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Life Sciences and Industry Magazine Winter Edition 2024 | Volume 23 | 20 €

The proteins strike back

Thomas Lingelbach, CEO of French Valneva SE, on the vaccine maker’s latest approval and his strategy.

Antibodies & more

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INTRO

European Biotechnology | Winter Edition | Vol. 23 | 2024

The golden age of engineered therapeutic antibodies Therapeutic antibodies today represent a cornerstone of the treatment of various diseases including cancer, infectious, autoimmune, cardiovascular, haematological, metabolic, neurologic and ocular diseases, and make up a major proportion of blockbuster drugs with global sales of more than US$230bn in 2023.

Since the first approval of monoclonal antibodies more than 25 years ago, the field has seen the emergence of engineered antibodies, e.g.

Fc-engineered antibodies, antibody drug conjugates (ADCs) and bispecific antibodies (bsAbs). Notably, as of today, 13 ADCs and 17 bsAbs have been approved by health authorities and already account for more than US$10bn and US$8bn in global sales, respectively.

DR CHRISTIAN KLEIN, CXO in residence and drug hunter at the earlystage VC specialist Curie.Bio, has 22 years of industry experience in the field of therapeutic antibodies, co-authored 220 publications and is co-inventor of 240 patent families.

The biochemist joined Roche pRED in 2002 and co-led teams pioneering the development of CrossMabs, 2+1 TCBs, 4-1BB/CD28 costimulators and PD1-cis immunocytokines.

He contributed to 32 clinical NMEs for Roche of which four are approved and to numerous collaborations with biotech companies.

It is important to note that bsAbs are increasingly being applied for the treatment of diseases beyond oncology. Based on the recent therapeutic progress, ADCs and bsAbs represent the fastest growing class of therapeutic antibodies in (pre-)clinical development and have been a major driver of deal-making in the biopharmaceutical industry in the past years. Interestingly, the first bispecific antibodies approved, catumxomab and blinatumomab, were originally developed by academic start-ups in Munich, Germany.

ADCs and bsAbs continue to be an attractive area of research for innovative biotech companies due to the availability of technologies allowing a comparably rapid identification and optimisation of development candidates, the progress made with the manufacturing of complex molecules, and the generally favourable clinical development success rates for therapeutic antibodies.

Picture: © Curie.Bio

BsAbs are particularly attractive from a conceptual point of view, as they allow the mediation of completely novel mechanisms of action for the therapy of various diseases that cannot be achieved with conventional monospecific antibodies. This includes, for example, the recruitment and engagement of immune cell subsets for tumour cell killing, e.g., with T-cell engagers, mimicking of blood coagulation factors, dual-targeted bispecific ADCs with selectivity for defined cancer types, cis-targeting of T-cell subsets with dual checkpoint inhibitors or cytokines, degradation of cell surface proteins, transport of antibodies across the blood-brain-barrier, triggering of cytokine receptors with cytokine mimetics or activation mechanisms that can switch bsAbs on/off in the tumour microenvironment to prevent undesired peripheral toxicities, and many more.

It is amazing to see how researchers after 50 years of antibody engineering continue to come up with novel and ingenious solutions to tackle therapeutic challenges and to observe how novel methods like single-cell sequencing, proteomics, cryo-EM, machine learning and artificial intelligence help to further accelerate therapeutic innovation. Given all this progress and the diversity of ideas pursued in biotech companies and biopharmaceutical industry, I firmly believe that the golden age of engineered antibodies and their use for synthetic L ­biology is only about to start. Their potential is beyond our imagination.

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CONTENTS

European Biotechnology | Winter Edition | Vol. 23 | 2024

COVER STORY

INSIGHT EUROPE

REGIONAL NEWS

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58 Northern Europe: Sweden, Denmark, Norway and Finland

Country alliance calls for launch of a European protein strategy

8 Climate and biodiversity paralysis in Baku and Cali 11 Commission seeks industry input over Novo/Calalent acquisition

ECONOMY 20 Interview: Thomas Lingelbach, CEO, Valneva SE 22 Analyst commentary 23 European Biotech Stocks

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A Golden Age for protein engineering Monoclonal antibodies laid the foundation for precision medicine, and still dominate the US$417bn biologics market. However, after decades of development, new treatments are now hitting the market. Among them: improved versions of artificial bispecific antibodies, antibody-drug conjugates and other engineered proteins used in immunoreceptor-based therapies such as CAR-T and TCR-T cell therapies. We took a deep dive into what bioengineers were talking about at the most recent iteration of the PEGS Europe summit.

60 Western Europe: France, Belgium, The Netherlands, Luxembourg and the UK 62 Central Europe: Germany, Switzerland and Austria 64 Southern Europe: Italy, Spain and Slovenia 66 Eastern Europe: Poland and Hungary

SCIENCE & TECHNOLOGY

26 Novartis writes down MorphoSys deal

67 Researchers discover fat memory

27 Radiopharma acquisitions

68 Biotechnological climate rescue

28 30 years of BIO-Europe

70 New data on NK cell engager

32 Update on clinical trials

71 Turning macrophages from bad to good; Testing gene function

35 Unified Patent Court: quo vadis?

72 Nobel Prize award ceremony 37 In focus: Protein engineering 38 Interview: Nina Kreymborg, SVP/CSO Partner Team, Curie.bio 39 Getting to the next stage in ADC development 41 Precision oncology 42 Pharma industry at CPHI 49 Italy’s genius move to captial

74 One in a billion: Basel Institute of Immune Engineering

PICK & MIX 56 Biopeople 75 News from associations 79 New products 80 Company index 81 Events 82 Encore

IMPRINT European Biotechnology (ISSN 2364-2351) is published quarterly by: BIOCOM Interrelations GmbH, Jacobsenweg 61, D-13509 Berlin, Germany, Tel.: +49-30-264921-0, Fax: +49-30-264921-11, Email: service@european-biotechnology.com, Internet: www.european-biotechnology.com; Publisher: Andreas Mietzsch; Editorial Team: Thomas Gabrielczyk (Editor in Chief), Derrick Williams (Co-editor), Dr. Georg Kääb, Uta Mommert, Maren Kühr, Dr. Christian Kähler; Anette Mertens; Advertising: Oliver Schnell, +49-30-264921-45, Christian Böhm, +49-30-264921-49, Andreas Macht, +49-30-26492154; Distribution: Nancy Weinert +49-30-264921-40; Graphic Design: Michaela Reblin; Production: Martina Willnow; Printed at: Königsdruck, Berlin; European Biotechnology Life Sciences & Industry Magazine is only regularly available through subscription with a BIOCOM CARD. Annual subscription BIOCOM CARD Europe: €80 for private individuals (students €40) incl. VAT, €120 plus VAT for corporates. Prices includes postage & packaging. Ordered subscriptions can be cancelled within two weeks directly at BIOCOM AG. The subscription is initially valid for one calendar year and is automatically renewed every year after. The subscription can be cancelled at any time and is valid until the end of that calendar month. 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: © Mirror-images stock.adobe.com; ® BIOCOM is a registered trademark of BIOCOM AG, Berlin, Germany.

