EBM 2/2018 Summer

ISSN 2364-2351 | A 60711 |

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

Interview Novartis CEO Vasant Narasimhan reveals why he bets on one-time curative treatments and digital tools

Haemophilia A

Fixing the leak Nanobots

Agrochemistry

Bioeconomy

Biofairs Compass

Microscopic drug delivery systems – the next big thing

Bayer-Monsanto to bet on genome editing in crop design

Global policy leaders lay out agenda to push biologisation

The ultimate guide to leading Life Sciences Events in H2/2018

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European Biotechnology | Summer Edition | Vol. 17 | 2018

Intro

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Single-use plastics: New EU rules to reduce marine litter Plastics are magical materials, and they will be even more important in the future than they are today. But they lead to microplastics in the environment, especially noticeable as “marine littering.”

The European Commission is now proposing, among other things, a ban on certain single-use plastic products, including “plastic cotton buds, cutlery, plates, straws, drink stirrers, and sticks for balloons, which will all have to be made exclusively from more sustainable materials instead.” The Commission’s legislative proposal must then be negotiated with the member states and the European Parliament.

And here substantial changes should still be made – because so far industry and politics continued to fail in this area.

Michael Carus The founder and Managing Director of the nova-Institute studied physics and mathematics at the University of Cologne. Carus became a lecturer at the University of Tübingen, on the topics of ecology, nuclear energy, and radioactivity. He worked as a science journalist and scientist at the KATALYSE Environmental Institute with a focus on energy, ecology, and renewable resources, and two years in the solar industry. In 1994, he founded the nova-Institute for Ecology and Innovation.

Microplastics have been in the public eye for at least ten years.

The plastics industry has waited until the public pressure became too high to ignore. Then their argument was, what can our plastics do if people do not handle our products properly and politicians do not organise better recycling programmes?

But in fact, the plastics industry can do something about it. For years, there has been another solution for plastic products that are practically impossible to recycle or whose preparation is far too costly: biodegradable plastics.

The European Commission has spent several million Euros over the last ten years to develop and certify such plastics. Plastics that are biodegradable in water, soil, home compost or industrial composting and do not leave any microparticles behind.

And today there are many producers of biodegradable plastics; there are certifications and labels. But these new plastics are still a little too expensive to become sure-fire success. And now they don’t even get a chance in the new European plastics strategy!

Picture: Nova Institute, Cologne

Seize the opportunity for innovation and sustainability now. We prohibit single-use products if they are not biodegradable. But let us give biodegradable plastics, which have been successfully developed for years, their chance on the market! We also need alternatives to plastic products that, even when used properly, end up in the environment and are difficult or impossible to recycle. A few examples would be mulch films, tree protection covers, plant clips, binding yarns, strings for lawn trimmers, carrier polymers for fertilizers and pesticides, and even plastic baits at sea. Let us take a step forward in all of Europe. Because now is the time when the rules for the coming decades are being made.

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Further reading: http://bio-based.eu/policy/#innprobiofacts

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Contents

European Biotechnology | Summer Edition | Vol. 17 | 2018

Cover Story

Insight Europe

regional news

6 User-driven early certainty: EPO steps back

66 Northern Europe: Sweden, Denmark, Norway and Finland

10 Launch of European PNAS; More rights for European CDMOs 11 European Commission proposes €100m budget for Horizon Europe

Economy 17 Interview (Haemophilia): Gallia Levy, Global Development Team Leader, Hemlibra, Roche AG

68 Western Europe:

France, Belgium, The Netherlands

and the UK

70 Central Europe:

Germany, Switzerland

and Austria 72 Southern Europe: Italy, Spain, Greece, Slovenia, and Greece

19 Update on clinical trials 22 Interview (Strategy):

Vas Narasimhan, CEO, Novartis AG

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Stopping the bleed Since factor VIII replacement therapies hit the market, life expectancy for haemo­ philia patients has risen to normal levels.

But around 25% of those who suffer from haemophilia A still have no therapeutic options, because their immune systems form antibodies against clotting products that can stop bleeding. Researchers and companies in the growing US$15bn haemo­philia medications market are feverishly exploring new ways to identify patients at risk and offer them alternative treatments, while a series of mergers and acquisitions have changed the playing field for established markets and players.

24 EMA News

74 Eastern Europe:

Poland, Czech Republic and

Hungary

Science & Technology

25 Analyst commentary 26 Euro Biotech Stocks

80 F irst mesenchymal stem cell therapy hits the European market

28 Interview (Bioeconomy Finance): Rob Carlson, Managing Director, Bioeconomy Capital

82 Approved diabetes medicine helps PAH patients

30 Headwinds in sustainable industry

and manufacturing

Service

33 Falsified medicines deadline nears 34 Interview; Hannes Teissl, Polpharma Biologics 36 Interview: Federico Pollano, Rentschler Biopharma

75 Biopeople 84 News from partner associations: Swiss Biotech Association, Medtec Europe and Europa­Bio 88 Events 89 Company index/New products 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 (CoMarcus 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: Naeblys/istockphoto.com; Supplement: ASEBIO, EFIB/BIOCOM; ® BIOCOM is a registered trademark of BIOCOM AG, Berlin, Germany.

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editor), Dr. Martin Laqua, Helene Märzhäuser, Sandra Wirsching; Advertising: Oliver Schnell, +49-30-2649-2145, Christian Böhm, +49-30-2649-2149, Andreas Macht, +49-30-2649-2154; Distribution:

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Contents

European Biotechnology | Summer Edition | Vol. 17 | 2018

Drug Delivery

Agri-biotech

Editorial

Consolidation up top

Global discharge

They co-created Agent Orange. Now agri-biotech giants Bayer and Monsanto are about to merge into a single mega­ entity for pushing genetic engineering technologies in the crop design market.

European Biotechnology takes a look at what consumers and farmers can expect, and how new products will be regulated in the age of the ‘Big Four’.

60

Nanobot healthcare They’re small, fast – and could be the future of medicine. Nanobots have already been used in animal trials to attack tumours, and have proven effective. But there are still a few problems to overcome before doctors begin injecting millions of tiny machines into humans. Not least that researchers still have to figure out how to get rid of the microscopic helpers once they’ve done their job.

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Pictures: iordani/fotolia.com (top), loneroc/shutterstock.com (middle), ABLinc. (bottom)

SPECIAL

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Event compass 39 Intro: update on EU events 40 NLS Days, Stockholm 42 European Biotech Week 44 Biospain, Seville

46 bioLIVE, Madrid

48 BIO Japan, Yokohama 50 EFIB, Toulouse

52 European Business Development

Conference, Hanover, Germany 54 BIO Europe, Copenhagen 56 Pharmalab, Düsseldorf

58 Biofit, Lille

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At the recent Global Bioeconomy Summit (see. p. 30), US researcher John Schramski had an interesting message. He sees our planet as an accumulator that’s been charged up by hundreds of millions of years of photosynthesis. Until now, he said, Earth has been able to effortlessly top up reserves. But as energy consumption by humans exploded over the past century, its currency of biomass and fossil fuel has been almost fully depleted. “We have to slow down,“ Schramski warns – because without our natural resources we won’t survive.

An interesting aspect of the international meeting was that two major lobbies were apparent. There were those who pushed the idea that we all need to focus on sustainability, because no one knows how much longer we can go on exploiting our planet (see p. 32). On the other side were those who primarily see the economic opportunities attached to green technology (see p. 28).

Maybe biologisation of the industry is about both. Making money, but with the right biotechnologies for rebalancing economic, social and ecological imbalances.

The challenge now is to separate those who tout old technology to make money under green labels from those offering the right solutions.

Thomas Gabrielczyk Editor-in-Chief

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Insight Europe

European Biotechnology | Summer Edition | Vol. 17 | 2018

User-driven early certainty: EPO steps back EU It was too good to be true. Following harsh criticism from industry, the European Patent

Office (EPO) drafted a widely applauded proposal to allow exemptions to its Early Certainty Initiative in Examination. One month later, the EPO withdrew UDEC following a recommendation from Business Europe – the only business association sitting next to decision-makers in the EPO’s Administrative Council – not to bring UDEC into force in July.

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by the EPO,” which “could lead to doubts over the openness and transparency of the process.” Demands from other attendants for publication of the UDEC proposal and submission of written feedback had been ignored by the EPO. Business Europe’s press office did not answer press requests asking for background information on its position paper. The perceived lack of transparency in decision-making was reinforced by contradictory information from the EPO and other sources:

›› While it was envisaged at the meeting

previous meetings on Early Certainty a bit confused because – in their perception – members of the association so far showed “diverging,” if not “indifferent” attitudes towards UDEC. After a February meeting of the EPO‘s Committee on Patent Law, the EPO Administrative Council decided in March to follow all points proposed by Business Europe and to present a revised paper under the incoming EPO President António Campinos later this year.

Lack of transparency and quality The Chartered Institute of Patent Attorneys (CIPA), which had pushed the EPO to “hold a dedicated consultation on this significant change to European prosecution” noted that “attendence to the [UDEC] consultation was strictly by direct invitation

that there would be only a marginal effect for the EPO and the member states in terms of national renewal fees, insiders had told European Biotechnology that implementation of Early Certainty without the option of postponement of examination through UDEC would lead to a huge shift in fees from the EPO to the national patent offices – resulting in earlier and higher cost for the users (European Biotechnology, Spring Edition).

The annual renewal fee for a pending patent at the EPO is tenfold lower than the fee payable to the national patent offices after a patent has been granted and nationalised in 30 European countries (the standard case). A three-year earlier nationalisation of the 96,000 patents issued in 2016 would have resulted in flushing nearly €1.47bn more into the national patent offices. ›› There is also contradictory information concerning the quality level EPOgranted patents will have under Early Certainty in Examination: EPO Presi-

Picture: Fotolia.com/ Oliver Raupach

Since last autumn, the EPO had worked hard to find ways to allow exemptions from its Early Certainty of Examination initiative, which was drafted to cut the current examination time from 22 months to 12 months on average. The result, dubbed User-driven Early Certainty (UDEC), had not only been warmly welcomed by the biopharma sector but also by global IT and engineering giants, who were looking for possibilities to get patent protection for moonshot research resulting in longerterm product breakthroughs.

Just before a three-hour stakeholder meeting in February aimed to discuss the EPO’s UDEC solution – which allowed “applicants to postpone the start of substantive examination for a maximum of three years,”(see European Biotechnology, Spring Edition) – Business Europe sharply criticised the proposal. Business Europe, the only industry association that has observer status both in the EPO Committee on Patent Law and the EPO‘s Administrative Council, called on the EPO not to enter UDEC into force on 1 July 2018. Major issues must be resolved, the association stressed through a press release, including third party uncertainty, potential derogation of the Paris criteria – a plan devised by EU heads dating back to 1999, when the pace of patent issuance was incomparibly slow, to cut examination time to 24 months – and the public perception that UDEC was an industry-driven initiative, and could cast a bad light on the EPO’s decision making. The association called on the EPO to initiate a full impact assessment – a move that left attendants of

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Insight Europe

European Biotechnology | Summer Edition | Vol. 17 | 2018

the quality level of patents granted would be equally high as before. Biotech Association BIO Deutschland urged the EPO to establish an optional DEPACE mechanism (such as UDEC) to prevent negative effects due to the acceleration of patent examination. “Currently, quality is very high.

However, if the pressure increases on patent examiners to examine as many applications as possible, quality will suffer,” predicted Dr. Helmut Buschmann, Head of Patent Affairs at Bayer spin-out AiCuris last year. As quality of patents is relevant when it comes to litigation, “Biotech investors will assess how robust the patent portfolio is when it is challenged.” Pointing to increasingly automated working routines of the EPO examiners, Dr. Jürgen Dressel, Head of Global Patent Litigation Strategy at Novartis Pharma, adds: “It would be bitterly disappointing for an applicant, who is totally dependent on a high-quality assessment of his invention, to get a quick refusal based only on formal reasons, such as lack of clarity.”

dent Benoît Batistelli said on his blog that the EPO has established several measures to maintain the high quality level of patents, even under the higher throughput of accelerated examination, and created a Standing Advisory Committee before the EPO (SACEPO) Working Party on Quality in January 2017 to “provide another channel to gather feedback on quality at the EPO based on the experiences of major user groups.” An open letter sent in May from 924 EPO patent examiners to the EPO‘s Administrative Council, which controls Batistelli, reads clearly different: Patent quality has fallen, thanks to the push by the EPO management to approve more of them, it says. The underwriters confirm that they are “submitted to constraints that are no longer compatible with fulfilling appropriately our duties within the Search and Ex-

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amination divisions.” They warn that throughput may not come at the expense of the validity of patents granted – “timelines and number of products should not be the only criteria to assess the Office …” ›› Promises from the outgoing EPO President Batistelli to hire more examiners to maintain the high quality level of European patents are not (yet?) reflected in EPO statistics on workforce.

According to Niclas Morey, Principal Director User Support & Quality Management at the EPO, “quality is the EPO President’s number one priority.” Decreasing quality of patents has been a major concern of EPO users in the past, as decreasing quality jeopardises industry investments and revenues. Pharma associations VFA and EFPIA welcomed Early Certainty in Examination only under the prerequisite that

However, Dressel wonders why the EPO didn’t make use of an instrument that already exists: “From a pharma applicant’s standpoint, the PACE procedure is sufficient to create legal certainty. If there is a third party interest apparent, for example, from Third Party Observations, now the EPO already switches automatically to accelerated examination.” Using the PACE procedure for patentees and third parties would solve the conflicts arising from Early Certainty in Examination: As the EPO has already met the Paris criteria, it could offer the option of faster examination for users in sectors that need rapid patent issuance. This would take some of the workload off examiners, leading to remaining high patent quality and would resolve any third party uncertainty. Additionally, it could prevent a decrease in innovation by leaving the cost for high-tech SMEs as low as it is. Any conspiracy theory suggesting that Early Certainty would grant national patent offices higher annual revenues through fees coming in by earlier nationalisation would be invalidated. L

Picture: EPO staff

PACE vs UDEC?

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insight

News Fighting Cancer MEPs have proposed to earmark €400m of the proposed €7.7bn Health pillar of the Horizon Europe programme to make pediatric cancers a chronic instead a deadly disease within the next 20 years. An strategy paper presented by EVP health rapporteur Peter Liese in May, proposes to double the current research budget for rare pediatric cancers that are neglected by the industry because of its low ROI. It calls for cross-border research, cross-linking of cancer registries for improved enrolment of patients into clinical trials, implementation of EU Health Technology Assessment for better access to treatments for all, and a push for digitalisation of patient data.

US loves sugar drinks The US administration has torpedoed the WHO’s plan to recommend a 20%+ tax on oversugared drinks, intended to fight obesity, diabetes, cancer, and life-threatening secondary diseases. While most of the Commission on Non-Communicable Diseases’s 26 members backed a tax on sugar-sweetened beverages, the US representative blocked it.

The move was enthusiastically welcomed by the International Food and Beverage Alliance (IFBA) — a foodgiant interest group that includes Coca-Cola (Atlanta) and PepsiCo. (Harrison). A growing body of evidence suggests that overweight- and sugartriggered inflammations initiate diseases that lead to 40 million deaths annually. Eric Hargan, the U.S. deputy secretary for Health and Human services, said there was no proof that a sugar tax would improve health outcomes.

European Biotechnology | Summer Edition | Vol. 17 | 2018

No hype but science Science A new journal from Europe,

4open (www.4open–sciences.org), is set to break the current bias of leading science journals to overrepresented certain science trends vs excellent science stemming from fields that make less economic or funding impact. “When preparing 4open, we were seeking to attract any excellence in science. This includes every research result, positive AND negative, that helps advance science, in and outside the current trends. 4open is a journal both for established teams and young researchers,” said editor-in-chief, Prof. Dr. Björn Brücher.

This summer the first papers will be published. 4open has a peer-reviewed, open-

Balancing CDMO’s competitivity Manufacturing The European Commission plans to back the rights of European generics and biosimilar makers against non-European competitors. Currently, EU producers are not allowed to export biosimilar versions of a drug produced in the EU right after expiry of its patent, because 86% of them have a Supplementary Protection Certificate (SPC) under Regulation EC 469/ 2009. SPCs extend patent protection for medicinal products that must undergo lengthy testing and clinical trials prior to obtaining regulatory market-

Commissioner Elzbieta Bienkowska

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access following a fair article processing charge model. 4open covers all four core disciplines of natural sciences: Life Sciences & Medicine (Editor-in-Chief Prof. Björn Brücher); (Chemistry & Applied Chemistry (Editor-in-Chief, TBA soon); Physics & Applied Physics (Editor-in-Chief Prof. Elias Brinks); and Mathematics & Applied Mathematics (Editor-in-Chief Prof. Theodore Simos), which includes Materials & Engineering. According to Dr. Claus Roll, Managing Editor at EDP Sciences, “the peer review process is entirely independent of the APC decision and will in no way alter any decision on scientific merit that the editor should take.”

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ing approval for 3.5 years on average. For non-EU biosimilar exporters this does not apply. At the end of May, Industry Commissioner Elzbieta Bienkowska proposed to introduce an ‘export manufacturing waiver’ to SPCs in order to “eliminate an unintended competitive disadvantage to Europe’s pharmaceutical companies when they go to export markets.” According to Bienkowska, the amendment could generate additional €1bn net sales per year for EU-based biosimilar makers. The waiver would allow EU companies to manufacture generics or biosimilars for export to non-EU markets where their protection has expired or never existed.

Marc Alexander Mahl, President of Medicines for Europe, stressed that “the launch of the SPC manufacturing waiver legislative proposal is a very positive step to create manufacturing jobs in Europe, and to boost competitiveness by allowing EU companies to compete on a level playing field. However, this proposal should allow companies – especially SMEs – to prepare for ‘day 1 launch’ after expiry in Europe. Without this, European patients will not get timely access to European manufactured generic and biosimilar medicines.

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Picture: Aduiovisual Service of the EC

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Insight Europe

European Biotechnology | Summer Edition | Vol. 17 | 2018

EC earmarks €97.6m for Horizon

Jyrki Katainen, Competitiveness Vice-President of the EC and Research Commissioner Carlos Moedas presenting Horizon Europe in June

Funding In Brussels, European Commissioners Jyrki Katainen and Carlos Moedas proposed a budget increase of 25% for the next European Research and Innovation programme Horizon Europe (2021-27) compared to Horizon 2020. In summer, however, the EC’s High Level Group recommended a budget of at least €120bn. Predecessors to the EU’s ninth framework programme have had budgets of €50.5bn (FP7) and €74.9bn (Horizon 2020), respectively. Christian Ehler and Dan Nica, the MEPs that will steer the programme through the European Parliament, however, said they want to fight for the €120bn budget. Ehler said the budget proposed by the European Commission “does not live up to its ambition” to meet global challenges. EFPIA’s Secretary General, Nathalie Moll, com-

mented: “It‘s good, but of course we had pinned our hopes on something close to the High Level Group report.” Horizon Europe is built on three thematic pillars, which will be complemented by InvestEU, an €15.2bn investment support programme to speed up commercialistation of R&D results. The EC expects it to attract further investments of €650bn.

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pie: €7.7bn is earmarked for health; €8bn for inclusive and secure societies; €10bn for the digital and industry mission; €15bn for climate, energy and mobility; and an additional €10bn for food and natural resources. ›› The novel €13.5bn Open Innovation pillar aims to make Europe a front runner in market-creating innovation. €10.5bn has been earmarked for the European Innovation Council (EIC), a one-stop shop for high potential and breakthrough technologies and innovative companies with potential for scaling up. EIC has been inspired by tDARPA, the US agency responsible for ground-breaking innovations such as the Internet, the GPS, and stealth technology. The EIC will fund moonshot research and the new focus won’t come at the expense of the European Institute of Technology (EIT), which will receive €3bn (Horizon 2020: €2.7bn).

›› An Open Science pillar earmarks

Additionally, the Commission‘s JRC stands to get €2.2 bn through fellowships and exchanges as well as funding to projects driven by researchers themselves, through the European Research Council and the Marie-Skłodowska-Curie actions.

€25.8bn for basic research – €16.6 bn for the European Research Council ERC, €6.8bn for Marie Sklodowska-Curie Actions, and €2.4bn for research infrastructures. ›› A Global challenges pillar is designed to support research relating to societal challenges. Its five missions will get €52.7bn, the biggest slice of the

While the UK was FP7’s biggest beneficiary in FP7 – with tax contributions of only €5.4bn but FP7 funding of €8.7bn – it will be the biggest looser in Horizon Europe because of Brexit. Observers told European Biotechnology they expect the UK to get less support than other associated nations such Israel or Ukraine.

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Rubrik

European Biotechnology | Winter Edition | Vol. 16 | 2017

Pictures: xxx

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HAematology

European Biotechnology | Summer Edition | Vol. 17 | 2018

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Closing the gap in haemophilia therapy Factor VIII inhibitors About 25% of the people who suffer from haemophilia A have no

therapeutic options, because their immune system forms antibodies against clotting products that can stop bleeding. Researchers and companies in the growing US$15.8bn haemophilia market are feverishly exploring new ways to identify patients at risk and offer them alternative treatments. A series of mergers and acquisitions have changed the playing field for established markets and players.

Pictures: PEI (right), selvanegra/istockphoto.com (left)

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very time Michael fell when he was a child, his parents had to rush him to the hospital. “Between the ages of one and six, we were there pretty much every day,” his mother remembers. Her son is one of 320,000 people worldwide with haemophilia A, the more common form of the genetic condition. People living with the hereditary disease either don’t produce enough of a clotting protein called factor VIII, or they lack it completely. Because their blood doesn’t clot properly, it can lead to uncontrolled bleeding. The disease is called ‘mild’ when FVIII levels are 5%-40% of normal levels, ‘moderate’ when between 1%-5%, and ‘severe’ when they’re under 1%. Michael has the severe form. Injections with factor VIII, the current standard of care, can prevent and treat bleeding episodes. “I try to do what I can, and not spend too much time thinking about what I can’t do,” says Michael, now a young man. “For me, that’s a kind of motto in life.” Starting in the 1950s, prophylactic factor VIII infusions were derived to treat haemophiliacs with plasma-derived factor VIII products from donors. In the 1990s, complement­ary treatments with recombinant factor VIII proteins hit the scene. Prophylactic factor VIII replacement therapy has now cut the average number of bleeds from more than 40 a year to under two. Today, a child born with severe haemophilia can expect to have a normal lifespan. But besides annual treatment costs of US$150,000-$300,000 per

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patient, other serious hurdles remain.

Prophylactic therapy patients continue to need drugs that will decrease their need for immuno­suppressants. The half-life of the active factor VIII protein is also short, and needs to be extended. And most importantly, a significant number of patients simply don’t respond to treatment.

Almost one in three people with severe haemophilia A also develops inhibitors –

Zoe Waibler Head Product Assessor for Immunologic Drugs, Paul Ehrlich Institute, Langen (Germany)

? !

hy is it important to find factors W in the blood that boost factor VIII inhibitor formation?

It’s a prerequisite for developing new approaches to haemophilia therapies, which prevent the formation of these inhibitors against factor-VIII products.

antibodies that identify the recombinant blood clotting factor VIII as foreign, and stop it from working. For the big players in the currently US$15.8bn field – Shire, Biogen/Bioverativ, Novo Nordisk, Pfizer and others (see table, p. 14) – new approaches to solving those problems could have a big impact on revenues. The market is growing. Analysts from Transparency Market Research predict it will surpass US$25bn by 2024.

The huge unmet medical need and associated potential has triggered major acquisitions, with former market leaders under new ownership. Biogen­haemophilia spinout Bioverativ, for instance, was taken over by Sanofi for US$11.8bn. In a US$62bn acquisition, haemophilia amd haematology giant Shire plc agreed in May to a takeover by Takeda. Approaches for circumventing the immuno­genicity and inhibitor problem – such as factor VIII products with fully human glycosylation patterns, gene therapies or bi­specific antibodies that mimic the effects of factor VIII with less or no potential for inhibitor formation – have the potential to change the field dramatically.

Predicting inhibitor formation However, current claims involving reduced immunogenicity and reduced potential for inhibitor formation are still speculative, say haemophila experts like Kenneth Lieuw (J Blood Med, 8;67-73). Ev-

14.06.2018 13:21:45 Uhr

14

HAematology

idence from a 2016 study (NEJM, 374, p.

2054-2064) suggesting that patients who received recombinant factor VIII products had a higher risk of developing anti­factor VIII antibodies than people receiving plasma­-derived factor VIII was not confirmed in a 2017 analysis conducted by the European Medicines Agency. The EMA subsequently concluded that the risk of inhibitor development should be evaluated individually for each medicine, regard­less of class.

It still isn’t clear though what exactly determines the immunogenicity of factor VIII products – and thus their efficacy. It

European Biotechnology | Summer Edition | Vol. 17 | 2018

appears to involve ethnicity (black people are twice as likely to develop problems as white people), genetic mutation (particularly in the F8 gene), and environmental factors.

Worry about potential bleeds can have a major impact on quality of life Also under discussion are the differences in post-translational modification patterns of FVIII. These appear to

depend on the cell line used – whether non-mammalian cell lines (e.g., CHO or BHK) or human cell lines (HEK) – and the role played by the factor VIII chaperone (VWF) in both increasing the halflife of FVIII and reducing the endo­cytosis of FVIII by antigen­-presenting cells. Research recently showed that secondgeneration products had higher inhibitor rates than third­-generation products.

And the experts also say claims that factor VIII products with extended half-lives are also less immunogenic still have to be proven clinically. Investigations into extending the half-life of current recom-

Available FVIII products. VWF: Von Willebrand Factor (Factor VIII chaperone); BDD: B domain deleted; EHL, extended half-life

Generation

Products/Companies

FVIII

Technology

Half-life [h]

FDA approved

› Plasma derived

Antihaemophilic factor (Hemofil M®/ Shire_Baxalta, Koate- DVI®/Bayer, Monarc-M®, Monoclate-P®/ CSL Behring)

Full length

Pooled human plasma

14.8–17.5

1966 (Hemofil M), 1974 (Koate-DVI)

› Plasma derived/VWF complex

Antihaemophilic factor/VWF complex (Alphanate®/Grifols, Humate-P®/ CSL Behring, Wilate®/ Octapharma)

Full length with VWF

Pooled human plasma

12.2–17.9

1978 (Alphanate), 1986 (Humate-P), 08/2009 (Wilate)

› Recombinant: 1st generation

Antihaemophilic factor recombinant (Recombinate®)/Shire-Baxalta

Full length

BSA in culture and human albumin as stabiliser

14.6 ± 4.9

12/ 1992

› Recombinant: 2nd generation

rFVIII-FS (Helixate®/CSL Behring, Kogenate®/Bayer)

Full length

Human plasma protein solution in culture

13.74

06/2000

› Recombinant: 3rd generation

Antihaemophilic factor recombinant (Advate®/Shire, Kovaltry®)/Bayer

Full length

No human or animal protein added

12–14.2

07/2003 (Advate), 03/2016 (Kovaltry)

› Recombinant: 2nd generation

Moroctocog alfa (ReFacto®)/Pfizer

BDD

Human plasma protein solution in culture

14.5 ± 5.3

03/2000

› Recombinant: 3rd generation

Moroctocog alfa (Xyntha®), Pfizer Turoctocog alfa (Novoeight®)/Novo Nordisk

BDD

No human or animal protein added

10.8–12

02/2008 (Xyntha), 10/2013 (Novoeight)

› Recombinant: 4th generation

Simoctocog alfa (Nuwiq®)/Octapharma

BDD

HEK cells to allow human glycosylation

17.1 ± 11.2

09/2015

› Recombinant: 3rd generation, EHL

Octocog alfa pegol (Adynovate®)/Shire

BDD-PEGylated

PEGylation to parent drug Advate

14.69 ± 3.79

12/2016

› Recombinant: 4th generation, EHL

rFVIII–Fc (Eloctate®)/Bioverativ&SOBI

BDD-rFVIII–Fc

HEK cells to allow human glycosylation

19.7 ± 2.3

06/2014

› Recombinant: 3rd generation, EHL

rFVIII-SC (Afstyla®)/CSL Behring

EHL single chain

No human or animal protein added

14.2

05/2016

› Novel bispecific antibody

Emicizumab (Hemlibra®)/Roche

–

Bispecific antibody with FVIII-mimetic function

–

11/2017

› Recombinant: 3rd generation, EHL

N8-GP/Novo Nordisk

BD-modified glycoPEGylated

GlycoPEGylated addition to FVIII

18.4–19.04

filed for approval

› Recombinant: 3rd generation, EHL

BAY94-9027/Bayer

BDD-PEGylated

Site-specific addition of PEG side chain

13.7–28.1

filed for approval

12-16_EB_Summer_2018_hemophilia_tg.indd 14

14.06.2018 13:21:51 Uhr

HC

HC

LC

LC

FIXa

Phospholipid membrane

FX

Fig. 1: Mode of action of Roche’s bispecific antibody Hemlibra (emicizumab) bridges FIXa and FX to restore function of missing FVIIIa, which is needed for effective hemostasis.

binant coagulation factors have taken a range of approaches, including reduction of exposure to clearance receptors through PEGylation, rescue of endocytosed proteins from intracellular degradation by crystallizable fragment (Fc) fusion and albumin fusion proteins, and enhanced interactions with VWF. At the end of March, immunologists at the German regulatory authority Paul Ehrlich Institute reported that bacterial danger signals such as lipopolysaccharide (LPS) in the blood boost T-cell mediated immune responses against factor VIII. The team led by Zoe Waibler said that LPS co­administered with a factor VIII product increased the amount of activated antigen­­-presenting dendritic cells (DCs) versus factor VIII alone. However, more research has to be carried out to find bio­markers that accurately identify untreated patients with a high risk for inhibitor formation.

The dawn of a new age in the field – bispecific antibodies and gene therapies A closely watched drug in the haemophilia A field is Roche’s recently approved, once-weekly bispecific antibody Hemlibra (emicizumab). With one of its two Fab-arms (see Fig. 1) the new medicine approved to treat people with haemophilia A with inhibitors binds to Factor IXa and Factor X, mimicking the role that factor VIII plays in the blood-clotting cascade, particularly the intrinsic activation of platelets (see graphic, p. 16).

Results from late-stage pivotal studies show that Hemlibra reduced bleeding rates significantly. Lead investigators stressed that five deaths that occurred in clinical testing were not attributable to the bispecific antibody. In May, however, after 600 patients had been treated with the factor VIII alternative, Roche announced the first patient-terminated Hemlibra therapy after the subject formed anti­bodies against emicizumab (see interview, p. 17). Circumventing factor VIII administration therefore appears to not necessarily be a long-term solution to the problem of inhibitor formation. Despite that outlook, analysts predict peak sales of US$4bn for Hemlibra – even before Roche applied to extend the label significantly through an FDA-accepted Supplemental Biologics License Application (sBLA) in June. Data from a subgroup of the company’s Haven 3 study suggest that Hemlibra could additionally outperform current plasma-derived or recombinantly produced factor VIII

Trianni Mouse Antibodies are a Match for Humans The Trianni MouseTM platform is the only transgenic antibody discovery platform ever developed that offers the entirety of human antibody variable gene diversity in a single organism.

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European Biotechnology | Summer Edition | Vol. 17 | 2018

Amino Acid position

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

Exceptional Human Antibody Discovery 12-16_EB_Summer_2018_hemophilia_tg.indd 15

14.06.2018 13:21:57 Uhr

HAematology

European Biotechnology | Summer Edition | Vol. 17 | 2018

of Hemlibra in preventing anti-antibodies have yet to be proven, gene therapies are currently gaining momentum in the public eye, even though all are only in early development stages.

