Ebm2017 summer

ISSN 2364-2351 | A 60711 |

Life Sciences and Industry Magazine Summer Edition 2017 | Volume 16 | 20 €

Interview Daniel Oliver: the CEO of crowdfunding platform Capital Cell on the future of alternative financing

Agri-CRISPR & Co.

Brave new food

Bioeconomy

Orphan Drugs

Allergies

Biofairs Compass

Uncertainty about review of EU strategy hampers investments

How can healthcare systems establish value-based pricing?

New biotech solutions target oversensitive immune systems

Your guide to relevant EU life sciences events in H2/2017

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Intro

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Benefits and challenges in pharma innovation We are living in a world of cutting-edge science, which holds the potential to transform the landscape for patients living with common and rare diseases within the next five years. This is of particular importance as we face a demographic evolution that will see an already-aging population expand significantly and rapidly across the globe.

The scientific advances that we are witnessing mean that we know more about ill health than ever before. The knowledge that we have gained is being translated into new therapies to treat a wide variety of often age-related conditions, including cancer, Alzheimer’s disease, and type 1 diabetes. We are also making progress in the fight against rarer conditions, such as haemophilia.

Nathalie Moll was appointed Director General of the European Federation of Pharmaceutical Industries and Asscociations (EFPIA) in 2017. Previously, she was the Secretary General of EuropaBio, the European Association for Bioindustries. After graduating with Honours in Biochemistry and Biotechnology from St Andrews University, Scotland, and working for a stage at the European Commission, Nathalie has spent 20 years employed in the biotech industry at EU and national level in associations and corporate positions.

Improved treatments offer hope and help to patients, carers, and their families. This has a positive impact on the wider society, helping people lead healthier, more productive lives. In fact, industry pipelines are brimming with innovation. CAR-T cell therapy will transform the way that we address blood cancers and disorders, potentially increasing the life expectancy of a patient with acute lymphoblastic leukaemia by over 60 years.

Cell therapy, in which living cells are injected into the patient to treat the causes of their disease, may be used to treat common conditions such as type 1 diabetes. This novel therapy can be used to control blood sugar without the need for constant insulin injections. This will aid in the restoration of normal pancreatic functionality and, as a result, will restrict the onset of serious, long-term health conditions. That is good news for the estimated four million people in Europe who live with type 1 diabetes.

Picture: EFPIA

Gene therapies, which repair the direct cause of genetic disease, by introducing genetic material into cells to compensate for abnormal, ill-expressed or missing genes, have the potential to relieve or even cure rare diseases where the patient’s quality of life and prognosis are poor, such as haemophilia B. In fact, gene therapy could mean that patients might avoid a lifetime of prophylactic or bypass therapy.

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It is already becoming clear that the launch of new technologies, along with the resulting opportunities created for patients, will pose challenges to healthcare systems. Developing new ways to assess the costs and benefits of these innovations will be essential if their introduction is to be managed effectively. Early planning and action will enable the careful introduction of new treatments in ways that ensure their most effective use, maximise their best affordability and – most importantly – enable all eligible patients to benefit as soon as possible. EFPIA and our members want to work with partners to help prepare for these exciting new advances to ensure that patients with unmet medical needs are able to benefit at the earliest opportunity.

L

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Contents

European Biotechnology | Summer Edition | Vol. 16 | 2017

Cover Story

Insight Europe

regional news

6 European Commission: Update on EU bioeconomy strategy still not on solid ground

64 Northern Europe:

Sweden, Denmark, Finland,

and Norway

10 Academic inventors of genome editing enter another battle on CRISPR patents; IP Flash

66 Western Europe:

France, Belgium, The Netherlands,

and the UK

68 Central Europe:

Germany, Switzerland,

and Austria

11 GM acreage growing globally and EU-wide 12 Guest comment: Brexit and patents

Economy 21 Update on clinical trials 24 Focus Biomanufacturing: Bright future for biomanufacturers

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CRISPRed crops and agbiotech’s future European consumers have consistently been averse to allowing GM crops onto fields and into supermarkets on the continent, despite huge efforts by trade organisations and many politicians to force the issue. But how will they react to genome­ edited versions of plants, which don’t contain DNA foreign to the species, but have simply been engineered to optimise specific characteristics? Will GEOs be able to bypass the regulatory hurdles that have stopped companies like Monsanto cold?

An era of brave new food awaits.

28 Focus Biomanufacturing Interview: “Making biologics economic”; Federico Pollano, Business Development & Contract Manufacturing Director, Polpharma 30 Human Resources intelligence;

Patheon taken over by Thermo­

Fisher Scientific in US$7.2bn deal 31 Analyst commentary 32 Euro Biotech Stocks 34 Interview: Daniel Oliver, CEO, Capital Cell, Barcelona (Spain) 73 Start-up story:

Juvabis GmbH, Zurich (Switzerland)

70 Southern Europe: Italy, Spain, Slovenia, Portugal, Cyprus, and Greece 72 Eastern Europe:

Poland, Czech Republic, Slovak

Republic, and Lithuania

Science & Technology 79 Immuno-oncology: Anti-Angio­ genesis provides promising strategy to block tumour immune evasion 80 First bio-based PET-recycling technology set to prevent further ocean pollution

Service 81 News from partner associations: Swiss Biotech Association, BIO Deutschland, Drug Information Association, Europa­Bio, European BiotechnologyNetwork,and Medtech Europe 88 Company index 89 Events 90 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), Uta Mommert, Dr. Martin Laqua, Sascha Karberg, 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: Oliver-Sven 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: © Andrey Volokhatiuk/fotolia.com; ® BIOCOM is a registered trademark of BIOCOM AG, Berlin, Germany.

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Picture: Andrey Volokhatiuk/fotolia.com

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Contents

European Biotechnology | Summer Edition | Vol. 16 | 2017

Orphan Drugs

DNA Phenotyping

Editorial

It’s so CRISPy

Help save my life More and more drugs for rare diseases are hitting the market, thanks to quasimonopolies granted to developers as an incentive to motivate R&D in the sector.

Now that Big Pharma is beginning to dominate the field, discussion has shifted to overpricing, instead of providing affordable ways of reimbursement. Could networking and data exchange across Europe help resolve the confict?

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Biotech vs. Allergies

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Estimates say that by 2025, half of all Europeans could suffer from some type of allergy. The reasons for allergy development are still largely a mystery, but researchers are beginning to make progress in treating them. The most promising path is allergen immunotherapy – a method with roots dating back over a century.

Pictures: groupcheers/fotolia.de (top), masterzphotofo/fotolia.com (middle), fotolia.com/ Sashkin (bottom)

SPECIAL

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EU Event Compass 43 Intro: Mark your calendar 44 Nordic Life Science Days, Stockholm 46 DIA OpEx, Berlin 48 European Biotech Week 50 BioPharm America, Boston 52 BioJapan/RegMed Japan, Yokohama 54 CPhI worldwide, Frankfurt 56 Pharmalab, Düsseldorf/Neuss 58 Fraunhofer Life Sciences Symposium, Leipzig 60 BioFIT 2016, Strasbourg 62 EMBL Autumn Conferences &

Courses, Heidelberg

Rejecting genetically engineered crops has become a tradition in Europe, as citizens increasingly express a yearning for the’natural’ country life.

NGOs like Friends of the Earth or Greenpeace have built funding campaigns on the idea. So, do agribiotech companies really stand a chance when they say they’d like to introduce a new generation of engineered crops through the back door? Even though it really is impossible to distinguish genome­-edited crops from breeds conventionally mutated by untargeted shot-gun radiation, science-based discussions on whether or not to label such products as GMOs is damning them to an unwinnable battle. What still counts more than facts is that CRISPRed plants are perceived not as ‘natural’, but probably the industry’s next food scandal.

On page14, our cover story shows what kind of value creation CRISPR & Co. could contribute in the long run to healthier, more fruitful crops that are better adapted to the demands of climate change.

However, the next generation of crops won’t ever become a business success here without acceptance from the European public. To gain it, the industry will have to do more than produce great products. In an era of alienation from our biological roots, it will somehow have to learn from NGOs to address urbanite demands for a more ‘natural’ living experience.

Thomas Gabrielczyk Editor-in-Chief

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Insight Europe

European Biotechnology | Summer Edition | Vol. 16 | 2017

Update of bioeconomy strategy unsure bioeconomy Uncertainty regarding the amount of future funding and political support

from the European Commission for the bioeconomy is set to hamper investments into the switch from oil-based industry production to renewable, bio-based manufacture in Europe.

The schedule for the review of the bioeconomy strategy has been delayed until the end of 2017.

More importantly, it is not yet certain if the strategy will be updated.

“The discussion whether there will be a new strategy is still open,” said Lino Paula from DG Research and Innovation. In late March, at the Bio­step Forum “Creating Networks for the Transition to a Bio-based and Circular Economy” in Brussels, Paula announced that the results of the review would not be available before the end of the year. Originally, the plan was to conclude the review at the end of 2016 (see European Biotechnology, Spring 2016).

Accordingly, it remains unclear for investors, industry, and private-public partnerships, such as the €3.7bn Biobased Industry JU, whether the European Commission will change the initial

strategy adopted in 2012. With Horizon 2020, the Commission had doubled its funding for the bioeconomy compared to FP7, to an amount of about €4bn.

Short story, long decision After the adoption of the Circular Economy Action Plan, the Commission decided to examine the contribution of its bioeconomy strategy to the circular economy. The debate as to whether the bio­e conomy strategy needed a revision or not continued at the Environment Council (ENV) in June 2016. This year, the Commission expects several expert reports, including one in June, the

Bioeconomy Stakeholders Manifesto, a societal agenda for bioeconomy finalised by the European Bioeconomy Panel: a group of primary producers, policymakers, public administrations, scientists, and researchers, as well as civil society interest groups. Finally, in mid-November 2017, results of the current evaluation of the strategy are to be presented at a Bioeconomy Day in Brussels, Waldemar Kütt, Head of Unit Bioeconomy Strategy at DG Research, told European Biotechnology. “A decision on a possible revision of the bioeconomy strategy will likely be taken early 2018.” If the strategy is then revised, an updated review will be available at the end of 2018 at the earliest.

Picture: artjazz/fotolia.com

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Previous announcements said that it would be published in 2017 (see European Biotechnology, Spring Edition 2016).

Preparing the ground for a circular bioeconomy According to Paula, it is important that “stakeholders get involved and give input now,” in order to assure that the outcomes of the bio-based value chains do fit the needs of society. At the BioSTEP meeting, 55 experts gathered to discuss how the input and needs of the highly diverse stakeholders crucial to a successful transition to bio-based and circular production processes could be merged. In April, BioSTEP published a white paper summarising its recommendations for a commonly accepted governance of the bioeconomy:

›› Support the networking of SMEs: As

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A diagram for the circular bioeconomy: products, restorative and regenerative by design, are produced by intertwining biological and technical cycles, in order to decouple economic development from the consumption of finite resources.

tion/evaluation stage) of the bioeconomy and circular economy strategies, according to the bio­STEP paper.

Starting nationally While consensus building at the EU level often is difficult, due to divergent regional needs and preferences, local and national bioeconomy strategies are setting starting points for broader coalitions. According to the Lodz paper published last year (see European Biotechnology, Winter edition 2016), “there is not a single global bio­economy. It’s local by nature.”

The policy paper recommends using ESIF funds (€20bn in total) to implement local bioeconomy solutions, to network regionally, and only then, to create an integrated effort, including the education of the civil society.

A potential way forward has been demonstrated by national bioeconomy strategies implemented, for example, in Germany and, most recently, in Italy and in France. Recently, the French government announced a national bioeconomy strategy (European Biotechnology, Spring

2017) and is now looking for input from other nations to determine the best means for implementation. In April, several German ministers announced that the biologising of industry could become as important as digitalisation in the next legislators’ term starting this autumn.

While Europe has positioned itself as a technology leader, bio-based production has moved to Asia. According to the latest market survey provided by the Cologne-based nova-Institute, growth in production capacities for biopolymers has decreased from 10% annually, from 2012 – 2014 to just 4% in 2015 and 2016, due to low oil prices and a lack of political support. According to nova-Institute, political support from the French and Italian governments for bioplastic bags contributes to the 10% annual growth rate for biobased PLA. According to nova-Institute, biopolymers are still, as of yet, a niche market that needs political support.

By 2021, the experts predict biopolymers will contribute 8.5 million tonnes to the 300 million-tonne plastics market – just 2% bio- versus 98% oil-based products. L t.gabrielczyk@biocom.eu

Pictures: Ellen MacArthur Foundation

the development of bio-based products and processes is often hampered by a lack of cooperation and investment, BioSTEP recommends that public agencies act as matchmakers. Creating a coherent regulatory framework would be crucial for supporting more investments in the field. ›› Create public acceptance: As a first step for creating broad acceptance of bio-based products and processes, Bio­step recommends involving NGOs and civil society organisations in discussions regarding the implementation of the bio-based and circular economy. Trust in biobased products (versus distrust in green claims from the industry) would be a precondition for market uptake. Thus, development of a common understanding of benefits and risks would be crucial for fostering a positive perception in the general public. However, only the right mix of communication tools (namely, education, information, discussion, or knowledge production) will bring the message to the specific target group. ›› Create opportunities for input at all stages of strategy development: Besides built-in participation, stakeholders must have the opportunity for intervention in later stages (at the implementa-

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Insight Europe

Patent battle CRISPR genome Editing The patent battle over the groundbreaking CRISPRbased genome editing technologies that is mounting between European researcher Emanuelle Charpentier and co-workers and stakeholders supporting US genome editing expert Feng Zhang from Broad Institute escalated in April. In the US, UCBerkeley (Charpentier’s partner Jennifer Doudna) – supported by Charpentier and the University of Vienna – filed an appeal with the federal Court of Appeals against the ruling of the US Patent and Trademark Office, claiming that UC-Berkeley and the Broad Institute’s respective patents on CRISPR Cas9 technology did not interfere, thus leaving them both free to pursue unique patents. In Europe, a similar case is pending, as Charpentier claimed that the European Patent Office intended to grant her/UC Berkeley and University Vienna a broad patent covering CRISPR/ Cas9 gene editing technology.

The patent dispute is not driven by the desire to restrict researchers from applying the technology but by the commercial interests of the inventors. Charpentier has licenced her CRISPR Cas9 IP to CRISPR Therapeutics, a public company that had a market capitalisation of about US$683m at the end of April. Zhang has licenced IP to Editas Medicine, which had a market capitalisation of US$771.26m at the time. Last December, Editas licensed IP from Zhang’s lab for his CRISPR-Cpf1 technology. Cpf1 is much smaller than the Cas9 endonuclease. In April, it was shown to be able to correct defects in the dystrophin gene, which cause Duchenne muscular dystrophy. Cpf1 demonstrated a similar efficiency to that of the Cas9 enzyme. 

European Biotechnology | Summer Edition | Vol. 16 | 2017

IP Flash

By Dr. Jörg Thomaier, CEO Bayer IP & Head of IP Bayer Group, Speaker at www.unitarypatentsystem.eu, Bayer AG, Germany

The main issue impacting Bayer’s patent tremely supportive of the new Unitary filing strategy is the cost-effectiveness of Patent System (UPS) and has been one the UPS and the efficient enforcement of of the driving forces behind it within the patents through the UPC in one proceedGerman industry. However, the compa- ing. In the life science area, firms usualny will not be putting its full portfolio ly file in a number of European countries through the UPS and the Unified Patent anyway, because it is more cost-effective Court (UPC). Instead, Bayer will screen to do process that way. As it stands at the moment, the its portfolio and UPS will be a very hold back many effective system. of its valued patBayer sees advantages for Yet, the biggest ents. Bayer’s deenforcement across Europe! challenge for the cision to withhold UPC is to develop has less to do with the UPS (the patent system should work a reliable, predictable, and identifiable perfectly with the EPO), and more to do jurisprudence in a relatively short amount with the fact that any UPS patent auto- of time. When it comes to pharmaceutimatically falls under the UPC. The UPC cal company strategies, Bayer tends not is a completely new jurisdiction that to be mainstream. In fact, during the prebrings uncertainties with it, and there paratory work and the development disis a lack of regulation around the sup- cussions for the UPS/UPC, Bayer was plementary protection certificates (SPC) very much alone. A few pharmaceutiand the UPS. After an initial settling-in cal companies said that they would add period, the UPC will probably be an ef- some patents in and leave some out, fective and reliable system. Yet, until IP but others said that they would opt-out professionals have had the opportunity all their patents. Others said that they to get a feel for the predictability and re- would see how the system developed liability of the courts in the UPC, Bayer before making any decisions. However, cannot afford to risk putting its most val- it is difficult to observe the development ued patents into the UPS/UPC. Never- of an empty system. Many other comtheless, the goal is to have almost all the panies see the disadvantages and risks of the system. They perceive the risks in company’s filings in the system.

Why not put everything in there from revocating an important patent in one the beginning? This is largely deter- spot for the entirety of Europe. However, mined by the enforcement and effec- at Bayer, we see the advantages of this tiveness of the UPC itself and the avail- new system for Europe, particularly for its enforcement throughout Europe.  ability of an SPC system.

Claims Bayer has always been ex-

Picture: Feng Zhang, MIT (below), Bayer AG (below)

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European Biotechnology | Summer Edition | Vol. 16 | 2017

GM acreage growing both world- and EU-wide ISAAA Statistics GMO world market adoption is growing further. While global GMO cultivation areas have increased by 3% to 185.1 million hectares in 2016 versus 179.7m hectares in 2015, GM crop cultivation in Europe rose 17%, from 116,870 hectares in 2015 to 136,363 hectares, due mainly to expansion in Spain.

Biotech crops have become a vital agricultural resource for farmers around the world, because of the immense benefits for improved productivity and profitability, as well as conservation efforts,” said Paul Teng, Chairman of the Board of the International Service for the Acquisition of Agri-biotech Applications (ISAAA), which published the annual GMO statistics.

Whilst adoption in the US, the Americas, and Asia was high, Europe and Africa still lag behind.

EU opt out rules fail to accelerate GM approvals In Europe, resistance against GMO products remained high.

Only four countries – Spain (129,081 ha), Portugal (7,069 ha), Slovakia (138 ha), and the Czech Republic (75 ha) planted GMO crops. Efforts by the European Commission to speed up GMO market approval of safety-assessed GMOs by granting member states the right to opt out from acreage failed in late March: Applications for market approval for three GM maize crops (Syngenta’s Bt11 maize, Dow Agrosciences’ GM Maize 1507, and BASF/Monsantos’s Mon810 maize) to be cultivated in the EU failed because EU countries did not change their voting behaviour. They did not reach a qualified majority pro or against the insect-resistant crops.

The next Big Thing in plant biotech As biotech crops enter the third decade of planting/commercialization, the ISAAA project game changing innovations can double food production. Genome editing and new breeding technologies have already entered the market. In addition, health-improving products like soybean for humans and animals (containing omega-3 fatty acids, high oleic acid, low phytate, and high stearic acid), potatoes (with modified starch/sugar), alfalfa (with low lignin), and non-browning potatoes are already available; non-browning apples are projected to be available on the US market in 2017, as well as major staple crops that are enhanced with beta-carotene and ferritin and already in the advanced stages of development. Innate™ potato series have been commercialised in the US, with 2,500 hectares of potatoes grown and 70,000 non-browning apple trees (~81 hectares) planted. Acceptance of these two biotech crops can contribute to the reduction of food waste due to browning and easy spoilage of products, the ISAAA reported. 

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Brexit and patents IP On 23 June 2016, the UK voted to leave the EU and, thereby, decided for Brexit. As

of today, it is still uncertain what the exact implications of this decision will be, including important questions regarding how the political and legal nature of the future relationship between the UK and the EU will be. › Dr. Markus Engelhard and Dr. Dennis Kretschmann, Boehmert & Boehmert

Existing EP (bundle) patents The existing/old European system for patent rights is based on a centralised application process handled at the European Patent Office (EPO), in which a single patent application matures to grant through the EPO and, thereafter, is

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Dr. Markus Engelhard (German Patent Attorney and European Patent and Trademark Attorney, Boehmert&Boehmert) is active in the protection of intellectual property in all fields of life sciences, pharmacology, and biotechnology, having a particular focus on therapeutic biomolecules and pharmaceutically active agents.

split up into its national parts (“EP bundle patent”).

The underlying European Patent Convention (EPC) is an international treaty that is not based on EU law. In fact, a considerable number of EPC member states, even today, are not EU members.

It is likely that the UK will continue to participate in this system, irrespective of the future nature of the relationship between the UK and the European Union.

One of the areas that may be affected in the near future, however, is the new Unitary Patent (UP) system and the Unified Patent Court (UPC). In a nutshell, the UPsystem envisages the granting of a single, unitary patent through the EPO for

all participating EU member states, and the enforcement of all European patent rights in a new, unified European court system. The system requires ratification in 13 member states in order to come into effect, amongst which there must be France, Germany, and the United Kingdom. Germany and the UK have not ratified yet. Towards the end of last year, the new UK Government surprisingly announced that they would move ahead with the ratification process as planned.

The website of the Unified Patent Court envisions a start of the system in December 2017, but with the recent announcement of a general election in the UK, a considerable degree of uncertainty has returned. Many observers still expect, however, that the system will come into operation in the spring of 2018, although this timetable has also most recently been put into doubt, since news has emerged that the German Constitutional Court has preliminarily stopped the German ratification process of the UPC system Without intending for this article to replace the necessary, detailed legal advice of a qualified patent attorney, the following will, therefore, look at some of the details of the UP system:

The Unitary Patent (UP) and the Unified Patent Court (UPC) Unit ar y Patent prote c tion can b e claimed within one month of the granting of a European patent. Such a unitary patent will cover the territory of all signatory states, and it will be possible to have both the unitary patent and to vali-

Pictures: Boehmert&Boehmert

With the exception of Article 50 of the Lisbon Treaty, there is at present little guidance on what effects the exit of the UK from the European Union will have on the overall legal landscape. This uncertainty is exacerbated by the imminent general election in the UK and the uncertain outcome of the Brexit negotiations.

Very recently, the European Commission and the European Medicines Agency (EMA) published a Questions-andAnswers paper providing some guidance on the legal consequences of Brexit on marketing authorisation holders of centrally authorised medicinal products.

According to the paper, there are a series of drastic consequences of Brexit on regulatory approval issues, including the requirement for UK-based central marketing authorisation holders to transfer their authorisation to a holder established in the European Economic Area (EEA).

Hence, in the regulatory field, this already foreshadows some of the possibly painful consequences of the UK’s withdrawal from the EU. Brexit will, however, also have an effect on the patent system. The following will attempt to address some of the issues that may be of relevance in this context:

15.06.2017 12:22:26 Uhr

Pictures: xBoehmert&Boehmert

European Biotechnology | Summer Edition | Vol. 16 | 2017

date the European patent for states outside of the unitary patent system. However, the new Unitary Patent system not only affects newly granted EP-patents, but also subjects all validations of existing European patents in those countries that have ratified to the jurisdiction of the Unified Patent Court. Patent owners can choose for each of their patents to use the new system, or they can request that their respective European patent(s) are exempt through “opting out.” Opting out can be effected by a simple request via the UPC Registry, during a limited time period before the agreement comes into force, the so-called “sunrise period,” and, thereafter, under certain conditions, also during a transitional period of seven years. Currently, the sunrise period has not yet begun, but it may be expected likely to start towards the end of 2017.

The implication of the choice between opting out or staying in the new system is that any European patent that is under the jurisdiction of the Unified Patent Court, namely any unitary patent and any European bundle patent that has not been opted-out, must be litigated at the UPC. The patent can be enforced in the UP-signatory countries through single proceedings before the UPC, but, at the same time, there also comes the risk of a central attack, namely a central revocation action

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Dr. Dennis Kretschmann (German Patent Attorney and European Patent and Trademark Attorney, Boehmert&Boehmert) focuses on the development and management of patent portfolios in the areas of physics, optics, medical technology, IT, and software.

against the patent. By opting out of the system, the respective European patent will not be under the UPC jurisdiction, and any litigation concerning the patent will be dealt with on a national level.

Opting out There are different strategies with respect to the question of whether to opt-out or stay in. Not opting out gives patent owners the possibility of immediately using the new system, namely

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asserting their patent(s) at the UPC and obtaining European wide injunctions.

In contrast thereto, opting out provides patent owners with the certainty that they can continue to use the already existent European national litigation systems. There is a plurality of considerations that one might wish to employ in order to decide on an opt-out/stay-in strategy, for example: Patents that are potentially useful for a Europe-wide litigation should stay in, whereas if the focus is on the safeguarding and hedging of patents from a central attack, such patents should be protected by opting them out. If a patent is to be enforced in a country where it may be difficult to assert patents, staying in the UP system may be advantageous.

In the same manner, patent owners may also wish to think about filing direct national patent applications in core European countries, thus avoiding the question of opting out or staying in altogether. If the patent is the subject of a license contract, licensees should be consulted about opting out or staying in, and licensing contracts should be reviewed and, possibly, updated to reflect the new options.

Ultimately, in the words of a famous Nobel-laureate singer-songwriter, the times, they are a-changin,’ as well for patent owners.

L

15.06.2017 12:22:33 Uhr

Rubrik

European Biotechnology | Spring Edition | Vol. 16 | 2017

Mashed potatoes, lightly smoked?

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Pictures: xxx

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Genome Editing

European Biotechnology | Summer Edition | Vol. 16 | 2017

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Brave new food CRISPR & Co. The possibilities offered by CRISPR/Cas9, TALENs and other new genome editing

Pictures: frica Studio/fotolia.com (left); Cellectis SA (right)

technologies are making the mouths of plant breeders water – and not just because the methods give seed developers new options when it comes to optimising traits such as yield, resistance to environmental stress, diseases or pests. Gene-edited plants could soon make inroads even with Europe’s strict regulators, and throw open the door to tastier, healthier food.

Last year, an exceptional dinner for actors, politicians, journalists and other city celebrities was planned at a haute cuisine restaurant in New York. It was billed as a world first, a meal of the future – the launch of an expedition into an age of new food. On the menu: tofu and soy burger, lightly smoked mashed potatoes, and soy milk and strawberry fontaine­ bleau for dessert. Not all that exceptional on the surface...but all were made with ingredients from gene-edited plants designed by biotech company Calyxt. André Choulika, head and founder of the Cellectis Group, Calyxt’s mother organisation, explains that the event mirrored a similar dinner given in Paris 250 years ago: “When we were having chips and fries at Calyxt made from one of the first harvests of our genome-edited potatoes, I thought: ‘This is a historic event.’” The chips were made from potatoes with a gene that had been edited to inactivate the enzyme responsible for the degradation of sugars in the tuber, keeping them sweeter in cold storage and reducing the formation of the carcinogen acrylamide during the frying process. “While I was thinking that billions of people could eat such food in the future, I was reminded of Antoine Augustin Parmentier,” Choulika says. The 18th-century French botanist shot to fame for his role in making the potato a pillar of France’s food supply. To overcome myths that the foreign tuber was toxic – some skeptics even claimed it transmitted leprosy – Parmentier invited members of the elite class like King Louis XVI and American ambassador Benjamin Franklin to enjoy a range

14_20_EB_Summer_2017_Cover_CRISPR_sk.indd 15

of potato recipes. The sly promoter also had potato fields guarded during the day, but left them unguarded at night, giving farmers the chance to steal the ‘valuable’ plant. It’s hard to say how much those tricks contributed to making potatoes a staple food for hundreds of millions of people in the EU alone. But Choulika decided to revive the idea “to enable a new food revolution that will influence the 21st and further centuries.”

Calyxt’s dinner will probably not convince the European public to put aside

its concerns on genetically modified organisms (GMOs) or their gene-edited organism cousins (GEOs), but the event did raise public awareness of new genome editing technologies, and how much they could change humanity’s food supply in the very near future. Practically every major seed company and leading breeder is already pursuing genome editing, at least for research purposes. And a big reason why is the game-changing genescissor technology CRISPR/Cas9.

CRISPR – a booster for plant breeding

André CHoulika CEO, Cellectis Group

? !

What will be the Next Big Thing in plant breeding?

Most of the effort in biotech­ nology tries to focus on the farm­ er’s needs, in a kind of race for pro­ ductivity. But we don’t need more yield. We already produce more than we can even consume. Calyxt is therefore trying to improve the quality of food.“

Take Bayer, for example. If the German giant is given the go to acquire Monsanto, it will control about 40% of the global seed and pesticide market. CRISPR/ Cas9 is “a relatively new technology in our plant breeding activities,” says Adrian Percy, Head of Research and Development at Bayer’s Crop Science division.

Even so, the company “has been working on genome editing for a few years now, using different types of nucleases like meganucleases and TALENs” (Transcription Activator-Like Effector Nucleases).

According to Percy, the goal is to speed up development in plant breeding and bio­ technology, particularly when it comes to introducing disease resistance or insect resistance traits into new varieties. Another area of high interest is increasing plant resistance to a­biotic stress factors like salinity and drought. “And then, of course, also to more generally help increase plant yield,” Percy adds. In early research projects, Bayer is evaluating the technology, pre-

15.06.2017 12:23:56 Uhr

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Genome Editing

European Biotechnology | Summer Edition | Vol. 16 | 2017

SP5G gene, which delays the phase. In terms of disease resistance, disrupting the promoter of SWEET genes in rice induces resistance to bacterial blight, and mildew resistance in wheat could be achieved by knock-outs of the MLO-A1 genes. Future targets for increasing yield could be genes involved in the efficiency of photo­synthesis or seed growth and number.

“One of the advantages of CRISPR is multiplexing”

dominantly for use in cereals, cotton, canola or oilseed rape in Europe, as well as soybeans and also vegetable seeds. “The potential of this technology is just enormous,” Percy says. “I can see this being very, very broadly used.”

CRISPRed corn – made to be waxy Bayer’s bioengineers want to dramatically shorten development cycles for new varieties, which can currently take up to 10 years or more. With genome editing, Percy hopes to cut that time in half. “To save years on development of new plant varieties is obviously an advantage to us as a business, but also a big advantage to our customers. That’s because we see the emergence of new plant diseases and the impact of volatile weather patterns happening very quickly, and there’s an urgent need to adapt plants to changing climate cycles.”

While Bayer’s genome editing attempts are still in the research phase, DuPont Pioneer has taken things a step farther.

The seed specialist has already received USDA approval for a CRISPR/Cas-edited ‘waxy’ corn variety that contains about 97% amylopectin starch instead of the standard 75%. Through the involvement of its subsidiary Danisco, a company that was active in basic research into CRISPR/ Cas-systems in nature, DuPont Pioneer

14_20_EB_Summer_2017_Cover_CRISPR_sk.indd 16

holds a couple of CRISPR/Cas patents.

