel accommodation, L excursion, and all meals.

An update on bioseparation

Welcome note   For the 11 th edition of the HIC/DSP confer ence, w e hav e set up an exciting TACKLING FUTURE CHALLENGES - 11TH HIC/DSP B programme, wellFEBRUARY 18-21, 2019 | INTERLAKEN SWITZERLAN balanced bet ween CONFERENCE TOPICS basic research and Trends in process industrial applications. chromatography and integrated manufa

Method development and mechanistic understanding of Mixed mode multimodal - the orthogon We are delighted that /some greatchromatography keyDSP applications and case studies: note lecturers such as Roman NeciAntibody constructs na from Shire, Klaus Graumann from Blood & plasma proteins Phoenestra, and Stefan Hepbildikler Oligonucleotides and peptides from Roche will share their insights. Viruses, vaccines and gene therapy vectors Hydrophobic separations - a HIC/RPC legacy

Moreover, during the five different regularContact sessions, by recogus atchaired hic-dsp@tosoh.com nised exper ts from both academia and industry, participants will have the opportunity to learn about the latest developments in the downstream processing world, and to acquaint themselves with the industrial perspective of downstream processing and how this technique is used for the production of bio­pharmaceuticals.

Alois Jungbauer Chair of the Scientific Committee 11th HIC/DSP University of Natural Resources and Life Sciences Vienna, Austria

Pictures: Swiss Paragliding & Adventure | Photograph by Markus Zimmermann

Bioseparation & DSP

06.12.2018 14:38:30 Uhr

REGIS TE TODAY R ! w ww.hi



TACKLING FUTURE CHALLENGES - 11TH HIC/DSP BIOSEPARATION CONFERENCE FEBRUARY 18-21, 2019 | INTERLAKEN SWITZERLAND CONFERENCE TOPICS Trends in process chromatography and integrated manufacturing Method development and mechanistic understanding of bioprocesses Mixed mode / multimodal chromatography - the orthogonality DSP applications and case studies: Antibody constructs Blood & plasma proteins Oligonucleotides and peptides Viruses, vaccines and gene therapy vectors Hydrophobic separations - a HIC/RPC legacy Contact us at hic-dsp@tosoh.com

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06.12.2018 14:38:47 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

26 February 2019 Kap Europa, Frankfurt, Germany

Chemistry makes ... “You are crazy” Bioeconomy is revolutionising chemical production. The 3rd ECP will bring innovators together in Frankfurt on 26 February 2019: Start-ups, mediumsized businesses, large companies, investors and service providers.

The ECP is unique. In just two years this Speed Dating event has established itself for the chemical industry and its user industries. More than 1,000 participants will meet to interact on 26 February 2019 in Frankfurt in 20-minute partnering meetings, or to bring themselves up to date. Some of the large companies already signed up: Archroma, Air Liquide, Arlanxeo, Bayer,  BASF, Beiersdorf, Brenntag, Celanese, Clariant, Covestro, Croda, Daikin,  Evonik, Fujifilm, Haldor Topsoe, Henkel, Heraeus, Jowat, Kuraray, Lanxess, LG, Lonza, Merck, Mitsui, Metsä, Procter &  Gamble, Roche Diagnostics, Saltigo,

› Quick facts Registration www.ecp2019.com more than 2,500 Partnerings Contact bengs@ecp2019.com Phone: +49-170-297 1837

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Sanofi, Seppic, Symrise, tesa, and  Thyssenkrupp. The ECP is about 20-minute Partnering discussions. Participants arrange these in advance. Then there are the Pitches – short, six-minute presentations reserved for start-ups and small -to-medium-sized companies. Large companies and investors are allocated 15 minutes. Partners and sponsors also give 60-minute workshops on topics like financing, internationalization, digitalization, and the circular economy. These core activities are complemented by a Keynote at the beginning, an exhibition, and many opportunities for informal networking the day before, on the day and the day after the event at a breakfast for all who are still in the city. The ECP br ings people together across disciplines, structures, regions, national borders, and cultures in the shortest possible time. A visit to the ECP is therefore a complement to  established fairs and congresses and a targeted investment in the future. L

Dr. Holger Bengs Initiator of ECP

Pictures: ECP

European Chemistry Partnering  … the world go around. Today the  

GREETING  “Holger Bengs, you are crazy.  We have so many events in our industry,” said some of my net work par tners before the 1st ECP in Febr uar y 2017. But 140 participants that day experienced something very different: ECP is unique! It’s all about rapid interchange between very different characters from very different companies and industries. Answers to the big questions of our time can only be provided by innovation that stems from thinking outside the box. The Bioeconomy is slowly changing chemical produc tion: enzymes instead of heating; new substances from nature’s building blocks and with the help of biotechnological methods; and finally digitization is generating further impulses first in our minds and then in the market.  At the 3rd ECP on 26 February 2019, we expect over 1,000 decision-makers, creative and innovative people from the chemical industry and its user industries at Kap Europa in Frankfurt – just a ten-minute walk from the main train station, 20 minutes by taxi from the  airport. Be there!

06.12.2018 14:39:05 Uhr


g for C Europe’s unique Speed Datin

1 0% OFF 9 1 0 2 ry a ru b e 26 F with code in Frankfurt/Germany ECP10

3rd Unique speed dating for the chemical industry and all related business areas Chemistry, Bioeconomy, Digitization, Engineering, Nanotechnology, Analytics, Polymers, New Materials, Big Data, Circular Economy, Biorenewables, etc. 1st ECP 16.02.17 Participants

2nd ECP 23.02.18

3rd ECP* 26.02.19








Start-ups and SMEs














Partnerings Big Players and Investors


Register Now!


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06.12.2018 14:39:20 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

AMR expert meeting Novel Antimicrobials And AMR Diagnostics 2019   In its 12 th edition,

the two-day conference is focusing on business strategies and current investment trends in the field of Antimicrobial Resistance (AMR) on the public and private level. More than 70 speakers will highlight AMR innovation in therapeutics and diagnostics for human and animal health. Is it worth to invest in companies developing new antimicrobials or diagnostics to tackle multiresistant pathogens that are spreading more and more globally? Yes, because in 2015 the burden of antibiotic-resistant infections in Europe was already comparable to that

› Quick facts Call for poster abstracts Submission deadline: 9 January 2019 Pre-conference workshop “Resistance testing – beyond serial pass experiments” – jointly organised by Novo REPAIR Impact Fund,  CARB-X, GARDP and Wellcome Trust    www.amr-conference.com

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of flu, tuberculosis and HIV combined: According to a study by the European Centre for Disease Prevention and Control (ECDC) published in the L ancet Infectious Diseases journal, an estimated 33,110 deaths could be attributed to multidrug-resistant superbugs in 2015. Specialists say that around 70 percent of infection-causing bacteria are already resistant to at least one antibiotic available. Given this background, AMR innovation in human and animal health, in therapeutics and diagnostics, is urgently needed. The conference, which is supported by BEAM Alliance, provides the ideal platform to meet all relevant stakeholders at once. It focuses on applied research from academia and small and medium-sized companies (SMEs). Speakers from the financing industry, the pharma and diagnostic industry, the policy and regulatory side, as well

as many different SMEs and start-ups will provide a broad insight into current challenges, promising success stories and best practices. With 70+ high-level speakers in 12 sessions, the event organiser BIOCOM AG brought together a packed agenda of relevant topics in human and animal health addressed during the conference. Alongside technology-oriented sessions, there will be debates about push and pull incentives with representatives from NICE, UK, and the US to explore ongoing pilot projects. Wellcome Trust will host a session around AMR surveillance and its relevance for R&D processes. Another track will dive into clinical development challenges, providing insights from late-stage SMEs as well as from regulatory bodies. For the first time, a session on animal health will highlight new approaches in this field. Offering investor’s partnering, an investors talk, and a start-up pitch, financing will be a priority topic during the event. In the Policy Forum, WHO and UNCTAD will present a first concept of a new global AMR investment fund (see p. 20). Copenhagen-based Novo REPAIR Impact Fund will provide an update on its activity and US-based CARB-X is going to talk about its European expansion. Another panel debate with representatives from the Global AMR R&D hub and JPI AMR will discuss the current status of international coordination. L

Picture: BIOCOM AG

14-15 March 2019 Radisson Blu Hotel Berlin, Germany

06.12.2018 14:41:08 Uhr

Mar 14|15

2019 Berlin | Germany


12 th Berlin Conference on Life Sciences

Novel Antimicrobials and AMR Diagnostics 2019 This conference is a platform to discuss strategies and the specific challenges faced by SMEs in bringing new antimicrobial treatments and diagnostics to the market.

What you can expect: Supporting Partners:

European Biotechnology ©Sebastian Kaulitzki/stock.adobe.com


Media Partner:

t 350+ attendees, 70+ high-level speakers discussing current AMR issues t Focus on human and animal health t Topics: Financing and funding | Start-up pitch | Clinical development and market access | Therapeutics and diagnostics | R&D trends t Policy forum, supported by WHO and UNCTAD t Poster session, exhibition and pre-scheduled one-to-one investor meetings t SMEs and academics benefit from a 50% discount off the full fee

Early Bird Deadline: 15 Jan – save 20%

amr-conference.com #AMRconference

Organisation: BIOCOM AG I Lützowstraße 33–36 I 10785 Berlin Katja Boelcker I amr@biocom.de I Tel. +49 (0)30 264921-51

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06.12.2018 14:44:04 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

25–27 March 2019 Messe Wien Vienna, Austria

BIO-Europe spring 2019  The 13th annual BIO-Europe Spring® interna-

tional partnering conference will meet in Vienna, Austria, March 25–27, 2019, at the Messe Wien Exhibition and Congress Center. This premier annual springtime event brings life science executives to Europe’s most innovative biopharma clusters. The 13th annual BIO-Europe Spring® international partnering conference will be held in Vienna, Austria, for the first time, March 25–27, 2019, at the Messe Wien Exhibition and Congress Center. The event is highly regarded among companies across the life science value chain, from large biotech and pharma companies to financiers and innovative startups. BIO-Europe Spring offers powerful opportunities for you to network with the right par tners, with over 2,500 attendees from 1,400 companies and 54+ countries. With a focus on  European innovation and global collaboration, the event is the premier

› Quick facts Registration Please visit ebdgroup.com/bes

56_EB_Autumn_2018_Compass_BIO-EuropeSpring_tg.indd 56

springtime par tnering conference bringing together a “who’s who” from biotech, pharma, and finance in the most innovative biopharma clusters in Europe. The event is also sought after by attendees for the variety and high caliber of presenting companies, ranging from academic innovators and start-up bio­tech companies to mid-size pharma and biotech, which bring their innovative technologies, therapies, and solutions with the goal of securing development and commercialization partners. BIO-Europe Spring also features a diverse list of industry leaders speaking on workshops and panels. Leading pharmaceutical companies, including all of the big names in pharma, sponsor the event, sending teams of scouts to discover new and innovative products. Informal networking events in stunning local venues lend further dealmaking opportunities. The 2018 event boasted 15,000 scheduled one-to-one meetings with 3,600+ licensing opportunities posted. L

Join us in Vienna G R E E TI N G   B I O E u r o p e S p r i n g ®, held in enticing biotech hotspots every spring, is the best place to solidify your str ategies for the next year. This conference is a key event for global biotech, pharma ,and investors who attend in search of new collaboration partners and deal opportunities. This year, BIOEurope Spring will be held in Vienna, Austria, for the first time. BIO-Europe Spring is expected to draw a high caliber of companies to this vibrant biotech hub, not only from Europe but from across the globe, to fuel the insatiable drug development industry. The event brings a high quality and variety of companies to present their licensing opportunities directly to potential partners, resulting in alliances that literally change the world. Vienna boasts over 450 life science organizations employing nearly 37,000 people in scientific innovation and medical research. With over 2,500 attendees last year, BIO-Europe Spring continues to bring global executives to locations that drive the industry’s growing demand for transformational breakthroughs. See you in Vienna in March, 2019! Anna Chrisman Managing Director EBD Group & KNect365 Life Sciences

Pictures: EBD Group

Partnering deluxe

06.12.2018 14:44:46 Uhr

V I E N N A , AU S T R I A / / M A RC H 2 5 – 27, 2 019

Ignite powerful partnerships with life science leaders

BIO-Europe Spring® is the premier springtime partnering conference [kbg`bg`mh`^ma^kZ pahlpah _khf[bhm^\a%iaZkfZZg]_bgZg\^bg the most innovative biopharma clusters in Europe. What to expect: • 13,000+ one-to-one partnering meetings • 3,500+ licensing opportunities to access • 2,600+ international executives from biotech, pharma, and finance • 1,500+ companies representing 50+ countries • 120 biotech, pharmaceutical, next generation and academic innovator presentations • 70 C-level speakers on plenary sessions and business development workshops • 65 exhibitors in the high-traffic heart of the conference Produced by

Supported by

FIND OUT MORE: ebdgroup.com/bes

57_EB_Winter_2018_BES.indd 1

06.12.2018 14:45:10 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

28–29 March 2019 NH Collection Friedrichstraße Berlin, Germany


the name says it all. In order to keep up to date, we have to stay abreast of changes. At this congress, some of the latest topics in the development of medicinal products and medical devices will be presented.

The phar maceutical l andscape is changing, and one has to keep pace with various trends while people, science, and the regulatory environment are moving forward. The future looks different, but does this mean for better or for worse? The 2019 Annual Congress on Pharmaceutical Medicine will help to answer this question. The event provides the opportunity to look closer at selected trend-setting topics. In a total of six symposia

› Quick facts Exhibition Interested to exhibit at this event? Please contact: aussteller@degepe.eu Advertising Become an advertiser in the PM QM, the journal of pharmaceutical medicine and quality management and benefit from over 3000 national/ international recipients and readers! Send your inquiry to anzeigen@degepe.eu

58_EB_Winter_2018_Compass_DGPharMed.indd 58

and a panel discussion, more than 20 experts will share their experiences with up to 300 participants. They will share their insights gained and lessons learned, as well as in their visions of areas like biomarkers, gene therapy, the blend of clinical trials and the regulator y area, as well as the rapidly expanding subject of medical devices. In the panel discussion, the compa­ tibility of money, corruption, and data protection will be discussed. In addition, in a “hot topics” session, talking points such as Brexit, health technology assessment (HTA), and reimbursement strategies, as well as the privacy shield, will be presented. DGPharMed is thrilled to present this interesting and inspiring mix of current and future-focused topics in pharmaceutical medicine. Participants can benefit from the event’s early bird rates valid until January 25, 2019: €490 for DGPharMed members and €640 for nonmembers. The organisers look forward to welcoming you in Berlin on 28–29 March, 2019. L

Stay on top! GREETINGS  While the pharmaceutical landscape around us develops further, we are called upon to find new pathways in order to maintain oversight. At the 35th Annual Congress on Pharmaceutical Medicine, we invite you to accept the dare and explore new approaches to biomarkers, gene therapy, medical devices, and other advanced topics. It is not unusual to be facing new regulations, but still we do not know exac tly how to cope w ith obligations originating from recently developed regulations. By sharing best practices in conducting clinical trials and pharma­covigilance, the annual ­D GPharMed congress can help to manage such challenges. On behalf of the programme committee and as the DGPharMed host, I cordially invite you to join us at the NH Collection Berlin Friedrichstraße on 28–29 March 2019 to listen to interesting presentations and participate in active and lively discussions on forward-looking subjects. The full programme will soon be available online at dgpharmed-jahreskongress.de. Prof. Dr. Christoph Gleiter President   DGPharMed e.V.

Pictures: DGPharMed

Off to new pastures

06.12.2018 14:50:21 Uhr

Foto: shutterstock.com/canadastock

35th DGPharMed Annual Meeting Access to new therapies: From challenge to solution! March 28-29, 2019 · Berlin NH Collection Berlin Mitte Friedrichstrasse Early-Bird-Rates until

January 24th 2019


· Biosimilars - Development and regional differences, market access, pharmacovigilance, HCP and patient acceptance · Falsified Medicine Directive - First experiences

Foto: shutterstock.com/xxx

· EU Health Technology Assessment - One assessment fits all? · Pediatric drug development - Challenges and possible solutions · Big data - Usefulness and usability · The new European Medical Device Regulation (MDR) and Evaluation of clinical data in medical device development · Medical Devices - apps, combination products, clinical trials and new regulations *Please note: the congress will be held in German.

Registration: www.dgpharmed-jahreskongress.de

Organisation: PRIME Consulting GmbH · Paulusstraße 1 · 40237 Düsseldorf · Tel.: 0211 49767-20 · www.primecon.eu

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06.12.2018 14:50:41 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

7 May 2019 Congress Centre Basel Basel, Switzerland

Swiss Biotech Day  In 2018, more than 600 senior life science

executives from across Europe met at the leading Biotech conference in Switzerland. In 2019, the event will again offer an inspiring programme.

Another record-breaking attendance confirmed the leading role of the Swiss Biotech Day as an industry networking platform. Only a few places in the world can compete with the density and variety of biotech stakeholders and their international partners from more than 20 countries gathered in Basel. From world-leading research groups, to investors, biotech entrepreneurs, startups and patent specialists – the event covers the entire value chain. Highlights of this year's conference includ-

ed the keynote from Novartis CEO, Vas Narasimhan, the launch of the Swiss Biotech Success Stories for remarkable industry achievements, and the Swiss Biotech Association’s 20 year anniversary. Owing to the constant growth, the Swiss Biotech Day on 7 May 2019 will offer more space at the congress centre of Messe Basel for exhibitors and present an inspiring programme with plenty of room for networking. An emphasis will lie on opportunities and

An amazing day

tors, researchers, analysts, political decision-makers, and industry stakeholders in Switzerland. To support the continuous growth and expansion of the event, the Swiss Biotech Day 2019 will be held on the more spacious top floors of the congress centre at the Messe Basel.