Haemostasis Extrinsic Activation on TF-bearing cells TF + VIIa

Boost for gene therapies

Xa+ + Va

Intrinsic Activation on platelets

Thrombin

Platelet Aggregation XIa VIIIa + IXa Xa + Va PROPAGATION

When an injury occurs, platelets are initially attracted and bind to collagen at the surface of the damaged blood vessel wall. At the same time, extrinsic (by tissue factor = TF on cells) and intrinsic coagulation pathways (by thrombin) are activated. Activation begins when tissue factor (TF) is exposed at the surface of the vessel wall. It binds factor VIIa, leading to activation of factor Xa – a molecule that links extrinsic and intrinsic coagulation pathways. This forms a small amount of thrombin. Activation of the intrinsic coagulation cascade ends in the formation of a Xa/Va complex that activates thrombin, leading to the so-called ‘thrombin burst’. Thrombin attracts more platelets and activates fibrin, which forms strands that stabilise the growing blood clot.

L

Thrombin

Fibrin

Blood Fibrin

Microparticles Thrombin Platelets

Endothelium TF

TF

TF

TF

TF

VIIa

TF

TF

TF

TF

TF

TF

Initiation

Propagation

Stabilisation

Platelets bind to collagen

Recruitment of platelets to growing thrombus

Platelet-platelet interaction

Amplification of the coagulation cascade

Fibrin deposition

Tissue

TF-dependent initiation of coagulation

medicines by reducing bleeds more effectively than the current standard strategy for non-inhibitor forming haemophilia A patients. Based on a subgroup analysis of its haemophilia study population of 152 subjects, Roche announced that Hemlibra demonstrated a statistically significant reduction of 68% in treated bleeds after switching from factor VIII products to Hemlibra. That makes it the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the standard of care.

Competitors appear concerned Roche’s antibody could put pressure on

12-16_EB_Summer_2018_hemophilia_tg.indd 16

TF

their factor VIII products. Even before its board accepted Takeda’s take­over bid, Shire filed an injunction against Roche, claiming the Swiss drug­maker had spread an “inaccurate and misleading characterisation of the serious adverse events that occurred in the HAVEN 1 [study]” and had also “disparaged” the safety of Shire’s own by­passing agent FEIBA (factor VIII inhibitor bypassing activity). It contains pro­enzymes from the prothrombin complex factors, prothrombin, FVII, FIX and FX, but only very small amounts of their activation products, except FVIIa. As real-world benefits

At the May meeting of the board from the Alliance for Regenerative Medicine, FDA Commissioner Scott Gottlieb announced that the agency plans to accelerate market approval for haemophilia A gene therapies. The FDA wants to approve products based on the levels of factor VIII that patients produce after treatment, as opposed to counting numbers of retrospective bleeds. Within that framework, some US companies have generated interesting results In a Phase I/II study, BioMarin Pharmaceutical found hints that a dose of 6x1013 vg/kg of its AAV-delivered gene therapy valoctocogene roxaparvovec (BMN270) raised factor VIII levels to 59% after 24 months of treatment. Mean factor VIII usage was reduced by 96% through a single injection of the gene therapy. Enrolment for the ongoing pivotal GENEr8-1 Phase III trial on 130 patients will be complete next year.

Pfizer and Sangamo Biosciences, which raised US$200m in April, are also in Phase I/II testing of the AAV-delivered factor VIII gene therapy SB-525.

And Shire/Takeda have an AAV8-based gene therapy in Phase I testing that was renamed from BAX 888 to SHP654, following the 2016 Baxalta takeover. Last but not least, Dutch UniQure N.V. also has a gene therapy in the pipeline.

Gene therapies have potential drawbacks, among them the risk of developing antibodies to the viral vectors used to deliver the genetic material to cells.

According to Bioverativ, there’s still a long way to go in establishing safety, efficacy and durability in the field, so recombinant factor VIII products will certainly play a leading role for many years to come. After all, people with haemophilia A like Michael tend to be highly averse to risk.

L t.gabrielczyk@biocom.eu

Pictures: Roche AG ((left), AHA, (above): from: Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1687-1693

16

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Interview

17

Determined to reduce the risk of bleeds Hemlibra Analysts say Roche’s bispecific antibody Hemlibra will rock the US$15bn haemophilia

A market, given that it may circumvent therapy resistance that affects the 30% of patients who form antibodies against recombinant factor VIII products. European Biotechnology spoke with Dr. Gallia Levy, Associate Group Medical Director at Roche, who led clinical development of Hemlibra.

EuroBiotech_Who developed the Hemlibra concept?

Levy_Hemlibra was discovered by Chugai

Pharmaceutical Co., Ltd. and is being codeveloped by Chugai, Roche and Genentech. Hemlibra is the first new prophylactic medicine in over 20 years to treat people with haemophilia A with inhibitors to factor VIII. It’s a bispecific factor IXa- and factor X-directed antibody designed to bring together factor IXa and factor X, which activate the natural coagulation cascade and restore the blood clotting process for people with haemophilia A. Hemlibra resulted from the persistence of our Chugai scientists to screen more than 40,000 monoclonal antibodies over ten years.

EuroBiotech_How many haemophilia A patients resistant to factor VIII prophylaxis may be treated with this new treatment option?

Levy_Nearly one in three people with se-

Pictures: Pictures: Genentech/ VINCE TARRY STUDIOS

vere haemophilia A can develop inhibitors to factor VIII replacement therapies, putting them at greater risk for life-threatening bleeds or repeated bleeds that can cause long-term joint damage. In addition, people with inhibitors have a 70% increased risk of death compared to those without inhibitors.

EuroBiotech_What is the major benefit of Hemlibra for patients with haemophilia A compared to factor VIII prophylaxis? Could you please summarise the clinical results that led to FDA and EMA approval of Hemlibra?

Levy_Hemlibra is as a once-weekly sub-

cutaneous injection. In 2017, the US FDA

17-18_EB_Summer_2018_Interview_Levy_Hemlibra_tg.indd 17

Gallia Levy, PhD, Associate Group Medical Director at Roche is the Global Development Team Leader, Hemlibra. Prior to leading the global development program for Hemlibra, Gallia Levy held a number of positions in early and late stage drug development. Following her MD and PhD at the University of Michigan, Dr. Levy practiced internal medicine at Stanford University and pursued a hematology fellowship at the University of California. She is board-certified in hematology.

approved Hemlibra for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with haemophilia A with factor VIII inhibitors, and earlier this year, the Euro-

pean Commission approved Hemlibra for people with haemophilia A with inhibitors. The approvals were based on pivotal clinical studies in people with haemophilia A with factor VIII inhibitors: ›› In the phase III HAVEN 1 study, people 12 years or older who received Hemlibra prophylaxis had a statistically significant reduction in treated bleeds of 87% compared to those who received no prophylaxis. In a first-of-its-kind intra-patient analysis, Hemlibra prophylaxis resulted in a statistically significant reduction in treated bleeds of 79% compared to previous treatment with bypassing agent prophylaxis for which data were collected in a non-interventional study prior to enrolment into the pivotal study. ›› Interim results from the pivotal HAVEN 2 study in children 12 years or younger showed that 87% of children who received Hemlibra prophylaxis experienced zero treated bleeds. In an intrapatient analysis of 13 children who had participated in the non-interventional study, Hemlibra prophylaxis resulted in a 99% reduction in treated bleeds compared to previous treatment with a BPA either as prophylaxis (n=12) or ondemand (n=1). ›› In addition, the US FDA also granted Breakthrough Designation (BTD) for Hemlibra in haemophilia A without inhibitors in April 2018. This additional designation is based on data from the phase III HAVEN 3 study in people 12 years or older with haemophilia A without factor VIII inhibitors. Hemlibra was the first medicine to show su-

14.06.2018 13:24:48 Uhr

18

Interview

perior efficacy compared to prior factor VIII prophylaxis; this was done as an in an intra-patient comparison in patients who had previously participated in the non-interventional study. These new data are not yet covered in the market authorisation but have been submitted to health authorities. ›› Roche also reported positive interim results from the phase III HAVEN 4 study evaluating Hemlibra prophylaxis dosed once every four weeks in adults and adolescents 12 years of age or older with haemophilia A with and without inhibitors to factor VIII. EuroBiotech_Did you observe any adverse effects during treatment with Hemlibra?

Levy_In the clinical studies supporting the

the HAVEN 2 study, the most common AEs, occurring in 10% or more of people treated with Hemlibra in pooled studies, were injection site reactions, headache and joint pain, so-called arthralgia.

EuroBiotech_What’s the current interpretation of the five patient deaths that occurred in course of Hemlibra treatment?

Levy_For all five, the treating physician or

investigator’s assessment was that the cause of death was unrelated to Hemlibra. Three of these patients had been participating in a compassionate use programme, one had participated in a clinical trial, and one was taking Hemlibra through an expanded access programme, which allows patients who are not participating in a clinical trial to have access to investigational medicines prior to approval. We were deeply saddened to learn about these deaths and take all reports of death and safety events very seriously.

For each report, we followed our safety assessment and reporting processes to ensure prompt evaluation of the event and continued broader patient safety.

EuroBiotech_What percentage of patients formed antibodies against Hemlibra in the clinical trials you conducted?

Levy_We recently learned that a patient in

our phase III HAVEN 2 clinical trial developed an anti-drug antibody to Hemlibra

that led to reduced efficacy. As with all therapeutic proteins, there is a potential for the development of anti-drug antibodies with Hemlibra, as indicated on the US and EU Hemlibra product labels. The patient and his family have decided to discontinue treatment with Hemlibra, and he will resume treatment with his previous medicine. To date, more than 600 people with haemophilia A have been treated with Hemlibra worldwide, including in clinical trials. This is the first confirmed report of a detectable anti-drug antibody that has impacted the efficacy of Hemlibra in a person with haemophilia A. We continue to monitor for the development of anti-drug antibodies to Hemlibra in ongoing studies globally.The development of anti-drug antibodies to Hemlibra is distinct from the development of inhibitors to factor VIII. Anti-drug antibodies to Hemlibra may affect whether the medicine works, but they do not change the severity of the underlying disorder. On the other hand, for the nearly one in five people with haemophilia A who develop inhibitors to factor VIII, the inhibitors not only affect the efficacy of factor VIII replacement therapies, but they can also affect any natural factor VIII in the body. Inhibitors to factor VIII put people with haemophilia A at greater risk for life-threatening bleeds or repeated bleeds that can cause long-term joint damage.

L t.gabrielczyk@biocom.eu

Pictures: xxx

US and EU approvals in people with haemophilia A with inhibitors to factor VIII, the most common adverse events from pooled clinical studies, occurring in 10% or more of people treated with Hemlibra, were injection site reactions and headache. In the HAVEN 1 study, three people experienced thrombotic microangiopathy (TMA) events and two people experienced serious thrombotic events when on average, a cumulative amount of more than 100 U/kg/24 hours of activated prothrombin complex concentrate was administered for 24 hours or more while receiving Hemlibra prophylaxis. In

European Biotechnology | Summer Edition | Vol. 17 | 2018

17-18_EB_Summer_2018_Interview_Levy_Hemlibra_tg.indd 18

15.06.2018 11:25:24 Uhr

Update on clinical trials Diabetic retinopathy/AMD

ˆ

VEGF blocker Eylea (aflibercept), which is co-developed in ophtalmological indications by Bayer AG and Regeneron Pharmaceuticals Inc under a 2006 deal, has met the 24-week primary endpoint of the pivotal Panorama Phase III trial. The fusion protein, comprised of extracellular VEGF-receptor 1 and 2-fragments with the Fc portion of IgG1, improved the Diabetic Retinopathy Severity Scale (DRSS) in 58% of patients with non-proliferative diabetic retinopathy without diabetic macular edema vs placebo (6%) with four to five injections on average.

This year, after the second read-out at 52 weeks of treatment, Regeneron plans to apply to the FDA for label extension of Eylea. The VEGF blocker is FDA-approved for wet age-related macular degeneration and diabetic macular edema in patients with diabetic retinopathy or retinal vein occlusion. Bayer holds the ex-US commercialisation rights.

In an investigator-driven Phase I trial at University College London, a patch of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells improved visual acuity in two patients with severe wet age-related macular degeneration. The patch improved best corrected visual acuity (BCVA) at 12 months by 29 letters in the first patient and by 21 letters in the second patient. It also improved the patients’ reading speed to 82.8 and 47.8 words per minute, respectively, from baseline reading speeds of 1.7 and 0 words per minute. Pfizer Inc returned the development rights of PF05206388 due to “strategic commercial reasons“ but its originators at University College London plan to restart clinical development soon.

In April, Belgian ThromboGenics BV came up with initial data from a Phase I/ II study evaluating its anti-PIGF antibody THR-317 for Diabetic Macular Edema (DME). According to the company, 30% of 40 anti-VEGF treatment-naĂŻve patients

19-21_EB_Summer_2018_Trial_tg.indd 19

had a 15-letters gain in Best Corrected Visual Acuity (BVCA) after three monthly intravitreal injections with an 8mg dose. No dose-limiting toxicities or relevant safety events were reported at either dose level. Based on these results, ThromboGenics said it plans to initiate an additional study by Q2 2018 in which THR-317 will be combined with an antiVEGF antibody.

GenSight Biologics SA gene therapy for Leber’s hereditary optic neuropathy GS010 (rAAV2/2-ND4) missed the primary endpoint of improvement in best corrected visual acuity (BCVA) in the Phase III REVERSE study on 37 LHON patients.

NSCLC

ˆ

AstraZeneca plc’s PD-L1 checkpoint inhibitor durvalumab (Imfinzi) has met the second endpoint in the pivotal PACIFIC Phase III study in patients with locally spreading non-resectable non-small cell lung cancer (NSCLC). The drug met the overall survival improvement endpoint vs placebo at a planned interim analysis, the company announced without revealing any details. In May 2017, the antibody met an 11.2 months benefit in progression-free survival vs placebo, the first primary endpoint of PACIFIC. German Mologen AG­’s TLR9 agonist lefitolimod (MGN1703) missed the Phase II IMPULSE trial endpoint of improvement in overall survival in patients with small cell lung cancer (SCLC). The addition of lefitolimod to standard maintenance chemotherapy didn’t have a relevant OS effect on 103 chemotherapy responders enrolled in the trial. In patients with few activated B cells, and in COPD patients the treatment, it did not have a quantified effect.

At the end of May, Roche AG announced that atezolimumab plus chemotherapy met its co-primary endpoints of overall survival (OS) and progression-free survival (PFS) as first-line treatment for

OPIS INNOVATION.

European Biotechnology | Summer Edition | Vol. 17 | 2018

14.06.2018 13:26:23 Uhr

20

Regulatory Affairs

European Biotechnology | Summer Edition | Vol. 17 | 2018

News Early end

Milky Way Human milk oligosaccharide producer Jennewein Biotechnologie GmbH has kicked off a EU food ingredient registration study of an infant formula that contains five human milk oligosaccharides (HMOs) at the concentrations naturally found in human breast milk. The company plans to compare the development of the gut microbiome in infants fed on formula with and without HMOs to investigate the prebiotic effects of the formulation.

FDA knocks down CRISPR CRISPR Therapeutics AG. In late May, the FDA placed a clinical hold on the IND for a Phase I/II trial of CrispR Therapeutics’s CTX001 to treat sickle cell disease. The ex-vivo gene therapy, which adds a gene for fetal hemoglobin to hemapoetic stem cells to prevent blood transfusions required to correct oxygene deprivation of the blood of sickle cell carriers, is being co-developed under an 2015 agreement with Vertex Pharmaceuticals. A European Phase I/II trial of CTX001 is ready to be started in the second half of 2018.

19-21_EB_Summer_2018_Trial_tg.indd 20

Roche’s PD-L1 blocker Tecentriq met endpoints in three Phase III NSCLC studies.

stage IV nonsquamous non-small-cell lung cancer (NSCLC). Roche enrolled 724 patients and compared a Tecentriq plus carboplatin or Abraxane nab-paclitaxel combo with chemo-monotherapy (carboplatin and Abraxane alone) in the Phase III IMpower130 study. Roche’s US arm Genentech said details of the study will be announced at an upcoming scientific meeting. Experts expect them to be reported at ESMO in mid-October. In April, Genentech’s competitor Merck & Co. detailed data from its Phase III KEYNOTE-189 trial at AACR. The company’s PD-1 blocker pembrolizumab (Keytruda) plus chemotherapy (Alimta pemetrexed and cisplatin or carboplatin) led to a median progression-free survival of 8.8 months vs 4.9 months for chemotherapy alone. Median overall survival was not yet reached after follow-up for 10.5 months; for chemo-monotherapy it was 11.3 months. IMpower-130 is the third Phase III trial of Roche to show a survival benefit to initial treatment with Tecentriq-based combinations in NSCLC (see graphic). In March, Roche’s IMpower150 study met the co-primary OS endpoint at interim analysis. Furthermore, Roche’s IMpower131 study met the co-primary PFS endpoint that month.

Multiple melanoma

Following reports of an increase in mortality in a study that combined Genmab A/S’s anti-CD38 daratumumab with a PD-L1 blocker, Genmab’s partner, Janssen Biotech Inc, has ended a study combining daratumumab with its PD1 blocker JNJ-63723283 in multiple myeloma.

In an interim review of a Phase Ib/II

study of daratumumab plus Roche’s anti-PDL1 antibody atezolizumab (CALLISTO/LUC2001) in patients with previously treated non-small-cell lung cancer (NSCLC), a Data Monitoring Committee (DMC) noted a numerical increase in mortality-related events in the combination arm over atezolimumab monotherapy. Furthermore, the combo showed no efficacy benefit vs atezolimumab monotherapy. Based on these results, Janssen decided to terminate a Phase I study (MMY2036), in which daratumumab was tested in combination with Janssen’s PD1 blocker (JNJ-63723283) in patients with multiple myeloma.

Pancreatic cancer

Targovax ASA reported two-year overall survival figures in pancreatic cancer from its completed open-label Phase I/ II ESPAC4 trial in May. The cancer-neoantigen-targeting cancer immunotherapy TG01 significantly prolonged two-year overall survival of patients with resected pancreatic cancer vs standard therapy.

Median overall survival was 33.4 months vs 27.6 months. In 32 patients with resected pancreatic cancer, the survival benefit of TG01 plus chemotherapy was about six months vs standard gemcitabine chemotherapy. For the first 19 patient cohort – who received TG01 injections before, during, and after adjuvant chemotherapy treatment – Targovax reported a survival rate of 68% and median overall survival of 33.1 months. For the second cohort of 13 patients – who received a reduced dose of TG01 injections before and after gemcitabine treatment – the two-year survival rate was even higher (77%, 10/13 pa-

Picture: © fotolia/RAJCREATIONZS

ADC Therapeutics SAS has terminated development of its Her-2targetting antibody-drug conjugate (ADC) ADCT-502 following analysis of Phase I data of patients with advanced solid tumors with HER2 expression. The company said ADCT502 “did not achieve the necessary efficacy at tolerated doses required for patient benefit.”

14.06.2018 13:26:30 Uhr

European Biotechnology | Summer Edition | Vol. 17 | 2018

tients) than in the first cohort. However, In June Targovax said it will terminate development of TG01 for this indication and instead prioritise development of its RAS neoantigen-targeting cancer vaccine TG02 in colorectal cancer. The update to its clinical development strategy came after data presented at an ASCO meeting indicated that Folfirinox chemotherapy improved median OS up to two years compared to gemcitabine and capecitabine in patients with resected pancreas cancer. The company said that the the new Folfirinox median survival benchmark of close to five years means that a combination trial is not practically feasible for Targovax.

Colorectal cancer

In May, Roche AG and Exelixis Inc missed the primary endpoint of improving overall survival in a Phase III trial with their drug combo atezolizumab/ cobimetinib vs the multikinase blocker regorafenib (Bayer AG) in 363 patients with advanced or metastatic colorectal cancer. In April, the companies temporarily halted a Phase II trial in patients with metastatic colorectal cancer after four deaths had occurred, including a case of treatment-related cardiogenic shock. Tecentric (atezolizumab) is a PD-L1 checkpoint inhibitor developed

by Roche’s US arm Genentech. Cotelic (cobimetinib) is a MEK inhibitor developed by Exelixis.

In mid-May, Cosmo Pharmaceuticals NV (Dublin) received a Complete Response Letter from the FDA on its NDA for its visualisation aid candidate Methylene Blue MMX to increase detection of lesions in the colon. Though Cosmo presented clinical significance in a Phase III level, the FDA said the data were not robust enough to show a benefit. The agency recommended conducting a second Phase III study that would provide additional data required for market approval.

ALS

At the end of May, Dutch Treeway NV (Rotterdam) reported promising Phase I results for its new formulation of edavarone, TW001, designed to treat amyo-

19-21_EB_Summer_2018_Trial_tg.indd 21

trophic lateral sclerosis (ALS). The study compared the bioavailability of orally administered TW001 to Radicavaâ, an FDA-approved, intravenous formulation of edaravoneto to treat ALS. TW001 showed good bioavailability, as well as no safety concerns. Treeway said it has initiated the upscaling program and preparations for a pivotal Phase III study.

Edaravone is a neuroprotective agent that reduces oxidative stress, a key contributor to neuronal death in ALS. Previous clinical studies suggest that edavarone can slow down disease progression in ALS patients by one-third through its neuroprotective properties.

Atopic Dermatitis

Sanofi’s and Regeneron Pharmaceuticals’s IL4a/IL13-targeting antibody, dupimab, has met the primary endpoint of the pivotal Phase III trial in adolescents suffering from moderate-to-severe atopic dermatitis. Duplimab monotherapy significantly improved overall disease severity at 16 weeks. Twenty-four percent of patients who received weight-based dosing of Duplixent ® every two weeks (200 mg or 300 mg) and 18% of patients who received a fixed dose of duplimab every four weeks (300 mg) achieved the primary endpoint – clear or almost clear skin vs 2% with placebo. Furthermore, 41.5% of patients who received duplima every two weeks and 38% of patients who received duplima every four weeks achieved 75% or greater skin improvement (EASI-75) compared to 8% with placebo. Also, there was a 66% improvement in the duplimab every two weeks group and 65% improvement in the duplimab every four weeks group in average percent change from baseline in EASI score compared with a 24% improvement in the placebo group. Finally, there was a 48% improvement in the duplimab every two weeks group and 45.5% improvement in the duplimab every four weeks group in average percent change from baseline in the pruritus numerical rating scale (NRS) compared with a 19% improvement in the placebo group. Duplimab’s safety profile was consistent with that seen in adults.

L

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14.06.2018 13:26:36 Uhr

22

Interview

European Biotechnology | Summer Edition | Vol. 17 | 2018

Playing the game of high-end technologies Novartis At this year’s Swiss Biotech Day, Vas Narasimhan, the newly appointed CEO of Swiss

pharma giant Novartis, introduced himself to the Swiss biotech industry with a stimulating talk.

He wants to make Novartis an agile company rapidly adapting to changing conditions, he said in Basel. Talking to EuroBiotech, Narasimhan went into more detail and also corrected a common misconception about his office.

EuroBiotech_Everyone seems to be excited about you taking over the helm of Novartis. Do you already feel the weight of the expectations?

Vasant Narasimhan_It’s a question many

people have asked me. I think it shows there’s a lot of aspirations people have.

People want to see something more from companies like ours – across all the dimensions, be it scientific innovations or how we behave as a company and I as a leader. We will always do our best to reach them, although we of course also may fall short from time to time.

EuroBiotech_You earned a medical degree from Harvard University and in the past you’ve been working regularly in Africa on different healthcare problems.

Do you think you can keep up with the tradition as a CEO? Narasimhan_The way of engaging is dif-

ferent now. I’ve been in Africa this year to visit the Novartis Foundation in Ghana and the Novartis Access to Malaria Medicine programme in Kenya and South Africa. I’m not going there as a village public health worker like in the past; I’m trying to address the problems on a bigger scale. My passion for those issues has not changed. My goal is to create a momentum in the pharma industry to combat malaria, leprosy, and other diseases, with more energy than before.

22-23_EB_Summer_2018_Interview_Narasimhan_ml.indd 22

Vasant Narasimhan A US native, Narasimhan was appointed Chief Executive Officer of Novartis in February 2018. Previously, he was Global Head of Drug Development and Chief Medical Officer for the Swiss pharma corporation. Earlier on, the trained physician served as the company’s Global Head of Development.

Before joining Novartis in 2005, he worked at McKinsey & Company.

EuroBiotech_There’s a lot of buzz around the spaceship-like nature of your office, aka the “control tower.”.What is so unique about the Nerve software system,

about the spaceship part. I’m sitting in an open-space office and Nerve is not running on my desk. Nerve is our control centre for all of our development projects.

We were inspired by, for instance, Boeing. This company is able to monitor all of their engines on all of their planes around the world in real-time to analyse their data to understand performance. What we did over two years is that we integrated eleven development systems we have into a data layer that allows us to do machine learning. The outcome is that we can now predict how a clinical trial is getting operationalised: Is it set up on time?

Is it enrolling on time? Is the quality good?

Are the budgets on time? The team can see those predictions so that they can adapt what they do ahead of time. This changes everything. Rather than waiting for a trial to not enroll in time we can predict that and act beforehand. The idea is to reduce our costs and increase quality and speed across all of our clinical trials.

In that command centre you can see all 500 clinical trials of Novartis at the same time and how they are performing. Experts estimate that by better use of technology in a clinical trial, 15% to 20% of costs and time can be saved. We hope to see savings in this order of magnitude also at Novartis.

Pictures: BIOCOM AG

and what do you hope you can leverage for Novartis and for the patients by implementing it?

Narasimhan_So there’s a misconception

13.06.2018 15:17:33 Uhr

European Biotechnology | Summer Edition | Vol. 17 | 2018

EuroBiotech_Where do you source the digital expertise and what kind of startups are interesting for Novartis?

Narasimhan _ The architecture of the

Nerve platform was built in-house at Novartis. However, the algorithms were developed with McKinsey’s Quantum Black unit in the UK. We struck two deals in the first quarter. One is with a company called Pear Thera­peutics. It develops an app-based and FDA-labelled therapeutic.

It’s a cognitive behavioural therapy for patients with addiction. So you basically treat the patient with the app. Compelling for us were their clinical trials where their app-based technology outperformed real drugs. The other deal we struck with a company called Science37.

It tries to bring the clinical trial to the patient’s home. To participate in a trial they don’t have to go to a trial site anymore.

Also here physicians and participants communicate via an app.

EuroBiotech_What kind of e -health products are interesting for Novartis?

Which ones are not?

Narasimhan_Our interest in the space is

primarily in labelled e-health solutions.

There could be reimbursement, there could be the ability to combine it with a drug. Our goal is not to move into consumer healthcare apps.

EuroBiotech_What is the essence of the Novartis legacy? And what do you think needs to be changed in the corporation?

Narasimhan _The company has an ex-

traordinary legacy. 250 years ago it was a dye-making company. Later, the focus shifted to chemicals, then to pharmaceuticals roughly 100 years ago. We’re one of three companies in the world that has licensed over one hundred novel medicines. In many therapeutic areas we led a revolution – in ophtamology, certain areas of oncology, immunology, and cardiovascular diseases. To continue that success story, we have to be outstanding in five dimensions. We have to transform our culture to be much more inspired, empowered, and open. This is also because we need to be an attractive em-

ployer to millenials. Number two is that we have to pivot even harder to really high-end, transformative innovation.

Thirdly, we have to be even more operationally excellent. Reimbursement pressure and other pricing issues will continue to increase. So we have to price our medicines reasonably. The fourth pillar is to really go big on data and digital. Some of our competition will come from tech companies in the future. So we will have to be prepared. Number five is the question: how do we return more to society across all dimensions? This includes how patients in need find access to our medicines, especially in poor countries fighting with seemingly insurmountable problems like HIV and malaria infections. All of these five goals will take time to reach.

But I feel confident that, guided by them, we will head into the right direction.

EuroBiotech_Novartis is building up a gene and cell therapy franchise with Kymriah and AV XS -10 1 as the most promi­nent therapies. Are you going to continue into this direc tion? What makes you so confident that this is a path that leads to commercial success, especially with most of the therapies being one-time curative treatments?

Narasimhan_If we come up with some-

thing that has high efficacy and a high cure rate; also high one-time payments are considered hugely cost-effective by payors. When you compare the costs to a chronic treatment that goes on for 20, 30, or even 50 years, it is much more attractive for the healthcare system to reimburse the one-time treatment. I think we can come up with solutions to make this business model very attractive. They key for us will be to keep innovating. After the market entry of a therapy, the incident patient population will be cured within a couple of years.

Then you should have the next therapy up in your sleeve. I’d rather be in the game of high-end technology because I believe that Novartis can continue to regularly churn out innovative therapies for new indications. I don’t feel worried about that at all.

L m.laqua@biocom.eu

CANDOR – Originator of LowCross-Buffer® – innovative solutions – highest quality standards – expert technical support for optimizing reliability of your immunoassays

CANDOR Bioscience GmbH

22-23_EB_Summer_2018_Interview_Narasimhan_ml.indd 23

13.06.2018 15:17:38 Uhr

24

Regulatory Affairs

European Biotechnology | Summer Edition | Vol. 17 | 2018

EMA anticipates Brexit Centralised Procedure Calls from the British Prime Minister Theresa May and the UK’s Biotech Industry Association (BIA) to keep the UK closely linked to the EMA’s decision processes, despite Brexit, have been unsuccessful. Though the MHRA currently assesses around a fifth of all EU medicines, the agency will lose its involvement in evaluating and monitoring medicines for the European Medicines Agency (EMA) in March 2019, notby 2020, the transition period proposed by May and the BIA. In mid-April, the EMA appointed new rapporteurs and co-rapporteurs for 370 centrally authorised products under post-marketing surveillance of the MHRA. The EMA said the MHRA could no longer engage in “centralised regulatory procedures” carried out by the CHMP, CVMP, PRAC, and CAT unless a later date for Brexit is agreed upon. The agency

communicated the new (co)-rapporteurships will become the marketing authorisation holders by the end of April.

www.ema.europa.eu

From London to Amsterdam

Another milestone concerning the relocation of the EMA was met in April. The EMA and the Netherlands finalised the text of the Seat Agreement, which describes how the agency, its bodies, and its employees will be treated by the Dutch Government once they start operating in the Netherlands. The EMA said the agreement was an important step in relocating the EMA from London to Amsterdam as a result of Brexit, as it ensures that EMA can function properly and independently in the Netherlands.

However, the EMA‘s attempt to make the transition from London to Amsterdam as smooth as possible might be ham-

pered by delays and rent increases. Most recently, Germany’s Süddeutsche Zeitung reported that the completion of the new EMA building will be delayed extending temporary housing of the staff. In April, Nature added further concerns, reporting the Netherlands “demanded a 34% increase” in the rent for 2019, which was fixed at €320 per square metre in the Dutch bid. The EMA rejected the claim but has also to manage legal actions started by Milan’s Major, who don’t want to accept that the final decision over the EMA’s headquarters was drawn by lot between Amsterdam and Milan.

L

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

Drug name

Indication

Company

Status

› Rubraca (rucaparib)

Third line treatment of relapsed ovarian cancer

Clovis Oncology UK Ltd

MA rec.

› Juluca (dolutegravir/rilpivirine)

Treatment of HIV infection

ViiV Healthcare UK Ltd

MA rec.

› Kanjinti (biosimilar trastuzumab)

Treatment of breast and gastric cancer

Amgen Europe B.V.

MA rec.

› Zessly (biosimilar infliximab)

Treatment of rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and psoriasis

Sandoz GmbH

MA rec.

› Dexxience (betrixaban)

Prevention of venous thromboembolism

Portola Pharma UK Ltd

MA refusal

› Eladynos (abaloparatide)

Treatment of osteoporosis

Radius International Ltd

MA refusal

› Aplidin (plitidepsin)

Treatment of multiple myeloma

PharmaMar

MA refusal

› Masitinib

Treatment of amyotrophic lateral sclerosis

AB Science Ltd

MA reexamin.

› Zydelig (idelalisib)

Treatment of chronic lymphocytic leukaemia (CLL)

Gilead Sciences Int. Ltd

MA withdrawn

› Biktarvy (fixed dose combination of bictegravir, emtricitabine and tenofovir alafenamide)

Treatment of adults with HIV-1 infection without evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir

Gilead Sciences Int. Ltd

MA rec.