It integrated genome editing technology into its breeding programmes over two years ago. “We certainly see this as a technology that we would like to apply essentially in all of our meaningful crops – soybean, corn, oil-seed rape – for Europe sunflower, wheat, rice – you name it,” says Neal Gutterson. DuPont’s vice president of R&D says his firm is focussing on many of the same traits that interest other breeders: “Drought tolerance and better water use are really high-valued traits for our customers,” he reports.

“And disease resistance is a trait category that we think is relevant to all kinds of crops and ways to impact yield.” DuPont has also kicked off programmes to improve the value of certain crops, trying to improve for example the quality of oil protein farmers get from certain varieties of soybean.

A SWEET gene to resist blight Although the companies don’t provide any details about the genes they aim to target with genome editing, there are obvious candidates. Drought tolerance, for instance, could be achieved by increasing the expression of the ARGOS8 gene, which down-regulates the hormone ethylene, an inhibitor of plant growth. Other adaptations to climate change could involve changing when a crop flowers via a deletion of the

Dinner fo the 21st century October 20, 2016 Soy blinis, smoked salmon Tofu & soy burger Soybeans hummus, giit-head bream, lemon –– Lightly smoked mashed potatoes Oven-baked potatoe pie Fermented potato blinis, confit sardine –– Soy, marinated fish, caviar –– Cookpot of soy, seasonal vegetables, herb & top pesto –– Beef, potatoes in the fireplace, cooking jus –– Soy milk & strawberry fontainebleau

It took the Lab-Ducasse Conseil’s chef six months to prepare the GE dinner.

Pictures: Cellectis

Cellectis CEO Andrè Choulika (left) invited a select group to a New York dinner made with genome-edited food such as anti-acrylamide potatoes.

Germany-based BASF AG also recognises the potential of genome editing, but is more reluctant at the moment to publicise details about its development plans.

“CRISPR/Cas is a technology that will find broad application in a variety of fields in the life and biosciences,” says BASF Senior VP Plant Science Research Burkhard Kröger. “Applications are in the optimisation of plant traits as well as in industrial biotechnology.” Kröger believes the most important advantage of CRISPR/Cas is the precision of the genetic modification compared to conventional methods like radiation or chemical based mutagenesis. “Genome editing does not induce unwanted side effects in the genome that subsequently have to be bred out via cumbersome, time-consuming crossbreeding.”

15.06.2017 12:25:30 Uhr

European Biotechnology | Summer Edition | Vol. 16 | 2017

Headquartered in Einbeck, Germany, the KWS Group is already evaluating CRISPR/ Cas9 and other genome editing technologies in their research programmes, especially in areas such as improving disease resistance of crops like sugar beet. “One of the advantages of CRISPR is the option of editing more than one target gene,” says Anja Matzk, the firm’s Head of Regulatory Affairs. Such “multiplexing” allows rapid trait-stacking and editing of whole gene networks while the genetic background – the result of hundreds of years of breeding – remains untouched.

Game-changer in breeding history This is why genome editing, for the first time in breeding history, could substantially improve complex quantitative traits like drought tolerance or yield. Multiplexing is particularly useful in crops with more than the usual diploid set of chromosomes – among them wheat and corn, which are polyploid. Genome editing allows breeders to target all of the alleles at once, which was hard to achieve with either breeding or classical genetic modification technologies. “CRISPR can be used to change all the alleles in tetraor hexaploid genomes, which is otherwise very laborious and time-consuming due to the necessity of multiple generations of backcrosses,” Matzk says. Exactly how much time the breeder could save with genome editing, however, depends heavily on the crop. “In terms of breeding, sugar beet is a laborious plant, because it is biennial. With corn, on the other hand, you can harvest three generations in a year.” KWS believes the time savings using CRISPR/Cas would be huge. Instead of six or seven generations, only two or three could be necessary to develop a new variety, Matzk says. “Potentially we could halve the time it takes to progress a breed, which is a substantial improvement.”

Many companies though are still on the fence when it comes to deciding whether Crispr/Cas is the right genome editing system to reach their goals. “Clearly, CRISPR/Cas9 or CRISPR/cpf1 have

the capacity to be much more versatile and efficient in their use, so I’m sure that we would gravitate towards these newer technologies,” Bayer’s Adrian Percy says. “But we also anticipate that there will be new versions coming out, because it’s a very fast-moving area of science.” The crop science specialist makes it clear that Bayer will definitely not focus on just one technology yet. “We keep an open mind to all of these technology areas, so that we can pick the right tool for the right application. In some areas, we look more to CRISPR-based systems.

With others, where we have more experience, we work with TALENs.” Bayer has licensing agreements with the patent consortium around CRISPR/Cas9-inventors Emmanuelle Charpentier and Jennifer Doudna. BASF decided to reach a global licensing agreement with the Broad Institute of MIT and Harvard for the use of CRISPR/Cas9 genome-editing technology instead – despite the ongoing patent battle between the two groups. “If the patent situation should change, we will react proportionately,” Kröger says, adding that although CRISPR/Cas has “the greatest potential”, the company also keeps an eye on other genome editing methods.

Finger? Crispr? Maybe Talen?

Despite the hype surrounding CRISPR/ Cas9, breeders are well-advised not to abandon other genome editing technologies too quickly. For instance, oligo­ nucleotide directed mutagenesis (ODM), is one of the simpler methods that doesn’t employ enzymes. It’s been used by companies like Californian Cibus to develop herbicide-tolerant canola, flax, and rice, as well as a Phytophora­-resistant potato. Three European countries – Sweden, Germany and the UK – have categorised ODM as mutagenesis, which is not subject to European GMO regulations. Never­ theless, due to a pending decision from the European Commission, Cibus’ varieties are not yet marketed in the EU. Just like plants developed with enzyme-based genome editing technologies like CRISPR/ Cas, zinc fingers, and TALENs, they’re in a

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15.06.2017 12:25:35 Uhr

Genome Editing

‘CRISPR is a tool’

Neal Gutterson VP of research at DuPont Pioneer, Johnston, Iowa (US)

EuroBiotech_Is the delayed EU decision on how to regulate GEOs altering your breeding strategy?

Gutterson__There is a risk of uncertainty in

the regulatory paradigm, the public perception, the social license. And that’s a global issue. Certainly, the outcome in different regions may impact our specific choices – whether we focus more on wheat, rice, corn or soybeans. We’re keeping an eye on EU. EuroBiotech_Is CRISPR GMO, or not?

Gutterson_It’s a tool. And the tool could

be used to achieve many things. It could introduce recombinant, transgenic genes into the genome. Those cases are without a doubt GMO products. But there is a set of applications of the CRISPR technology that we see as delivering essentially the same category of outcomes as you would get from conventional breeding. Those categories of outcomes you might think of as being non-GMO – as the USDA has decided, too. Like moving a resistance gene from one to another variety of corn. The same achievement could be met by breeding as well as using CRISPR/Cas as a tool. Especially if you want to bring two or three different resistant genes together in one variety. That is possible but could be quite challenging with conventional breeding.

CRISPR/Cas could simplify this substantially. That shouldn’t be considered a GMO.

European Biotechnology | Summer Edition | Vol. 16 | 2017

legal limbo. Developed in 2012, CRISPR/ Cas is the youngest, cheapest and fastest of these methods, but it may not be the best for editing plant products. “People got excited about CRISPR/Cas because it is very easily designed. Every scientist can design an oligo­nucleotide – the guide-RNA – and can become a gene editor,“ says André Choulika from Cellectis. “We’re gene­editing geeks who have worked with every new gene­-editing technology that came out in the last 17 years. And we’ve been very excited about CRISPR/Cas, too.“

Thousands of unintended mutations Originally, Cellectis focused on another, more cumbersome enzyme-based genome editing tool called Meganuclease, then switched to TALEN technology in 2011. Now Choulika has decided not to adopt CRISPR/Cas, due to what he calls “a lack of specificity and efficiency.”

What put him off CRISPR/Cas most, he says, were the off-target effects. “CRISPR/ Cas is absolutely great to do research, but it is not meant to develop products. We tried it; we don’t like it.“ Target site specificity of CRISPR/Cas genome editing does indeed remain controversial, with evaluation of the frequency of unintended off-target editing in crops showing inconclusive results, at least according to Armin Scheben and David Edwards from the University of Western Australia in Perth in a 2017 Science perspective (DOI 10.1126/science.aal4680).

In a May 2017 Nature M ethods paper (DOI 10.1038/nmeth.4293), scientists described thousands of unintended off­ target-mutations in gene-edited mice after whole-genome sequencing of their DNA. In plants, Scheben and Edwards add, the number of potential off-target edits is even higher than in animals, because many crops are polyploid and have high levels of repetitive DNA. Choulika isn’t convinced by the Australian researchers’ notion that off-target editing can be reduced by using variants of the Cas enzyme and other improvements of the technology. If CRISPR/Cas is so advantagous, he asks, then where is the expected “tsunami“

of CRISPR/Cas-edited plants? “Most recent USDA filings for new varieties have come from Calyxt, and we are a 25-person company...not comparable to Dupont or Bayer,“ Choulika says. “It’s not the fact that we’re better. We just use the better technology – TALENs.“ Instead of focusing on the traits affecting yield, disease and abiotic stress resistances that bigger breeders are fixated on, Calyxt is pursuing a slightly different path.

“Most of the effort in biotech­nology tries to focus on the farmer’s needs, in a kind of race for productivity,“ Choulika says.

“But we don’t need more yield. We already produce more than we can even consume.“ Hunger, the scientist says, has more to do with wars than plant yield. Calyxt is therefore trying to improve the quality of food, along with the health of both consumers and farmers. Its port­folio includes reduced trans-fat soybean oil, an improved-quality potato, canola oil lower in saturated fat, and low-gluten wheat.

And regarding farmer health, it developed a powdery mildew-resistant wheat – “a pathogen that you usually spray with chemicals,“ Coulika says.

“CRISPR will lead to a change in the regulatory paradigm.”

European regulators still haven’t decided whether any of these varieties might one day reach the European market. Lawmakers have delayed a decision for almost two years now. “I’m deeply convinced that they would take a decision to regulate such products reasonably,“ Choulika believes, adding that genome editing is no different than the chemical or radiation mutagenesis that has been standard practice for the past 150 years. “Why should we regulate it differently than every­thing that is already on the market? Everything we eat has been mutated by chemicals or physical means.“ If the EU authorities make the decision to regulate gene­- edited organisms as they have in the past with GMOs that carry cross­species traits, they would “throw Europe back into the Dark Ages, and it will be totally out of the game.“

Pictures: DuPont Pioneer

18

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15.06.201730.05.17 12:26:2014:50 Uhr

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Genome Editing

European Biotechnology | Summer Edition | Vol. 16 | 2017

N terminus

Meganuclease

C terminus

5’ C A C A G A T T C C G A A T C G A T A T C A G A A A G C T T T C 3’ T C G T C T A A G G C T T A G C T A T A G T C T T T C G A A A G Right ZFP

Zinc Finger Nuclease (ZFP: Zinc finger protein)

Fok1 (+) 5’ T C C C C T G C T T G G C T G G G C G C A G T G G C T C A T G C 3’ A G G G G A C G A A C C G A C C C G C G T C A C C G A G T A C G Fok1 (–)

TAL effectors

Left ZFP Fok1 (–)

TALEN

5’ G C A G T T C A C T A T N N N N N N N N G C G G T A A T G A T C

(Transcription Activatorlike Effector Nuclease)

3’ C G T C A A G T G A T A N N N N N N N N C G C C A T T A C T A G Fok1 (+) tracrRNA gRNA

Cas9

T C A A G T G A T A G T C T G C C A T

CRISPR/Cas9

crRNA

5’ G C A T G A G T T C A C T A T C A G A C G G T A N C C A T G C A 3’ C G T A C T C A A G T G A T A G T C T G C C A T N G G T A C G T PAM sequence

Mechanisms of action across a range of genome-editing technologies

“Ultimately, genome editing will lead to a change in the regulatory paradigm,” Bayer’s Adrian Percy hopes. “This technology is so important and so revolutionary. It will not just benefit companies like Bayer, but also the public and farmers around the world,” he thinks. “We really have to find a way that it is sensibly regulated using sound science.” If genome editing is simply used as a gene knock-out tool or to make very subtle changes in the genetic code with no foreign genetic material introduced into the plant, Percy thinks that the resulting organisms need to be regulated in a “completely different way than the traditional GMO, where you are actually integrating foreign genetic material into a plant.” China could be the first case in point as governments grapple with rethinking regulation procedures due to CRISPR/Cas et al. “They have an enormous challenge in front of them in terms of feeding their population, and seem to be willing to re-evaluate and look favourably on these new technologies,” Percy says. In Japan, for the first time in the

country’s history, a food research institute was allowed to plant a genome­-edited rice variety outdoors this June. “But countries closer to home, like the UK, also seem to favour these types of new technologies.”

In the US, genome-edited plants like the Calyxt potato have been accepted by the USDA, and don’t have to go through the GMO regulation process.

Calls for legal certainty Many in the sector say that, what’s vital now is that the EU makes a decision quickly. “Legal certainty is extremely important, especially for a lengthy process like breeding,” KWS’s Matzk says. “As a global company, we prefer global solutions, although this is very difficult to obtain, at least in my lifetime.” She believes she has a good rule of thumb: “Every­thing that could be created by nature or classical breeding shouldn’t be regulated.” That sounds like a straightforward definition. But what if you change not just one base pair in a

gene, but ten or twenty different base pairs across the gene? That’s perfectly possible with multiplex genome editing by having the DNA cutting enzyme work on multiple targets. That would mean you could end up with a gene that more closely resembles its homolog in a distantly related species. Matzk agress that “the distinction might not be crystal clear.“ But it would be a bad move, she insists, if every single case had to be reviewed and regulated, because that would prevent legal certainty and reduce innovation. “To define general categories with clear criteria – this is a GMO and needs to be regulated, whereas this is a GEO and does not need to be regulated – would already be a huge help,“ Matzk says. “With borderline cases, one would have to talk with the regulators, of course.“ André Choulika is looking forward to a decision as well. He hopes the ruling could pave the way for another historic dinner.

This time in Paris – leading the Old World into a new world of genome edited food. L

s.karberg@biocom.eu

European Biotechnology | Summer Edition | Vol. 16 | 2017

Update of ongoing clinical trials AIDS

French Abivax SAS’s (Paris) reported in May that the application of 50 or 150 mg doses of its HIV drug candidate ABX464 over 28 days was not sufficient to prevent viral rebound from HIV reservoirs.

However, 7 of 14 patients treated with a combo of darunavir, ritonavir, and cobicistat, plus the viral replication blocker, responded to the treatment within the ongoing Phase IIa study as shown by a 25% reduction in HIV blood DNA levels in chronically-infected patients. Accordingly, Abivax has extended treatment cycles to 56 and 84 days, respectively, in order to investigate if the primary study endpoint will be impacted by a longer treatment period. Results will be available by autumn 2016. ABX464 prevents rev-mediated export of unspliced viral transcripts to the cytoplasm.

Infection

Following the end of the partnership with Swiss drug major Roche, antibiotics developer Polyphor Ltd (Allschwil) is heading for Phase III trials of its Pseudomonas aeruginosa-targeting lead antibiotic Murepavadin (POL7080) this year.

Trice daily injections of 2.5 mg/kg of cyclic peptide antibiotic targeting LPS assembly protein OstA over two weeks led to a complete response in 90% of 12 patients enrolled with ventilator-associated pneumonia at day 9 and a 28-day mortality of 8.3%. If confirmed in a larger patient population, this would be significant progress. According to the company, 20 – 50% of patients die from ventilator-associated pneumonia caused by the infection with the Gram-negative pathogen. Multiple doses of the novel agent were tolerated well by the intent-to-treat patient population, Polyphor reported.

Rectal Cancer

Oslo-based Targovax A/S has initiated exploratory Phase Ib testing of its treatment TG02, a mix of the eight most common protein fragments encoded by the mutated RAS oncogene in patients with

21-23_EB_Summer_2017_Trial_tg.indd 21

colorectal cancer. In the pilot study, the company plans to enroll 10 patients with recurrent rectal cancer to assess if they’ll express TG02-specific T cells infiltrating and killing locally treatment-recurrent rectal tumour cells. If the first patient cohort in the open-label, single-arm trial responds to the treatment, a follow-up group of ten further patients will receive a combo of TG02 and Merck & Co’s PD1blocker pembrolizumab, in order to evaluate if TG02 can boost T cell responses in colorectal cancer. In pancreatic cancer, Targovax lead candidate TG01, which follows the same treatment approach, induced T-cell activity against the deadly cancer. Targovax hopes that this can be translated into an overall survival benefit.

At the beginning of May, Dublin-based Allergan plc and its partner Pfizer reported Phase III data from 879 patients with hospital-acquired pneumonia, which was treated with a combo of ceftazidime and avibactam, a broad-spectrum beta lactamase blocker. Trice daily infusions of the combination led to clinical cure rates of 68.8% and 77.4%, three weeks after randomization versus 73% and 78.1% for intravenously administrated meropenem demonstrating non-inferiority, a coprimary endpoint.

Diabetes

In May, Lyon-based Poxel S.A. provided proof-of-concept of its type-2 diabetes treatment imeglimin (PXL008). In 299 patients, the mitochondrial permeability transition pore blocker significantly reduced the level of glycated hemoglobin A1c, a surrogate marker reflecting the three-month average plasma glucose concentration, compared to placebo after twice daily administration over 24 weeks.

PXL008 also reduced fasting glucose concentration. The company said it plans to commence a pivotal Phase III study in Japan, home to a US$5.5bn diabetes market. In the US and in the EU, where regulators want to see cardiotoxicity data, the company is seeking licensors.

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15.06.2017 12:26:36 Uhr

Regulatory Affairs

European Biotechnology | Summer Edition | Vol. 16 | 2017

News Innate immunity killer German-US innate immunity expert Rigontec has launched Firstin-Human testing of its RIG-I agonist RGT100. The activation of RIG-1, a sensor protein of the innate immune system that triggers the decay of intracellular RNA pools and cell death, is a novel approach to re-activate immune cells to attack body cells that have become malignant. RGT100-001 will be directly injected into tumours to assess the safety and pharmacokinetics of the drug. Later, Rigontec will also assess if there is a therapeutic window for the treatment.

Triple attack

It’s still a matter of discussion whether B or T cell attack causes MS. Multiple Sclerosis

Nerviano Medical Sciences’ ROS-1, ALK, and TrkA-C blocker entrectinib has performed well in 32 patients with NSCLC enrolled in an ongoing Phase II study. The oral drug candidate, licenced to San Diegobased Ignyta Inc., showed an objective response rate in 75% of NSCLC patients lasting for 17 months and led to a median progression-free survival of 19 months. Upon enrollment of all 300 patients in autumn, Nerviano will get a milestone payment. The plan is to develop entrectinib as treatment for TRK fusion-positive cancers and ROS1 fusion-positive NSCLC.

Safe anti-viral London-based RSV specialist ReViral has reported positive safety and pharmacokinetics outcomes of its Phase I programme of RV521 in healthy volunteers. The company said enrollment for Phase II trials with the fusion inhibitor will begin in Q3/2017.

Treatment options for patients with progressive forms of multiple sclerosis are getting better. In May, Paris-based AB Science SA reported that its Phase III candidate c-Kit blocker masitinib designed to treat relapse-free, secondary progressive and primary progressive multiple sclerosis was recommended to be continued after treatment of the 600th patient by an independent data monitoring committee (IDMC). The primary endpoint is the change from baseline in the Expanded Disability Status Scale (EDSS) over 96 weeks. Secondary endpoints include MS Functional Composite (MSFC) and MS Quality of Life 54 items (MSQOL-54). Patients will receive a placebo or 4.5 mg/kg daily oral doses of masitinib or escalating daily doses of 4.5 – 6 mg/kg of masitinib. The company expects interim data in 2Q/2018.

At the end of March, Hoffmann-LaRoche AG had received the first EU market authorisation ever for a drug to treat primary progressive multiple sclerosis, which affects 15% of all MS cases. In Phase III trials, its humanised CD20 blocker ocrelizumab, which had failed previously in treating

rheumatic arthritis and lupus erythrematodes, proved to reduce MS-related disabilities. Secondary progressive MS, which follows relapsing-remitting MS, however, affects the majority of MS patients.

Pancreatic Cancer

Headline results, reported by Erytech Pharma SA at the end of March, suggest that the company’s L-asparaginase formulation eryaspase can extend progression free-survival (PFS) and overall survival (OS) in combination with treatment standard of care (gemcitabine/FOLFOX).

According to the EMA, the enzyme treatment itself has been already approved in a range of cancer indications. Erytech, however, enclosed it in blood-group compatible donor blood cells to prevent immune rejection, which could hinder the enzyme in depleting asparagine pools in tumours cells. In theory, asparagine depletion leads to tumour cell death, because the external asparagine supply is essential for the survival of tumour cells but not normal cells, which produce the amino acid on their own. The company, which withdrew an EU MAA for eryaspase in ALL in March, said that the drug was well-tolerated by the 140 patients enrolled in the trial.

Picture: Ralwel/fotolia.com

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Lung cancer

After having received market authorisation in Europe and the US for alectinib as a second-line treatment for ALK-positive NSCLC, Roche has presented data that qualifies the oral drug as first-line therapy. Announcing headline results from the global Phase III ALEX study, Roche said that Alecensa (alectinib) was superior in terms of progression-free survival to crizotinib, the current standard of care for patients with anaplastic lymphoma kinase (ALK)-positive, nonsmall cell lung cancer in advanced stage.

Roche said concrete figures will be presented at an upcoming meeting and that it will file globally for market authorisation of Alecensa as first-line treatment. In the US, the oral drug was granted Breakthrough Therapy designation in 2016.

Pictures: xxx

French Transgene SA has started Phase II efficacy testing of its therapeutic cancer vaccine TG4010 and Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) in non-squamous, non-small cell lung cancer (NSCLC). In the pilot study, 33 patients with metastatic, non-squamous NSCSLC retractive to first-line standard therapy (platinum-based chemotherapy) will be enrolled at UC Davis to determine the overall response rate as a measure to estimate superiority of the combo over Opdivo monotherapy. Readout is expected to be available in Q4/2017. Secondary

endpoints include progression-free survival and overall survival. Karen Kelly, MD, a world-renowned expert of lung cancer and Associate Director for Clinical Research at UC Davis Comprehensive Cancer Centre (USA, California), is the Principal Investigator of this Phase II study. According to Transgene’s pipeline, the company also expects a readout of a study investigating the same combo as first-line therapy at the end of the year. TG4010 is a therapeutic cancer vaccine in which a modified vaccinia Ankara expression vector produces the tumour-associated antigen MUC1 and the cytokine interleukin 2. In a proof-of concept study, published in Lancet, a TG4010/ platinum-based chemotherapy combo showed efficacy as measured by progression-free survival versus chemo mono­ therapy in a biomarker-selected NSCLC subpopulation without known activations of EGFR mutations. Opdivo is approved in the USA for the second-line treatment of advanced, non-small cell lung cancer. The TG4010/Opdivo trial is being conducted via a collaborative arrangement with UC Davis. The investigator-initiated study led

by UC Davis Medical Centre is financially supported by Transgene. Bristol-Myers Squibb is supplying Opdivo. In 2014, Novartis did not exercise an option to licence TG4010 following the announcement of the first of two Phase IIb trials conducted with the compound plus chemotherapy.

Regulatory Affairs

NASH

In mid-April, Irish Allergan and Swiss Novartis agreed to start a proof-of-concept study of a combination of their NASH candidates cenicriviroc (Allergan) and FXR agonist LJN452 (Novartis). As analysts expect an addressable market of US$35bn for treatments of NASH, progressive fibrotic chronic liver inflammation caused by the buildup of fat, which affects at least 2% to 5% of Americans, several companies race for approval of the very first NASH monotherapy. While Genfit’s PPAR agonist elafibranor and Intercept’s FXR agonist obeticholic acid (OCA) are both currently being tested in Phase III studies, Gilead’s FXR agonist Px104 and Shire’s ASBT inhibitor volixibat follow up with fast-track Phase II trials. Now, Novartis and Allergan have decided to combine Novartis’ FXR agonist LJN452 with Allergan’s dual chemokine receptor (CCR2 and CCR5)-targeting candidate drug cenicriviroc in Phase IIb tests of NASH patients. Financial details of the deal were not disclosed. In the proof-ofconcept study, the partners will assess the safety, efficacy, and tolerability of this new approach to treating NASH. While cenicriviroc, which gained FDA fast track status last year, is currently being evaluated in Phase III trials, Novartis fast-track FXR candidate LJN452 has just entered Phase II testing.

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Focus

European Biotechnology | Summer Edition | Vol. 16 | 2017

Bright future for biomanufacturers Biomanufacturing Progress in process engineering and media optimisation has resulted

in significant productivity increases in upstream processing driving transformations at drug developers and CDMOs. At BPI Europe in Amsterdam, companies showed strategies and product launches pinpointing the way towards what could become a new industry paradigm: continuous processing and flexible modular production plants, which both address changed production needs.

Cost pressure, increased productivity of fed-batch processes, and the growing number of biologics tailored to increasingly small subpopulations are encouraging the adoption of smaller scale bioprocesses more than ever. “Fifty per cent of the current clinical pipeline can be supplied from 5k or smaller bio­reactors,” said Jelto Swaving, Director of Business Management at Patheon, at BPI Europe, the annual meeting of the European bio­manufacturing community – just one month before Thermo Fisher Scientific announced that it will acquire the world-largest CDMO for US$7.2bn. According to David Radspinner, General Manager, BioPark, GE Health-

care, “80% of [biologic] drugs in development do not fit into the existing infrastructure.” Because the share of biologics in the pipelines has already reached 40% of all drugs and is growing further, according to the latest survey of market intelligence company Bioplan Associates, industry majors such as GE Healthcare, Thermo Fisher Scientific, or emerging CDMOs such as Polpharma have rapidly added modular facilities with single-use equipment to their offerings, plants which can be built very quickly and adapted to rapidly changing production needs.

GE Healthcare Life Sciences, one of the exhibitors in Amsterdam, provided a

virtual 3D visit to its Flexfactory for the 850 visitors from the sector.

Smaller and flexible facilities “KUBio, our modular facility can reduce build costs up to 50% – time to market is 18 month compared to [the] three years that traditional facilities need to be designed and built. One has just been opened in Wuhan, China,” Radspinner told European Biotechnology. “A Bio­Park with four factories, supported by Ireland’s investment agency IDA Ireland, is under construction at Loughbeg, Ringaskiddy, Co. Cork.” GE’s €150m investment will fund land, design, and construction, as well as equipping and commissioning the site, while the four modular, single-use units will be bought and operated by independent biopharma companies.

European CDMOs, such as Polpharma (see page 28), have already capitalised on the trend towards modular facilities. Polpharma has invested €100m to build a 12 × 2000 L modular, single use and fill & finish facility in Warsaw, offering full-range, GMP-compliant services to European bio­ pharma companies.

Over 110 exhibitors presented their latest biomanufacturing offerings to the 850 experts at BPI Europe.

24-26_EB_Summer_2017_Biomanu_Focus_BPI Europe_tg.indd 24

Both the process productivity of currently 3.5g/l (according to Bioplan Associates) and the reduced production cost (see figure above presented by Eliana Clark,

Pictures: BIOCOM

Products demonstrate potential for further improvement

15.06.2017 12:29:33 Uhr

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Focus

European Biotechnology | Summer Edition | Vol. 16 | 2017

Dedicated Single Product Facilities

FDA Guidance on Multi-Product mfg

Multi-Product Facilities

Flexible Manufacturing

Intro of Disposable Technologies

Next Generation Bioprocessing

Intro of 20kl large scale ”6 pack“ plants Emerging Contract Manufacturers

1976

1980

1985

1990

1995

2000

2005

2010

2015

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10 g/L

<<

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Serum-based processes

Chemically Defined Media, High Titer Processes

Low Efficiency Purification Processes

Platform Purification Processes

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(>50% Recovery)

Disruption?

Evolution of manufacturing technologies

Global Manufacturing Operations, Biogen Inc) are subject to further optimisation.

Exhibitors such as Oxford Genetics suggested that further improvements could be achieved through cell line optimisation, using CRISPR or synthetic biology. Additionally, automated selection solutions that facilitate the screening for the best cell clones were featured at BPI Europe. While companies such as Cytena suggested that single cell printers that spot cell clones in standard microwell plates may be the solution, Cambridge-based Sphere Fluidics globally launched a microfluidics-based cell sorter that encloses cell clones in oil picodroplets stabilised by biocompatible surfactants, which can be screened using optical readouts or assays employing mass spectrometry. The globally unique system generates 100,000 of these mini-test-tubes per minute, with cell viabilities at over 90%, Commercial Manager Klaudyna Johnstone told European Biotechnology. At the show, Biogen’s Eliana Clark doubted that production in CHO cells will allow significant improvements in process productivity in the long term. She announced that Biogen will present the results of the firstever systematic comparison of “alternative eukaryotic production systems” to CHO cells in Q3/2017.

Despite huge improvements in cell line development, synthetic media, and upstream processing , downstream

24-26_EB_Summer_2017_Biomanu_Focus_BPI Europe_tg.indd 26

processing (DSP) of batches has only shown incremental improvement over the past few years. After the US FDA indicated that it is going to accept continuous bio­processing solutions, the conservative bioprocessing industry began watching the new solutions presented in Amsterdam like a hawk. Lewa Process Technology presented a hybrid solution for the continuous DSP of monoclonal antibodies that can be applied to close the gap in either the high titre upstream fed-batch or the perfusion processes

The road to continuous DSP “It’s not a question if continuous manufacturing is coming, but a question when it will enter the marketplace,” Fleming Carlsen, Sales Director Europe & Asia at Lewa, told European Biotechnogy. At the exhibition, the company pre-launched a GMP-compliant scale up system, dubbed Ecoprime Twin, based on the Contichrom Cube, a twin-column configuration for continuous mAb purification, equipped with protein A columns that allow purification of 1.5 kg of monoclonal antibodies per day. Ecoprime Twin can boost the purification capacity to 31 kg/day, depending on the selected column size.

Pall Life Sciences, par t of Danaher, showcased another multi-column system with single flow path dubbed

Cadence BIO SMB for lab scale, which is set to be launched this year. According to the company, the system can reduce depth filtration requirement up to 80%, shows lower buffer consumption, and possesses a much smaller footprint than centrifugation or depth filter solutions.