GREETING  I am very happy to invite you to the Swiss Biotech Day 2019. The SBD has proven to be a lot more than the Annual General Assembly of the Swiss Biotech Association. It has become the key networ king pl at for m for biotech entrepreneurs, inves-

60_EB_Winter_2018_Compass_SBD19_ml.indd 60

Join us in Basel for an intense and stimulating day! Michael Altorfer CEO, Swiss Biotech Association

› Quick facts REGISTRATION www.swissbiotechday.ch Phone: +41-43-508-11 21 register@swissbiotechday.ch Highlights

›› Swiss Biotech Report 2019 ›› One-on-one partnering ›› Exhibition ›› Swiss Biotech Success Stories celebration

Pictures: André Springer/SBA

Robust growth

synergies offered by the close collaboration of pharma and biotech. Platforms will be provided to discuss new developments in research and development, production, data management, artificial intelligence, and innovative financing. The release of the Swiss Biotech Report, highlighting the most important trends and facts on the development of the Swiss biotech industry, and the celebration of the Swiss Biotech Success Stories’ laureates of 2019 are on the agenda as well. Adding the traditional Swiss Biotech Association’s General Assembly, sessions on fostering closer cooperation between companies and investors, partnering talks in a private setting, discussions with experts on financing, and presentations of emerging companies, the Swiss Biotech Day will be as multi-faceted as the nature of the life sciences L industry.

06.12.2018 14:51:57 Uhr


Picture: © Basel Tourismus

The leading Life Sciences Conference in Switzerland and Annual General Assembly of the Swiss Biotech Association

MAY 7, 2019 Congress Center Basel

Join the upcoming Swiss Biotech Day and take the chance to meet senior experts from the life science industry and academia from across Europe.

Find out more at swissbiotechday.ch

Event Highlights: › 650+ attendees from 20+ countries › Swiss Biotech Success Stories Awards › Parallel tracks on innovative emerging and clinical stage biotech companies ... ONE BIOTECH CLUSTER › Thematically focused panel discussions › Pre-scheduled one-to-one partnering meetings for all attendees › High-traffic exhibition with ongoing catering



Supporting Partners:

European Biotechnology NET WORK

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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 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 Media Partners: 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

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.

Domenico Alexakis is Executive Director of the Swiss Biotech Association.


...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 Organized by: the executive office of Swiss Biotech.


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

06.12.2018 14:52:09 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

15 –16 May 2019   Cologne   Germany

15 – 16 May 2019 Maternushaus Cologne, Germany

Int. Conference on BIO-based Materials  For the 12 th time, the Inter-

national Conference on Bio-based Materials will present the technology leaders in the fields of bio-based chemistry and materials.

Despite the harsh economic environment, a few innovative companies have found markets for their new bio-based building blocks, chemicals, and polymers. We will introduce you to the technology leaders our planet needs for a sustainable future. The chemical industry may only develop into a sustainable sector once it bids farewell to all fossil raw materials and uses nothing but renewable carbon as a raw material in organic chemistry. Only a full phase-out of fossil carbon will help prevent a further increase in CO2 levels. All

of the fossil carbon extracted from the ground will sooner or later be released into the atmosphere, where the CO2 concentration will go up as a consequence. The bioeconomy will play a crucial role in providing renewable carbon.Today, PLA is produced by two leading companies, bio-based PBS has become commercially available, and soon the first bio-based PP will enter the market while bio-based PE production capacities will be expanded at the same time. Bio-based polymers can be found in almost all application sec-

Join the bio-shift

direct CO 2 use. So far, the increased use of renewable carbon has been limited to mechanical recycling and more wood in construction and paper packaging. But there is much more at stake. The entire base of the chemical and plastics industry must be converted. Whether and how this is possible we will discuss broadly in 2019: Come to Cologne in May to learn what's possible in bio-based chemistry and plastics.

GREETING  While the shift towards renewable energies is progressing rapidly and consistently in the energy sector, the corresponding shift in raw materials towards renewable carbon is taking its time. Renewable carbon can be obtained from rec ycling, biomass, and

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Michael Carus, Managing Director, nova-Institute

› Quick facts REGISTRATION http://bio-based-conference.com/ registration/ Contact Dominik Vogt Phone +49 (0)2233 - 48 14 49 dominik.vogt@nova-institut.de www.bio-based-conference.com

Pictures: nova-institut

Evolving bioeconomy

tors, such as packaging, consumer goods, toys, automotive, textiles, and coating. New bio-based building blocks are also available for body care, cosmetics, food ingredients, and pharmaceuticals. On top of that, more and more biogenic side streams from the food industry are utilised via biotechnology as part of the circular bioeconomy. In Cologne, technology leaders will present and discuss their latest innovations to about 200 international participants, primarily from industry. The 12th International Conference on Biobased Materials will include an accompanying exhibition with 30 exhibitors, professional matchmaking, and workshops (on first and second generation biorefineries, in-depth B2C market research, standards and norms as well as hurdles and barriers). It will once again provide one of the leading platforms for industrial networking in the European bioeconomy with a wide range of opportunities for discussion and making business contacts. L

06.12.2018 14:53:07 Uhr

7 th 20 – 21 March 2019, Maternushaus, Cologne (Germany)

Meet international experts at one of the leading events on Carbon Capture and Utilization (CCU) in the world. The political framework conditions for CCU have improved considerably in recent months: The new version of the Renewable Energy Directive (RED II), entering into force in 2020, opens the doors for all CO2 uses, including the use of industrial exhaust gases for all types of fuels. Stakeholders will showcase enhanced and new applications using CO2 as feedstock.

The conference at a glance: More than 200 participants and 20 exhibitors expected Topics are the new political framework, renewable energy and hydrogen production, carbon capture technologies, CO2-based fuels, chemicals and polymers, CO2-based proteins, mineralisation and artificial photosynthesis Sessions will be: Visions / Strategy, Sustainability, Hydrogen Production / Carbon Capture, Artificial Photosynthesis, CO2 for Chemistry and Polymers, CO2 for Fuels, CO2 for Mineralisation

For the first time the Innovation Award for the “Best CO2 Utilisation 2019” will be granted at the conference to the young, innovative CCU industry for finding suitable applications and markets for CO2-based products and technologies.

New advisory board with well-known experts on CCU technologies

20 – 21 March 2019 · Maternushaus, Cologne, Germany


Evolution of the Bioeconomy: Survival of the Fittest? Learning from Success. Despite the harsh environment, several innovative companies find markets for their new bio-based building blocks, chemicals and polymers. We will introduce you to the technology leaders our planet needs for a sustainable future. The conference at a glance: More than 250 participants and 30 exhibitors are expected Vision & Policy Bio-based Polymers and Building Blocks Biodegradable Solutions Biorefineries NEW: Bio-based Fine Chemicals (Food Ingredients, Flavours, Body Care, Cosmetics, Pharmaceuticals) Workshops on First and Second Generation Biorefineries, on In-depth B2C Market Research and on Standards and Norms, Hurdles and Barriers

15-16 May 2019 · Maternushaus, Cologne, Germany

16th International Conference of the European Industrial Hemp Association

The nova Innovation Award “Bio-based Material of the Year” will be granted to the young, innovative bio-based chemicals and materials industry for finding suitable applications and markets for bio-based products.


The EIHA Conference is established as the largest meeting of experts on industrial hemp in Europe and indeed worldwide! Specialists from all over the world will meet in order to exchange information regarding the latest developments in hemp applications for fibres, shivs, seeds and oil as well as cannabinoids.

The conference at a glance: More than 350 participants and 30 exhibitors from 40 countries expected CBD as Food Supplement and Pharmaceutical Hemp Seeds, Oil and Proteins Fibres & Shives Biocomposites Construction Insulation Textiles

5-6 June 2019 · Maternushaus, Cologne, Germany

For more information, please contact: Dominik Vogt +49 (0) 2233 48 14 – 49 dominik.vogt@nova-institut.de

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The Innovation Award “Hemp Product of the Year 2019” will be granted to the young, innovative industrial hemp industry for finding suitable applications and markets for industrial hemp based products.



06.12.2018 14:53:39 Uhr


Euro Biofairs Compass

European Biotechnology | Winter Edition | Vol. 17 | 2018

24 June – 4 September 2019 France, Germany, Sweden, Switzerland, UK

Amgen Scholars Europe:  An undergraduate Summer Research

Programme in Science and Biotechnology. Every year, 75 selected undergraduate students throughout Europe get the opportunity to engage in hands-on research at five of Europe’s premier educational institutions.

Inspiring the Scientists of Tomorrow –  S e l e c t e d s t u d e n t s t a k e p a r t i n  important university research projects where they gain lab experience and contribute to the advancement of science. The guidance from faculty mentors, including some of Europe’s top academic scientists, is a key element of the programme. Scholars additionally participate in engaging scientific seminars, workshops, and networking events. The signature symposium, hosted at the University of Cambridge ever y September, is where all 75 students

› Quick facts Applications 1 Nov. 2018 – 1 Feb. 2019 More information www.amgenscholars.com European students can also apply   for the Asia program

hear first-hand from leading scientists in industry and academia. The European symposium provides students with a valuable opportunity to discuss their research, learn about drug discovery and development, and network with other Amgen Scholars from Europe. Amgen Scholars Europe Programme applicants must be undergraduate students enrolled in colleges or universities in countries that are participating in the EHEA and the Bologna Process. Applicants must have not completed their bachelor’s or first degree (or its equivalent) prior to participation. In addition, the programme is looking for a strong record of academic performance and an interest in pursuing a Ph.D. Financial support is a vital component of the Amgen Scholars Programme. Details vary by host institution, but the scholarship usually includes a stipend and covers accommodation, as well as travel costs. Application deadline: 1 February 2019

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Alumni Spotlight GREETING  I realized that with a sciencebased career I will not only improve my own mind, but also the world around me. My project at LMU was about the molecular background of mechanisms in evolution. We modified the genome of different fly species in order to fluorescently label a protein called Yellow, which is very important for the wing pigmentation. This way we can observe its expression over the complete development of the fly under the microscope and find out how diversification happens. Working together closely with renowned scientists in well-equipped laboratories, I wanted to gain a deeper understanding and more knowledge about life sciences. Not only did I want to find answers to the many questions I had, but also wanted to find more questions to ask and study in the future. Furthermore, I hoped to learn more about the dynamics and structures of actual research groups and about how to present research. Amgen Scholars was the perfect opportunity to fulfill these ambitions and motivations. Lisa Rodermund Alumna, hosted in 2015 at LMU Munich, Germany. Currently a Ph.D. student at the University of Oxford.

Pictures: Amgen Scholars

Discover potential

06.12.2018 14:54:40 Uhr

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06.12.2018 14:54:53 Uhr


Artificial Intelligence

European Biotechnology | Winter Edition | Vol. 17 | 2018

Can machines learn to discover drugs? billion-euro blockbuster molecule is ready! AI-driven drug development is exciting investor interest, while Big Pharma is also asking what forms of artifical intelligence can be slotted in at what stages in the process. AI-powered drug repurposing has seen some candidates enter clinical stage testing, but it’s still unclear whether the technology is already powerful enough for de novo molecule discovery.

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Picture: foxaon1987/shutterstock.com

Artificial Intelligence  Take the right dataset, add an ingenious algorithm or two – and voilá! Your

06.12.2018 14:59:20 Uhr

Artificial Intelligence

European Biotechnology | Winter Edition | Vol. 17 | 2018


y boasting their technology is a “bioscience machine brain to discover new medicines and cures for diseases”, British drug discovery start-up Benevolentai has clearly overstated its case – even in the eyes of AI advocates. But that didn’t slow investors down. The confident self-promotion was backed by a recent funding round that now values Benevolentai at an estimated US$2bn. According to Bruce Booth, a partner at venture capital firm Atlas Ventures, it is unquestionable that computation is and will play an important role in drug R&D. But he remains sceptical it’ll be as transformational as all the hype claims. “Biology,” he says,”is the untamed beast.” It’s easy to understand why claims being made by AI developers are falling on fertile ground. The pace of drug discovery and the time it takes to bring a drug to market hasn’t improved significantly in the last 40 years. Even worse for the industry – productivity has shown a downward trajectory in terms of return on investment. It’s a counterintuitive statistic in an age of new and exciting technologies like genome editing, high­-throughput screening, and structure-based drug design. “Each of these technologies provides us valuable insights,” says Andrew Hopkins, the CEO of Exscientia Ltd. His start-up is one of many British companies seeking to leverage artificial intelligence for drug discovery and development. When asked why all those shiny new molecular biology technologies still haven’t improved productivity in bio­ tech and pharma industries, Hopkins says they can actually make existing processes more complicated. “Grea­ter insight plus greater complexity does not necessarily result in greater productivity.” Of course, he’s also convinced that this is where AI can make a difference.

Picture: Exscientia

Boom? Hype? Neither? “What we are trying to do is improve decisionmaking itself, so that researchers are put into a position to tackle more complicated projects and deal with larger datasets,” says Hopkins. “It’s a true enabling technology that allows us to integrate all the other technological ad-

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vances. So far, the bottleneck has been the human brain. AI helps us overcome cognitive limits.” Hopkins isn’t the only one convinced that AI is a panacea for industry woes. The technology is already driving sizeable business activities in healthcare. Besides drug discovery, AI companies are developing business models in areas like finding better biomarkers, optimising clinical trial design, matching patients with treatments, health record management, medical imaging and surgery assistance. Consultants at Accenture Strategy estimate a current annual growth rate of 40% for the market. AI in healthcare was just a US$0.6bn market back in 2014. But it’ll be worth US$6.6bn by 2021. A good indication for accelerating growth is the number of healthcare-focused

Andrew Hopkins  CEO of Exscientia Ltd. & Professor for Medicinal Informatics at the University of Dundee

? !

Will AI leave a mark in drug discovery?

I think we are now at the cusp to have significant evidence that AI can make a sustained contribution to drug discovery. This is very exciting, because you can see the field is accelerating. There are many new companies active in the space. Some provide customers with AI as an add-on to an existing in-house process. Besides these AI service providers, companies like Exscientia are offering to automate the entire process.


AI deals which – according to market analyst company CB Insights – rose from less than 20 in 2012 to about 170 in 2017. The number of newcomers per year, as indicated by a disclosed first equity round, rose from 7 to 77 over the same time period. In total, healthcare AI start-ups have raised US$4.3bn across 576 deals since 2013, topping all other industries in AI deal activity. And that includes cybersecurity and commerce. But enough numbers for the moment. Let’s go over some basics.

Getting the terms right What exactly is AI? The elastic term has been applied to technologies invented as far back as the 1950s. “The basic tools of AI everyone is using have been around for several years now but their application has improved massively in the last couple of years,” says David Williams.The CEO of British drug discovery start-up Nanna Thera­peutics adds that generally speaking, AI is a set of computer science techniques that allows – with increasing levels of technical advancement – software to learn from experience, to adapt to new inputs, and to complete tasks that resemble human intelligence. Nowadays existing methods are grouped under what is called ‘narrow AI’, with the most advanced forms able to find creative solutions that no human could ever think of to specific tasks. AI limits are now being pushed further to try to achieve what’s called ‘general AI’. That’s an artificial intelligence able to reflect like humans do. In healthcare, the most important AI technology is machine learning, especially its newest iterations, which have been dubbed ‘deep machine learning’. A machine learning model is created by feeding data into a learning algorithm. So someone has to first write that algorithm, then train it with data that’s accurate and reliable. Over time, models can be re-trained with newer data, increasing their effectiveness. While the data aspect is extremely important for AI in drug discovery, lets focus first on the algorithms used. Basically, there are two types of them – supervised and unsupervised. Supervised learning algorithms make predictions based on a set of exam-

07.12.2018 12:52:48 Uhr


Artificial Intelligence

European Biotechnology | Winter Edition | Vol. 17 | 2018

The black box dilemma In a lot of machine learning algorithms, the decision­making processes have grown completely opaque. They’re a black box. Once a decision has been taken, there’s no way to backtrack and figure out why particular choices were made. You can’t ask the machine to explain itself. For many applications, this is proving a real challenge. One example: an AI recommends a patient receive a drug the physician would not have chosen because of its toxicity. Is it actually the best choice available? Or is there a flaw in the data or the algorithms? There’s no way to tell. Some up-and-coming companies claim to have solved the black box dilemma. One is Pattern Computer Inc. (US), which focuses on ‘pattern discovery’. Traditional AI is about pattern recognition – telling the computer to watch out for something specific in the data. Pattern Computer coined the term ‘pattern discovery’ to imply its computers don’t need to be told what to look out for – they just find patterns. And the startup claims users can learn everything their AI has learned, tremendously improving insight into e.g. a disease mechanism. In collaboration with Ben Brown at the Uni-

ples. For this machine learning method, it’s important to know the value of interest. Because the model is being fed with correct answers, predictions from supervised learning algorithms are more precise than from unsuper­vised learning algorithms. In unsupervised learning, data points aren’t associated with labels. Instead, the goal of an unsupervised learning algorithm is to organise data in some way, or to describe its structure. This can mean grouping it into clusters, or finding different ways of looking at complex data so that it appears simpler or more organised. This form of training is less specific, not least because the people analysing the output might not even know the right answers themselves. That said, unsupervised learning can pro-

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versity of Birmingham (UK), the Pattern Computer AI sifted for example through genomic data from breast cancer patients looking at important aspects of genomic architecture – for pathways, or relationships between pathways, rather than individual genes. Exploring a space as large as the scientists did is impossible with brute force calculation. No computer on Earth can cope with 1040 computations. The system, which is a mix of a proprietary device and software architecture, was able to reduce the number of computations by several orders of magnitude. After a single day’s run on the breast cancer data, it came up with a computationally-derived hypothesis that the underlying cause for disease in a high-risk group of patients was the misguided interaction of three specific genes. Confirmatory lab work still has to be done, but making an actionable – in this case druggable – discovery within a few hours is impressive. Although AI methods for identifying two-way relationships or hypothesis-based higher order interactions do exist, the ‘best-fit’ hypothesis discovery of a three-way relationship as shown by Pattern Computer is a first. L

vide great benefits when an algorithm is tuned properly to fill in the blanks. So for supervised machine learning, it’s crucial to have a massive set of high­quality data. For unsupervised machine learning, human experts capable of putting the results into perspective are critical. “Many of our staff worked in Big Pharma before joining us,” says Exscientia’s Andrew Hopkins. People with an in-depth understanding of the challenges of drug discovery are crucial to interpretation, as there are many domain-specific hurdles of AI implementation. An algorithmic set-up might work well with protein structure data but not at all on high-content screening data. The insight that combining AI and bio­ logy expertise might be the way to go is

reflected by a whole new range of cooperation models. Drug developers are buying equity in AI start-ups, joint ventures are happening, and licensing in silico-generated drug candidate programmes has grown common. “We so far nominated four molecules as preclinical candidates, and hopefully next year we will see the first ones move into the clinic,” says Hopkins. According to him, Exscientia’s pharma partnerships with GSK and Sanofi bring more than just financial benefits: “We are learning by being exposed to new problems. Creating new algorithms to solve them enhances the system in its entirety. This way the solutions to more and more design problems are provided by algorithms.”