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CONTENTS

European Biotechnology | Winter Edition | Vol. 23 | 2024

CLIMATE CHANGE

BIO-EUROPE

EDITORIAL

No will to zero

Stress test for Council Germany, Denmark and 19 supporting states have called on the EU Commission to adopt a protein strategy that prominently includes cultured protein for food and feed, but Hungary is likely to contest the idea. It holds the EU Council presidency and leads a blocking minority calling for rules on banning and approving laboratory foods similar to those in place for medicines.

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Spotlight Scandinavia

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In the latest BIO-Europe in Stockholm, representatives from Sweden, Denmark, Norway and Lithuania grabbed the chance to step out of the shadows. The positive messaging came through loud and clear, along with a load of impressive data about the power of the region’s innovation motor.

Pictures: Freepik - Consilium (left above); Informa /EBD Group (middle); BIOCOM AG (right)

SPECIAL

The fight against climate change and species extinction is a popular topic among politicians. It is becoming increasingly difficult to deny the consequences of global inaction, and looking the other way no longer helps. A lot of money was promised in Montreal back in 2022. At the UN COP15 Biodiversity Conference, negotiators agreed to set up a provisional fund to help heal environmental damage by protecting 30% of land and marine areas and pushing back invasive species. To date, only 2% of the promised cash has been raised. At the follow-up conference in Cali (COP16), further negotiations on the US$200bn biodiversity fund by 2030 agreed in Montreal failed.

At the same time, climate diplomats at COP29 in Baku argued about the financing of climate protection funds (p.

8). Estimates say around US$2,400bn is needed per year to limit global warming to 2°C by 2100. The countries of the Global South, which are responsible for just 5% of greenhouse gas emissions (CHG), called for US$1,300bn. But wealthy nations only countered with an offer of US$300bn. Since the Paris Agreement, CHG emissions have risen by 9% instead of falling by 67.5% as agreed.

Collective action – like that sometimes seen during the pandemic – is critical.

Now that the potential of biotechnology in medicine has grown clear, the biologisation of industry is next. It’s the only way for us all to win in the end.

Biofairs Compass 44 BIO-Europe Spring 2025, Milan, Italy 46 GMP Pharma Conference, Wiesbaden, Germany

Thomas Gabrielczyk Editor-in-Chief

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INSIGHT EUROPE

European Biotechnology | Winter Edition | Vol. 23 | 2024

Country alliance calls for EU protein strategy A dispute is brewing in Europe over climate-friendly protein production in fermenters between EU member states that are in favour of or against protein production independent of agricultural land. Germany, Denmark and supporters called on the EU Commission to formulate a European protein strategy. This is about more than just limiting feed imports from overseas.

PROTEIN ALTERNATIVES

The call of Denmark and Germany at the Agri-Council in mid-November to establish an EU protein strategy sounds harmless. “We believe that changes need to be made to our protein supply – both for food and for feed,’ write the lead agriculture ministers Çem Özdemir (Germany) and Magnus Heunicke (Denmark), supported by Czechia, Estonia, Ireland, Luxembourg, and more. “The supply must comprise more high-quality proteins whose production is less harmful to our climate and bio­diversity. A production of proteins in the EU that is increasingly based on plant protein could reduce the impact that food and feed consumption currently have on our climate, environment and nature. We know that there is a rising global demand for protein, and companies in the EU can contribute to meeting the future need by providing high-quality proteins that are more climate-friendly,” the joint document says.

Broad impact for nutrition In fact, the call came directly after a series of national bans (see European Bio technology 1/2024, 2/2024 and p. 66) and protests against new biotechnological, agriculture-free methods to produce food and feed protein with less greenhouse gas (CHG) emissions that might impact the business of farmers.

To understand what’s behind the call, you need to know three things: › Globally, agricultural emissions cause 17% of global greenhouse gas emissions, according to figures of the FAO. In Europe, at least 71% of farmland

Hungarian agriculture minister István Nagy (left-hand side) with Polish EU Commissioner Janusz Wojchiechowski

is used to feed livestock, while only 20% of feed protein needs to be imported. When policy makers speak of “plant-derived protein”, the term also includes proteins produced by photosynthetic algae, or plant proteins made by precision fermentation, where microorganisms are programmed to secrete plant proteins. Other alternative protein sources include insects or bio­ mass of naturally-occurring bacteria or fungi, according to a study commissioned by the European Parliament. › that Denmark, Germany and their supporters are not only funding such “plant-based protein” with €195m and €41m, respectively, but are also working on other non-agricultural methods of protein production for feed and food, i.e. cell-based food, milk, fish, coffee and more in the Copenhagen CPHLabs Food Incubator and the Berlin food cluster KitchenTown. › that the protein strategy proposal is a deliberate provocation of the current

Hungarian Council Presidency and its right-wing alliance partner Italy, who both received warnings from the EU Commission over their (draft) laws intended to ban fermenter-made meat and who prioritise traditional agriculture instead (see p. 66). The agriculture ministers of Austria, Italy, France, Poland, Spain and Hungary supported such a ban through exclusion of cellbased and fermented foods from the EU Novel Food authorisation in a joint note to the Agricultural Council this January.

German agriculture spokeswoman Renate Kühnast from the still governing party (Alliance 90/The Greens) got to the heart of the unspoken issue when stating: ”We will have less meat consumption and a shift towards plant-based proteins, precision fermentation and cultured meat. It is not yet possible to predict which of these will later have what share of the market.

But in view of the climate crisis and loss of biodiversity, […] nothing can be ruled out.” Christina Stumpp from Germany’s

Picture: © Alexandros Michailidis

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INSIGHT EUROPE

European Biotechnology | Winter Edition | Vol. 23 | 2024

next-to be Christian-Democratic government confirms that “cultivated meat can be a supplement to conventional meat if it is transparently labelled and affordable for consumers. The results so far are promising and we should not sleep through this development. More speed in authorisation would therefore be desirable.” This in mind, it is questionable whether the blocking minority in the EU – Hungary, Italy, and supporters in the Council, who want to protect their farmers’ businesses – will vote for the protein strategy once the new EU Commission is confirmed.