Chromatography systems like those presented in Amsterdam could replace the serial batch process of loading, washing, eluating, regenerating, and equilibrating, which uses only 70% of the sorbent’s binding capacity by employing multiple smaller columns and second-pass columns that need less sorbent, as it is serially moving through the same process until saturation of the expensive sorbent. Carlsen estimates that it will take the first systems, now applied in R&D, seven to eight years to enter commercial production.

Time for change Carlsen believes that the risk-averse sector will switch technologies when experiences demonstrate that the new processes lead to significantly higher quality and productivity. According to Bioplan Associates’ President Eric Lander, continuous bio­processing and associated services was the most requested topic among biomanufacturers and CDMOs in Bioplan’s 2016 sector survey.

L t.gabrielczyk@biocom.eu

Pictures: Biogen Inc./eliana Clark

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15.06.2017 12:34:46 Uhr

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Focus

European Biotechnology | Summer Edition | Vol. 16 | 2017

Making biologics economic Polpharma After having set up a R&D hub for the biomanufacturing of clinical trial supplies in

Gdansk, Polpharma is expanding its European footprint with a €100m investment in Warsaw.

Several take-overs previously made the company a one-stop shop for biomanufacturing.

European Biotechnology spoke with Federico Pollano, Director Contract Manufacturing and Business Development at the CDMO and bio­similars maker, about Polpharma’s strategy and expansion of biologics production.

EuroBiotech_Originally a generics producer, Pol­pharma has rapidly entered the biologics space in the past few years.

What’s the vision and strategy driving that expansion?

Pollano_With 80 years of experience in

EuroBiotech_What about large scale manufacturing?

Pollano_With a view to the growing

the manufacturing of small molecule drugs, Polpharma has been a unparalleled success story starting in the CEE market and expanding into the European market. Today, the private company in the number one pharmaceutical company in Poland. Our strategic plan is to replicate that success in the biopharmaceutical space.

E u r o Bi ote c h _You invested a lot of money, didn’t you?

Pollano_Exactly, backed by investments

of some €100m, we commenced our expansion in 2013. Today, we have a proprietary pipeline of five biosimilars codeveloped with our joint-venture Bioeq in Munich. However, our main business focus remains in the CDMO market. We want to become one of the bio­pharma CDMO majors in Europe. Seeing the cost of goods becoming a top priority in very early bio­pharmaceutical development, we started with a high upfront investment into our R&D centre in Gdansk in 2013, offering high throughput process development, analytical and R&D labs, and a modular, single-use GMP pilot facility for clinical study supply. Production capacity is currently being upgraded from up to 1,000L to 2,000L scale.

Besides production using different eukaryotic production cells, we are currently expanding our microbial manufacturing to the 500L scale, and the fill

Federico Pollano, Business Development & Contract Manufacturing Director at Polpharma, has been working in the pharmaceutical industry for 26 years. From 2008 until 2015, he was Managing Director at Richter-Helm-Biotec, and from 2005 until 2007, he led the generics business at Helm AG. Prior to that, he had leading positions at BioGenerix AG ratiopharm, Glaxo­Wellcome, and Zambon.

and finish capacities there to 5,000 vials and syringes. Since we acquired Utrechtbased CHO cell line developer Biocereos and its proprietary CHObc cell line technology to produce protein NMEs and biosimilars at maximal yield last year, Polpharma covers the entire value chain from cell line and bioprocess development over biologics production, DSP, and fill and finish.

adoption of personalised medicine, gene therapy and orphan drugs, I’m not convinced that this is the future in biomanufacturing, but for sure, that smaller, highyield batches are. Thus, the next logical step in Polpharma’s expansion was to build a larger scale, modular, single-use production and fill and finish plant. A €100m facility, set to start production in the first half of 2019, is under construction near Warsaw. Why modular and single use? Studies and our experience at the mirror-facility in Gdansk have shown that modular single-use can cut time-tomarket and capital expenditure by 50%.

It can cut change-over times by a factor of five, while increasing output compared to less flexible, stainless steel tanks.

E u r o B i o t e c h _To w h a t d e g r e e c a n Pol­p harma address special customer needs?

Pollano_ At the current stage, we still have

the freedom to operate in Warsaw, which means that we can even discuss the establishment of stainless steel or perfusion reactor equipment if required. However, the flexible, modular, single-use approach in USP and DSP, together with lyophilisation capacities and, finally, a fill and finishing line of 30,000 vials or syringes is at the core of our expansion. We are open to production with alternatives to CHO cell lines and are already conducting projects with plant cells. And, we are currently discussing how we can combine small and large molecule know-how at Polpharma for the manufacture of ADCs. L

Pictures: Polpharma

28

Passion for Performance

Rentschler – A world-class biopharmaceutical CDMO •��Full-service�provider�from�gene�to�vial�and�from�concept�to�market� •���Contract�development�and�manufacturing�with�quality�excellence •��Experts�in�mammalian�cell�culture •��State-of-the�art�facilities�and�technologies •���Extensive�track�record�with�more�than�40�years�in�biopharma •���We�are�a�biotechnology�pioneer� •���We�are�listening�to�our�clients •��We�fi�nd�solutions�where�others�don’t�even�look

Rentschler Biotechnologie GmbH Erwin-Rentschler-Str.�21�·�88471�Laupheim�·�Germany info@rentschler.de�·�www.rentschler.de

29_EB_Summer_2017_Rentschler.indd 1

15.06.2017 12:35:40 Uhr

ECONOMY

Thermo enters CMO world Acquisition Lab equipment giant Thermo Fisher Scientific Inc. is growing even bigger. In May, the US company presented its board-approved plans to acquire Patheon NV for US$7.2bn in cash.

The contract development and manufacturing organisation (CDMO) is active in a high-growth market, serving the pharma and biotech industry. Incorporated in the Netherlands, Patheon is originally a Canadian company that followed a merger and acquisition path similar to Thermo’s in the last years. Arguably, the most remarkable deal was the US$2.65bn acquisition of the pharmaceutical products business Dutch Royal DSM in 2014. Thermo will commence a tender offer to acquire all of the issued and outstanding shares of Patheon for US$35.00 per share in cash and confirmed that affiliates of JLL Partners and Royal DSM – which collectively hold an approximate 73% majority of Patheon shares – have agreed to tender their shares in the transaction.

Patheon has an extensive network of state-of-the-art facilities located primarily in North America and Europe, and approximately 9,000 employees. The company

generated a 2016 revenue of US$1.9bn and will be integrated into Thermo’s Laboratory Products and Services segment which generated US$7.03bn in revenue last year. The world leader in science necessities expects the acquired CDMO services to complement their existing business. Whether with research, clinical trials, or production, Thermo said that it’s now a stronger partner for pharmaceutical and biotech customers. 

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European Biotechnology | Summer Edition | Vol. 16 | 2017

HR Flash

By Sébastien Stoitzner, CEO at Gensearch – Paris, Cologne, Frankfurt, and Basel Gensearch, Paris, France Talents The European Biotech mar- › about how competitive the market is, ket is extremely dynamic, acknowl- › that the skills you need are rare, edged as being number two in the › that the time lines are short, world of market rankings. This is a › that more than 75% of biotechs are headed by first-time CEOs, with a cause for celebration! scientific background and no busiA number of European governments ness experience, have invested a significant amount of public resources, including public fund- › and that most of those companies do not have an HR Manager, ing, to create de­dicated clusters that you should think have been instru“Wait a minute, mental in developing a strong biBusiness failures are mostly maybe we need to address the talotech eco­system. due to the Human Factor. ent issues first?”

In addition to Then, some quesp u b l i c i nv e s ttions arise: m e nt , ve nt u r e capitalists have been quite active as › F or VCs: during your due diligence on top of science and the potential well. They have contributed greatly to market, do you assess people systemthe structuring and professionalisation atically with specific tools and solid of the European Biotech market. processes?

As human resources professionals, we have observed that those companies › For clusters: do you provide your members with the support and soluinvest almost all their energy into two tions they need in terms of talent? specific areas for their business: raising money and making science move for- › For biotech companies: do you have a plan to attract the international talward. It makes sense, does it not? ent you need, do you assess these Yes, it does! people, and then how do you develHowever, we are convinced that a third op and retain them? area should be addressed with the same energy and the same professional ap- › For CEOs: would coaching be relevant to enable you to attain your proach: talent acquisition and talent demilestones earlier? velopment. At the end of the day, when you want to be successful at raising Business failures are due primarily to the money or at making science move for- human factor. There are solutions to anticipate and address these issues. One ward, people are the key, are they not? merely needs to go and look for them. 

When you think:

Pictures: Patheon (left), Gensearch (top)

30

15.06.2017 12:36:41 Uhr

European Biotechnology | Summer Edition | Vol. 16 | 2017

Stock Markets

A liver epidemic ignored by patients and payors?

Martin Laqua Editor – Biotech and pharma companies are betting billions of euro on liver dis-

ease NASH. Yet, is all the craze justified? The case is at issue, as analysts predict the global market for NASH medicines to range from US$8bn to as much as US$35bn per year.

Long-established New York market research company H.C. Wainwright & Co. is proud of its own traditions. If the company organises an inaugural investor conference, it is surely not focused on a random, voguish biopharma topic. Among the 16 attending companies were big pharma as well as small biotech groups – all united in their ambition to grab a share of what consulting company Global­data believes to have “extreme blockbuster potential”: drugs against non-alcoholic steatohepatitis (NASH). Looking at the seven major markets – the US, France, Germany, Italy, Spain, the UK, and Japan – Globaldata expects a compound annual growth rate (CAGR) of 45%. That means that during the next 10 years, the field is

projected to swell forty-fold, from US$618m in 2016 to US$25.3bn in 2026 (other analysts project market sizes somewhere between US$8bn to US$35bn). Being closely linked to metabolic diseases like diabetes type 2, the NASH epidemic will inevitably occur in Western markets where people become obese more frequently.

However, there is a caveat. As NASH is a progressive disease, it is an asymptomatic one for quite some time – until the final stages of liver cirrhosis. Also, for many patients, the disease will stop progressing before any limitations are observable. To convince patients and payors that taking (and paying for) a NASH drug is good to do, a few details have to be resolved. First, non-

invasive diagnostics must reach the market, because diagnosing NASH by taking liver biopsies is simply too risky to undertake.

Such tests are developed, for instance, by European companies like One Way Liver S.L. (Spain), Biopredictive S.A.S. (France), or Siemens Healthineers (Germany).

Second, drugs have to enter the market.

Big companies like Novartis and Allergan have built a portfolio of NASH drugs, but there are still some smaller bio­tech players around possessing trump cards. First in line is French biotech Genfit SA, which many believe will have the first NASH drug on the market. Due to the lack of properly diagnosed patients and an overage of drug developers doing clinical studies, Genfit ran into recruitment troubles with its Phase III study for its lead candidate, Elafibranor.

The trial will be delayed four to six months, Genfit announced this spring.

L

News from the floor Nicox SA French-based ophthalmic

company Nicox received FDA approval for its candidate Zerviate (AC-170) against ocular itching in late May. After the stocks gained 30% to €12.85, Zacks Investment Research lowered its rating from a hold to a sell in a report in early June.

Picture: BIOCOM AG

Novo Nordisk A /S Trading at

DKK285, Swiss banking house UBS has left its rating of Novo Nordisk shares on “buy” with a target of DKK350. The diabetes drug semaglutide is a growth driv-

er, commented analyst Michael Leuchten in a study published in June. The medium-term profitability targets of the Danish company are more than realistic.

Novartis AG “Promising results with its CAR-T technology” is a major reason why Vontobel Research maintains its price target for CHF78. Novartis’ closely-watched candidate CTL019 had elicited a strong response in cancer patients in a mid-stage trial. The Swiss company is a leader in this area of cell therapies, but peak sales of the approved drug probably won’t ex-

ceed US$208m, according to Vontobel’s Stefan Schneider.

Erytech Pharma SA Oddo reiterated its “buy” recommendation on Erytech’s shares twice in the past months, when the French clinical-stage biopharma company celebrated the positive outcome of a Phase IIb study for its pancreatic cancer treatment. The stock soared from €14 to €29. Oddo then raised its target from €29 to €70, believing Erytech’s candidate to be a ”real game-changer.” 

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32

Euro Biotech Stocks

COMPANY

QUOTE

M-Cap

European Biotechnology | Summer Edition | Vol. 16 | 2017

52 weeks indicator low high

COMPANY

QUOTE

M-Cap

4D Pharma plc

3.10

197,700k

Blirt SA

0.39

3,100k

4SC AG

4.10

78,700k

Bone Therapeutics SA

9.50

71,100k

1.12

8,800k

Brain AG

18.33

295,800k

AB Science SA

10.04

407,100k

C4X Discovery Holdings plc

0.98

45,300k

AB-Biotics SA

1.76

22,200k

Cantargia AB

0.61

19,300k

Abcam Ltd

11.01

2,228,700k

Carbios SAS

7.25

27,500k

Abivax SA

13.63

130,500k

Cassiopea SpA

31.03

309,800k 761,500k

A1M Pharma AS

Ablynx NV

11.99

730,800k

Cellectis SA

21.80

Abzena Ltd

0.46

103,100k

Cellink AB

10.92

66,600k

Acarix AB

1.92

50,100k

8.81

396,500k

252.19

25,117,600k

40.21

378,900k

Actelion Pharmaceuticals Ltd

Nasdaq in llama love IPO Belgian-Dutch ArgenX is listed on Euronext Brussels. To im-

prove fundraising in the US, the clinical-stage biotechnology company pulled off an IPO on Nasdaq in May. Clearly, the llama antibody-based technology has some fans there: raising US$114.7m in the IPO, ArgenX ended up more than 50% above its initial target. This success became also notable in Brussels, when the stock price rose sharply by 24%.

L

Celon Pharma SA Celyad SA Cerenis Therapeutics SA

1.88

37,900k

Circassia Pharmaceuticals plc

0.99

330,100k

Co.don AG

3.08

166,700k

148.73

2,220,400k

Curetis AG

5.06

78,600k

Cytotools AG

11.93

25,200k

Cyxone AB

0.56

8,800k

59.70

1,453,000k

Cosmo Pharmaceuticals NV

DBV Technologies SA Deinove SA

2.12

22,100k

Diamyd Medical AB

0.52

24,800k

72.50

3,950,000k

Diasorin SpA Diaxonhit Therapeutics SA

0.28

50,700k

Elanix Technologies AG

5.80

38,900k 27,700k

e-Therapeutics plc

0.10

Active Biotech AB

0.51

48,900k

Ellen AB

0.03

2,300k

Addex Therapeutics Ltd

2.15

33,100k

Enzymatica AB

0.28

20,100k

Adocia SAS

21.20

143,100k

ALK-Abelló A/S

133.13

1,341,600k

Allergy Therapeutics plc

0.29

171,100k

Alligator Bioscience AB

3.09

223,000k

Annexin Pharmaceuticals AB

0.87

Aqua Bio Technology ASA

0.96

Argenx SE

18.24

Epigenomics AG Erytech Pharma SA Esperite NV

7.28

167,200k

26.81

313,400k

0.60

7,800k

Eurofins Cerep SA

100.00

25,200k

5,000k

Eurofins Scientific SE

492.00

8,250,000k

6,700k

Evgen Pharma plc

0.22

15,900k

486,900k

Evolva SA

0.41

183,800k

13.60

1,930,000k

Arocell AB

0.56

15,200k

Evotec AG

Asit Biotech SA

6.33

80,800k

Expres2ion Biotech Holding AB

0.52

4,500k

Avacta Group plc

0.96

65,600k

Faron Pharmaceuticals Oy

8.30

231,600k 35,900k

Avantium Holding NV

10.23

263,300k

Fermentalg SA

3.00

Basilea Pharmaceutica AG

69.39

812,800k

Fit Biotech Oy

0.06

3,100k

Bavarian Nordic A/S

47.67

1,472,700k

Formycon AG

39.40

345,900k 3,512,000k

Bergenbio ASA

2.31

112,400k

Galapagos NV

70.42

Bio-On SpA

19.45

362,200k

Genedrive plc

0.48

9,000k

Biocartis NV

10.40

460,500k

Geneuro SA

9.58

141,200k

Biofrontera AG Biogaia AB

4.11

163,900k

Genfit SA

36.90

634,500k

Genmab A/S

29.50

920,700k

188.54

11,271,100k

Bioinvent International AB

0.25

74,700k

Genomed SA

4.55

6,000k

Biomed-Lublin SA

0.32

14,300k

Genomic Vision SA

4.30

18,300k

Biomérieux SA

196.70

7,589,000k

Bionaturis SA

2.02

9,500k

Biophytis

3.20

Bioporto Diagnostics A/S

0.35

Biosearch Life SA

0.49

Biotec Pharmacon ASA Bioventix plc Biovica International AB

Genovis AB

0.31

19,100k

Genoway SA

2.25

14,400k

25,700k

Gensight Biologics SA

6.70

130,900k

49,200k

Genticel SA

2.03

159,600k

29,400k

Genus plc

21.27

1,305,200k

0.65

26,800k

Global Bioenergies SA

20.38

73,000k

21.56

110,800k

Hansa Medical AB

18.83

678,100k

1.24

10,200k

0.17

40,500k

32-33_EB_Summer_2017_economy_stockmarketlist_ml.indd 32

Hofseth Biocare ASA

52 weeks indicator low high

15.06.2017 12:39:20 Uhr

Euro Biotech Stocks

European Biotechnology | Summer Edition | Vol. 16 | 2017

COMPANY

QUOTE

M-Cap

52 weeks indicator low high

COMPANY

QUOTE

M-Cap

Horizon Discovery Group plc

2.12

204,400k

Paion AG

2.72

Hvivo plc

1.26

98,300k

PCI Biotech Holding ASA

2.43

60,200k

Hybrigenics SA

0.78

27,900k

Pharma Mar SA

3.77

838,800k

Immunicum AB

1.84

50,600k

Pharming Group NV

Immunodiagnostic Systems plc

3.27

96,300k

Pharnext SA

Immunovia AB

10.41

175,000k

Immupharma plc

0.56

Index Pharm. Holding AB

0.45

0.32

159,000k

10.36

111,800k

Photocure ASA

2.78

58,700k

74,400k

Physiomics plc

0.01

700k

28,700k

Plant Advanced Technologies SA

24.84

22,300k

Poxel SA

7.65

172,400k

Premaitha Health plc

0.11

27,000k

Infant Bacterial Therapeutics AB

9.09

50,100k

12.15

644,900k

Integragen SA

3.05

19,800k

Probi AB

60.74

681,100k

Intervacc AB

0.68

11,000k

Probiodrug AG

17.49

144,800k

Inventiva SA

7.56

124,800k

Proteome Sciences plc

0.06

16,100k

Isofol Medical AB

2.50

79,000k

Qiagen NV

30.59

6,801,000k 68,700k

ISR Holding AB

0.77

12,800k

Quantum Genomics SAS

7.95

Kancera AB

0.28

38,700k

Relief Therapeutics Holding AG

0.01

18,400k

Karo Pharma AB

4.05

333,000k

Reneuron Group plc

0.02

70,600k

Salvarx Group plc

7.51

106,700k

Kuros Biosciences AG

14.43

91,600k

Santhera Pharmaceuticals AG

0.35

13,000k

55.83

349,200k

Lysogene SA

5.80

70,300k

Sareum Holdings plc

0.01

26,100k

Mabion Ltd

23.3

267,300k

Scancell Holdings plc

0.11

35,200k

MDxHealth SA

5.00

249,300k

Selvita SA

16.27

218,700k

Medical Prognosis Institute A/S

1.29

30,700k

Medigene AG

12.34

Medivir AB Mereo Biopharma Group plc

Sensorion SA

6.92

49,400k

266,500k

Shield Therapeutics plc

1.90

205,700k

8.29

169,700k

Silence Therapeutics plc

1.08

74,300k

3.64

257,100k

Simris Alg AB

1.56

14,800k

Metabolic Explorer SA

2.47

56,800k

Skinbiotherapeutics plc

Midatech Pharma plc

1.21

59,100k

Stallergenes Greer plc

27.20

563,700k

Summit Therapeutics plc

2.00

124,100k

0.41

175,200k

Swedish Orphan Biovitrum AB

14.01

3,773,700k

Sygnis AG

1.73

78,000k

Synairgen Research Ltd

0.11

10,400k

Targovax ASA

2.41

95,900k

Molecular Partners AG Molecular Medicine SpA Mologen AG

0.13

15,100k

35.82

716,900k

3.98

133,600k

63.20

1,843,000k

Motif Bio plc

0.36

69,800k

Nanobiotix SA

21.95

382,800k

Theradiag SA

2.36

20,400k

NEL ASA

0.20

147,800k

Thrombogenics NV

3.18

115,100k 221,000k

Morphosys AG

Neol Biosolutions SA

0.67

6,200k

Tigenix NV

0.86

Neovacs SA

0.86

40,300k

Tissue Regenix Group plc

0.16

118,200k

Neuron Biopharma SA

0.18

2,000k

Tiziana Life Sciences plc

1.91

183,800k

Neurosearch A/S

0.48

12,000k

Transgene SA

3.34

188,400k

Neurovive Pharmaceutical AB

0.38

18,800k

Txcell SA

2.20

43,500k

Newron Pharmaceuticals SpA

19.41

307,700k

Valirx plc

0.02

3,300k

Nicox SA

12.02

308,800k

Valneva SE

3.08

239,500k

Vectura Group plc

1.27

863,700k

Veloxis Pharmaceuticals A/S

0.15

264,100k

Nordic Nanovector ASA

11.04

539,000k

Novozymes Biopharma DK A/S

40.34

12,243,200k

Noxxon Pharma NV

16.23

35,700k

Vernalis plc

0.19

107,700k

1.64

71,300k

Verona Pharma plc

1.48

153,900k

1.58

80,700k

Vita 34 AG

6.54

20,700k

12.80

87,800k

Wilex AG

3.00

43,800k 217,200k

Nuevolution A/S Oncimmune Holdings plc Oncodesign Biotechnology SA Oncopeptides AB

5.10

202,400k

Wilson Therapeutics AB

8.50

Onxeo SA

4.83

225,800k

Xbrane Biopharma AB

0.38

10,900k

Optibiotix Health plc

0.82

64,300k

Xintela AB

12.40

326,900k

Oryzon Genomics SA

2.55

73,200k

Zealand Pharmaceuticals A/S

16.34

430,600k

OSE Pharma SA

6.74

96,600k

Oxford Biodynamics plc

1.58

136,100k

Oxford Biomedica plc

0.06

184,800k

32-33_EB_Summer_2017_economy_stockmarketlist_ml.indd 33

52 weeks indicator low high

156,700k

Innate Pharma SA

Kiadis Pharma BV

33

All quotes are listed in euro. All data is provided without guarantee. The effective date is 12 June 2017.

These dedicated biotech companies are listed on European stock markets.

15.06.2017 12:39:25 Uhr

34

Economy

European Biotechnology | Summer Edition | Vol. 16 | 2017

Fuelling EU biotech Crowdfunding Spanish Capital Cell was one of the first equity crowdfunding platforms

that specialised in life sciences and biotech projects in Europe. In March, the group raised more than €1m through funding through the Spanish biotech campaign Bionure – a new record. EuroBiotech talked to Capital Cell founder Daniel Oliver about their recent expansion into the UK and the development of the European life sciences crowdfunding scene. ed through one vehicle, so that they can consolidate their power together.

EuroBiotech_Your recent Bionure campaign raised more than €1m with the suppor t of over 2 5 0 investors. Has crowd-investing developed into an established tool for Spanish biotech companies?

Daniel Oliver_ The market is far more

EuroBiotech_What sort of investors did you attract in Spain?

Daniel Oliver_ Spain is not very known

for risk investments, but with our platform, we mobilised capital through different kinds of investors. I would say 40% of those who are investing in Capital Cell projects are somehow related to the health environment. That can be CLevels at biotech or pharma companies, academic researchers, nurses, regulatory consultants – people who already know the market. In Spain, we have had up to 30% of cross boarder investments from 25 different countries. However, it is not particularly easy. If you want to invest in a Spanish campaign, you physically have to go to the embassy and obtain special documents that you can’t get online. We are still far from a unified legislation.

34-35_EB_Summer_2017_Interview_Capital Cell_FINAL_hm.indd 34

Daniel Oliver founded Spanish Capital Cell in 2015, one of the first European life sciences crowdfunding platforms. The biologist is also a member of the European Crowdfunding Stakeholder Forum and a funding member of the European Equity Crowdfunding Association (ELA). Since May 2017, his platform acts internationally from Spain and the UK.

EuroBiotech_ Do you follow up with your projects when they have ended?

Daniel Oliver_ We don’t really get in-

volved in companies once they are done funding, as the financial security in Spain would not permit us to keep up. We deal with a lot of small investors. We prefer for them to be aggregat-

sense from a business perspective. It is a huge financial market and has one of the most booming biotech communities in the world. Capital Cell is now a British and a Spanish company. All together, we have 12 employees. In Spain, we work like a service hub. We do project analysis, finance, and marketing. The office in the UK provides business development and compliance. During our expansion, we got help from the European Commission. I am a member of the European Equity Crowdfunding Association and the European Crowdfunding Stakeholder Forum, so I was quite familiar with the legislation in the UK and Europe.

EuroBiotech_How many campaigns are you running in the UK right now?

Daniel Oliver_ We just launched at the

end of May, and we have an agreement with Angels in MedCity, one of the largest invest-groups in the UK specialising in health. Currently, there are five companies’ campaigns that we are running. For example, there is a cancer treatment company (Combat Medical), another company developing therapeutics for inflammation (Ducentis Biotherapeutics), and an Israeli company that is trying to find a biologic solution for mosquitovectored disease (Forrest Innovations). We expect to launch another 12 campaigns

Pictures: Capital Cell

mature than a couple of years ago when we have started with Capital Cell. There are many more people now who have already invested. When we started our first few campaigns, 98% of our investors had never invested in a company before. Now, we have a richer ecosystem of people who are not afraid to invest in health or even in drug development or biotech. Bionure has been our largest campaign and, I think, probably in health also in Southern Europe.

EuroBiotech_Why did you move to the UK and how did you manage the international expansion?

Daniel Oliver_ The UK makes a lot of

15.06.2017 12:40:08 Uhr

Economy

European Biotechnology | Summer Edition | Vol. 16 | 2017

this year, including a Spanish company specialising in data analysis. We have also been in discussions with companies from Germany, Norway, and Ireland. This is one reason why we chose the UK, because it is a very active financial market and companies across all Europe are happy to raise money in the UK. EuroBiotech_What are the main differences bet ween the crowdfunding scenes in the UK and in Spain?

Daniel Oliver_ What we see in the UK is

that scientific companies are much more prepared in the business and financial sense. It is easier to find lead investors who organise the operations. The UK is not just a more powerful market, it is also a more demanding one. If you want to raise money in the UK, you need to proof that you have a outstanding product, a global range, and that you have a world class team, and so on. In both countries, life sciences are equally challenging and fascinating.

E u r o B i o t e c h _ W h a t a b o u t B r e x i t?

Wouldn’t it be easier to stick to countries who will stay in the European Union?

Daniel Oliver_ Maybe. But even if the

operating in more than one European country. Does crowdfunding exist on a European level?

Daniel Oliver_ I wouldn’t say no. The

UK had never been in the European Union, we would still have moved there. Alternative financing in the UK is four times higher than in all the other countries in Europe combined. The average investment in Spain is €1.08 Euro, in the UK it is €65, both per person. Furthermore, when we were looking around, we saw that the UK legislation on crowdfunding is probably the most open and the most forward. Every other country in Europe is very restrictive when it comes to financial regulations. Equity crowdfunding particularly requires looser financial regulations, needing them to be kinder and more open to a lot of things like online signature for example.

problem with equity crowdfunding is that it is not regulated in all European countries or in one legislation. Yet, there are networks like the European Crowdfunding Stakeholder Forum, for example. It is a group of 50 people from across the European Union which the European Commission has put together to consult with regarding the creation of future European crowdfunding legislations. It is very difficult to internationalise crowdfunding activities. Only a few generalist platforms are active in more countries, like “Invesdor” from Finland or “crowdcube” from the UK. I am afraid that the prospect of a Europeanwide equity crowdfunding structure is, at present, a bit too optimistic. Maybe give it two or three more years.  h.maerzhaeuser@biocom.eu

EuroBiotech_There are a few generalist and life sciences specialised platforms

35

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15.06.2017 12:40:13 Uhr

36

Orphan Drugs

European Biotechnology | Summer Edition | Vol. 16 | 2017

Treating a rarity â&#x20AC;&#x201C; how to pay for value? might have misused market monopolies related to orphan drugs (ODs) to overprice their compounds, the status has come under closer scrutiny. Neither the US nor Europe currently have consistent approaches for deriving value for OD therapies. Pooling expertise and scattered patient data across borders could help ease both diagnosis and development, providing a foundation for pricing and giving patients much faster access to treatments.

36-40_EB_Summer_2017_OD_aktuell_tg.indd 36

Picture: masterzphotofo/fotolia.com

Rare diseasesâ&#x20AC;&#x192; Since US senators in February conveyed the impression that drug developers

15.06.2017 12:40:47 Uhr

Orphan Drugs

European Biotechnology | Summer Edition | Vol. 16 | 2017

B

efore Miriam Klein received the most expensive drug in the world, she had been admitted to the hospital around 40 times for unbearable abdominal pain and pancreatitis caused by lipoprotein lipase deficency (LPDL) – an ultra-rare genetic defect that affects the breakdown of fat in the body. But since being given injections of uniqure’s gene therapy Glybera two years ago, “she lives like you and me”, according to Dr. Elisabeth Steinhagen-Thiessen, her physician at Berlin’s Charité Hospital.

“My disease is still part of my life,” says the 44-year-old patient, “but it doesn’t take centre stage like before.”

Klein is one of the just 350 people who suffer from LPDL in a European population of 510 million. Though Steinhagen­ Thiessen knows patients from other countries who are still hoping to receive the therapy, it has been widely rejected

by European payors due to its €1m cost per patient. Dutch Health Minister Edith Schippers branded the therapy “part of a pattern of price-gouging by drug companies”. In April, uniqure announced it will not seek renewal of its EU conditional market authorisation this autumn due to “limited patient demand”. Only patients who are approved for treatment prior to October 25 of this year will have further access to the gene therapy.

number of orphan drugs (currently 500 in the US and 128 in Europe) and their market share – 41% of US market approvals in 2016 were for treatments of rare diseases – are projected to grow rapidly.