Small team, big value Hopkins earned recognition for forming the indication and discovery group of US pharma major Pfizer in 2000. The UK site was one of the industry’s first drug re­purposing units to use computational methodologies to mine the literature. Pfizer was trying to institutionalise the success of sildenafil – Viagra. “The results were a significant increase in fieldof-use patents and the initiation of Phase II trials for new indications. We realised that a small team of people could generate a lot of value by mining information correctly,” Hopkins remembers. Back around 2005, many companies emerged with an IT-based approach to repurpose drugs. Since then, more expansive data­ bases have been developed in lock-step with more elaborate algorithms. Exscientia published the first version of its automated drug discovery technology in 2012, and continued to improve it since. “It was a long journey, but the technology has now proven itself capable of making huge contributions to the discovery of new molecules,” the AI expert asserts. That’s a positive take on the situation. First-movers like E-Therapeutics (UK) had to realign themselves as clinical candidates didn’t fulfill expectations. But a new wave of companies – including Exscientia, Benevolentai and Insilico Medicine – seem to have a sounder foundation, both technically and financially. They all share a com-

07.12.2018 12:52:56 Uhr

Artificial Intelligence

European Biotechnology | Winter Edition | Vol. 17 | 2018


An overview of the companies that are currently focused on AI-driven drug development


Business model


AI used for

Of note

› A2A Pharmaceuticals (2016)

Preclinical-stage drug developer

US$3m financing (2018)

hit generation to alter protein-protein interactions

Duchenne Muscular Dystrophy-focused JV with Insilico (US) announced (2018)

› Acellera Ltd. (2006)

Fee for service

undisclosed (revenue-driven growth)

binding pocket identification, ADMET profile improvement

Duchenne Muscular Dystrophy-focused JV with Insilico (US) announced (2018)

› Ainet

Fee for service


antibody & T-cell discovery

ETH Zurich spin-off relies on cell-free protein synthesis


› Antiverse




antibody drug discovery

› Ardigen


Fee for service

kick-off financing of PLN3.7m; spin-off of Polish drug developer Selvita SA

hit generation, lead optimisation

› Atomwise (2012)

Royalty for service

early-stage venture, US$51m (two rounds)

hit discovery, drug repurposing, mechanism discovery

partnerships with Monsanto (2017), Merck & Co., Abbvie, Pfizer

› Benevolent AI (2013) with its biotech-focused unit Benevolent AI Bio

Clinical-stage drug developer, plans to enter advanced materials, agriculture & energy storage sectors

mid-stage venture, US$207m (two rounds), pre-money valuation at US$2.1bn; partnership with an undisclosed US pharma in Alzheimer’s Disease

target identification, lead optimisation, clinical trial design

in-licensed clinical-stage drug candidate from Janssen NV, part of J&J (US), now in Phase IIb; bought its own AI supercomputer (2017); acquired a facility to keep late-stage drug development in-house (2018)

› Berg Health (2008)

Clinical-stage drug developer

undisclosed (revenue-driven growth)

biomarker identification (that leads to drug repurposing)

partnerships with Sanofi & AstraZeneca (both 2017)

Fee for service, strategic partnering

undisclosed (revenue-driven growth)

drug repurposing, clinical trial analysis, target discovery

partnerships with Pfizer, Novartis, Astellas

› E-Therapeutics (2003)

Preclinical-stage drug developer

public market (IPO, market cap GBP17.8m)

proprietary platform to fuel its own pipeline; 2018 collaborations with Intellegens & Biorelate (both UK) to add their AI tools to the platform

first clinical candidates shelved; collaboration with C4X Discovery to find treatments for Parkinson’s disease

› Evaxion (2008)

Fee for service

undisclosed (revenue-driven growth), grants

antigen and neoepitope discovery

partnerships with Moderna, Bavarian Nordic

› Euretos (2012)

Fee for service

undisclosed (revenue-driven growth)

mode-of-action & biomarker discovery, target validation

› Exscientia (2012)

Preclinical-stage drug developer

mid-stage venture, undisclosed VC round (2016); German Evotec bought minority stake for €15m

lead-like hit discovery

partnerships with Sanofi, Janssen, Sumitomo Dainippon and GSK;

› Innoplexus (2011)

Fee for service

two undisclosed VC rounds

various applications along the value chain

also service provider for the financial industry

› Insilico Medicine (2014)

Neutraceuticals & clinical-stage drug developer

early-stage venture, US$13.1m (two rounds), undisclosed VC investment by Wuxi Apptec (China, 2018)

drug repurposing, target identification, lead generation, clinical study design

formation of drug discovery joint venture Juvenescence AI with its investor holding Juvenescence Ltd. (UK, 2017)

› Mind the Byte (2011)

Software as a service, Consultancy

€0.5bn via two crowdinvesting campaigns, loans, EU project funding

mode of action discovery, hit & target discovery & expansion,

› Nanna Therapeutics (2003)

Preclinical-stage drug developer

early-stage venture, undisclosed VC round, partnership with Boehringer (2018)

lead-like hit discovery

formerly Bactevo; miniaturised wet-lab as core technology

› Nimbus Therapeutics (2009)

Clinical-stage drug developer

late-stage venture, US$137m (five rounds), partnerships with Celgene, Gilead, Genentech, Charles River & Proteros

target selection

AI platform developed by Nimbus’ co-founding company Schrödinger Inc. (US)

› Pharnext (2007)

Clinical-stage drug developer

public market (IPO 2016, market cap €121m)

drug repurposing (finding drug combinations)

coined the term pleotherapy

› Relay Therapeutics (2016)

Preclinical-stage drug developer

early-stage venture, US$120m (two rounds)

lead-like hit discovery

Visualising & computing dynamic ligand-protein interactions anywhere on a protein – not just at the active site

› Schrödinger (1990)

IT developer, clinical-stage drug developer

late-stage venture, US$132m (four rounds), partnerships with Janssen (J&J), Ono Pharmaceutical, Takeda and Sanofi

all along the computational drug design process

JV with Chinese Wuxi Apptec (Faxian Therapeutics, 2018); also works for materials science industry works with simulations of cells

› Biovista


› Turbine


Fee for service

undisclosed (revenue-driven growth)

biomarker discovery, clinical trial design, drug repurposing

› Twoxar


Preclinical-stage drug developer

early-stage venture, US$14.3m (two rounds), collaboration with Santen for glaucoma treatments

one-stop-shop from hit generation to drug

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07.12.2018 12:53:05 Uhr

Artificial Intelligence

mon goal: to build traditional fully-integrated drug development companies. “Just as molecular biology was a tool adopted in many areas across the value chain 40 years ago, so is AI now,” Hopkins adds. “Companies like Amgen, Genentech and Biogen took molecular bio­logy to the core of their business model and became the first generation of bio­tech. We see something ana­ logous here. While AI is being adopted by existing companies at different speed and thoroughness, there will be a few big winners, with AI being at the heart of what they do.” Needless to say, Exscientia wants to be one of them.

Generating data in-house David Williams is also bullish about his firm’s approach. While the business model (internal and partnered programmes) and the focus on a specific disease domain (mitochondria bio­logy) are nothing out of the ordinary, Nanna Therapeutics does a few things differently on the tech side. “We deve­loped a high-throughput method of synthesising medicinally-relevant tag-less small mole­cules that are fed into a high-content screening platform able to perform and screen billions of functional and phenotypic assays in a single day. That gives us a big advantage – we generate a lot of high-quality and highly consistent data in-house,” explains Williams. That brings a second important aspect into the limelight: data. It dictates what the AI spits out at the other end. If the answer to a question you’ve asked just doesn’t come, its time to start tinkering with the algorithms. This is especially likely to occur when working with small datasets in supervised machine learning algorithms, where you have to carve out a big chunk of the data to train the AI. “If you have a big enough dataset, the answer is much easier to find,” Nanna’s CEO explains. Without revealing the nature of the firm’s in-house generated small molecules (atom number and variety), Williams says that Nanna can synthesise billions of different molecules. For comparison: combining 17 atoms of carbon, nitrogen, sulphur, oxygen, hydrogen and the halogens results in a chemical space made up of

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European Biotechnology | Winter Edition | Vol. 17 | 2018

David Williams  CEO Nanna Therapeutics Ltd.


What do workflows in a drug discovery project actually look like?


We want to make drug-like molecules in as few steps as possible. Before starting the synthesis, there’s a lot of work done in silico. We design a core scaffold, we decorate it with various chemical constituents, we run physico­-chemical predictions, we also check how each virtual compound could interact with a wide spread of different biological structures. This results in a compound library of between one and ten million molecules that is then synthesised. Later, all are tested using our microfluidics platform to assess their impact on e.g. certain cell types (the primary assay) followed by a variety of drug property and safety assessments. With all that data at hand, AI helps us decide where to head next in the chemical space – and where not.

166 billion possible molecules. “Across the whole industry, pharmaceutical companies have less than 20 million plate-based small molecules from which to launch a programme,” Nanna’s CEO says. “Starting with 1 or 2 million compounds and using an iterative and linear process of primary, secondary and tertiary screening, each company will attempt to identify the best compounds in successive steps,” he explains. “Our goal is to completely transform this process. Accessing billions of whichever molecules we want, we do all

the necessary screening in parallel on everything right at the very start – and avoid the iterative process – to identify interesting hits within a few weeks.” Surprisingly, Williams admits that Nanna is not terribly sophisticated in the way it uses AI. The quality and quantity of the data allows the company to rely on relatively straightforward, mostly open-source software. Less surprisingly, Williams is concerned about the way some of the ‘cuttingedge’ AI technologies are being hyped at the moment: “These companies just try to squeeze out the few grains of gold left inside the data everyone has looked at dozens of times. I’ll leave it up to them, because we don’t have to look very hard to find a nugget here and there in our data.”

Small molecules ahead Most activity in AI drug discovery centers around small molecules. A one-stop-shop for AI-based biologics discovery is not an obvious business model, due to the size of the molecules and the complexity of their assembly, interactions and decomposition. That said, a few companies are using AI to focus on certain aspects of biologics drug discovery. They include Antiverse and Peptone in the UK (anti­bodies), Pepticom in Israel (peptides), Deep Genomics in Canada (oligo­nucleotides) and Envisagenics in the US (RNA). Two very ambitious startups are Canada-based ProteinQure, which aims to design peptide-based therapeutics de novo and US-based Resonant Therapeutics, which says it can find relevant new drug targets and corresponding therapeutic antibodies in cancer tissue samples. Danish Evaxion Biotech is among the few start-ups using AI to discover vaccines for infectious diseases and cancer. Another low-profile area is the AI-driven discovery of proteins and peptides for the materials science, cosmetics or food industries. Examples for the former are London-based Labgenius and Nuritas from Dublin, with the latter being pursued by multinationals BASF and Nestlé. It certainly takes an effort to see your way through all the hype. But AI proponents say it’ll just get better and better. L m.laqua@biocom.eu

Picture: Nanna Therapeutics


07.12.2018 12:53:13 Uhr

European Biotechnology | Winter Edition | Vol. 17 | 2018



Rentschler Fill Solutions starts new facility CDMO  Just two years after laying the cornerstone, Rentschler Fill Solutions has inaugurated a

state-of-the-art fill and finish facility in Rankweil, Austria, which provides aseptic filling and freezedrying of pharmaceutical and biopharmaceutical products on both a clinical and commercial scale.

Pictures: Rentschler Fill Solutions / Säly

Quality and time to market is key in the expanding biopharmaceutical market, which grew at a CGAR of 8% between 2010 and 2017. Rentschler Biopharma’s CEO Frank Mathias was well aware that providing end-to-end solutions in the growing CDMO market could speed up market delivery of biologics when he inked an partnership with Rentschler Fill Solutions GmbH back in June 2017: “We are seeing more and more demand not only in terms of manufacturing for clinical studies but for commercial-scale manufacturing and market supply,” he said. “It is not enough to develop innovative drugs. The capabilities and resources for production and filling are

a crucial part of ensuring that new treatments are available for patients,” Dr. Margit Klotz, General Manager Operations at Rentschler Fill Solutions, commented. This November, just two years after laying the cornerstone, Rentschler Fill Solutions inaugurated a state-of-the-art aseptic fill and finish facility. The facility provides scalable supply of liquid and freeze-dried products for clinical and small-to-mid-scale commercial supply with a total annual capacity of 3.5 million vials. It has GMP approval for the European market. Reinhold Elsässer, Managing Director of Rentschler Fill Solutions, expects FDA authorisa-

tion by 2019 due to an agreement with its US customer Ultragenyx Pharmaceutical, Inc., announced in May this year, covering the fill and finish of an injectable recombinant protein, Mepsevii TM (vestronidase alfa), for US commercial supply. With Rentschler Biopharma and Leukocare as strategic partners, Rentschler Fill Solutions can also provide seamless therapeutic protein production, including stabilisation of protein formulations through Leukocare’s SPS® platform, and Rentschler Biopharma’s offering of developing and manufacturing of biopharmaL ceuticals.  t.gabrielczyk@biocom.eu

Rentschler Fill Solutions‘ fill and finish facility in Rankweil, Austria, has enough space for future capacity growth with the maturing biopharma market. A) new facility B) aseptic filling C) Reinhold Elsässer (left), Dr Margit Klotz (5th from left) & team cutting the red tape at the inauguration, which hosted over 200 guests.

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Metabolic control of CHOBC® for production of biologics CDMO  Process optimisation for biologics is obligatory for efficient processing and reduction

of Cost of Goods (COGs). Especially in the development of biosimilar antibodies, low COGs to manufacture the antibody provides a competitive advantage compared to competing biosimilar developers. The major advantage of our own CHOBC® platform is that all available expertise and newly obtained knowledge can be directly leveraged for process optimization.

During the last decade, process development for biologics has evolved into a highly professional expertise resulting in high titer processes, along with decreasing COGs. However, only limited amounts of the available knowledge from 60 years of literature is currently being used to understand the intracellular metabolism of the used host cell lines. Although spent medium-analysis provides information on extracellular metabolite concentrations, all the metabolic action relevant for the quality of the product occurs intracellularly at completely different metabolite concentrations. Therefore, metabolic understanding and, more importantly, metabolic control of our CHOBC® platform has been developed. This facilitates easy transfer to the developBiosimilar 1 Out-licensed

Biosimilar 2 Out-licensed

Omalizumab Available for out-licensing

ment laboratories in Gdansk at Polpharma Biologics and allows us to produce clinical trial material at our GMP suite. This direct interfacility collaboration and process understanding is the foundation for development of GMP processes to be transferred to the large manufacturing facility, which is currently being built in Duchnice, located near Warsaw, Poland. The newly built facility of 30,000 m2 is based on disposable fermentation and equipped with stateof-the-art hardware.

SPOT™ for optimal productivity In current practice, the method used most often by the upstream process (USP) development teams to achieve high producIpilimumab Available for out-licensing

Vedolizumab Available for out-licensing

Pertuzumab Available for out-licensing

7 6 5 4 3 2 1 0 SPOT





Biosimilar 1

Biosimilar 2

Biosimilar 3

Biosimilar 4

Biosimilar 5






SPOTTM induced increase (%)


Biosimilar 6 190% Source: Polpharma

Figure 1: SPOT™ induced productivity increase. Compare first transparent bar of every color with the others of that color.

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tivity is to increase the viable cell density (VCD) in their upstream processes. Although high VCD results in higher product titers, this strategy also creates challenges for the downstream processing (DSP) teams, since clarification of more cells is more difficult and requires for high filter surfaces. In addition, higher VCD also results in higher host-cell related impurities which must be removed by DSP. Therefore, we developed USP technologies to increase volumetric productivity, without a major increase in VCD, by increasing the cell specific productivity of production cell lines. For this reason, the proprietary SPOT™ technology was developed, which aims to increase specific productivity per cell rather than the current USP optimization, resulting in higher VCD. This technology has been used in various programs and increases specific productivity (up to 200 pg/cell/day) and ultimately therefore also increases volumetric productivity up to 400% in various programs (up to 8 g/L; Figure 1). An additional technology, which was developed to increase specific productivity, is based on increasing the cellular volume rather than increasing the VCD. Using this strategy, total biomass increases in the absence of major VCD increases. Examples to be used in the process to induce the increase in cell volume are amino acids like citrulline and a sugar like sucrose. The use of citrulline decreased the VCD in the USP process of our ustekinumab program for 60% at comparable productivity as in the

Pictures: Polpharma

› Dr. Louis Boon, Chief Scientific Officer, Bioceros (member of the Polpharma Biologics Group)

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European Biotechnology | Winter Edition | Vol. 17 | 2018






using SLIM


Gas mix Flow

Gas mix Stirrer speed

Stirrer speed

lower stirrer speed X lower flow X lower oxygen levels

Figure 2: SLIM™ technology improves process efficiency. Compare the flow rates (orange lines), the stirrer speed (green line), and the oxygen level in the gas mix (light blue line) of CHOBC® (left) to CHOBC® using SLIM™ (right).

absence of citrulline. Reductions of host cell protein content in the presence of citrulline were 40%, while the filterability for clarification was increased by 40%/gram of product. The latter has huge consequences for the GMP footprint of the clarification filters and, furthermore, reduces the dead volume of the clarification filters, resulting in less product loss, and consequently lower COGs.

Pictures: Polpharma

SLIMTM for efficient bioprocessing One of the major drawbacks of current bioprocessing is that all high-producing processes demand high sparging and agitation rates and moreover consume high amounts of feed and oxygen. Besides pushing the current bioreactor systems to the limit, the induction of shear stress and product oxidation in current bioprocessing raises questions about the sustainability of current bioprocessing. Moreover, since the feed of the process is an expensive part of total production costs, the high consumption increases COGs. To find a solution for these process challenges, we leveraged our intracellular metabolic understanding of our CHOBC® platform to perform metabolic engineering (in the absence of any genetic manipulation). The outcome of these studies resulted in our SLIM™ technology, which enables our CHOBC® host cell line to become much more energy efficient and therefore more sus-

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tainable in the future. The SLIM™ technology facilitates better transfectability and supports single cell growth, enabling better outgrowth of cell lines. Confirmative to our metabolic engineering design, in bioreactors the SLIM™ technology reduces the need for high agitation and sparging rates and reduces the oxygen and feed consumption (Figure 2). This results in better product quality at lower prices and far away from bioreactor hardware limits.