› Aimovig (erenumab)

Treatment of migraine

Amgen Europe B.V.

MA rec.

› Rxulti (brexpiprazole)

Treatment of schizophrenia

Otsuka Pharmaceutical Co. Ltd

MA rec.

› AAV vector serotype 8 containing codon-optimised F8 cDNA encoding the B-domain deleted human coagulation factor VIII

Treatment of haemophilia A

Baxalta Innovations GmbH

OD status granted

› AAV vector serotype 9 containing the human CLN1 gene

Treatment of neuronal ceroid lipofuscinosis

Abeona Therapeutics Europe SL

OD status granted

24_EB_Summer_2018_EMA_tg.indd 24

13.06.2018 15:17:54 Uhr

financial markets

European Biotechnology | Summer Edition | Vol. 17 | 2018

25

Skilful asset swapping in the time of big data Thomas SchieSSle Independent investment analyst, Managing Director EQUI.TS GmbH_ Big

data analytics is poised to change the way business is done in the life sciences. A string of recent M&A transactions illustrate this trend.

Recently, multi-billion dollar merger and acquisition campaigns have caused a stir worldwide. For example, Sanofi bought antibody specialists Ablynx, and Gilead acquired cell therapy developer Kite Pharma (competitors of Bluebird Inc. and Medigene AG) to enter the field of cancer therapies with genetically engineered cells. Novartis responded with the expansion of its own gene therapy business and swallowed Avexis for US8.7bn.

The new Novartis CEO, Vas Narasimhan, justified his spending spree, calling the acquisition an “extraordinary opportunity.”

The deal will also benefit in-town rival Roche, who owns a 4.2% stake in Avexis and should therefore expect close to US$340m coming in. Among other things, the money is expected to fund the acqui-

sition of the private US company Viewics. With the Californian’s analytical tools and cloud-based IT solutions, Roche plans to amke more data-driven, and hence better, decisions in its labs, plants, and offices. Obviously, without big data, there will be neither drug development nor diagnostics in the future. This is also smooth sailing for recently listed Roche competitor Siemens Healthineers AG. Developing its “Digital Ecosystem Platform,” Viewics was an important business partner for Siemens – at least in the past.

Less disruptive, but more continuously changing is the over-the-counter (OTC) landscape. This is mainly due to the nature of the business model. To leverage value, you have to master branding and complexity – both fields where big data expertise

comes in handy. For Bayer, the division was – and still is – so important that former CEO Marijn Dekkers spent more than €10bn in 2014 to purchase the OTC medicines from US competitor Merck & Co. Under OTC manager Jörg Reinhard Bayer rose to global No. 2. After leaving Bayer, Reinhard made his mark at Novartis. Following a trade deal with GSK under his aegis, Reinhard created a joint venture that is clearly the No. 1 in the OTC industry. Fast forward 2018: Novartis boss Narasimhan thinks now is the time to sell the 36.5% stake in the JV for US$13bn to partner GSK. Also leaving the OTC business is German Merck KGaA which –after negotiating with Nestlé and Reckitt Benckiser – sold its unit in the end for €3.4bn in cash to Procter & Gamble.

Without a doubt, the US consumer goods giant has more branding and marketing power than Merck, where the unit was deemed too small.

L

News from the floor ASIT Biotech SA Equity research company Edison started to cover Belgian allergy immunotherapy expert ASIT Biotech in May. With a price of €3.79 per share, Edison recommended buying the stock. Its price target: €7.3.

Picture: Equi.ts

Cellectis SA After Cellectis said its

third off-the-shelf UCART candidate, UCART22, in acute B-cell lymphoblastic leukaemia (B-ALL), is on track to Phase I testing, Oppenheimer analyst

25_EB_Summer_2018_market-sentiment_ml.indd 25

Hartaj Singh maintained a “Buy” rating on Cellectis in mid-June and set a price target of €37.45. The company’s shares traded at €24.86.

Horizon Discovery Group plc Following a hostile takeover bid by British Abcam plc in May, Cowen analyst Doug Schenkel said he considered the offer of 181 pence per share (total GBP270m) as too low. But instead of upping the ante, Abcam withdrew its bid. Shares of Horizon were at 180 pence in June.

Novozymes Biopharma A/S Credit Suisse raised the Novozymes share price target to DKK350, saying the stock now has an “outperform” instead of a “neutral” rating. Novozymes traded for DKK330 in mid-June.

Roche AG The analysts of Bern-

stein Research have rated Roche with a “market perform” rating. The price target was set to CHF244.00. At a current price of CHF209.80, there is upside potential of 16.30%. 

14.06.2018 13:27:51 Uhr

26

financial markets

COMPANY

QUOTE

European Biotechnology | Summer Edition | Vol. 17 | 2018

M-Cap

52 weeks indicator low high

COMPANY

QUOTE

M-Cap

4D Pharma plc

1.58

100,000k

C4X Discovery Holdings plc

1.04

48,000k

4SC AG

5.00

160,000k

Cantargia AB

1.54

99,000k

A1M Pharma AS

0.38

3,000k

Carbios SAS

7.25

34,000k

AB Science SA

4.28

175,000k

Cassiopea SpA

31.16

310,000k

Cellectis SA

24.86

1,100,000k

Cellink AB

13.24

100,000k

7.39

330,000k

24.60

280,000k

AB-Biotics SA

3.20

40,000k

Abcam plc

14.20

2,900,000k

Abivax SA

6.65

66,000k

Celon Pharma SA

Abzena plc

0.21

45,000k

Celyad SA

Acarix AB

0.85

20,000k

Cerenis Therapeutics SA

1.94

37,000k

Active Biotech AB

0.24

38,000k

Circassia Pharmaceuticals plc

1.05

340,000k

Not afraid of vertigo Otology It’s been an exciting first half of the year for listed

French drug developer Sensorion. After identifying a new potential blood biomarker for noise-induced hearing loss, the outer hair cell protein prestin, the company successfully raised €8.65m from institutional investors through a capital increase in May. But the newsflow is not going to stop anytime soon. Still this year, data from a Phase II study in a severe form of vertigo, namely acute unilateral vestibulopathy, with Sensorion’s lead candidate SENS-111 (Seliforant) is expected. The molecule belongs to a new class of histamine type 4 receptor antagonists.

L

Co.don AG

6.52

120,000k

100.42

1,500,000k

Curetis AG

5.54

85,000k

Cytotools AG

8.48

19,000k

Cyxone AB

0.66

12,000k

DBV Technologies SA

36.14

1,100,000k

Cosmo Pharmaceuticals NV

Deinove SA

3.34

42,000k

Destiny Pharma plc

1.25

54,000k

Diamyd Medical AB

0.41

23,000k

88.95

5,000,000k

Diaxonhit Therapeutics SA

4.85

48,000k

Elanix Technologies AG

1.72

14,000k

e-Therapeutics plc

0.08

22,000k

Diasorin SpA

Ellen AB

0.03

5,400k

Enzymatica AB

0.38

28,000k

Epigenomics AG Erytech Pharma SA

2.51

75,000k

15.86

290,000k

Addex Therapeutics Ltd

2.55

73,000k

Esperite NV

ADL Bionatur Solutions SA

2.24

76,000k

Eurofins Scientific SE

Adocia SAS

18.80

130,000k

Evgen Pharma plc

0.31

23,000k

Advicenne SACA

12.07

97,000k

Evolva SA

0.22

170,000k

ALK-Abelló A/S

Evotec AG

14.89

2,200,000k

0.38

10,000k

424.20

7,500,000k

143.71

1,600,000k

Allergy Therapeutics plc

0.31

180,000k

Expres2ion Biotech Holding AB

0.77

9,500k

Alligator Bioscience AB

3.05

220,000k

Faron Pharmaceuticals Oy

1.33

39,000k

Annexin Pharmaceuticals AB

0.36

2,100k

Fermentalg SA

3.57

60,000k

Aqua Bio Technology ASA

0.62

4,200k

Fit Biotech Oy

0.00

1,500k

Argenx SE

85.80

2,800,000k

Formycon AG

36.90

340,000k

Arocell AB

0.68

27,000k

Galapagos NV

87.28

4,400,000k

Asit Biotech SA

3.79

62,000k

Genedrive plc

0.43

7,900k

Avacta Group plc

0.39

27,000k

Geneuro SA

5.94

87,000k

Avantium Holding NV

5.84

150,000k

Genfit SA

23.88

750,000k

Basilea Pharmaceutica AG

60.42

720,000k

Genmab A/S

128.61

7,900,000k

Bavarian Nordic A/S

26.72

860,000k

Genomed SA

5.52

7,600k

4.47

240,000k

Genomic Vision SA

1.22

7,200k

Bio-On SpA

42.00

800,000k

Genovis AB

0.38

23,000k

Biocartis NV

12.70

650,000k

Genoway SA

1.69

10,000k

5.58

260,000k

Gensight Biologics SA

3.33

81,000k

39.49

690,000k

Genkyotex SA

1.67

130,000k

Bioinvent International AB

0.19

69,000k

Genus plc

30.14

1,800,000k

Biomed-Lublin SA

0.28

18,000k

Global Bioenergies SA

16.00

72,000k

77.20

9,300,000k

Hansa Medical AB

22.11

840,000k

Bergenbio ASA

Biofrontera AG Biogaia AB

Biomérieux SA Biophytis

2.76

37,000k

Heidelberg Pharma AG

2.61

74,000k

Bioporto Diagnostics A/S

0.42

64,000k

Herantis Pharma Oyj

6.50

32,000k

Biosearch Life SA

1.25

74,000k

Hofseth Biocare ASA

0.20

47,000k

Biotec Pharmacon ASA

0.59

25,000k

Horizon Discovery Group plc

1.84

290,000k

31.58

170,000k

Hvivo plc

0.24

19,000k

0.91

17,000k

Hybrigenics SA

0.52

23,000k

Idorsia Ltd.

22.33

2,600,000k

0.68

34,000k

Bioventix plc Biovica International AB Bone Therapeutics SA

11.46

87,000k

Brain AG

21.10

390,000k

26-27_EB_Summer_2018_stock-list2_ml.indd 26

Immunicum AB

52 weeks indicator low high

13.06.2018 15:32:33 Uhr

financial markets

European Biotechnology | Summer Edition | Vol. 17 | 2018

COMPANY Immunodiagnostic Systems plc

QUOTE

M-Cap

52 weeks indicator low high

COMPANY

QUOTE

M-Cap

2.74

81,000k

Immunovia AB

16.45

280,000k

Plant Advanced Technologies SA

22.60

23,000k

Immupharma plc

0.26

37,000k

Polyphor AG

28.22

300,000k 180,000k

Physiomics plc

0.05

0.70

44,000k

Poxel SA

7.21

Infant Bacterial Therapeutics AB

17.68

200,000k

Premaitha Health plc

0.10

38,000k

Innate Pharma SA

5.54

300,000k

Probi AB

40.19

470,000k

Integragen SA

1.80

12,000k

Probiodrug AG

4.89

39,000k

Intervacc AB

0.45

17,000k

Promore Pharma AB

1.68

33,000k

Inventiva SA

7.76

170,000k

Proteome Sciences plc

0.04

12,000k

Isofol Medical AB

2.41

77,000k

Qiagen NV

31.00

7,050,000k

ISR Holding AB

0.69

13,000k

Quantum Genomics SAS

2.06

23,000k

Kancera AB

0.10

15,000k

Relief Therapeutics Holding AG

0.01

17,000k

Karo Pharma AB

2.96

490,000k

Reneuron Group plc

0.78

25,000k

Kiadis Pharma BV

10.40

210,000k

Salvarx Group plc

0.30

11,000k

6.94

58,000k

Saniona AB

3.59

84,000k

14.98

98,000k

Lysogene SA

2.12

26,000k

Mabion Ltd

27.59

380,000k

Sareum Holdings plc

0.01

26,000k

3.84

230,000k

Scancell Holdings plc

0.17

65,000k

MDxHealth SA Medical Prognosis Institute A/S

0.91

22,000k

Medigene AG

13.12

320,000k

Medivir AB

4.03

Mereo Biopharma Group plc

3.57

Santhera Pharmaceuticals AG

Selvita SA

13.56

220,000k

Sensorion SA

3.39

44,000k

98,000k

Shield Therapeutics plc

0.43

52,000k

250,000k

Silence Therapeutics plc

1.67

120,000k

Metabolic Explorer SA

2.21

51,000k

Simris Alg AB

0.86

9,000k

Midatech Pharma plc

0.33

20,000k

Skinbiotherapeutics plc

0.21

25,000k

Molecular Partners AG

28.90

580,000k

20.65

430,000k

Stallergenes Greer plc

Molecular Medicine SpA

0.49

230,000k

Summit Therapeutics plc

Mologen AG

0.92

35,000k

Morphosys AG

Swedish Orphan Biovitrum AB

2.21

180,000k

18.37

5,070,000k 72,000k

91.00

2,900,000k

Sygnis AG

1.43

Motif Bio plc

0.36

110,000k

Synairgen Research Ltd

0.16

15,000k

Nanobiotix SA

9.82

200,000k

Targovax ASA

1.58

89,000k

NEL ASA

0.31

310,000k

Theradiag SA

1.59

13,000k

Neol Biosolutions SA

0.25

2,300k

Theranexus SADIR

15.60

49,000k

Thrombogenics NV

5.91

230,000k

Tigenix NV

1.78

530,000k 150,000k

Neovacs SA

0.35

31,000k

Neuron Biopharma SA

0.30

4,700k

Neurosearch A/S

0.64

16,000k

Tissue Regenix Group plc

0.12

Neurovive Pharmaceutical AB

0.30

27,000k

Tiziana Life Sciences plc

0.62

68,000k

Newron Pharmaceuticals SpA

9.18

170,000k

Transgene SA

3.18

200,000k

Nicox SA

8.36

250,000k

Txcell SA

0.86

19,000k

Nordic Nanovector ASA

5.07

240,000k

Valirx plc

0.03

12,000k

44.05

13,000,000k

Valneva SE

3.84

300,000k

Novozymes Biopharma DK A/S Noxxon Pharma NV

2.18

6,300k

Vectura Group plc

0.95

640,000k

Nuevolution A/S

1.66

81,000k

Veloxis Pharmaceuticals A/S

0.12

210,000k

Oncimmune Holdings plc

1.44

89,000k

Vernalis plc

0.07

36,000k

Oncoarendi Therapeutics SA

7.05

94,000k

Verona Pharma plc

1.76

180,000k

Oncodesign Biotechnology SA

10.05

69,000k

Vita 34 AG

Oncopeptides AB

13.17

560,000k

Onxeo SA

1.31

66,000k

Xintela AB

Optibiotix Health plc

0.78

65,000k

Zealand Pharmaceuticals A/S

Orphazyme A/S

8.07

160,000k

Oryzon Genomics SA

2.80

95,000k

OSE Pharma SA

4.20

61,000k

Oxford Biodynamics plc

2.36

210,000k

Oxford Biomedica plc

11.21

740,000k

Paion AG

2.04

130,000k

PCI Biotech Holding ASA

5.18

130,000k

Pharma Mar SA

1.50

340,000k

Pharming Group NV

1.40

840,000k

Pharnext SA

7.26

78,000k

Photocure ASA

2.95

66,000k

26-27_EB_Summer_2018_stock-list2_ml.indd 27

Xbrane Biopharma AB

52 weeks indicator low high

3,900k

Index Pharm. Holding AB

Kuros Biosciences AG

27

15.00

63,000k

4.83

30,000k

0.31

9,300k

12.85

400,000k

All quotes are listed in euro. All data is provided without guarantee. The effective date is 11 June 2018.

These dedicated biotech companies are listed on European stock markets.

13.06.2018 15:18:52 Uhr

28

Finance

European Biotechnology | Summer Edition | Vol. 17 | 2018

“Biology is going to win” Industrial Biotech Bioeconomy has become a top priority for almost 50 nations

across the globe. At the Global Bioeconomy Summit, European Biotechnology met with Rob Carlson, Managing Director at Bioeconomy Capital, who wants to create monitoring mechanisms for bioengineered products to track the market dynamics and ROI of microbe-made, high-value chemicals.

stands its own bioeconomy very well, because the mechanisms to do so are broken or nonexistent. For example, the North American Industrial Classification System supposedly provides a code for every product and service in the US economy. These NAICS codes are used by the US government to keep track of the revenues and employment in many different industries. However, there is no code for biotechnology. Of course there are marketing reports and surveys, but these are often targeted at specific products. So what are the consequences? We have no exact idea about the size of the market and no ability to measure the return on government investment of R&D funds. That’s particularly striking for the bioeconomy, where many people are talking about potential benefits but have only very limited data about the risk and the cost. And here I mean economic activity that is at risk if policies do not support it or accidentally restrict it. We need to develop a better understanding of this industry, because it turns out that it is remarkably large.

EuroBiotech_In the end you published industry revenue data researched by yourself in a Nature Biotech paper...

Carlson_I went digging for the best infor-

mation available using many different sources. We at Bioeconomy Capital estimate that US revenues from engineered biological systems were the equivalent of more than 2% of GDP in 2012, or

28-29_EB_Summer_2018_Interview_Rob Carlson_tg.indd 28

greater than USD324bn, summed across bio­logics, crops, and industrial biotech.

We put all the data we collected online, freely available. By 2016, total US revenues climbed to at least $370bn. For context, this means that US biotechnology revenues are consistently larger than the global semiconductor industry.

While the US revenue for drugs and GM crops were both about USD115bn in 2016, the industrial portion was more than $140bn. The bioengineering/syn-

thetic biology market was estimated to be about USD2bn in 2015, and is forecasted to grow ten-fold by 2020, with a CAGR of 45%, according to BCC Market Research and Transparency Market Research. The rapid market maturation of the bioeconomy is an enormous investment opportunity. Biotechnology is a much larger portion of the economy than most people realize.

EuroBiotech_How large is it?

Carlson_Biological engineering is current-

ly still very immature when compared to well-developed disciplines such as electrical or aeronautical engineering. We think there is no obvious limit to how large the bioeconomy can become. Today, industrial biotech makes up USD80– 90bn of the $500bn US chemicals market. Those biochemicals are out-competing petrochemicals in both price and, for improved molecules, performance.

Given that exact copies of petroleumbased products can be produced in microorganisms that are minimally regulated, it is just a question of time, and investment, for such products to broadly replace petroleum-based products from the market.

Rob Carlson is the Managing Director of Bioeconomy Capital, which set up a bioeconomy fund for industrial biotech tool and process providers. Carlson is the inventor of “Carlson Curves” and originator of the first estimates of global biotech revenues. Carlson earned a doctorate in Physics from Princeton University in 1997.

EuroBiotech_Chemical production has been optimised over decades in highly integrated and efficient production networks. Why do you think that microbemade products could be more economical?

Carlson_We invest in companies such as

Arzeda and Zymergen that establish manufacturing systems in microbes engineered to produce chemicals using novel enzymatic pathways. These organisms

Pictures: German Bioeconomy Council

EuroBiotech_Dr. Carlson, for ten years you have been lobbying to include information about biobased products and services into the NAICS. Why? Carlson_There is no country that under-

15.06.2018 11:26:51 Uhr

Finance

European Biotechnology | Summer Edition | Vol. 17 | 2018

29

Emerging R&D Services | USD2bn Biopharma Ingredients | USD27bn Crops

Food & Feed Ingredients | USD16bn

>USD110bn Biofuels | USD6bn

Industrial

Biochemicals | USD88bn

>USD150bn

Biologics >USD150bn

Estimated 2016 US biotechnology and industrial biotechnology revenues.

make between thousands and millions of litres of beer in a brewery and run production economically. Processes that allow the manufacture of many different products just by swapping the production strain or feedstock. We identify and invest

in the picks and shovels that will accelerate this revolution. The future of chemical production looks a lot like a microbrewery that turns out a different kind of beer every week.

L t.gabrielczyk@biocom.eu

5

A liphatic polycarbonates (APC) – cyclic Cellulose Acetate Epoxies

4

E thylene propylene diene monomer rubber (EBDM) P olyamides (PA)

in million tonnes

can use different feedstocks in a process that resembles beer-brewing and is minimally regulated in the US, as are most processes that take place in a contained environment. The difference in cost is not trivial: The last new petrochemical production facility built in the world cost more than USD30bn, at least 100-fold more than a large brewery. Brewing is also far more scalable and flexible; you cannot build an economically-viable oil refinery today for less than about USD15bn. Even the maintenance on petrochemical facilities can run upwards of USD1bn per year on average, which by itself is far more than any fermentation facility. Given our newly demonstrated ability to brew chemicals like we brew beer, it’s pretty clear which one will succeed economically in the long term.

P oly(butylene adipate-co-terephthalate) (PBAT)

3

P olybutylene succinate (PBS) and copolymers

2

P olytrimethylene terephthalate (PTT) P olyethylene terephthalate (PET) P olyethylene furanoate (PEF)

1

P olyethylene (PE) P olyhydroxyalkanoates (PHA)

Pictures: nova institute (right), Bioeconomy Capital (above)

EuroBiotech_ A brewery for organisms whose pathways have been optimised using synthetic biology?

Carlson_The US places more emphasis on

regulating end-products than manufacturing methods. This favors biological products that are identical in structure to their petrochemical counterparts, because biology is increasingly the lower cost manufacturing route. We believe biology can outperform even optimised chemical processes, depending on several factors: We look for processes that are highly flexible and require low investment – you can

28-29_EB_Summer_2018_Interview_Rob Carlson_tg.indd 29

P olylactic acid (PLA)

0 2011

S tarch blends

2012

2013

2014

2015

2016

2017

2018

2019

2020

2021

2022

Cost curbs bio-based growth Nova Institute Growth in 17 bio-based building blocks (CAGR of 5-6%) will dominate growth in 15 bio-based polymers (CAGR 3-4%) from 2017–2022, according to a new market analysis from nova-Institute in Cologne, Germany (www.biobased.eu/reports). Overall, low crude oil prices challenge adoption of the 15 biobased polymers. With a CAGR of 10% by 2022, Europe has the highest growth of bio-based polymer capacities compared to other regions of the world.

L

14.06.2018 13:30:12 Uhr

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European Biotechnology | Summer Edition | Vol. 17 | 2018

GBS: Sustainable industry manufacture gets headwind Bioeconomy International collaboration is needed to sustain the growing world population

without collapsing the planet’s resources, biodiversity, and climate. A communique published at the end of the Global Bioeconomy Summit (GBS) outlines policy measures needed to create a biobased economy for all and to support technological advances in the area.

the anniversary of the GBS. Japan will become the fiftieth country next year, Yuhi Sakamoto, Deputy General of Secretary at Japan's Association of Bioindustries Executives (JABEX), told European Biotechnology at the meeting.

There are huge regional differences in how various nations pursue the shift to sustainable food, cosmetics, energy, chemicals, and industry production. Thus, international collaboration and best-practice policies are needed to meet the overall goal of fighting global threats, such as climate change, hunger,

German Research Minister Anja Karliczek announced investments into a renewed six-year bioeconomy research strategy and agenda that will make biobased production a top priority, at the opening of the Global Bioeconomy Summit before 800 high-ranking stakeholders.

30-32_EB_Summer_2018_Focus Bioeconomy_GBS_Iintro_tg.indd 30

loss of biodiversity, depletion of natural resources, and inequality (see interview p. 33). “Sustainable Bioeconomy for All,” a communique published at the end of the GBS, recommends international coordination on bioeconomy R&D, governance, and capacity-building. For most stakeholders, however, the bioeconomy also offers vast new business opportunities as consumers turn their choices to green solutions.

Resource-rich nations willing to participate Damages to our biosphere resulting from unsustainable resource use have become increasingly evident globally. “African species are disappearing at double the rate of the world average,” said Ameenah Gurib-Fakim, former President of Mauritius. “A climate change of 1.5° C will have a direct impact on Africa’s GDP,” she added. “The exponentional growth of energy consumption during the past seven decades is discharging the battery of biologically stored energies built up by our planet in 4.5 billion years of evolution,” warned John Schramski, engineer and ecologist from the University of Georgia. “We already see the first signs of instability in our biosphere. We must change our lifestyles and slow down,” he stressed. Author Ian Goldin, former policy advisor to Nelson Mandela and a globalisation expert, told European Biotechnology that the current economies of scale can’t lead to sustainability. “We can have both good and bad effects from connectivity

Picture: German Bioeconomy Council

More than 800 policy leaders, NGOs, and industry representatives, from more than 70 nations, met at the 2nd Global Bioeconomy Summit (GBS, 19–20 April 2018) in Berlin to discuss the challenges and opportunities in shifting from the current unsustainable industry production to a sustainable biobased economy. Since 2015, when the German Bioeconomy Council launched the world policy meeting on the bioeconomy, with support from the German Research Ministry, 49 nations have adopted national bioeconomy strategies, outlined in an study update published on

14.06.2018 13:33:01 Uhr

European Biotechnology | Summer Edition | Vol. 17 | 2018

and progress,” he said, and pointing to globalisation, “the choices we make increasingly touch others in the world and impact on our planet.”

While stakeholders such as Navi Radjou called for low-tech innovation – such as a 20 cent centrifuge or a fridge that runs without electricity – to be developed within a “frugal, concious bioeconomy,” most of the keynote speakers agreed that high-tech R&D will discover how to process natural resources more effectively and help establish circularity, improving global agriculture, industrial production, and health. However, eve-

rybody seemed to agree with Radjou’s conclusion: “We must create more value with less resources.”

Stakeholders from resource-rich tropical countries – such as Ecuador’s Enviroment Minister, Tarsicio Granizo, and Eduardo Trigo, Senior Bioeconomy Advisor to the Ministry of Agroindustry, Argentina – emphasized that establishing a bioeconomy will lead to economic growth in their countries. With an eye to benefit sharing, Ameenah Gurib-Fakim said, “We must merge the African traditional knowledge with technology to plant a tree together.”

focus

31

“Highly innovative (meta)genomics technologies and bioinformatics are a reality today” in enzyme optimisation for food, textile, and bio-based energy production, Thomas Videbaek, Executive Vice President and COO for Research, Innovation and Supply at Novozymes, told European Biotechnology (see interview below). Rob Carlson, Managing Director of Bioeconomy Capital, which invests in synthetic biology companies, said that microbial high-value product manufacturing platforms, which allow production of multiple products in low-investment brewery-like plants, will be rapidly

“Microbial game-changers” Novozymes How do novel technologies affect the world's largest

enzyme producer? At the GBS, European Biotechnology asked Thomas Videbaeck, PhD, COO and Executive VP Research, Innovation and Supply.

EuroBiotech_How does the new commitment by policymakers to accelerate the bio­economy affect your business?

Videbaeck_Novozymes has been an en-

Picture: Novo Nordisk

zyme producer for more than 60 years and bioeconomy is our core business. So we are not talking about the future but our current reality. However, it's correct that we have seen more interest in the area over the past two decades or so.

That's very helpful and we certainly see more understanding about what kind of solutions the bioeconomy can provide.

Look at the biofuel industry in the US: it caused a shift towards the bioeconomy, creating half a million jobs and significant reduction in CO2 emissions. The sugars from first and second generation biomass sources are already available now. We can convert them into biofuels and chemical building blocks.

EuroBiotech_ How long will it take for the chemical industry to embrace biobased plants to replace petrochemicallybased production networks, which have been optimised for several decades?

30-32_EB_Summer_2018_Focus Bioeconomy_GBS_Iintro_tg.indd 31

Videbaeck_I think an important factor is the cost. A new biobased process doesn't offer the same earnings and economy of scale as a petrochemical process that has been optimised over decades. But it has to be competitive. So it will be a long transition, but may be sped up, depending on political pressure. It could take decades, but it will happen. We already see molecules in the market that can replace petroleum-based products. For the sake of the next generation, the world needs to do things differently.

EuroBiotech_What impact does the progress in molecular biology have on the bioeconomy and Novozymes's work?

Videbaeck_Metagenomics, data digitali-

sation, and gene-editing have significantly improved our opportunities to screen functionalities, without the need to cultivate a microbe, and to optimise enzymes.

We use artificial intelligence to compare regions in molecules and to find the best suited enzyme candidate or to interpret changes in fermentation parameters.

Thomas Videbaeck is the VP and COO for Research, Innovation, and Supply at Novozymes, where he has held diverse key functions since 1998, spanning both the commercial and operational side of the business. Previously, the chemical engineer and B.Com. in International Business (Copenhagen Business School) worked for Novo Nordisk A/S.

EuroBiotech_Will we see synthetic organisms in the future?

Videbaeck_From Novozymes’s perspec-

tive, they will not be necessary. We have very good production strains and our strategy is to take the natural basis and optimise it. So finding new backbones for laundry enzymes is more interesting for us. L

14.06.2018 13:33:07 Uhr

focus

European Biotechnology | Summer Edition | Vol. 17 | 2018

“Fundamental change needed” Globalisation What must be done to ensure the growing world

population depletes fewer natural resources? European Biotechnology asked Ian Goldin, globalisation expert, at the GBS 2018.

EuroBiotech_Can we have both sustainability and an economics of scale?

Goldin_ No. We need to be more con-

Huge investment

cerned about changing our consumption and our production; otherwise we will destroy our planet.

At the GBS, the German research minister Anja Karliczek announced an update to Germany’s €2.1bn strategic research agenda, set up in 2012; along with the start of a broad stakeholder discussion, including civil society, to define the goals of an agenda “From Biology to Innovation;” and another project aimed at monitoring the development of the bioeconomy.

EuroBiotech_What should be done?

Goldin_I think the interests of people in

poor countries are the same as those in rich countries: to have clean water and air and sustainable products. We need to change relative prices, starting with a high carbon tax, to make sure that we move towards zero carbon globally over the next 20 years. That would change the dynamics of investment in solar, wind, and regenerative energies in which we have seen rapid technological progress and – for solar energy – an expontenial drop in cost. Today, it's cheaper than most other energy forms that are subsidised and traded. So we need a carbon tax and incentives to move towards zero carbon. I think we should ban dirty fuels and energy.

Ian Goldin is the Director of the Oxford Martin Program on Technological and Economic Change. The former economic adviser to Nelson Mandela, and former Vice President of the World Bank was Founding Director of the Oxford Martin School (2006–2016). Goldin has a BA and a BSc from the University of Cape Town, an MSc from the London School of Economics, and an MA and Doctorate from the University of Oxford.

EuroBiotech_Why is that?

Goldin_Buying dirty energy, as Germany

does from Poland, is a backdoor escape from solving the world’s problems and a form of greenwashing: carbon doesn't care where it enters the atmosphere.

There is also a high need for tech and capital transfer into developing countries – not just supply transfer but also knowhow transfer, as technologies must be adapted to the local environment.

EuroBiotech_Can we prevent greenwashing on biobased processes?

Goldin_We need to track cradle-to grave,

establish, and independently monitor accurate standards to know, for example,

30-32_EB_Summer_2018_Focus Bioeconomy_GBS_Iintro_tg.indd 32

adopted by industry (see interview p. 28) because of low investment costs. The GBS Communique recommends creating a common knowledge base for the bioeconomy in order to internationally coordinate the development of policies.

It calls for monitoring the status quo and the progress of the bioeconomy to recognise unwanted side-effects and to actively drive bioeconomies into the right direction.

where intermediates come from. We might use blockchain technology to trace them back to the source.

EuroBiotech_What is the role of the consumer in establishing a sustainable bioeconomy?

Goldin_Consumer choices are shaped by

information. So we should spread accurate information to consumers and policymakers. I think in 20 to 30 years we will be moving towards veganism or vegetarism because there is so much evidence about environmental, resource problems, and cruelity associated with meat and milk. L

“To survive in the 21st century we need a global bioeconomy governance“ Suvit Maesincee, Minister of Science and Technology, Thailand

Previously, Karliczek had underscored her clear committment to R&D on CRISPRbased genome engineering technologies, even in crops, a hotly debated topic in Germany. It may be not used in Germany, due to public concerns. However, application of such technologies in other parts of the world may be helpful. German Agriculture Minister, Julia Klöckner, said at the GBS, “We want to master the shift to a biobased economy.”