The US, Japanese and EU orphan drug acts from 1983, 1993, and 2000 respectively grant market exclusivity for several years as an incentive for developing ODs (see p. 40). But watchdogs now suspect some developers of abusing their monopolies.

“ The healthcare budget impact of orphan drugs will remain small.”

Payors and policymakers are concerned that orphan drugs could strain healthcare budgets, while developers and patient groups are lobbying for better access to ODs. Market figures do clearly indicate

Pictures: ADKÄ/German Medical Association

Big Pharma’s new model This is far from the first time that orphan drug pricing has come under fire. As long ago as the early 1990s, a US$300,000 price tag for Genzyme’s Gaucher disease therapy ceradase spawned Senate hearings, government audits and sharp criticism from payors, physicians and the media. Because target populations in mono­genetic diseases are typically extremely small (80% of the estimated 7,000 orphan diseases are genetic), prices for therapies designed to correct the underlying defect can run up to US$700,000, since the volume­-based system used to calculate prices for treatments in more common indications doesn’t apply.

Criticism towards overpricing has grown much louder recently because the

36-40_EB_Summer_2017_OD_aktuell_tg.indd 37

Wolf-Dieter Ludwig Head, German Medical Association’s Committee of Medicinal Products

? !

What has to change to improve the quality of orphan drugs?

“Compared to other drugs, ODs are evaluated less rigorously in pivotal studies. That’s partly due to low numbers of enrolled patients, trial designs that aren’t randomised, surrogate endpoints with weak significance and follow-ups that are too short. There’s therefore good cause to raise the regulatory requirements, raise the share of RCTs and include patient-relevant endpoints.”

37

that pharma companies have refocused pipelines to target smaller patient populations in medically underserved indications in order to overcome “unhealthy 5% annual growth rates”, according to retired pharma manager Jürgen Kleemann (Pharmind (2013) 75 , 4, 562-574)) in the overall pharma market in a post-blockbuster era.

A growing pipeline In May, QuintilesIMS analysts forecast that the number of approvals would rise from 66 in the last five years to as many as 90 by 2022. Evaluate’s “Orphan Drug Report 2017” predicts that OD sales will grow twice as fast globally (11.1%) as the total pharma market (US$110bn in 2016) to US$209 by 2022. “Orphan drugs are set to account for 21.4% of global prescription sales in 2022,” study author Andreas Hadjivaliliou told European Biot­ echnology.

What’s more, the average cost per patient treated with an orphan drug in the US shot from US$116,216 in 2012 to US$140,443 in 2016. Median cost was also over five times higher than for nonorphan drugs last year. In the EU, where Evaluate is still analysing cost-per­-patient data, the analysts forecast ODs will account for 55% of the European pipeline’s cumulative value in 2022. One reason, says the life science commercial intelligence provider, is that drugs targeting smaller patient populations – orphans and personalised meds – allow a price premium over non-orphans. An analysis conducted by a Belgian research team headed by Philippe Wilder (Brit J Clin Pharm, doi: 10.1111/j.1365-2125.2010.03877.x) also suggests orphan drugs are reimbursed more often than non-orphan drugs (88% of 25 ODs vs 63% of 117 non-ODs).

Around two-thirds of OD approvals are currently in oncology indications.

Hadjivaliliou’s co-author Lisa Urquhart says the “image of the plucky small bio­ tech striving to develop treatments for rare diseases largely ignored by Big Pharma is long gone”, and that this year Big Pharma is again dominating the sector. “Seven of the top ten companies by orphan drug sales are global industry players,” she says. Niels Riedemann agrees: “Initial-

15.06.2017 12:40:54 Uhr

38

Orphan Drugs

European Biotechnology | Summer Edition | Vol. 16 | 2017

Projected sales of drugs with the orphan drug label in Europe by 2022

Product

Company

Phase

Drug class

2106 sales

2022 sales

› Opdivo (nivolumab)

Bristol-Myers Squibb

Marketed

PD1 blocker

US$523m

US$2,435m

› Revlimid (lenalidomide)

Celgene

Marketed

immuno­ modulator

US$1,245m

US$1,990m

› Soliris (eculizumab)

Alexion Pharmaceuticals

Marketed

anti-C5 mAB

US$898m

US$1,466m

› Keytruda (pembrolizumab)

MSD

Marketed

PD1 blocker

US$161m

US$1,425m

› Imbruvica (ibrutinib)

Johnson & Johnson

Marketed

BTK blocker

US$348m

US$1,258m

› Advate (procoagulant)

Shire

Marketed

rec. Factor VIII

US$788m

US$1,084m

› Darzalex (daratumumab)

Johnson & Johnson

Marketed

anti-CD38 mAB

US$6m

US$944m

ly, biotech companies filled the orphandrug niche because clinical development costs are significantly lower,” says the CEO of infection specialist InflaRx. “Fewer patients are needed to provide clinical proof-of-concept than in classical, large indications. However, the US$2bn+ revenues of orphan drug pioneers like Alexion with eculizumab showed markets could be huge even in the rare disease space.

So it’s not surprising Big Pharma has entered it through acquisitions and pipeline products.”

Media reports foster mistrust Driven by budget constraints, three US Senators in February launched an investigation into six-figure annual costs for orphan drugs and potential malpractice by the pharmaceutical industry. Previous reports from US media suggested that 70 repurposed drugs initially designed for mass market use have now been given orphan drug approval, while others received multiple seven-year US market exclusivity periods in different orphan indications. Several reports in European mass media have also suggested overpricing is a common pattern in the industry. And public trust has been further eroded by reports of marketing malpractices and safety violations that led to fines totalling US$14bn from 2005-2012, according to Kleemann.

Published reports cited by the the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE), however, contradict the picture of overpriced drugs drawn by newspapers and interest groups.

Model calculations from 2011, it claims, suggest OD expenditures peaked in 2016 at just 4.6% of the EU’s total pharmaceutical expenditures (Orphanet Jl of Rare Diseases, doi:10.1186/1750-1172-6-62). That’s in line with statements from the EU pharma industry federation EFPIA, which told European Biotechnology that “expenditure is expected to plateau and stabilise between 4–5% of total expenditures by 2020.” It says that incoming bio­similars – set to replace about 70 orphan medicinal products by 2019 – “are expected to help balance cost for healthcare systems.” Bertram Häussler, the head of Berlin-based market research institute IGES projects the budget impact will double from 3.1% by 2020 and then stabilise at that level.

“We should not forget,” states EFPIA, “that governments negotiate the prices that companies are allowed to charge, either directly or indirectly. The price of a medicine is based on the value it brings to patients, healthcare systems and society. It provides the appropriate revenue for companies to invest in new therapy development.” In his view “the orphan medicine designation needs to be protected to further attract a high level of investment in R&D.” Most of the current debate on

high-priced drugs for small patient populations is about the fair value they provide to patients, and how this value can be determined quickly in order to grant rapid access to life-saving treatments. But according to MEP Peter Liese (EVP), a melange of views and national interests is still hampering a European-wide health technology assessment (HTA), and what’s needed is a way to overcome the requirement for companies to go through 28 different HTA procedures in EU Member States in order to be reimbursed. EUCOPE agrees. “Better and faster access to therapies, in particular for patients that have no other alternative, is a critical issue to address,” says Dr. Oliver Sude, Legal Counsel at the European trade association for medium-sized companies in the field of pharmaceuticals and biotechnologies.

“Hence, we urge closer collaboration between industry and payors towards finding suitable solutions that guarantee the possibility for patients to receive the best possible treatment without limitations like budget constraints.”

Improving patient access At the end of April, a non-profit alliance of 751 rare disease patient organisations from 66 countries called for better access to orphan drugs through so-called compassionate use programmes. “Compassionate use programmes can save lives by providing early access to promising new medicines for rare disease patients,” said François Houÿez, the Health Policy Advisor at EURORDIS. “Patients [with orphan diseases] are desperate, and willing to take a higher risk to use a medicine that is not authorised.” The organisation is demanding the application of the European Medicine Agency’s fast-track Adaptive Pathways or PRIME schemes to patients who need the product most urgently, hinging full approval on additional confirmatory studies. Further­more, EURORDIS proposes establishing the French Temporary Use Authorisation system in all EU Member States, and including compassionate use in the EU’s Cross-Border Healthcare Act. Those moves are in line with demands made by pharma group EFPIA:

Orphan Drugs

European Biotechnology | Summer Edition | Vol. 16 | 2017

39

Some facts about orphan drugs Before governments established Orphan Drug Acts in the US (1983), Japan (1993), and Europe (2000), very few drugs for treating rare diseases had been attempted or approved (US: 10, EU: 8). In the era of the blockbuster model of drug development, there simply weren’t enough patients involved for a company to even recoup R&D costs, much less turn a profit. But by creating incentives such as market exclusivity (US: 7 years, EU: 10 years), fee reductions at regulatory authorites (US, EU) or R&D cost reductions (US: 50% tax credit, grants for clinical development), the acts created incentives that made orphan drug (OD) development more attractive for companies.

The Acts also define what makes a rare disease. It must be life-threatening or chronically debilitating, and it may have no existing satisfactory method

of diagnosis, prevention and treatment.

If these exist, then an OD must provide significant benefit in comparison. In the US, a disease is considered ‘rare’ when it affects less than 200,000 patients; in the EU, when it affects less than five in 10,000 people (<255,000 patients), and in Japan 4 in 10,000 (<50,000) patients.

Accordingly, 6,000-8,000 known diseases are now defined as rare diseases based on estimations of their prevalence.

In total, they affect more than 60 million people in the three markets.

So far, about 500 ODs have been approved in the US and around 130 have been authorised in the EU, 95 of which currently have active OD status. Though several thousand drugs in development have received OD status (for current list see i.e. register of designated orphan medicinal products), most rare diseases remain untreatable, and even diagnosis is

What is a RARE DISEASE ?

Any disease, disorder, illness or condition affecting fewer than 200,000 people in the United States and less than 1 in 2,000 persons (255,000) in the EU is considered rare.

1in 10 7,000

Americans has a RARE DISEASE

Europeans has a RARE DISEASE

30 million people have a serious, lifelong condition

More than half are children

1in 17

RARE DISEASES exist, with about 700 approved treatments in the US and EU

at times impossible. To speed up access to ODs, regulatory agencies often grant conditional market approval or greenlight compassionate use programmes.

However, the OD Acts are far from perfect, especially as some indications appear more attractive to developers than others. 44% of approved ODs in the EU are for rare cancers (including all blood cancers, renal cell carcinoma, pancreatic, gastric, thyroid and pediatric cancers), and 21% for metabolic disorders (see graphic). About 80% of all rare diseases have identified genetic origins, and 50% of them affect children.

Medical and scientific knowledge about rare diseases continues to lag behind, although the number of studies involving them is on the rise. An average of five new diseases are now described every week in scientific publications.

80% of RARE DISEASES ARE GENETICALLY BASED.

Indications in which orphan drugs have been developed.

44% Cancer 21% Metabolism 7% Neurology 6% Cardiovascular

5% Pulmonary 4% Infections 13% Others

ONLY 10% of all RARE DISEASES have treatments.

Pictures: NORD/vfA/BIOCOM

Patients with RARE DISEASES are frequently misdiagnosed or undiagnosed.

There are around 100 types of cancer. Approximately 50% of people who suffer from it are battling a RARE cancer.

RARE cancers include brain, pancreatic, ovarian, thyroid and stomach cancers, leukemia & lymphoma, and all pediatric cancers.

36-40_EB_Summer_2017_OD_aktuell_tg.indd 39

15.06.2017 12:41:17 Uhr

ORPHAN DrugS

“In order to continue to keep the budget impact of orphan medicines manageable, innovative arrangements like managed entry agreements and early access schemes can be used. They provide flexibility to manage evidential and financial uncertainty when evaluating orphan medicines, while enabling timely patient access.” Critics, however, say granting companies conditional market access based on an ever-decreasing database is exactly the wrong direction to take. The head of Germany’s Institute for Quality and Efficiency in Healthcare (IQWiG) Jürgen Windeler, on the other hand, insists that highly conclusive studies are feasible even in the orphan drug field, and suggests compromises concerning significance levels might be required only when it comes to ultra-rare conditions.

Slicing patient pools From the EFPIA’s perspective, “the difficulty in (very) rare disease is that we cannot extend the sample size, and will have to generate generalisable evidence on a small heterogeneous patient population.

The variability in the datasets cannot be offset by the volume of data gathered, as in more common diseases.” A recent review of 68 marketing authorisation application dossiers and EMA assessment reports carried out at Utrecht University shows that EMA regulatory standards are just as high for ODs as they are for nonorphan medicines. That might be true, but healthcare stakeholders have repeatedly demanded an increase in the number of

European Biotechnology | Summer Edition | Vol. 16 | 2017

randomised, placebo-controlled trials for orphan diseases. Besides assuring an adequate evidence level despite limited numbers of patients enrolled, another pharma critic concern is that heretofore broad indications could be sliced through biomarker-based molecular tumour classification. Experts at the EMA have stressed at several congresses that it is a misperception that large cancer indications could be simply sliced into orphan indications through patient selection – an issue that’s been brought up by oncologists like WolfDieter Ludwig, Head of the Committee for Medicinal Products at the German Medical Association (ADKÄ). He has suggested the “orphanisation” of common diseases through precision medicine could become a problem in the future.

A post-marketing data dilemma Pharma critics also argue that OD developers will have little interest in possibly jeopardising their conditional market authorisation with postmarketing study data that could throw the initial positive benefit:risk ratio into question. An EMA study shows that about 50% of the drugs given conditional market approval still haven’t received full approval 10 years later (see European Biotechnology, Spring 2017). According to the EMA, however, getting data from post-marketing studies hasn’t been a problem: “Submission of specific obligations results was often done in advance of the imposed due date, and very few submissions were delayed,” a spokesman told European Biotechn ­ ology.

EU Health Commissioner Vytenis Andriukaitis at the launch of the ERNs

“Compliance in terms of study conduct can be considered generally acceptable, since new studies were only imposed rarely and based on new results, not driven by non-compliance.”

The Next Big Thing in OD Digitalisation of patient data and crossborder collaboration between clinicians are set to improve diagnostics and treatment of patients with rare diseases. Currently, diagnosing an orphan disease takes six years on average, and recruiting suitable patients for clinical trails is laborious. The launch of the European Reference Networks for orphan diseases at the EU Council meeting in Vilnius this March marked a milestone in overcoming current limitations by creating reference networks (ERNs) that pool the expertise of 900 medical units across 26 Member States in 24 rare disease areas. The infrastructure for data exchange created with funds from the Commission, “will lead to easier access to specialised experts in orphan diseases, collection of data and better pharmacovigilance,” an EMA spokesman told European Biotechnology. “Moreover it will boost clinical research and post-marketing studies,” he believes.

The plan is to provide ‘virtual’ advisory boards of medical specialists across different disciplines with digitalised patient data.

“A key concept of this initiative is that the information travels rather than the patient, so ERNs must have the capacity to use IT, telemedicine and e-health tools,” said EU Health Commissioner Vytenis Andriukaitis. This will provide the groundwork for genome analysis and bioIT-based pathway analytics. Next-gen sequencing market leader Illumina has already launched a programme dubbed iHope aimed at identifying the genetic causes of undiagnosed rare diseases in children, while Belgianbased Diploid has developed an IT expert system that autonomously diagnoses orphan diseases. So digitalised medicine and cross­-border research might mark the next evolutionary step not only in developing more ODs, but also in evaluating their fair value.

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t.gabrielczyk@biocom.eu

Pictures:Audiovisual Service of the EC

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II Guide to Life Sciences Events

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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.

European Biotechnology European Biotechnology Network AISBL Rue de la Science 14b | 1040 Brussels, Belgium Tel: +32 (0)2 733 72 37 office@european-biotechnology.net

www.european-biotechnology.net

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C O R P O R AT E M E M B E R S 1/17

NET WORK

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Seasonal event update

tion a c i n u Commemination + diss for EU-funded s service a ti consor

Event Guide The EuroBioFairs Compass shows you which conference,

trade fair, or partnering show to mark on your event calender.

Spotlight on partnering Starting on 25 September, an entire week will be dedicated to communicating the benefits of biotech to the public. The European Biotech Week (see p. 50) is organised by EuropaBio, the European Association for Bioindustries, and features more than 200 events across Europe.

Biotech-pharma partnering will be at the centre of EBD Group’s BioPharm America Event (see p. 52) in Boston. The tenth annual partnering event in the global life sciences hub (26 – 27 September) is a unique opportunity to get in touch with global decision makers in search of innovation. Hundreds of executives are set to attend from venture capital, pharma, academia, and biotech.

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Enterprises aiming to expand in the Far East are well-advised to attend Asia’s largest biotech show (15,000 visitors), BioJapan 2017 (11 – 13 October, see p. 54) in Yokohama.

Keen on discovering the latest trends in the pharmaceutical industry? Then, don't miss the CPhI Worldwide. This year, the branch will meet in Frankfurt, Germany (24 – 26 October, see p. 56). Last time, the show attracted more than 42,000 life sciences professionals, and 2,550 companies showcased their work. ©Robert Kneschke/fotolia.com

Every manager, scientist, or business developer has a very individual, specific network; thus, their must-attend events differ significantly. Where to meet potential new partners and how to widen one’s scope beyond the well-known terrain can be quite difficult to determine.

Euro Biofairs Compass will help you navigate the European meeting jungle in the months to come. Whether you’re looking for a licensing partner, require funding, or just want to find out more about the latest R&D developments and services, our event guide will show you every­thing you need to know about what each event provides.

Based on advanced partnering and networking tools, Nordic Life Science Days (see p. 46) showcases the best that the Nordic region has to offer. The mix of conference, partnering, and exhibition is hosted in Malmö (12–14 September).

Held in Berlin, the DIA’s Clinical & Regulatory Operational Excellence Forum (13–14 September) networks clinicians with regulatory affairs specialists in order to shorten turnaround times (p. 48)

The translational pathway For the fifth year running, Pharma­Lab (see p. 58) calls upon the latest regulatory and scientific developments in all laboratory areas of the pharmaceutical industry (8 – 9 November). This event, to be held in Düsseldorf, is accompanied by an exhibition, in which suppliers of lab equipment and contract laboratories present their offerings.

In the midst of international efforts to solve the global challenge of antibiotic resistance, the Twelfth Fraunhofer Life Science Symposium in Leipzig, Germany (8 – 9 November) will provide an update on the latest progress in the diagnosis of infectious diseases (see p. 60).

More than 1,200 delegates are expected to attend BioFIT 2017 (see p. 62) in Strasbourg, a must-be event for everyone who is interested in partnering, technology transfer, and early licencing (28 – 29 November – 1 December).

To keep up with progress in the latest life sciences technologies, EMBL is hosting one of the world's most a d v a n c e d C our s e & C onf eren ce Programmes (see p. 64) covering the hottest topics in Heidelberg.

Just turn the page to learn everything you need to know about Europe’s mustattend events in the biotech industry. L

Excellent R&D projects deserve excellent communication. With more than 30 years of experience in life sciences, BIOCOM is the perfect partner for your professional communication and dissemination needs in Horizon 2020 and other projects. › Project branding and preparation of communications materials › Creation, maintenance and updating of the project website › Press and media work, incl. videos › Organisation of conferences and workshops

Interested?

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

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12 – 14 September, 2017 MalmöMässan Malmö – Sweden

FIFth Nordic Life Science Days NLSDays offers networking and

knowledge for anyone interested in the Nordic life science, biotechnologies, pharmaceuticals, medical devices, and e-health businesses.

We offer a wealth of opportunities to connect.

Bringing together the best talents in life science, offering amazing networking and partnering opportunities, and providing inputs and content on the most recent trends: Nordic Life Science Days attracts leading decision makers from the Life Science sector, not only from biotech, pharma, and medtech but also from finances, research, policy, and regulatory authorities.

A warm climate GREETINGS Nordic Life Science Days is the largest Nordic partnering conference dedicated to the life science industry. Since its inception in 2013, the event has nurtured a community of people from the world of life science, and created a unique place to do business.

Mos t at tendee s express their delight in the informal atmosphere, com-

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Based on cutting-edge and advanced partnering and networking tools, Nordic Life Science Days showcases the best that the Nordic region has to offer.

The Nordic way of conducting life science business The Nordic region is proud to host some of the world’s most innovative biotech,

bined with an organized approach to meeting highly relevant people. Return visitors come back because they feel they belong to our growing community.

We hope to welcome you, too.

We create a space for meaningful encounters, with one-on-one meetings being one of the main features of NLS Days. Additionally, the high quality of topics and presenters provide insight into the most recent trends in science and business.

Olivier Duchamp Managing Director, NLSDays CEO, Bionordic Services

Meetings on your terms Ever y meeting is an opportunity. At NLSDays, we focus on meeting quality, not quantity. We provide ample time for you to meet your fellow delegates in a stress-free environment.

NLSDays is a SwedenBIO event produced by Bionordic.

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› Quick facts Highlights from NLSDays 2016

›› 1,070 Participants ›› 36 Countries ›› 12,000+ Meeting Requests ›› 2,200+ Scheduled Meetings

Contact Olivier Duchamp +33 (0)608 804 515 olivier.duchamp@bionordic.com www.nlsdays.com www.bionordic.com

Pictures: camille_sonally

Partnering at its best

medtech, and pharma companies. It also has the twelfth strongest economy, making it the perfect place to invest. Set in the vibrant city of Malmö, in the heart of the Medicon Valley, the conference offers super sessions, workshops, company presentations, innovation posters, exhibition, face-toface meetings, and unique receptions, providing numerous opportunities to network with peers, potential partners, and investors.

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nordic partnering at its best

nordic life science days 12—14 september malmö—copenhagen malmömässan

a

event, produced by

partner with the Nordic life science community in the heart of the Medicon Valley photographer: camille_sonally

official conference hosts

register at

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13 – 14 September, 2017 Mercure Hotel MOA, Berlin, Germany

Showcasing Success!

Clinical and Regulatory Operational Excellence Forum Surpass-

ing the realm of mere ideas, this gathering integrates you into the solutions, with real-life successes from within Clinical and Regulatory Operations.

Going beyond GREETINGS DIA is listening to its customer needs, and I am pleased to announce the launch of a novel format that crosses Clinical and Regulatory boundaries along the medicines development value

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“ The new format is a great opportunity to discuss best practice solutions openly.”

Michael Horn, Head of Division Licensing, BfArM, Germany Inspection readiness in a PRIME or Breakthrough Designation environment with real-time data interpretation and Q&A is challenging and requires an experienced team. Additional metrics for quality, timeliness, and completeness must be implemented. Unneces-

chain by connecting Clinical and Regulatory Operations in a very interactive manner, where participants can work through proven solutions that have been already successfully implemented.

› Quick facts ›› A new conference built on partnership case studies.

›› Active audience engagement is encouraged.

›› The exhibition is open, so as to connect attendees with solutions.

Holger Adelmann Senior Vice President, Managing ­Director DIA EMEA

›› Group discounts are available.

Learn more at diaglobal.org/OpEx

Pictures: DIA

Increasing complexities within today's medicines development environment require a close link between Clinical Operations and Regulatory Operations.

Improved coordination will shorten turnaround times, diminish queries, and reduce redundancy in development plans.

Regulatory strategies and supporting documentation must be established early, prior to the planning of Clinical Development programmes. Working solutions for high volume data and feasible concepts for the integration of ever-increasing data diversity need to be understood and then implemented appropriately.

sary information in submitted data or documents for a regulatory submission are confusing the review process and must be avoided.

How do we, as a community of likeminded problem-solvers, go about tackling these complex issues? We must open our thinking and our organisational strategies to innovative approaches in coordinations and partnerships.

Discussing these topics in a purely conceptual manner often does not support individuals looking to excel in their performance with data, documents, and dossiers throughout their daily workload. Quite often, experts are also lacking the oversight and connectivity with other stakeholders along the value chain. The solution is to bring together authorities across the fields of Electronic Data Management, Clinical Operations, Pharmacovigilance, and Regulatory Affairs. This upcoming DIA Clinical & Regulatory Operational Excellence Forum provides the neutral setting for this collaboration.

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Join the dots in Clinical & Regulatory Operations

Clinical & Regulatory Operational Excellence Forum 13-14 September 2017 | Berlin, Germany The increasing complexities in today’s drug development environment require a close link between Clinical Operations and Regulatory Operations by embracing working solutions and partnerships.

This highly interactive forum will enable you to perform complex tasks to the highest operational standards, to shorten turnaround times, and to reduce queries and recreation in your development programmes.

Featured topics • • • • •

Clinical Operations, eTMF Regulatory Operations Pharmacovigilance Electronic Data Management Quality, CMC, Serialization, Compliance

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25 September – 01 October, 2017 All around Europe

European Biotech Week European Biotech Week calls on the

biotech community to start planning events and activities for the week of September 25 to make biotech more accessible, understandable, and, hopefully, exciting.

At EuropaBio, the European Association for Bioindustries, we realise how important it is to foster dialogue and information sharing in the scientifically complex and often misunderstood area of biotechnology. Our members are committed to developing tools and solutions for some of the world’s main challenges, and we have a responsibility to share what we know and to facilitate an open discussion among all stakeholders to accompany these developments.

European Biotech Week was first coined in 2013 to mark the 60 year anniversary of the discovery of DNA’s structure.

Every year, together with its member National Associations, EuropaBio promotes the week and provides a platform for all biotech supporters to pool their events and raise awareness about the products and the benefits that biotechnology brings in areas as diverse as healthcare, agriculture, food, energy, and industrial processing.

Better together

tection like biotechnology. The biotech industry should be proud of its achievements and present its current successes and future plans to end-users. We really hope that European Biotech Week becomes a self-perpetuating week that opens doors to a better understanding of the world in which we live. It is a unique opportunity for those people, organisations, and companies who care about biotech to unravel and debate why there’s no science like biotech science!

GREETING Few other sectors enhance quality of life, knowledge, innovation, productivity, and environmental pro-

The EuropaBio team

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Collaborate and contribute EuropaBio strongly encourages all biotech supporters to join forces and participate in whatever way that fits best with their mission and resources. L

› Quick facts IN 2016

›› 60% of Europe ›› 135 events ›› 60+ media pick-ups around the world CONTACT Cosmin Popa, Communications ­Manager, EuropaBio c.popa@europabio.org www.biotechweek.org

Pictures: EuropaBio

Tribute to biotech

Year after year, the participation in European Biotech Week has increased, with a record 16 countries having taken part in the 2016 edition. The 130+ initiatives organised in the areas of science, education, policy, media, and finance involved thousands of European participants. Importantly, numerous events were related to jobs and training, including career fairs and hands-on laboratories for adults, students, and children, competitions, open door meetings with companies, research institutes, and museums, as well as theatrical shows.

At the national level, in 2015, the initiative was even awarded a medal by the Italian President of the Republic.

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Get involved in European Biotech Week!

If you are familiar with biotechnology, you know the field provides incredibly innovative solutions for the benefit of mankind despite it often being unknown or misunderstood. That is why the biotech community needs you or your organisation to help raise awareness and make biotech more accessible.

Now in its fifth year, European Biotech Week has offered all supporters of biotechnology the opportunity to host events and develop initiatives that contribute to an increased dialogue and understanding of this amazing technology.

1

Potential activities are as varied as the supporters themselves, and the organisers of the Week1 always encourage new ideas and feedback. For inspiration, flip through the magazines of the past editions on www.biotechweek.org.

There are no fees or hidden costs involved.

All organisers can pool their activities on www.biotechweek.org for increased visibility and promotion, and they will later be featured in a widely-distributed post-week magazine.

Interested? Please contact Cosmin Popa (hello@biotechweek.org).

EuropaBio â&#x20AC;&#x201C; the European Association for Bioindustries â&#x20AC;&#x201C; together with its member National Biotech Associations

Part of

biotechweek biotechweek www.biotechweek.org

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B IOP HARM A M E R I C A 2017 TM

SEPTEMBER 26–27, 2017 // BOSTON, MA

26 – 27 September, 2017 Sheraton Boston Hotel, Boston, MA

BioPharm america 2017 The tenth annual BioPharm America™, held

in Boston 26 – 27 September 2017, is a unique partnering event that brings attendees unparalleled access to decision makers from around the world in search of innovation. Hundreds of global executives attend from venture capital, pharma, academia, and biotech.

BioPharm America™ brings together star tup companies, established biotech, and entrepreneur s from academia to attend, in search of finance, pharma, and development partners. The focus is on innovation and forging new business relationships between dealmakers from the life science ecosystem to engage and de-risk the enormous task of drug development. Held in Boston, life science exec-

› Quick facts Highlights

›› 850+ delegates from ›› 500+ different companies ›› 2,400+ one-to-one meetings ›› Panel discussions, presentations ›› Networking Contact email: conferences@ebdgroup.com Phone +1 760 930 0500 www.ebdgroup.com/bpa

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utives from around the globe gather to identify, meet, and enter into strategic relationships facilitated by partnering- ONE®, the world’s leading web-based partnering system. Delegates can request and schedule meetings tailored to their strategic business goals in order to create a dynamic personalized partnering agenda.

Leading pharmaceutical companies attending include Amgen, AstraZeneca, Bayer HealthCare, Biogen, Boehringer Ingelheim, Genentech, Sanofi Genzyme, Ironwood, Johnson & Johnson Innovation, Merck, Novo Nordisk, and Pfizer.

BioPharm America is the only event in North America based on the same reputable formula as EBD Group’s accl aimed European event s BIO- Europe® and BIO-Europe Spring®. The event attracted 850+ delegates from 525 companies who participated in 2,350+ scheduled one-on-one meetings in 2016.

For more information and online registration visit ebdgroup.com/bpa. L

See you in Boston GREETINGS There is no other event quite like BioPharm America™ where biotech entrepreneurs and biopharma executives and investors from across the life science industry convene with the goal of commercializing innovation.

This year, BioPharm America delegates enjoy full access to select, concurrent activities at Biotech Week Boston.

The impetus behind the intensive business development activity at BioPharm America is a two-day conference program that features thought leaders and executives from across the life science industry. Engaging panel discussions cover topics of interest to dealmakers, including licensing, investment, and business development.

In addition, BioPharm America features special tracks specifically designed to help startups and young companies get on the radar of the global life science community and make the connections that matter.

Access capital, innovation, and partners, and meet more key decision makers in two days than you could all year.

Join us in Boston this year, 26 – 27 September 2017.