CHOBC® CQA modulation toolbox While using the SPOT™ technology, specific productivity is increased and the SLIM™ technology improved the efficiency of the process – the upstream scientists leverage the platform knowledge and metabolic understanding to design and develop a process modulation toolbox to specifically modify CQAs on the biosimilars that are not similar to the originator profile. Upstream process technology was developed to specifically increase or decrease specific glycan structures on antibodies. Methods were developed to specifically modify terminal galactosylation, core-fucosylation, and mannosylation on the biosimilar. In addition, methods were developed to influence the charge profiles of the biosimilar, including decreasing acidic variants and increasing/decreasing basic variants. Interestingly, the above described citrul-


line addition to the process not only results in cell swelling and reduction of VCD, but also in a reduction of acid variants and an increase in basic variants. These modulatory strategies, which do not limit productivity, deliver high producing biosimilar antibody processes, enabling us to ultimately produce those biosimilar drugs at low COGs. The developed modulation toolbox can also be used beyond biosimilars for novel biological entities. Since high terminal galactosylation on antibodies can increase their CDC effector function and low core-fucosylation can improve the ADCC effector function, the modulation toolbox can obviously also be used to tweak the anticipated biological effectiveness of a novel product. For a mechanism of action of a therapeutic antibody that needs effector functions, the USP process can be modulated to high terminal galactosylation or low core-fucosylation, while for a novel antagonist antibody the reverse can be designed in the USP process. These simple USP adjustments to the production process of a therapeutic antibody can eliminate the need for coupling of toxic compounds, as been done in ADC, to increase the cell-killing potential of the targeting antibody. The above described SPOT™ and SLIM™ technologies and the process modulation toolbox clearly show the value of detailed knowledge of the intracellular mechanism by which the therapeutic protein of interest is being produced and its quality is modified. Conclusively, the extensive and ever-increasing knowledge about our CHOBC® platform is and will be directly leveraged in our USP processes to generate high amounts at an optimal quality of therapeutic proteins. The Polpharma Biologics groups will develop a broad portfolio of high producing biosimilar processes, which will be used to strengthen our internal biosimilar pipeline, but are also available for out-licensing purposes. The extensive platform knowledge and the flexible integration of the group members is also available for customers who wish to profit from our in-depth manufacturing expertise and L flexible capacities.

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Northern EUROPE

European Biotechnology | Winter Edition | Vol. 17 | 2018

SOBI stocks up antibody therapies

Sustainability  Radio-frequency identification (RFID) tags containing electronically-stored information are widely used by commerce, logistics, and other industries. While they remain controversial from a data privacy perspective, Finnish-Swedish wood processing and packaging specialist Stora Enso successfully addressed the environmental footprint of these tags. The company’s ECO RFID tag technology is a paper-based and plastic-free solution that is fully recyclable, Stora Enso claims: “The ECO tag can be recycled in an environmentally friendly way together with paper and board materials. Moreover, it offers high conductivity at a lower cost compared with graphene or silver-printed antennas. The material content of RFID tags can affect the recovery of other materials. For instance, aluminium antennas can reduce the amount and/or quality of recycled glass if they cannot be separated within the recycling process. 

RFID tag based on a paper label

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hold 8.1% of the total shares and votes in SOBI. Additionally, SOBI agreed on milestone-related payments, like US$470m depending on scored sales of Synagis. “We see the acquisition as a stepping stone to drive sustainable growth in the US and make SOBI more attractive for partnering,” said Guido Oelkers, President and CEO at SOBI. With the acquisition, SOBI strengthens its US presence by doubling both the revenue and employee number there. As expected, another recent pipeline extension received approval in the US. Developed by Swiss Novimmune SA and bought by SOBI this summer in a CHF450m (SEK4,050m) deal, the interferon gamma neutralising antibody emapalumab (trade name Gamifant) can now be marketed as the first and only treatment for primary haemophagocytic lymphohistiocytosis, an ultra-rare hyperinL flammation disorder.

Galecto unperturbed Financing  After Bristol-Myers Squibb Co. (NYSE:BMY) did not pull its exclusive option in 2017 to acquire Galecto Biotech AB (Copenhagen) in a US$444m deal sealed in late 2014, the Danish biotech pondered a while over its options. This autumn, the respite ended with the news of venture capitalists fuelling the growth of the company with providing a €79m series C round. Led by its first, and now also largest investor, Novo Seeds, the early stage investment arm of Novo Holdings, various existing and new investors like Ysios Capital and OrbiMed joined in. Galecto will now take its lead programme TD139, an inhaled galectin-3 inhibitor, into Phase II/III for idiopathic pulmonary fibrosis (IPF). The financing will also enable clinical studies for two additional programmes, Richard Marshall, Galecto’s Chief Medical Officer, told Euro­Biotech. “One galectin-3 inhibitor will target ocu-

lar fibrosis and another non-alcoholic steatohepatitis (NASH).” While other developers of galectin-3 inhibitors, namely US-based Galectin Therapeutics (NASDAQ: GALT), hitched their horses to the NASH bandwagon, Galecto Biotech pushed forward with work in IPF. Galecto believes its drypowder formulation can treat the fibrotic disease directly in the lungs. By avoiding systemic exposure, the eminent risks of off-target effects of TD139 are reduced. Galectin-3 is a protein made predominantly in immune cells in the body, which binds to specific glycoproteins. By binding them, galectin-3 has many effects, such as modulating the interaction of cells and receptors, the immune response, the behavior of cancer cells, inflammation, and scarring of organs. Galecto was founded in 2011, building on research from the University of Lund, Sweden, and the UniL versity of Edinburgh, UK.

Picture: Stora Enso

Recyclable tag

Antiinfectives  British-Swedish pharma company AstraZeneca plc (AZ) has sold US rights to its off-patent blockbuster respiratory syncytial virus (RSV) treatment Synagis (palivizumab) and a 50% share on future earnings of its Phase II RSV-prophylactic follow-on antibody MEDI8897 to Swedish Orphan Biovitrum AB (SOBI, STO:SOBI). RSV cause serious lower respiratory tract infections (LRTI). While MEDI8897 will continue to be co-developed by AZ and Sanofi under a 2017 deal for the prevention of LRTI caused by RSV in a larger patient population, SOBI will participate in AstraZeneca’s 50% share of US profits and losses. Between AZ and Sanofi, which is responsible for commercialisation, all costs and profits are shared equally. Under the deal with AZ, SOBI will pay US$1.5bn upfront, US$0.5bn thereof in newly issued SOBI shares. Following completion of the acquisition, AZ will

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Opening up new frontiers Str ategy   Novo Nordisk A/S (NOVOB:DC) revealed its plans to restructure its entire Research & Development (R&D) organisation in early autumn. Consequently, the company will lay off 400 employees from R&D roles in Denmark and China. Remaining employees will face new challenges as the Danish company plans to shuffle positions and projects meaning relocations within the organization. The plan also foresees the creation of a new business development unit in Cambridge (US) and four new “bio­tech-like” research centers. These units – based in Denmark (2x), the US, and the UK – will pursue novel treatment modalities and platform technologies and will operate as satellites of Novo Nordisk’s central R&D function. The UK unit, the Novo Nordisk Research Centre Oxford (NNRCO), is already open. Here, 100 researchers will focus on type 2 diabetes and cardiometa­bolic conditions L that accompany the disease.

Picture: Bioescalator, University of Oxford

KGaA (Germany) and Pfizer Inc. (US) have several combination trials with their jointly developed human anti-programmed death ligand-1 (PD-L1) antibody avelumab running. And they keep on adding new ones. In November, a multi-indication Phase Ib/ II clinical trial in patients with advanced head and neck cancer and gastric adenocarcinoma with ilixadencel as the second therapy was announced. The cell therapy is developed by Immunicum AB from Gothenburg. Immunicum’s approach is based on allogeneic dendritic cells that get activated by a proprietary process before the cells are injected directly into the tumour to teach the patient’s immune system how to attack the cancer. Ilixadencel, the lead programme, is currently in Phase II where it is tested in combination with a with tyrosine kinase inhibitor.

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News Hurdle cleared   Drug delivery technology developer LIDDS AB (FN:LIDDS) received the Swedish Medical Product Agency’s approval to begin its second clinical project: LIDDS will test a combination of its controlled and sustained drug release system Nanozolid with docetaxel in solid tumours. The ongoing clinical project is a Phase IIb study in prostate cancer.

Last tranche Novo Nordisk will invest about £115m at the NNRCO over a period of 10 years. Like the start-up incubator Bioescalator, the NNRCO is situated in the brand new Innovation Building.

Big pharma tests Immunicum Immunooncology  Merck

Northern EUROPE

Immunicum will be responsible for conducting the new study with avelumab and continues to retain all commercial rights to ilixadencel. In late September, Immunicum’s stock took off without apparent reason. Nasdaq Stockholm decided to halt trading and Immunicum issued a statement that rumours about “negotiations for a new development collaboration with a global pharmaceutical company” are true. After clarifying that no payments to Immunicum are expected, the stock price cooled off – and did not invigorate when the successfully negotiated deal was announced a couple of weeks later. Klas Palin, analyst at Swedish equity research company Redeye, considers the agreement as an “important external vali­dation of ilixadencel.” Another potential upside is the possibility of improved L access to patients, Palin believes.

  Molecular diagnostics company Mobidiag Ltd. received the final €4m tranche of a €15m sum secured in June 2016 from the European Investment Bank. Mobidiag says the funding so far helped to launch and commercialise its Novodiag system and two assays for detection of gastrointestinal infections.

From waste to plane   Norway is taking action to require the use of renewable aviation fuel. In October, the country’s Ministry of Climate and Environment announced it will require aviation fuel to contain at least 0.5% advanced biofuel starting in 2020.

Hassle-free vaccines   Sol-gel encapsulation expert Delsitech Ltd. from Turku received a grant from the from the Bill & Melinda Gates Foundation in October. Using its proprietary biodegradable silica-based technology Delsitech will start to develop formulations of viral vaccines that allow long-term storage at just 4 °C instead of -80 °C.

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Reviving immunometabolics

Microbiome   Belgian microbiome specialist A-Mansia Biotech S.A. has extended its €13m Series A financing round from April by an additional €5m from venture capital firm Innovation Industries. The company said it will use the proceeds – from the investor consortium around Seventure Partners, SRIW, Nivelinvest, the Walloon Region, and business angels – to progress its pipeline based on the gut bacterium Akkermansia muciniphila. After company founders, Willem M. de Vos (Wageningen University) and Patrice D. Cani (UCL), proved in mice that daily administration of A. muciniphila improved metabolic disorders and inflammatory conditions, the safety of a nutritional supplement made from the gatekeeper to the intestinal barrier is now being investigated in an ongoing Phase I study. Subjects with insulin resistance, hyperglycemia, high blood cholesterol, and visceral fat accumulation were characterized to carry lower amounts of A. muciniphila in the gut. The company aims to show that its supplement helps to maintain health and immunity, normal glycaemia, normal blood cholesterol levels, and avoid excessive weight gain. The assets from the financing will also be used to identify active compounds from A. muciniphila. Microbiomics, however, is still in its infancy. Last October, a US team reported that high abundance of A. municiphila triggered higher levels of proinflammatory T cells and a reduced level of IL-10 secreting regulatory T cells leading to a higher risk to develop multiple sclerosis (European Biotechnology, Winter 2017). L

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Modulation of AMPK, mTOR, and HIF-1amediated signalling has been linked to a shift in the ratio of effector T cells to regulatory T cells and tumour-promoting (M2) and tumour-attacking (M1) macrophages. The company has experienced management and prominent co-founders. CEO Neil Weir came in from UCB SA. Sitryx cofounders include Luke O’Neill from Trinity College Dublin; Jonathan Powell from Johns Hopkins University; Jeff Rathmell from Vanderbilt University; and Michael Rosenblum from UCLA San Francisco. L

Closing in on cancer Licensing   British drug major AstraZeneca plc (London) has filled up its immunoncology assets through an €5bn extension of its 2015 partnership with French Innate Pharma SA (Marseille). At the end of October, AstraZeneca (AZ) exercised its option to licence Innate’s NKG2A-targeting T and NK cell checkpoint inhibitor monalizumab for US$170m upfron. The antibody was originally developed by Novo Nordisk. Currently, monalizumab is in Phase II testing for diverse solid cancers as a monotherapy and in dose escalation Phase I testing in combination with AZ’s PD-L1 checkpoint inhibitor durvalumab in end-stage therapy-resistant patients with colorectal cancer. In exchange, Innate Pharma acquired Eu-

ropean commercialisation rights to AZ’s recently approved hairy leukemia antibody-drug conjugate moxetumomab pasudotox-tdfk for US$50m, which links an CD22 antibody fragment to a domain of Pseudomonas exotoxin-A (PE38). Under the terms of the new agreement, AZ also secured new licence options towards up to five preclinical pipeline candidates from Innate’ Pharma. One of which is IPH5201, which targets the membrane bound enzyme ENTPD1 on regulatory T cells, thereby creating an immunosuppressive tumour microenvironment. Milestones for all programmes that might be approved in the future sum up to US$4.925m plus royalties. AZ also bought a 9.8% stake in Innate Pharma. L

Monalizumab (blue) prevents interaction with HLA-E molecules and boosted NK cells and CD8 T cells anti-tumour activity, compared to PD-L1 monotherapy, in mice.

Picture: Innate Pharmaceuticals SA


Physiology   Otto Warburg was the first who proposed to attack cancer through its altered energy metabolism. In October, Oxford-based immunoncology player Sitryx Therapeutics Ltd., a spin-out of GlaxoSmithKline’s Immunology Network, followed suit, bagging $30m from SV Health Investors, Sofinnova Partners, Longwood Fund, and GSK plc. Sitryx Therapeutics has licenced six programmes from GSK in immunometabolics, an approach aimed to break T cell anergy in the microenvironment of solid tumours.

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European Biotechnology | Winter Edition | Vol. 17 | 2018



News Blow for cell therapy

Keeping your gut clean R&D  French Enterome SA has added a licence agreement with Takeda to its deal portfolio, projecting possible payments of US$640m. In October, Japanese drug giant Takeda said it will pay US$50 upfront for a global licence of EB8018, Enterome’s lead bacterial inflammation blocker, targeting Crohn’s disease, that might have “the potential to expand to other gastrointestinal (GI) disorders and liver diseases.” Takeda also assured it will “make a future equity investment in the company” but did not disclose exact figures. Enterome and Takeda will co-develop EB8018 under the joint agreement and, if approved, the product will be co-promoted in the US under a profit/cost sharing structure. Takeda will receive an exclusive license to commercialise EB8018

outside of the US, and Enterome will be eligible to receive royalties on net sales generated in these territories. EB8018 is a gut-restricted small molecule drug that inhibits FimH-mediated inflammation, which is often caused by invasive E. coli bacteria, without disrupting the local microbiome. EB8018 was originally discovered by Vertex Pharmaceuticals, Inc. Currently, the drug is being tested in a Phase Ib dose finding study. The global agreement is the second collaboration between Enterome and Takeda. In 2016, the two companies entered a strategic drug discovery collaboration focused on microbiome targets across multiple GI disorders, including inflammatory bowel disease and motilL ity disorders.


Industry incubator R&D   Sanofi and Evotec have launched a drug discovery alliance aimed at exploiting academic early stage drug discoveries across multiple therapeutic areas. Under the programme, dubbed Lab 31, Sanofi will provide funds that will be used to validate and optimise drug candidates from academic groups on Evo-

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tec’s industrial screening and drug discovery platforms. Over the next three years, the companies will focus on the generation and advancement of small molecule programmes through lead optimisation. For each project, Sanofi has the option to assume development responsibility upon the achievement of milestone criteria. L

Two Spear T cell therapies developed by Adaptimmune Therapeutics have failed to show hints to efficacy in ongoing clinical Phase I dose escalation trials, the company reported at the ESMO meeting in Munich. In 11 patients enrolled with melanoma, lung cancer, or head and neck cancer, T cells equipped with an engineered T cell receptor targeting melanomaassociated testis antigen A10 (MAGEA10) didn’t show any response. The same was true for MAGEA4 T cells administrated to six women with ovarian cancer. The study is designed to end in 2020. The MAGEA4 study is designed to end in Q4/2019.

Yes or no? Angle plc for the first time reported successful harvest of fetal cells from the peripheral blood of pregnant women for the detection of fetal abnormalities.

Biobank update The UK Biobank has reported over 14,000 deaths, 79,000 participants with cancer diagnoses, and 400,000 participants with at least one hospital admission. Correlation analyses of quality-controlled SNP markers and whole genome data from 488,377 Britons are expected to deliver hints to genetic risk factors of diseases. Researchers announced that they are in the process of completing imaging data and add clinical data to the medical resource. The medical output of the project is expected to show if Big Data analyses can have the invoked impact towards improving medicaments.

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Centr al EUROPE

European Biotechnology | Winter Edition | Vol. 17 | 2018

Epigenetics comeback

Drug development  On its way to becoming a fully integrated bio­ pharma company, German Morphosys AG made big strides this autumn. Extending an alliance with Danish dermatology company Leo Pharma A/S to develop new peptide-derived therapeutics, the German biologics specialist now owns an exclusive option to secure worldwide rights to any drugs arising from the collaboration in the field of oncology. In the process of setting up structures for marketing drugs, Morphosys’ focus is on cancer. This also became clear a few weeks later when the company announced its second strategic partnership with Shanghai-based I-Mab Bio­pharma. Similar to a 2017 deal around anti-CD38 antibody MOR202, the regional licensing deal for cancer candidate MOR210 hands over development and commercialization rights to I-Mab in China, Hong Kong, Macau, Taiwan and South Korea. Morphosys will receive US$3.5m upfront, and up to US$101.5m in milestones and single-digit royalties on net sales of the so far preclinical anti-C5aR antibody. More importantly, I-Mab will perform and fund all global development activities for MOR210, including clinical trials in China and the U.S., towards clinical proofof-concept in oncology – and Morphosys will retain MOR210 rights in the rest of the world. Another anti-C5aR antibody, developed by Innate Pharma (France) and AstraZeneca (UK) to treat selected solid tumours, is currently being evaluated in a L Phase I/II study.