While it is not yet clear which ministry will coordinate the set-up of the agenda, the process will start this summer. German economy minister, Peter Altmaier, who brought up the idea of an all-industries-covering approach based on biobased production, has strong ambitions to do so. The German Bioeconomy Council proposed to fuel the renewed ioeconomy R&D strategy with €3bn over the next six years.

L

t.gabrielczyk@biocom.eu

Picture: BIOCOM AG

32

15.06.2018 11:29:57 Uhr

Economy

European Biotechnology | Summer Edition | Vol. 17 | 2018

33

Meet the FMD deadline with security labels Thema The implementation phase of the falsified medicines directive 2011/62 is coming up

soon. The obligatory safety features – a unique identifier and an anti-tampering device – must be applied to pharmaceutical packaging by 9 Feb. 2019. One solution gains increasing relevance: security labels. Tamper-evident, pre-serialized, and combination labels each have numerous practical benefits for simpler and faster implementation. › Philip Falkenstein, Product Manager Serialization & Tamper-Verification, Bähren Druck

Pictures: Bährendruck

Security labels have already gained widespread appeal as a popular anti-tampering device. Typically a clear filmic label with perforation is used to seal medical packages. These labels have several advantages: they allow easy machine or manual processing; have little or no effect on the package’s artwork and construction; and are recognised by consumers as protection against manipulation.

However, in order to realize these advantages without delay, the right label selection must be made with care.

The main challenge is the varnish on the folding box. These coatings can weaken the bond between the label and the carton surface. But the carton type and printed area can also influence adhesive strength. Standard permanent glue reach-

es its limits. Therefore, it is recommended to select proven materials which have been specially developed for use as a tamper verification feature. Even though their costs are slightly higher, you avoid expensive product recalls in the supply chain due to peeling, missing, or ineffective labels.

Permanent application is also a basic requirement for pre-serialised labels. Indeed the majority of drugs are serialised inline during the packaging process. But if printing on the carton is not effective or possible, pre-serialised labels come into play.

Shoe box formats provide the best examples. In many cases, the dimensions are not suitable for inline serialisation processing. Pre-serialised labels can also

Security label solutions to implement Directive 2011/62: tamper-evident labels, preserialized labels, and 2-in-1 combination labels by Bähren Druck.

33_EB_Summer_2018_Baehren-Druck.indd 33

be an alternative for medium and small batch sizes. In this case, the set-up times of inline systems and the risk of rejection of faulty products due to misprints have a considerable influence on the economic efficiency of inline serialisation. The possibility of manual label application is another strength. This is particularly true with regard to a 2-in-1 label solution, which allows two processes to be completed in one step.

Prevent high investments Furthermore, there are some scenarios in which pharma companies want to avoid high investment in serialisation equipment. Pre-serialised labels can even allow companies to outsource the entire complex serialisation process to a packaging specialist, who will guarantee that print quality, data structure, and specific barcode requirements comply with regulation 2016/161.

Given that the clock is ticking away, plus the fact that some companies may not finish their serialisation project in time, pre-serialised labels are also a possible interim solution to fulfil the requirements by February 9 2019.

Of course, the use of pre-serialised labels requires a clear agreement between the pharma company and the packaging manufacturer. Defining basic questions relating to the serial number, data interfaces, and reporting is a crucial step during the onboarding process.

L

13.06.2018 15:33:22 Uhr

34

Economy

European Biotechnology | Summer Edition | Vol. 17 | 2018

“We like to partner” Polpharma Biologics Within a short time, Polpharma has built a biosimilar pipeline from

scratch and a one-stop-shop CDMO business. European Biotechnology spoke with Hannes Teissl, VP of the Management Board, about the company’s business strategy, differentiation from competitors, and expansion in both business fields.

at Duchnice, 20 km from the Warsaw airport, must be seen in the context of our existing locations in Gdansk and Utrecht.

The concept behind it is to complete our product supply cycle, which starts at Bioceros in Utrecht, from cell line generation. We then move our products to Gdansk, where we have all the technologies in place to develop biologics and biosimilars: process industrialisation, upscale, extensive analytical and process development,and GMP manufacturing.

Our commercial supply for the first two bio­similar programmes will take place out of Gdansk. For future projects, the much larger plant at Duchnice will come into play. Strategically, our goal is that Polpharma Biologics controls all the steps in the value chain, i.e. supply, quality, development, and project management. That is where our investment goes. For commercialisation, we then partner with the best companies to market a certain product.

We love to partner. Thus, Polpharma is entering the global market by offering development and production capabilities.

EuroBiotech_As the CDMO market undergoes consolidation, many large suppliers have begun to refocus their activities on smaller biotech customers. What advantages does a mid-sized CDMO such as Polpharma have over larger competitors?

Teissl_First of all, we offer a fully integrat-

ed approach. You won’t find many CDMOs who offer you a true one-stopshop – from cell line to full-scale process

34-35_EB_Summer_2018_Interview_Polpharma_tg.indd 34

Hannes Teissl joined Polpharma in 2012 with the objective to build a biologics business from scratch. As a Vice President of the Management Board and Biologics Head Teissl has established both an attractive biosimilars pipeline and a solid foundation as a trusted CDMO service provider. Prior to Polpharma, he worked for 22 years at Sandoz, Novartis’ generics and biosimilar business, in various international management positions.

development to GMP manufacturing – in a full range of technologies – microbial, mammalian, fill and finish, liquid, lyo – everything! For our clients, that’s an important element. Of course you can buy a commercially available cell line, but if you have a direct access to a proprietary cell line system you know these cell lines in-

side out. We have been working with our system for 11 years and we still learn, every day. It’s important to have such knowhow, including a modulation toolbox, to fine-tune our process, particularly when it comes to establishing biosimilarity with high confidence. So having full control is a big advantage. Regarding production, we build up in a modular way. As a private company, we are solely driven by what makes sense commercially. We have a long-term committment from our investor, who is passionate about biotechnology with all its uncertainties. Finally we have built a highly motivated and customer-oriented team – a good mix of veterans and hungry young scientists. We are flexible, focused and dedicated to make our clients‘ products a real success. We are passionate about it and we have capacity available – right now!

EuroBiotech_Do you think its an advantage to be located in Poland?

Teissl_Because we are based in Poland,

our labour costs are lower compared to most other parts of Europe. Biotechnology has also been made a development area by the Polish government, therefore there is substantial support for what we do. That’s a positive environment. We are just kicking off a biologics academy in collaboration with local universities in which we will train our own talents. Poland will become a new biotechnology hub and will expand to reach a global scale. Our products meet all regulatory requirements in the US, Japan, and the EU. We are ideally positioned to be a trusted source of biologics products and services.

EuroBiotech_What is the advantage of having a dual business model – with pro-

Picture: Polypharma Biologics

EuroBiotech_Polpharma is currently building a production plant near Warsaw, complementing its capabilities with commercial-scale biologics manufacturing. What’s the vision and strategy in this field?

Teissl_This new above €100m investment

13.06.2018 15:34:09 Uhr

Economy

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35

Picture: Polypharma Biologics

prietary biosimilars and know-how in contract manufacturing – in contrast to pure service companies?

Teissl_We have this dual business model,

but it’s important to know that we established our capabilities in the biosimilar field first. We will file our first products to the FDA at the beginning of 2019; we have proven that we can deliver. Now, for our second step, we are approaching the CDMO market. Although we keep these two businesses strictly separated, clients can rely on a knowledge base that has been built over many years. For us as a service company, the two businesses allow for optimal capacity utilisation and productivity. Some people might feel there is competition between our proprietary biosimilar pipeline and our customer-focussed CDMO business. But remember, even for our own programmes we will have commercial partners join us. Insofar we, as Polpharma, will not compete with our CDMO clients. Both areas just differ by when and how to share risks and

responsibilities. For Polpharma Biologics, however, building an integrated CDMO business is not tactical but strategic, which means customer service is our top priority.

EuroBiotech_Both markets are growing.

Do you want to grow organically, or do you think acquisitions are needed to remain at the top in Europe?

Teissl_We are not really thinking about ac-

quisitions in biologics, but we always like

to partner. The acquisition of Bioceros was a strong fit to complete our offerings.

However, apart from cell line generation we have successfully built all necessary capabilities in-house. Maybe some day in the future we might want to open a US branch, but there is currently no decision whether to buy or build. Now, we are focussed on getting our state-of-the-art Duchnice plant operational by 2020 and increase our teams accordingly.

L t.gabrielczyk@biocom.eu

60

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13.06.2018 15:34:14 Uhr

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Economy

European Biotechnology | Summer Edition | Vol. 17 | 2018

Combining established and novel technologies Rentschler Biopharma Last year, Rentschler Biopharma SE formed a strategic alliance with

formulation specialist Leukocare AG. European Biotechnology spoke with Federico Pollano about the impact Leukocare’s SPS® technology will have on the market and how Rentschler Biopharma combines tried-and-tested technologies with new innovations to lead the CDMO market.

nent risks, potential benefits, and impacts with our customers to find the best solution.

EuroBiotech_Rentschler Biopharma has been investing in new services. Have you seen initial impacts from the recent strategic amendments in formulation technology and fill and finish?

Pollano_The importance of formulation of

EuroBiotech_ Everyone in the CDMO field is talking about time-to-market.

How does Rentschler Biopharma handle established vs novel technologies to ensure timely delivery?

Pollano_Based on our 40 years’ experience in all facets of biomanufacturing, we tend

to be very conservative when we make a

36_EB_Summer_2018_Interview_Rentschler_tg.indd 36

Federico Pollano is Senior Vice President for Business Development and joined Rentschler Biopharma SE from Polpharma Biologics, where he was Global Director Contract Manufacturing and Business Development. Pollano has an industry track record of more than 25 years, including senior management positions at Richter-Helm Biotec and Helm Pharmaceuticals.

promise, such as bringing customers from zero to Phase I in 12 months. In our view, quality, scalability, and a robust process are more important than speed.

Don’t get me wrong; we are capable of deli­vering rapid results, but before we promise to do so, we discuss the imma-

needs. Rentschler Biopharma has both technologies in operation. In the 2010s, we pioneered single-use manufacturing – we were among the first adopters in the CDMO business. In fact, 120 of the 350 batches Rentschler Biopharma has conducted since 2000 were single-use. While 1000l single-use bioreactors are best suited for clinical trial supply, our twin 3,000l stainless steel and 2,000l single-use bio­ reactors are ideally suited for mid-scale commercial supply – that is in total, up to 100,000l annually. A recent study conducted by Bioprocess Technical Consultants says that two-thirds of all commercial processes are feasible in mid-scale bioreactors up to 5000l.

EuroBiotech_At Swiss Biotech Day, Rentschler Biopharma announced its business strategy for 2025. Could you tell us a bit about your plans?

Pollano_We want to reinforce our posi-

tion as a technology leader, expanding into regions where we have not been very active in the past, including Asia.

We will continue using our tried-and-tested technologies but also broaden our knowledge of molecular entities, e.g. bispecific antibodies, as well as new trends and therapeutic modalities.

L t.gabrielczyk@biocom.eu

Picture: Rentschler Biophaerma SE

protein and antibody drugs is currently being underestimated. Last year, we partnered with Leukocare to complement our capabilities in formulation development.

Particularly in the US, we have won new customers, who want to replace the standard formulation of their compound with features that extend the unique selling proposition of the molecule. Leukocare’s SPS® technology improves antibody drugs’ stability at temperatures above the freezing point – up to room temperature. You can imagine what impact this may have – not only on logistics but also on production and purification.

The platform comes with a tool that allows in silico modeling of different formulation options for a specific molecule.

The Rentschler family also invested into a fill and finish facility, which will become operational this summer. These are two examples of how we complement our portfolio as a full-service CDMO with solutions that give our customers a competitive edge.

EuroBiotech_Rentschler Biopharma offers both disposable and stainless steel equipment. Which do you prefer?

Pollano_It depends upon a customer’s

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35th DGPharMed Annual Meeting March 28-29, 2019 · Berlin NH Collection Berlin Mitte Friedrichstrasse

Programme & registration online: www.dgpharmed-jahreskongress.de Organisation: PRIME Consulting GmbH · Paulusstraße 1 · 40237 Düsseldorf · Tel.: +49 211 49767-20 · www.primecon.eu

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Events across Europe EuroBiofairs Compass Each manager, scientist, and business developer has their own individual,

specific network — and so, too, their must-attend events vary significantly. Where to meet potential new partners and how to widen one’s scope beyond well-known terrain can be quite difficult to determine. Euro Biofairs Compass will help you navigate the European meeting jungle in H2/2018.

Based on advanced partnering and networking tools, Nordic Life Science Days (see p. 40) showcases the best that the Nordic region has to offer. The mix of conference, partnering, and exhibition is hosted in Stockholm (10–12 September).

Picture: UBM

What biotech has to offer Starting on 24 September, an entire week will be dedicated to communicating the progress in biotech to the public. The European Biotech Week (see p. 42) is organised by EuropaBio and featured more than 150 events across Europe in its 2017 edition.

Identifying and finding business opportunities – that's what one of the largest biotech events in Europe is about: biospain (25 – 27 September 2018, Seville, p 44). Last year's edition saw more than 750 licencing opportunities for the 800 companies attending. bioLIVE, a brand-new event, relevant to everyone working in the bio-

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processing and manufacturing field, will take place in Madrid (9 – 11 October 2018, Madrid), adjacent to the largest pharma meeting, the CPhI Worldwide. Its ambition: to bring CDMOs and potential customers together (p. 46).

Companies aiming to expand in the Far East are well-advised to attend Asia’s largest biotech show, Bio­Japan 2018 (10 – 12 October, p. 48) in Yokohama, which will be held together with Regenerative Medicine Japan.

The market-leading annual event in Europe for Industrial Biotechnology and the Bioeconomy, EFIB, will take place this year in Toulouse (16 – 18 October 2018, p. 50). New industrial biotech processes as well as finance will be just few of the topics to be covered – a must-attend.

From 17 – 18 October business development executives from pharma corporations and biotech companies will meet investors at the European partnering conference EBDC at in Hanover (p.52).

Another partnering must-attend will come to Copenhagen for the first time:

From 5 – 7 November the 24th edition of BIO Europe (p. 54) will be the place to see and be seen for over 4,000 executives from over 60 countries for highlevel networking, partnering meetings, strategic panel discussions, world-class workshops.

For the sixth year running, Pharma­ Lab (20 – 21 November 2018, p. 56) calls upon the latest regulatory and scientific developments in all laborator y areas of the pharmaceutical industr y. This event, to be held in Düsseldorf, is accompanied by an exhibition, in which suppliers of lab equipment and contract laboratories present their offerings.

More than 1,200 delegates are expected to attend BioFIT 2018 (see p.

58) in Strasbourg, a must-do event for everyone who is interested in partnering, technology transfer, and early licencing (4 – 5 December).

Just turn the page to learn ever ything you need to know about Europe’s must-attend events in the biotech industry.

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10–12 September, 2018 Stockholm Waterfront, Stockholm, Sweden

Sixth Nordic Life Science Days NLSDays offers networking and know­

ledge for anyone interested in the Nordic life sciences, biotechnologies, pharmaceuticals, medical devices, and e-health businesses. The event provides a wealth of opportunities to connect.

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

Based on cutting-edge and advanced partnering and networking tools, Nordic

› Quick facts Highlights from NLSDays 2017 ›› 1,300+ participants ›› 40 countries ›› 17,000+ meeting requests ›› 3,000+ scheduled meetings Contact Olivier Duchamp Phone +33 (0)608 804 515 olivier.duchamp@bionordic.com www.nlsdays.com

Life Science Days showcases the best that the Nordic region has to offer.

The Nordic way of conducting the life sciences business The Nordic region is proud to host some of the world’s most innovative biotech, medtech, and pharma companies. It also has the twelfth strongest econo­ my, making it the perfect place to invest.

Set in the vibrant city of Stockholm, the conference offers super sessions, work­ shops, company presentations, exhibi­ tions, face-to-face meetings, and unique receptions, providing numerous oppor­ tunities to network with peers, potential partners, and investors.

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

NLSDays is a SwedenBIO event pro- duced by Bionordic.

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A warm climate GREETING Nordic Life Science Days is the largest Nor­ dic partnering con­ ference dedicated to the life sciences in­ dustry. Since its in­ ception in 2013, the event has nurtured a community of peo­ ple from the world of life sciences, and created a unique place to do business.

Most attendees express their delight in the informal atmosphere, combined with an organised approach to meeting highly relevant people. Returning visitors come back because they feel they belong to our growing community. For Uli Wendt, a seasoned business developer at French pharma company Sanofi, the event is not to be missed: “NLSDays is a great fo­ rum to connect with innovators across the Nordic region, which is an innova­ tion hotspot in metabolism research. I value the informal atmosphere and feel that the conference delivers strong out­ comes for the time invested.”

We hope to welcome you, too. We cre­ ate a space for meaningful encounters, with one-on-one meetings being one of the main features of NLSDays. Addition­ ally, the high quality of topics and pre­ senters provide insight into the most re­ cent trends in science and business.

Olivier Duchamp Director General, NLSDays CEO, Bionordic Services

Pictures: NLSDays

Partnering at its best

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24–30 September, 2018 All around Europe

European Biotech Week European Biotech Week calls on the biotech

community to start planning events and activities for the week of 24 – 30 September 2018 to make biotech more accessible, understandable, and 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 to solve some of the world’s main challenges, and we have a responsibility to share what we know and facilitate an open discussion among all stakeholders to accompany these developments.

EuropaBio developed the European Bio­ tech Week in 2013 to mark the 60-year anniversary of the discovery of DNA’s structure. Each 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 benefits that biotechnology brings in areas as diverse as healthcare, agriculture, food, energy, and industrial processing.

A proud heritage

knowledge, innovation, productivity, and environmental protection quite like it.

Those who are passionate about biotech should speak confidently of its achievements, potential, and challenges. With over 150 events organised last year in 19 countries, we are delighted that the European Biotech Week initiative has become a key part of the biotech calendar that opens the doors to a better understanding of the world we live in. We hope you will join the celebration this year!

GREETING Biotechnology is one of the most exciting fields to be a part of in 2018. Few others enhance quality of life,

The EuropaBio team

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Collaborate and contribute EuropaBio strongly encourages all biotech supporters to join forces and participate in whatever way best fits with their mission and resources. To get some inspiration from past events, visit the week’s website at www.biotechweek.org or get in contact with us at hello@biotechweek.org.

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› Quick facts IN 2017 ››154 events ››19 countries ››68 media pick-ups across 11 nations CONTACT Clément Robijns Communications & Events Officer, EuropaBio C.Robijns@europabio.org www.biotechweek.org

Pictures: EuropaBio

Tribute to biotech

Year upon year, the participation in European Biotech Week has increased, with a record 19 countries taking part in the 2017 edition. The 150+ initiatives organised in the areas of science, education, policy, media, and finance involved thousands of Europeans. Importantly, numerous events were related to jobs and training, including career fairs and hands-on laboratories for adults, students, and children; competitions; open doors in companies, research institutes, and museums; and even theatrical shows.

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25–27 September, 2018 FIBES Exhibition & Congress Centre, Seville (Spain)

BIOSpain Spain is an excellent location to attract foreign investors.

From the 25th to the 27th of September 2018, the FIBES Exhibition & Congress Centre in Seville (Spain) will be the stage for BIOSPAIN, a forum for all the actors in the biotechnology sector to share knowledge, ideas and experiences.

BIOSPAIN is the largest biotech event organised by a national bioindustr y association in Europe. It is organised

by ASEBIO, the Spanish Bioindustry Association, and this years’ edition is co-organised by the Government of Andalusia. The event hosts twice as many sessions – 35 on average as the rest of the industry events. The sessions are grouped into different sections – partnering, trade fair, confer-

› Quick facts Highlights

›› 800 companies ›› 230 exhibitors ›› 3.000 one-to-one meetings ›› 50 investors ›› 1,750 attendees Contact www.biospain2018.org Phone +34 912 109 374 dfernandez@asebio.com

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ences and investors’ forum. According to a survey carried out after the last edition in 2016, 84.81% of attendees had identified real business opportunities. BIOSPAIN 2016 attracted a diverse group of attendees, from biotechnology companies (47.4%); pharmaceutical companies (10%); investors (5.2%); professionals from the services and consulting sector (10.6%); medical technology companies (2.5%); suppliers and engineering companies (4%) and public / non-profit organizations (20%). The majority of the delegates came from the health sciences sector.

Among the main topics that will be addressed during BIOSPAIN 2018 are: Alzheimer’s, Advanced Therapies, agro-food, biobanks, financing programs, the circular economy, artificial intelligence, genetic editing, immunotherapy, resistance to antibiotics, precision medicine and a lot more.

All information about the event can be found online: www.biospain2018.org.

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Back to the roots GREETING We return to Andalusia for the 9th BIOSPAIN edition, ten years after organising BIOSPAIN in Granada.

Since then, our evolution as a sector, and as an event, has gone hand in hand with an upward curve that already places us, on the one hand, as a pole of attraction for international investors, and on the other hand, as the most important partnering event organised entirely by a biotechnology association in Europe and the third largest in the number of companies and b2b meetings.

In this edition, we would like to thank the Junta de Andalusia, the government of Andalusia, for supporting our event, for which we hope to reach, at least, the same participation figures as, or even higher than, those obtained at BIOSPAIN 2016.

BIOSPAIN 2018 will offer a prominent role to the investment forum, taking into account the outstanding level of investors, both national and international, who will attend.

We are expecting you with the hope that you have a successful experience at BIOSPAIN in the beautiful city of Seville!!!!

Jordi Mardí ASEBIO President

Pictures: ASEBIO

Return to Andalusia

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25th-27th September, 2018 SEVILLE, SPAIN www.biospain2018.org

800 companies

233 exhibitors

+750 licensing opportunities

29 countries represented

50 investors

49 sessions on the conference program

1.750 attendees

3rd largest biotech partnering event in Europe

3.000 one-to-one meetings Registration

Code:

EBN10 (10% Discou

nt)

Organized by:

Platinum Sponsor:

Spanish Bioindustry Association

BIOSPAIN 2018 is part of the European Biotechnology Week

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9–11 October, 2018 IFEMA, Madrid, Spain

BioLive bioLIVE offers a unique opportunity for any company active in biop-

harma to put a spotlight on their offering in front of the entire pharma industry. It features excellent science and technology, development, and partnering opportunities through cutting-edge onsite content and matchmaking.

The first-ever edition of bioLIVE – a new event dedicated to bioprocessing and manufacturing – will take place adjacent to CPhI Worldwide in October. This exciting new addition will feature a live content stage, dedicated sessions, and exhibitors from across some of bio’s most prominent companies. It’s a unique platform connecting biotechs, big pharma, and service providers across the whole value chain in large molecules.

› Quick facts Highlights

›› 1400 attendees ›› 45+ hours of presentations ›› 30 exhibitors ›› adjacent to CPhI worldwide Contact bioLIVE team e-mail: bioLIVEcustomerservice@ ubm.com Phone +31 (0)20 708 1637

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To help industry executives look ahead at key trends and developments, bioLIVE will feature sessions on the industry’s hottest issues. The agenda includes topics as diverse as accelerating bioprocessing innovation, artificial intelligence in biomanufacturing, and building a skilled bioprocessing workforce to single-use technology innovation and the increased domestic capacity in China.

The event will include an international mix of exhibitors, with industry heavyweights such as Samsung Biologics, and a plethora of high-level speakers. Bringing the small and large molecule worlds together for this first time, bioLIVE creates a vital platform where both industries can learn from each other. The synergies and the exceptional audience of CPhI Worldwide, with 45,000 visitors over three days, will significantly benefit any company involved in the event. “The launch of bioLIVE will help accelerate the development of the bio supply chain, improve knowledge exchange, and create a more collaborative bio/pharma environment,” says Eric Langer, President and Managing Partner, BioPlan Associates.

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Opposites attract!

GREETINGS The biologics industr y is at a crucial stage in its development, as drugs are becoming more complex, volumes are increasing, and pharma is turning to contract service providers to overcome manufacturing challenges. Initially, biologic developers did production in-house with only activities like fill/finish being handed over to contractors. But now, even novel areas like cell and gene therapies are being outsourced. In addition, emerging biotechs, with little inhouse manufacturing or development capabilities, are now an integral part of the drug pipeline. Complex challenges, development timelines, and the need to lower overall costs industry-wide requires increased access to newer technologies in both upstream and downstream processing.

This complexity means the industry needs an event around which it can centralize its supply chain, and it is why we introduced bioLIVE. In fact, experts from our White Paper suggest that there are a number of cross sector learnings – everything from PAT to supply chain management and even scale-up process improvements. What is most exciting is that we are only just beginning.

Rutger Oudejans Brand Director at UBM

Pictures: ebd group

Biologics at CPhI!

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1400 ATTENDEES

45+ HOURS OF CONTENT

3

IFEMA MADRID • SPAIN • 9-11 OCTOBER 2018

DAYS OF NETWORKING OPPORTUNITIES

At The Heart Of Business And Innovation In Biopharma Evolve faster, successfully deal with challenges and achieve your business goals. Exhibit at bioLIVE, a new focused event with an exhibition and live content stage, bringing the worlds of small and large molecules together.

Be a thought leader at the forefront of innovation Showcase your latest products and services Meet the right buyers

Exhibit at bioLIVE More information at

www.bio.live ADJACENT TO

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10–12 October, 2018 Pacifico Yokohoma, Japan

BioJapan & Regenerative Medicine Japan This year marks the

20th anniversary of BioJapan, Asia’s premier partnering event for the global biotechnology industry. Over 1,000 organisations from industry and academia around the world are expected to take part in this year’s partnering, for over 9,000 discussions in total.

Interest in pursuing partnerships with European organisations is on the rise at BioJapan, and accordingly, the presence of national and regional European delegations is more and more apparent.

European organisations made up just short of a quarter of participants in last year’s partnering event, and the high number of expected returnees in 2018 stands testament to their success.

Besides the partnering and exhibition, the three days of the event (October 1012) will host a jam-packed seminar and

› Quick facts Contact biojapan@jtbcom.co.jp Phone: (+81) 3 5657 0758 www.ics-expo.jp/biojapan Partnering Opening in July at a cost of 70,000 JPY per account (approximately EUR600)

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presentation track, including both Japanese and English sessions from pharma, academia, biotechs, ventures, and other organisations. The full schedule will be available online in the coming weeks, and we anticipate new sessions will continue to be announced right up to the start of the event.

Along with the 20th edition of the longstanding BioJapan, October will also see the return of Regenerative Medicine Japan, a concurrently held exhibition now in its third year. Thanks to recent legislative changes in Japan, the country now boasts a unique environment for the development of regenerative medicine products, with a new conditional approval stage allowing for a time to market of only a couple of years. Accordingly, great growth in the sector is expected in Japan, making the exhibition an exciting prospect for those interested in exploring new opportunities.

The partnering and exhibition spaces are entirely shared between the twinned events, with a full participation cost of aprox. €600 per account. L

Asian Prospects GREETING The increasing number of Eur op e an p ar ticipants at BioJapan in recent years is an encouraging sign of the increasing internationalisation of the Japanese biotechnology industry.

We’ve felt a lot more interest among Japanese organisations in working with teams from overseas, and the number of returning companies and associations from overseas tells us that interest is mutual! We are expecting an even larger international delegation than ever, both in the exhibition and in the partnering.

What’s more, with the 2020 Tokyo Olympics now only two years away, the country is doubling down on its efforts to develop a more international-facing infrastructure, so now is the perfect time to visit and build relationships with Japanese companies.

2018 is a special year for BioJapan, as this October we’ll be celebrating the exhibition’s 20th anniversary. We hope you’ll join us in Yokohama to celebrate with us! We look forward welcoming old and new friends to Japan to make this year’s event even more successful than ever.

Sakayu Shimizu Chairman BioJapan Organizing Committee

Pictures: BioJapan

Partnering in Asia

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16–18 October, 2018 Toulouse, France

EFIB 2018 About 600 attendees are expected to join the 11th edition of

the “European Forum for Industrial Biotechnology and the Bioeconomy” in Toulouse, France. The two-day event will showcase how bio-based solutions help to meet the UN Sustainable Development Goals (SDGs). The START-UP VILLAGE@EFIB initiative welcomes founders in the exhibition.

Companies focusing on industrial biotechnology and bioeconomy are contributing towards achieving 11 out of 17 SDGs, enabling smarter, more efficient use of precious natural resources, developing renewable alternatives to traditional fossil-carbon products, helping to mitigate the impacts of climate change, reducing energy consumption and manmade emissions to soil, air, and water. These are the main results of a new

EuropaBio report about the impact of industrial biotech towards meeting global challenges. “It is critical for Europe to develop a more competitive and sustainable bioeconomy. The EU’s ‘Horizon Europe’ proposal will be key to ensuring that the right investments are made to address societal challenges and deliver on the UN SDGs,” said Joanna Dupont-Inglis, EuropaBio Deputy Secretary General. During EFIB 2018 in Toulouse, which is organised

Grand challenges

join us in celebrating the Industrial Biotech community‘s latest achievements in harnessing the power of innovation to deliver solutions to global grand challenges. Influential brands and industry leaders, as well as start-ups and entrepreneurs will meet in Toulouse, France, with a broad range of stakeholders and policy-makers to discuss the transformative potential of Industrial Biotechnology to create a more sustainable future.

GREETING In the last decade, EFIB delegates, exhibitors, sponsors and speakers have been showcasing innovative products and processes that deliver solutions to the UN Sustainable Development Goals.

This year, we invite you to

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Joanna Dupont-Inglis, EuropaBio Deputy Secretary General

Special invitation to start-ups For the first time, EFIB offers small and medium-sized companies (SMEs) a reduced fee. Start-ups are invited to take part in the Pitchfest and the START-UP VILLAGE@EFIB. L

› Quick facts Highlights

›› 60+ speakers ›› Reduced fee for SMEs and start-ups ›› 1-to-1-Partnering & Exhibition CONTACT Clément Robijns Communications & Events Officer, EuropaBio C.Robijns@europabio.org www.efibforum.org

Pictures: EuropaBio (left), SergiyN/shutterstock.com (top)

Meeting the SDGs

by EuropaBio with the support of BIOCOM AG and Toulouse White Biotechnology (twb), more than 60 international speakers from the industrial biotechnology and bioeconomy arena are expected to highlight the impact of industry-driven innovation to meet the UN SDGs. Presentations in the fields of plastics, nutrition and food, marine biotechnology, synthetic biology, and sustainable aviation, amongst other topics, are planned. Innovations in the areas of processing, packaging, cosmetics, and textiles will be showcased as well.

Another session will discuss financial incentives of circular bioeconomy with investors and VCs.

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17–18 October, 2018 Hanover Congress Center Hanover, Germany

EBDC BIO Deutschland’s annual European business development

event, the EBDC, will bring together experts from pharma and biotech with investors and other experts. This year’s motto is “Bridging Medical Innovation in Europe.”

Half of innovation is anchored in external collaboration. The EBDC provides a forum for making contacts and discussing topics and trends relevant to the drug development market. The conference’s participants come from a wide range of backgrounds. Business development executives from international pharmaceutical corporations and European biotech companies will meet with representatives from private equity and venture capi-

tal companies. This is an ideal occasion to meet experts from all areas of business development and make contacts that will offer your company significant strategic and operational advantages.

Werner Lanthaler, CEO of Evotec, and Niels Emmerich, VP Global Head of Search and Evaluation AbbVie, will give the keynotes of the conference. The EBDC also offers spotlight talks on unmet medical needs – such as neurologi-

Meet experts

cal biotechnology was 8.8 bn Euro and Germany’s biotech sector continues to grow. This year’s EBDC will take place in the German state of Lower Saxony.

The state’s strengths include a strong research community and an innovative entrepreneurial environment. I would like to personally encourage you to attend the EBDC and partner with our innovative German biotech companies.