Anna Chrisman Group Managing Director EBD Group

Pictures: ebd group

Global opportunities

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MORE CONNECTIONS = GREATER SUCCESS BioPharm America™ is now part of Biotech Week Boston

B IOP HARM

A M E R I C A 2017 TM

SEPTEMBER 26–27 // BOSTON, MA, USA

ACCESS MORE Capital, Innovation, and Partners PARTNERSHIPS • 2,400+ one-to-one meetings between biotech, pharma and investors • Build relationships with 800+ key decision makers at evening events

INNOVATION • More innovation than ever before with special pricing for qualified startups • Startup Pitch Competition to a panel of BD execs, VCs, and industry experts

BREAKTHROUGH SCIENCE • Translational Impact Forum promoting scientific research along the drug discovery journey

EXPERT ADVICE • 80+ life science thought leaders speaking on the latest trends and groundbreaking ideas • Startup toolkit program to equip early stage biotech with tools for success

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FIND OUT MORE: ebdgroup.com/bpa Use code “EBN” when you register Produced by

Supported by

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11 – 13 October, 2017 Pacifico Yokohama, Japan

BioJapan & Regenerative Medicine Japan The 19 th iteration of Asia’s

largest biotech event is set to take place 11 – 13 October 2017 in Yokohama, Japan. With over 15,000 visitors and more than 900 partnering organisations anticipated, this year’s edition is set to bring together key players from around the world for over 8,000 business discussions.

BioJapan, Asia’s premier partnering event for the global biotechnology industry, has played a vital role in bringing together Japanese and international organizations for almost two decades.

Along with playing host to almost every top pharmaceutical company in Japan for the past few years, the 2016 introduction of BioJapan’s all-new twinned exhibition, Regenerative Medicine Japan, was also met with wide acclaim.

With almost 900 organisations from Japan and abroad having held more

› Quick facts Partnering Opening in July at cost of just JPY70,000 per account (approximately EUR600) Contact biojapan@jtbcom.co.jp Phone: (+81) 3 5657 0758 www.ics-expo.jp/biojapan

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than 7,000 business discussions over the course of the twinned events’ 2016 partnering, this year’s iteration is well on track to surpass itself once again. The introduction of three new zones within the exhibition hall focusing on healthcare, digital tech, and smart cells, is also set to attract visitors from a broad range of industries to inspire innovation in some of the world’s most rapidly developing fields.

What’s more, since the partnering system is entirely shared between the two co- located exhibitions, the potential for crossfield collaboration is greater than ever.

In recent years, Japan has been working to further develop its position as a major player in the field of regenerative medicine: the country now boasts the fastest approval system for regenerative medicine products in the world, taking as little as two to three years to hit the market with provisional approval. It’s with this progress in mind that expectations are high for Regenerative Medicine Japan to continue to grow into a major event on the calendar of related organisations around the world.

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See you in Japan!

GREETING We are proud that over the last few years, Bio­ Japan has really become a must-visit event in the A sia- P aci f ic r e gio n . I f y ou’r e l o o k in g to forge relationships with new par tners in Japan and Asia, BioJapan is the place: 75% of the 886 organizations participating in last year’s Partnering are based in Asia and Oceania, and 52% are in Japan specifically. What’s more, the event also boasts a solid roster of attendees from around the world, thanks, in part, to our many returning foreign pavilions and clusters. We’re anticipating even more participants from overseas than ever, and with several delegations from Europe, the US, and Asia set to return to the exhibition, taking part has never been easier!

We al so hope that at tendees at the event will enjoy Japan’s famed hospitality. The twinned exhibitions’ social events will certainly contribute to making participation a special experience, and we are ver y much looking for ward to welcoming old and new friends alike to Yokohama this year.

See you in Yokohama!

Sakayu Shimizu Chairman BioJapan Organizing Committee

Pictures: BioJapan

Partnering in Asia

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24–26 October, 2017 Messe Frankfurt, Frankfurt am Main, Germany

CPhI Worldwide After last year’s record-breaking event, the world’s

most prominent pharma executives are ready to gather again for three days of collaboration, information dissemination, and discussions that will define the future of the industry. The CPhI Worldwide will take place on 24 – 26 October 2017 at the Messe Frankfurt, Germany.

Last year’s exhibition saw an all-time record attendance of over 42,000 people, with 2,550+ exhibitors from 156 countries.

Based on this success, at CPhI Worldwide 2017, there will be over 20 dedicated zones covering ingredients, APIs, excipients, contract services, packaging, biopharma, machinery, and many more.

Running concurrently with the pharmaceutical ingredients halls are four other

› Quick facts Tickets After registering online, free Visitor passes are available. Super early bird prices for VIP and VIP Exclusive tickets available until 6 August 2017.

Training and education There are over 150 free seminars on specialist topics and regional updates. http://www.cphi.com/europe

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nearby brands, helping visitors quickly identify the right event for their business’s needs: ICSE, InnoPack, P-MEC, and Finished Dosage Formulation.

On 23 October, the day prior to CPhI Worldwide, the ninth annual CPhI PreConnect Congress will convene. This platform gathers experts and thought leaders from the entire pharmaceutical supply chain to provide insights into the latest, vanguard developments. This year’s conference will examine engaging and forward thinking topics, including the future of continuous processing, CRISPR, gene editing, and combatting antimicrobial resistance.

Beyond the exhibition floor, the CPhI Annual Report will be launched, providing insights into the industry’s hottest topics and issues. Finally, the expanded CPhI Awards – which saw 12 categories last year, plus more entries than ever before – will return with the industry’s best companies honoured during a prestigious ceremony.

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Pharma prospering GREE TING S Welcome to this year’s CPhI Worldwide! The event returns in a year when many developments and potential changes are sweeping across the global pharma landscape – with Britain’s exit from the EU and the new administration in Washington being the most notable, not to mention a new CPhI event for North America. More broadly, the three hotbeds of biotechnology innovation – San Diego, San Francisco, and Boston – have experienced a notable resurgence. In addition, the new Marketing Authorization Holder (MAH) pilot in China is providing innovation opportunities for Chinese biotechs, and globally, generics are taking hold from Japan to the emerging markets. Given the above-mentioned developments, we are presenting the event at a truly prosperous time for the industry.

It’s an ever-evolving pharma landscape and CPhI Worldwide is an opportunity for our industry to bring its collective mind together, filter the noise of the digital age, and focus on the latest trends, technologies, and opportunities. Above all else, though, it is a platform for the industry to drive forward new partnerships, do business, and grow.

Orhan Caglayan UBM EMEA; Brand Director Europe, Middle East and Africa

Pictures: CPhI

Thinking ahead

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products, people & solutions Pharma contract services Pharma contract services

contract services

contract services

Co-located with:

24 - 26 October 2017

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CPhI Worldwide:

The world's leading pharmaceutical exhibition Bringing every aspect of the pharmaceutical supply chain together in one location

“Big pharma, small pharma, specialty pharma and packaging.. everyone is here!”

“You have to be here to be a big player in the industry!”

Cedric Roesler *,6 +Pќ^H`

WHAT VISITORS SAID ABOUT THE 2016 SHOW*

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rate CPhI Worldwide as the leading global gathering of the pharmaceutical industry

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80%

agree that CPhI Worldwide is the most important show in the pharmaceutical industry’s calendar

Industry developments: Z[H` \W [V KH[L VU THYRL[ UL^Z HUK [YLUKZ K\YPUN [OL Pre-Connect Congress, CPhI Pharma Innovation Awards and Pharma 0UZPNO[ )YPLÄUNZ

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believe that CPhI Worldwide is a great show [V ÄUK UL^ I\ZPULZZ opportunities

Free access: 1 ticket, 5 shows, MYLL ZLTPUHYZ PUUV]H[PVU [V\YZ PUUV]H[PVU NHSSLY` HUK TH[JOTHRPUN

* post show survey 2016

Register now: gotocphi.com/register Organised by:

2017 EXHIBITORS INCLUDE: CPhI WW visitor ad 2017 210x275 v1.indd 1 55_EB_Summer_2017_CPHI.indd 1

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PharmaLab

17

Congress & Exhibition

Analytics Bioanalytics Microbiology Düsseldorf, 7/8 November 2017

7 – 8 November, 2017 Swissotel Congress Centrum, Düsseldorf / Neuss, Germany

Pharmalab PharmaLab focuses on the key questions concerning

quality control professionals in analytics, bioanalytics, and microbiology.

This year, the annual meeting – always held in conjunction with a parallel exhibition – will celebrate its fifth anniversary.

In recent months, there have been a number of changes in the relevant guides and chapters of the pharmacopoeias in Europe and in the US, as in, for example, the revision of USP <223> “Validation of Alternative Microbiological Methods” and EP 5.1.6 “Alternative Methods for Control of Microbiological Quality,” as well as the chapters USP <55> and EP 5.1.2 for Biological Indicators. In view of the ongoing activities with regard to “low endotoxin recovery,” as well as to

the European initiatives to reduce the necessary animal experiments in the lab (3R ​​s trategy), the revision of the EP chapters “Monocyte-activation test (2.6.30)” and the “Guidelines for using the test for bacterial endotoxins (5.1.10)” are quite interesting.

For Lab Experts

current regulator y developments, new methods, and practical experience with you. Moreover, take advantage of the exhibition with some 30 exhibitors to get to know regarding the latest lab technology and services. We look forward to seeing you there.

GREETING Join us on 7 and 8 November in Düsseldorf for an information exchange and a discussion on the topics in analytics, bioanalytics, and microbiology that keep you busy in the lab. Almost 60 speakers from authorities, industry, and contract labs, as well as from research, will share

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However, microbiological topics are not the only focus of those responsible in authorities and industry. Biopharmaceutical products have become increasingly im-

Axel H. Schroeder (left) & Dr. Günter Brendelberger Concept Heidelberg, Operations Directors

These issues build the core of six international and four German-speaking conferences at PharmaLab, allowing you to become familiar with the current state of development.

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› Quick facts CONTACT & REGISTRATION www.pharmalab-congress.com HIGHLIGHTS

›› Key speakers from the US, Belgium, the Czech Republic, the UK, Denmark, France, Italy, the Netherlands, Germany, and more ›› Ten conferences with over 60 lectures in English or German ›› Networking options & social event

Pictures: Concept Heidelberg

Focus Lab

portant. Their highly complex structure requires constantly optimised or newly developed assays or analytical methods for the determination of potency, quality, or comparability. Further, to qualify new systems and to validate the methods calls for the use of countless measurement data and, in turn, these days, mostly computer-based statistical tools and systems. This increasing automation and the establishment of Laboratory Integrated Management Systems (LIMS) means data integrity plays a decisive role. Compliance with GAMP and Annex 11 of the GMP Guide and the requirements of CFR21 Part 11 represent a real challenge for all laboratories, whether with regard to quality control or development.

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Bioanalytics, Analytics and Microbiology – Congress & Exhibition – Swissôtel Düsseldorf/Neuss 7/8 November 2017 www.pharmalab-congress.com Scan code to learn more

No matter whether bioassays, chemical analytics or microbiological testing, PharmaLab provides the ideal forum to discuss current trends, developments and applications in the pharmaceutical lab. And for you as a solutions provider the PharmaLab exhibition is thus the right platform to present your latest technologies and services for the modern lab.

Create your own programme out of the following conferences:

Bioanalytics

Analytics

Microbiology

Validation Approach of

Computerised Systems in

Endotoxin and Pyrogen Testing

Rapid Microbiological Methods

Bioassays using Statistical Methods

Bioassays und Proteinanalytik*

Analytical Laboratories

cGMP Compliance Trends in Analytical Laboratories

Methodenvalidierung bei Wirkund Hilfsstoffen*

Leachables und Extractables*

Optimierung von Laborprozessen*

and Mycoplasma Testing

Pharmacopoeial Microbiology

Update – USP and EP Developments

Media Partner: German speaking Conferences

*

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Euro Biofairs Compass

European Biotechnology | Summer Edition | Vol. 16 | 2017

8–9 November, 2017 Institute for Cell Therapy and Immunology, Leipzig, Germany

Fraunhofer Life science symposium 2017 Latest Developments in

the Diagnosis of Infectious Diseases: The annual symposium wants to provide an overview on point-of-care diagnostics in the identification of emerging infections. The Twelfth Fraunhofer Life Science Symposium Leipzig 2017 is held 8 – 9 November 2017 in Leipzig.

After the great successes of recent years, the Fraunhofer Life Science Symposium is one again being held for the twelfth time in 2017. This symposium offers the opportunity to present, hear about, and discuss new scientific developments.

Among others, main topics include: ›› Point-of-care diagnostic ›› Nucleic acid based diagnostics ›› Serology bases diagnostics and much more.

› Quick facts Tickets Check out our early bird fee and our special students fee!

Contact Fraunhofer Institute for Cell Therapy and Immunology info@fs-leipzig.com Phone +49 341 35536-9320 www.fs-leipzig.com

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Keynote speakers from around the world will provide current insights into the exciting field of infectious diseases. The presentation of Heike Sichtig from US Food and Drug Administration, for example, will outline studies for evaluating the use of NGS-based devices and showcase the FDA-ARGOS database resource as an aid in infectious disease diagnostics, as well as for gaining a better understanding of potential NGS clinical implementation strategies. Luisa Barzon from the University of Padova, Italy will present on “Next Generation Sequencing in Infection Diagnostics” during the Fraunhofer Life Science Symposium. “I know Ms Barzon from a very fruitful cooperation in the field of dengue virus diagnostics. Therefore, I am looking forward to her talk and sincerely hope to get to talk to her afterwards,” states Alexandra Rockstroh, Fraunhofer IZI. The Fraunhofer Life Science Symposium 2017 takes place at the Fraunhofer Institute for Cell Therapy and Immunology. About 200 researchers, clinicians, and industry experts are expected to attend.

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Fighting infections GREETINGS E xpanding worldwide traffic and the globalization of human contact are creating new challenges in the prevention of and the protection against infectious diseases. It is increasingly important to fight the proliferative propagation of viral, bacterial, and fungal infections. Thus, fast, correct, and differentiated diagnoses of pathogens are essential. It is, therefore, a great pleasure to announce the Twelfth Fraunhofer Life Science Symposium 2017, which will focus on rapidly evolving technologies used to analyse and diagnose pathogens.

We would like to invite you to present your scientific work and also to meet renowned keynote speakers, as well as other scientists from the exciting field of infectious diseases. This symposium offers you the opportunity to present, hear about, and discuss new scientific developments, encounter new people, and meet old friends and colleagues.

With the industrial exhibition, you will surely find a good platform to communicate your expectations and needs for your research with business partners.

We are looking forward to meeting you in the beautiful city of Leipzig!

Frank Emmrich Institute Director, Fraunhofer Institute for Cell Therapy and Immunology

Pictures: Fraunhofer IZI

Infection update

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Fraunhofer Life Science Symposium Leipzig 2017

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Euro Biofairs Compass

European Biotechnology | Summer Edition | Vol. 16 | 2017

28 – 29 November, 2017 Strasbourg Convention Centre, Strasbourg, France

Biofit Since 2010, BioFIT has confirmed its position as the leading part-

nering event in Europe for technology transfer, academia-industry colla­ borations, and early-stage innovations in the Life Sciences field. The sixth edition of BioFIT will take place on 28 and 29 November 2017. More than 1,200 delegates from 35 countries are expected to come to Strasbourg.

With the highest attendance rate of academics, TTOs, and research institutions, together with big pharma, biotech startups, and (pre-)seed/Series A investors, BioFIT is the place where academia-industry collaborations get started. The event has acquired an entirely new dimension, becoming the market place in Europe for sourcing early-stage innovations stemming from public research institutions, academic spin-offs, and emerging

Bouquet of topics GREETINGS The 2017 conference programme is designed to address the needs of the audience, providing solutions and best practices for every player in the sector. One of the topics will address the position of Big Data and health IT companies in the therapeutic innovation chain. Will they

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biotech companies. BioFIT operates as a platform to encourage new partnerships, source innovative and competitive earlystage R&D projects, facilitate collaborative projects, and increase licensing opportunities in the Life Sciences.

What is inside BioFIT? Thanks to the business convention, all attendees can schedule up to 40

participate or lead? Also, how can bio­ tech, pharma, and academia foster fruitful collaborations? Another topic is how to license early-stage assets. What are the difficulties in nurturing these assets? Last but not least, the challenges for bioentrepreneurs at (pre-) seed & Series A stages are discussed.

For instance, shared risk or competition for emerging assets: How should the pharma-VC relationship function?

Etienne Vervaecke General Manager of Eurasanté

In addition, the 15 roundtable and panel discussions of BioFIT 2017 will feature 60 high-level speakers from around the world discussing, amongst other topics, how Europe can overcome the shortage of bioentrepreneurs.

Finally, so as to promote public research and innovative start-ups, BioFIT’s pre­ sentation sessions give young entrepreneurs, researchers, and tech transfer professionals the opportunity to present their projects and find industrial partners or investors who can support them. L

› Quick facts CONTACT msatola@eurasante.com +33 (0)3 59 39 01 82 www.biofit-event.com @BIOFIT_EVENT 2016 FIGURES

›› 1,150 delegates ›› 30 countries represented ›› 2,500 one-to-one meetings ›› 800 licensing opportunities

Pictures: Eurasanté

Sourcing innovations

one-on-one meetings over the course of two days. At the platform opening one month before the event, they can not only identify potential partners among the registrants, but also scout future licen­ sing opportunities. Afterwards, each participant can manage her/his own schedule to save time and attend confe­ rences or presentation sessions.

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A 360° approach to source early-stage innovations in Life Sciences

www.biofit-event.com @biofit_event

2nd edition 12th and 13th June 2018 Strasbourg

DISCOVER...

A 360° APPROACH

TO BUILD INNOVATION PARTNERSHIPS, SOURCE LICENSING DEALS AND ACCELERATE MARKET ACCESS IN MEDTECH

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www.medfit-event.com

@MedFIT_event

www.medfit-event.com

@MedFIT_event

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European Biotechnology | Summer Edition | Vol. 16 | 2017

May – December 2017 EICAT Heidelberg, Germany

EMBL Events The 2017 autumn European Molecular Biology Laborato-

ries (EMBL) Course & Conference Programme offers a plenty of training opportunities for researchers at the EMBL’s Advanced Training Centre (EICAT) in Heidelberg, Germany

EMBL’s dedicated approach to the new frontiers of molecular biology and life sciences, its top-class logistics and organisation, and its popularity amongst European and international scientists all make the EMBL events programme one of the first choices in molecular biology training. With 15 conferences and 32 courses left to complete the year, the programme offers events on emerging and ground-breaking topics, as well as more established research.

Upcoming, new conferences include Mammalian Genetics and Genomics, Single to Multi-Omics, Centrosomes and Spindle Pole Bodies, Quantitative Principles in Biology, The Nucleosome and Revolutions in Structural Biology: Celebrating the 100 th Anniversary of Sir John Kendrew. Our well-established meetings include Protein Synthesis and Translational Control, The Non-Coding Genome, Seeing is Believing, and Cancer Genomics.

Exciting science

ideas, EMBL strives to bring together scientists from diverse disciplines, leading to innovative thinking and creating synergies. Our stunning training centre mimics the molecular architecture of the DNA double helix, a vibrant place for exciting science and efficient networking. You are invited to join us at the EMBL Advanced Training Centre!

GREETING Advanced Training is one of EMBL’s core missions, with an annual scientific programme of 25 – 30 conferences and 60 courses across all topics of molecular biology and the life sciences. As science advances through the exchange of knowledge, concepts, and

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Dr. Jürgen Deka, Scientific Coordinator EMBL International Centre for Advanced Training (EICAT)

› Quick facts REGISTRATION www.embl.org/events/ Contact EMBL Heidelberg Meyerhofstraße 1 69117 Heidelberg Germany Phone +49 6221 387 - 8797 events@embl.de

Pictures: xxx

2017 EMBL events

If you are looking for hands-on experience with the latest next-generation sequencing (NGS) techniques, bio­ informatics tools, microscopy methods, or practical molecular biology workflows, EMBL has the theoretical and practical courses to cover all your training needs.

In addition, EMBL is constantly improving the attendee experience by providing services like on-site childcare for conferences, multiple networking opportunities, digital information in the course and conference apps, as well as financial assistance at most events.

This year, EMBL is celebrating 40 years of training, which has influenced the career paths of thousands of researchers, with many now returning as organisers or speakers. You are invite to attend one of the events and become part of this scientific community.

See the full list of on-site training opportunities at www.embl.org/events L

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Sweet taste and biodiesel

Protein Design Researchers at Stockholm-based Karolinska Institute have synthesised lung surfactant by mimicking the production of spider silk. Lung surfactance is used in the care of preterm babies; it reduces the surface tension in the newborns’ pulmonary alveoli, allowing them to be inflated at the moment of birth. The paper, published in Nature C ommunic ations (doi:10.1038/ncomms15504), indicates that the new drug is just as effective in an animal model as the biological drugs currently in use, which are produced from pig lungs in an expensive and complicated process.

The new production method is much simpler and cheaper, the scientists said. “[It] is based on the method spiders use to keep their extremely easily aggregated proteins soluble for silk-spinning,” explained Jan Johansson at Karolinska Institute’s Department of Neurobiology, Care Sciences and Society. “We chose to produce lung surfactant protein C because it is probably the world’s most aggregationinclined protein.”

Added Johansson: “The method will also hopefully enable the production of other biological drugs.”

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In a similar campaign, Neste joined forces last year with the Chemical Industry Federation of Finland and other partners to use Christmas ham roast fats to recycling into fuel. Then, as now, the proceeds were donated to charity.

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BergenBio shifts into high gear Stock market For years, BerGenBio has been tipped as one of the most promising bio­pharma companies in Norway. Now, the Bergen-based drug developer is making good on that promise.

In early April, BerGenBio completed its IPO on the Oslo Stock Exchange. There, 16 million shares were offered, raising NOK400m (€42.3m), an impressive sum against the background of the current lackluster stock market climate. In addition, BerGenBio said it will start two collaborative Phase II combination studies this year for its lead cancer treatment BGB324 with Merck & Co’s PD-1 checkpoint inhibitor pembrolizumab for patients with adenocarcinoma and triple-negative breast cancer. The clinical trials will be sponsored by BerGenBio, while Merck will provide the trial with Keytruda. Financial details were not disclosed. Preclinical data from 2015 indicate that BGB324 showed enhanced tumour clearance, survival, and tumour infiltration of cytotoxic T lymphocytes compared with checkpoint inhibition (CTLA-4, PD1) alone.

The money raised in the IPO will allow BerGenBio to advance its most promising drug candidates, said CEO Richard

Godfrey: “The IPO proceeds will support our plans to take BGB324 through multiple Phase II clinical trials during the next 18 months, which we believe will deliver further, compelling efficacy data for this novel medicine. In addition, we intend to advance our biomarker program as we look to develop a companion diagnostic that can identify the cancer patients who are most likely to benefit from BGB324 treatment.” The company also intends to advance BGB149, an anti-Axl antibody, through Phase I, and to progress its discovery programmes.

BerGenBio’s lead candidate BGB324 (formerly R-428), which the Norwegian company licensed from Rigel Pharmaceuticals in 2010, has passed Phase Ib testing in acute myeloid leukaemia, myeloid dysplastic syndrome, and non-small cell lung cancer (in combination with Roche’s erlonitib). Besides its selective Axl kinase inhibitor, the Norwegian company also has an anti-Axl kinase antibody and an antibody drug conjugate (ADC) under preclinical development. Treatment responders are set to be stratified prior to therapy by a companion diagnostics test that measures Axl kinase expression. J

Picture: Lena Holm, Karolinska Institute (left), BootstrapGiver/Pixabay (CCO, right)

Spider to infant

B i o e c o n o m y H o m e r S im p son goes green? A Finnish donut maker has teamed up with biofuel producer Neste Oil to produce biodiesel from the fat used to fry the tasty treats. The “Doughnut Trick” campaign is meant to remind Finnish people about the potential of the circular economy and recycling. “We want to illustrate how waste and residues can be reused to produce new products, in this case high-quality Neste MY renewable diesel,” adds Johan Lunabba, Director of Sustainability at Neste. From the oil that is needed to fry three doughnuts, enough diesel can be refined to drive a distance of about one kilometer.

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Guarding against microbes A M R The Nordic countries are collaborating on combatting antimicrobial resistance. In April, the Nordic Council adopted a white paper addressing the threat that AMR poses to health at local, regional, and international level. It also aimed to identify and formulate a number of Nordic initiatives and priorities for action. The report details a strategy with seven, overall objectives that can be implemented through 12 initiatives. They were developed on the basis of a 2016 hearing

entitled “You Don’t Die from Pneumonia, Do You …?”, at the request of the Danish Presidency of the Nordic Council Presidium and the President of the Council, Henrik Dam Kristensen. Experts from all five Nordic countries and the appropriate academic environments attended.

The Nordic Council has declared its support for the initiatives and recommends that the Nordic Council of Ministers prepare and initiate the implementation. The report is available from the council’s portal at http://www.norden.org/nordpub. L

So much for chicken feed!

Pictures: congerdesign/Fotolia (CC0)

P r o b i ot i c s In the spring, Novozymes announced a strategic collaboration with Boehringer Ingelheim Animal Health. The aim is to develop probiotics for global poultry production, in particular, for hatcheries. Boehringer Ingelheim will market and distribute Novozymes’ FloraMax probiotic product for the US poultry industry and plans on expanding to other markets globally in the coming years. “Collaborating with Novozymes enables Boehringer Ingelheim to enter an exciting new segment of products to provide alternatives in an environment that is increasingly challenged by antibiotic bans,” commented George Heidgerken, Global Head of Livestock at Boehringer Ingelheim. “Poultry producers are looking for improved ways to deliver on the grow-

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ing global need for sustainable protein.”

Probiotics are naturally occurring microbes that can improve the gut flora of poultry and other animals. Research has demonstrated that a robust gut flora can significantly improve animal health, potentially dispensing with the need for antibiotic growth promoters. The rising global consumption of meat, along with legislative and consumer-driven curbs on the use of antibiotics as growth promoters in animal farming, have increased demand for alternatives, such as probiotics. “We are excited to collaborate with Boehringer Ingelheim to develop a range of probiotic solutions for poultry that will improve sustainability in the industry,” said Susanne Palsten Buchardt, Vice President of Animal Health & Nutrition at Novozymes. J

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News Phase II setback Genmab A/S has announced that its CD38-targeting Phase II candidate daratumab did not reach the expected overall response rates in lymphoma patients. Subsequently, codeveloper Janssen decided not to initiate Stage 2 of the Phase II study of daratumumab in three types of relapsed or refractory non-Hodgkin’s lymphoma. Other ongoing or planned studies with daratumumab will not be affected by the decision, Genmab CEO Jan van de Winkel said.

Pre-IPO money In preparation for its Initial Public Offering at the Nasdaq Stockholm exchange at the end of 2017, Lytix Biopharma has raised NOK80m (approximately €8.4m) in a repair issue financing round. The proceeds will fund the rest of the Phase I study for the oncolytic immunotherapy LTX315, which is being developed for triple-negative breast cancer (TNBC), malignant melanoma, and solid tumours. In TNBC, a first cohort generated evidence that combining LTX315 with pembrolizumab was safe.

Trial financing Cancer med developer Targovax ASA has doubled its cash and equivalents as of 31 December 2016 by raising NOK200m (€21m) in a private placement of new shares. The net proceeds are sufficient to finance five data read-outs from clinical trials through 2018, in addition to the three planned data-read outs in the second half of 2017, the company said.

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WESTERN EUROPE

European Biotechnology | Summer Edition | Vol. 16 | 2017

Galapagos cashes in

Money boost Finance In April, Advent France Biotechnology closed its first Life Sciences seed fund at €64.75m. The venture capital group will invest seed money particularly in French start-ups and company founders developing “breakthrough technologies.” Besides Bpifrance’s €600m National Seed Fund (Fonds National d’Amorçage), the “EU InnovFin Finance for Innovators” initiative and the European Fund for Strategic Investments, Bpifrance, private companies, and family offices have also contributed investments to the new fund.

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Stocks At the end of April, autoimmune specialist Galapagos NV closed a €363.9m public offering of 4,312,500 American Depositary Shares (GLPG) at US-$90.00 underwritten by Morgan Stanley. From the first day of trading, the company’s market capitalisation increased from US$4.22bn to US$4.39bn in midJune. Galapagos’ ordinary shares are currently listed on Euronext Amsterdam and Euronext Brussels.

The company’s Phase II lead compound filgotinib has been licenced by Gilead Sciences to treat ankylosing spondylitis and psoriac arthritis. Furthermore, Galapagos runs Phase III pro-

grammes with its JAK1 inhibitor in rheumatoid arthritis, Crohn’s disease, and ulcerative colitis (UC) and Phase II studies in small bowel and fistulising CD. Additionally, Galapagos is conducting Phase I tests with MOR-106, an anti-IL17C antibody designed for treatment of patients with atopic dermatitis. The company expects to announce headline results of its oral Phase II selective autotaxin inhibitor, GLPG1690, in idiopathic pulmonary disease (IPF) patients in H2/2017. After successful Phase I testing, it is still unclear as to what Galapagos and its partner Servier will do next regarding the development of GLPG1972 in osteoarthritis patients.

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Fuelling R&D

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Uniqure withdraws €1.1m drug Uniqure/Chiesi With treatment cost of up to €1.1m per patient, gene therapy Glybera (alipogene tiparvovec) was the most expensive therapy ever approved in Europe. At the end of April, Uniqure announced it will not prolong its conditional market authorisation for the treatment of the rare inherited disease lipoprotein lipase deficiency (LPLD), due to “limited patient demand.” Patients treated before 25 October 2017 will be further supplied with Glybera under uniqure’s commercialisation deal with Chiesi Farmaceutici “at a nominal price.” However, Uniqure announced it will terminate the Phase IV post-approval study, 50% co-financed by Chiesi, a €31m equity stakeholder in the Dutch company. According to the deal, Commercialisation of Uniqure’s haemophilia B gene therapy won’t be affected by the Glybera withdrawal. Up to 600 patients in the EU suffer from LPDL. L

Picture: Uniqure

Immuno-oncology Fastgrowing cancer immune therapy specialist Adaptimmune has raised US$42m through the purchase of 7 million American Depositary Shares (ADS) at US$6 to satisfy its need for R&D money. As the company’s R&D pipeline has recently expanded from 9 to 11 candidates, R&D cost rose accordingly, from US$40.5m to US$63.8m. Additionally, staff has doubled in size. Net proceeds of the offering will be used to advance the company’s wholly-owned pipeline of SPEAR T-cell candidates with an anti NY-ESO therapy to treat synovial sarcoma in Phase I/II. The company said that, together with a previous public offering of US$66m, it is now well-financed to develop its Spear T-cell therapies until 2019.