On the road again Farmers’ lobby groups from Italy, the Czech Republic, France, Poland, Portugal and Spain have already marked their territory and for now protested in an open letter against new guidelines for Novel Food applications published in October by EU food watchdog EFSA. The guideline draft,

which is set to come into force in February 2025, includes cell-based and fermented foods, and streamlining approval times. The EU authority also clarified that food safety remains its highest priority when recommending novel food products for market authorisation. However, farmer associations demanded to establish the same evaluation criteria for cultured meat as reserved for new medicines, and called to suspend market authorisation for cell culture products on ethical and social grounds. Changing the rules for approving cultured meat is the responsibility of EU legislators and not EFSA, responded Bernhard Url, the Director of the EU food safety watchdog.

Following an EFSA application of French food-tech company Gourmey SAS for a cell-based duck liver pâté (Foie gras), in July, Finland’s Enifer Oy seeked Novel Food authorisation for its mycoprotein-based ingredient PEKILO from EFSA at the end of October. The dry

powder is to be produced by biomass fermentation of Paecilomyces variotii KCL-24 in a new €33m production facility that can produce up to 3,000 tonnes mycoprotein annually from food industry side streams. Enifer’s long-term plan is to market PEKILO as dry powder to food producers, but for now, it is focused on supplying pet food (Purina) and aquaculture (Skretting) companies. However, as market applications are being planned in Singapore and the US, where approval times for novel food products for human consumption are three times shorter (< 12 months) than in Europe, meat and dairy alternatives marketed by Enifer’s partner Valio will be introduced rapidly.

Enifer’s process goes back to the 1970s, when byproducts from the forest industry were fermented into animal feed ingredients. Thus, the feed is proven to be an excellent source of protein for live stock, particularly pigs and poultry. t.gabrielczyk@biocom.eu

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INSIGHT EUROPE

European Biotechnology | Winter Edition | Vol. 23 | 2024

Climate paralysis at COP29 in Baku Climate finance, which expires next year, was at the centre of negotiations between the climate diplomats at the COP29 summit from 11 to 22 November.

Increasing extreme weather events are calling for a multiplication of the budget, although the main emitters (45%), the USA and China, are clearly holding back.

COP-29

With a global increase in CHG emissions of 1.3%, 2023 was not only the year with the highest global CO2 emissions since records began, but also the year in which the 1.5°C target by 2100 agreed in the Paris Agreement from 2015 was exceeded for the very first time. These numbers are part of the latest report published by the United Nations Environment Programme (UNEP) at the end of October.

According to the report, we are currently at 1.63°C. The average CO2 content of the atmosphere has risen from preindustrial 278 ppm to currently 420 ppm, according to new data from the World Metereologic Organisation (WMO). UNEP Director Inger Andersen calculated that global emissions should have fallen by 7.5% annually since Paris. According to the UNEP report titled ‘No more hot air, please’, even if all the climate reduction measures ever proposed to date were implemented, the projected warming by

the end of this century would amount to at least 2.6°C, with 3.1°C being a more likely scenario.

Proof of emissions According to new data from the CHG monitoring system Climate TRACE (climatetrace.org), which is based on 300 satellites, the increase in CO2 equivalents last year was 0.7% and will rise to 1.38% this year – mainly due to huge increases of CHG emissions from developing countries, whose methane emissions from oil and gas production and landfill sites do not appear in conventional estimation models. Climate TRACE makes it possible to channel the global climate reduction expenditure of currently around US$100bn to the locations of the greatest CHG emission reduction potential, which the new version of the AI-supported measurement system can identi-

fy with a high degree of reliability in every country across the world. “Despite pledges and promises, global greenhouse gas emissions continue their steady rise […] that disproportionately impacts communities with fewer resources,” said former US Vice President and Climate TRACE co-founder Al Gore at the United Nation’s COP 29 meeting. “But when climate leadership at the global and national levels has faltered, it is state and local leaders who have stepped in to fill the void. Now, with the help of breakthroughs in AI, Climate TRACE is filling an information void that has previously hindered local leaders from taking effective action to combat the global climate crisis and environmental injustice.”

For the fourth year in a row, Climate TRACE data show that oil and gas emissions from production and transport are three times higher than reported and not yet updated in official inventories, despite pledges for increased transparency and mitigation. Missing reporting on methane emissions drives much of this gap, in part because many countries do not yet include methane in their Nationally Determined Contributions (NDCs).

Unlike Switzerland, which before the start of the COP 29 climate conference in Baku had called for the world’s ten largest emitters to be made to pay a CO2 levy in view of the 13-fold increase in global spending on CHG reduction requested by poor countries affected and the management of the worst climate disasters, the supporters of Climate TRACE see a great opportunity for counter-financing in certificate trading as high-

Picture: © BPB

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impact opportunities for emissions reductions, which are disproportionately concentrated in developing countries.

Money for climate rescue The main topics for the international climate diplomats who travelled to the COP 29 conference in Baku, Azerbaijan, in mid-November “in 45 private jets”, according to environmentalists, were therefore to persuade the donor countries to make commitments to provide more money for climate protection in developing countries. In the end, wealthier countries proposed to give US$300 billion per year by 2035 to developing nations to help tackle climate change. Further goals were to concretise the ‘move away’ from coal, oil and gas, as agreed last year, to define national CHG reduction targets (NDCs) by 2035, and to reach a global agreement on how to trade CHG certificates globally. Around 71% of CHG certificate trade, according to Climate TRACE, has so far been concentrated in the developed countries.

At COP-29, the Independent HighLevel Expert Group on Climate Finance estimated the annual financing requirements of emerging and developing countries except China to be 24 times higher than the current budget: Approximately US$2.4 trillion are needed every year for climate action by 2030, of which US$1tr will have to come from external funds.

And by 2035, this number will escalate to US$3.1-3.5tr, and external funding to US$1.3tr, the report says. Even at the halfway point of COP 29, however, none of the climate diplomats expected a list that would commit the governments of the donor countries to concrete annual payments in order to provide the necessary increase in international climate financing from 2026 onwards. According to German climate diplomat Jennifer Morgan, the European community of states wants to pay more. But the private sector must also contribute, she said.

However, Europe rejected any compensation payments demanded by developing countries for climate damage that has already been proven to have occurred.

European Biotechnology | Winter Edition | Vol. 23 | 2024

Prior to the conference, the European Parliament had overwhelmingly demanded that all large and emerging economies with high emissions and gross domestic product to make a financial contribution to global climate protection measures and commit to moving away from the fossil fuel economy.