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EPZM) in November. Epi­z yme will receive an upfront payment of US$15m and an additional US$5m in research funding in 2019. Further payments for research, development, and other milestones could add up to US$280m. The partners plan to set up two programmes: one with a small molecule drug targeting a certain helicase and another a certain histone acetyltransferase (HAT). The targets identified by Epi­ zyme are enzymes within the helicase and HAT families that when dysregulated have been linked to the development of cancers that currently lack therapeutic options. Focussing on a personalized medicine approach, Boehringer points out that both targets have stratification biomarkers that allow the easy identification of patients with defined mutations. Boehringer seems to be diversifying its cancer drug candidate portfolio of checkpoint inhibitors and immunotherapy modulators. Another indicator is the September acquisition of Austrian virotherapy specialist Viratherapeutics. L

In search for antigens Imaging  Matching available immunotherapies with patients who benefit the most is the aim of a new research project dubbed Immunoquant. Funded by the German federal government, the scientists want to develop more sensitive technologies for detecting tumour antigens on cells from a patient. As seen in the illustration, with dSTORM super-resolution microscopy tumour-associated antigens on primary tumour L cells can be visualized and quantified.

Picture: AG Markus Sauer/Julius-Maximilians-Universität Würzburg

Coming of age

Oncology  “It is even clearer today that to tackle the key oncogenic drivers of cancer you need to be drug hunting at both the genetic and epigenetic level,” says Darryl McConnell, Boehringer Ingelheim Research Site Head Austria. The German pharma company wants to develop new medicines against lung and other solid tumour cancers. To do so, it is betting on two novel epigenetic targets, which have been historically viewed as undruggable. “We started our epigenetics drug discovery efforts in 2011 with collaborations with the Institute for Molecular Pathology in Vienna and the Structural Genomics Consortium. Now, we are excited to further strengthen our epigenetics initiative with Epizyme, a perfect partner with their track record in pioneering new epi­genetic protein families and our shared passion for drugging so-called undruggable targets,” McConell told EuroBiotech. In a deal worth US$300m (plus tiered royalties), Boeh­ringer started the collaboration with US-based Epizyme Inc. (Nasdaq:

06.12.2018 15:02:50 Uhr

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European Biotechnology | Winter Edition | Vol. 17 | 2018


Finding plastics-making microbes News Bioeconomy A German fermentation technology for converting lignocellulosic residues into fuel or chemicals has attracted the interest of Chinese investors that started to pour €2bn into the scaleup of the process. Scoring that success in early summer, Blucon Biotech GmbH is on track to optimise the method by lev-

eraging a collaboration with fellow German microbe expert Brain AG announced this autumn. Scanning its archives, Brain will identify and develop special microbial production strains for Blucon. The first aim is to bring down production costs of the bioplastic polylactic acid (PLA) so it can compete with fossil fuel-based plastics. L

Plastic pellets on display

Picture: Adobe Stock/Diak

Delayed, but on track Cancer Vaccines  Therapeutic cancer vaccine developer Amal Therapeutics SA celebrated the second closing of its series B financing round in November. Adding €21.2m (CHF24.2m), the final result stands at just over €29m (CHF33.2m). All existing investors – Boeh­r inger Ingelheim Venture Fund (BIVF), BioMedPartners and Helsinn Investment Fund, VI Partners, High-Tech Gründerfonds, and Schroder Adveq – participated in the follow-up round to a €8m round closed in September 2017. Amal (which means “hope“ in Arabian) said it will use the proceeds to start Phase I testing with its lead recombinant protein-based vaccine programme next summer – one year later than envisioned at the time of its 2016 series A round. The proof-of-concept of the technology will be carried out in colo­rectal cancer. Last year, Amal exchanged its previous lead candidate, ATP124, for a new one, ATP128. “While performing some validation experiments, we decided to change one antigen in the multi-antigenic domain from the original ATP124 asset, thus generating ATP128,” a spokesperson told EuroBiotech. The proprietary self-adju-

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vanting peptide/protein-based vaccination technology platform generates fusion molecules. More specifically, the platform incorporates three components: CPP, a novel cell-penetrating peptide for antigen delivery; Mad, a multi-antigenic domain delivering the chimeric cargo for an multiantigenic immune response; and TLRag, a TLR peptide-agonist for self-adjuvanticity. Frank Kalkbrenner, BIVF’s representative on Amal’s Board, thinks of ATP128 as a “potentially game-changing drug in the immunotherapy field.” The company will use its Kisima cancer antigen delivery technology to add further therapeutic vaccine candidates to its pipeline – for instance, a novel candidate for use in the prevention and treatment of glio­ blastoma that has recently been filed for patent protection. Usually, protein vaccines primarily activate helper T cells, because the antigens are mostly presented on MHC class II molecules of antigen presenting cells. The University of Geneva spin-out’s technology also improves MHC class I molecule presentation using a novel pathway relying on cell penetrating protein domains to bring the recomL binant proteins inside cells.

Autumn stumbling  Affimed (NASDAQ:AFMD) got off a rollercoaster autumn lightly. After a transformative deal with Roche group’s Genentech division this summer, the German biotech (with a Dutch NV) experienced a blow when its blood cancer candidate AFM11 was put on clinical hold after a death and two cases of severe neurotoxicity. Affimed’s stock dropped by 30%. However, by early November the dust had settled and the stock price was back on track.

Tackling the AMR issue   In November, Swiss- based holding Roivant Sciences received US$200m from new investors, raising the valuation of the drug deve­loper to about US$7bn. The tightly filled bag became a little lighter a week later when Roivant spent US$10m upfront for rights to SAL200, containing bacteriophage-derived endolysin as its active pharmaceutical ingredient. The SAL200 deal with Intron Bio from South Korea is worth up to US$670m. The technology could solve the issue of antimicrobial resistance in bacterial pathogens. A Phase II clinical trial will be initiated in 2019.

Unbar the peanut bar   Industry giant Nestlé SA believes in the allergy immunotherapy concept brought forward by its partner Aimmune Therapeutics Inc. (USA). Investing another US$98m, Nestlé Health Science now owns 19% of Aimmune. Despite mixed data, the oral drug AR101 against peanut allergy could get FDA approval next year.

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Newron bags €40m EIB loan

Lawsuit   Boehringer Ingelheims‘ Nolotil (metamizole) is one of the most widely distributed painkillers worldwide, but it can lead to a dangerous and unpredictable side effect, known as agranulocytosis, that lowers the patient’s white cell count and can even lead to death. Following reports, released two months ago, of British citizens who died after being prescribed the medication in Spain, the Spanish health authority “Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)” has intervened and has issued guidelines to hospitals, medical clinics, and pharmacies effectively prohibiting the sale or prescription of Nolotil to tourists. According to Spanish newspaper El Pais, AEMPS’ note said: “The AEMPS has reviewed the situation in Spain due to recent reports of agranulocytosis filed with the Spanish Pharmaceutical Monitoring System, particularly in patients of British origin.” There are already more than 200 victim reports and the number is increasing daily. To date, the estimated personal and material damages is already at more than €500m that will be taken into account in a lawsuit against manufacturer Boehringer Ingelheim. Despite being a very popular pain medication in Spain and Latin America, Nolotil is not licensed for use in the UK, the Republic of Ireland, the US, or Sweden, among other countries. L

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Evenamide as a symptomatic add-on therapy to clozapine for the treatment of schizophrenia. Newron plans to directly market orphan drugs emerging from its clinical pipeline. EIB financing is intended to boost Newron’s R&D activities and will primarily be used to support the company’s pivotal and post approval stage development programmes. The Italian neurology specialist company has a strong pipeline of treatments for rare disease patients at various stages of clinical development, including Sarizotan for patients with Rett syndrome and ralfinamide for patients with specific rare pain indications. Newron is also developing Evenamide as the potential first add-on therapy for the treatment of patients with positive symptoms of schizophrenia. L

Tumour malignancy supported Epigenetics   In November, researchers at IRB Barcelona reported that tumours may become more aggressive following treatment with drugs that inhibit epigenetic factors. In Nature Cell Biology, a team headed by Salvador Aznar Benitah and Fran Supek reported that genetic inactivation of histone H3 lysine 9 (H3K9) methyltransferase G9a altered the pattern and number of mutations that tumours accumulate. In mice with squamous skin carcinoma, inhibition of the methyltransferase in the epidermis triggered large genetic alterations, such as duplications and

the loss of different regions of DNA, stopping tumour growth initially. “This finding would make you think that epigenetic factors are good therapeutic targets. But the genomic instability also brought about the appearance of mutated tumour cells, which eventually developed into highly aggressive tumours,” said Alexandra Avgustinova, first author of the study. Following a latency period, tumours in the knock-out mice showed an expanded cancer progenitor pool, pronounced genomic instability, and frequent loss-of-function p53 mutations compared to wild-type counterparts. The authors warn that special care should be taken regarding chromatin modifying drugs. “We are not saying that this is going to happen in every case, but it is something that needs to be studied in greater depth before deciding whether drugs targeting epigenetic factors should be used in clinical practice or not,” said Benitah, who heads the Stem Cell and Cancer Laboratory at IRB Barcelona. L

Picture: Alexandra Avgustinova, IRB Barcelona.

No Nolotil for tourists

Investment   Newron Pharmaceuticals has announced that it has signed a financing agreement with the European Investment Bank (EIB), which will allow the company to borrow up to €40m over the coming years to support the development of the company’s latestage pipeline. The CNS drug developer’s share price has been on a downturn for months. For Newron, key pipeline inflection points loom in 2019. The company’s product safinamide is the first New Chemical Entity in a decade approved in Europe and the U.S. for the treatment of Parkinson’s disease (PD). Newron has two advanced product candidates in late-stage clinical development: Sarizotan for the treatment of respiratory disturbances in Rett syndrome, which is evaluated in the ongoing potentially pivotal STARS study, and

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European Biotechnology | Winter Edition | Vol. 17 | 2018



News New ADC presented

Tapping a billion-euro market Cannabis  Last year, Greece legalised the use of medical cannabis and also lifted the ban on growing and producing it. In an attempt to tap into the market, worth billions, the Economy and Development Ministry at the end of November issued the first two licences to private companies allowing the growth of medical cannabis. “There is huge interest, mainly from Canada and Israel … some of them (potential investors) are huge,“ said Deputy Economy Minister Stergios Pitsiorlas during a press conferece. It involves a €9.5m investment in Larissa, central Greece, and a €12.5m investment in Corinth, in the Peloponnese.

Up to 12 more licenses could be granted by the end of the year, creating about 770 news jobs and representing a total investment of €185m to €200m. Most of the investment is expected to come from Canada and Israel. Under Greece’s licensing system, medicinal cannabis products would be available on prescription from chemists. Nevertheless, Health Minister Andreas Xanthos explained that it would not be subsidised through state health insurance schemes. Several countries, including Britain, Germany, Italy and Denmark, already allow the prescription of medicinal cannabis (see cover story on page 12). L

Bio-on partners with Unilever

Picture: Pixabay

Environmental Impact  Personal

care giant Unilever and Bio-on have partnered to develop personal care products that boast a smaller – or even nonexistent – environmental impact. The partnership will leverage Bio-on’s technology for natural, biodegradable microplastics and Unilever’s vast brand presence, which includes products such as Dove, Glysolid, and Sunsilk. “For Unilever, developing a partnership with such an excellent Italian company as Bio-on is an important step towards the goals we have set ourselves with the Unilever Sustainable Living Plan, primarily to halve the environmental impact of our products by 2030,” says Fulvio Guarneri, Chairman and CEO of Unilever Italia. Bio-on will work with Unilever through two new companies, which will focus 100% on exploiting exclusive technologies to develop, pro-

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duce and supply personal care products. “Research into innovative products and cutting-edge formulations that respect the environment and people is now a priority in the personal care sector,” explains Marco Astorri, Chairman and CEO of Bio-on. “We are very pleased to work alongside such a major player as Unilever, with which we will have the great opportunity to introduce real sustainable innovation whilst reaching an increasingly broad consumer base.” Bio-on S.p.A has developed an exclusive process for the production of a family of polymers called PHAs (polyhydroxyalkanoates) from agricultural waste, including molasses and sugar cane and sugar beet syrups. It has been classified as 100% natural and completely biodegradable from United States Department of Agriculture in 2015. L

  At the World ADC Congress in San Diego Spanish PharmaMar SA presented the new antibody drug conjugate (ADC) MI180021, the result of linking trastuzumab with the marine molecule PM160057. This ADC has shown potent and highly selective activity in tumour cells that overexpress HER2, as found in certain breast, gastric and pancreas cancers, among others. PM160057 belongs to a new family of molecules of marine origin that kill tumour cells by binding to DNA. This family of new chemical structures with novel mechanisms of action offer the opportunity to develop a new generation of ADCs, also called “magic bullets.” This research has already led to the licensing of the first family of active molecules to Seattle Genetics, world leader in ADCs, for which PharmaMar received an initial payment of $5m.

Boosting Circular Economy   At the end of November, bioplastics manufacturer Novamont and water utility company Gruppo CAP announced their collaboration to promote the circular economy in Italy. They have identified a series of potential projects at which their joint research efforts will be targeted. The first of which will address the ecodesign of microplastics for the cosmetics industry and the production of raw materials from wastewater. It follows from the Gruppo CAP’s current work at its plants on the recovery and enhancement of products and by-products derived from sewage sludge, such as PHA materials.

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Biosimilar repurposing

Nutrigenomics  Being established ten years ago obviously did not impede Geneplanet’s chances of succeeding at this year’s Central European Start-up Awards. In October in Warsaw (Poland), the Lubljana-based genetic testing company was selected as the winner in the biotech segment. Geneplanet’s standard Nutrifit product contains 29 different DNA tests from the field of nutrition, metabolic properties, sport, and health. Nutrifit premium contains 58. However, the company’s pivotal event this year was likely another one: This summer Geneplanet d.o.o. sealed a €10m equity deal with Zurich-based JF Investments AG. The funds will be used to set up Health Intelligence – a platform integra­ting biological data with information from smart health devices and wearables to provide recommendations based on objective needs. 

toid arthritis. But they are also frequently used off-label to treat relapsing-remitting MS, and emerging evidence suggests that patients with progressive MS may also benefit from treatment with rituximab. That’s why Mabion is interested in positioning MabionCD20 in MS, pursuing both a monotherapy and a combination therapy approach. Although Roche has its very own MS drug, ocrelizumab, Mabion believes it can carve out some market share. CEO Artur Chabowski assumes that the optimisation of manufacturing processes at the new plant will enable Mabion to market a therapy which would be cheaper than the current drugs used in the treatment of both forms of MS: “This is currently the most important project in our pipeline.” The outline for the clinical programme is expected to L be published by year-end.

At Mabion’s headquarters close to the Polish city of Łódz

Cheap diamond Brain change

Mapping Poles

Diagnostics  Czech scientists have deve­loped a novel production method for irradiated nanodiamonds and other nano­ materials suitable for use in highly sensitive diagnostics of diseases, including cancer. Current irradiation techniques can’t be scaled-up easily. The new method of nanocrystal preparation is much cheaper, the scientists claim (Nature Communications, doi: 10.1038/s41467-018-06789-8). 

Genomics  A consortium made up of European Centre for Bioinformatics and Genomics (ECBiG) and the company Centrum Badań DNA (both from Poznań), will start recruiting Poles for the most ambitious genetic project in Poland’s history in December. They will collect whole-genome data from about 5,000 people, including representatives of all ethnic groups, and create a genomic map of Poland. 

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Cancer Research  Kraków’s Jagiellonian University began a partnership with the Roswell Park Comprehensive Cancer Center in Buffalo (US). The academic collaboration will see the centers exchanging staff, students, and scientific resources to jointly undertake basic, translational, and clinical research. For instance, the organizations plan to develop innovative clinical trial designs for cancer therapies. 

Picture: Mabion

Beyond genes

Multiple Sclerosis   After successfully raking in PLN175m (€40.8m) this spring, Polish biopharma Mabion SA is on track to expand its production capacity in Konstantynów Łódzki, a town close to Łódz. In November, Mabion received the local authorities’ green light to start construction work. After a strategy change in 2017, the bio­similars company started to enter the field of innovative medicines. But that does not necessarily mean they intend to buy or to develop new molecules. Instead, the Polish biotech wants to establish its lead asset, clinical-stage biosimilar MabionCD20, as a treatment for multiple sclerosis (MS). Originator drug rituximab, sold by Swiss pharma group Roche as Mabthera, and its biosimilar versions are approved as treatments for diffuse large B-cell lymphoma as well as for rheuma-

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Money maker

Pictures: Roche left, above), REDX (left), Rentschler Biopharma (middle, ablove), Aldevron (middle(, Neurimmune (right, abkove), Puretech (reight

parexel  Parexel International Corporation has appointed Greg Rush as new Executive Vice President and Chief Finan cial O f f icer.Mr. Rush joins Parexel from Syneos Health, Inc. (former INC Re search Holdings, Inc.) where he was Executive VP and CFO since 2013. Previously, he act- Greg Rush e d as S enior VP and CFO of Tekelec, which was acquired by Oracle. He also held positions of increasing responsibility at Siebel Systems, Quintiles Transnational Holdings, PricewaterhouseCoopers and Ernst & Young. He is a Certified Public Accountant and has a Bachelor of Science in Business Administration and a Master of Accounting from the University of North Carolina. L

Legalisator Novartis AG The Swiss pharma major named Klaus Moosmayer as Chief Ethics Risk and Compliance Officer. Moosmaye r will t ake over from Shannon Thyme Klinger, who was appointed Group General Counsel, in December. Since 2014, Moosmayer has been the Chief Compliance OfKlaus Moosmayer ficer at Siemens. Previously, he served for four years as the Chief Counsel Compliance at the medtech giant, where he helped building up Siemens’ new compliance system. Prior to joining Siemens, Dr. Moosmayer practiced Law in Germany, specializing in white collar crime, Litigation, and Business Law. He holds a Doctor of Jurispru-

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dence (J.D) degree from Freiburg University. Since 2013, he has been Chair of the Anti-Corruption Taskforce of the Business and Industry Advisory Committee at the Organization for Economic Co-operation and Development (OECD).  L

Cancer killer Zelluna Immunotherapies AS  The Oslo-based autologous cell therapy player appointed Dr. Namir Hassan as new Chief Scientific Officer (CSO). Hassan joins Zelluna from Immunocore Ltd where he managed the company’s biology, preclinical and biomarker units targeting cancer. Dr. Hassan also worked in dis cover y re search at Glaxo SmithKline Plc and at the Ludwig Institute for Cancer Research. He received a Doctor of Philosophy from the University of Oxford in T cell biology.  L Namiur Hassan

mAB advisor Sphere Fluidics   Automated single cell analysis specialist Sphere Fluidics announced in mid-August that Tris Vaughan, Vice President R&D Antibody Discovery and Protein Engineering for MedImmune, has joined its scientific advisory board (SAB). Dr Vaughan has held several key roles in AstraZeneca’s US-based biologics arm, where he currently leads a team of 120 scientists. Prior to joining MedImmune, he was a postdoctoral fellow at the University of Toronto and a graduate of the Univer sit y of Le e ds Genetics Department.  L Tris Vaughan



CAR-T executor Cellectis Sa  The US arm of the French specialist for gene-edited allogeneic CAR T-cells has hired Stefan Scherer from Novartis Pharma Corp as new Senior Vice President Clinical Development and Deputy Chief Medical Officer. The board-certified physician brings two decades of bio-pharma business experience to Cellectis. Prior to Novartis, Scherer served as CMO at Swiss Biocartis SA in Switzerland. Previously, he held key roles at Roche/ Genentech. L Stefan Scherer

New boss Cell Medica plc   Chimeric antigen receptor (CAR)-T cell therapy expert Chris Nowers has joined British Cell Medica as new Chief Executive Officer and Executive Director from Kite Pharma. At Kite, which was acquired by Gilead Science for US$12bn shortly before US market authorisation of Yescarta last year, Nowers led the European, Middle East and African business expansion. Prior to his role at Kite, he has had a career spanning more than 25 years in the bio­ Chris Nowers pharmacutical industry. He has held a number of senior leadership roles that included CEO of Avantogen Oncology, General Management roles at Amgen, and senior global and regional commercial leadership roles at Bristol-Myers Squibb (BMS).According to Nowers, “Cell Medica has an exciting array of technologies that will help unlock the potential of personalised cellular immunotherapies for both blood cancers and solid tumours.” L

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Race against time Bioeconomy  After a quick start out the gates in 2012, the European Commission proceeded to

carry out a lengthy review of its bioeconomy strategy – slamming the brakes on investor interest in EU bio­techs developing solutions for the move to a low-carbon, zero-waste economy. Following several reports that suggested the bloc will miss internationally agreed sustainability targets, the EC now wants to speed up the switch to biobased production. Industry stakeholders presented a huge range of promising technologies at the EFIB, but are still awaiting the go-ahead.