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News Japanese take-over

Cash for sustainable bottles IPO Dutch Shell spin-out Avantium BV has raised €103m through the issuance of 9,401,793 shares at €11 in oversubscribed Euronext Brussels IPO. With a market capitalisation of €277m, the Dutch plastics maker has now enough money in its coffers to cofinance the establishment of the first-ever, commercial-scale plant for 100% recyclable and bio-based plastics. Under an agreement dating back to October 2016, Avantium and BASF formed Synvina, which will now use the capital to produce furandicarboxylic acid (FDCA), and its polymer – the high performance plastics polyethylenefuranoate (PEF) – at BASF’s Antwerp production site.

PEF is made from plant-derived fructose.

It outperforms the current standard plastic PET for beverages packaging, as it is 100% recyclable, lighter, and releases sig-

nificantly less CO2 that PET. PEF applications include bottles, fibres, films, biofuels, as well as furan-dicarboxylic-acid-based polyamides used for engineering plastics, nylons, and fibres. Coca Cola Company, Toyobo, ALPLA, Mitsui, and Danone have already signed on to use PEF produced at BASF’s Verbund Site, which can produce up to 50,000 metric tons annually.

Avantium had previously cancelled two efforts to go public (2007 and 2016) following weak investor demand. Just a few weeks before Avantium’s IPO, main investor Sofinnova Partners announced the €106m closing of its Sofinnova IB I Fund dedicated entirely to renewable chemistry. At the end of May, Synvina received interim approval from European PET Bottle Platform for the disposal of PEF through existing recovery systems.

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Gene therapy investment

Picture: BASF/Avantium

AAV Paris-based gene ther-

apy specialist Vivet Therapeutics raised €37.5m in May. The Series A round was led by Novartis Venture Fund and Columbus Venture Partners. Roche Venture Fund, HealthCap, Kurma Partners, and Ysios Capital acted as co-investors. Vivet’s CEO Jean-Philippe Combal said the funds will be used particularly to push the development of the company’s preclinical

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lead candidate VTX801, a gene therapy designed to correct the rare autosomalrecessively inherited Wilson’s disease.

The vector dubbed Anc80 licenced from Massachusetts Eye and Ear Hospital and the University of Navarra (Pamplona, Spain) expresses a functional form of the ATP7B gene, which encodes an ATP-dependent transporter required to prevent accumulation of toxic copper in liver cells. L

In mid-May, Japanese pharma major Astellas took over private Belgian drug developer Ogeda S.A. for a €500m payment up front, and up to €300m in milestones. With the deal including the NK3 receptor blocker fezolinetant (ESN364), Astellas complements its pipeline.

Currently, Ogeda’s lead is being in three Phase IIa programmes to treat menopausal hot flashes, polycystic ovary syndrome (PCOS), and uterine fibroids.

Salmon fed by whiskey Scotch start-up Horizon Proteins has announced that it will commence commercial protein production from left-overs of the whiskey fermentation process. In April, the company said it had successfully demonstrated the feasibility of its process and was now establishing a production hub in the North East of Scotland. The company’s plan, after having finalised a VC financing round, is to produce up to 12,000 tonnes of protein annually – 15% of the salmon farming industry’s demands. Proteins are being extracted from the pot ale leftovers from the fermentation process.

Scale up the volume French industrial biotech company Global Bioenergies SA (Evry) has scaled up its bio-based isobutene process in the Leuna demo plant (Germany) to 5,000 litres, 10 times more than the output of the company’s pilot plant in Pomacle.

First batches of the process that converts plant sugars to the outgassing biofuel will be produced by June.

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Pieris on a winning streak

Inthera rushes Drug Discovery Inthera Bioscience AG, a clinical-stage biopharmaceutical company from Schlieren, raised CHF10.5m (€9.6m) in a Series A round to advance the development of its small molecule-inhibitors of protein-protein interactions. The company claims its proprietary technology yields first-in-class drug candidates – so called oxopiperazines that can be modularly assembled in a peptide-like fashion. Inthera’s lead candidate is designed to attack cancers associated with human papilloma virus. As with the €3.4m seed round just one and a half years ago, venture capitalists Merck Ventures, Aglaia BioMedical Ventures and Novo Seeds contributed equally. L

Anticalins are a new class of protein therapeutics that are significantly smaller than monoclonal antibodies.

Anticalin Platform After scoring deals with French pharma company Servier and Japanese pharma group Aska, Nasdaq-listed Pieris Pharmaceuticals, Inc. struck again in May. Winning over British-Swedish pharma heavyweight Astrazeneca, Pieris could receive up to US$2.1bn in a deal for respiratory candidate PRS-060. According to a joint statement, Astrazeneca has already paid US$45m and will inject an additional US$12.5m when it progresses moderate

to severe asthma candidate PRS-060 into Phase I later this year. Beyond the main candidate, four other anticalins with undisclosed targets are also part of the deal.

Astrazeneca wants to determine if Pieris’s anticalin platform is suitable to deliver inhalable drugs for a range of indications.

Pieris moved its headquarters to Boston (US) in the past, but remains committed to strengthening its former home base in the Southern German town of Freising in the future.

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Immunooncology German Merck KGaA has secured an exclusive option on UK’s F-Star Biotechnology Ltd’s preclinical bi-specific PD-L1/LAG checkpoint inhibitor FS118 and four other candidates.

The deal includes a €115m upfront payment from Merck. If the pharma company exercises the option, F-Star is eligible to cash in up to €900m. The deal focuses primarily on F-Star’s most advanced bi-specific asset FS118, a programme run through F-Star Delta, one of four asset-related satellite companies of the Cambridge-based biotech. The deal also includes four bi-specific IgG-like antibodies in discovery stage, which target immune checkpoints.

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Diagnostics Southern German DNA sequencing and genetic testing company GATC Biotech is being acquired by Eurofins Scientific SE based in Luxembourg.

The purchase price was not disclosed. Eurofins stated that it wanted to boost its nucleid acid testing capabilities. Founded in 1990, GATC now has 140 employees in Constance and Cologne. The firm provides services for some 10,000 customers and scores annual revenues around €20m.

“We are excited to be joining the Eurofins family of laboratories and look forward to the next phase of our development within the Group,” Peter Pohl, GATC CEO and cofounder, said in a statement.

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Clinical Diagnostics German Epigenomics AG and minority shareholder Cathay Fortune International Company from China have agreed for Cathay to take over the Berlin-based diagnostics company for €7.52 per share in cash – a premium of almost 50%. The takeover of Epigenomics will be handled by Cathay’s subsidiary Blitz F16-83 GmbH (coming Summit Hero Holding GmbH). The voluntary public takeover offer was published in early June (company value at €171m). If the transaction is successful, Blitz has agreed to provide cash of up to €6.46m. Despite resistance from some of its own stockholders, Epigenomics leaders support the offer. L

Picture: Pieris

Billion euro deal GATC acquired Takeover offer

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European Biotechnology | Summer Edition | Vol. 16 | 2017

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Switzerland’s most important industry Swiss Biotech Day 2017 “Lonza is a complex animal,” Richard Ridinger said at this year’s Swiss Biotech Day in Basel.

The company’s CEO referred to their 120 years of history and numerous metamorphoses along the way. “We see ourselves as a player serving clients throughout the healthcare continuum - from patented prescription drugs to well-being products,” Ridinger explained. The CMO organisation with 15 production sites recently closed a portfolio gap on the fill-and-finish flank by acquiring US competitor Capsugel. Yet, Lonza is keeping its high pace, Ridinger insisted: “Later this year, we plan to open the biggest viral therapy production site in the world in the US.” Several professionals in the audience surely got excited when Lonza’s chief promised to answer the most pressing question in the field of cell therapies: “Two weeks and a full lab to produce a treatment for one patient, that‘s not to finance! We are quite advanced to make these individualized medicines affordable.”

The Swiss Biotech Day 2017 brought together more than 500 Life Sciences industry executives from across Europe. The event seems to gain traction among industry experts. As was the case last year, the organisers Swiss Biotech Association (SBA) and BIOCOM could again celebrate a record number of attendees. In addition to holding their annual general assembly, the SBA also presented the Swiss Biotech Report 2017 at the event in the Congress Centre Basel. According to the report, the chemistry, pharma, and biotech sector contributed 44.8% of all Swiss exports in 2016. It is by far the country’s most important export industry. CHF80.3bn of the sector’s record CHF94.3bn originate from pharma, diagnostics, and (medical) biotech companies. The remaining CHF10bn came from agrochemical, plastics and fine chemical companies. Big pharma companies are responsible for the lion’s share of the exports, but more and more their success also depends on innovations made by small and medium-

sized biotech companies. In Basel, visitors could get a first-hand impression of 15 up and coming young companies from Switzerland. The “Emerging Companies” track was presented by Johnson & Johnson (J&J) Innovation. The idea-scouting arm of the world‘s largest healthcare company was represented by innovation expert Nerida Scott, who explained in her keynote lecture how “Accelerating Innovation Around the World” works best. J&J uses a variety of tools, including four innovation centres on three continents. “Since 2014, we have explored more than 7,100 opportunities,” said Scott. The J&J manager also talked about the outcome for the company: “Our JLABS incubators, for instance, had 140 companies in residence and 33 of them progressed to collaborations.”

Next year, the Swiss Biotech Day will take place on 3 May. The event will be in its 20th year, and it seems certain that even more biopharma VIPs will show up in Basel.

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Pictures: André Springer/SBA

EY partner Jürg Zürcher (left), moderator Monika Jones, Christian Moser from the Swiss Federal Institute of Intellectual Property, and SBA President Dominik Escher discussing the state of the Swiss biotech industry at the Swiss Biotech Day 2017.

In transition

In anticipation In celebration

Microscopy Heidelberg-based Lu­ xendo, a spin-off of the European Molecular Biology Laboratory (EMBL), was sold to Bruker Corporation (US) in May for an undisclosed sum. Luxendo develops and manu­factures proprietary, light-sheet fluorescence microscopy instruments. 

Cell Therapy Applying for a EU marketing authorisation, Codon AG received the official positive opinion from the Committee for Medicinal Products for Human Use for its articular cartilage product in May. Starting at €2.75 in January, Codon’s stocks traded at €10 in June. 

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Immunotherapy The European Commission has granted Viennese private biotech company Apeiron Biologics AG marketing authorisation for Dinutuximab beta Apeiron, an antibody-based immunotherapy of the rare paediatric orphan oncology condition neuroblastoma. 

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Record funding for antibiotics

Oncology Menarini-Silicon Biosystems Inc., a wholly-owned subsidiary of Bologna-based Menarini Group, has completed the take-over of the Cellsearch Circulating Tumour Cell System from Janssen Diagnostics. The acquisition will mark Menarini’s first entry into the US diagnostics market. Cellsearch is the only clinically validated blood test cleared by the FDA for detecting circulating cells (CTCs). These are cells spread from the primary tumour into the blood. Cellsearch systems can be used for patients with metastatic breast, prostate, and colorectal cancers. The test is also approved by the China Food and Drug Administration for use in monitoring metastatic breast cancer patients. Menarini would like to combine the CTC portfolio with its DEPArray platform for image-based, digital cell-sorting and isolation.

New manufacturing sites Menarini also expanded its manufacturing capabilities for oncological drugs by setting up new facilities in Pisa and Berlin. In Pisa, manufacturing sites have been built for the production of clinical batches of potent antitumoural compounds. The new facility will manufacture both small molecules and biological macromolecules, such as antibody-drug conjugates (ADC), obtained through the conjugation of monoclonal antibodies with potent toxins. The research centre in Berlin has been built for packaging, labelling, storage, and distribution of clinical trial supplies of antitumoural compounds, including ADCs. 

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Vojmir Urlep (left) and Prime Minister Miro Cerar (right) at the opening ceremony.

Meeting point

Expansion fund

Conference For the third time, Barcelona invited the international biotech and pharma communities to join BIO Europe Spring. More than 15,200 meetings occurred over the three-day conference. While Italian-based company Newron finally reported approval from the US regulatory Food and Drug Administration (FDA), for the use of Xadago to treat Parkinson’s disease as an add-on therapy to levodopa/carbidopa, Spain had its secondlargest life science VC financing in history.

Spanish investor Ysios Capital, along with Spanish bank Caixa, announced a €34.4m round for catheter company MedLumics, based in Tres Cantos near Madrid. Capital Cell, the Spanish life sciences crowdfunding platform, reported a record closing: Around 250 investors raised more than €1m for Spanish biotech company Bionure. 

Financing In May, the in-vitro point-of-care diagnostic company Biosurfit SA drew down the second €6m part of a €12m loan signed with the European Investment Bank (EIB) in November 2015. “The expected launch of our new lipids and inflammation panels during 2017 necessitated our upgrading our manufacturing capacity. The EIB funds will support the construction and commissioning of this facility and our continued commercial roll-out in both existing and new markets, including the US and Asia, following the necessary regulatory approval,” states João Garcia da Fonseca, CEO of Biosurfit. The new facility in Azambuja (near Lisbon) will include automated manufacturing space and a R&D lab space. The construction is expected to start in Q2 17. 

Picture: Lek

Rise capabilities

key countries that provides a transparent and secure business environment,” emphasises Cerar. Lek has been operating in Prevalje for almost 40 years. The broadspectrum antibiotic is sold in more than 60 global markets, including the USA. Annually, more than half a billion tablets are manufactured in Prevalje.

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Investment In April, an important visitor came to the village of Prevalje.

Miro Cerar, the Prime Minister of the Republic of Slovenia, laid the symbolic foundation stone for a new production plant of Lek, a Sandoz company. In the future, an unnamed broad-spectrum antibiotic will be produced there. Novartis has made its largest investment in Slovenia so far: The first investment stage is €85m starting in 2017, and the total value will amount to €105m, with more than 150 new jobs. “With this investment in a new production plant in Prevalje, Novartis reaffirmed its intention of a longterm presence in Slovenia,” says Vojmir Urlep, President of the Board of Management of the Sandoz company Lek. Since 2003, Novartis has invested more than €1.9bn in Slovenia. “Around €1bn has been dedicated to development, the rest has been spent to the modernisation and expansion of production capacities.

The Government of the Republic of Slovenia welcomes the decision of Novartis which recognises Slovenia as one of the

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European Biotechnology | Summer Edition | Vol. 16 | 2017

New EMBL site opens in Barcelona disease modelling Afters years of budget cuts and political neglect, welcome news has come for the Spanish scientific community in April. The Spanish Economy Minister Luis de Guindos and European Molecular Biology Laboratory (EMBL) Director-General Iain Mattaj signed an agreement for a new, world-class disease modelling EMBL facility on the campus of Barcelona’s Biomedical Research Park (PRBB). “The site will be one of the few places in the world where scientists can access state-of-the-art microscopy and modelling technologies specifically designed for studying tissues,“ states Mattaj. Researchers across the globe expect human tissue models for drug development to provide more realistic predictions for disease mechanisms, thus decreasing the current 90% failure rate of clinical development. At the new EMBL for tissue biology and disease modelling, scientists will tackle flaws in how cells arrange three-dimensionally and interact at the tissue level when they, for example, become cancerous, lose immune tolerance, or turn necrotic.

Their findings are expected to inspire

drug development by delivering novel targets and potential disease modulators. The site will house state-of-theart imaging facilities, such as one of the few SPIM microscopes, making pioneering technologies available to scientists worldwide. The Spanish and the Catalan government, alongside with the Centre for Genomic Regulation, have supported the initiative from the beginning. EMBL will invest €16m in the new site during the first five years. Spain will contribute €6m until 2021. The Catalan government will cover the €400,000 annual bill for rent and maintenance.

The new EMBL will complement the biomedical cluster in Barcelona already established at the PRBB and will bring collaboration in biomedical research to the next level. Barcelona will be the first new EMBL site to be established in almost 20 years. Including this center, EMBL operates across six sites, with the others located in Heidelberg (Germany), Hamburg (Germany), Grenoble (France), Hinxton (UK), and Monterotondo (Italy). Barcelona will be the institute’s sixth site in Europe and will being operating in September 2017. 

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News New office opened The international healthcare company Orphan Biovitrum AB (Sobi), headquartered in Sweden, opened a new office in Athens at the beginning of May. It will become a new member of Greek Haemophilia Society. “We aim through close dialogue and cooperation with the Greek authorities to provide high quality care and sustainable access to treatment for people living with rare diseases in Greece,” says Sergio Lai, General Manager for Sobi, Italy, Greece, Cyprus, and Malta.

EU fund for bioplastics The BioBarr project, short for “New bio-based food packaging materials with enhanced barrier properties” has received €4m of funding.

The food packaging project is based on the PHA biopolymers produced

by Italian Bio-on’s technologies. Milano-based Tecnoalimenti S.C.p.A. has been tasked with the coordination of the project, which started in June and will run for four years.

Picture: Comai, Mayer & Swoger/CRG

Fighting rare diseases

The internal structure of a developing mouse head, imaged with a SPIM-microscope like the one that will be used in EMBL in Barcelona.

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Swiss Santhera Pharmaceuticals has signed an agreement with Pharmathen to market Raxone in Greece and Cyprus. Raxone is one of the first treatment options for the rare Leber’s hereditary optic neuropathy (LHON) disease. Pharmathen is focused on the development and marketing of pharmaceuticals, with a strong position in generics. “The partnership with Santhera demonstrates our strong commitment to providing innovative solutions in the field of rare diseases,” says Pharmathen’s President Vasileios Katsos.

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Selvita celebrates two premieres

Licensing The aspiring Czech drug developer Sotio has grabbed what its CEO Ladislav Bartonicek calls a firstin-class cancer metabolism programme: The Lead Discovery Center GmbH (LDC), Max Planck Innovation GmbH (both in Germany), and Sotio a.s. have signed a collaboration and license agreement providing Sotio with exclusive rights to an oncology programme addressing a novel target in tumour metabolism. The target was discovered at the Max Planck Institute for Biology of Aging in Cologne and jointly advanced by the LDC and Max Planck scientists into drug discovery. Bartonicek added: “Targeting cancer metabolism is a highly attractive and innovative approach for the treatment of cancer.”

Under the terms of the agreement, the LDC and its academic partners will perform further lead optimization and identify corresponding biomarkers for the programme in collaboration with Sotio. Upon nomination of a pre-clinical candidate, the Czech biotech company will be responsible for preclinical and clinical development, as well as subsequent marketing and commercialization. The LDC is eligible to receive research funding from Sotio, as well as publicly unknown upfront, development, and sales milestone payments, plus royalties on net sales of the product.

Sotio’s home turf are therapies based on activated dendritic cells for the treatment of cancer and autoimmune diseases. 

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over of the trial later in 2017. Both companies will collaborate on additional preclinical research on PIM/FLT3 targets. The upfront payment is €4.8m, with Selvita eligible for a total of €89.1m in potential milestone payments, and non-specified single to low-double digit royalties and cost sharing. For Selvita, 2017 is “a breakthrough year” for two reasons: The trial start is a first for a Selvita medicinal product, and the Menarini deal is the company’s first global license agreement.

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Axon starts no. 4 Indrops wins Neuroscience In April, Slovakian-Cyprian biotech company Axon Neuroscience SE said it plans to start a pilot phase I study in patients suffering from the non-fluent variant of Primary Progressive Aphasia (nfvPPA) – a subgroup of Frontotemporal Dementia (FTD).

The newly announced clinical study – developed in cooperation with the German FTLD Consortium – will be the company’s fourth. This is for the first time that nfvPPA patients worldwide will have the opportunity to participate in a clinical programme with disease-modifying potential, said Matej Ondrus, Axon’s Medical Director.

As with the other three clinical studies, Axon will be evaluating the potential of its active tau vaccine AADvac1. The antibodies elicited by vaccination with AADvac1 are designed to recognize pathological tau protein in the brain. Preliminary data suggests that the antibody response in patients can stop or slow down the progression of Alzheimer’s Disease. 

Microfluidics The inaugural Lithuanian-American Innovation Award went to Linas Mažutis. Together with colleagues from Harvard University (US), the scientist developed Indrops, a technique for the efficient isolation and sequencing of single cells. Short for indexing droplets, Indrops makes it possible to barcode and sequence the transcriptome or genome of 15,000 individual cells per hour with minimal reagent use. The process works at a fraction of the cost of present commercial platforms. The Baltic American Freedom Foundation, the American-Lithuanian Business Council, and the US Embassy in Vilnius established this award. It was designed to be granted to a Lithuanian individual, organization, university, or firm that has developed an innovation in collaboration with a US partner. Among the five 2017 nominees was another life sciences innovator: Virginijus Siksnys, one of the developers of CRISPR/Cas9 genome editing technology. 

Picture: Selvita

Sotio strikes new cancer target

Drug Discovery Selvita has sealed its first deal for a proprietary clinical-stage asset. In late March, the Polish drug discovery company announced that it has out-licensed its lead asset SEL24 (a dual PIM/FLT3 kinase inhibitor) to German affiliate Berlin-Chemie of Italian pharma group Menarini. Selvita will be responsible for the continuation of the current Phase I/II trial for acute myeloid leukaemia, with the first patient enrolled this spring, until the Menarini’s estimated take-

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Start-up Story

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Too deadly to ignore

Juvabis Leaders worldwide have been awakened to the fact that the bottom of the barrel has

been scraped with regards to antibiotics. As new antimicrobials are fewer and farther between and resistances are mounting, new approaches are garnering more and more attention. A Swiss start-up has developed a unique technology platform to design new drugs to fight bacteria.

Juvabis’ founding story is everything but unique, muses co-founder Sven Hobbie.

A group of Swiss researchers develop a new technology, file the patent, and decide to commercialise their IP. That’s how it goes...however, reality is rarely that straightforward. It took a seven-year detour across the world before Hobbie got the company off the ground. “I worked at MIT, both in Singapore and Boston,” he explains. There, he was exposed to a vigorous commercialisation of science.

Hobbie felt inspired. He knew that back in Zurich, there was great potential to address the increasing problem of antibacterial resistance.

He returned to Zurich but not without misgivings. “I left a lot behind to venture into this start-up,” he says with a smile.

“But the risk of antimicrobial resistance is too deadly to do nothing.” Together with his Zurich colleagues Erik Böttger and Andrea Vasella, as well as David Crich at Wayne State University, Hobbie founded Juvabis – with a seemingly simple approach. “We focus on those bacterial drug targets that have proven most successful in medical history and apply

Picture: Hypromine

Company Profile

Juvabis GmbH Founded in 2015 Based in Zurich CEO: Sven Hobbie Web: www.juvabis.com

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Sven Hobbie Juvabis, CEO

? !

How are you going to change the world? e are going to save lives by W bolstering the treatment options for infectious disease.

innovative chemistry to develop new therapeutics. Since both the drug targets and the compound classes have been clinically validated, there is a high chance of efficacy in humans and limited safety concerns.” These characteristics will allow Juvabis to rapidly process its leads into clinical trials, Hobbie points out. It is crucial that drug candidates circumvent all relevant resistance mechanisms known to date. Of course, there is no guarantee that new resistances will not emerge, but that is true for any new antibiotic, Hobbie stresses.

Today, new antibiotics are used much more carefully than in previous decades.

This is exactly why big pharma has been

hesitant to invest for some time. “You cannot flood the market with a new antimicrobial,” says Hobbie. New drugs would be held back to function as a last resort: this is not a profitable outlook. However, policies worldwide are beginning to change in light of dwindling anti-bacterial resources. “In [the] future, economic models will be put in place to make sure that revenue will not depend on [the] volume sold but on how the antimicrobial performs, for example, by being able to set a high price on new drugs, or by market entry rewards.”

Where big pharma companies are still afraid to tread, smaller biotechs like Juvabis are picking up the slack – and the risk.

“It’s true. Policy changes to incentivise antimicrobial drug development are an ongoing process,” says Hobbie. “We anticipate changes for the better, but critical details have yet to be finalised.” So far, though, he is not worried.

“We have a big advantage,” Hobbie explains. “Our preclinical development projects have greatly benefitted from support by the ENABLE programme.”

The IMI project seeks to promote the development of new antibiotics against gram-negative bacteria. Juvabis is still in the pre-seed stage, working from Zurich University, though now, everything is set to move quickly. The company expects to be fully funded by the end of the year, with the first product scheduled to move to clinical trials as early as next year.

Until then, much work still needs to be done. CEO Hobbie, is especially on the job 24-7, but he tackles it with humour.

“With a start-up, you need funding for hiring people, but you need manpower to maximise the chances of getting funding,” he says. “It is a Catch-22.”

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u.mommert@biocom.eu

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AllergIES

European Biotechnology | Summer Edition | Vol. 16 | 2017

Public Enemy Number One advances in the field are causing numerous experts to say it’s widely under­used. The goal of allergen immunotherapy (AIT) is to induce a specific immune tolerance by confronting patients with increasing levels of allergens. AIT developers are now working on improving efficacy and safety, while at the same time trying to speed up the still lengthy process of desensitisation. Peanuts in particular are in the crosshairs, as they cause one of the most life-threatening common allergies in humans.

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Picture: groupcheers/fotolia.de

Allergen Immunotherapy The concept has been around for more than a century, but recent

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AllergIES

European Biotechnology | Summer Edition | Vol. 16 | 2017

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heezing, itching, sneezing, rash – life’s a challenge for people who suffer from allergies.

First coined in 1906, the term ‘allergy’ was ini­tially used to describe a “specifically altered reactivity of the organism”.

Today, an allergy is defined as “an immun­ ologically mediated hypersensitivity that can lead to a variety of different diseases via different pathomechanisms”. To treat it, a wide range of approaches in diagnosis, therapy and prevention have now come under scrutiny. When it comes to treatments that can actually change the course of the disease (and not just alleviate the symptoms), allergen immunotherapy (AIT) – often called ‘specific immunotherapy’ – is widely viewed as the only option that promises some success.

Pure allergen extracts frequently cause unwanted side effects, including lifethreatening ana­phylactic shock. But AIT products have become safer from decade to decade. There’s a massive amount of data supporting both efficacy and safety for respiratory allergies and venom hypersensitivities. New results also indicate that AIT might be a promising option for treating food allergies and atopic dermatitis.

Retraining the immune system One closely-watched company trying to establish AIT in the food allergy realm is French-based DBV Technologies. “We reeducate the patient’s immune system to tolerate the allergen presence,” DBV CEO Pierre-Henri Benhamou told Euro p­ ean Biotech. Although the company also for instance develops therapies against cow’s milk allergy in infants, its main focus is peanuts. “Some patients in our clinical studies react to a single milligram of peanut protein – that’s 1/250 of a single peanut. Some of them experience life-threatening reactions. Among the top eight food allergies that account for 90% of all medical cases, this is probably the most prevalent,” says Benhamou.

Although the statistics vary from country to country, the prevalence of peanut intolerance among Western society populations lies between 0.5%-3%. Like egg

or milk allergies, an allergy to peanuts occurs mostly in childhood. But while many children outgrow the former, only one in five people with a peanut allergy will ever tolerate the legume. So far, medical advice has been limited to warning sufferers to avoid peanuts at all costs, and always have access to an epinephrine auto­ injector to calm down the immune system if they are unexpectedly exposed. For years, the reference desensitisation method was the sub­cutaneous application of allergens. “But many patients experience severe side effects as a result, and sadly, fatalities have been reported in the clinical development of peanut allergy treatments,” recalls the DBV co-founder.

“We believe that patients will ultimately benefit by having different approved treatment options available.“ Not surprisingly, the most recently deve­ loped therapeutic hopefuls are not sub­ cutaneous immunotherapies (SCIT). DBV has developed skin patches that create what the company dubs an ‘epicutaneous immunotherapy’ (ECIT). Product candidates from US company Aimmune, on the other hand, are administered orally (oral immunotherapy: OIT). Pilot studies of intra­lymphatic immunotherapy (ILIT) also show promising data for some allergens. Most AIT providers currently offer SCIT and SLIT (sublingual immuno­ therapy) products. Whereas OIT entails the ingestion of a tiny amount of protein powder taken from a capsule and sprinkled over food, SLIT typically involves protein in the form of a liquid or a tablet that is placed under the tongue for two to three minutes before swallowing. (For a brief overview of European AIT providers, see table on p. 77.)

DBV and Aimmune both expose patients to a complete cocktail of peanut proteins, but Australia’s Aravax takes a different approach. The company claims it can distinguish between good and bad peanut protein elements. Its SCIT there-

fore utilises only peptides that represent selected, allergy-causing fragments of peanut proteins and omits parts of the molecules that cause life-threatening anaphylactic reactions. Market potential is huge.

“It is exciting to see innovation in the field, and we believe that patients will ultimately benefit by having different approved treatment options available,“ Benhamou points out. In the peanut allergy space, DBV and Aimmune are setting the stage for a showdown in late 2017. That’s when readouts of crucial Phase III trials are expected. Because both methods have their pros and cons, analysts are recommending that investors buy stocks in both public companies. In addition to efficacy and safety, other factors like marketing power, consumer preference and cost will be decisive in which therapy achieves better sales.

“There’s a potent network of immune cells called Langerhans cells in the skin,” Benhamou explains. “After contact with an allergen, these cells carry the allergenic and other proteins to the lymph nodes, where the person’s immune reaction is modified. Given the allerge­nic proteins do not enter the bloodstream, our therapy aims to avoid causing severe or life-threatening systemic reactions, such as anaphylaxis. Safety is of upmost importance for these patients, and this mechanism allows for potential benefits, which have been observed in our clinical trials thus far.”

How AIT works Unlike other hypersensitivities, allergic reactions are mediated by allergen-specific antibodies of the immunoglobulin E (IgE) type. The concept behind AIT is to give repeated doses of an allergen, stimulating an immune response in the body, and encouraging the patient’s body to extend the bounds of immunological tolerance. This tolerance leads to the reduction or even elimination of symptoms induced by allergens binding to IgE antibodies. In general, T helper 2 (Th2) lymphocytes produce cytokines, which in turn promote the activity of mast cells along with that of basophils and eosinophils – the predominant effector cells that cause allergic inflammation.

AIT suppresses Th2-type lymphocytes,

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AllergIES

mast cells, basophils, eosinophils and al­ lergen-specific IgE production.

Given the general acceptance of AIT in the field of allergic rhinitis and allergic asthma, it’s somewhat puzzling that less than 10% of patients with these condi­ tions are treated with the therapy. In a po­ sition paper from 2015, the international community of allergy specia­lists said AIT is still under­used due to a lack of agree­ ment in documented efficacy, insufficient data on cost-effectiveness, differing edu­ cational levels of physicians, and a lack of awareness of AIT in the general pop­ ulation. Some experts also feel applica­ ble products and proper dosage regimens are lacking. The European Academy of Allergy and Clinical Immunology (EAACI) is currently making a concerted effort to work on AIT guidelines for healthcare pro­ fessionals. Its goal is to develop evidencebased recommendations to support the practical implementation of AIT in man­ aging patient health. The project started in April 2015, and will end later this year.