China, which stated that it had voluntarily invested US$26bn from 2016 to date, and the USA under the new President Donald Trump, who wants to withdraw from the Paris Agreement again in his second term and discontinue the Biden administration’s annual climate protection levy of US$11bn, are not expected to make any contribution. UN SecretaryGeneral António Guterres nevertheless appealed for money to at least install early warning systems in view of increasing weather extremes. “Early warning systems could reduce the cost of heat-triggered catastrophes”, which Guterres put at US$316bn per year. “COP29 must build on the momentum, and deliver a new finance goal that sees a surge in funds for climate action. Together we can and must protect people around the world.”

CHG certificate trade However, on the very first day of the UN Climate Change Conference, a preliminary agreement was reached on standards for global trading in UN-certified carbon credits in accordance with Article 6.4 of the Paris Agreement. Under rules yet to be defined, countries and companies will be able to acquire credits for climate protection projects – such as the replacement of fossil energy production with CO2-neutral alternatives. One credit will correspond to one tonne of carbon dioxide saved. Once such an international market for emissions trading (Article 6.2 of the Paris agreement already provides for bilateral certificate trading between states) is operational, countries with high GDPs that emit a lot of greenhouse gases could offset their emissions in a form of indulgence trading by buying credits from countries that have already reduced their own emissions beyond the promised level. These buyers could then

use the credits to reduce their emissions – at least on paper – and thus achieve national climate targets. So far, this market has developed outside of any international rules and was mainly used by companies wanting to claim CO2 neutrality for products by trading carbon credits. The fears of greenwashing, which does not offer any holistic environmental and climate protection, are correspondingly high. French L’Oreal has its single-use plastic packaging for cosmetics produced in a climate-neutral way by the US synbio company Lanzatech (see interview. p.

68), but is nevertheless contributing to a further increase in the microplastic pollution of the environment.

While proponents argue the new market will form the gold standard for emissions trading, unlocking billions in finance for emissions mitigation projects in the developing world, opponents say it will be a gate for greenwashing. Buyers, who are mostly located in wealthier countries, would be able to meet their climate goals by buying credits from projects that actually cut pollution.

In Baku, first movers such as Brazil, the UK and United Arab Emirates have started publishing their updated Nationally Determined Contributions (NDCs) for 2035.

Due by February 2025, these NDCs must lay out their national decarbonisation and resilience plans to 2035. The British administration publicly announced a reduction target of 81% compared to the reference year 1990, thus setting an example for the G20 summit in Brazil, which is taking place at the same time. However, details will not be known until the deadline in February, it was said. Although already pledged at COP28, Brazil and the United Arab Emirates did not give the green light for the fossil fuel phase-out. As this issue went to print, many countries were still waiting to see what the next move from major emitters and key economies will be, including that of the EU, China, Japan, Canada, India and Indonesia. Industry lobby associations used COP29 to make commitments, for example to zero-emission fuel standards. However,  enough money is not in sight. t.gabrielczyk@biocom.eu

European Biotechnology | Winter Edition | Vol. 23 | 2024

INSIGHT EUROPE

Commission seeks industry input over Novo/Catalent deal As part of its antitrust review of Novo Holdings' planned US$16.5bn acquisition of CDMO Catalent at the end of October, the European Commission has put the brakes on and asked competitors and CDMOs for their views on the deal, which will see Novo Nordisk expand production capacity for its obesity/diabetes blockbuster semaglutide.

O BESITY MARKET

According to Kasim Kutay, CEO of Novo Holdings, the takeover of the world´s largest contract manufacturing organisation (CMO) Catalent announced in early February is crucial to build enough production capacity for Novo Nordisk’s diabetes and obesity blockbuster medicine semaglutide. Catalent sites in Belgium, Italy, and the US will fill enough of Novo´s injection pens to end global demand-driven shortages which first occurred in 2023.

As part of its antitrust review of the takeover, the European Commission has now sent out the “usual questionnaire” for takeovers of this size to competitors and other CDMOs, according to an EC spokesperson. The responses are meant to help the Commission decide by 6 December whether to approve the takeover or to initiate a four-month detailed investigation in the event of antitrust concerns.

Novo and Catalent had originally aimed for approval by the end of October.

Picture: © K KStock - stock.adobe.com

Takeover set to close soon While the Commission is keeping a low profile on the content of the questions, it leaked in mid-November that its antitrust experts would like to obtain information on the consequences of the acquisition on the CDMO, the fill and finish, and the obesity market. Further questions on soft gels and dissolved pills obviously have nothing to do with Wegovy and other obesity treatments that are expected to make US$150bn in annual sales by 2030.

At the same time, the US Federal Trade Commission has already ended two Q&A rounds, focussing primarily on the impact

of Novo’s take-over on the Danish company’s main competitor in this market segment, US-based Eli Lilly & Company.

Patent and biosimilars issues In October, Novo and Viatris’ Mylan Pharmaceuticals said that they had reached an undisclosed settlement in the case IPR2023-007240F concerning the patent 10,335,462 on semaglutide. An USPTO board had considered whether to cancel a Novo patent covering the use of specific dosages of the diabetes drug Zepbound and the obesity medicine Wegovy, but the companies ended their ­inter pares review without a hearing. Whilst the core patents on semaglutide expire in 2026, initally in China, secondary patents protecting different formulations, diverse preparation methods, and different dosing regimes for semaglutide are set to expire as late as 2033.

The fiercest competition from semaglutide biosimilars threatens Novo Nordisk in the world´s largest obesity market, China, where drugmakers are develop-

ing at least 15 generic versions of its diabetes drug, Ozempic, and weight-loss treatment drug, Wegovy. According to Reuters, at least eleven semaglutide drug candidates from Chinese firms are in pivotal clinical trials, according to records in clinical trial databases.

Front-runner Hangzhou Jiuyuan Gene Engineering has applied for market authorisation of an Ozempic biosimilar in April. Most other biosimilar producers expect approval of the diabetes medicine in H2/2025, but will have to pause commercialisation until patent expiry in 2026. Analysts from Jefferies estimated in an October report that semaglutide drugs from Chinese United Laboratories will be launched for diabetes in 2025 and for obesity in 2027. If shown to be as safe and effective as Novo’s, the Chinese products will increase competition and bring down prices. Goldman Sachs analysts estimated in an August report that biosimilars could lead to a price reduction of around 25% for semaglutide-based  medicines in China. t.gabrielczyk@biocom.eu

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PROTEIN ENGINEERING

European Biotechnology | Winter Edition | Vol. 23 | 2024

Pictures: © xxx

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PROTEIN ENGINEERING

European Biotechnology | Winter Edition | Vol. 23 | 2024

New proteins on the block Monoclonal antibodies still dominate the US$417bn biologics market.