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European Biotechnology | Winter Edition | Vol. 17 | 2018


n official statements, policymakers have left no doubt that the planet is in a bad state and that it’s time for action. “The consequences of climate change are already perceptible around the world, and they are existential,“ stressed German President Frank-Walter Steinmeier back in October, two months before December’s COP24 climate conference in Katowice. There the aim is to take concrete measures to limit global warming as close as possible to 1.5º C above pre-industrial levels by 2030 in a bid to avoid disastrous droughts, storms, migration, hunger, rising sea levels, ocean acid­ification, spread of mosquito-borne diseases and loss of biodiversity In speeches ten years ago, German poli­ ticians promised to reduce annual emissions of CO2 and other long-lived greenhouse gases by 40% by 2020 compared to levels of CO2 equivalents (CO2eq) measured in 1990. So far the country has cut those emissions by around 28%. Compared to other EU member states and the rest of the world, that’s quite a bit.

Pictures: WWF (left), Global Bioeconimy Summit/BIOCOM AG (right)

Five minutes to midnight According to a special report issued by the Intergovernmental Panel on Climate Change (IPCC), “it’s high time to act, because damage is accumulative and not reversible.” It warns that the projected rise from currently 1° C to 1.5° C will occur ten years earlier than previously projected. With reports of a 2017 record high of 53.5 billion tonnes (gigatonnes, Gt) of CO2 dispersed into the atmosphere, the panel stresses the situation demands drastic and rapid counteractions. To hit the under-1.5° target, says the IPCC, we now have to achieve a decrease of 45% or more in CO2 levels compared to 1990 by 2030, and zero emissions by 2050. “It’s no longer about the what but about the how. The scientific verdict is clear: global emissions must be halved by 2030 if we want to stand a chance of remaining well below 2° C,” comments Johan Rockström, the designated director of the Potsdam Institute for Climate Impact Research. However, a research team headed by Laure Resplandy reported in late October that ocean heat uptake is actually

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over 60% higher than the IPCC’s highest estimates. This suggests our planet is more sensitive to emissions caused by the combustion of fossil resources than previously thought (Nature, doi: s41586018-0651-8). Those results were backed up by a study that found Greenland’s ice sheet is melting faster than at any point in the last 350 years. “Melt increases nonlinearly with rising temperatures,” writes lead author Luke Trusel in Nature (doi: s41586-018-0752-4). Other authors predict that sea warming above the 1.5° C threshold will reduce Polar and Atlantic cod populations by up to 90%.

The solution? Bioeconomy! What does this mean in concrete terms? Even if consumers across Europe would reduce their individual CO2 emissions by 50% by reducing airline travel, meat consumption, car travel, etc., that would lower annual emissions by just 2.15 Gt. As the IPCC projects a 42–58 Gt cut in emissions is necessary to limit global warming to 1.5°, completely new paths to carbon-neutral production in indus-

Ian Goldin  Director Oxford Martin Programme on Technological and Economic Change

? !

Can we have both sustainability and an economics of scale?

 o. We need to be more conN cerned about changing our consumption. Otherwise we will destroy our planet.


try and agriculture are required. In 2012, the EC took the first step towards this kind of new production paradigm when it launched its Bio­economy Strategy. Since then, biotech SMEs have developed a huge array of technologies to reduce CO2 emissions through enzymatic conversion of plants and other renewable resources into chemicals, plastics or biofuels. The bio-based processes complement non-biological solutions such as solar cells that effectively produce sustainable energy. Besides climate change, sustainable biotechnologies are also addressing other global threats, including marine plastic, new protein sources for a rapidly growing population, and crops with features tailor­ed to climate change (see table, p. 86) At the European Forum for Industrial Bio­technology and Bioeconomy (EFIB) in Toulouse (30 Sept. –2 Oct.), which is the most important meeting for the emerging new industry in Europe, the CEO of the UN’s Global Compact Lise Kingo reiterated that its high time to replace the unsustainable way we live, move, produce, consume and throw away by switching to a circular bioeconomy. “We are facing a future in which there is more plastic garbage than fish in our oceans. More than eight million tonnes of plastic waste are added each year. They damage more than 400 species, and are found in the stomachs of sea birds, whales and fish,“ she said, adding that “around three billion people source their protein from the sea (so) we have to give up our usual way of doing business immediately!“ She also told 500 industry representatives, policymakers and investors at the event that “we can turn global threats into business opportunities” (see Fig. 1, p. 87).

Biotech’s massive potential Some of the biotechnologies showcase d by SMEs and chemistr y giants at the EFIB impressively demonstrated how biotech solutions could offer huge market chances while helping the environ­ment. French-based Carbios SA for example is tackling the growing problem of plastic pollution. To date, an estimated 8.3 billion tonnes of plastic

“We think it’s very important to

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Table 1: European industrial biotech startups in bioeconomy showcased at the EFIB.

Company (Country)

Founded Business


Abolis Biotechnologies


Metabolic engineering of microbes for fine chemicals production from renewable sugars


Algaepro AS


Aquaculture feed additives from microalgae with CO2, N, P captured from industrial processes


Algae Natural Food


CO2-consuming microalgae production process for food, cosmetics, nutraceuticals




Production of highly digestible protein-rich yeast-based feed ingredient from wood




CO2-consuming formate production as feedstock for microbial fine chemical synthesis


BES Europe


Microbial biosensors for online detection of biochemical oxygen demand/toxins




Low CO2-emission aromatics production from biomass or plastics waste/composites




Low CO2-emission microbial production of phosphorylated fine chemicals


Bluegene Technologies


Design of microbes by synbio technology for sustainable conversions into fine chemicals


Cambridge Glycoscience


Sugar substitutes from abundant plant material to reduce sugar content in food products




Proprietary FAST continuous-fermentation process for cost-effective bio-based production




In silico prediction and optimisation of proteins and enzymes for industrial use


Evologic Technologies


Biostimulant seed coating with symbiotic fungus replacing the need for fertiliser


Green Spot Technologies


Fermentation of low carb/fat, high-fibre/protein flour from fruit/vegetable by-products




Sustainable production of bacterial structural colour biomimetics




Process engineering to enable cost-effective biomanufacturing of lipids/biosurfactants




AI-based in silico modeling/optimisation of industrial production strains


Kaffe Bueno


Upcycling of coffee waste into ingredients for the cosmetics/nutraceuticals/food markets


Mosspiration Biotech


Moss-based fragance production




Photobioreactor for microalgae production




Bio-based production of textile dyes




Hemp/flax-based production of nontoxic, non-inflammable, recyclable thermoset resins




Metabolic design of production strains for fine chemicals/food or biopolymer synthesis


waste have entered the oceans – about 90% of that from landfills in Africa, Asia and the Middle East. Carbios, which will begin construction of a demon­s tration plant next year, has invented a technology that could help revolutionise the production and recycling of one of the most common plastics found in our oceans – polyethlene terephthalate (PET). As presented by deputy CEO Martin Stephan at the EFIB, the process is based on engineered cyano­bacterial enzymes that allow the complete depolymerisation of PET to mono­mers. These can then subsequently be used to polymerise 100% native PET from PET waste. In other words,

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Carbios’ process makes the plastic a valuable resource that is worth collecting, even in countries without collection systems. According to Ward Mosmuller, DSM’s EU Affairs Director, this fits with the Commission’s new focus on circular zero-waste end products. Carbios’ technology is set to support the €2bn initiative “Clean Oceans”, which was launched in October by the European Investment Bank (EIB), German Development Bank (KfW) and Agence Française de Developpement (AfD). It’s dedicated to sustainable solutions aimed at reducing marine plastic. An EC proposal to ban the top 10 single­-use plastics that contribute

to marine litter by 2021 – and to improve PET bottle collection – received backing from MEPs in October. Under its rules, producers would have to partially cover the costs of waste management and cleanup, as well as add labels on how to dispose of the packaging properly. If established, the ban might rock the US$375bn plastics packaging market, which provides 15 million jobs and is currently growing at 5% annually. However Michael Carus, founder and Managing Director of consultancy novaInstitute, says the ban would hurt bio­ plastics producers who’ve established alternative production methods for PET

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European Biotechnology | Winter Edition | Vol. 17 | 2018

and other plastics made from plant sugars, which lead to polymers with better CO2 footprints than those currently made by the petro­chemicals industry. Another exhibiting startup company at the EFIB startup village, Germanbased b.fab GmbH (Dortmund), makes platform chemicals through fermentation of formate, providing sustain­ably produced chemical building blocks to the chemical industry. According to CEO Frank Kensy, b.fab uses the feedstock as a central mediator to bind and store CO2 and H2 in liquid form. The process begins with the electro­chemical conversion of (atmospheric) CO2 and H2 (from water) to formate using renewable (solar) energy. Harnessing synthetic bio­logy, b.fab designs specific pathways for formate conversion into value­-added chemicals. Also noteworthy was a pitch by Magellan Life Sciences, which wants to replace sugar with a recombinantly produced protein sweetener from a non-cultivatable African fruit. Replacing carbohydrates with the protein is expected to help prevent common sugar­related diseases like diabetes.

of the Western and Eastern EU member states.“ Climate experts say, however, that because renew­able resources are limited, they would be better used in high-tech applications than lowtech ones such as bioenergy generated through agricultural bio­gas. Furthermore, Burtschler pointed out that the 14 actions emphasise the importance of agriculture, forestry and fisheries in setting up socially accepted local bioeconomies in rural areas. Burtschler’s and several Commissioners’ key message – that setting up a bioeconomy could particularly help farmers, foresters and fishers create a new business focus – led to irritation, however, as it didn’t make it clear that high(bio)tech was the key driver enabling CO2-neutral conversions.

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Back in November, the European Parliament’s Chief Negotiator for Horizon Europe, Christian Ehler, stressed that he doubted “tripling the budget for research into food and natural resources” (to a proposed €10bn)… “should be the priority for a research programme. Is Europe about agricultural subsidies, or would we like to see ourselves eye-to-eye with Chinese ambitions?” he said. Industry stakeholders were also shocked about the Commission’s communication strategy. They had repeatedly called for a clear commitment towards biotech and the bio­logisation of the economy. “We must stop marginalising the bioeconomy as an additional agricultural market,” warned BRAIN AG founder Holger Zinke, who is a member of the German Bioeconomy Council.

Bioeconomy value creation in a range of sectors Jobs


value creation

18 million

€2.3 trillion


A whole lot of lip service Following an internal two-year process of negotiations, discussions and review involving several DGs, the European Commission in October published a 14-point bioeconomy action plan designed to add momentum to its Bio­ economy Strategy. In the process, it partly fused the programme with the Circular Economy Strategy pushed in 2015 by DG Growth. At the EFIB, Deputy Head of DG Research Wolfgang Burtsch­ler confirmed that “implementation of bio-based products and services must come even faster.” He added that “to achieve the UN Sustainable Development Goals and limit global warming to 1.5° C by 2030, as agreed in Paris, we need to cut annual CO2 emissions by 45% by 2030.” That would only work, he said, “if we strengthen our efforts.” Burtschler’s take was that “at the moment, Europe is breathing with two lungs – those




Added Value










































(€ billion)

(€ billion)

Source: Ronzon & M’Barek, 2018; https://doi.org/10.3390/su10061745; European Commission’s Knowledge Centre for Bioeconomy

Fig. 1: “Jobs and Growth” – the foundation of EC President Jean-Claude Juncker’s belief system. Experts from the EC’s Knowledge Centre for Bioeconomy have calculated revenues and jobs for a circular bio-economy.

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At the EFIB, however, finance experts, Burtschler and represent­atives from the Bio-Based Industry Joint Undertaking (BBI JU) agreed that switching from a petro– economy optimised over decades to a sustainable bio(tech)-based circular economy will not come about without ‘massive’ political and financial support. The question is – what exactly does ‘massive’ mean?

Investors look to hard science “Given the high production costs, it’s still difficult to get paid for a sustainable product,” said Renee Henze, global bio­materials marketing director at DuPont Industrial Biosciences. Felipe Ortega from the European Investment Bank (EIB)

European Biotechnology | Winter Edition | Vol. 17 | 2018

stressed at the EFIB that the EC is determined to prioritise the bio­economy with the launch of a €100m Circular Bioeconomy Investment Fund that’s designed to trigger co-investment. Though stakeholders applauded the approach, many said it would be a drop in the ocean given the minimum €50m cost for a demonstration plant. Other industry stake­holders told European Biotechnology anonymously that although funds are important, a reliable framework for product approval is even more key to investing and commercialisation. “Although there’s strong wording towards establishing a bioeconomy, restrictions for biotechs are rising. Decision­making is inconsistent, and appears to be increasingly politically mo-

Bioeconomy action plan EC  According to EC Research Commissioner Carlos Moedas, €3.85bn has been invested in the bio­economy via Horizon 2020. However, that value­­-added potential was not sufficiently exploited, says Jyrki Katainen, EC Vice-President for Jobs, Growth, Investment & Competitiveness. The New Action Plan is made up of 14 actions aimed at accelerating the switch to food, feed and industry production from renewable, climate-neutral biobased resources. Six actions fall under the first priority: “Strengthen and scale up the bio-based sectors, unlock investments and markets”:

›› Launch of a €100m bioeconomy investment platform for market entry support and risk reduction. ›› Facilitate development of sustainable biorefineries across Europe. ›› Develop decomposable bio-based plastic substitutes to reduce marine litter and plastic pollution. ›› Promote the development of standards and seals. ›› Analyse the opportunities/bottlenecks in the use of bio-based innovations to support market launch.

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›› Network among contributing industries in product development. The EC also wants to “Deploy local bioeconomies rapidly across Europe” by:

›› Launching pilot actions for the development of bioeconomies in rural, coastal and urban areas. ›› Launching Strategic Deployment Agenda for sustainable food & farm systems, forestry & biobased products. ›› Promoting education, training and skills across the bioeconomy. ›› Supporting regions and member states to develop Bioeconomy Strategies. The third action – “Understand the ecological boundaries of the bioeconomy” – is dedicated to:

›› Monitoring progress towards a sustainable bioeconomy.

›› Enhancing knowledge on biodiversity and ecosystems.

›› Promoting good practices to operate the bioeconomy within safe ecological limits. ›› Enhancing the benefits of bio­diversity in primary production. L

tivated, not science­-based,” an industry representative told European Biotechnology. “Most biomass-related innovations – whether involving plants, microbes or enzymes – are strictly regulated.” That creates a climate hostile to innovation. One where investment has been increasingly been put on ice because no one can estimate returns. “We have started to calculate our most innovative products even without the EU market,” confirmed the industry representative. Zinke and industry leaders are calling for incentives allowing the activation of an innovation-oriented capital market ecosytem to help drive the bioeconomy.

Are we talking a carbon tax? In November, stakeholders that hammered out recent recommendations for the UN Emissions Gap Report called for fiscal reforms to foster the low-carbon transition. “The most effective means of reducing emissions and achieving the Paris climate targets is a high carbon price,” concludes the UN report, which points to the successful implementation of carbon taxes in both Sweden and Switzerland. Currently nearly 90% of CO2 emissions have no adequate carbon price. Experts say reaching the 2° C target will require carbon-emission tariffs between €34-€68/tonne by 2020. Sweden and Switzerland, however, charge businesses €120 or €80 per tonne CO2 respectively. Most other countries have encountered political hurdles in implementing strict emissions pricing schemes and in reducing subsidies for fossil fuels. How­ever, a carbon tax may become the key driver to investments into the bioeconomy. It provides the ultimate incentive to reduce CO2 emissions. “Change must be financed,” says climate expert Rockström, adding that “the Green Climate Fund needs reliable and substantial contributions from industrialised countries, and at the same time should set strict rules for payments – for example giving only funds to countries that have introduced CO2 pricing.” That could mark the starting point for investments in innovations for reducing emissions – hopeL fully not only in speeches. t.gabrielczyk@biocom.eu

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Science & Technology

Zeroing in specifically on HER2 Antibody Engineering  Since the first clinical test of the very first HER2-T cell engaging antibodies, drug-related toxicities have remained an issue for drug developers. Dose escalation trials dating back to 2006 provided severe toxicity for Trion Pharma‘s/Fresenius‘ bispecific antiHER2 x anti-CD3 antibody ertumaxomab. Cardiotoxicity and other side effects have also been reported for other antibodies targeting HER2, due to the fact that the receptor protein is not exclusively expressed on tumour cells but also produced at physiologic levels in normal epithelia. Now, Spanish researchers at Vall d’Hebron Institute of Oncology (VHIO) might have found a way out.