› Quick facts

Dr. Peter Heinrich Chairman of Board BIO Deutschland

Contact event@biodeutschland.org

GREETING Germany is one of the world’s leading medical biotech nations and the majority of German biotech SMEs are active in the medical sector. About one-third of those develop new drugs. In 2016, the estimated total gross added value in the sector of medi-

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Registration and information under: http://bit.ly/EBDC2018

Registration http://bit.ly/EBDC2018 Highlights ›› 150 attendees ›› 20 slots for speed meetings ›› Spotlight talks and presentations ›› Start-up pitches

Pictures: BIO Deutschland, iStock/Rost-9D

Bridging Innovation

cal diseases – as well as company presentations and pitches from pre-seed start-ups. Topics of our symposia will include: challenges in cell and gene therapy, big data and digitization in drug development and patient care, as well as exits for biotechs – before and after the IPO. EBDC attendees will have great opportunities for partnering and networking.

We offer 20 slots for speed meetings and plenty of additional time for conventional meetings. The first conference day will conclude with a network reception and dinner.

The venue, Hanover Congress Center HCC, is centrally located, 15 minutes from Hanover Central Station and 40 minutes from Hanover Airport via ground transportation. This means easy access to a valuable conference and networking experience.

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European

Biotech

Partnering

© iStock/Rost-9D

@ EBDC 2018

EBDC 2018 at a glance: High class with familiar atmosphere: 150 attendees Perfect platform to liaise with Central Europe’s biotech industry Sophisticated line-up of speakers Main sessions on gene & cell therapy, exits for biotech, brexit impact and big data & digitization 20 slots for speedmeetings and lots of time for conventional meetings Spotlight talks on unmet medical needs Presentations of R&D companies Pitches of pre-seed start-ups Networking Reception & Dinner

Organizer:

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Platinum-Sponsor:

© iStock/weight

Bridging Medical Innovation in Europe

European Business Development Conference

17 to 18 October 2018 Hanover, Germany

Gold-Sponsors:

Conference Supporter:

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5–7 November, 2018 Bella Center Copenhagen, Copenhagen, Denmark

BIO-Europe 2018 The 24th annual international partnering conference

BIO-Europe® will be held in Copenhagen, Denmark. Europe’s largest life sciences partnering conference offers powerful opportunities to network with the right partners across the biotech value chain.

The 24th annual international partnering conference BIO-Europe will be held for the first time in Copenhagen, Denmark. The event offers countless opportunities to network with the right partners among over 4,000 executives from over 60 countries and brings together hundreds of the world’s most innovative leaders across the biotech value chain for high-level networking, prescheduled partnering meetings, strategic panel discussions, world-class workshops

› Quick facts Pre-event course Do you want to hone your negotiation skills? Go for it on November 2–4, 2018 by attending the course “Advanced Business Development.”

Registration discount The early bird discount is available through August 31, 2018.

Please visit ebdgroup.knect365.com/bioeurope/

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and more. The event is also highly regarded for the variety and high calibre of presenting companies, ranging from biotech startups and academic innovators to next-generation, midsize pharma and biotech companies that will bring their innovative techno­logies, therapies, and solutions to the event with the goal of securing deve­lopment and commercialisation partners.

If the partnering can be considered the engine, the presenting companies are the fuel that drives the event. BIO-Europe also features a diverse list of industry leaders speaking on workshops and panels. Leading pharmaceutical companies, including all of the big names in pharma, sponsor the event, sending teams of scouts to engage around new and innovative products. Informal networking events in stunning local venues lend further dealmaking opportunities. The 2017 event boasted a major increase across the board, with an all-time record of 4,007 attendees, 24,199 scheduled one-to-one meetings, and 5,142 licensing opportunities posted from among 2,199 companies that attended from 61 countries.

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Must-attend GREETING There is tangible excitement around the arrival of BIO-Europe every year. This event is a key strategic ele­ ment for global bio­ tech, pharma, and investment companies that attend in search of new collaboration partners and deal opportunities.

To add to the anticipation, this year BIO-Europe will be held in Copenhagen, Denmark, for the first time. BIOEurope is expected to draw a high calibre of companies to this vibrant life sciences hub, not only from Europe but from across the globe, to fuel the insatiable drug development industry.

The event brings a high quality and wide variety of companies to present their licensing opportunities directly to potential partners, resulting in allian­ ces that literally change the world.

With over 4,000 attendees last year, this event – which pioneered partnering 24 years ago – continues to stoke the engine that drives the industry’s growing demand for transformational breakthroughs.

See you in Copenhagen this November!

Anna Chrisman EBD Group & KNect365 Life Sciences Managing Director

Pictures: EBD Group

Unchartered waters

13.06.2018 15:44:38 Uhr

Save EUR 200, Early Bird deadline is August 31 24TH ANNUAL INTERNATIONAL PARTNERING CONFERENCE

NOVEMBER 5–7, 2018 / / COPENHAGEN, DENMARK

Photo by Martin Heiberg, Copenhagen Media Center.

This "must-attend" event is Europe's largest life science partnering conference.

BIO-Europe's world-class workshops, panels and active exhibition along with thousands of prescheduled one-to-one meetings make this event an unrivaled forum for companies across the biotech value chain to meet and do business.

WHAT YOU CAN EXPECT:

4,000+ Attendees

150+

Company presentations

5,000+ Licensing Opportunities

24,000+ 2,000+ 100+ One-to-one meetings

Companies

Exhibitors

Find out more: ebdgroup.com/bioeurope Produced by

In collaboration with

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13.06.2018 15:57:13 Uhr

56

Euro Biofairs Compass

European Biotechnology | Summer Edition | Vol. 17 | 2018

20–21 November, 2018 Crowne Plaza Düsseldorf, Düsseldorf / Neuss, Germany

Pharmalab 2018 PharmaLab focuses on the key questions concerning

QC and QA professionals in analytics, bioanalytics, and microbiology.

This year, the meeting and exhibition highlights the regulatory challenges and their impact on pharmaceutical and biopharmaceutical quality labs.

In recent months, there have been a number of changes in the relevant authority guides and chapters of the pharmacopoeias in Europe and in the US, as, for example, the draft Annex 1 of the EU GMP Guideline with an increased focus on Quality Risk Management (QRM), a new stand-alone guideline on GMP for ATMP, and new drafts of the USP Packaging Chapters. Additionally, modern analytical and microbiological lab systems are increasingly automated and

› Quick facts Contact & Registration www.pharmalab-congress.com Highlights ›› Key speakers from the US, Japan, the UK, Denmark, Italy, the Netherlands, Germany, and others ›› Ten conferences and two workshops with over 60 lectures ›› Networking opportunities and social events

56_EB_Summer_2018_LO2_Compass_Pharmalab_ml.indd 56

computer-based. These developments lead to new challenges – like qualifying such new systems and validating the methods or establishing Laboratory Integrated Management Systems (LIMS). And this, in turn, calls for compliance with the GMP Guide Annex 11, PIC/S Data Management and Integrity Practices, and the latest FDA Data Integrity requirements.

Floodlight on a neglected topic These issues build the core of six English- and four German-speaking conferences at PharmaLab, which also for the first time will finally wade into an oftenneglected topic whose responsibility lies somewhere between QA, QC, and manufacturing: pest control. Although many national and international regulatory guidelines ask for a conclusive concept of pest control for pharmaceutical and biopharmaceutical manufacturers, they do not provide details on what to do and how to do it. PharmaLab therefore wants to provide the platform for an information exchange and to discuss a structured cooperation of the parties involved.

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Forum for lab professionals GREETING Join us on 20 and 21 November in Düsseldor f/Neuss at the 6th PharmaLab for an information exchange and to discuss the topics in analytics, bioanalytics, and microbiology that keep you busy in the lab. Among other issues, activities related to “low endotoxin recovery” and the European initiatives to reduce animal experi­ments in labs (3R ​​strategy), are still a strong focus for biopharma companies, contract labs, and authorities. Both of them will be broadly discussed at PharmaLab. Almost 60 speakers from authorities, industry, contract labs, and research will share with you current regulatory developments, new methods and practical experience. Also, take advantage of the exhibition, with around 30 exhibitors, to get to know the latest lab technology and services. We look forward to seeing you there.

Pictures: Concept Heidelberg

QC/QA lab challenges

Dr. Günter Brendelberger Axel Schroeder, Concept Heidelberg, Operations Directors

14.06.2018 13:43:48 Uhr

Bioanalytics, Analytics and Microbiology – Congress & Exhibition – Crowne Plaza Düsseldorf/Neuss 20/21 November 2018 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

Analytical Challenges for Biologi-

Computerised Systems in

cal Drug Substances and Products

Anforderungen an ATMP/ Neuartige Therapien*

Analytical Laboratories

QC Compliance Trends in Analytical Laboratories

Methodenvalidierung bei Wirk- und Hilfsstoffen*

Optimierung von Laborprozessen*

Endotoxin and Pyrogen Testing

Rapid Microbiological Methods

Media Partner: *

57_EB_Summer_2018_Concept-Heidelberg.indd 1

German speaking Conferences

and Mycoplasma Testing

Pest Control – from classic trap to

digital control

Mikrobiologische Nährmedien –

von der Auswahl bis zur Qualifizierung

Pharmaceutical Quality Training. Conferences. Services.

13.06.2018 15:57:47 Uhr

58

Euro Biofairs Compass

European Biotechnology | Summer Edition | Vol. 17 | 2018

4–5 December, 2018 Lille Grand Palais, Lille, France

Biofit 2018 In December, BioFIT will gather 1,200 international actors

from the life sciences sector. The event aims to foster partnerships bet­ ween academia and industry, between big companies and start-ups, and to offer a European marketplace for pre-seed, seed, and Series A invest­ ment in the field of life sciences.

This year, the plenary session will ask how far and how fast will the earlystage investment market in biotech globalise. Seed investment actors are indeed often perceived as geographi­ cally anchored, despite the recent trend among early-stage investors to invest in more diverse geographic areas.

Moreover, an entire conference track will be dedicated to identifying the right funding sources for early-stage inno­

vations. New collaborative models be­ tween academia and industry will be presented in a comprehensive session of panel discussions that will cover, for instance, the use of artificial intelligence in life sciences which impacts the drug discovery processes at all stages, and may influence the shape of collabora­ tive research. Collaborations between animal health and human health play­ ers will also be highlighted. Examples

Tapping reservoirs

academic institutions and technology transfer organisations willing to promote their IP and their research capacities, and industry players willing to tap into the reservoir of innovations and technol­ ogies that the academic world and startups can offer. BioFIT also addresses the needs of start-ups to partner with estab­ lished industry players and with the ear­ ly-stage investment community.

› Quick facts

Etienne Vervaecke General Commissioner of BioFIT & General Manager of Eurasanté

Registration Early bird tariff runs until June 30.

GREETING The life sciences industry is increasingly looking to external sources for early-stage innovations, and resort­ ing to external col­ laborations with aca­ demic institutions and young companies. To facilitate these con­ nections, BioFIT en­ ables one-to-one in­ teractions between

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Expected 2018 key figures 1,200 delegates 35+ countries represented 35 one-to-one meetings / participant 15 conference sessions 50 oral presentations of start-ups and licensing opportunities 80 speakers & 100 exhibitors Picture: Eurasanté

Sourcing innovations

of the role patient organisations play as new partners in the development of life sciences innovation projects will be dis­ cussed. Many initiatives often taken joint­ ly by universities, venture firms, compa­ nies, charities, and governments aim to better bridge the gap between a promis­ ing academic result and a transferrable asset. A complete track of panel discus­ sions will provide BioFIT’s audience with numerous examples of those so-called maturation or pre-seed schemes.

BioFIT also offers the opportunity to detect the most innovative and prom­ ising start-ups, R&D projects, and li­ censing opportunities in order to foster partnerships and business develop­ ment in the life sciences field. Finally, the event's 7th edition will include many hosted events, like the R&D dating for animal health and innovation, the 5th European Genomic Institute for Diabe­ tes Symposium, and the career-boosting “Would-be CEO Networking Lunch.” L

13.06.2018 15:58:06 Uhr

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@BIOFIT_EVENT 13.06.2018 15:58:21 Uhr

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Drug Delivery

European Biotechnology | Summer Edition | Vol. 17 | 2018

Nanobots: Fiction becoming reality nanobots targeting pathogens or conditions directly have now become reality in research labs worldwide. But to enter clinical trials, scientists still have to overcome two major hurdles – visualising the tiny machines inside the body, and preventing a potential immune response.

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Pictures: Biodesign Institute, Arizona State University

Drug Delivery  Once confined to speculative and science fiction, miniature micro- or

13.06.2018 17:02:17 Uhr

European Biotechnology | Summer Edition | Vol. 17 | 2018

Pictures: Multi-Scale Robotics Laboratory (MSRL) at ETH Zurich

W

hat can we really do to fight cancer? Bradley Nelson posed that question in a speech at the annual World Economic Forum in Davos 2016. And the Director of the Multi-Scale Robotics Laboratory (MSRL) at ETH Zurich is far from the only one asking that question. Scientists all over the world are feverishly searching for new ways to beat one of humankind’s oldest enemies. Blunt tools like chemotherapy and radiotherapy are often ineffective, and they destroy a lot of healthy tissue in addition to the malignancy. So what if we could come up with tiny, intelligent machines – just millimeters to nano­meters in size – that were programmed to kill only tumor cells?

Where once only sci-fi authors dared to tread, researchers are now taking huge steps forward, designing micro and nanobots that can be used to carry and release drugs throughout the body, and specifically home in on malignant cells.

A study published in February by Arizona State University (ASU) and the Chinese National Center for Nanoscience and Technology (NCNST) showed how the partners successfully programmed DNA nanobots to shrink tumors by cutting off their blood supply (Nature Biotechnology, DOI:10.1038/nbt.4071). “We have developed the first fully autonomous, DNA robotic system for a very precise drug design and targeted cancer therapy,” said Hao Yan, Director of the ASU Biodesign Institute’s Center for Molecular Design.

Each nanobot is made from a flat, rectangular DNA origami sheet that’s 90 nanometers long and 60 nanometers wide.

Attached to its surface is a key bloodclotting enzyme called thrombin. The enzyme can block tumor blood flow by clotting the blood within the vessels that feed cancer growth, causing localized embolisms that lead to the death of its tissue. In mice, the researchers showed that treatment successfully blocked tumor blood supply, and generated tumor tissue damage within 24 hours – with no detectable adverse effects on healthy tissue. After attacking tumors, most of the nanorobotic systems were also cleared and degraded by the body within 24 hours. “This tech-

60-64_EB_18_Bots_HM.indd 61

nology is a strategy that can be used for many types of cancer, since all solid tumor-feeding blood vessels are essentially the same,” says Yan (see graphic, p. 63).

Inspired by Hollywood The idea of miniaturised robotic doctors taking a journey into the depths of the body to solve a health issue was first popularised by Hollywood in the 1960’s.

In the film “Fantastic Voyage”, scientists were shrunk to microscopic size along

Drug Delivery

61

with a submarine and implanted in the body of an injured scientist to perform delicate brain surgery. During their mission, the crew faces many obstacles, including an arteriovenous fistula that forces them to detour through the heart, and they only survive when full-scale doctors in the macroworld induce temporary cardiac arrest in the patient. But finally, of course, they manage to reach the blood clot in the scientist’s brain and are able to successfully break it down. Film­makers, however, have an advantage that scientists don’t have. They aren’t restricted by the laws of physics – and what happens when things get very, very small.

“It’s like if you were trying to make a nano cellphone.

You’d have to squeeze all the components into a tiny space, and it would still have to function as you want.”

Salvador pané i vidal Senior Research Scientist at the Multi-Scale Robotics Lab (MSRL) at ETH Zurich

?

What do you have to take into account if you design a micro or nanobot for treating diseases?

!

There are many aspects you have to consider at the same time – like how much drug you can load, or which obstacles or fluids your system has to face until it reaches its point of action. Understanding the path of the nanobot to the target helps us to define which locomotion strategies are more convenient, but also how the surface of the nanobot has to be engineered to be an efficient therapeutic nanoswimmer. For example, you may have to make your nanobots invisible to macrophages, or prevent undesired biomass from covering them. So to be able to target your bio­medical applications, you need to design devices that integrate all these features.

“When we talk about nanobots we’re referring to devices that exhibit at least one dimension in the nanoscale,” says Dr. Salvador Pané i Vidal, Senior Research Scientist at the MSRL in Zurich. Nanobots shouldn’t be confused with so-called nanocapsules or nanocontainers, which are passive systems that are already finding applications in medicine today. The term ’nanobots’ refers to active, intelligent nanomachines that would travel through the body on a certain mission – whether it’s the targeted transport of drugs to diseased cells, diagnosing conditions or perhaps one day even performing surgery at the micro­scale.

Scientists working in the field of micro and nanodevices for targeted drug delivery have spent a lot of time on the locomotion problem, trying to find good ways to make the bots move. One effective solution is based on bacteria that ‘swim’ with a corkscrewing rotation of flagellar filaments. “We’ve understood many things. For example, how locomotion can be beneficial, how to shape these structures at micro- and nano-

13.06.2018 17:02:25 Uhr

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Drug Delivery

scales, and how to functionalise them – for example, for drug transport,” says Pané i Vidal. “Different researchers have worked on many of the aspects individ­ ually. For instance, we started by inves­ tigating locomotion at small scales, but now we need to focus on other aspects such as corrosion, biodegrability or multi­ tasking. All these features have to be syn­ ergistically integrated and evaluated for each specific application.” The senior re­ search scientist recently received an ERC Consolidator grant for his project “High­ ly Integrated Nanoscale Robots for Target­ ed Delivery to the Central Nervous Sys­ tem”. Together with Bradley Nelson at the MSRL, his team designs porous structures that can load therapeutic payloads, which are then remotely controlled by magnetic fields. These fields can be used to move the structures wirelessly, or to get them to generate fields of their own. Perfecting such systems will allow the researchers to use the same source of energy for both locomotion and triggering functionalities, such as on-demand release of drugs and cell electrostimulation. “What I’m trying to do is to design nanorobotic structures that can navigate through the cerebrospi­ nal fluid and repair damaged neural cir­ cuitry by electrostimulation,” explains

European Biotechnology | Summer Edition | Vol. 17 | 2018

Pané i Vidal. “But we have to take into ac­ count that the structure has to swim in the complex milieu of the cerebrospinal fluid, and we still don’t know every kind of in­ teraction nanobots will have to face“. Fol­ low-up tests will examine how the drug delivery systems interact in vitro with cells of the cerebrospinal fluid, as well as how they move in a pulsating flow.

Getting them out of the body As in most Hollywood blockbusters, the characters in “Fantastic Voyage” have to struggle for their lives before reaching their happy end, and not everyone makes it. The mini-scientists are attacked by white blood cells, one character is killed, and their tiny sub is destroyed. In a lastditch attempt at escape, the remaining members of the expedition swim to one of the eyes and are finally able to get out of the patient’s body through a tear duct.

But what happens in real life to nano or microrobots placed in the body after they fulfill their appointed tasks?

Before any of the tiny devices can be used in tests involving humans, research­ ers in the field have to have a reliable way to remove or stop them. Even if it sends a therapy back to the starting point,

Types of micromotors To perform their tasks in the body, micro­bots have to be powered. There are three types of micromotors classed according to their mode of propulsion. ›› Physical micromotors are propelled by varying fields, like a helix of mag­ netic material spinning around its axis. Magnetic swimmers mimic the flagellae that propel some bacteria.

For example, a magnetically driven helix can capture a sperm cell and guide it to an egg cell for fertilisation.

Such devices are easy to control (NanoLetters, DOI: 16(1), 555-561) ›› Chemical micromotors transform fuel into energy (Chem . R ev., DOI: 10.1021/cr400273r). Often a cata­

lyst like platinum, silver or palladi­ um in the micromotor reacts with surrounding fluids. The motors may be guided by chemical or thermal gradients, or by applying magnet­ ic fields, light or ultrasound. For invivo uses, they need to co-opt ener­ gy sources present in the body, such as glucose or urea (ACS Nano, DOI: 10.1021/acsnano.6b04108). ›› Biohybrid micromotors combine a biological agent such as a bacterium. muscle or sperm cell with a synthetic element (Materials, DOI: 25(45),65816588, 2013). They can be directed by cells, microorganisms or through ex­ ternal fields.

researchers will have to build in safe­ ty switches that can turn everything off.

But that could prove to be a very tedious and complex procedure, especially when many nanobots have been introduced.

“Creating robotic systems that can be propelled and guided in the body has been and still is a Holy Grail in the field of delivery system engineering.”

There are different approaches to mak­ ing devices biodegradable and bio­ absorbable. Together with Li Zhang from the Chinese University of Hong Kong, Kostas Kostarelos from the University of Manchester for example created micro­ bots made from spirulina algae (S ci ence Robotics, DOI: 10.1126/scirobotics. aau0448). By dipping millions of spir­ ulina into iron-oxide nanoparticles, Ko­ starelos acquired the ability to steer the devices through magnetic fields and finetune the rate at which the algae degrade inside the body. “Our work takes advan­ tage of some elements offered by nature, such as fluorescence, degradability and shape. But we add engineered features such as magnetisation and biological ac­ tivity to come up with the proof-of-con­ cept behind our bio-hybrid, magnetically propelled microbots,“ says Kostarelos.

The nano- and microbots at the MSRL Zurich are being designed to remain in the body. When it has fullfilled its task, the degradable and bioabsorbable micro­ bot has to be able to break into pieces, be absorbed by the body and excreted via the body’s normal elimination paths.

Bradley Nelson and his team are current­ ly using biodegradable polymers that are produced through fabrication techniques like two-photon polymerisation, a kind of 3D printing technique.

Where the tire meets the road: immunoresponse & visualisation To enter clinical trials, future microbots will have to overcome two major hur­

Cel­ liza­ oLet­ 60-64_EB_18_Bots_HM.indd 62

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Drug Delivery

European Biotechnology | Summer Edition | Vol. 17 | 2018

63

DNA nanobots take on cancer Scientists from Arizona State University (ASU) and the Chinese National Center for Nanoscience and Technology have built an autonomous DNA robot programmed to transport payloads and present them specifically in tumors.

Each nanobot is made from a flat, rectangular DNA origami sheet, 90 nm x 60 nm in size. It’s functionalised on the outside with a DNA aptamer that binds nucleolin, a protein specific­ally

Thrombin bound to DNA

expressed on tumor-associated endo­ thelial cells. The cavity inside contains the blood coagulation protease thrombin. DNA origami was used to develop the thrombin-conjugated DNA nanotube, which shields the protease from circulatory substrates (2). The nucleolintargeting aptamer serves both as a targeting domain and as a molecular trigger to mechanically open the DNA nanobot.

When it opens, the thrombin inside is

exposed, activating coagulation at the tumor site (3,4). In mouse models, the researchers demonstrated that when injected, the DNA nanobots delivered thrombin specifically to tumor-associated blood vessels, inducing intravascular thrombosis that in turn caused tumor necrosis and the inhibition of tumor growth. The nanobot proved safe and immunologically inert in both mice and Bama miniature pigs.

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Tumour-targeting DNA

The DNA sheet is folded over to form a hollow tube

1

Blood vessel

2

3

DNA nanobot

Tumour

The nanobots include a DNA aptamer that targets a protein found in high numbers on the surface of tumor cells. This protein directs the nanobot to the tumor cells, where thrombin is released and causes on-site blood supply blockages. That can lead to tissue death, and even-

Pictures: Jason Drees, Biodesign Institute, Arizona State University

tually cause the tumor to shrink.

4

5

Source: Jason Drees, Biodesign Institute, Arizona State University (Nature Biotechnology, DOI:10.1038/nbt.4071)

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6

© BIOCOM

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Drug Delivery

European Biotechnology | Summer Edition | Vol. 17 | 2018

A helical micromotor helps an immotile but otherwise healthy bovine sperm cell reach an egg in culture.

dles. First, they’ll need to be biocompatible and removable or stabilisable after use. Second, researchers need to be able to see and control them while they perform their tasks inside the body.

“Visualisation can be seen as a key bottle­neck for the further development of micro and nanorobotic devices,” says Mariana Medina-Sánchez, group leader at the Institute for Integrative Nano­s ciences (IIN) at the Leibniz IFW Dresden. She and her team under the mentoring of Oliver Schmidt, director of the IIN-IFW Dresden, are working on speeding up sperm cells with 3D printed bots, then using them to treat cervical cancer (ACS Nano, DOI: 0.1021/ acsnano.7b06398).

Radiology, ultrasound, infrared and MRI methods are too coarse, insensitive and slow to track micro­d evices deep within the body. Normal clinical MRI (with magnetic field strengths of up to three tesla) can resolve structures that are around 300 μm in diameter – enough to image blood vessels. Higher magnetic fields can resolve 100 μm, but require expensive infrastructure. A promising approach to one day visualise bots inside the body is being developed by German ­based iThera Medical GmbH. The team there is manipu-

60-64_EB_18_Bots_HM.indd 64

lating light, sound and electro­magnetic waves to minimise the two main effects that cause images to blur: diffraction and scattering. “Our opto­acoustic devices work in the near infra­red range, which offers the advantages of deep tissue imaging (in vivo up to 3 cm) in real time with a resolution in the µm range that is in the size of single micromotors. In addition, by the acquisition of several wavelengths and spectral unmixing, we might be able to specifically distinguish the spectral signatures of the micromotors from intrinsic tissue molecules in future in vivo studies,“ claims Jing Claussen, an applications specialist at iThera who is working together with the IIN and Medina-Sánchez to track and visualise the spermbots. “We are conducting experiments to determine the spatial and temporal resolution of this technique. So far it looks promising compared to infrared or ultrasound imaging modalities,“ according to MedinaSánchez.

Natural swimmers against cervical cancer “Sperm cells are great candidates for drug transport and delivery in the female reproductive tract. Compared to other cellular drug carriers, they have

the ability to swim in viscoelastic and intricate environments, and deliver drugs into cells through membrane fusion,“ says Medina-Sánchez. Her spermbots are loaded with an anticancer drug (doxorubicin hydrochloride, DOX) and integrated with engineered magnetic caps that function as an artificial prostheses.

Thanks to the magnetic harness, the scientists are able to now guide the biohybrid sperm cell towards an tumor spheroid cultured in vitro, and then cut it free to deliver the drug locally. Although the technology has not yet been demonstrated in vivo, Medina-Sanchez is optimistic that one day, such sperm-hybrid systems could help with assisted fertilisation and targeted drug delivery – particularly in the sperm’s natural environment, the female reproductive tract. The spermbots could be injected into the uterus through a catheter.

Big challenges for small bots All scientists working in the field of nano or microbots face identical hurdles. “The main challenges are the control and imaging in vivo, as the current imaging techniques lack spatial and temporal resolution. Additionally, materials and structures should be deeply analysed in the areas of undesired immunoresponse, cytotoxicity and biodegradability effects, among other factors,“ notes Medina-Sánchez. Microrobotics researchers, materials scientists and bioimaging and medical specialists will have to work together to solve those problems. Regulatory agencies also need to put directives in place for testing therapeutics that are based on microbots. “The goal is a microbot that can sense, diagnose and act autonomously, while people monitor it and retain control in case of malfunction,” said Medina-Sánchez and IIN IFW director Oliver Schmidt in their Nature commentary (DOI: 545, 406408,2017).

Whether they’re made of DNA, poly­ mers, microorganisms like spirulina or sperm cells, researchers have come a lot closer in the last few years to making a fantastic voyage of their own.

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h.maerzhaeuser@biocom.eu

Pictures: M. Medina-Sánchez, L. Schwarz, A. K. Meyer, F. Hebenstreit & O. G. Schmidt/Nano Lett. 16, 555–561 (2016)

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Economy

European Biotechnology | Summer Edition | Vol. 17 | 2018

65

Exchanging success stories and stories of courage Swiss Biotech Day 2018 Artificial intelligence, cell therapy, and antibodies – it might sound like

Picture: BIOCOM AG

a life sciences buzzword bingo. But these topics, and many more, took centre stage at this year‘s Swiss Biotech Day. With more than 600 participants the annually held spring event at Congress Center Basel was more popular than ever before in its 11-year history.

The annual Swiss Biotech Day has evolved into the place-to-be if you want to make your life sciences business lift off in Switzerland. But it is also a perfect platform to boast about recent successes. When Holger Müller, Chief Commerical Officer of Biognosys AG in Schlieren, presented his business in the Emerging Biotech companies track of the Basel event, the ink under a transformative deal with US company Freenome barely had dried. Freenome’s artificial intelligence (AI) genomics platform is poised to detect cancer at its earliest stages and help clinicians optimise the next generation of precision therapies. But instead of solely relying on circulating fragments of tumour DNA, Freenome chose to add protein data to its analysis. Partner of choice is Biognosys, whose next-generation proteomics technology delivers unbiased quantitative information about hundreds of proteins and thousands of peptides from a single sample analysis.

Among the event‘s 40 presenting companies, you could also listen to cumulative Swiss AI expertise. Sophia Genetics, for instance, was founded back in 2011 to help clinicians with genomic data analyses. As it stands, VP Business Development Esteban Czwan said, Sophia helps to diagnose one patient every five minutes. The software as a service platform is already being used by 480 hospitals in 60 countries around the globe. The afternoon programme included a session on fostering closer cooperations between Swiss and British life sciences companies and investors. Because of Brexit, the United Kingdom is trying to align more

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More than 600 visitors, 30 exhibitors and 525 partnering meetings – the Swiss Biotech Day in Basel is marked in red in the calendars of Swiss and international industry representatives. In 2019, it will take place on 7 May. closely with Switzerland. Unlike most EU countries, both countries have a strong track record of life sciences sucesses.

Moreover, a discussion about financing biotech projects and companies, with experts from KPMG, SIX Swiss Exchange and venture capital firm Biomedpartners, among others, was well-received.

Setting a tone for an intense day, Vasant Narasimhan, the newly appointed CEO of Swiss pharma giant Novartis AG, introduced himself to the Swiss biotech industry in the morning. In his stimulating talk, he reminded the audience about the work of Carl June, whom he named as the pioneer who laid the foundations of Novartis’ groundbreaking CAR-T cell therapy Kymriah. Looking back, Narasim-

han called Kymriah “a success story and a story of courage.“ He said: “We had to re-think how we work, as we we’re developing an entirely new paradigm. Taking a patient’s cells, reprogramming them, and giving them back – this was something totally new.“ Narasimhan also commented on China as an up-and-coming competitor in the innovative medicines space: “China rapidly has modernised the regulatory framework and is determined to pivot to a more innovation-oriented economy.“ Especially in the relatively new field of cell and gene therapies, China sees a window of opportunity to reach a leading position worldwide, the Novartis manager said in Basel.

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m.laqua@biocom.eu

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Northern EUROPE

European Biotechnology | Summer Edition | Vol. 17 | 2018

A match made in Scandinavia

Combination trials That’s what you can call a setback. First, the Data Monitoring Committee of a Phase Ib/II study of daratumumab plus atezolizumab (Roche’s anti PD-L1 antibody) in patients with previously treated non-small cell lung cancer recommended ending the trial due to lack of benefit in the combination treatment arm. Then, listed Danish daratumumab developer Genmab A/S had to swallow the news that partner Janssen pulled the plug on a Phase I study with daratumumab and Janssen’s PD-L1 blocker JNJ-63723283 in patients with multiple myeloma.

Maybe even more disconcerting than the lack of benefit is the Committee’s observation of a numerical increase in mortality-related events in the combination arm. Following the news, shares of Genmab immediately plummeted by 20%.

In August 2012, Genmab granted Janssen Biotech, part of pharma multinational Johnson & Johnson, an exclusive worldwide license to develop, manufacture, and commercialise daratumumab in a US$1bn deal.

In 2015, the anti-CD38 antibody – sold as Darzalex – was approved as a treatment for multiple myeloma in patients who had received at least three prior therapies. Four more approvals for myeloma indications have followed since then. Combining the drug with cancer immunotherapies was a way to capture markets beyond haematological malignancies, like for instance solid tumours. This setback again demonstrates that combining different cancer therapies to improve response rates and clinical outcomes is anything but a no-brainer.