Prevention is the best cure According to the EAACI, 150 million EU citizens (out of 500 million) suffer from

European Biotechnology | Summer Edition | Vol. 16 | 2017

chronic allergic disease – and the trend is upwards. It estimates that by 2025, more than 50% of all Europeans will be afflicted by at least one type of allergy.

The non-profit organisation therefore believes that in addition to therapeutic interventions, prevention is vital to con­ trolling the growing public health bur­ den. Because robust data is still miss­ ing, EAACI guidelines currently don’t recommend AIT as a means to prevent allergic sensitization or allergy disease – with one exception. They say children and adolescents with persistent season­ al allergic rhinitis triggered by grass or birch pollen may benefit from a threeyear AIT. According to published data, treated subjects were less likely to de­ velop asthma in the two years posttreatment.

Asked about the company’s plans concerning allergy prevention, the Ex­ ecutive VP for R&D at Danish allergy specialist ALK-Abelló told EuroBiotech that over the next decade, the firm is committed to developing treatments for hay fever and treatment/prevention of asthma. “We’ll focus strongly on asth­ ma, and extensively on children,” says Henrik Jacobi. “Can we modify exist­

ing disease or prevent them from devel­ oping the disease? We believe it would be of huge value to society and patients if we could achieve some progress in the field.“ ALK­- Abelló claims its prod­ ucts accounted for around 40% of glo­ bal AIT sales in 2016. Along with other big firms in the sector like Allergophar­ ma or Hal Allergy, the Danish specialist will likely grow in the future as regula­ tors in many countries increasingly de­ mand costly approvals. That will knock out smaller competitors that don’t have the stamina and funding to take prod­ ucts through clinical trials. In Germany, for example, there were over 6,600 AIT products on the market pre-2008. When regulators began wanting approvals sim­ ilar to those for other drugs, less than 200 products actually went through the trials process. In 2016, there were just 90 available on the German market.

Recombinant allergens Aiming to achieve better efficacy, an improved safety profile and faster tol­ erance with fewer applications, sever­ al firms have pushed new technologies over the years. Austrian company Bio­

Birch pollen is one of the most common airborne allergens in spring. As the trees bloom, they release grains of pollen that are scattered by the wind. A single birch tree can produce up to five million pollen grains.

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Picture: Ingo Bartussek/fotolia.de

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may is a pioneer in the field of recombinant allergens. Founded in 1984, it’s also a contract manufacturer for microbially produced recombinant proteins, as well as plasmid and minicircle DNA. Then French (now British) therapeutic allergen provider Stallergenes showed in a clinical study setting that Biomay’s recombinant allergens have an effect similar to naturally extracted counterparts.

The Austrian firm is currently working on a “third-generation grass pollen allergy vaccine”. After successfully completing a Phase IIb study in January, Bio­ may CEO Rainer Henning commented: “We could demon­s trate that BM32 is able to significantly improve the incapacitating symptoms of grass pollen allergy in the very first season after treatment started, which is obviously very important for adherence to the therapy. We will now work to expeditiously move BM32 into Phase III trials.” And Biomay’s candidates are no longer just recombinantly produced allergens. Deploying its proprietary peptide carrier fusion technology, they are more like vaccines containing linear peptides that are parts of B-cell epitopes. These peptides are fused to an immunogenic carrier ele­m ent and expressed as fusion proteins by recombinant technology.

Peptide carrier fusion vaccines induce a focused, allergen-specific IgG response that is directed against parts of the IgE epitope, and blocks the binding of IgE.

The deplorable case of Circassia A Phase III failure would doubtless be a heavy blow to both patients and Bio­ may investors. But it probably wouldn’t receive the attention given British company Circassia when their Toleromune house dust mite (Phase IIb) and cat dander (Phase III) candidates couldn’t beat placebo treatment. Founded on its AIT technology, Circassia delivered a £200m IPO in 2014 – the largest ever for a UK biotech. But the company has now abandoned the tech­n ology and the field of AIT altogether, and is instead focusing on respiratory disease therapies.

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European companies working on (and investing in) allergy immunotherapies

Company (country) Asset

Allergens

ALK-Abelló A/S

SLIT drops, SLIT tablet and SCIT injectable solutions; allergens from natural extracts

grass pollen, ragweed pollen, house dust mite, Japanese cedar pollen, tree pollen

Allergopharma GmbH & Co. KG (100% subsidiary of Merck KGaA)

SLIT drops and SCIT injectable solutions; allergens from natural extracts; partly chemically modified to produce hypoallergic allergoids; R&D on recombinantly produced allergens

grass pollen, tree pollen, cat dander, hamster dander, mildew, house dust mite

Allergy Therapeutics plc

SLIT drops and SCIT injectable solutions; modified, standardised allergen extracts (allergoids); micro­crystalline tyrosine adjuvant & monophosphoryl lipid A adjuvant technologies; R&D platform based on virus-like particles

grass pollen, tree pollen, ragweed pollen, peanut, house dust mite

Anergis SA

clinical-stage company; contiguous overlapping peptides (COP) technology; recombinantly produced allergy vaccines

birch pollen (Phase IIb), bee venom, ragweed pollen, house dust mite (all preclinical)

Asit Biotech SA

clinical-stage company; ASIT+ technology platform based on size-selected allergen fragments from natural extracts, SCIT

grass pollen (Phase III), house dust mite (Phase I ready)

Biomay AG

clinical-stage company; peptide carrier fusion technology (PCFiT); recombinantly produced allergy vaccines

grass pollen (BM32, Phase III ready), house dust mite, ragweed, birch pollen, cat dander, bee/ wasp venom (all preclinical)

Circassia Pharmaceuticals plc

clinical-stage company; Toleromune T cell epitope desensitisation technology, synthetic peptide immuno-regulatory epitopes (SPIRE) vaccine

house dust mite, cat dander (all abandoned due to lack of efficacy)

clinical-stage company; isolated, modified recombinant allergens; administration route not communicated so far

birch pollen, grass pollen, dog dander, horse dander, cat dander, mugwort (all preclinical)

DBV Technologies SA

clinical-stage company; Viaskin patch technology (epicutaneous immunotherapy, ECIT); allergens from natural extracts

peanut (Phase III), milk (Phase II), egg (preclinical)

HAL Allergy Holding B.V. (Haarlems Allergenen Laboratorium)

SLIT drops and SCIT injectable solutions; allergens from natural extracts, partly chemically modified to produce hypoallergic allergoids

house dust mite, wasp/bee venom, grass pollen, tree pollen, ragweed pollen, olive, peanut, fish, peach

Laboratorios Leti S.L.

SLIT drops and SCIT injectable solutions; allergens from natural extracts, partly chemically modified to produce hypo­allergic allergoids (proprietary depigmentation technology)

house dust mite, tree pollen, grass pollen, bee/wasp venom

Roxall Medizin GmbH (acquired BIAL-Aristeguí in 01/17)

SLIT sprays and SCIT injectable solutions; R&D in recombinant allergen production

house dust mite, pollen, cat dander, mildew

Stallergenes Greer plc

SLIT drops, SLIT tablet and SCIT injectable solutions; allergens from natural extracts; birch pollen allergen rBet v 1 first recombinant allergen in a clinical study as an active substance (2009, produced under a license agreement with Austrian Biomay); R&D collaboration with DBV on a birch pollen patch

grass pollen, birch pollen, house dust mite, Japanese cedar pollen

Desentum Oy

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AllergIES

Biomay, Circassia and Australian-based Aravax are all working on so-called peptide immuno­therapies – employing linear peptide sequences that mimic fragments of the native allergen. But this is just one approach to reducing allergenicity while maintaining immunogenicity.

While whole allergen molecules with intact B-cell epitopes can readily crosslink specific IgE molecules on the surface of effector cells, peptide-based approaches leave these epitopes out of the process entirely. Instead, they’re based on the use of peptides that represent major Tcell epitopes of the allergen.

Many ways to solve the problem?

Similar to peptide-based AIT, physical modifications of allergen molecules can reduce or eliminate IgE reactivity, and thus allergenicity. Such approaches have come in many forms: chemical modification, conjugation with synthetic bacterial DNA motifs, point mutations in native allergen gene sequences, and the use of allergen multimers, fragments and peptides of various lengths. Several products called ‘allergoids’ made by different developers are already on the market, and can be administered subcutaneously or orally.

Although ALK-Abelló has been very sucessful with its recently launched SLIT tablets, the company has also been exploring “next-generation allergy immuno­ therapies”. Executive VP Jacobi explains: “The theory is that with synthetic vaccines, it will be possible to eliminate some of the allergic side effects by removing the IgE binding epitopes from the vaccines. But the problem is that so far it has not been possible to produce synthetic vaccines that match natural allergens in terms of clinical efficacy.”

Getting help where it’s needed Arguably the most exciting area in AIT right now is the field of food allergies.

One compelling aspect in the complex picture they present is the role played by the microbiome. Australian scientists, for example, recently showed that peanut desensitisation treatment combined with

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cost for direct management of the allergic disease (e.g. purchase of drugs, allergenfree foods, hospitalisation and specialist medical care) it’s nearly impossible to estimate the indirect costs such as lost time from work or school or loss of productivity. What’s certain is that they’re huge.

180° turn in prevention Dr. Pierre-Henri Benhamou Co-founder, Chairman and CEO of DBV Technologies SA

? !

How does the epicutaneous delivery of allergens work?

Our Viaskin Peanut patch is dosed with API-grade peanut proteins that are maintained intact by electro­static forces. In the center of the patch is a polymerised membrane. Using our proprietary electrospray technology, peanut protein is sprayed onto the membrane with a high voltage of up to 20,000 V. After applying the patch on intact skin, a condensation chamber is formed increasing the hydration of the skin, and the protein starts to be solubilised. The allergen is then concentrated in the superficial layers of the skin.

a probiotic (Lactobacillus rhamnosus) significantly improved outcomes. Backed by venture capital, Probiotic Therapies for Allergy (ProTA Therapeutics) was founded in 2016 to develop and commercialise the technology into a marketable product.

As mentioned at the start of this article, food allergy reactions appear to be on the rise mainly among children. The last decade has seen a seven-fold increase in reported hospital admissions for food anaphylaxis in the UK and Australia in kids 14 and under. The potentially life-threatening nature of the condition makes food allergies a major public health concern, and also has considerable economic implications. Besides the

The application of AIT in food allergy was fueled by a 2008 landmark study headed by Gideon Lack, a professor at King’s College London. It was also a turning point in the field of allergy prevention. Lack noticed that rates of peanut allergy were extremely low in Israel, where almost every child is given Bamba – a teething snack that contains peanuts. Comparing rates of the condition among Jewish children in Britain and children from Israel, he discovered that the allergy is ten times more common among youngsters in the UK. A subsequent placebo­- controlled trial found that infants who had been given foods like peanut butter were far less likely to be allergic to them later. Lack concluded that the early introduction of peanuts in a child’s diet significantly decreased the frequency of developing peanut allergy among children at high risk, and also modulated immune responses to peanuts.

Traditionally, physicians have recommended avoiding substances like peanuts in the first year of life. The assumption was that delaying exposure to an allergen could provide protection. Now new 2017 guidelines published by the USbased National Institute of Allergy and Infectious Diseases call for parents to begin giving babies foods that contain peanuts, cooked egg and dairy as early as four to six months of age. Can that turn the tide and reverse prevalence trends in food allergies? Hopes are high – for the children who have been affected already, as well. Therapeutic products made by ALK-Abelló, DBV, Aimmune and the other companies active in the field of AIT research will soon be changing many more lives. m.laqua@biocom.eu

Picture: DBV

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Science & Technology

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Blocking the tumour’s immune evasion strategies Checkpoint modulation

Belgian, Swiss, and US researchers have found a new way to boost efficacy in cancer immunotherapy. In mid-April, they reported that cancer cells actively block tumour infiltration of cytotoxic T cells, but that this process can be reversed using angiogenesis blockers. Some Big pharma companies have already jumped on the bandwagon of angiogenesis/ PDL1 combination therapy.

“The network of blood vessels itself is an important regulator of immunity because it controls white blood cell traffic.

By preventing the infiltration of white blood cells, the cancer is able to evade the host’s immune system,” said lead author Gabriele Bergers from VIB-KU

Leuven, Belgium. In animal models for breast and pancreatic cancer, Bergers and co-workers provided evidence that therapy with checkpoint inhibitors, such as anti-PD-L1, can sensitise and prolong the efficacy of anti-angiogenic therapy, and, conversely, anti-angiogenic thera-

py can improve anti-PD-L1 treatment, specifically when intratumoral vessels are generated that facilitate enhanced white blood cell infiltration, activity and tumour cell destruction (S cience Translational Medicine, doi: 10.1126/scitranslmed.aak9679).

Picture: Nicolle Rager Fuller-Courtesy- National Science Foundation

Opening the gates for T cells

Co-administration of immunotherapy and angiogenesis blockers can help overcome the tumour’s tactics to evade from the body’s immune response.

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Combining anti-angiogenic and immunestimulating therapies in the treatment of tumours provided T cells, which excreted the immune activating cytokine interferon-g, with gates through which they could infiltrate the tumour and its microenvironment. There, the PD-L1-checkpoint inhibitors reversed the paralysation of T-cells by tumour cells, which – as a reaction to incoming T cells – overexpress the PD-L1 protein that binds to the PD-1 receptor on T-cells, shutting down their immune activity.

“We observed that the combination of immune system-activating and anti-angiogenic antibodies caused a kind of positive feedback loop,” stressed study coauthor Elizabeth Allen. “The result is the growth of specific blood vessels that deliver cancer-fighting immune cells into the tumour. These high endothelial venules (HEVs) are normally found in lymphoid organs, such as lymph nodes, where they help transport white blood cells. For the first time, we showed that the growth of such HEVs can be therapeutically induced in tumours.” In animal models for breast cancer and pancreatic neuroendocrine tumours, but not in glioblastoma

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Cleaning up the oceans

(GBM), the anti-VEGFR2-antibody-triggered growth of HEVs in tumours led to cancer cell death and tumour shrinkage.

Boosting HEVs The researchers found that HEVs promoted lymphocy te infiltration and activity through activation of lymphotoxin b receptor (LTbR) signalling. Further activation of LTbbR signalling in tumour vessels using an agonistic antibody enhanced HEV formation, immunity, and subsequent apoptosis and necrosis in pancreatic and mammary tumours. Finally, LTbR agonists induced HEVs in recalcitrant GBM, enhanced cytotoxic T cell (CTL) activity and, thus, sensitised tumours to antiangiogenic/anti–PD-L1 therapy.

“Our preclinical studies provide evidence that anti–PD-L1 therapy can sensitize tumours to antiangiogenic therapy and prolong its efficacy, and, conversely, antiangiogenic therapy can improve anti–PD-L1 treatment, specifically when it generates intratumoral HEVs that facilitate enhanced CTL infiltration, activity, and tumour cell destruction,” the authors conclude.

Industry activities In order to broaden patient populations that respond to cancer immunotherapies and anti-angiogenesis, Big Pharma

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companies such as Roche have already begun to test combinations of angiogenesis blockers and checkpoint modulators. Roche is in Phase I/II testing of a bispecific Ang2/VEGF-antibody dubbed vanucizumab (RG7221) with its CD40 agonist RG7876.

Innovative T cell approach In May, German Merck KGaA and its partner Pfizer entered into a research collaboration with Swiss/German vaccine maker Vaximm. Under the agreement, the partners will combine Merck’s PD-L1 blocker avelumab with Vaximm’s VXM01, an oral attenuated Salmonella vaccine overexpressing the VEGF-receptor 2 (VEGFR2). The bacterial vector, which tends to accumulate into solid tumours on its own, is designed to activate T cells to attack the tumour vasculature.

Two years ago, Vaximm reported preliminary hints of efficacy from a Phase I study carried out in pancreatic cancer patients (O ncoimmunology: e1001217).

Under the terms of the agreement, Vaximm will be responsible for conducting two, non-blinded Phase I/II trials – one in glioblastoma and the other in metastatic colorectal cancer. According to Vaximm, VXM01 increased infiltration of various immune cells into the tumour in preclinical tests. Clinically, this was associated with improved patient survival. 

t.gabrielczyk@biocom.eu

Industrial process by 2020 While not disclosing the exact time needed for PET degradation, Carbios said that it is “scalable for industrial use as an alternative to common thermomechanical PET recycling processes.” According to its CEO, Jean-Claude Lumaret, the process developed within the Thanaplast project allows repolymersation into virgin PET with no quality loss or drastic presorting or pretreatment requirement.

“Our PET biorecycling technology follows a new life-cycle model of circular economy,” he said. “Our innovation can help to close the loop by recycling PET plastics into similar-quality products.”

In 2016, the company turned profitable for the first time in its history. It reported 2016 revenues of €8.9m, an operating income of €3.5m, and a net income of €5.0m 

Picture: Vaxxim

Animation of Vaximm’s oral T killer cell activating Salmonella vaccine

Carbios French green chemistry pioneer, Carbios SA (Clermont-Ferrand) announced in March that it has secured equity financing of €2.5m from Kepler Cheuvreux through the acquisition of 380,000 shares over 24 months. The company will use the funds for further development of its enzymatic depolymerisation process for plastic bottles and is set to reach demonstration scale from the current pilot scale by 2020.

The company told European Biotech nology that its esterase-based recycling process runs under mild conditions and can completely depolymerise all kind of polyethylene terephtalate (PET) plastics into its monomers (monoethylene glycol and terephtalic acid). With 64 million tonnes of annual production, PET is the most common non-degradable plastics used in packaging and the most significant polluter of the oceans. According to estimates of the WHO, there will be more PET in the oceans than fish.

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European Biotechnology | Summer Edition | Vol. 16 | 2017

Active capital Danish Analysis IRIS Groups has

published a report that closely examines Danish biotech, based on the consultancy’s life science database. It benchmarks the Copenhagen region (where 95% of Denmark’s biotech companies are situated) against the regions Basel, Boston, Cambridge, Munich, Paris, and Stockholm-Uppsala.

The results demonstrate that the Danish capital’s biotech cluster – and the overall bio­tech sector in Denmark – have weaker framework conditions than those in the other clusters. “This is probably a major reason why the cluster grows at a slower rate, and why the potential of public research is not exploited to the same extent as in other regions,” the report states.  ›› Download the full report (in Danish only) at http://danskbiotek.dk

Choosing a seat EMA Many European cities have staked out a claim to be the new seat of the European Medicines Agency, following Britain’s exit from the EU. In an open letter, the Pharmaceutical Industry Heads of Research and EFPIA shared their views on the matter, stressing that the operations of the agency cannot bear disruptions. Thus, “the Council’s deliberations on the Agency’s future location need to be conducted on the basis of very essential criteria and put for decision as early on as possible, preferably at its meeting in June this year,” the letter states. It lists fundamental requirements for the new location of the EMA, naming first and foremost connectivity and excellent transport, but also both the availability of and attractiveness for staff needed. Among the signees were heads of research from Novartis, Bayer Pharmaceuticals, Roche, Novo Nordisk, and GlaxoSmithKline.

A survey from our online portal, european-biotechnology.com, sees Copenhagen as the most probably choice for the new EMA seat. 

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European Biotechnology is published in cooperation with the following organisations: European Biotechnology NET WORK

Europe: european-biotechnology.net

Belgium: medtecheurope.org

Switzerland: swissbiotech.org

Germany: biodeutschland.org

Europe: eapb.org

Europe: diahome.org

Europe: europabio.org

Ireland: ibec.ie/ibia

Denmark: danskbiotek.dk

The Netherlands: hollandbio.nl

Spain: asebio.com

Portugal: www.apbio.pt

Austria: lifescienceaustria.at

France: france-biotech.org

Council of European BioRegions

CMYK

Italy: assobiotec.it

Sweden: swedenbio.com

Hungary: hungarianbiotech.org

Europe: cebr.net

Europe: ebe-biopharma.org

Norway: biotekforum.no

Finland: finbio.net

Belgium: bio.be

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

EuroBiotechNews covers the biotechnology sector of the current 28 EU member states, Norway, and Switzerland. If you would like to subscribe, please refer to www.eurobiotechnews.eu

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Attend and present EBDC 2017 in Heidelberg The European Business Development

Upcoming events

Conference (EBDC) – a special two day networking event for decision makers from Biotech, Pharma, and the Investment sector – will take place 10 and 11 October 2017 in Heidelberg, Germany.

› 10–11 October 2017, Heidelberg 11th European Business Develop­ ment Conference

sciences industry, whether they are from the pharmaceutical industry or invest­ ment companies. An effective and wellestablished format to gain the attention of these players are company presentations.

EBDC would like to encourage you to apply for such a company presentation.

More than 100 experts will give their full attention to your 15-minute pitch (includ­ ing five minutes for Q&A).

Apply for your company presenta­ tion by registering online with the EBDC (1,095 EUR for members of BIO Deutsch­ land or of one of our international part­ ners, for example, BIA, HollandBio, and SwissBiotech, 1,975 EUR for non-mem­ bers). Regular attendance without pres­ entation is possible as well and equally welcome (545 EUR for members of BIO

German Health Minister speaks German Biotechnology Days The eighth edition of the German Biotechnol­ ogy Days was held on 5 and 6 April in Hanover, Germany. This year, the lead­ ing networking platform for the German biotech industry also drew over 800 par­ ticipants. During numerous symposia and plenaries, the two-day event show­ cased the wide-range of research and applications in the field of biotechnol­ ogy. In his keynote talk in the opening plenary, Rodger Novak, CEO of CRISPR Therapeutics, spoke about the huge po­ tential of genome editing in the differ­ ent areas of biotechnology. He empha­ sised that this technology could lead to the next medical breakthrough. During his visit to the exhibition, German Health Minister Hermann Gröhe learned about

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the latest biotech products and servic­ es being offered in the healthcare indus­ try. During his talk, the minister stressed what an important contribution biotech­ nology makes to medical R&D, diagnos­ tics, and the drug supply chain. Oliver Schacht, CEO of the biotech firm Curetis,

Deutschland or of one of our internation­ al partners, 985 EUR for non-members).

Heidelberg itself is the perfect place for our conference. The Biotech Clus­ ter is one of the most important medical hubs in Germany: a place where startups, small businesses, major research fa­ cilities, and global players collaborate, from research and development to pro­ duction; an ecosystem where science produces market-oriented research and international cooperation generates new prospects. Join us at the EBDC 2017 in Heidelberg where health innovation is made in Germany.

L ›› More: www.biodeutschland.org/en/ european-business-developmentconference-2017.html

also presented an energetic keynote to round off the opening session. He called on the biotech community to “stop com­ plaining and get to work” and urged the policymakers in attendance to be bolder and “just add a zero” to biotech start-up support and growth financing for inno­ vative companies. The next German Bi­ otech Days will take place on 18 and 19 April 2018 in Berlin, Germany.

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German federal health minister Hermann Gröhe

Pictures: © Sera Kurc und Constantin Falk

The opening keynotes will be held by Pao­ la Casarosa (Corporate Vice President for Business Development and Licensing at Boehringer Ingelheim) and Christoph Hüls (Head of Merck Group Innovation Strate­ gy, Chief Innovation Officer). The confer­ ence programme further offers symposia on “Advances in Oncology” and “Immu­ nology and Inflammation” as well as a panel discussion on “Financing and Busi­ ness Development for Pharma and Bio­ tech.” We expect speakers from AbbVie, Almirall, Amgen, BaselLauch, Boehring­ er Ingelheim, EMBL Venture, EY, Immu­ nocore, Menarini, Merck, Nextech Invest, Selvita, and Teva, among others.

An innovative medical biotech or pharmaceutical company needs to have the right partners to succeed in the life

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Challenging complexity Swiss biotech report This year’s Swiss Biotech Report discusses

Upcoming events

the increasing levels of complexity in the field of biotechnology, explaining how this action is driving exciting change in the Swiss biotechnology sector. Contributions from the steering group range from the insights of an evolutionary biologist to news of the latest programs and networks.

› 07–08 September 2017, Wädenswil BioTech 2017: Sensor Technology and Online Analytics ›1 1–13 September 2017, Basel Basel Life & NTN Swiss Biotech Research Day ›2 8 September 2017 Swiss Biotech Fall Day

Swiss players Over the past two decades, the biotech industry has matured into an established business with numerous commercial products generating high returns on investment. In parallel, novel technologies, new players and additional fields of application have continued to increase overall diversity. The analysis of the Swiss Federal Institute of Intellectual Property demonstrates that all along, patents have been instrumental in pro-

tecting products and encouraging investment in this high risk/high potential industry. Consequently, the patent landscape for biotechnology and, especially freedom-to-operate analysis, has become complex.

As every year, the facts and figures give an overview over the past year and its performance.

L ›› Download the report: www.swissbiotechreport.ch.

Pictures: SBA

Navigating the biotech ecosystem BLXcellence Biotechnology, as an industrial ecosystem, is not only scientifically complex but also individually diverse. How well do scientists, business people, and all other biotech professionals work together? Is the ecosystem operating optimally? These are difficult questions to answer, because there is no common reference, no benchmark, no standard.

A wide variety of standards already do exist in specific areas, but a global bioproficiency standard is missing. In its absence, business and science remain dis-

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connected for many stakeholders. To be effective, a bioproficiency standard would need to be appealing to all bio­tech stakeholders and easily implementable. This may sound like a gargantuan task, but it doesn’t have to be if the objective is to define and learn a common language. As the preferred educational provider of the Swiss Biotech Association, offering science courses to all non-biologists in the industry, we have already partially defined this standard: the minimum knowledge in life sciences that empowers all non-biologists to work

Directory The Swiss Biotech Directory 2017/2018 is now available.

L ›› www.swissbiotech.org/company-map

with a higher degree of confidence. This minimum knowledge revolves around some 350 words that describe basic molecular biology and basic pharmacology, as well as the fundamentals of red, green, and white biotechnologies. This is a surprisingly small body of knowledge, considering all the domains it embraces.

Would a bioproficiency standard benefit the biotechnology ecosystem? There is only one way to answer such a question: experiment! And this is exactly what we would like to do.

L Interested in participating? Contact info@ loroch.ch ›› www.biolink.express/blxcellence

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Biosimilars labelling Biosimilars labelling EuropaBio has developed recommenda-

Upcoming events

tions for changes to the Summary of Product Characteristics (SmPC) of biosimilars that would result in an enhanced level of transparency for the label.

› 25 September–1 October 2017 All over Europe European Biotech Week › 9 –11 October 2017, Brussels European Forum for Industrial Biotechnology and the Bioeconomy

Biotech fete European Biotech Week The Euro-

pean Biotech Week takes place between 25 September and 1 October this year.

The European Medicines Agency building in London

EuropaBio members believe that the current EU approach to labelling does not reflect the specificities of biosimilars and that the SmPC of a biosimilar product should contain additional information to facilitate greater transparency for physicians and patients.

Based on interactions that EuropaBio had with various stakeholders, including physicians and patients over recent years, the conclusion was that label transparency would be enhanced by implementing the following small

yet meaningful changes to the biosimilar SmPC: ›› 1. Adding a statement with the definition of biosimilarity ›› 2. Adding a direct link to the EPAR next to the biosimilarity statement ›› 3. Moving the biosimilarity statement to the top of the SmPC A full position paper is available at ­europabio.org/healthcare-biotech and provides a basis for future exchanges and next steps in this area with regulators and other stakeholders.

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Green G-Nome



See page 50 for more information!

›› www.biotechweek.org

Red-letter day EFIB 2017 Europe’s leading event for industrial biotechnology and the bioeconomy returns to The SQUARE in Brussels for its 10th anniversary edition from 9 – 11 October. With over 650 partici-

G-Nome is ready to guide you to new heights of knowledge regarding genetically modified crops. This new guide is a must-read for any­one wanting to understand the role and untapped potential of GM crops in ­Europe.  ›› Read it on europabio.org/agricultural-biotech

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pants, EFIB fosters engagement between policy makers and a broad range of stakeholders connected with the existing biobased value chain.  ›› Register at www.efibforum.com

Pictures: Shutterstock (top left); EuropaBio

GM Crops & Policies The Green

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Value & Access in Basel Value, Access, and Regulatory Strategy Workshop The

Pictures: DIA

workshop taking place in October in Basel aims to bridge the divide on Value & Access through aligned goals and ongoing collaboration.

According to the Access to mation on the effectiveness Medicine Foundation, two and cost-effectiveness of billion people still do not each medicine is available. have access to the mediProcesses to optimise availcines they need. Whilst this able budgets to pay for inmostly refers to developing novative but also effective countries, there is plenty to new medicines need to be be addressed across develin place, and health techoped countries as well. The nology assessment should famous “post code lottery,” by Inka Heikkinen, be enabled to collect inforindicating that access can Senior Scientist, DIA EMEA mation that is valuable for also depend on where one all stakeholders – includlives, budget, and governance of health ing the public,” said Dr. Wija Oortwijn, care, led to the establishment of NICE a founding Member of the International in the UK in 1999. Equalising access in Society for Health Technology AssessEurope has come a long way since, but ments and Sector Leader for Health and the work is increasingly complex with Partner of Ecorys. specialty treatments and recession-driven reductions in health care spend. As a Breaking down the silos fellow member of the medicines development community, we have lofty goals This fall, a new workshop on Value, Acto address that gap. cess, and Regulatory Strategy aims to Operating within any role as part of break down the silos between reguthe full life cycle of medicines developlators and HTA bodies by providing a ment now requires foresight into areas of neutral forum for open collaboration. value demonstration and access for gloA connective network will discuss: data bal patients. This can mean transformcollection infrastructure (e.g. patient reging the existing R&D model from one of istries), joint early dialogue experience, one-size-fits-all drug development to inincluding next steps, methodologies for novating towards niche patient needs, or evidence generation that are acceptable unlocking unique partnerships in terms to both regulators and HTA, and alignof collaboration along the medicines dement of requirements across the EU. Provelopment chain. gramme Committee member Katarzyna These transformations are not going to Kolasa, DrSc, shares unique experiences be solved in a single meeting but, rathfrom Central and Eastern Europe. “To ener, through continuous conversations and sure the right balance between equity and collaborations across organisations and efficiency in decision making, the current regulatory authorities. DIA brought some HTA framework has to be further augthought-provoking conversations to the mented to allow all conflicting criteria to table during the BioVenture Day and DIA be addressed to a satisfactory degree.”