The beauty of precise targeting

Pictures: VHIO

In October, the VHIO researchers and antibody engineers at Roche pRED in Schlieren reported that targeting a highly oncogenic domain of HER2, which is present in 40% of the 10% of breast cancer patients that carry HER2, prevents those side effects, paving the way to redirecting T cells to tumours exclusively expressing the new target (Sci. Translat. Med., doi: 10.1126/scitransmed.aat1445).

Irene Rius Ruiz and colleagues zeroed in on the p95HER2 fragment of HER2, which most recently was filed for patent. They found that p95HER2 was not present in samples from 36 normal human tissues, indicating that the fragment is only expressed in cancer cells. The researchers then designed a two-pronged T-cell-bispecific engager that binds to both p95HER2 and the CD3 receptor present at the surface of T cells and found that it impaired tumour growth in several mouse models of HER2-positive breast cancer while sparing the cells that contained the complete version of HER2 protein. However, competitors continue to redirect CAR-T cells or bispecific antibodies towards HER2. Next year, Swiss Glenmark Pharmaceuticals SA will complete a Phase I dose escalation trial of GBR 1302, its bispecific anti-HER2 x anti-CD3 antibody, on 60 patients (NCT02829372). Academic investigators restarted clinical testing of Trion’s anti-HER2 x antiCD3 bispecific antibody ertumaxomab (NCT01569412) in 2016. Meanwhile, researchers at Southwest Hospital in Beijing conduct Phase I trials with HER2-CAR-T L cells (NCT02713984).

First author Irene Rius Ruiz (right hand side) found that a bispecific antibody guiding T cells towards p95HER2 (blue) binds to malignant (brown) but not intact (pink) epithelial cells.

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News Cellular audit   Researchers at Inselspital Bern and Stanford University School of Medicine have for the first time isolated and cultivated progenitors of functional cochlear hair cells. Until now, loss of the cells, which convert vibrations into chemical signals that are transferred into spiral ganglia of the auditory nerve (Nat. Comm., doi: 10.1038 / s41467-018-06334-7), was thought to be irreversible. According to research director Pascal Senn, it will now be possible to test new drugs for hearing impairment directly on human cells.

Antigen mimicry A new method developed by Swiss, Danish, and British researchers allows to detect hardto-trace tumour DNA in the blood (or ctDNA). It makes use of differences in the size of ctDNA fragments, rather than genomic changes in ctDNA. ctDNA is difficult to identify because it is typically outnumbered by much larger quantities of noncancerous DNA that also circulates in the blood. Previous research has shown that fragments of circulating DNA from fetuses can be distinguished from maternal DNA because of their shorter lengths. Taking inspiration from this discovery, Mouliere et al. used whole-genome sequencing to survey the sizes of ctDNA fragments in 344 plasma samples from 200 cancer patients. They found that focusing on fragments between 90 and 150 base pairs long improved detection of ctDNA from patients with brain, renal, and pancreatic cancer. The authors say that size selection could have an impact on the detection of other types of DNA in body fluids.

07.12.2018 13:03:45 Uhr


Science & Technology

European Biotechnology | Winter Edition | Vol. 17 | 2018

Killing off the metastasis switch Metastasis  Researchers at the German Cancer Research Center (DKFZ) and the Heidelberg

HI-STEM have identified a central switch protein that promotes metastasis in breast tumours of mice undergoing cellular stress by changing the tumour microenvironment.

less favorable was the course of the individual disease. Metastases contained more JNK-active cells than primary tumours. In mice xenograted with human breast tumours, the oncologists found micrometastases, which contained up to 50% JNK-active cells. In advanced metastases, JNK was only active in about 15% of the cells. “JNK promotes mobility and invasiveness, which is required for the colonisation of new tissues and will be shut down once the metastasis has become established,” explains first author Jacob Insua-Rodríguez.

Lung cancer micrometastasis in the mouse: JNK is active in the red-labeled cells; cancer cells are green; cell nuclei are blue.

Metastatic progression is a major burden for cancer patients and often follows chemotherapy resistance. German oncologists have found a protein that triggers this process: Under stress conditions found in solid tumours – such as nutrient and oxygene depletion, excessive DNA repair or even under chemotherapy – the regulatory enzyme JNK activates a stem cell programme in breast cancer cells that changes the tumour microenvironment favouring the aggressive spread (EMBO Molecular Medicine 2018, dDoi: 10.15252/emmm.201809003). Understanding the process delivers novel targets to keep cancer spread at bay.

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Applying chemotherapy to breast tumours, the team of Thordur Oskarsson at DKFZ in Heidelberg, Germany, found that cytotoxic therapy induced JNK activity, limiting the effectiveness of the treatment. Oskarsson points out that, however, the new results open up new opportunities: “We've got three so far identified unknown starting points where new drugs could zero in to slow cancer spread and prevent resistance,” he said.

The more JNK the worse The more JNK activity Oskarsson’s team detected in the breast cancer tissue, the

At the molecular level, breast cancer cells changed their expression profile to a mRNA pattern known from breast stem cells that led to the production the extracellular matrix proteins SPP1 and TNC. Switching off the SPP1 or TNC gene in xenografted tumours had no negative consequences, despite JNK overexpression. When treated with chemotherapy, both tumour growth and the number of lung metastases were significantly lower in SPP1– TNC– mice than in SPP1+TNC+ mice. “We now know that we can turn off the key switch for the aggressiveness of breast cancer cells with specific drugs, so that the production of the two major molecular players SPP1 and TNC can stop, thereby reducing metastasis,” concludes Oskarsson. “In this way, we will be able to investigate even better in the future what leads to the metastasis and therapy resistance of breast cancer“ – a new avenue in breast cancer therapy. L  t.gabrielczyk@biocom.eu

Pictures: © Tsunaki Hongu/DKFZ

Matrix protein execute changes

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Science & Technology

Shaping the tumour niche Immunology  A research consortium headed by IMBA-cofounder Josef Penninger has found the well-known co-factor tetrahydrobiopterin (BH4, THB) of amino acid and monoamine neurotransmitter synthesis plays a prominent role in the development of autoimmunity and cancer. In November (Nature, s41586-018-07012), they reported that BH4 mediates effector T cell (Teff) activity and proliferation and antagonises kyurenine-mediated activation of immunosuppressive regulatory T cells (Tregs) and Teff apoptosis. Genetic inactivation of GTP cyclohydrolase 1 (GCH1), the rate-limiting enzyme in the BH4 synthesis, or inhibition of sepiapterin reductase, the terminal enzyme in the BH4 synthetic pathway, impaired the proliferation of mature mouse

and human Teffs. As BH4 production in activated T cells is linked to alterations in iron metabolism and mitochondrial bioenergetics, in vivo blockade of BH4 synthesis abrogated T-cell-mediated autoimmunity and allergic inflammation. Enhancing BH4 levels through GCH1 overexpression augmented responses by CD4+- and CD8+- cells, increasing their antitumour activity in vivo and markedly reduced tumour growth in mice. The new data identify GCH1, SPR, and their downstream metabolite BH4 as critical regulators of T cell biology that may be readily manipulated to either block autoimmunity or enhance anticancer immunity if a therapeutic window is available. A SPR antagonist, QM385, has been L already screened.

Pictures: Jovanche Vitanovski /123rf.com

Give me sugar, baby Cancer  UK researchers have slowed tumour growth by simply putting mice with human tumour xenografts on a diet in which glucose is replaced by the sugar mannose (Nature, doi: doi: 10.1038/ s41586-018-0729-3). Feeding mannose, either alone or alongside chemotherapy, through a feeding tube three times a week and continuously via their drinking water was well-tolerated and appeared to reduce tumour growth both alone and in combination with doxorubicin. The researchers, headed by Kevin Ryan from Cancer Research UK in Glasgow, suggestthe monosaccharide interferes with the energy metabolism (glacolysis) of tumour cells. Recent reports suggest that high serum levels of mannose were significantly associated with recurrence and overall survival cancer patients for unknown reasons. In the new study, Ryan’s team found out that cell sensitivity to mannose correlated with lower levels of the enzyme phosphomannose isomerase (PMI) that catalyses the conversion from mannose6-phosphate into fructose 6-phosphate

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(F6P), which enters glycolysis. The authors tested for PMI levels in tumour cells from ovarian, renal, breast, prostate, and colorectal tumours and report differing cellular PMI levels both among and within tumour types. In particular, colorectal tumours had low levels of PMI, and mice with colorectal cancer developed significantly fewer tumours when administered the sugar. If confirmed by further experiments, mannose treatment could potentially represent a simple, safe way to target tumour growth in many cancers. L


News NAD enhancer   TES Pharma s.r.l. has presented a novel treatment approach for acute kidney injury (AKI) and non-alcoholic fatty liver disease (NALFD) in Nature (doi: s41586-018-0645-6). TES991 and a backup compound, both enhancers of mitochondrial function that have been filed for patent by Johan Auwerx' lab at EFPL, reduced the activity of a-amino-b-carboxymuconate-e-semialdehyde decarboxylase, an enzyme regulating NAD+ de novo synthesis, in mice with NALFD or AKI. Specifically, the drug candidate boosted NAD+ concentrations and, subsequently, sirtuin 1 and 3 levels in both models and reduced hepatic steatosis or limited kidney damage. Sirtuin1 and 3 proteins deacetylate key metabolic transcriptional regulators that trigger amelioration of metabolic disease

Antigen mimicry Swiss, Spanish, and US researchers have identified a bacterial variant of a human enzyme named GDP-L-fucose synthase in the human gut microbiota that can trigger the development of multiple sclerosis (MS). When examining CD4+ T cells from the cerebrospinal fluid (CSF) of 31 MS patients, first author Mireia Sospedra from University Hospital Zurich found 12 of them displayed reactivity to the enzyme. What‘s more, CSF-derived T cells from four of these MS patients cross-reacted to an variant of the enzyme produced by gut bacteria. The findings support the idea that bacterial molecular mimics may provide the missing trigger for disturbing the balance of regulatory to effector T cells, which enable immune tolerance.

06.12.2018 15:10:31 Uhr



European Biotechnology | Winter Edition | Vol. 17 | 2018

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

Europe: european-biotechnology.net

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European Biotechnology covers the biotechnology sector of the current 28 EU member states, Norway and Switzerland. If you would like to subscribe, please refer to european-biotechnology.com

Clear signal SPC m anufacturing waiver  In

November, the Parliament’s Health Committee (ENVI) sent a clear signal of support with the adoption of a “Day One” launch possibility to supply European patients with European manufactured medicines. The SPC manufacturing waiver aims to correct the current implementation of the Supplementary Protection Certificate system, which blocks manufacturers from producing generic or biosimilar medicines for export to non-EU countries where the SPC does not apply, or from producing and stockpiling these medicines to allow for “Day One” launches after SPC expiry in the EU. Because of the current restrictions, the EU pharma industry is forced to delocalise production to non-EU countries, like Canada or the United States. “We welcome the Health Committee’s efforts to improve the SPC manufacturing waiver in relation to day one launch and the protection of confidential business information. We hope that this progress, together with a more reasonable date of application, will be agreed to the Parliament and the Council in a future final agreement. We urge the Parliament’s Legal Committee to adopt a final opinion that includes these important priorities for health, for jobs, and for a robust pharmaceutical eco-system,” said Adrian van den Hoven, Director General  of Medicines for Europe.

A look forward BIO-Europe 2019 After LISAvienna, on behalf of the umbrella brand Life Science Austria, successfully organised Austria’s participation at BIO-Europe in Copenhagen, the association is pleased to host the renowned BIO-Europe Spring conference next year in Vienna. It will take place from March 25 to 27 and offers opportunities for startups, biotech and pharma service providers, the finance sector, and global players to meet one another and explore new collaborations and investments. 


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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 | Winter | Vol. | 2018 European technologies, Biotechnology Edition wherever it makes sense. The 17 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 “Swiss Biotech” (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.

The race to innovate and pathways to ROI

Domenico Alexakis is Executive Director of the Swiss Biotech Association.

Swiss Biotech Day Fall  Over 150 senior executives from the Swiss

biotech industry met at the Swiss Biotech Day Fall in late September to focus on lessons learned from the race to innovate and take a fresh look on product portfolio and financial exposure.

The meeting was held at Biopôle in Lausanne and aligned with EuropaBIO’s European Biotech Week, providing valuable inputs on how the industry hedges its bets in terms of product portfolio and financial exposure. The fast-paced halfday program organised by the Swiss Biotech Association was accompanied by an overview of the biotech industry, which continues to invest record amounts of capital into research and development. Swiss start-ups are making headway too: for the first time, the sector attracted more than one and a half billion Swiss francs in venture capital in 2017. Dr. Francesco De Rubertis, Founding Partner at Medicxi, discussed the venture capital firm’s “asset-centric model” and reassured the audience that it is people before science that make an asset great, with some 70 percent of Medicxi investments being European. Basel-based Roivant raised 1.7 billion Swiss francs in just two financing rounds and creates

value in biotech by establishing separate entities or “Vants.” Sascha Bucher, head of Roivant Global Transactions, explained that such Vants are small entrepreneurial biotech companies which help drive efficiency in R&D and commercialization. As ObsEva’s CEO, Dr. Ernest Loumaye, explained in his talk on hybrid growth strategy, there are clear regulatory benefits for Swiss biotechs in a dual stock exchange listing. The discussion showed that a Swiss incorporated company listed on a foreign exchange may be vulnerable to unsolicited takeovers. ObsEva mitigated this risk by listing its equity on the Swiss stock exchange in addition to the NASDAQ, thus benefiting from the Swiss takeover regime. The Swiss Biotech Day Fall closed with the presentation by Marcus Kracht, CFO and Deputy CEO at Vifor Fresenius Medical Care Renal Pharma. The joint venture company is a 2018 laureate of the recently launched Swiss Biotech Success

Swiss Biotech Day Fall: Sharing perspectives and plenty of room for networking.

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...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.




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

› 7 May 2019, Basel Swiss Biotech Day & Swiss Biotech Success Stories celebration swissbiotechday.ch

Stories campaign and was created by Vifor Pharma and the medtech company Fresenius. This vertical integration between a pharmaceutical and medical device company created a powerful distribution platform for dialysis patients and enabled Vifor Pharma to become a gloL bal leader in nephrology.

Successes 2019 Stories  The Swiss Biotech Success

Stories demonstrate the benefits of the biotech sciences for social development. Biogen, Roche Glycart, Okairos, Selexis, and Vifor Fresenius Medical Care Renal Pharma were honored this year. An independent jury of experts will select the next Swiss Biotech Success Stories, which are announced at the Swiss Biotech Day on 7 May 2019.

A sponsor view “Biotech is one of the most innovative sectors in Switzerland. The Swiss Biotech Success Stories accentuate past industry highlights and act as motivator for future achievements. The successive partners leading the banking group Mirabaud have all been driven by the same entrepreneurial spirit and pursued an approach focused on managing risks as well as enabling innovation since 1819. Mirabaud is very proud to support this campaign and the laureates who earned extraordinary merits for their scientific, medical or commercial achievements.” L

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Upcoming events › 24 – 29 September, Europe Biotech Week 2019 www.biotechweek.org

European Biotech SME Awards  Over 40 SMEs from Europe

have competed for this year’s Most Innovative European Biotech SME Awards. The winners of the 9th edition of the EuropaBio Most Innovative Biotech SME Awards are these three companies: Genoscience Pharma (healthcare biotech, France), Lactips (industrial biotech, France), and Phytowelt GreenTechnologies (agricultural biotech, Germany). Read below a few quotes from some of the 2018 Jury Members: “The jury was delighted to recognise Genoscience

Pharma for their highly innovative approach to a cancer therapy against cancer stem cells. Most chemotherapies are not yet effective against these cells and their research on liver cancer has great potential. They are undoubtedly an innovator to watch and recognise.” – MEP Dr. Paul Rübig. “The technological potential of Lactips is vast and many industrial actors

Toulouse hosted EFIB Bioeconomy comunity  Speakers at the 11th edition of EFIB called for Europe to continue its commitment to building a sustainable, circular bioeconomy. Leading industry and policy experts met between 16 and 18 October in Toulouse for the 11th annual European Forum for Industrial

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Biotechnology and the Bioeconomy (EFIB). Besides displaying a wealth of innovation demonstrating Europe’s strong response to SDG challenges and the potential of the circular bioeconomy, #EFIB2018 also featured Lise Kingo, CEO and Executive Director, United Nations Global Compact; Jean Tirole, 2014 Nobel Laureate in Economic Sciences; and the European Commission’s Deputy Director General, DG RTD, Wolfgang Burtscher, amongst more than 80 speakers. As a novelty this year, the conference had a dedicated Start-Up Village, a new meeting point where the 500 delegates could meet with up to 24 L start-ups from 11 countries.

would be able to profit from their innovations. In line with the EU’s mission to create clean alternatives to fossilbased products, which are more sustainable and efficient, Lactips provides a disruptive innovation that has a diverse field of application.” – MEP Dr. Paul Rübig. “Phytowelt GreenTechnologies’ creative innovation is enabling the company to produce and commercialise a highquality product, which is increasingly in demand, whilst using less resources, land and energy.” – Joanna Dupont-IngL lis, Secretary General, EuropaBio.

European Biotech week Happening   In total, 136 events took place in 18 countries during the 6th edition of the European Biotech Week from the 24 – 30 September 2018. The events attracted a broad range of participants, from researchers and professionals to curious students, across all age groups. Initiatives throughout the week were as diverse as the organisers themselves. They included conferences, workshops, handson laboratories, exhibitions, and opendoor days with companies, research insti tutes and museums.