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Peter Buhl Jensen will be the new company’s CEO.

However, the merged company’s name will be Oncology Venture. The shareholders of Oncology Venture will have a slight majority in the combined company (51.3%) that will continue to be listed on Nasdaq First North Stockholm. Headquarters will be in Hørsholm, Denmark.

The companies had already announced their boards’ decisions to accomplish a merger back in March. The two businesses are quite distinct from each other. Medical Prognosis Institute has a proprietary patient screening technology to predict a patient’s response to drugs; Oncology Venture is a cancer-focused drug developer with six previously discontinued, then in-licensed small molecule drugs. Interestingly, the company claims near-term revenue will be generated by the drug development business (out-licensing of Phase III-ready assets). In the long run, the service sector is also expected to generate revenues by providing clinical oncologists with a patient screening service to enable them to make more informed choices regarding the selection of optimal drug treatment regimes. Operational synergies are expected to amount to a little more than SEK2m (€0.2m). L

For a shipshape junction Funding A drug development newcomer based in Århus managed to secure one of the largest Series A financings in Scandinavia of all time.

This spring, NMD Pharma A/S successfully raised €38m from new investors INKEF Capital and Roche Venture Fund, and existing investors Novo Seeds and Lundbeckfonden Emerge. The company was founded in 2016 with a €2.7m seed investment. With the new capital, two small molecule treatments for orphan neuromuscular disorders will be advanced to clinical proof-of-concept.

The NMD approach is based upon research into the role muscle-specific chloride ion channel CIC-1 plays in transmis-

sion at the neuromuscular junction – and hence skeletal muscle function. Existing preclinical data suggest the inhibition of CIC-1 could improve function in fast- and slow-twitch muscle fibers. NMD thinks the mechanism of action is also applicable to a range of conditions beyond orphan diseases. “Muscle weakness due to neuromuscular transmission defects is a core symptom severely impacting morbidity and mortality across a wide range of neurological disorders. There is a continued high unmet medical need due to lack of effective treatments and we are pleased to bring these first-in-class therapies to patients,” says Morten Graugaard Døssing, Principal at Novo Seeds.

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Picture: Medical Prognosis Institute

Stock implosion

Cancer Two listed Scandinavian biotech companies are about to merge into one. Medical Prognosis Institute A/S (Nasdaq First North Stockholm) in Denmark and Oncology Venture Sweden AB (Aktie Torget) in Sweden aim to create what they call a “one-stop-shop for personalised cancer treatments.” By the end of May, the merger had been approved by the shareholders of both companies. Medical Prognosis Institute will continue as a legal entity, and Oncology Venture will not.

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What a combination Drug delivery PCI Biotech Holding ASA (Oslo) has inked a preclinical research collaboration deal with the Canadian immunotherapy specialist IMV Inc (Nova Scotia, Canada), formerly known as Immunovaccine Inc. The companies will evaluate the compatibility of IMV’s liposomal freeze-dried formulation technology and DPX cancer vaccine candidates with PCI Biotech’s photochemical internalisation (PCI) platform, which induces endosomal release. After assessing the potential immunogenicity and therapeutic benefit of vaccine candidates delivered by PCI’s formulation technology in vivo, the companies will decide if they want to start a development partnership.

PCI Biotech uses its photochemical internalisation (PCI) platform to deliv-

er three different kinds of cancer medicines to tumours: chemotherapeutics (fimaChem platform), cancer-immune therapies (fimaVacc), and nucleic-acid based medicines (fimaNAc). Targeted local drug delivery promises less adverse effects, better T-cell induction in therapeutic vaccines, and targeted mRNA and siRNA therapeutics delivery.

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PCI’s light-induced drug release in the cell

Picture: fPCI Biotech ASA

Alexion buys Wilson for €639m Takeover A public offer from orphan drug major Alexion Pharmaceuticals Inc. has been welcomed by Wilson Therapeutics’s Board of Directors as well as its shareholders. By the beginning of June, Alexion’s offer of SEK232 per share drew 97.7% of the total number of shares and votes.

Alexion’s offer represents a 70% premium compared to the closing share price on the last trading day prior to announcement of its offer. Investors joining in at the initial public offering (IPO) of Wilson Therapeutics AB two years ago (SEK49 per share) are surely happy about a nearly five-fold return. In total, Alexion will spend SEK6,564bn (€638.8m) to acquire the sole Wilson product: WTX101.

The first-in-class selective agent (tetrathiomolybdate) is in Phase III testing. WTX101 stably complexes copper with proteins and restores the natural biliary excretion of excess copper. The drug candidate has US and EU orphan drug statuses and FDA fast-track status to treat Wilson’s disease, an autosomal recessively inherited defect

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of the ATP7B gene that triggers copper accumulation in the brain and liver leading to serious hepatic, neurologic, or psychiatric symptoms. If approved, WTX101 could become an alternative to current therapy regimes that aim to reduce the cell-toxic copper accumulation using copper-free diet, zinc actetate, or quite unselective, adverse-effect-prone chelating agents for bivalent cations. The complexes formed by existing therapies are often unstable and mostly excreted via the renal route. Phase II data of WTX101 suggest that tetrathiomolybdate can rapidly lower and control toxic-free copper levels and improve symptoms in Wilson’s disease patients. The data also suggest that the candidate is generally well-tolerated.

For Alexion, the takeover would secure a long-term financial revenue stream because potentially competing approaches, such an AAV-based gene therapy developed by French Vivet Therapeutics, are currently in preclinical deve­lopment stage.

Wilson already has applied for delisting of its shares from Nasdaq Stockholm.

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News Hurdle cleared After the acquisition of land to build a second generation biomass plant in Kemi, Northern Finland, in October 2016, the €900m project moved forward this April. Chinese investor-backed Sunshine Kaidi Finland New Energy Co. Oy received the local water and environment authority’s permission to built a plant that will produce 225,000 metric tons of biofuel per year (75% biodiesel, 25% biogasoline) utilising sawmill byproducts, leftover bark, and locally sourced wood.

Healthy horses In an oversubscribed rights issue, Swedish animal vaccine developer Intervacc AB secured SEK61.3m (€5.9m) this spring. Some proceeds will be used to transfer the manufacturing technology of the vaccine Strangvac to CMO partner 3P Biopharmaceuticals (Spain). 3P will produce two commercial batches of Strangvac, each with 30,000 doses. Strangvac – which protects against the highly contagious equine disease strangles caused by Streptococcus equi – is Intervacc’s first vaccine candidate.

Business scale-up In May, Molecular diagnostics firm Mobidiag Oy raised €4m from Finnish investor Springvest, and others, to fund the scale-up of the production of its Novodiag and Ampli­diag instruments, and of its global sales activities.

Mobi­diag had merged with Amplidiag (Finland) and Genewave (France) in 2013 to form a strong diagnostics firm focussed on gastrointestinal infections and antimicrobial resistance.

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Funding to fight AMR

Antibiotics French Deinove SA has acquired Morphochem’s Clostridium difficile (CDI) antibiotic MCB3837 as part of its acquisition of the Austrian company Biovertis. Morphochem is Biovertis’s German subsidiary. MCB3837 is a watersoluble injectable small-molecule prodrug of the active substance MCB3681, which has shown promising Phase I activity against Clostridium difficile gastrointestinal infections (CDI), one of 12 antibiotic-resistant priority pathogens listed by the WHO and the CDC. The novel antibiotic has been granted Qualified Infectious Disease Product (QIDP) status and FDA Fast Track designation, and is ready for Phase II testing.

Deinove will acquire Biovertis and Morphochem without paying any cash, but rather through an in-kind contribution of the company’s major shareholder TVM Capital and other shareholders, who will become Deinove shareholders through the transaction within Article L. 225-147 of the French Commercial Code.

Two investment funds managed by TVM Capital, which hold 82.98% of the contributed rights, will receive 500,001 Deinove shares to which will be attached eight million warrants (Bons d’attribution d’actions, BAA). The total value of the rights amounts to €900,001.80. The eight million warrants will only be exercisable by their holders in the event of reaching various milestones in the development of the drug candidate. The transaction adds to Deinove’s AGIR discovery programme of new antibiotics and its recent agreement with RedX Pharma.

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local to global will allow surveillance to be strengthened in low to medium income countries – where the burden of infectious diseases is highest but data are currently limited.”

Also in May, the REPAIR Impact Fund, which was presented at the 11th IP Conference on Life Sciences in Berlin this March, closed its first round for proposals for the 2018 investment round (see European Biotechnology, Spring edition 2018) with 54 applications. “We will not be able to fund all proposals,” said Aleks Engels, partner at the Novo Foundation. “We are seeking to build a portfolio of approximately 20 investments over three to five years, which means that in any given investment round, we can only fund a few investments. This translates to less than 10% of the proposals we received this round. That fraction is quite scary and humbling given the quality of the proposals.”

Also in May, the German Research Minister Anja Karliczek and colloborators from 17 further countries launched the Global AMR Hub at the World Health Assembly in Geneva. The goal of the hub is to coordinate research on antimicrobial resistance (AMR) globally.

The Hub has 18 members including Russia, China, USA, and France, the Bill and Melinda Gates Foundation, the Wellcome Trust and the European Commission.

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The 54 proposals for the REPAIR Impact Fund broken down into key categories.

Lead optimisation

Pre-clinical

Phase 1

› Small molecule Tx › Peptide TX › Large molecule TX and Vx › Enzyme inhibitor › Anti-virulence factor › Phage › Other

Picture: Novo Holdings

CDI acquisition

Antibiotic resistance The UK Government is boosting its contribution to global initiatives that fight antimicrobioal resistance (AMR). In May, the Bill and Melinda Gates Foundation joined with the UK government to back CARB-X, a UK-US public private partnership (PPP) “dedicated to fund development of antimicrobial products,” said CARB-X Director, Kevin Outtersons. While the UK government will invest £20m (€22.8m), the Foundation will contribute US$25m (€21.3m). According to Outterson, the new funds will be used for “vaccines, monoclonal antibodies, and alternatives to classical antibiotics, such as drugs that target the microbiome. The money will particularly be invested with a view to the “health needs in low- and middle-income countries.”

The CARB-X investment is part of the UK’s contribution of £30m (€34.2m) into four projects of the Global AMR Innovation Fund (GAMRIF). Another £5m of the investment will be fueled in a partnership with Argentina to tackle AMR in agriculture. Furthermore, £5m will go to the Foundation for Innovative New Diagnostics (FIND), a global non-profit group focused on developing, evaluating, and delivering affordable diagnostic tests for poverty-related diseases. The three-year project is focussed on connectivity for diagnostics. “Connecting diagnostics to surveillance systems at various levels from

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News Cancer niche modifier

Cancer pipeline swap Type 2 diabetes French pharma company Servier has complemented its cancer drug portfolio, acquiring British Shire plc’s oncology pipeline, which earned about US$260m last year.

The US$2.4bn cash deal includes the acute lymphoblastic leukemia (ALL) drug pegaspargase (Oncaspar) and late-stage ALL drug candidate calaspargase pegol plus the ex-US rights for a nano-formulation of the chemotherapeutic irinotecan (Onivyde). Servier will also receive the rights on several licenced drug can-

didates, including CAR-T cells developed

by Precision Biosciences and checkpoint modulators co-developed with Symphogen vs several targets.

Shire’s divestment came shortly before a €52.4bn takeover bid by Japan’s major drugmaker Takeda, which expected to close the transaction by H1/2019. Together the orphan drug (haemophilia), gastroenerology and neurology specialist Shire, and oncology, gasteroenterology and neurology-focussed Takeda generated combined revenues of €25.3bn in 2017.

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Picture: Africa Studio/fotolia.com

More value for less effort CDx British antibody developer Abcam and Chinese companion diagnostics specialist Shuwen Biotech have announced plans to establish an alliance for Companion Diagnostic (CDx) kit development. The companies said their alliance was a response to the increasing development needs from bio­pharma companies and healthcare professionals. Details of the joint work still had to be determined upon the announcement. However, a US study published in mid-May (Health Affairs, doi: 10.1377/hlthaff.2017.1580) proved that the companies have a nose for expanding markets. According to the study, targeted

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drugs were approved by the FDA an average of 1.7 years faster than non-precision medicines (5.8 vs 7.5 years), providing faster time-to-market. Furthermore, precision medicines typically required only one pivotal efficacy trial for approval, and trial sponsors needed to recruit fewer patients in their pivotal trials (305 vs 584 in non-precision medicines), reducing development costs. In addition, about 48% of the precision medicines qualified for the FDA’s breakthrough therapy designation.

Trials with precision medicines were less likely to be randomised, blinded, or controlled with a comparator.

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Ose Immunotherapeutics SA has licenced global commercialisation rights of its preclinical CD47 blocker OSE-172 to Boehringer Ingelheim, which hopes to complement its immunoncology portfolio with a tumour microenvironment modifier that reactivates effector T cell responses. Under the agreement, Boehringer Ingelheim will pay €15m upfront and €15m for starting Phase I testing of OSE-172 by 2019. Furthermore, the contract holds out the prospect to grant €1.1bn in development, commercialisation, and sales milestones.

Outsourcing deal British GlaxoSmithKline has passed its orphan autologous cell and gene therapy pipeline to BritishUS Orchard Therapeutics in which it acquired a 19.9% equity stake. Under the deal, GSK will receive royalties and commercial milestones from the gene therapy specialist for immune deficiencies and inherited metabolic disorders. Orchard receives the commercial rights on Strimvelis, an EU-approved autologous ex vivo gene therapy for adenosine deaminase deficiency, two late-stage clinical programmes in registrational studies for metachromatic leukodystrophy (MLD) and Wiskott Aldrich syndrome (WAS), and a clinical programme for beta thalassaemia, as well as three preclinical programmes. Orchard will will assume all obligations arising from GSK’s 2010 collaboration agreement with the Ospedale San Raffaele and Fondazione Telethon and from GSK’s collaboration agreement with MolMed, the exclusive manufacturer of Strimvelis.

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Centr al EUROPE

No more itching Drug development A Swissbased joint venture is destined to bring a drug candidate against chronic kidney disease-associated pruritus (CKD-aP) to market. Vifor Fresenius Medical Care Renal Pharma Ltd. has licenced ex-US/Japanese/Korean rights to commercialise antiitching drug CR845 (difelikefalin). Under the terms of the agreement, drug developer Cara Therapeutics (US) will receive an upfront payment of US$50m in cash and an equity investment of US$20m. Vifor Pharma did not disclose the amount of potential future milestones and sales royalties.

Cara retains development and commercialisation rights for CR845 injection for the treatment of CKD-aP in the US, where in 2017 the FDA granted breakthrough designation for the treatment.

Pruritus affects about 20 million people in the US. Cara will solely promote the peripherally acting kappa opioid receptor agonist in all non-FMC clinics in the US. “CR845 injection is a first-in-class, innovative investigational medicine for treating a highly debilitating disease. It is a natural fit to our leading product portfolio in nephrology,” said Stefan Schulze, President of the Executive Committee of Vifor Pharma. “Sixty to 70% of dialysis patients experience CKD-aP. Nearly 20% suffer from a very severe form, which is associated with much lower survival. And despite this clear unmet medical need, there is no approved treatment for CKD-aP in Europe or the US,” he added.

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European Biotechnology | Summer Edition | Vol. 17 | 2018

Affiris on track

Matching assets

Morbus Parkinson A synthetically produced a-synuclein (aSyn)-mimicking peptide scored what Affiris’ CEO Oliver Siegel calls “encouraging data” in a set of four consecutive Phase I studies with results from in total 26 patients – 21 receiving active treatment and 5 standard of care medication. Patients with early Parkinson’s disease received two doses of Affitope PD01A formulated with adjuvant.

Both doses were locally and systemically well tolerated. In addition, PD01A showed a clear immune response against the peptide itself and cross-reactivity against aSyn targeted epitope over time. For the private Viennese-based company the long-term data of PD01A is crucial as some fundraising is expected later this year.

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Drug Delivery By joining their proprietary technologies in a research project, two Swiss companies plan to develop a fast allergy immunotherapy. Anergis SA brings in its core technology based on Contiguous Overlapping Peptides (COP), which together contain the full amino acid sequence of major allergens. The delivery method has been mastered by Mymetics, a Swiss-born vaccine specialist with a Dutch laboratory: virosomes. Pre-clinical studies will evaluate the immunogenicity profile of Anergis’s peptides designed to treat birch allergy (the Bet v1 COP) when presented on Mymetics’ proprietary virosomes, and will compare the results to Anergis’ AllerT product (Bet v1 COP combined with aluminum hydroxide).

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Polyphor ends IPO draught Antiinfectives The long-awaited IPO of Swiss antibiotics and cancer thera­ peutics developer Polyphor was finally brought off successfully in mid-May. Setting the issue price per share at CHF38 – at the upper end of the announced range – Polyphor raked in CHF155m by placing more than four million new shares on the SIX Swiss Exchange in Zurich. In mid-June the price had dropped to below CHF33, bringing the market capitalisation of Polyphor down to CHF347m.

Apart from the spin-offs Cassiopea (from Cosmo, 2015) and Idorsia (from Actelion, 2017), the stock market debut of

Polyphor is the first in the field of biotechnology at SIX since Molecular Partners AG in 2014 – and the biggest biotech IPO in Switzerland for more than ten years.

Polyphor was founded in 1996 and is a 65-employee, clinical-stage biopharmaceutical company based in Allschwil near Basel. It focuses on the development of macrocycle drugs that address antibiotic resistance and improve therapy outcomes in cancer. Its Outer Membrane Protein Targeting Antibiotics (OMPTA) is the first new class of antibiotics against Gram-negative bacteria to have reached Phase III stage in the past 50 years.

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First day of trading for Polyphor’s shares at SIX was 15 May 2018.

Picture: SIX Group AG

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Evotec and Celgene on next level News Deal inflation

At Evotec’s headquarters in Hamburg, Germany Cancer German Evotec AG and Celgene Corporation (USA) have entered into a strategic drug discovery and deve­ lopment partnership to identify new thera­ peutics in oncology. Under the terms of the May 2018 agreement, Evotec will re­ ceive an upfront payment of US$65m and is eligible to receive milestone payments as well as tiered royalties on each licensed programme. Celgene receives exclusive opt-in rights to license worldwide rights to all programmes developed within this col­ laboration.

It’s not the first deal between the two companies. In December 2016, Evotec and Celgene signed a five-year contract under which Evotec uses its proprietary CELMoD library and induced pluripotent stem cell

(iPSC)-derived disease models to find new compounds in neurodegenerative diseas­ es. Under the 2016 deal, Evotec received an upfront payment of US$45m and an initial US$5m milestone for a successful screening campaign. Potential milestones amount up to US$250m plus double-digit royalties on product sales generated by li­ cenced programmes in return for exclusive commercialisation rights. Cord Dohrmann, Evotec’s Chief Scientific Officer, said, “We are excited about the opportunity to enter into a second major alliance with our Cel­ gene counterparts. Our first alliance has already shown that both companies and teams are committed to working togeth­ er and pursuing the same goals to develop new and better therapies for patients.“ L

Picture: Evotec

Novartis enters SMA race Acquisition Swiss drug major No­ vartis has secured a potential stake in the multibillion-dollar market of treatments for the orphan genetic muscle disease spi­ nal muscular atrophy (SMA). The compa­ ny acquired Avexis Inc, whose SMA gene therapy AVXS-101 – potentially the firstever one-time therapy for the disease – is in Phase III testing. With the US$8.7bn takeover, Novartis challenges Biogen’s US and EU approved antisense oligonu­ cleotide Spinraza (nusinersen), which has been marketed since 2016/2017 at an an­ nual price of US$750,000 per patient. The splicing modifier originally developed by Ionis Pharmaceuticals turns SMN2 mRNA into a functional form of the defective

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SMN1 version. Swiss Roche is also head­ ing for market approval with a splicing modifier of SMN2, code-named RG7916, in pivotal clinical trials. With LMI070, No­ vartis has also a modulator of SMN2 in Phase III testing to treat SMA. However, the Avexis takeover is adding a gene ther­ apy approach to the drug major’s portfo­ lio that can be also used to correct other inherited orphan diseases without treat­ ment option: besides AVXS-101, which delivers a functional copy of the deficient SMN gene, Avexis’ adeno-associated viral vector portfolio includes preclinical assets to treat patients with Rett syndrome and SOD2-deficient amyotrophic lateral scle­ rosis (ALS).

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CAR-T cell developer Bluebird Bio Inc. has extended its US$1bn deal with cancer neoantigen TCR specialist Medigene AG by two new targets to six targets in total – adding US$500m of potential milestone payments to the licence agreement. On top, Me­ digene received US$8m upfront.

Going all-in In May, US biotech company Bio­ gen has exercised the option of a oneoff payment of US$50m to Swiss de­ veloper Neurimmune. If the partners’ Alzheimer’s candidate Aducanumab is approved, the sales-related payments to Neurimmune will thus be reduced by 5% – to a number in the “high sin­ gle-digit to low double digit” range.

Analysts estimate a 35% chance the Alzheimer’s drug will be approved.

The biggest one Antibody developer Morphosys AG announced the successful clos­ ing of its Nasdaq IPO through an ADS Offering in late April. Total gross proceeds of the secondary listing of US$239m denote the so far biggest Nasdaq IPO of any German biotech company, the company said.

Precision diagnostics In order to be able to offer bet­ ter NGS-based molecular diagnostic tests, Qiagen NV partnered with US startup Freenome Inc. in June. Work will focus on companion diagnostics that ought to help developers of im­ muno-oncological drugs to estimate patient responses early on.

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NTC got an eye on Spain

Bribery Allegations of kickbacks by pharma companies don’t usually threaten the political establishment of a country, but that could be the case in Greece, according to the news site Politico. In May, the Greek parliament ended a probe into alleged kickbacks paid by Swiss pharma giant Novartis to senior politicians, saying it did not have the jurisdiction to investigate bribery and money laundering claims. Lawmakers from the ruling coalition said a special parliamentary commission was not competent to examine the case and sent it back to the courts, state news agency ANA reported.

Novartis is suspected of having bribed decision-makers and doctors between 2006 and 2015 to secure inflated prices for its products, even though cheaper alternatives were available. Ten former government officials, including two former prime ministers – Antonis Samaras and Panagiotis Pikrammenos – are implicated in the case. Novartis’s overcharging alone is estimated to have cost the Greek state some €3bn ($3.7bn). Overall, corruption across the health sector cost Greece some €23bn between 2000 and 2015, investigators said. According to Novartis, it had been cooperating with US and Greek authorities for over a year now while conducting an internal audit of its own. It has already paid multimillion-dollar fines in the US, China, and South Korea to settle corruption cases. 

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more, we firmly believe in the importance of having in our portfolio consolidated and successful products, alongside new offerings, that maintain a fundamental role in the treatment of eye diseases.”

The agreement with Novartis strengthens the NTC portfolio in ophthalmology, particularly in Spain, a country in which the company intends to open commercial operations in 2018.

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Sanifit succeeds in Phase II Clinical Trials At the end of May, Mallorca-based Sanifit announced positive results of its Phase II clinical trial targeting calciphylaxis (CUA) with its lead candidate SNF472. The drug, given as intravenous formulation, promoted wound healing and reduced pain in haemodialysis patients with cardiovascular diseases linked to calcification. “The results of this open-label, single-arm Phase II trial of SNF472 show that this agent has potential to improve wound healing and reduce pain in patients with CUA, who currently have no approved treatments for this severe disease. SNF472 was well tolerated by subjects enrolled in the trial and showed improvement across several important measures of effect,” states Vincent Brandenburg, nephrologist at University Hospital of the RWTJ Aachen, Germany, who conducted the study. Details of the study will be released later this year.

Calciphylaxis affects around 4% of patients in the late stage of chronic kidney disease. Fifty-five percent of patients with calciphylaxis die within a year of being diagnosed and suffer from painful skin ulcers and a high risk of infection.

There is currently no effective treatment for calciphylaxis. In contrast to other approaches, like calcimimetics and phosphate binders that prevent calcium formation in blood vessels, SNF472 targets the calcium directly. It prevents calcification by binding to the growing sites of HAP crystals, a mineral form of calcium, in a patient’s arteries.

In 2015, Sanifit raised €36.6m in a Series C funding to develop SFN472 The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted SNF472 orphan drug designation for the treatment of CUA. Currently Sanifit is preparing for a Phase III clinical study.

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Picture: pixabay/inspired images

Drug scandal roils politics

ACquisition Privately-held Italian pharmaceutical company NTC has acquired some Novartis ocular antibiotic products, including broad spectrum antibiotic therapies to treat eye diseases. Countries covered under the agreement include Spain, Portugal, Italy, and Poland. Financial terms of the deal have not been disclosed. “This agreement reinforces our industrial development program in ophthalmology,” says Riccardo Carbucicchio, chief executive and chairman of NTC, adding: “In fact, we are strongly committed to making new therapeutic solutions available in ophthalmology to enable specialists to offer drugs, medical devices, and supplements to improve the compliance of their patients. Many of our new products are designed and developed with the help of expert ophthalmologists, with whom we have established important research and development collaborations. Further-

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European Biotechnology | Summer Edition | Vol. 17 | 2018

Crowdfunding goes blockchain

Picture: fotolia.de/leowolfert

C r o w d i n v e s tm e n t S p anish Capital Cell continues to be a pioneer in the health crowdfunding scene and launched a new self-funding fundraising round to create the first ICO marketplace for health via Blockchain. Initial Coin Offering (ICO) is a method of crowdfunding used by companies whose business model is based on crypto currencies. It is used by start-ups to bypass the arbitrary and regulated capital-raising process required by venture capitalists or banks. Seeking to raise €700,000 for its new ICO marketplace, the Barcelona-based platform has already secured more than €900,000 from more than 198 investors. The project will remain open to investors until it hits €1.1m.

The money raised in the new round will be used to create Cell.Market, an investment marketplace for biotechnology and health via ICOs. The task of Capital Cell will be harness the knowledge of the best experts in the Healthcare & Biomedicine fields to analyse and filter what it considers to be the best investment opportunities for the biotech firms. Furthermore, Capital Cell is also looking to create its own cryptocurrency, the CELL. “Blockchain is a mighty development of the Internet, and it has huge disruptive potential. It means increased decentralisation, security, and transactional possibilities, and it opens a world of new paths for personal health and large-scale healthcare organisation. Anyone who is serious about investing in the Healthcare revolution must start looking this way,” Daniel Oliver, founder of Capital Cell, told European Biotechnology Magazine.

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Capital Cell was one of the first equity crowdfunding platforms that specialised in life sciences and biotech projects in Europe (see European Biotechnology M agazine, Summer issue 2017). In 2017, in addition to Spain, the company entered into the UK market. According to its founder Daniel Oliver, 80% of Spanish people still don’t trust both online investments and payments. Blockchain could help to sort this out. “Bringing into the system the transparency required will give a boost to the whole industry, so that the old grey-haired investor will have the ultimate technologic tool knocking on the door. My feeling is that this time, this new tool may be powerful enough to re-shape the whole thing,“ states Oliver. Cell.Market aims to explain how to invest in an ICO and Oliver spelled out why Blockchain is likely to change healthcare. “We are starting to see the rise of some of the crowdinvesting models (particularly crowdlending) and a few new products, such as crowdfunds, but the real revolution will come with cryptocrowdfunding - if the regulators don’t blow it, naturally.”

To date, the Spanish and British company counts 24 successful investment rounds for 20 companies that are developing new treatments and technologies for health applications. Last year, Capital Cell raised more than €1m for the Spanish biotech campaign Bionure with more than 250 investors – the largest crowdfunding campaign in Southern Europe.

Recent campaigns of Capital Cell that are running right now includeFesia and Tech4Freedom, which are both funded over 75%.

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News Collaboration announced In May, BIA Separations, a Slovenian biochromatography development and manufacturing company, and Biomay, a contact manufacturer of cGMP biopharmaceuticals, announced a collaboration on the high-yield production of large DNA plasmids. “Monoliths have been wellestablished for some time as the best purification tools for smaller singlegene plasmids and we are pleased to now adapt them to the purification of larger pDNA molecules,“ states Aleš Štrancar, CEO of BIA Separations.

Monolith chromatographic columns support effective purification for plasmids up to at least 60 kbp.

€52m investment Its a premier in Greece: For the first time, the European Bank for Reconstruction and Development (EBRD) supports a Public-Private Partnership in Greece. At the end of April, the Biomedical Research Foundation of the Academy of Athens (BRFAA) and EBRD signed a cooperation agreement. The venture includes the construction, acquisition of equipment, and facility management of a new building for the provision of specialised services in the field of personalised medicine. Furthermore, the project includes the renovation of the Loverdeion building, in order to create a unit for clinical trials of generic drugs. The total investment is estimated to be approximately €52 m. The project will be prepared under the EBRD’s Infrastructure Project Preparation Facility (IPPF). The BRFAA is a non-profit institute dedicated to understanding, treating, and preventing human diseases through biomedical research.

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EASTERN EUROPE

European Biotechnology | Summer Edition | Vol. 17 | 2018

Call 14-3-3 Drug discovery Binding more than 200 signaling proteins, 14-3-3 proteins are true master switches within eukaryo­tic cells. These conserved regulatory molecules play a crucial role in many cellular processes including aspects of cell growth. Although implicated in a number of different neurodegenerative diseases, as well as cancer, these targets have proven difficult to drug using traditional methods, due to their manifold protein-protein interactions. In May, an alliance of Czech research Institute CEITEC in Brno and German start-up Dynabind in Dresden took up the challenge to discover and develop drug candidates targeting human 14-3-3 protein complexes.

“My motivation to enter a collaboration with Dynabind comes from our earlier discussions about the extraordinary potential of their DNA-Encoded Library,“ comments Jozef Hritz, the project’s mastermind at CEITEC, the Central European Institute of Technology. “The identified molecules would present a wide range of applications in both the academic and pharmaceutical sectors,” adds Hritz.

Dynabind has developed a Dynamic Library platform for DNA-Encoded Library drug discovery. Hundreds of millions of potential affector molecules can be rapidly generated and tweaked in situ in order to find not only potent – but also specific – binders for the targets, the company claims. Dyna­bind’s CEO, Michael Thompson, is looking forward to the partnership: “We are always keen for an opportunity to work with innovative targets.”

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CRO When French Citoxlab Group said it would acquire a majority stake in Hungarian drug transporter research specialist Solvo Biotechnology this spring, Solvo’s leader Ernö Duda expressed confidence that “joining Citoxlab Group is a good opportunity for the future international development of Solvo Biotechnology and its team.” Duda founded Solvo back in 1999 in the southern Hungarian city of Szeged. Over the years, Solvo served 600 customers and grew to a headcount of 100. The preclini­cal CRO specialised in drug transporter studies and the assessment of drug-drug interactions. As trans-

porter studies are a regulatory requirement for entering large clinical trials, Citoxlab hopes to enter a burgeoning sector.

Financial details were not disclosed, but Solvo’s management will retain minority ownership of the company and remain in place. Citoxlab so far employs 1,200 people who work at nine sites in France, the U.S., and Canada. Citixlab also had ties to Hungary before as it operates a site in Veszprém near Lake Balaton. Through this new acquisition Citoxlab reinforces its leading position in the non-clinical CRO field, with consolidated sales of US$167m (€136m).

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IPO netted

Path to Phase III

Drug discovery Since mid-April, shares of Oncoarendi Therapeutics SA are traded on Warsaw Stock Exchange. The total value of the public offering of 2 million Series F shares amounted to PLN58m gross. 1.86 million shares went to institutional investors, 140,000 shares were alotted to individual investors. The issue price was PLN29 per share, a price level that was held the first weeks after the IPO. The fresh funds will be spent on the development of new drugs in the field of oncology and respiratory diseases. Lead candidate OATD-01 against asthma, idiopathic pulmonary fibrosis, and sarcoidosis is in Phase I development.