After decades of development, however, improved antibodies and protein formats with better target selectivity and safety profiles are now hitting markets and pipelines. A range of bi­specific antibodies and antibody-drug conjugates – along with CAR-Ts, TCR-RTs and NK cell-based immunoreceptor constructs – were in focus at the PEGS Europe Summit.

PEGS EUROPE 2024

Pictures: © AddMeshCube - stock.adobe.com; Mabswitch

S

ince the first antibody drug (muromonab-CD3) was approved back in 1986, monoclonal antibodies (mAbs) have emerged as the dominant class in the global US$417bn market for biologics. At the end of 2023, sales stood at more than US$230bn. However, as tumours – in addition to auto­ immune diseases still one the most important application fields of mAbs – are moving targets, newly engineered antibody and engineered protein formats that unite complementary cell-killing mechanisms in a single molecule have been developed, approved and are increasingly leaving clinical pipelines for the market.

They include refined bispecific antibodies, antibody drug conjugates (ADCs) and targeted radio­pharmaceuticals, as well as immune-receptor-based cell therapies such as CAR-T and TCR-T cell therapies.

Every year at the PEGS Europe Summit, the CSOs of bio/pharma companies provide a detailed overview of newly developed therapeutic modalities, and thus an outlook for the future. This year in Barcelona, the 16th summit helped clarify why the approval of bispecific antibody formats has increased dramatically (13 out of 18 approvals in the past three years) and why improved ADCs, CAR-Ts, TCR-Ts and new modalities are entering the market.

The freshly engineered formats promise to reduce current problems of bispecif-

ic antibody and T-cell therapies such as cyto­kine release syndrome (CRS), neurotoxicity, and on-target/off-tumour toxicity.

In addition, targeting two targets simultaneously increases selectivity, and allows

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drug developers to combine complementary cancer-killing mechanisms that could reduce resistance to cancer therapies and improve efficacy.

“Based on recent therapeutic progress, ADCs and bispecific antibodies (bsAbs) represent the fastest-growing class of thera­ peutic antibodies in development and have been a major driver of deal­making in the biopharmaceutical industry in the past years,” emphasised Dr Christian Klein at the PEGS summit, which took place from 5-7 November. The patent champion (240!) in protein engineering, who moved to early-stage investor Curie.Bio in the summer after 22 years at Roche pRED (see p. 3, p. 38) started with a brief summary of the 14 bispecifics (and 17 – still mono­ specific – ADCs on the market) approved until December 2023. But he quickly turned to what’s new, interesting and probably a business case. And there is a lot of ground to cover, as around 50% of bispecific antibodies are already in late phase testing (Phase II or III, see Fig. 1, p. 14).

New age for bispecifics According to Klein, T-cell engagers (TCEs), together with cancer immunotherapies, now account for almost 80% of the bispecific antibodies clinically developed to fight cancer. They are also increasingly used in indications beyond haematological

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PROTEIN ENGINEERING

cancers, namely solid tumours and auto­ immune diseases (TCEs and dual­-ligand blockers). Dual-ligand inhibitors such as faricimab (VEGFxAng2) from Roche, which was approved by the FDA in 2022 for the treatment of wet age­-related macular degeneration (AMD), have already found their way into ophthalmology. And Sweden’s BioArctic AB is working on an advanced version of Roche pRED’s transferrin receptor-mediated brain shuttle technology, which was presented for the first time at the PEGS Europe Summit. According to data revealed in Barcelona, the brain transporter platform, which was licensed to Esai last year, was able to increase brain exposure to an anti-amyloid beta antibody by 70-fold. Bispecific anti­ bodies in the obesity field have also already been the subject of licencing agreements, such as the as yet unnamed dual activin type IIA and IIB receptor modulator from Swiss SixPeaks Bio AG, for which AstraZeneca has an option since May.

Approvals in 2024 A total of three “classic” TCEs have been given the green light by the regulatory authorities this year, including one for solid tumours. In May, Amgen’s DLLxC3-BiTE format tarlatamab-dlle got FDA approval as a second-line treatment for extensive stage small cell lung cancer (ES-SCLC). In August, Regeneron’s previously FDA-rejected, hinge-stabilised Fc-binding-reduced CD20 x CD3 bispecific IgGπ antibody odronextamab received EU approval as a third-line therapy for patients with follicular lymphoma and diffuse large B-cell lymphoma.

Both share the CD3-related (CRS) toxicity of first-generation products. The very first bispecific T cell engager (EpCAM xCD3) Remo­vab (catamaxumab, Trion Pharma) against malignant ascites (approved 2009, withdrawn 2014) is set to be reapproved in the EU and marketed by Lindis Bio­tech/ Pharmanovia later this year. There were also two approvals for candidates with an alternative design: › At the end of November, Zymeworks Inc’s/Jazz Pharmaceuticals Inc’s biparatopic HER2 signalling blocker zanidatamab-hrii got the FDA stamp.

European Biotechnology | Winter Edition | Vol. 23 | 2024

Fig. 1: According to estimates of the Antibody Society, about 300 bispecific antibodies are in clinical evelopment, mostly in oncology, with 73% of them against solid tumours. The first approved drug in that class (Removab, 2009) from German Trion Pharma (EpCam x CD3) against malignant ascites was a T-cell engager (TCE). TCEs are artificial bispecific antibodies that attach to tumour-associated antigens (TAA) with one of their binding regions and to the CD3 receptor on T killer cells with another, thus redirecting T cells to kill cancer cells. Most TCEs today are IgG-like antibodies, because these are more stable compared to BiTEs, which consist of two single-chain variable fragments (scFvs) of different antibodies. Other upcoming modalities include bispecific ADCs, multispecific antibodies, and bispecifics that bind to two different targets or those that trigger decay of tumour-driving receptors.

Binding of zanidatamab with two different extracellular epitopes on HER2 (D2 + D4), previously targeted separately by Roche’s blockbuster HER2 anti­bodies Herceptin and Perjeta, results in internalisation leading to a reduction of the receptor on the tumour cell surface. It unites three tumour cell­ killing mechanisms in one antibody: CDC (complement­-dependent cytotoxicity), ADCC (antibody-dependent cellular cyto­toxicity) and ADCP (antibody­ dependent cellular phagocytosis).

According to Klein, combining MoAs that are not accessible to monoclonal antibodies exactly is what makes some of the novel bispecific constructs so interesting. › Another new approach, pioneered

by Chinese biotech Akeso Biopharma Co. Ltd, is combining different immune checkpoint inhibitors in a bispecific antibody. Back in 2022, Akeso Bio

received NMPA approval for the very first-(PD1 x CTLA4) drug in this new class of cancer immune therapies. Interest in a bispecific combination that unites checkpoint inhibition with angio­ genesis through PD-(L)1xVEGF bispecific antibodies blew up after Akeso Bio and Summit Therapeutics celebrated a first-time victory of ivonescimab (SMT112) over MSD’s US$15bn per year blockbuster pembrolizumab in a headto-head Phase III trial. That was followed by approval of the drug in China as a first-line NSCLC treatment. The results – objective response rates were 50% with ivonescimab versus 38.5% with pembrolizumab, disease control rates were 89.9% and 70.5%, respectively – is still sending shockwaves through the immuno-oncology industry (see p. 15).