EuroMeeting 2017. Experts shared addiTo further these discussion, the DIA tional thoughts in subsequent podcasts: EuroMeeting 2018 is set to provide in“We concluded that a health care system sights on questions such as: “How Can can only be truly effective if full inforPrecision Medicine Development Be Ex-

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Upcoming events › 13–14 September 2017, Berlin Clinical & Regulatory Operational Excellence Forum diaglobal.org/OpEx › 19–20 September 2017, London Registry Workshop – Preparing for Future Requirements diaglobal.org/Registry › 4 –5 October 2017, London 11th Annual Forum for Qualified Persons in Pharmacovigilance diaglobal.org/QPPV

ecuted in a Cost-effective Way and Deliver Compelling Endpoints in Small Populations?”; “Can Regulators and HTA Bodies Create Synergies for Patient Access?”; and “How Can Better Outcomes Be Enabled by Big Data?”

Closing the two billion person gap “It’s not a problem of innovation per se, but the delivery and sustainability of this innovation...linking innovation to a system of reimbursability that, for instance, shows and certifies avoided costs. That would be very, very helpful,” said Dr. Luca Pani, current Member of the European Medicine Agency’s Committee for Human Medicine Products and Scientific Advice Working Party; he served as Director General of the Italian Medicines Agency from 2011 to 2016 Active engagement with an eye towards improved value across all stages of development will enable faster and more effective access to medicines for patients.

By collaborating across functions with a unified goal in mind, we can progress together towards closing the two billion person gap.

L ›› For more information, see: diaglobal.org/Regulatory-Workshop

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Try harder, Europe!

European Union In the recent parliamentary elections, the

populists have not won. So, is everything all right again?

The good news is that our democracy is clearly still alive. The example of Donald Trump has obviously shaken up many voters: lying and bad behaviour are not a serious substitute for reliability, diplomacy, and the give-and-take basis. Europe’s long-term crisis is still not over with this election result’s relief. The entire political system of the European Union must

be urgently reformed and, above all, simplified. Citizens must understand the democratic design they live in. Ask your neighbour whether he understands the political power structure between the Commission, the Council, the Parliament, or even the Euro Group. Nobody does. But for EBN members, european cooperation is already day-to-day routine.

European Biotechnology NET WORK

Featured Events › 7–8 September 2017, Wädenswil, Switzerland BioTech 2017 ›1 2–14 September 2017, Malmö, Sweden Nordic Life Science Days 2017 › 13–25

October 2017, Paris, France 9th Int. Conf. & Expo on Proteomics

New EuroGuide The 1st INNOLABS call is open BIOCOM AG The EBN member recent-

Campania Bioscience The cluster

ly published the new European Biotechnology S cience & I ndustry G uide 2017.

The book provides a wealth of information on companies, research institutions, tech parks, and providers acting in the life sciences and biotech industry.

Among them, 22 are corporate members of the European Biotechnology Network, which is also co-editor. In addition to the detailed portraits on some 170 pages, the seventh edition contains a summar y of BIOCOM‘s latest report “Analysis of European Biotech Companies on the Stock Markets: US vs Europe.” Readers will discover many success stories and current trends in the European biotech industry. This book (ISBN 978-3-92838362-2) is available for only €19.80 at local and online booksellers.

representing the life sciences ecosystem in the Campania Region of southern Italy announced that, within the framework of the INNOLABS project, the First Open Call for innovative projects in personalised healthcare is open for application submissions.

INNOLABS is a 2.5 year, €5m project, funded by the European Commission Horizon 2020. During this period of financial backing, a total amount of €3.75m will be invested directly in SMEs, in order to foster collaboration, the transfer of knowledge, and opportunities among European SMEs coming from health, biomedicine, and ICT sectors.

INNOLABS First Open Call for innovative projects in personalized healthcare is seeking applications from SMEs belonging to the health or biomedicine sector, to collaborate with the IT sector in order to develop cross-sectoral health solutions that will bring societies closer to the next generation advanced healthcare systems.

By applying to the call, up to 25 projects will obtain support valued at up to €50,000. In addition to the projects that will be selected to access the Acceleration Programme, another 25 final-

›› The EBN office has 20 complimentary copies for members. Be fast and write to: office@european-biotechnology.net

81-87_EB_Summer_2017_associations-UM_NEU.indd 86

ists would receive up to €10,000, to be spent on Innovation Services.

Teams eligible to apply for Open Call can be composed of at least two partners from different sectors of the value chain:

›› Teams must be led by an SMEs (under de EU definition) legally established as a business and based in a EU member state or Horizon 2020-associated country. ›› The other partner may be an end user, a large enterprise, another SME, etc. However, it is important to note that if the second partner is another SME, teams will get higher marks during the evaluation process. Horizon 2020 Seal of Excellence possession and Cross-national teams will also be positively evaluated. ›› Teams proposals must deliver a new product, process, or service addressing the set Open Call Challenges.

The submission deadline is 30 September 2017.

›› More information: Luigi Pavia l.pavia@campaniabioscience.it , Roberta Lauro r.lauro@campaniabioscience.it

15.06.2017 13:05:50 Uhr

European Biotechnology | Summer Edition | Vol. 16 | 2017

Transparency rules for the future Considerations Following in the footsteps of our American

Picture: Petar Neychev/fotolia.com

colleagues, MedTech Europe would like to offer some thoughts on the issue of transparency and disclosure laws and how certain adaptations could help to frame transparency for a new reality.

By the Legal and Compliance team of MedTech Europe

Over the last few years, a number of European countries have passed transparency or disclosure (sometimes also called “Sunshine”) laws which require life science industry to track and publicly report certain payments and transfers of value made to Healthcare Professionals (HCPs) and Healthcare Organisations (HCOs), such as hospitals or medical societies.

The objective of such laws is to provide patients with enhanced transparency regarding the relationships healthcare providers have with life science manufacturers, including medical technology companies. The new MedTech Europe Code of Ethical Business Practice upholds the same objective while addressing the fragmentation created by the different national rules. More importantly, the code goes a step further.

To explain further: the code, which entered into force this January, introduces several important changes to the way the

81-87_EB_Summer_2017_associations-UM_NEU.indd 87

medical technology industry interacts with HCPs. One key aspect is the prohibition for our member companies to directly support HCPs to attend Third Party Organised Educational Conferences (e.g. paying for their registration fee, travel, and lodging). Furthermore, the code introduces transparency requirements for educational grants. The key objective is for companies to stop selecting the HCPs who receive financial support to attend such conferences.

This change means that, from 1 January 2018, HCPs’ independent medical education can only be supported via educational grants. They will be provided to an independent third-party, such as a hospital or a scientific society, instead of taking the form of direct and unilateral transfers of value to an individual HCP (such as registration fee, travel, and lodging costs). Moreover, companies will no longer be involved in the selection of the

associations

87

Save the Date › 23–25 January 2018 European Medtech Forum

HCP recipient, and all grants will need to be published on a European-wide online platform (except where there are equivalent or more stringent national rules apply). This will make it easier for patients all over Europe to access the data, instead of having to search in dozens of websites.

In this environment, to the extent that one would consider reviewing these disclosure/Sunshine laws, we would welcome rules that are tailored to this new reality, supporting the major, ethical change that industry is driving globally.

For the moment, independently of the true costs for companies to comply with such laws, our companies are encountering issues with several national regulations making it operationally very burdensome (but never illegal) to provide educational grants. [...]

It is for this reason that we would like to invite all stakeholders to start a dialogue on how the environment is changing. It would be a great opportunity to explain why the industry is moving to a more transparent model and why national and regional laws have to be adapted to this new reality. Listening to what HCPs and HCOs are telling us, industry’s support of independent medical education is key for the patients, HCPs, and more generally, for the healthcare system. Our companies are keen to preserve this status quo. However, the operational difficulties that some of these national laws create for companies may actually compel them to stop providing educational grants, in which case there is the question of who will/should pick up the bill for the independent medical education for HCPs? L ›› Read full text: http://medtechviews.eu/

15.06.2017 13:05:56 Uhr

88

company index

AB Science SA (F). . . . . . . . . . . . . . . . . . . . . . . . 22 Abcam Ltd.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Abivax SAS (F) . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Actelion (CH). . . . . . . . . . . . . . . . . . . . . . . . . . . 90 Advent France Biotechnology. . . . . . . . . . . . . . . 66 Aglaia BioMedical Ventures B.V. (NL). . . . . . . . . 68 Aimmune (USA). . . . . . . . . . . . . . . . . . . . . . . . . 75 Alexion Europe SAS (F). . . . . . . . . . . . . . . . . . . . 38 ALK-Abelló A/S (DK). . . . . . . . . . . . . . . . . . . . . . 77 Allergan plc (IRL). . . . . . . . . . . . . . . . . . . . . 21, 23 Allergopharma GmbH & Co. KG (GER) . . . . . . . 77 Allergy Therapeutics plc (UK). . . . . . . . . . . . . . . 77 ALPLA (F). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Anergis SA (CH). . . . . . . . . . . . . . . . . . . . . . . . . 77 Apeiron Biologics AG (AT) . . . . . . . . . . . . . . . . . 69 arGEN-X BV (NL/B) . . . . . . . . . . . . . . . . . . . . . . 32 Asit Biotech SA (F) . . . . . . . . . . . . . . . . . . . . . . . 77 Aska Group (JP) . . . . . . . . . . . . . . . . . . . . . . . . . 68 Astellas Pharma (JP) . . . . . . . . . . . . . . . . . . . . . . 67 AstraZeneca AB (SE/UK). . . . . . . . . . . . . . . . . . . 68 Avantium Life Sciences BV (NL). . . . . . . . . . . . . 67 Axon Neuroscience SE (CY). . . . . . . . . . . . . . . . 72 BASF AG (GER). . . . . . . . . . . . . . . . . . . . . . . . . . 67 Bayer AG (GER) . . . . . . . . . . . . . . . . . . . . . . 10, 16 BerGenBio AS (N). . . . . . . . . . . . . . . . . . . . . . . . 64 BIOCOM AG (GER) . . . . . . . . . . . . 31, 43, 69, CP3 BioFIT 2017 | MedFIT. . . . . . . . . . . . . . . . . . 60, 61 Biogen Inc. (USA). . . . . . . . . . . . . . . . . . . . . . . . 26 BioJapan 2017. . . . . . . . . . . . . . . . . . . . . . . 52, 53 Biomay AG (AT). . . . . . . . . . . . . . . . . . . . . . . . . 77 Bionure (ES). . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 BioPlan Associates, Inc. (USA). . . . . . . . . . . . . . 24 Biopredictive S.A.S. (F). . . . . . . . . . . . . . . . . . . . 31 Biosurfit (PT). . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 Boehmert & Boehmert (GER) . . . . . . . . . . . . . . . 12 Boehringer Ingelheim (GER). . . . . . . . . . . . . . . . 65 Bpifrance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Bristol-Myers Squibb (USA) . . . . . . . . . . . . . 23, 38 Bruker Corp. (USA). . . . . . . . . . . . . . . . . . . . . . . 69 Caixa Capital Biomed (E) . . . . . . . . . . . . . . . . . . 70 CANDOR Bioscience GmbH (GER) . . . . . . . . . . 17 Capital Cell (ES). . . . . . . . . . . . . . . . . . . 34, 35, 70 Capsugel (B). . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Carbios SAS (F). . . . . . . . . . . . . . . . . . . . . . . . . . 80 Cathay Fortune (CN). . . . . . . . . . . . . . . . . . . . . . 68 Celgene Corp. (UK) . . . . . . . . . . . . . . . . . . . . . . 38 Cellectis SA (F). . . . . . . . . . . . . . . . . . . . . . . . . . 15 Chiesi Farmaceutici S.p.A. (IT) . . . . . . . . . . . . . . 66 Circassia Ltd. (UK) . . . . . . . . . . . . . . . . . . . . . . . 77 co.don AG (GER) . . . . . . . . . . . . . . . . . . . . . . . . 69 Coca-Cola (USA) . . . . . . . . . . . . . . . . . . . . . . . . 67 Columbus Venture Partners (ES) . . . . . . . . . . . . . 67 Concept Heidelberg (GER). . . . . . . . . . . . . . 56, 57 CPhI Worldwide 2017 (UK) . . . . . . . . . . . . . 54, 55 crowdcube (UK). . . . . . . . . . . . . . . . . . . . . . . . . 35 Danone (F). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 DBV Technologies (F). . . . . . . . . . . . . . . . . . 75, 78 Desentum Oy (FIN) . . . . . . . . . . . . . . . . . . . . . . 77 DIA Europe (CH) . . . . . . . . . . . . . . . . . . . . . 46, 47

European Biotechnology | Summer Edition | Vol. 16 | 2017

EBD Group (GER). . . . . . . . . . . . . . . . . . . . . 50, 51 EMBL (GER). . . . . . . . . . . . . . . . . . . . . . 62, 63, 71 Epigenomics AG (GER). . . . . . . . . . . . . . . . . . . . 68 Eppendorf AG/Bioprocess Center Europe (GER) . 19 Erytech Pharma (F). . . . . . . . . . . . . . . . . . . . 22, 31 Eurofins Scientific (F) . . . . . . . . . . . . . . . . . . . . . 68 EuropaBio/European Biotech Week (B). . . . . 48, 49 European Biotechnology Network (B). . . . . . . . . 42 FGK Clinical Research GmbH (GER) . . . . . . . . . 13 Fraunhofer-Institut für Zelltherapie und Immunologie (GER). . . . . . . . . . . . . . . . 58, 59 FUJIFILM Diosynth Biotechnologies (USA). . . . . 25 Galapagos NV (B). . . . . . . . . . . . . . . . . . . . . . . . 66 GATC Biotech AG (GER). . . . . . . . . . . . . . . . . . . 68 GE Healthcare (UK) . . . . . . . . . . . . . . . . . . . . . . 24 Genmab A/S (DK). . . . . . . . . . . . . . . . . . . . . . . . 65 GenSearch Germany . . . . . . . . . . . . . . . . . . . . . 30 Genzyme Corp. (USA) . . . . . . . . . . . . . . . . . . . . 37 Gilead Sciences Internation Ltd. (USA). . . . . . . . 66 H.C. Wainwright & Co. (USA) . . . . . . . . . . . . . . 31 HAL Allergy Holding B.V. (NL). . . . . . . . . . . . . . 77 HealthCap (SE). . . . . . . . . . . . . . . . . . . . . . . . . . 67 Horizon Discovery Ltd. (UK) . . . . . . . . . . . . . . . 67 IGES GmbH Berlin (GER). . . . . . . . . . . . . . . . . . 38 Ignyta Inc. (USA) . . . . . . . . . . . . . . . . . . . . . . . . 22 Inflarx GmbH (GER). . . . . . . . . . . . . . . . . . . . . . 38 Inthera Bioscience AG ((CH). . . . . . . . . . . . . . . . 68 Invesdor (FIN). . . . . . . . . . . . . . . . . . . . . . . . . . . 35 IRIS Group (DK). . . . . . . . . . . . . . . . . . . . . . . . . 81 Janssen Biotech Inc. (USA). . . . . . . . . . . . . . 70, 90 Johnson & Johnson (USA). . . . . . . . . . . . 38, 69, 90 Juvabis GmbH (CH) . . . . . . . . . . . . . . . . . . . . . . 73 Kurma Partners (F). . . . . . . . . . . . . . . . . . . . . . . . 67 KWS Saat AG (GER). . . . . . . . . . . . . . . . . . . . . . 17 Laboratorios LETI, S.L. (ES). . . . . . . . . . . . . . . . . 77 Lead-Discovery Center GmbH (GER). . . . . . . . . 72 Lek d.d. (SI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 LEWA GmbH (GER). . . . . . . . . . . . . . . . . . . . . . 26 Lonza (CH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Luxendo (GER). . . . . . . . . . . . . . . . . . . . . . . . . . 69 Lytix Biopharma A/S (N). . . . . . . . . . . . . . . . . . . 65 Max Planck Innovation GmbH (GER). . . . . . . . . 72 MedLumics (ES) . . . . . . . . . . . . . . . . . . . . . . . . . 70 Menarini-Silicon Bioystems Inc. (ES). . . . . . . . . . 70 Merck & Co. (USA). . . . . . . . . . . . . . . . . . . . . . . 64 Merck KGaA (GER). . . . . . . . . . . . . . . . . . . . . . . 80 Merck Ventures (NL). . . . . . . . . . . . . . . . . . . . . . 68 Mitsui Global Investment (JP). . . . . . . . . . . . . . . 67 MLM Medical Labs GmbH (GER). . . . . . . . . . . . . 9 MSD Sharp & Dohme (USA). . . . . . . . . . . . . . . . 38 Nerviano Medical Sciences Spa (IT). . . . . . . . . . 22 Neste Oil (FIN). . . . . . . . . . . . . . . . . . . . . . . . . . 64 Newron Pharmaceuticals S.p.A. (IT). . . . . . . . . . 70

Nicox S.A. (F). . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Nordic Life Science Day 2017 (SE). . . . . . . . 44, 45 Novartis AG (CH). . . . . . . . . . . . . . . . . . 23, 31, 70 Novartis Venture Fund (CH) . . . . . . . . . . . . . . . . 67 Novo Nordisk A/S (DK). . . . . . . . . . . . . . . . . . . . 31 Novo Seeds (DK) . . . . . . . . . . . . . . . . . . . . . . . . 68 Novozymes A/S (DK) . . . . . . . . . . . . . . . . . . . . . 65 Ogeda SA (B). . . . . . . . . . . . . . . . . . . . . . . . . . . 67 One Way Liver Genomics S.L. (ES). . . . . . . . . . . 31 OPIS s.r.l. (IT). . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Oxford Genetics Ltd (UK). . . . . . . . . . . . . . . . . . 26 Pall Life Sciences (USA) . . . . . . . . . . . . . . . . . . . 26 Patheon Inc. (NL). . . . . . . . . . . . . . . . . . . . . 24, 30 Pfizer CentreOne (USA). . . . . . . . . . . . . . . . . . CP4 Pharmathen S.A. (GR). . . . . . . . . . . . . . . . . . . . . 71 Pieris Pharmaceuticals Inc. (USA). . . . . . . . . . . . 68 polpharma biologics (PL) . . . . . . . . . . . CP2, 24, 28 Polyphor Ltd. (CH). . . . . . . . . . . . . . . . . . . . . . . 21 Poxel SA (F) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Premier Cercle UP/UPC. . . . . . . . . . . . . . . . . . . 11 QuintilesIMS (UK) . . . . . . . . . . . . . . . . . . . . . . . 37 Rentschler Biotechnologie GmbH (GER). . . . . . . 29 Reviral Ltd (UK) . . . . . . . . . . . . . . . . . . . . . . . . . 22 Rigontec GmbH (GER). . . . . . . . . . . . . . . . . . . . 22 Roche AG (CH). . . . . . . . . . . . . . . . . . . . 21, 22, 23 Roche Venture Fund (CH). . . . . . . . . . . . . . . . . . 67 Roxall Medizin GmbH (GER). . . . . . . . . . . . . . . 77 Sandoz AG (CH). . . . . . . . . . . . . . . . . . . . . . . . . 70 Santhera Pharmaceuticals (CH). . . . . . . . . . . . . . 71 Servier (F). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Shire plc (IRL). . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Siemens Healthineers (GER). . . . . . . . . . . . . . . . 31 Sofinnova (F) . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Sotio a.s. (CR). . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Sphere Fluidics Ltd (UK). . . . . . . . . . . . . . . . . . . 26 Stallergenes SA (F) . . . . . . . . . . . . . . . . . . . . . . . 77 Summit Hero Holding GmbH (GER). . . . . . . . . . 68 Swedish Orphan Biovitrum. . . . . . . . . . . . . . . . . 71 Synvina (B). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Targovax AS (N) . . . . . . . . . . . . . . . . . . . . . . 21, 65 Tecnoalimenti S.C.p.A (IT) . . . . . . . . . . . . . . . . . 71 Thermo Fisher Scientific (USA). . . . . . . . . . . 24, 30 Toyobo (JP). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Transgene SA (F). . . . . . . . . . . . . . . . . . . . . . . . . 23 Trianni Inc. (USA). . . . . . . . . . . . . . . . . . . . . . . . . 7 uniQure BV (NL) . . . . . . . . . . . . . . . . . . . . . . . . 66 Vaximm Holding AG (CH/GER) . . . . . . . . . . . . . 80 Vectron Biosolutions AS (F). . . . . . . . . . . . . . . . . 27 Vetter Pharma-Fertigung GmbH (GER) . . . . . . . . 21 Vivet Therapeutics (F). . . . . . . . . . . . . . . . . . . . . 67 Xell AG (GER). . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Ysios Capital Partners (ES). . . . . . . . . . . . . . . 67, 70

EVents

European Biotechnology | Summer Edition | Vol. 16 | 2017

Unitary Patent Munich, 5 July In the framework of its fifth edition, Premier Cercle gathers important stakeholders who devise the implementation of the future Unitary Patent System and the establishment of the Unified Patent Court. The Event is organised in collaboration with the European ­Patent Office.

www.unitarypatentsystem.eu

24.–28.7.17

Enzymes in the Environment: Activity, Ecology and Applications, Bangor (UK) Info: Chris Freeman, School of Biological Sciences, Bangor University, http://enzymes-in-the-environment.org/

25.7.–5.8.17

SymBioSE 2017, Lund (SE) Info: Lund University, https://symbiose2017sweden.com/

31.7.–1.8.17

3rd World Congress and Exhibition on Antibiotics and Antibiotic Resistance, Milan (IT) Info: Conferenceseries LLC, http://antibiotics.pharmaceuticalconferences.com

6.–10.8.17

10 th Biomedical Transporters Conference 2017, Lugano (CH) Info: Bioparadigms.org, www.bioparadigms.org

21.–23.8.17

Extracellular Electron Transfer: Mechanisms and Opportunities, Norwich (UK) Info: Biochemical Society, www.biochemistry.org

89

29.8.–1.9.17

The XV EAAE Congress – Towards Sustainable Agri-Food Systems: Balancing between Markets and Society, Parma (IT) Info: Prof. Dr. Filippo Arfini, Università degli Studi di Parma, www.eaae2017.it

4.–7.9.17

Whole-Cell Modeling Summer School, Barcelona (ES) Info: Ruben Ventura, WholeCell Org., www.wholecell.org/school-2017

Biotech Week 2 5 . S e p t e m b e r –1. O c to b e r , EU EuropaBio and its members’

national associations and companies encourage all biotech supporters to organise initiatives and events across Europe throughout the week to present their activities.

www.biotechweek.org

27.8.–1.9.17 3.–6.7.17

2nd DNA Replication as a Source of DNA Damage, Rome (IT) Info: Fusions Conferences, www.fusion-conferences.com/conference67.php

3.–4.7.17

Plant Genome Editing & Genome Engineering, Vienna (AT) Info: Vienna International Science Conferences & Events Association, www.viscea.org

7.–8.7.17

New Breeding Technologies in the Plant Sciences – Applications and Implications in Genome Editing, Gothenburg (SE) Info: Society for Experimental Biology, www.sebiology.org

9.–14.7.17

EAPR 2017 – 20 th Triennial Conference, Versailles (F) Info: Xavier Gautier, ARVALIS – Institut de vegetal, www.eapr2017.com

Pictures: Premier CercleTM/Bionordic Services AB/biotechweek.org

9.–13.7.17

FEMS 2017, Valencia (ES) Info: Kenes International, www.fems-microbiology2017.kenes.com

15.7.17

CNS2017, Antwerp (BE) Info: Organization for Computational Neurosciences, www.cnsorg.org/cns-2017

21.–25.7.17

ISMB/ECCB 2017, Prague (CZ) Info: Steven Leard, ISCB – International Society of Computational Biology, www.iscb.org/ismbeccb2017

89_EB_Summer_17_Events_mak.indd 89

YEAST 2017, Prague (CZ) Info: Institute of Microbiology Czech Academy of Sciences, www.yeast2017.cz

28.–29.8.17

14th International Conference and Exhibition on Pharmaceutical Formulations, Brussels (BE) Info: Conference Series LLC, http://formulation.pharmaceuticalconferences.com

Nordic Life Science 12–14 SeptembeR, Malmö Nor-

dic Life Science Days is the fastest growing partnering conference in the Nordic region ­d edicated to the life science industry for decision makers from biotech, pharma, and medtech, as well as finance, research, policy, and regulatory authorities.

www.nlsdays.com

6.–8.9.17

How Dead is Dead? – The Fifth Conference on Exploring the Edge of Bacterial Life, Vienna (AT) Info: Nina Strasser, ÖGHMP, http://oeghmp.at/events/hdid2017/

7.–8.9.17

Clinical Trials for Medical Devices – ctmd2017, Budapest (HUN) Info: BioEvents, www.ctmd2017.com

10.–13.9.17

Basel Life Science Week & MipTec 2017, Basel (CH) Info: www.basellife.org

17.–20.9.17

HUPO 2017, Dublin (IRL) Info: Human Proteome Organization, http://hupo2017.ie

19.–20.9.17

Swiss Medtech Expo, Luzern (CH) Info: Messe Luzern , www.medtech-expo.ch

19.–21.9.17

Influenza 2017, Oxford (UK) Info: Dr. Muhammad Suhail, St. Hilda’s College Oxford, http://lpmhealthcare.com/influenza-2017/

15.06.2017 13:07:44 Uhr

Encore

Winners & losers

European Biotechnology | Summer Edition | Vol. 16 | 2017

Tiny & organised

I’m in biotechnology because…

Attractive city In the

Structural Biology The tiny cir-

May poll of our news platform european-biotechnology.com, readers were asked which city in Europe would be most suitable to be the new seat of the European Medicines Agency after Brexit.

The Danish capital Copenhagen won the vote by a large margin.

cular chromosome of Mycoplasma pneumoniae is organised more like sophisticated genomes. The pathogen is one of the smallest-known, self-replicating organisms.

It only makes around 20 different DNA binding proteins that are responsible for organising the chromosome. Despite its size, the chromosome is organised in defined, three-dimensional structures. In particular, it is folded such that structural domains of between 15 and 30 kilobase pairs in length arise. These domains gua­rantee that certain genes are jointly turned on or off. The findings of scientists led by Luis Serrano from the Spanish Centre for Genomic Regulation were published in Nature Communications (doi: 10.1038/ncomms14665). 

Deprived city Although the results of

the 8 June election in the UK imply that Brexit will take a soft turn, the relocation of the European Medicines Agency out of London is still a foregone conclusion. The agency employs some 900 people and has an annual budget of more than €300m. 

John Brennan Secretary General, Europabio SE, Belgium

“… its role in society will keep growing. So, we must continue an open, fair, and constructive dialogue with all players involved to make sure that society, including our industry, thrives in a way that benefits all.”

Following Actelion’s path With Swiss Actelion being endocytosed by US pharma Johnson & Johnson (J&J), European biotechnology has lost its most glamorous public company. Who’s succeeding? With eleven thera­ peutic biotechs valued at over €1bn, the pool of applicants is fairly large. Genmab’s success is largely due to a US$1bn licensing deal with J&J affiliate Janssen Biotech around the anti-CD38 antibody daratumumab for multiple myeloma. The table excludes diagnostics, tools, service, and generics companies.

11.51

Genmab A/S 3.92

Swedish Orphan Biovitrum AB

3.54

Galapagos N.V. 2.53

BTG plx

2.42

Cosmo Pharmaceuticals N.V.

2.35

Abcam plc

1.97

Evotec AG

1.85

MorphoSys AG

1.70

Prothena Corp. plc Bavarian Nordic A/S

1.50

DBV Technologies S.A.

1.46 0

1

2

3

4

Valuations (in billion euro) are as of 12 June 2017.

Sources: BioCentury Online Intelligence (BCIQ), European Biotechnology

90

5

Drug makers only have two years from now to make their drugs and packaging counterfeit-resistant http://bit.ly/2swuCjb #serialisation @EuroBiotechNews @merckgroup and @pfizer claim second FDA nod for #cancer drug #Bavencio (avelumab) buff.ly/2pjeocd

@PMLiVEcom Bedside prod. of protein drugs could help payers by lowering prices, & ultimately

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lead to individualized treatments go.nature. com/2sgqNy6ics @NatureBiotech

Please follow us @EuroBiotechNews I continue to be a fan of @GSK and am excited about Emma Walmsley taking the helm. #leadership lnkd.in/dbfuCvd

@boccuzzillc

Next Magazine Quarterly European Biotechnology will turn up in the letter box again on 6 October. The deadline for advertisements in the autumn edition of the magazine is 18 September. In particular, CROs and CMOs should take the chance to gain their readers’ attention, as the issue will feature numerous CRO/CMO topics.

Questions can be directed to Andreas Macht (+49-30-264921-54) and Oliver Schnell (+49-30-264921-45), or drop us an email at marketing@biocom.de. 

Picture: Europabio/Veldemanphoto

Walmsley #serialisation bedside Autumn prospect

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SAVE THE DATE UI #FSMJO $POGFSFODF PO -JGF 4DJFODFT

Picture: Dimitar Marinov / fotolia.com

/PWFM "OUJNJDSPCJBMT BOE ".3 %JBHOPTUJDT

2 March 2018, Berlin, Germany Over it’s ten year’s history, the Berlin Conference has become a must-attend event for Life Science decision makers, business developers, investors and legal experts. The 11th conference will explore the exciting market for the development of novel antimicrobials and AMR diagnostics. › › › › › ›

Antimicrobial Market – Industry overview, SME engagement & financial insights Technology Perspective – New approaches to efficiently combat antimicrobial resistance Diagnostic Challenge – Promising molecular methods of detecting multiple drug resistance Legal Environment & Reimbursement – The challenges of bringing antimicrobials to the market R&D Trends – Research and development beyond antibiotics & public-private partnerships Start-up Pitch – Investor talk & new business models in the field of therapeutics and diagnostics

More informationen: www.berlin-conferences.com

Sponsor:

Supporting Partners:

Media Partner:

European Biotechnology NET WORK

Organisation: BIOCOM AG | Lützowstraße 33–36 | 10785 Berlin events@biocom.de | Tel. +49 (0)30 264921-53 | Fax +49 (0)30 264921-66

When it’s

YOUR

compound, every step matters.

www.pfizercentreone.com API

STERILE INJECTABLES

HIGHLY POTENT SOLIDS

PC1-16-0005/R2-210x275mm © 2016 Pfizer Inc. All rights reserved. Pfizer CentreOne is a Trademark of Pfizer Inc.

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