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cell therapy Interim Phase II data presented in June indicate that an experimental dendritic cell-based cancer therapy made by Czech biotech company Sotio a.s. is beneficial for patients with ovarian cancer. In the randomised, open label trial, patients with first recurrence of ovarian cancer received DCVAC/OvCa in combination with platinum-based chemotherapy. Designated by the European Medicines Agency as an orphan drug, DCVAC/OvCa decreased the risk of progression or death in first line maintenance treatment of ovarian cancer by almost 60%. Sotio’s CEO Radek Spisek said further clinical trials, including a Phase III, study will be initiated.

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Picture: Fotolia.de/Gorodenkoff

Solvo enters Citoxlab family

13.06.2018 16:02:38 Uhr

European Biotechnology | Summer Edition | Vol. 17 | 2018

Overperformer Sanofi French drug major Sanofi has named Dr. John Reed as their new Head of Global R&D. Reed, who brushed up Roche Pharma Research & Early Development (pRED)’s drug portfolio over the past five years, succeeds Elias Zerhouni, M.D., who will retire at the end of June. Dr. Reed will John C. Reed join Sanofi on April 30th to ensure a smooth transition. Previously Head of California-based SanfordBurnham Medical Research Institute, he successfully restructured Roche pRED’s organisation and portfolio with the result that Roche’s European organisation outperformed its ever-successul US arm, Genentech, in terms of programmes receiving Phase III investment support. L

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

Rocket woman Redx Pharma Plc Lisa Anson took the helm at the cancer and fibrosis company on 1 June. The new Chief Executive Officer (CEO) has been President of AstraZeneca UK since 2012 and brings significant leadership experience to the role. In addition to her current presidency of the Association of the British Pharmaceutical Industry (ABPI), she Lisa Anson brings experience from a huge variety of senior management roles at AZ in the US and the UK. She holds a MBA from INSEAD, France, and a First-class honours degree in Natural Sciences from Cambridge University. Upon graduation, she joined KPMG in London as a management consultant and then moved to California, where

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she worked for Salick Health Care (now Aptium), a cancer disease management company, prior to joining Zeneca Pharma (USA) in 1998 as a business development manager.

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Smart operator R e n t s c h l e r B i o p h a r m a S E Rentschler hired Thomas Rösch as the new VP Biopharma Engineering & Technology. He will be responsible for advanced biopharmaceutical engineering projects to enhance site and capacity.

Dr. Rösch has more than 16 years of in- Thomas Rösch dustry experience, including senior leadership positions in engineering, maintenance and project management. Prior to joining Rentschler Biopharma, he headed Global Engineering & Technology Pharma & Chemicals at Boeh­ringer Ingelheim Pharma.

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DNA dealer aldevron GmbH Plasmid DNA and antibody manufacturer Aldevron (former Genovac GmbH, Freiburg) has named Marc Wolff Chief Financial Officer. He will lead the global finance and accounting team across all Aldevron sites in the US and Europe. Wolff joins Aldevron from Sancilio Pharmaceuticals Company, Inc.; he also served as CFO at generic sterile product specialist JHP Pharmaceuticals. Prior to that, Wolff served in leadership roles in general management and finance at ReSearch Pharmaceutical Services, Catalent, and Cardinal Health.

L Marc Wolff

biopeople

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License dealer Neurimmune Sa French neurodegeneration specialist Neurimmune SA has hired Dr. Fabian Buller for the newly created position of Chief Business Officer. Dr. Buller has an impressive track record in business development and licensing transactions. Prior to joining Neurimmune, Dr. Buller served as Director New Ventures at Johnson & Johnson Innovation as well as Director Business Development of Covagen AG which was taken over by Janssen.

L Fabian Buller

Digital officer Puretech Health plc Sonde Health, the US branch of PureTech Health developing a voice-based technology platform for monitoring and diagnosing mental and physical medical conditions, has added Thai Lee, President and Chief Executive Officer of information provider SHI International Corporation, to its Board of Directors.

Under Ms. Lee’s leadership, SHI has transformed from a software reseller with US$1m in annual sales into a Thai Lee global provider of information technology products and solutions with 35 offices around the world and annual revenues of US$10 bn. Previously, Ms Lee was involved in brand management for Procter & Gamble. Ms. Lee has been recognised as a top leader and innovator in information technology. Lee holds a BA in Economics and Biology from Amherst College and an MBA in General Management and Leadership from Harvard Business School.

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13.06.2018 16:02:57 Uhr

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Agriculture

European Biotechnology | Summer Edition | Vol. 17 | 2018

A tractor entailing a fog of pesticides – a rare sight in a couple of years? Precision distribution of crop protecting agents via for instance drones could soon usher out mass spraying.

The future of agrochemistry Pesticides & Seeds  One of the world’s largest and most controversial mergers in the past few

Picture: fotolia.de/ValentinValkov

years was sealed in early June. German pharma and chemistry company Bayer has taken over US competitor Monsanto, forming the largest integrated provider of seeds, agrochemicals and digital farming solutions on the planet. The acquisition is part of a recent US$170bn deal binge that is already having a profound impact on the future of global agriculture.

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14.06.2018 13:50:08 Uhr

Agriculture

European Biotechnology | Summer Edition | Vol. 17 | 2018

T

he completion of Bayer ’s US$62.5bn (€51.6bn) acquisition of Monsanto on June 7, 2018 marks the end of a process of power concentration unlike that in any other industry in decades. The wave of mergers in the agrochemicals and seeds industry over the past three years has changed the face of the entire sector in that short period of time. The top three slots are now held by a European, a Chinese, and a US multinational. In the top spot in terms of revenue is German-based Bayer AG, previously third in terms of sales. The name of the company generations of environmentalists loved to hate – Monsanto – will be resigned to the dustbin of history after the American giant’s operations are integrated into Bayer’s crop science business.

Chinese-owned but largely Swiss-based Syngenta is a strong number two, after it was acquired by the state-owned giant Chemchina. And the new DowDuPont combination clearly moves up into position three. Complementing the Big Six now turned Big Four is German chemistry company BASF, which has been a big beneficiary of the windfall assets Bayer had to divest to get the merger with Monsanto done.

The shakeup has brought an even greater concentration of power in these four industry leaders. The oligopoly that dominates the market now carries a very large club indeed in the sector. So it comes as no surprise that competition authorities examined the individual mergers very closely, and demanded extensive divestitures. Along with BASF, smaller competitors like FMC (US) and Nufarm (Australia) have so far also been able to strengthen their businesses with assets from the merging companies.

No scarcity of scepticism Despite those divestitures, farmers don’t appear to be satisfied by antitrust authority measures. Before the giant merger, Bayer was the second largest supplier of pesticides worldwide, and a big seed company as well. Monsanto was the planet’s largest seed supplier, and one of the biggest sell-

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ers of its most frequently used pesticide – glyphosate. A survey among 1,000 fulltime US farmers organised in early 2018 by a coalition of farm groups revealed widespread scepticism about the merger. Over 90% expressed concern about the transaction. Among the top fears respondents shared were higher seed prices, less innovation and fewer seed varieties. And those fears are justified, argue Allen Grunes and Maurice Stucke, antitrust attorneys from The Konkurrenz Group (US). In a white paper on the competitive problems of the transaction between Bayer and Monsanto, they explain that US farmers – who unlike their European counterparts that are protec­ ted from seed price hikes by the European Commission – will see incomes shrink when seed prices rise. In terms of innovation, the merger will also have a bigger impact on the US than on Europe. Bayer and Monsanto are among just a handful of companies working on genetically modified (GM) crops. Less competition is not to be expected in Europe, as few GM crops are grown there. But in the US they make up a much bigger piece of the pie.

The merger will reduce the pressure to in-

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novate in the GM crop space dramatically, Grunes and Stucke believe.

While the market for seeds and crop protec tion sounds straight for ward enough, it isn’t really. Farmers all over the world will of course continue to buy soy, wheat or canola, plant their fields, and purchase chemicals to protect those crops from insects, fungi or weeds. But difficult-to-predict weather conditions have made for a surprisingly volatile market that’s been mired in a cyclical downturn since 2012. The companies are left hoping the market will stop falling this year or next.

Bespoke crop protection Generally, the business the Big Four will chase can be split into two fields: crop protection and seeds. The former has strong roots in chemistry, the latter in biology. In crop protection – which includes anything from treating seeds to fully grown plants – the seed treatment market is showing strong growth. According to a report released in May by Grand View Research, the sector will swell 9.6% annually until 2020, eventu-

Bayer Crop Science (including Monsanto & divestitures)

Seeds in %

40,000 (2017)

€20bn

46

Syngenta & Adama (ChemChina companies) 33,000 (2016)

€16.9bn

17.8

DowDuPont (Corteva Agrisciences division) 22,000 (2017)

€14.3bn

57

BASF Agricultural Solutions (including Bayer assets) 12,000 (2017)

€7.9bn

19

FMC Agricultural Solutions (including DowDuPont asset swap) €3.4bn*

5,400* (2017)

0

Nufarm (including divestitures from other companies) €2.1bn*

3,400 (2017 / 2018)

* estimates | Source: Data from annual reports & official press releases

5 © BIOCOM AG

After the merger mania: The world’s six largest agrochemistry/seed companies and divisions based on pro forma revenues. The pie chart indicates percentage of the companies’ business in seeds (orange), and agrochemistry business activities (dark green).

Corresponding years and number of employees in the unit are listed.

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Agriculture

ally reaching a size of US$5.6bn. Broadspectrum chemicals, on the other hand, are under heavy pressure due to environmental and (real or perceived) health issues. The trend is now toward focal application of chemicals to seeds and – with the help of digital tools – only the affected parts of the field. Another trend is biological solutions for containing disease, strengthening crops and fighting pests. Most biological crop protection products available today are either bene­ ficial microorganisms or pheromones, but research into bacteriophages, bacterial lysins, enyzmes and even antibodies is on the rise (see European Biotechnology Winter Issue, 2016).

At stake – the power to innovate In the seeds space, innovation is expected to be driven by genome editing technologies. CRISPR/Cas9, TALENs and other tools are giving seed developers new options when it comes to optimising traits like yield, resistance to environmental stress, diseases or pests (see European Biotechnology Summer Issue, 2017). To keep the pressure to innovate high in a postmerger era, the European Commission is forcing Bayer to divest its seeds business, including its soy, canola, cotton and vegetable assets. Bayer will sell them – as well as some crop protection agents and the digital farming platform Xarvio – to BASF. The deal is expected to close this summer, right before the Bayer-Monsanto merger. For the sale of those assets, which have a combined annual revenue of more than €2.2bn, Bayer will receive

European Biotechnology | Summer Edition | Vol. 17 | 2018

€7.6bn. For experts Grunes and Stucke, that transaction is highly problematic. “In the last few years, BASF has cut back its own bioscience efforts because of what the company calls ‘extremely high technical challenges’,” they write. For them it seems “highly unlikely” that BASF will be transformed into a more dynamic and innovative company by taking over Bayer’s divested units and technology. Ultimately, Grunes and Stucke expect a loss of innovation in the seed sector. Their final verdict on the US Justice Department’s decision to allow the merger? “A mistake.”

Markus Heldt, President of BASF’s Crop Protection division, obviously has a different opinion. “With our expanded port­folio across seeds and traits, chemical and biological crop protection, soil and plant health, and digital farming applications,” he says, “we will have even more tools to support farmers.”

Competitor One: ChemChina Kicking off the jumbo mergers in the industry over the past 18 months was China’s largest che­mistry company China National Chemical Corp. (ChemChina), which acquired Switzerland’s Syngenta in early 2017. The state-owned company paid US$43bn (CHF43.7bn) in cash for the privilege, making it the biggest acquisition of a foreign company by a Chinese company in history. Not long before, ChemChina had bought out the world’s then 7th biggest agrochemistry company Adama (Israel). The Syngenta deal was not only important to the Chinese giant because it will strengthen ChemChina’s

chemistry business, but also strategically, as Syngenta has a strong seeds business with a potent R&D arm.

A recent report by The Wall Street J ournal underlined China’s ambition, mentioning that Syngenta is modernising its biotech centre in Beijing, where plants and animals will be tweaked using modern genome editing technologies. Investments are in the seven-figure range, and 50 staff have begun working there so far – mainly on genome-edited plants. It appears that China skips the classic GMO age altogether as the country has yet to approve a foreign-developed GM crop for cultivation in the country.

Competitor Two: DowDuPont A couple of months after the ChemChina purchase, Dow Chemical Company and DuPont (both US) completed their merger of equals into DowDuPont Inc. Before long, an agriculture division within the company was formed by integrating Dow Agrosciences, DuPont Pioneer and DuPont Crop Protection into what is now called Corteva Agriscience. The merger required the divestiture of various cropprotection and seed portfolio elements to garner approval from US and foreign regulators. US company FMC Agricultural Solutions agreed to buy the bulk of the chemistry assets.

After the formation of DowDuPont, the process of splitting the company into three separate businesses was initiated. Recent updates from the merged giant on the timing and sequence of separating the three divisions into stand-alone, publicly traded companies expect the Materials Science division (“Dow”) to split off by the end of Q1/2019, and Agriculture (“Corteva Agriscience”) and Specialty Products (“Dupont”) divisions to split off by June 1, 2019.

With a focus on seed and crop protection, some analysts believe Corteva Agriscience could be a good fit with BASF.

Competitors Three & Four In 2018, the Big Six in the agrochemicals and seeds market back in 2015 are all set to morph into the Big Four.

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FMC is a pure-play chemistry company.

96% of its products are synthetic pesticides. In 2017, it acquired DuPont’s glo-

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Picture: Nufarm

European Biotechnology | Summer Edition | Vol. 17 | 2018

bal chewing-pest insecticide portfolio, its global cereal broadleaf herbicides, and a substantial portion of DuPont’s global crop-protection R&D capabilities. All together, they had a fair value of US$3.6bn. That helped make FMC the global number five in the agrochemistry and seeds business. Responding to worldwide demand for more specific, bio­logical crop protection solutions, FMC has intensified efforts to broaden its scope by partnering with Danish biotech heavy­weight Chr. Hansen in early June 2018. Chr. Hansen owns a collection of 30,000 microbial strains used in the food, pharmaceutical and agricultural industries. While the two companies say their existing mutual development pipeline will continue to be exclusive for the next five years, the agreement allows both to pursue new relationships with other partners if they wish. The two have launched several biobased products in the past, including the nematicides Quartzo and Presence.

Australian company Nufarm Ltd. was also able to grow business by acquiring competitor assets during the last couple of months of shakeups. For instance, it snapped up over 50 crop protection formulations for US$490m from Adama when owner ChemChina bought Syngenta. It has also purchased herbicides from FMC for US$85m. While Nufarm’s seed segment is tiny (5%) in comparison to its crop protection segment (95%), it’s seeing strong growth. The company has a lot of hope for an ω−3 canola programme that has already been greenlighted by regulatory authorities in Australia and New Zealand. The unique canola strain stably produces between 10% and 12% long-chain ω−3 fatty acids, with the majority as DHA (docosahexaenoic acid). The novel crop could go a long way toward making the production of fish oil from wild-caught fish obsolete. With selected genes from microalgae, the GM crop was developed together with Australian multi-site CSIRO, the Commonwealth Scientific and Industrial Research Organisation. Nufarm plans to sell the extracted oil to the aquaculture and food industries. By extracting the oil from plants instead of fish, it plans to

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Agriculture

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Midland, and Veramaris, a joint venture between Dutch Royal DSM and German Evonik Industries.

Digital impact behind the scenes

Scientists at Nufarm are leading the pack in the race to create canola plants rich in ω−3 fatty acids.

move up the value chain. “This will give us a competitive advantage over commodity seed players,” said Brent Zacharias, Group Executive of Nufarm’s seed division Nuseed. Interestingly, Nufarm has clashed in the past with BASF over intellectual property, although the German company’s challenges to Nufarm and CSIRO patents remained unsuccessful.

Stampeding into the omega-3 fatty acid market Many companies now view ω−3 fatty acids as a big business opportunity. BASF and US food company Cargill Inc. have been developing a genetically engineered ω−3 canola strain since 2009. The event LBFLFK ω−3 canola is genetically engineered to allow for the synthesis of long chain ω−3 polyunsaturated fatty acids – and for resistance to an imidazolinone herbicide. More specifically, the GM plant contains genes encoding seven fatty acid desaturases and three elongases originally isolated from organisms as diverse as oomycetes, green algae, diatoms, moss and flowering plants. They were introduced into a conventional canola variety by A. rhizogenes-mediated transformation. Besides Nufarm and BASF/ Cargill, DowDuPont is also deve­loping a ω−3 source from GM crops. Plant-based technologies are believed to be the most economical way to produce the valuable compound, but some companies are employing fermentation processes to reach the same goals – among them Dutch Corbion (taking over a former Bunge/Terravia project), US food giant Archer Daniels

The consolidation of the industry could have a profound effect in light of a more general trend – digitalisation. The race between the Big Four will be to increase farmer dependence on their digital platforms, which will result in them relying more and more on integrated seed and crop protection solutions. “There are a number of competing companies in this area,“ says Adrian Percy, Bayer Crop Science’s head of R&D. In a kind of Newton’s cradle effect, the digital services will change ownership in the wake of the merger. “The biggest step was taken by Monsanto, which invested almost US$1bn in this area,” Percy adds. In the US, Monsanto’s system “Field View” has been given positive reviews. In 2017, the company initially wanted to collect data from 25 million acres of land – and in the end managed to collect data from around 35 million. Now that Bayer owns the Field View system, it will sell its digital offering – Xarvio – to BASF. If and how BASF’s own digital platform Maglis will be combined with Xarvio has not been communicated.

The danger of a data monopoly is a real one. Monsanto set itself a goal in 2016 to build a centralised data platform for digital agriculture on which third parties can run specialised apps and services. Monsanto would then reap part of the revenue. Additionally, it could ban or penalise offers on the platform that relied on other crop protection agents than its own. Will Bayer, the platform’s new owner, try to establish a monopoly like those enjoyed

by Facebook or Apple? R&D head Percy waves the thought aside. Because agriculture is so diverse, he says, the scope and number of such tools would be so wide that one platform couldn’t possibly host them all. But only time will tell if that assumption holds water. Or if the farmers with their fears about the mergers will be proven right after all.

L m.laqua@biocom.eu

14.06.2018 13:50:34 Uhr

Science & Technology

News Lulling cancer Researchers at the Universities of Dundee and Newcastle have identified the proteasome protein ECM29 as a previously unknown target for the breast cancer drug palbociclib.

In patients with estrogen-receptorpositive breast cancer, a team headed by Matthias Trost and Mikael Björklund found that treatment with the CDK4 cell cycle blocker dissociated the proteasomal component ECM29. Once freed, the proteasome degraded proteins required for cell cycle progression and drove cells into senescence. At least for certain types of breast cancer, patients with low ECM29 levels had longer relapse-free survival times. Thus, the researchers believe that their findings could help identify patients who would profit most from palbociclib treatment.

Diagnostic tattoo Swiss synbio expert Manfred Fussenegger has designed a subcutanously implanted “tattoo“ that indicates hypercalcemia via colour change. Elevated levels of calcium in the blood are an early marker of conditions ranging from kidney failure to cancer. The implanted cells contain a calcium-sensing protein that induces melanin production in the skin, appearing on the skin as a dark patch. In mice with different cancers, the tattoos appeared only on the skin of hypercalcemic mice. Although the tattoo is still in the early stages of development, Fussenegger and colleagues say it could eventually offer clinicians a new method to detect some cancers and other diseases before they cause symptoms.

European Biotechnology | Summer Edition | Vol. 17 | 2018

Lungs under pressure Drug repurposing German researchers have reversed pulmonary arterial hypertension (PAH) by means of the approved diabetes drug pioglitazone. The team headed by Georg Hansmann and first author Ekaterina Legchenko say their findings could lead to new therapies for PAH and other chronic heart and lung conditions.  During pulmonary hypertension, maladaptive right ventricular hypertrophy alters mitochondrial metabolism, and occlusive pulmonary vascular remodeling can ultimately lead to the obstruction of small arteries, ending in right ventricular (RV) heart failure. RV heart failure leads to death in 25% to 50% of patients within five years of diagnosis with PAH, highlighting the need to find new treatments for the condition In S cience Tr ansl ational M edicine (doi: 10.1126/scitranslmed.aao0303) Legchenko et al from Hanover Medical School reported that activation of the peroxisome proliferator-activated receptor gamma (PPARg) via pioglitazone completely reverses severe PAH and vascular remodeling and prevented RV failure in the Sugen hypoxia rat model of pulmonary arterial hypertension. They eval-

uated mice with heart cells deficient in the receptor, a vasoprotective metabolic regulator in smooth muscle and endothelial cells, and observed that deletion of PPARg in cardiomyocytes led to biventricular systolic dysfunction and intramyocellular lipid accumulation in mice compared to control animals. Notably, epigenetic, transcriptional, and metabolic alterations were modulated by pioglitazone through miRNA/mRNA networks previously not associated with PAH/RV dysfunction. Consistently, premiR-197 and pre-miR-146b repressed genes that drive fatty acid transport/oxidation (Cpt1b and Fabp4) in primary cardiomyocytes. Hansmann‘s team recapitulated major pathogenic findings in human end-stage PAH: in the pressureoverloaded failing RV they found miR197 and miR-146b up-regulated; in peripheral pulmonary arteries miR-146b was overexpressed and miR-133b was down-regulated; and in plexiform vasculopathy miR-133b was up- and miR-146b down-regulated.

The authors call for conducting timely Phase I studies with pioglitazone and other drugs that activate PPARgamma in PAH patients.

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Mouse heart function under investigation at the Hansmann lab in Hanover, Germany.

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Picture: Hansmann/Science Translational Medicine

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European Biotechnology | Summer Edition | Vol. 17 | 2018

Science & Technology

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First-generation allogeneic MSC therapy heading EU MSCs Although mesenchymal stem cell therapies have been tested in nearly 500 clinical trials,

their limited expandibility, cell senescence, and the need for immunosuppression to prevent graft vs host disease prevented market success. In March, Belgian TiGenix got EU approval for Alofisel to treat complex perianal fistulas, a complication seen in approximately 3.75% of patients suffering from Crohn’s disease in Europe. In June, Japanese Takeda acquired TiGenix for €520m in cash.

According to TiGenix CEO, Eduardo Bravo, the market for TiGenix’s adipose-derived mesenchymal stem cell (eASC) therapy Alofisel®/Cx601 (darvadstrocel) is huge: “We estimate that over 125,000 adult Crohn’s disease patients suffer from perianal fistulas. More than 55,000 patients fit the expected label; 40% of them in the US.” In March, the European Commission granted the first market approval ever for an allogeneic mesenchymal stem cell therapy to treat the painful complex

perianal fistulas, defined by two or more open channels near the anus. In the US, the company plans to file a BLA in 2021.

So far, only systemic immunosuppressive therapy (infliximab) has been approved in Europe to treat fistulising Crohn’s disease, but high remission rates and increased susceptibility to infection were widely perceived as problematic side effects. Local administration of TiGenix eASCs (expanded adipose stem cells), which can make up 2% of the adipose tissue fraction

obtained through liposuction, have shown benefits compared to TNF blockers: In a pivotal Phase III trial on 212 Crohn’s disease patients with complex perianal fistulas, 56% of patients treated with Alofisel plus standard therapy achieved combined remission vs 39% of those just treated with standard of care.

According to US investigator Steven Wexner from Florida's Cleveland Clinic, the injection of 120 million eASCs was non-inferior to surgery, but without

Allogeneic stem cell approaches

Company

Product name

Sort of treatment

Disease type

Status

› Athersys Inc

MultiStem

Allogeneic multipotent adherent progenitor cells

Ischemic stroke/GVHD

Phase II

› Bone Therapeutics

Allob

Allogeneic osteoblast cell therapy derived from ex vivo-cultured bone marrow cells

Adjunct to spinal fusion surgery

Phase II

› Cynata Therapeutics Ltd

CYP-001

GMP compliant production of MSCs from induced pluripotent stem cells

Steroid-resistant acute graftversus-host-disease (GvHD)

Phase I

› JCR Pharmaceuticals, Mesoblast

Temcell HS

Allogeneic MSC therapy

Acute GHD in bone marrow transplant patients

Authorised in Japan since 2015

› Mesoblast

MPC-150-IM

Allogeneic MSCs

Congestive heart failure

Phase III

› Mesoblast

MSC-100-IV

Allogeneic MSCs

Acute graft- versus-host disease

Phase III

› Pluristem Therapeutics

PLX-PAD

Placenta-derived, mesenchymal-like, adherent stromal cells

Critical limb ischemia

Phase III

› Promethera Biosciences, Belgium

HepaStem

Liver-derived MSCs

Acute-on-chronic liver failure

Phase II

› ReNeuron (Bridgend, Wales)

CTX

Allogeneic neural stem cell therapy

Stroke disability

Phase II

› Rohto Pharmaceutical Co., Ltd.

ADR-001

Adipose-derived mesenchymal stem cells (ADMSCs)

Liver cirrhosis caused by NASH or hepatitis C

Phase I/II

› TiGenix, Takeda

Alofisel/Cx601 (darvadstrocel)

Allogeneic expanded adipose-derived stem cells (eASCs)

Complex perianal fistulas in adult Crohn's disease patients

CHMP recommendation in 12/17, EU approval in 3/2018

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Science & Technology

European Biotechnology | Summer Edition | Vol. 17 | 2018

IP issues of MSC treatments US company Osiris Therapeutics Inc. pioneered FDA-approved allogeneic intravenous hMSC therapies such as Prochymal for the treatment of GvHD. In 2013, the company and its IP portfolio was acquired by Australian Mesoblast Ltd., which relaunched a new formulation, Prochymal, under the brand name Temcell through its Japanese licensee JCR Pharmaceuticals Co. Ltd. Temcell is close to Phase III read out for other markets. Mesoblast's other candidates are made by MSC progenitor cells (MPCs). More importantly, along with Orisis, Meso­b last acquired key patents able to block commercialisation of any bone-marrow and adipose-

the additional risk of muscle damage and subsequent incontinence.

Compared to other first-generation MSC treatments such as bone-marrow derived MSCs (BM-MSCs), Human Adipose Derived Stem Cells (ASC) such as Alofisel showed less cell senescence, less potential to induce GvDH, and better expandibility and differentiation potential.

TiGenix in Takeda takeover TiGenix manufactures Alofisel in the company's Madrid facility, which holds a license from the Spanish Medicines and Medical Devices Agency, “using a highly standardized process.“ According to the company, eASC yields from standard liposuction can be 100 to 1,000 times higher than from other sources of first-generation stem cell approaches. Furthermore, they do not require overly complex growth conditions, do not lose their immunomodulatory characteristics in culture, and maintain cell stability during expansion. Finally, eASCs show low immunogenicity – measured by the presence of HLAs, co-stimulatory molecules, and ligands for neurokinin receptors – and are thus applicable for allogeneic treatment. TiGenix has already

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derived MSC therapy. TiGenix recently acquired an exclusive license under which it made an €20m upfront payment and will pay single-digit royalties to Mesoblast.

Second-generation products, however, can circumvent this IP monopoly. Australian Cynata Ltd. has patented a process that allows GMP-compliant manufacture of MSCs from induced pluripotent stem cell therapies (iPSCs) obtained from a single blood bank sample. iPSCs are an infinitely expandable starting material that can be differentiated into any cell, including MSCs, without undergoing cellular senescence for 10-70 cell passages.

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persuaded Japanese pharma major Takeda to become an early adopter. In 2016, Takeda took a license to except-US commercialisation for €25m upfront, a €10m equity investment, and potential milestones of up to €370m, including a €15m milestone for EU approval. In January 2018, Takeda offered to acquire all outstanding shares and ADR for €1.78 per share, totaling €520m for EU and US commercialisation rights to Alofisel. TiGenix's directors said it was a fair offer and agreed. Insiders, however, pointed out that Takeda will not only add US rights, but also further indications of Alofisel to its portfolio, such as sepsis, which globally affects 24 million people annually. After the first acceptance period of Takeda’s takeover bid, CEO Bravo was replaced by Sebastian Wehle, Senior Director at Takeda.

Beneficiaries of the takeover Australian Mesoblast Ltd appears the true winner of the takeover, which guarantees worldwide supply of the treatment. Because the company acquired key patents blocking commercialisation of MSC-based therapies, it is set to receive royalties from Alofisel sales for the local treatment of fis-

tulae in Europe (see box) and MSC-based therapies from other companies to be approved in the future. Pointing to a license agreement signed with TiGenix earlier this year, Silviu Itescu, CEO of Mesoblast, said: “Without a license from us they would not have been able to launch their product.”

However, Mesoblast will only have a short-term benefit as second-generation MSC-based therapies, which are not covered by its patents, have entered clinical testing. They do not use source MSCs from cell types, with limited potential for self-renewal, but from induced pluripotent stem cells (iPSCs) to manufacture the large amount of stem cells needed for a commercial therapeutic product supply.

Another Australian player “The first-generation approach to the manufacture of therapeutic MSCs is not practical. It relies upon deriving source material or precursors from donated tissue, primarily bone marrow or adipose tissue,” says Ross Macdonald, CEO of Cynata Therapeutics, an Australian company that acquired the rights to produce MSC progenitors – mesenchymoangioblast – from iPSCs GMP-compliantly from WARF at University of Wisconsin. Cynata’s Cymerus platform provides a source of MSCs that is independent of donor limitations and provides an “off-the-shelf” stem cell platform for therapeutic product use, with a pharmaceutical product business model and economies of scale, Macdonald suggests.

“All other technologies rely on supply from multi-donor-derived materials,“ he says. “We have only one donor and minimal expansion of the MSC itself is required to produce sufficient quantities… because cell expansion is undertaken at the level of the ipSCs.” MSCs, in contrast, are capable of substantial self-renewal, which are, however, often accompanied by important changes to the cell characteristics. In Australia and the UK, the company will soon complete a Phase I trial of an iPSC-derived allogeneic MSC product. Macdonald believes that it is a good time for MSC therapies as products have been registered and “the interest of Big Pharma growing.” L

t.gabrielczyk@biocom.eu

13.06.2018 16:03:42 Uhr

European Biotechnology | Summer Edition | Vol. 17 | 2018

Science & Technology

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A global CMO for medical media Stem Cell culture Biological Industries (BI) develops, manufactures, packs, and supplies

cell culture products for academic research, diagnostic labs, hospitals, and the biotechnology and biopharmaceutical industries. BI specialises in serum-free, xeno-free, animal componentfree media, as well as contract manufacturing services that range from raw material supply, through labeling and packaging, to ready-to-market product. › Dr. Sabine Hahnau-Jurth, Head of Sales and Marketing Europe, Biological Industries

Pictures: Biological Industries

Whether for basic research, drug discovery, or therapeutic applications, stem cell differentiation requires standardised culture methods to ensure reproducible and reliable results. To support stem cell research and production, Biological Industries (BI) offers a specific set of xenofree, animal-free cell culture media, stem cell reagents, and protocols. This evolving product portfolio offers a powerful base to support researchers in culturing, reprogramming, characterising, and differentiating stem cell colonies. From identifying colonies and their lineages to monitoring changing morphology, BI’s stem-cell products are accelerating researchers’ quest to understand disease processes.

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BI is dedicated to site alignment and production processes which allow clients to confidently use BI as their sole supplier of medical cell media products. Extensive experience in liquid manufacturing and packaging makes BI an excellent partner for companies moving their products from the laboratory and pilot-scale to full-scale production. BI scientists, equipped with their latest technologies, are available to offer direction on cell line, media, and process development challenges. The BI team will identify the best available medium and is able to scale-up to a commercial level within a short period of time. BI can be a reliable outsourcing partner to expand its clients’ capabilities. Though almost any of

the current catalogue cell culture media formulations can be adjusted to create a customised cell culture medium, BI’s media development and optimisation services are clearly focused on stem cell product development. BI’s tailored services include: sterile filtration and aseptic filling, flexible packaging in industrial single-use (bulk) bags from 0.5 to 2000 litres, pilot-scale freeze drying (lyophilisation), and an extensive range of Quality Control services.