In the field of haematological and solid cancers, what is still the dominant application field (73% solid tumours, see Fig. 1)

Picture: © Springer Nature Limited 2024

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European Biotechnology | Winter Edition | Vol. 23 | 2024

of the currently more than 50 different formats of bispecific antibodies, dual receptor tyrosine kinase blockers and biparatopic constructs such as zanidatamab are only one approach that will increasingly see clinical uptake. The overall goal of all developers of new T-cell engaging approaches, bispecific ADCs etc. is to increase tumour selectivity, eliminate tumour escape and reduce dose-limiting systemic toxicities. Also to hinder the T-cell exhaustion that often leads to relapse or non-responsiveness to redirected T-cell therapies. Several strategies discussed at PEGS Europe by start-ups and bio­pharma companies address this problem.

Early-stage approaches Yemi Onakunle, CEO of Mabswitch Inc (Los Angeles), presented a completely new technology in Barcelona that allows switching the T-cell binding affinity. According to him, this is instrumental to ameliorate TCE and CAR-T cell-therapy intrinsic toxicities caused by T-cell hyperactivation and chronic antigen stimulation. What he called “remote control” of an antibody’s affinity is achieved by inserting a universal calmodulin-derived allosteric modulator domain between the two protein domains (VH/VL), which affects the molecular geo­ metry of the antigen binding site of the anti­body. The modulator – or “switch” – can be modulated itself electrostatically by a range of small molecules that can be added or removed. Onakunle showed data from Off- and On-switches for TCEs, CARTs, ADCs or protein purification applications that altered the affinity of antibodies by two orders of magnitude. The universal allosteric affinity-switch worked independently of the paratope. The approach of the three-year old start-up, co-founded

by Phage display co-inventor Stefan Dübel, enables both increased and decreased affinity in antibodies, offering a tunable strategy to enhance CAR T cell or T-cell engager safety and efficacy in patients.

Other approaches aim to circumvent T-cell-born safety issues by using alternative effector cells, namely NK or so-called MAIT cells. Simon Plyte, CSO of Biomunex Pharmaceuticals SA (Paris), said using an

abundant tissue and tumour resident subset of cytotoxic non-conventional T cells that make up 20% of the T cell population could significantly widen the therapeutic index of T cell therapies. While the proprietary, bispecific BiXAb antibody­-mediated redirection of these MAIT cells (Mucosal Associated Invariant T cells) to TAAs lead to the elimination of cancer cells with a potency identical to that of classical CD3e T-cell engagers, MAIT engagers triggered neither cytokine release syndrome nor regulatory T-cell activation, because they are activated through binding to the iTCR. According to data shown by Plyte, tumourresident MAIT cells are able to eliminate autologous tumour cells in a MAIT-engager mediated manner, and can infiltrate and kill tumour cells in patient-derived 3D models of cancer.

Another approach, chosen by French Innate Pharma SA, which also has fourthgeneration ADCs in its portfolio, is to circumvent the T-cell-specific problems by using NK cells that neither induce CRS nor activate CD25+ regulatory T cells. The company’s tetraspecific B and NK cell engager IPH6501 exhibited higher anti-tumour efficacy and lower systemic toxicity

PROTEIN ENGINEERING

than CD20-targeting TCEs. The candidate currently undergoing Phase I/II trials, engaged NK cell-activating receptors (NKp46 and CD16), the CD20 TAA on B cell blasts and includes an IL-2 variant designed to avoid binding to CD25, limiting Treg activation and potential IL-2 related side effects (see p. 70).

Local activation In addition to these innate cell engagers, approaches in which probodies are first activated in the tumour were also discussed at PEGS Europe. Here, the binding sites are initially masked sterically or by attaching protective groups, which are cleaved off by TME specific proteases. Or they are engineered to be active only at acidic pH or high ATP concentrations. An alternative approach for dual tumour targeting at an early stage is based on the tumour-specific composition of a functional CD3e antibody fragment consisting of two bispecific antibodies with split CD3e binding moieties. These units must be designed to be inactive and circulate as separate units so that they are activated only after binding of the tumour antigen and

Shockwaves While Chinese Akeso Biopharma Co. Ltd/ Summit Therapeutics conducts clinical trials with its heterobiparatopic (PD1xVEGF) antibody ivonescimab across 16 indications, competitors have invested huge amounts of money to fill the hole in their pipelines. In mid­-November, German BioNTech SE made an US$800m + US$150m tender to acquire its Chinese partner Biotheus Inc in order to gain control of its cancer candidate PM8002 (now BNT327), a VEGF x PD-L1 bispecific anti­body in Phase I/II testing with a claimed “similar design” to ivonescimab.

Some days later Merck Sharp & Dohme, which markets pembrolizumab, hit back by announcing it will pay US$588m upfront plus up to US$2.7bn biobucks to acquire the global rights to Chinese LaNo-

va Medicines’ Phase I-ready PD-1x VEGF bispecific anti­body LM-299. The bispecifics race could heat up if MCT11 turns out to be safe and efficient in clinical trials.

Finally, in late October, four-year old Ottimo Pharma left stealth mode, announcing it will start clinical testing of a PD1 x VEGFR2 bifunctional antibody in early 2025. This latest series of deals – as previously in the field of ADCs, where Chinese biotechs sit on 42% of the pipeline – really shows that science is about international collaboration, not trade barriers. At the largest pharma event in Europe, the CPHI in Milan, a survey of 280 biopharma/CDMO/CRO decisionmakers revealed that a majority are opposed to blocking collaboration between US/Chinese biotechs through draft US laws. L

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PROTEIN ENGINEERING

European Biotechnology | Winter Edition | Vol. 23 | 2024

Fig. 2: Emerging concepts in the field of bispecific antibodies. A. Multispecific antibodies that i.e can simultaneously activate two co-stimulators of T-cell receptors (TCRs): CD3 and CD28. B. Different approaches aim to prevent off-target toxicity and boost tumour selectivity by using bispecific antibody prodrugs that are exclusively activated through enzymatic, pH- or binding-induced demasking when they reach the acidic tumour microenvironment (TME) or target site in the tumour. C. As many to-date undruggable pathogenesis drivers are not enzymes, their degradation through the proteasome has become a treatment option, even to prevent the expression of proteins that trigger tumour resistance. Bispecifics target these tumour proteins and ubiquitin-ligase induced tagging for specific degradation of such cancer drivers.