Pictures: EuropaBio

And the winners are

›1  Sept – 2 October, Brussels European Forum for Industrial Biotechnology and the Bioeconomy (EFIB) www.efibforum.com

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European Biotechnology | Winter Edition | Vol. 17 | 2018

Biotech Showcase 7.–9.1.19 San Fr ancisco   Bio-

tech Showcase™ is an investor conference during JPM 2019 devoted to providing private and public biotechnology and life science companies with an opportunity to present to, and meet with, investors and pharmaceutical executives.  https://ebdgroup.knect356.com/ biotech-showcase/


Innovation & Market Access in Biotech-, Pharma& Medtec-Management, Florence (IT) Info: Donau-Universität Krems, www.donau-uni.ac.at


Innovation for Health, Rotterdam (NL) Info: Hyphen Projects, www.innovationforhealth.nl


11th HIC/DSP conference, Interlaken (CH) Info: University of Natural Resources and Life Sciences www.hic-dsp.org


12th Berlin Conference on Life Sciences: Novel Antimicrobials and AMR Diagnostics, Berlin (GER) Info: Uta Holmer, BIOCOM AG http://berlin-conferences.com/home/

EUBIC Winter School 2019, Zakopane (PL) Info: European Bioinformatics Community (EUBIC) www.proteomics-academy.org/ eubic-winter-school-2019


2nd International GlycoBioTec Symposium, Berlin (GER) Info: Max Planck Institute for Dynamics of Complex Technical Systems www.mpi-magdeburg.mpg.de/glycobiotec2019


Arab Health, Dubai (VAE) Info: Informa PLC www.arabhealthonline.com


12 th Pharmacovigilance Conference, London (UK) Info: International Generic and Biosimilar Medicines Association, www.medicinesforeurope.com/events

Pictures: EBD Group/ MEDICINES FOR EUROPE AISBL/Concept Heidelberg


Zurich Life Science Day, Zurich (CH) Info: Life Science Zurich Young Scientist Network www.lifescience-youngscientists.uzh.ch


MD&M West, Anaheim (USA) Info: UBM LLC, https://mdmwest.mddionline.com


DIA Europe 2019, Vienna (AT) Info: DIA, www.diaglobal.org


Pharmapack 2019, Paris (F) Info: UBM, www.pharmapackeurope.com

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Global Food Summit 2019, Munich (GER) Info: Global Food Summit, www.globalfoodsummit.com/


XIII. EuPA Congress – Proteomic Forum 2019, Potsdam (GER) Info: DGPF/EuPA/Conventus, www.eupa2019.org


BIO-Europe Spring 2019, Vienna (AT) Info: Tom Voigt, EBD Group, www.ebdgroup.com/bes

ECA Course Annex

12 th Annual European Life Sciences CEO Forum & Exhibition, Zurich (CH) Info: Sachs Associates, www.sachsforum.coml

European Chemistry Partnering, Frankfurt am Main (GER) Info: Dr. Holger Bengs, BCNP Consultants GmbH https://european-chemistry-partnering.com






16.–17.5.19 Vienna   Concentrate on regulatory and practical requirements regarding biopharmaceutical production – in the ECA course Annex 2 & Co – GMP Compliance for Biopharmaceuticals. Join and benefit from practical examples and case studies. www.gmp-compliance.org


Swiss Symposium of Lab Automation, Rapperswil (CH) Info: ILT, www.ilt.hsr.ch


futurehealthcare, London (UK) Info: Pri-Med Global Exhibitions Ltd www.futurehealthcareuk.com

Biosimilar Medicines 28.–29.3.19 Amsterdam   During

the 17th Biosimilar Medicines Conference, experts in biosimilar medicines will gather and debate the evolving biosimilar medicines landscape and new trends. Sessions will cover all relevant areas of healthcare policy, market access, scientific developments, regulatory, and clinical experience.www.medicinesforeurope.com


35. Annual Congress Pharmaceutical Medicine – Access to new Therapies: from Challenge to Solution, Berlin (GER) Info: DGPharMed/Primecon, www.dgpharmed-jahreskongress.de


World Bio Markets, Amsterdam (NL) Info: Robert Wilson, Green Power Conferences http://worldbiomarkets.com


BioNanoMed 2019 – Nanotechnology in Biology & Medicine, Graz (AT) Info: Techkonnex – High-Tech-Promotion, www.bionanomed.at


Swiss Biotech Day 2019, Basel Info: SBA, www.swissbiotechday.ch


12 th International Conference on Bio-based Materials, Cologne (GER) Info: nova Institute www.bio-based.eu/conference

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company index /Product 

Smart sealer Candor bioscience GmbH   Liquid Plate Sealer® is a coating stabilizer for antibodies and antigens coated on polystyrene- or glass-surfaces. After immobilization of the antibodies or antigens and blocking, Liquid Plate Sealer® seals the plates with a uniform stabilizing layer demonstrating good solubility and without affecting the assay afterwards. Plates treated with Liquid Plate Sealer® can be stored for long periods after drying. Therefore you can build up stocks of coated ELISA plates to save time and money and to obtain more comparable results.

Liquid Plate Sealer® is used for stabilizing coated ELISA plates, immunochromatographic test strips (lateral flow assays), affinity chromatography columns, protein arrays and for similar applications. Liquid Plate Sealer ® is ready-to-use and available in bottle sizes of 50 ml, 125 ml and 500 ml. It is applicable for research kits and for commercial ELISA D kit production. Contact

CANDOR Bioscience GmbH Phone: +49 7522 795270 info@candor-bioscience.de www.candor-bioscience.com

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European Biotechnology | Winter Edition | Vol. 17 | 2018

A-Mansia Biotech S.A. (BE) 76 Abacus Medicine (DK) 22 Ablynx BV (BE) 29, 35 Accenture plc (IRL) 37 Acesion Pharma ApS (DK) 24 ActoBio Therapeutics Inc. (BE) 25 Adaptimmune Therapeutics (UK) 77 AdrenoMed AG (DE) 32, 34 Affimed GmbH (DE) 23, 79 Aimmune Therapeutics Inc. (US) 79 Algesiologikum MVZ GmbH (DE) 13 Amal Therapeutics S.A. (CH) 79 AmerisourceBergen (US) 38 Amgen Inc. (US) 23 Angle plc (UK) 77 Aphria Inc. (CA) 18 arGEN-X B.V. (NL) 29, 36 Asit Biotech SA (BE) 29 AstraZeneca AB (SE/UK) 35, 74, 76, 78 Atlas Venture (US) 67 Aurora Cannabis Inc. (CA) 18 aws Gründerfonds (AT) 22 b.fab GmbH (DE) 86, 87 BASF Venture Capital GmbH (DE) 3 Bayer SE (DE) 25 BCNP Consultants GmbH (DE) – ECP 52, 53 BenevolentAI (UK) 67 Bereskin & Parr (CA) 16 Bio-On S.p.a. (IT) 81 Biocartis Group NV (BE) 29 Bioceros Holding NV (NL) 72 BIOCOM AG (DE) 33, 54, 55, CP3, Suppl. Biogen GmbH (DE) 93 BioMedPartners AG (CH) 79 BioSystems Technology (UK) 21 BioVersys AG (CH) 21 Blucon Biotech GmbH (DE) 79 Boehmert & Boehmert (DE) 36 Boehringer Ingelheim (DE) 78, 80 Brahms AG (DE) 32 Brain AG (DE) 87, 79 Bridge Capital AG (DE) 20, 21 Bristol Myers Squibb (US) 74

CANDOR Bioscience GmbH (DE) Canopy Growth Corp. Inc. (CA) Carbios SAS (FR) CB Insights (US) Cell Medica plc (UK) Cellectis S.A. (FR) Celyad S.A. (BE) Centrexion Therapeutics (US) Centrum Badan DNA (PL)

96 18 85, 86 67 83 83, 98 29 22 82

Chronicled Inc. (US) Cronos Group Inc. (CA)

38 18

Dätwyler Schweiz AG 41, 42 DelSiTech Ltd (FIN) 75 Deutsche Biotech Innovation AG 32 DGPharMed / Annual Meeting (DE) 58, 59 DHL Vertriebs GmbH & Co. OHG (DE) 37 DIA Europe (CH) 46, 47 Dupont Industrial Biosciences (NL) 88 e-Therapeutics plc (UK) 68, 69 EBD Group (US) – BIO-Europe Spring 56, 57 Enterome SA (FR) 77 Eppendorf Bioprocess Center Europe (DE) 27 Escientia Ltd. (UK) 67 EuropaBio /European Biotech Week (BE) 11 Evaxion (DK) Evotec AG (DE)

70 22, 28, 77

FGK Clinical Research GmbH (DE) Fresenius Biotech GmbH (DE)

15 89

Galapagos NV (BE) 28, 29 Galectin Therapeutics (US) 74 Galecto Biotech AB (DK) 74 Genentech Inc. (US) 23, 38, 79 Geneplantet d.o.o. (SI) 82 GenkyoTex S.A. (CH/F) 24 Genmab A/S (DK) 29 Genoscience Pharma (FR) 94 GenSight Biologics (FR) 23 Gilead Ltd. (US) 28 Gilead Sciences Internation Ltd. (US) 23, 35 GlaxoSmithKline (UK) 68, 76 Glenmark Pharmaceuticals SA (CH) 89 Grifols S.A. (ES) 23 Gruppo CAP (IT) 81 HBM Bioventures (CH) 32 Helsinn Investment Fund (LU) 79 High Tech Gründerfonds GmbH (DE) 3, 79 I-Mab Biopharma (CN) 78 iMEAN (FR) 86 immatics biotechnologies GmbH (DE) 24 Immunicum AB (SE) 75 Innate Pharma SAS (FR) 76, 78 Innovation Industries (NL) 76 Intrexon Corp. (US) 25 Intron Bio (KR) 79 IQvia Commercial GmbH & Co. KG (DE) 13 Janssen Cilag Int. NV (BE)

24, 36

Pictures: Candor Bioscience


07.12.2018 13:09:38 Uhr

European Biotechnology | Winter Edition | Vol. 17 | 2018

JF Investments AG (CH) Johnson & Johnson (US)

82 24, 28, 36

Kiadis Pharma BV (NL) Kreditanstalt für Wiederaufbau (DE)

29 10

Labgenius (UK( Lactips (FR) LEO Pharma A/S (DK) Leukocare AG (DE) LIDDS AB (SE) LMU München|LMU Amgen Scholars Programm (DE) Longwood Fund (UK)

70 94 78 71 75 65 76

Mabion S.A. (PL) 82 Marinomed Biotechnologie GmbH (AT) 22 McKesson (US) 38 MDxHealth SA (BE) 29 Medicxi Ventures (CH/UK) 93 Merck KGaA (DE) 75 Mithra Biotech Inc. (TW) 29 MLM Medical Labs GmbH (DE) 19 Mobidiag Oy (FIN) 75 MorphoSys (DE) 29 MorphoSys AG (DE) 23, 78

Pictures: Promocell

Nanna Therapeutics (UK) 67 Nestle S.A. (CH) 70, 79 Newron Pharmaceuticals S.p.A. (IT) 80 Nicox (FR) 22 76 Nivelinvest (BE) nova-Institut | Biobased Materials (DE) 63,86 Novamont S.p.A. (IT) 81 Novartis AG (CH) 23, 35, 83 NovImmune S.A. (CH) 74 Novo Holdings (DK) 74 Novo Nordisk A/S (DK) 29, 75 Novo Seeds (DK) 74

company index /Product

Potter Clarkson LLP (UK) Privateer Holdings (US) Promocell GmbH (DE)

Regeneron Pharmaceuticals Inc. (US) 28 Rentschler Biopharma SE (DE) 71 Rentschler Fill Solutions (AT) 7, 71 Roche AG (CH) 23, 25, 79, 82, 93 Roivant Science (CH) 79, 93 Sangamo Biosciences Inc. (US) 25 Sanofi SA (FR) 29, 35, 68, 74, 77 SAP AG (DE) 38 Schroder Adveq (DE) 79 Selexis S.A. (CH) 93 Seventure Partners (FR) 76 Shimadzu (DE) CP2 Sitryx Therapeutics Ltd. (UK) 76 Sobi AB (SE) 23, 74 Sofinnova Partners (FR) 76 Sphere Fluidics (UK) 83 SphingoTec GmbH (DE) 32, 34 SRIW Group (BE) 76 Stora Enso Ventures Oy (FIN) 74 SV Health Investors (UK) 76 Swiss Biotech Association (CH) – SBD 60, 61 Takeda Pharmaceuticals (JP) 29, 77 TES Pharma s.r.l. 91 Themis Bioscience AG (AT) 22 Thermo Fisher Scientific (US) 32 TiGenix N.V. (BE) 29 Tilray Inc. (CA) 16 Tosoh Bioscience (DE) – 11th HIC/DSP 50, 51 Trianni, Inc. (US) 9 TRION Pharma GmbH (DE) 89 TVM Capital Life Science (DE) 28

Nuritas (IRL)


UBM B.V (NL) – Pharmapack 2019 UCB S.A. (BE) Unilever (CH) uniQure BV (NL)

Obseva AG (CH) Okairos AG (CH) OPIS s.r.l. (IT) OrbiMed Advisors (US) Orion Corporation (FIN) Oxurion NV (BE)

93 93 23 74 25 29

Vertex Pharmaceuticals Inc. (US) Vetter Pharma-Fertigung (DE) Vifor Pharma (CH) Voxcan (FR)

Parexel (US) 83 Pfizer Inc. (US) 25, 38, 68, 75 PharmaMar (ES) 81 Pharming Group N.V. (NL) 29 Phytowelt Green Technologies (DE) 94 Polpharma Biologics (PL) 72, 73, CP4

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17 16 97

Walloon Region (BE) Wellington Partners (DE) Wilhelm Bähren GmbH (DE)


Convenient and reliable P r o m o c e l l G m b H  P r o m o C ell’s Phagocytosis Assay Kits utilise heatkilled, red or green-fluorescently pre-labeled E. coli or Zymosan particles as a tool for rapid and accurate detection and quantification of in vitro phago­c ytosis. For the distinction between internalised and surface-bound fluorescently labeled E. coli/Zymosan, the kits include a solution to quench surface-bound fluorescence. The fast, simple and convenient fluorometric assays provide two different particles and fluorescent signals, which can be analysed using fluorescence microscopy, flow cytometry or a spectrofluorometer/fluorescence multiwell plate reader. The kits provide a robust, reliable and sensitive screening system for e.g. activators and/or inhibitors of phagocytosis and Toll-like Receptor (TLR) ligands

46, 49 24 81 25, 29 77 25 93 21 76 22, 32 39, 40

Ysios Capital Partners (ES)


Zelluna Immunotherapies AS (NO)



PromoCell GmbH Sickingenstrasse 63/65 69126 Heidelberg www.promocell.com info@promocell.com

07.12.2018 13:09:50 Uhr


What fascinates you the most about your job?

The bee lesson

Mohamad Mohty Professor at Sorbonne University and Co-founder of MaaT Pharma SA, Paris, France

Neuroscience  Most medicines can’t get through the blood-brain barrier. A notable exception are certain peptides in animal venoms. For instance, the bee-venom peptide apamin is known to accumulate in the central nervous system of people who’ve been stung by bees. Taking advantage of this feature, scientists at the Institute for Research in Biomedicine in Barcelona (Spain) designed a peptide that could carry drugs across the blood-brain barrier. In their experiments the scientists succesfully demonstrated that the system is useful for transporting nanoparticles across endothelial cell monolayers (Chemical Communications, doi: 10.1039/C8CC06725B). The small protein is derived from chlorotoxin, found in the ve­nom of the Giant Yellow Israeli Scorpion). î ‹

Hoax Warners The

claims of a Chinese scientist that under his guidance the first genome-edited humans have been born shook the science community to the core. Voices that say the proof for these #crisprbabies is still out are getting lost in the outcry. Fake news or not – for science the stakes are high. Fortune-Teller Cellectis’ CEO AndrĂŠ Choulika predicted in an opinion piece a month ago that the first baby with an updated genome would be born in 2040. It’s (probably) 2018. At least he guessed the correct continent (Asia) and proved his hypothesis (Europe and the US are losing the gene editing race).  î ‹

“When you manage patients with severe diseases like leukaemia, exploring innovative therapeutic frontiers like the microbiome provides an exciting new horizon towards improving patient outcomes.�

Alliance for genomes A pan-European database containing genomic information is getting traction. Last spring, 13 countries signed the declaration �Towards access to at least 1 million sequenced genomes in the European Union by 2022�; by November, six more EU member states had joined in. Bringing together fragmented infrastructure and expertise, the goal is to compile a large data set that will provide sufficient scale for clinically impactful research on new therapies and better treatment decisions.









Czech Republic




Finland Greece Italy Latvia Lithuania Luxembourg Malta

jet fuel @nanopore #Tesaro Ve♝⛽ đ&#x;›Ť Orlando đ&#x;›Ź London @VirginAtlantic flight powered by recycled waste gas from a steel mill. @LanzaTech converted the gas to ethanol that was upgraded to jet fuel with help from @PNNLab  @ENERGY No wonder Illumina is buying PacBio, @nanopore has them scared shitless. @ACastanza Great to see that @EU_Commission has named #bioeconomy as one of seven path-

98_EB_Winter_2018_Emcore.indd 98

ways towards a #climate neutral economy! #COP24 #SDGs  @BjoerneTore

Please follow us @EuroBiotechNews #GlaxoSmithKline said it will pay US$75 per share in cash to take over US #oncology player #Tesaro. https://bit.ly/2zIwHKU  @EuroBiotechNews

Next issue Spring edition Once again packed with opinion pieces, info nug get s and well-grounded stories, European Biotechnology’s Spring Edition will also feature editorial and industry-driven articles about bioprocessing topics. Publishing date is 14 March 2019; due date for advertisements is 25 February. Questions will be answered by Andreas Macht (+49-30-264921-54) and Oliver Schnell (-45). Or drop us an email: marketing@biocom.de. î ‹

Picture: MaaT Pharma

Winners & losers

European Biotechnology | Winter Edition | Vol. 17 | 2018

Source: European Commission


06.12.2018 15:20:13 Uhr

HORIZON EUROPE Excellent R&D projects deserve excellent communication. With more than 30 years of experience in life sciences, BIOCOMÂŽ is the perfect partner for your professional dissemination, communication and exploitation needs in EU-funded projects. Project branding and preparation of communications materials Creation and maintenance of the project website Media work, incl. social media and project videos Organisation of conferences and workshops


Picture: rakchai/fotolia.com

For more information, just head to www.biocom.de/comdis or contact Dr. Boris Mannhardt at b.mannhardt@biocom.de

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06.12.2018 15:33:17 Uhr

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06.12.2018 15:33:26 Uhr

Profile for BIOCOM AG

European Biotechnology Magazine 4/18  

European Biotechnology Magazine 4/18  

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