Quality standards are crucial As a manufacturer for the life science industry, Biological Industries is fully committed to the current Good Manufacturing Practices (cGMP) comprising local law, as well as international guidelines adopted by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA). BI’s quality systems comply with the international standards for Quality Management Systems as defined by the ISO 13485:2003 and is routinely audited by accredited external bodies. Their manufacturing facility is an ISO 9001:2015 and ISO 13485:2003 certified facility and their controlled-environment clean rooms are graded from ISO 8 up to ISO 5 (classified from class 100,000 to 100). Products are divided into two groups: ‘For Research Use Only’ and ‘For In Vitro Diagnostics’.

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13.06.2018 16:04:12 Uhr

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European Biotechnology | Summer Edition | Vol. 17 | 2018

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

Europe: european-biotechnology.net

Europe: medtecheurope.org

Europe: europabio.org

Austria: lifescienceaustria.at

Switzerland: swissbiotech.org

Spain: asebio.com

Guide online Precision Medicine SwedenBIO has launched a new report representing the first effort to map the Swedish Precision Medicine Industry Landscape and showcase precision medicine companies in Sweden to the global life science community. The report covers: ›› A comprehensive list of Swedish companies active in the field covering projects and products, development phase, and partnering status ›› Therapeutic and technology highlights include oncology, infectious diseases, imaging, and liquid biospies ›› National resources and platforms are also covered: Science for Life Laboratory, Human Protein Atlas and National biobanks, and quality registers.

It covers 76 companies developing products and services that have the potential to advance the precision medicine sector. The report can be found online at: www.swedenbio.com. 

EU project Europe: medicinesforeurope.com

Ireland: ibec.ie/ibia

Denmark: danskbiotek.dk

The Netherlands: hollandbio.nl

Germany: biodeutschland.org

Portugal: www.p-bio.org

UK: biopartner.co.uk

France: france-biotech.org

Council of European BioRegions

CMYK

Italy: assobiotec.it

Sweden: swedenbio.com

Hungary: hungarianbiotech.org

Europe: cebr.net

Europe: ebe-biopharma.org

Norway: biotekforum.no

Finland: finbio.net

Belgium: bio.be

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

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

Biovoices The Spanish Association of Biocompanies (ASEBIO) has joined the BIOVOICES project – with funding from the European HORIZON 2020 programme – which aims to promote knowledge of the bioeconomy among society. The main function of ASEBIO within this project is the classification of stakeholders in the field of bio-economics and the organisation of workshops (at least four European, two national, and four regional) in which it will define lines of action, barriers, and opportunities.

With a duration of three years and a budget of €3m, the project aims to encourage innovation and promote the positive perception of bioproducts, with the participation of 13 entities, including SMEs and public and private associations from 10 European countries, which will generate more than 50 events with more than 2,800 experts. 

EBE

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“WHITE BIOTECHNOLOGY” WORKING GROUP

sector is internationally visible. The project-specific participating companies (most of them young and internationally less savvy) find a comprehensive partner which is helping to put them in the public window.

Leading chemical companies are exploring the opportunities that have been opened up by modern bio- The participating Life Science Regions are important internal carriers of the dynamics in the Biotech sectechnology, especially in the field of “white” or industrial biotechnology.

And they Edition are also |applying | Summer | 2018 tor, thus enhancing the common understanding of the European Biotechnology Vol. 17these technologies, wherever it makes sense. The SBA takes industry. This and more knowledge is brought into Europa Bio, the European Biotech Association, where such initiatives seriously and has formed a working the SBA is an active member. group specifically dedicated to white biotechnology.

The Swiss Industrial Biocatalysis Consortium is an important partner in this effort. The group includes leading multinational companies that support white biotechnology as a pillar of economic growth. The planned activities are in agreement with OECD strategies.

In partnership with the Swiss Biotechnet (see pages 14/15) the SBA develops training programmes and useful support tools for the industry. It is of importance that the industry specifies its training needs so that the academic side can create tailor-made education.

This strategy ensures that the industry gets the right Domenico Alexakis workforce with the right education. The SBA profits is Executive Director from the marketing alliance “Swiss Biotech” (see box) of the Swiss Biotech in a multiplied form. Thanks to Swiss Biotech, the Association.

New records at the Swiss Biotech Day

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

associations

@

www.swissbiotechassociation.ch www.swissbiotech.org

› 27 September 2018, Lausanne Swiss Biotech Day Fall

try across Europe visited the Swiss Biotech Day in Basel – a record-breaking attendance. Record figures were also revealed for the Swiss biotech industry for 2017 in financing, infrastructure investment, and exports.

› 19 May 2019, Basel Swiss Biotech Day & Swiss Biotech Success Stories celebration

The value of pharmaceutical and biotechnology product exports in 2017 totalled CHF 83.8 bn, which is about 38% of the total Swiss expor t volume. The future for Swiss biotech also looks very promising: The solid development pipeline of the industry and the quality of its patents will secure Swiss biotechnology’s place on the global market in the longer term.

A varied and beneficial program At the annual get-together for the industry, sessions on fostering closer cooperation between companies and investors, partnering talks in a private setting, discussions with experts on financing, as well as presentations from more than a

The Swiss Biotech Association honored the high-spirited laureates Biogen, Glycart, Okairos, Selexis, and Vifor Fresenius Medical Care Renal Pharma for their major industry achievement. With the launch of its Swiss Biotech Success Stories campaign, the association also celebrated its 20th anniversary.

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Upcoming For Events further information please visit

SBD 2018 More than 600 senior executives from the life science indus-

This year‘s Swiss Biotech Day was full of highlights and records. Examples include the launch of the Swiss Biotech Success Stories, awarded for remarkable industry achievements, and the keynote from Novartis CEO, Vas Narasimhan.

The success of the Swiss biotech industry continues. In 2017, the 237 biotech companies and 60 suppliers of the industry employed more than 13,700 staff members (+2.5%) and their sales increased by 14% to reach CHF 3.79 bn. Compared to the previous year, capital investment in private and listed Swiss biotech companies doubled to CHF 1.64 bn – the highest figure since the Swiss Biotech report was first published. In addition, investment in research and development increased by more than 22% to CHF 1.39 bn.

Pictures: SBA

SWISS BIOTECH...

dozen young companies and start-ups, awaited the participants. On the occasion of its 20th anniversary, the Swiss Biotech Association launched its new campaign, the Swiss Biotech Success Stories, in the evening. The first recognitions, selected by an independent jury of experts, went to Biogen, Glycart, Okairos, Selexis, and Vifor Fresenius Medical Care Renal Pharma. In the future, more Swiss Biotech Success Stories will be added to cover all of the industry’s different facets. “Biotech is one of the most innovative sectors in Switzerland. The industry represents an unparalleled success story, attracting talents and investments from all around the globe,” said Michael Altorfer, CEO of the Swiss Biotech Association. “With Swiss Biotech Success Stories, we are honoring our pioneers, entrepreneurs, innovators, and leaders – all those extraordinary people who lead the way, open the horizon, and prepare the ground for lasting achievements.”

The Swiss Biotech Report is available digitally at: www.swissbiotech.org/report/swiss-biotech-report-2018.

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14.06.2018 13:52:51 Uhr

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UN’s sustainable development goals Europe Industrial biotechnology plays a fundamental role in deliver-

ing solutions for a large majority of the Sustainable Development Goals (SDG), both in the EU and globally.

Upcoming events › 24–30 September, Europe European Biotech Week www.biotechweek.org › 16–18 October, Toulouse European Forum for Industrial Biotechnology and the Bioeconomy (EFIB) www.efibforum.com

Website launched GMOinfo. eu Factual information

and feed, detergents, paper and pulp, textiles, as well as bioenergy, such as biofuels and biogas. It can also play an important role in bioremediation through water purification and soil recovery. As such, IB is increasingly recognised by most stakeholders as playing an important role in responding to some of the greatest global challenges and helping to achieve objectives under the UN’s SDG framework.

Read the report, which also includes policy recommendations for the EU, on the EuropaBio website at europabio.org/industrial-biotech.

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Thumbs down to SPC waiver Opinion EuropaBio reacted to the Eu-

ropean Commission’s recent proposal for a waiver of the rights of holders of Supplementary Protection Certificates for innovative medicines by arguing that it weakens the attractiveness of the EU as a hub for biopharmaceutical innovation. The approach of taking incentives

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away from one part of the biopharmaceutical industry to give to another part of the same industry is the wrong way to serve patients and foster innovation in Europe.

Read our take at europabio.org/healthcare-biotech.

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about GMOs in Europe can be hard to find, especially in languages other than English. Instead, there are a lot of misperceptions about a fascinating technology that has truly revolutionised food and farming in much of the developed and developing world.

This is why EuropaBio, together with partners in 11 countries, launched the GMOinfo.eu website, which includes important information about GMOs in 10 different languages.

The GMOinfo.eu page is operated by the Agricultural Biotechnology Council (abc) in partnership with EuropaBio. www.GMOinfo.eu 

Pictures: EuropaBio xxx

A new study from EuropaBio shows how Industrial Biotechnology (IB) contributes towards achieving eleven out of the seventeen SDGs by enabling smarter, more efficient use of precious natural resources, developing renewable alternatives to traditional fossil-carbon products, helping to mitigate the impacts of climate change, reducing energy consumption and manmade emissions to soil, air, and water. IB uses enzymes and micro-organisms to make bio-based products in sectors such as chemicals, bio-based plastics, biobased lubricants, bio-based solvents, food

13.06.2018 16:05:02 Uhr

European Biotechnology | Summer Edition | Vol. 17 | 2018

Thinking smarter, working harder

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The Medtech Forum 2019 › 14–16 May 2019, Paris

Medtech week The fourth annual MedTech Week took place in

June. Michelle Brennan, a Chair of the Board of MedTech Europe, draws her conclusions.

Pictures: Medtech Europa

During my tenure in the medical techpossible solutions to health systems, nology industry, including in my role care providers, and patients. Our longas Chair of the Board of MedTech Eustanding mission to deliver value at everope, I have been honored and humry stage of the care pathway means unbled on countless occasions to see the dergoing a medical procedure today has results of our industry’s contribution to never been safer, and predictive patient healthcare delivery. This June marked outcomes continue to improve. another of these occasions: From 4 - 8th of June, the industry celebratCommitment to ed MedTech Week. National medtech patients associations and companies organised activities across Europe to promote To maintain care standards, it is our rethe value of life-changing technolosponsibility to never settle for existing gies. Events have been held best practices, and to always in 15 dif ferent countries. strive to improve the physiThe range of topics included cal and figurative tools in the AMR/ HAIs, digital health, hands of our care providers. medical technologies, staOur commitment is unwatistics, and healthcare inforvering in the support of pamation through integrated, tient-centered, evidencedigital medical technology based healthcare, and the solutions. It is a week during role medical technolog y which organisations producplays in improving people’s ing life-changing technolo- Michelle Brennan, health and well-being across gies hold events and activi- Chair of the Board of Europe is more important ties to promote the value of MedTech Europe today than ever before. But their work. what about tomorrow?

MedTech mission to deliver value

Expand access and improve efficiencies

The MedTech Week initiative offered a collective opportunity to take a step back as an industry to observe and celebrate, but also to anticipate the impact that medical technology can have on patient lives and health outcomes in Europe. Currently, we are riding perhaps the steepest evolutionary curve in our history. We are thinking smarter and working harder to bring the best

It is universally agreed that our ageing population and the increasing prevalence of chronic disease will be one of the greatest barriers to high-quality and sustainable healthcare in Europe’s future.

Despite the strain this is already placing on resources, health systems must expand access to medical technologies while also improving efficiencies that will put value at the forefront of care: en-

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hancing patient experience and improving outcomes while reducing costs.

Medtech & value-based healthcare The medical technology industry is uniquely positioned to work collaboratively with decision-makers to help set the governing standards of value-based healthcare, and I believe we have a critical role to support health systems to look beyond budgets to holistic healthcare.

This is where innovation is born and how sustainable healthcare will flourish. We must remain accountable to ensure quality care reaches patients and innovations reach health providers in the years and decades to come. There is nothing more important than the health of our population and, quite rightly, people and populations will always ensure we evaluate our worth through the value we deliver. L Michelle Brennan, Chair of the Board of MedTech Europe and Company Group Chair, Johnson & Johnson Medical Devices Companies, Europe, Middle East & Africa (EMEA)

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Events

Medical Writing 5 July 2018 Martinsried Medi-

cal writing in clinical trials – what, who, why, and how? This workshop will address these questions and covers the tasks, the documents, and the timelines involved in the medical writing process in clinical trials. What’s the role of medical writers and how do they support the research team? www.bio-m.org

European Biotechnology | Summer Edition | Vol. 17 | 2018

2.–6.9.18

BiPoCo 2018 – 4th International Conference on Biobased Polymers and Composites, Balatonfüred (HUN) Info: Dora Tatraaljai, Department of Physical Chemistry and Materials Sciences, Budapest University of ­Technology and Economics www.bipoco2018.hu/

10.–12.9.18

Nordic Life Science Days 2018, Stockholm (SE) Info: Olivier Duchamp, Bionordic Services AB www.nlsdays.com

11.–14.9.18

Basel Life 2018, Basel (CH) Info: Congrex, www.basellife.org

18.9.18

5th Annual Risk Management and Pharmacovigilance Summit , Vienna (AT) Info: Allan Lloyds Group www.pharmariskandcovigilance.com

20.–22.9.18

2nd Global Conference on Plant Science and Molecular Biology, Rome (IT) Info: Magnus Group, http://plant-science-biologyconferences.magnusgroup.org

25.–27.9.18

Biospain 2018, Seville (ES) Info: Margarita Arriaga, Spanish Association of Biotech companies – Asebio https://www.biospain2018.org

30.9.–3.10.18

HUPO 2018, Orlando (USA) Info: Human Proteome Organization http://hupo2018.org/

Life Science Baltics 26 –27 September, Vilnius The goal of Life Science Baltics 2018 is to connect business and science to discuss the best new research and trends in the field of life sciences – biotechnology, pharmaceuticals, and medical devices.

www.lsb2018.com

20.–21.9.18

12 th World Congress on Biotechnology and Microbiology, Amsterdam (NL) Info: Alisa Paul, ConferenceSeries https://microbiology.annualcongress.com/

1.–4.7.18

European Congress on Biotechnology – ECB 2018, Geneva (CH) Info: European Federation of Biotechnology EFB www.ecb2018.com

1.–4.7.18

CTLS2018@VIB – Core Technologies For Life ­Sciences, Ghent (B) Info: VIB https://vibconferences.be

16.–17.7.18

International Conference on Synthetic Biology, Paris (F) Info: Meetings International www.meetingsint.com/conferences/syntheticbiology

19.–20.7.18

13th International Conference on Microbial Interactions & Microbial Ecology, Rome (IT) Info: ConferenceSeries https://microbialinteraction.conferenceseries.com/

9.–10.8.18

11th Edition of International Conference on ­Proteomics – Exploring Novel Drug in the Field of Proteomics, London (UK) Info: EuroSciCon Ltd, http://proteomics.euroscicon.com/

1.–3.9.18

4th Plant Protease and PCD System, Ghent (B) Info: VIB, https://vibconferences.be

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Structural Dynamics in Cellular Communication (2nd edition), Brussels (B) Info: VIB, https://vibconferences.be

24.–30.9.18

European Biotech Week 2018, EU Info: Mélanie Moxhet, EuropaBio www.biotechweek.org

BIOCAT 2018 26–30 August Hamburg The biennial Biocat congress series is focused on the rapidly evolving fields of biocatalysis and industrial biotechnology. The major topics to be addressed, inter alia, are: enzyme discovery, production and application; structure-function analysis and enzyme design; sustainable industrial processes. www.biocat-conference.

30.9.–2.10.18

Cell-Nerf Symposium: Neurotechnologies, Leuven (B) Info: VIB, https://vibconferences.be

1.–2.10.18

Refab 2018 – Revolution in Food and Biomass Production, Cologne (GER) Info: nova-institut, http://refab.info

2.–4.10.18

Medlab Europe, Barcelona (ES) Info: Informa Life Sciences https://www.medlabeurope.com/en/home.html

8.–9.10.18

Synthetic Glycobiology, Chicheley (UK) Info: The Royal Society https://royalsociety.org

9.–11.10.18

CPhI Worldwide 2018, Madrid (ES) Info: CPhI Global Office, www.cphi.com

9.–11.10.18

bioLIVE, Madrid (ES) Info: UBM, http://www.bio.live/

Pictures: BIOM/Carmen Steiner - footolia/https://ie.mfa.lt

28.–29.6.18

15.06.2018 10:06:13 Uhr

European Biotechnology | Summer Edition | Vol. 17 | 2018

3P Biopharmaceuticals S.L. (ES). . . . . . . . . . . . . . . . . . . . 67 Abcam (UK). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25, 69 Ablynx (B) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Adama (IL). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77, 78 ADC Therapeutics SAS (CH). . . . . . . . . . . . . . . . . . . . . . . 20 Affiris AG (AT). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 Aldevron GmbH (DE). . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Alexion Pharmaceuticals (USA) . . . . . . . . . . . . . . . . . . . . 67 Amgen Europe B.V. (CH). . . . . . . . . . . . . . . . . . . . . . . . . 24 Amplidiag Oy (FI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Anergis SA (CH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 ASEBIO (ES). . . . . . . . . . . . . . . . . . . . . . . . . 45, Supplement Asit Biotech SA (B). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 AstraZeneca AB (SE/UK). . . . . . . . . . . . . . . . . . . . . . . . . . 19 Avexis Inc. (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . 25, 71 BASF AG (DE). . . . . . . . . . . . . . . . . . . . . . . . . . . . 77, 78, 79 Bayer AG (DE) . . . . . . . . . . . . . . . . . . 19, 21, 25, 77, 78, 79 BIA Separations d.o.o. (SLO). . . . . . . . . . . . . . . . . . . . . . . 73 BIOCOM AG (DE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CP3 BioFIT 2018 (F). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Biogen Idec (USA) . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 71 Biognosys AG (CH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 BioJapan 2018 (JP). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Biological Industries (BI) Ltd. (USA) . . . . . . . . . . . . . . . . . 83 Biomarin Pharmaceuticals (USA) . . . . . . . . . . . . . . . . . . . 16 Biomay AG (AT). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 Bioverativ (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Biovertis AG (AT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 bluebird bio (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . 25, 71 Boehringer Ingelheim (DE). . . . . . . . . . . . . . . . . . . . . . . . 69 CANDOR Bioscience GmbH (DE) . . . . . . . . . . . . . . . . . .

Capital Cell (ES). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Cara Therapeutics (USA). . . . . . . . . . . . . . . . . . . . . . . . . .

Cargill Inc. (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Cassiopea SPA (IT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Celgene Corp. (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . .

Cellectis (F). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ChemChina (CN) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chugai Pharma Europe Ltd. (UK) . . . . . . . . . . . . . . . . . . .

Citoxlab Group (F). . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Clovis Oncology UK Ltd.. . . . . . . . . . . . . . . . . . . . . . . . .

Coca-Cola (USA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Concept Heidelberg (DE). . . . . . . . . . . . . . . . . . . . . . . . .

Cosmo Pharmaceuticals NV (NL). . . . . . . . . . . . . . . . . . .

CPhI / BioLive 2018 (NL) . . . . . . . . . . . . . . . . . . . . . . . . .

CRISPR Therapeutics (CH/USA) . . . . . . . . . . . . . . . . . . . .

Cynata Ltd. (AU). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

23 73 70 79 70 71 25 77 17 74 24 10 57 21 47 20 82

Deinove SA (F). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

DGPharMed/DGPharmMed Annual Meeting 2019 (DE). .

DowDuPont (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Dunn Labortechnik GmbH (GER . . . . . . . . . . . . . . . . . . .

Dynabind GmbH (DE) . . . . . . . . . . . . . . . . . . . . . . . . . . .

68 38 77 11 74

EFIB 2018 (B). . . . . . . . . . . . . . . . . . . . . . . . 51, Supplement EBD Group (CH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 Eppendorf AG - Bioprocess Center Europe (DE) . . . . . . . . . 7 EuropaBio /European Biotech Week (EU). . . . . . . . . . . . . 43 European Business Dev. Conf. 2018 (DE). . . . . . . . . . . . . 53 Evotec AG (DE). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Exelixis, Inc. (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 FESIA (ES). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 FGK Clinical Research GmbH (DE). . . . . . . . . . . . . . . . . . 18 FMC Agricultural Solutions (USA). . . . . . . . . . . . . . . . 77, 78 Freenome Inc. (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Genentech Inc. (USA). . . . . . . . . . . . . . . . . . . . . . 17, 20, 21 Genewave SAS (F) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Genmab A/S (DK). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 GenSight Biologics (F) . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Gilead Ltd. (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 GlaxoSmithKline (UK) . . . . . . . . . . . . . . . . . . . . . . . . 25, 69

company index /Product

Kite Pharma (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Lundbeckfond Ventures (DK) . . . . . . . . . . . . . . . . . . . . . . 66 Medical Prognosis Institute A/S (DK). . . . . . . . . . . . . . . . . 66 MediGene AG (DE). . . . . . . . . . . . . . . . . . . . . . . . . . . 25, 71 Merck & Co. (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . 20, 25 Merck KGaA (DE). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Mesoblast Ltd. (AU) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 Mobidiag Oy (FI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Molecular Partners AG (CH). . . . . . . . . . . . . . . . . . . . . . . 70 MolMed (IT). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Mologen AG (DE). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Monsanto (USA). . . . . . . . . . . . . . . . . . . . . . . . . . 77, 78, 79 MorphoSys AG (DE). . . . . . . . . . . . . . . . . . . . . . . . . . 68, 71 Mymetics S.A. (CH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 Nestle S.A. (CH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Neurimmune AG (CH). . . . . . . . . . . . . . . . . . . . . . . . 71, 75 NMD Pharma A/S (DK). . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Nordic Life Science Day (SE) 2018. . . . . . . . . . . . . . . . . . 41 nova-Institut GmbH (DE) . . . . . . . . . . . . . . . . . . . . . . . . . 29 Novartis AG (CH). . . . . . . . . . . . . . . . . . . . . . 22, 23, 71, 72 Novo Nordisk A/S (DK). . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Novo Seeds (DK) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Novozymes A/S (DK) . . . . . . . . . . . . . . . . . . . . . . . . . 25, 31 NTC Pharma (IT). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Nufarm Ltd. (AU). . . . . . . . . . . . . . . . . . . . . . . . . . . . 78, 79 Oncoarendi Therapeutics SA (PL). . . . . . . . . . . . . . . . . . .

Oncology Venture Sweden AB (SE). . . . . . . . . . . . . . . . . .

OPIS s.r.l. (IT). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Orchard Therapeutics (UK/USA). . . . . . . . . . . . . . . . . . . .

Ose Immunotherapeutics SA ( . . . . . . . . . . . . . . . . . . . . .

Osiris Therapeutics (USA). . . . . . . . . . . . . . . . . . . . . . . . .

Otsuka Pharmaceutical

74 66 19 69 69 82

89

Cancer research Promocell PromoKine’s Angiogenesis Assay Kit provides a simple, robust, easy to perform and semi-quantitative method to determine angiogenesis in vitro in less than 18 hours. It can be used for screening of angiogenesis modulators or studies of angiogenesis related signal transduction.

The assay is based on the measurement of the ability of endothelial cells to form 3D structures (tube formation) under the influence of distinct stimulators, and uses a proprietary endotoxin-free and growth factorreduced Extracellular Matrix Solution.

The Cell Migration/Chemotaxis Assay Kits are easy to use, sensitive and high throughput-adaptable systems. They uti-

PepsiCo. (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Pfizer (USA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16, 19 Polpharma Biologics (PL) . . . . . . . . . . . . . . . . . . 34, 35, CP4 Polyphor Ltd. (CH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 Procter & Gamble (USA). . . . . . . . . . . . . . . . . . . . . . . . . . 25 Promocell GmbH (DE). . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Puretech Health plc (USA). . . . . . . . . . . . . . . . . . . . . . . . 75 Qiagen NV (DE). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Reckitt Benckiser (UK) . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Redx Pharma (UK) . . . . . . . . . . . . . . . . . . . . . . . . . . . 68, 75 Regeneron Pharmaceuticals Inc. (USA). . . . . . . . . . . . 19, 21 Rentschler Biotechnologie GmbH (DE). . . . . . . . . . . . 36, 75 Roche Group (CH). . . . . . . . . . . . 15, 16, 17, 19, 21, 25, 71 Roche Venture Fund (CH). . . . . . . . . . . . . . . . . . . . . . . . . 66 Sangamo Biosciences Inc. (USA) . . . . . . . . . . . . . . . . . . . 16 Sanifit (ES) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Sanofi SA (F) . . . . . . . . . . . . . . . . . . . . . . . . . 13, 21, 25, 75 Servier (F). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Shimadzu (DE). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CP2 Shire plc (IRL). . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 16, 69 Shuwen Biotech (CN). . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Siemens Healthineers (DE). . . . . . . . . . . . . . . . . . . . . . . . 25 Solvo Biotechnology sro (HUN). . . . . . . . . . . . . . . . . . . . 74 Sophia Genetics (CH). . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Sotio a.s. (CZ). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 Springvest (FI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Sunshine Kaidi Finland New Energy Co. Oy (CN/FIN) . . . 67 Syngenta AG (CH) . . . . . . . . . . . . . . . . . . . . . . . . 77, 78, 79 Takeda Pharma A/S (DK). . . . . . . . . . . . . . . . 13, 16, 69, 82 Targovax AS (NO). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Tech4Freedom (ES). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 Thrombogenics (B). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 TiGenix (B). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81, 82 Trianni, Inc. (USA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 TVM Capital Life Science (DE). . . . . . . . . . . . . . . . . . . 9, 68 uniQure BV (NL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

lize a Boyden chamber, where the cells migrate through a semi-permeable membrane (three different pore sizes available) in response to stimulatory or inhibitory compounds.

The Cell Invasion Assay Kits also utilize a Boyden chamber that is coated with a layer of BME (Basement Membrane Extract), laminin, fibronectin, Collagen I or Collagen IV. The cells first traverse the matrix and then migrate through the semi-permeable membrane in the Boyden chamber in response to different stimuli. Cell migration as well as cell invasion can be analysed directly using a fluorescence plate reader. D

Pictures: PromoCell

Horizon Discovery Ltd. (UK) . . . . . . . . . . . . . . . . . . . . . . 25 Idorsia (CH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

INKEF Capital (NL). . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Intervac AB (SE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Ionis Pharmaceuticals (USA). . . . . . . . . . . . . . . . . . . . . . .

70 66 67 71

Janssen Biotech Inc. (USA). . . . . . . . . . . . . . . . . . . . . . . . 20 Jennewein Biotechnologie GmbH (DE). . . . . . . . . . . . . . . 20

89_EB_Summer_2018_Index_PI.indd 89

Versli Lietuva (LT). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Vertex Pharmaceuticals Inc. (USA). . . . . . . . . . . . . . . . . .

Vetter Pharma-Fertigung GmbH & Co.KG. . . . . . . . . . . . .

Vifor Pharma AG (AT). . . . . . . . . . . . . . . . . . . . . . . . . . . .

Vivet Therapeutics (F). . . . . . . . . . . . . . . . . . . . . . . . . . . .

35 20 21 70 67

Wilhelm Bähren GmbH & Co. KG (DE) . . . . . . . . . . . . . . 33 Wilson Therapeutics AB (SE). . . . . . . . . . . . . . . . . . . . . . . 67

Contact

PromoCell GmbH Sickingenstr 63/65, 69126 Heidelberg www.promokine.info info@promokine.info

15.06.2018 12:17:10 Uhr

Encore

Winners & losers

European Biotechnology | Summer Edition | Vol. 17 | 2018

Alien enzymes

What fascinates you the most about your job?

Organometallic Chemistry Biotechnologists have a crush on artificial metalloenzymes. Introducing synthetic metal cofactors to a protein framework opens up new possibilities. When natural enzymes are not suited for a certain reaction type, artificial metalloenzymes might be. Lately, researchers from the Universities of Basel and Geneva, as well as from ETH Zurich (all Switzerland), have shown that these new catalysts can perform their job also in living cells, interacting seamlessly with the cell‘s machinery (Nature Communications, doi: 10.1038/ s41467-018-04440-0). What the scientists did was to design a cell-pene­trating artificial metalloenzyme that accelerated the release of a hormone in the cell. The hormone activated a gene switch, leading to the production of fluorescent proteins. 

Biopolyester Kickoff Italian polyhydroxy-

alkanoates producer Bioon SpA is on a roll – with the stock up 50% within a month. First, the bioplastics specialist kicked off two new companies, one for urea-based fertilizer coatings, the other for new tobacco packaging solutions. Later in June, it opened its new biodegradable microbead plant.

Michael Roberts Founder & CSO of synbio pioneer Synpromics Ltd.

BioSuccinic Acid Write-off US-

“The only limitation on what is achievable stems from the boundary of our imagination; it astounds me when madcap concepts emerging from our eclectic group turn into viable sought-after solutions.”

Going for wheat straw Second generation biorefineries run on all kinds of agricultural wasteproducts. A new study assessed all sustainably available lignocellulosic residues in the 28 countries of the European Union to feed a high added-value materials and product bioeconomy (Journal of Cleaner Production, doi: org/10.1016/j. jclepro.2017.12.143). The most untapped potential lies in wheat straw, as approximately 49 Mt out of 96 Mt of total straw available is free to use for the bioeconomy.

Share of lignin, (hemi)celluloses & tannin in %

based biosuccinic acid producer Bioamber Inc. declared bankruptcy in May to restructure its finances. Due to low energy and raw material costs, the product couldn't compete with the conventionally made product. 

90

Rape straw

85

Wheat straw

Oats straw

Sunflower straw Barley straw Triticale straw Coniferous bark Rye straw

80 75

Source: A. Thorenz et al., Journal of Cleaner Production Volume 176, 1 March 2018

90

Maize stover

70 65 Broadleaf bark

60 55 50

0

5

10 15 20 25 30 35 40 Bioeconomic potential EU-28 in million tonnes

45

50

Novartis general counsel resigns over Michael Cohen payment @politico Fantastic to see @OxfordBioMedica's $843m deal with Axovant to commercialise Parkinson's disease gene therapies. BioMedica spun out of @UniofOxford 23y ago – they grow up so fast … @OxUInnovation Genome-Project write switches focus to produce a virus-resistant human cell line. #Genome #LifeScience @thepcrcompany

90_EB_Summer_2018_Encore_ml.indd 90

What a st reak for t he guys at @YsiosCapital in the last 2 months. TiGenix

Please follow us @EuroBiotechNews to Takeda ($500M all-cash), STAT Diagnostica to Qiagen ($200M) and now Prexton to Lundbeck ($100M u/f + $805M). Hats off!

@GerardCaelles

Autumn edition When autumn leaves

start to show their brightest colours, EuroBiotech counters with a new issue packed with bright ideas. The fall issue of the magazine includes a feature with a range of different CMO and CRO topics.

It will be published on 20 September 2018. Due date for advertisements is 3 September. Questions will be answered

by Andreas Macht (+49-30-264921-54) and Oliver Schnell (+49-30-264921-45). Or drop an email: marketing@biocom.de. 

Picture: Europabio/Veldemanphoto; FARBAI/fotolia.com (bacteria icons)

Cohen @YsiosCapital #Genome Next issue

14.06.2018 13:55:08 Uhr

14.|15.3.

2019 12 th Berlin Conference on Life Sciences

Novel Antimicrobials and AMR Diagnostics Save the date: On 14 and 15 March 2019, the Berlin Conference will once again be the meeting place for Life Science decision makers, business developers, investors and legal experts. The conference will explore the exciting market for the development of novel antimicrobials and AMR diagnostics.

Find more information at:

www.berlin-conferences.com

BIOCOM AG I Lützowstraße 33–36 I 10785 Berlin | Germany events@biocom.de I Tel. +49 (0)30 264921-53 I www.biocom.de

91_EB_Summer_2018_BerlinConference2019.indd 1

14.06.2018 13:58:48 Uhr

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