D. Systemic side effects of bispecific antibodies or TCEs can also be ameliorated via gene-therapy delivery, i.e. into CAR-T cells. E. Bispecifics that bind to cytokine receptors can also be used to trigger cell activation.

subsequent in situ assembly. However, it is tricky to produce the monomers because they tend to aggregate in solution.

At PEGS Europe, Thomas Spreter von Kreudenstein, Senior Director Protein Engineering and Multispecific Antibody Technologies at Zymeworks, presented a new conditional masking approach for Zymeworks’ cIL-12 cytokine fusion protein ZW270. Though IL-12 drugs have already shown the ability to turn ‘cold’ tumours ‘hot’, they also delivered poor responses – most likely due to toxicity and thus a low therapeutic index. After optimisation, an attenuated, masked IL-12 Fc (ZW270) showed anti-tumour efficacy in a human-

ised syngeneic mouse model in a dose range from 0.5 mg/kg-32 mg/kg, while reference mice with unmasked wild-type IL12 showed a maximal tolerated dose of less than 0.05 mg/kg. Testing is ongoing.

ADCs and radio-DARPiNs While the 13 approved antibody-drug conjugates (ADCs) enable the selective delivery of highly cytotoxic payloads linked to a tumour-targeting antibody with 50%60% objective response rate on average, challenges such as drug resistance, tumour heterogeneity and treatment-related adverse effects continue to hamper the medi-

cal success of this drug class, which saw its first approval in 2000 with Pfizer’s secondline CD33-positive AML therapy Gemtuzumab ozogamicin.

Different engineered ADC formats and – above all – new payloads were discussed at the PEGS Europe Summit, with the goal of widening the still too-narrow therapeutic index of the rapidly growing clinical pipeline (300 INDs this year, mostly in China, which holds 42% of it). New formats discussed included bispecific ADCs, conditionally active ADCs, immune-stimulating ADCs, protein-degrader ADCs and dual-payload ADCs. Premature payload release, poor tumour penetration, variable drug-to-antibody ratios and aggregation were the topics discussed most.

Joost Uitdehaag, Head of Biology at Crossfire Oncology BV, underlined the need for new non-chemical payloads, because these most common payloads limit the application of ADCs due to their high systemic toxicity. He highlighted kinase degraders targeting cancer-driving proteins, because the 80 approved kinase blockers would have better selectivity and are less toxic than anti-mitotics, tubulins and topo­isomerase I blockers. He reported on a Phase I-ready novel cell cycle kinase degrader payload called CFON 18801, which was screened from 300 candidates with kinase and cell-based HIBIT assays, and its application as part of a Degrader-Antibody-Conjugate (DAC) to target meta­static castration-resistant prostate cancer (mCRPC). In vitro, CFON 18801 showed a DC50 in the single-digit nM range, and completely arrested the cell cycle in S-Phase by full target degradation within 254 hours, inducing strong immunogenic cell death. CFONs allow a drug-to-antibody ratio from 2-8. Conjugation of CFON 18801 to an prostate cancer-specific antibody showed pico­molar cytotoxic activity outperforming a doxorubicin-based conjugate. Its in vivo efficacy is currently being assessed.

Justyna Mysliwy, Senior Director of Research at Iksuda Therapeutics Ltd in Newcastle’s Biosphere Life Science Ecosystem, presented the company’s intra­tumourally activated ADCs. Not long ago, the first HER2-positive breast, lung and gastric

Picture: © Springer Nature Limited 2024

16

PROTEIN ENGINEERING

cancer patient was enrolled in a dose­ escalation study of Iksuda’s lead candidate IKS104. The firm’s Chinese partner Fosun is already testing the probody ADC in Phase II/III trials, which is cleaved at low pH by the cancer lysosome-selective enzyme beta­-glucuronidase, thus avoiding the risk of on-target, off-site toxicity. The probody carries two PDB payloads per molecule.

Conjugation impact A novel conjugation approach was presented by David Spycher, CSO of Zürichbased Araris Biotech AG. Using microbial transglutaminase, Araris was able to link short, positively charged lysine-containing peptides to HER2-targeting anti­ bodies at their residue glutamine 295 (Q295) without the need for any protein engineering and at a stochiometric drug-to-antibody ratio of 2 or 4. When a-amanitin was used as a toxic payload, complete and long-lasting tumour remission was achieved together with highly reduced toxicity at all dose levels tested. Quantitative biodistribution studies performed with 111In-radiolabeled conjugates showed high tumour uptake and low accumulation of radioactivity in non-targeted tissues.

After raising €54m in Series A financing, Belgian ADC maker ATB Therapeutics BV now claims its technology has solved bioconjugation-related problems.

The ATBioFarm platform allows for one-step production of ADCs in tobac-

European Biotechnology | Winter Edition | Vol. 23 | 2024

co plants. They consist of a targeting anti­b ody, a cleavable but stable peptidic linker and a cell-killing enzymatic payload, and are made by just transferring the encoding DNA sequence into a tobacco-compatible vector that is expressed within the plant cells. According to the technology’s inventor COO Max Houry, the ADC-like fusion proteins circumvent common problems of bacterial and mammalian expression systems that occur in the process of attaching toxic payloads in a defined stochiometry to the targeting antibody. Additionally, in contrast to typical payloads, ATbodies use enzymatic cell-killing mechanisms that are complementary to the mode of action of chemotherapeutics Andreas Bosshard from Molecular Partners AG explained ways of reducing the renal toxicity of radio-Darpin conjugates derived from ankyrin-repeat proteins. To minimise accumulation of radio­isotopes in the renal glomerulus, Darpins were produced in which positive surface charges were partly or fully exchanged with negative ones. Although radio­-Darpins with fully exchanged charges were significantly less toxic, they were also less effective in reaching the tumour.

Bispecific ADCs also show increased tumour selectivity. Last December, Bristol Myers Squibb licenced global, exChina rights for the Phase III first-in-class bispecific (EGFRxHER3) ADC izalontamab brengitecan (BL-B01D1) from Chinese Syst­Immune Co. Ltd for US$800m

The next PEGS Europe will be held on 11-13 Nov. 2025 in the Lisbon Congress Center

up-front plus US$500m near-term payments in a US$8.4bn biobucks deal. As the toxic camptothecin payload (DAR 7.5-8) still belongs to the classical payload trio – supertoxic anti-mitotics, DNA alkylating agents and dominating topo­ isomerase 1 inhibitors (53%) – the recommended dose in humans is still low (2.5mg/kg, preclinically 10 mg/kg) and miles away from what is regarded as optimal for good biodistribution (6-10 mg/ kg, see interview p. 40). How­ever, the reported objective response rate was 60% in Phase I/II, with neutropenia as the most reported adverse effect (ADE).

A new approach?

A discovery by scientists at the University of Pittsburgh and the UPMC Hillman Cancer Center is kindling hopes of ending the stealth strategies of solid tumours that put immune cell therapeutics to sleep in the TME once and for all. The team discovered that lactic acid pumped out of the tumour appears to contribute significantly to socalled T-cell exhaustion. At the same time, they discovered that this lactate sensitivity disappears when they blocked the T-cell lactate transporter MCT11 with antibodies (Nature Immunology, doi: 10.1038/s41590024-01999-3). The antibody, which significantly improved the control of tumour growth in mice, is now to be tested clinically. “Blocking access to inhibitory meta­ bolites is a completely new approach to how we can reactivate the immune system,” said lead author Greg Delgoffe, Director of the Tumour Microenvironment Center at UPMC Hillman. “If we get rid of MCT11, there is no difference in the expression of co-inhibitory receptors on T cells,” Delgoffe added. “MCT11 is an attractive therapeutic target because it is almost exclusively expressed by exhausted T cells that concentrate in tumours.

This makes it a potentially more selective and targeted treatment option compared to other immunotherapies, such as PD1 checkpoint blockers.” Bispecific (PD1 x MCT11) Innate engagers could therefore be a future option in the ongoing fight against  cancer. t.gabrielczyk@biocom.eu

Picture: Robson90 - stock.adobe.com

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INTERVIEW

European Biotechnology | Winter Edition | Vol. 23 | 2024

Vaccines from the assembly line – the Valneva way Valneva SE, listed on Euronext, has received marketing authorisation from the European Commission for its single-dose vaccine IXCHIQ® for the prevention of Chikungunya virus disease. Lyme disease, Zika, Japanese encephalitis, Shigella and others are in the pipeline.

European Biotechnology talks strategy with CEO and vaccine veteran Thomas Lingelbach.

VACCINES

appropriate market size and can scale up the industrialisation of such vaccines.

EuroBiotech_The great vaccine euphoria has subsided considerably since the pandemic. How does Valneva see itself in this changing environment?

Thomas Lingelbach_The vaccine industry

EuroBiotech_Like your partner Pfizer in the Lyme disease vaccine?

Lingelbach_ Exactly. Lyme disease is a

has changed a lot in recent years, it has consolidated a lot. There used to be a large number of medium-sized companies that covered the entire vaccine development and value chain. They have all more or less disappeared. Now there is still a little activity within Big Pharma.

In Europe, there is only Bavarian Nordic and us, Valneva, as independent vaccine developers.

EuroBiotech_How can you hold your own?

Lingelbach_We are clearly focussing on

indications that nobody else does but where there is a medical need. In areas where prophylaxis is not available and treatment is very limited. You can call this a niche player or a specialist. But with our track record of three vaccines on the market, we are not a noname in the scene.

EuroBiotech_Are you focussing on very specific technologies?

Lingelbach_On the contrary, we are tech-

nology-agnostic, we do everything – except mRNA, we leave that to others.

EuroBiotech_But it was the mRNA players that won the race during the pandemic. Do you think this time is a special case and their ambitions are already fading from the vaccine sector?

Lingelbach_Moderna is still there, but in

indications that continue to target a bil-

THOMAS LINGELBACH, CEO Valneva SE, is an established vaccine industry leader with a breadth of experience including senior and executive management roles with Intercell, Novartis and Chiron. He has a strong emphasis on technical development and operations.

lion-dollar market with respiratory diseases, just like most of the other big pharma players that are still active in vaccines.

EuroBiotech_Isn’t it always a difficult balancing act for niche players to target exactly the right market size? You also have projects in the pipeline that are not just ‘niche’.

Lingelbach_Yes, I’m not saying that we

don’t do such things if we can. However, we then look for a partner that has the

market worth US$1bn-5bn, according to expert estimates. This also requires a vaccination infrastructure for distribution on a scale up to the doctor and an expensive Phase III trial. That is why we have partnered with Pfizer based on our Phase II data. However, this is not an isolated case; we are also playing on this keyboard with projects for herpes/EpsteinBarr virus, where we can map the preclinical phase well. But we will not take the next steps without a strong partner.

EuroBiotech_If you win Pfizer as a partner, you’re doing something right, aren’t you?

Lingelbach_Our quality is right, as I said,

we have developed and launched three vaccines on the market. Our positioning is also clear, we are not competing with the big players. And we address medical needs, we don’t do a me-too. If the Lyme disease vaccine works, we will be looked at differently.

EuroBiotech_It’s not your special technological expertise that convinces a partner, but ...?

Lingelbach_Of course, technological ex-

pertise is attributed to us, and rightly so.

We can make vaccines. We have been around for several decades now with our predecessor company Intercell and have a wealth of experience that has been uti-

Picture: © Valneva SE

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European Biotechnology | Winter Edition | Vol. 23 | 2024

lised almost everywhere else. The fact that we don’t have a specific technology as our sole focus even helps us to convince people that we approach each vaccine project from scratch and select the most suitable technology for development rather than being predetermined.

EuroBiotech_Let’s talk about these niches in which Valneva operates. Can the indications – with the exception of Lyme disease – be described as diseases of the global South, are you developing for these countries?

Lingelbach_The regions of such diseases

are southern – for now. But we have two perspectives on this. On the one hand, we are developing so-called ‘travel vaccines’, i.e. for visitors to these regions where certain disease vectors and the infectious diseases they cause are endemic or predominantly at home. Japanese encephalitis, chikungunya and Zika virus can be included in this category. But this is just a snapshot of the present. On the other hand, climate change is gradually shifting the borders of these currently endemic regions from the global South to the North.

Various new mosquito species can now also be found north of the Alps. In the case of Lyme disease, it is clearly recognisable that it is spreading further north.

EuroBiotech_Is the climate crisis a ticket for expansion and new markets for your vaccines?

Lingelbach_I really don’t want to be mis-

understood and come across as a profiteer of climate change. On the contrary, we are trying to offer concrete solutions for real challenges that this climate change will have in nature and, sooner or later, in our immediate surroundings and environment. We are now supporting these regions with our vaccines, with local partner companies. We ourselves do not want to become active as a company in Japan, Africa, Asia or India, but instead grant licences.

EuroBiotech_The situation is different for Lyme disease, isn´t it?

Lingelbach_As I said, Lyme disease is a

special case. The disease is already on

the move in the western world, so this is a completely different market situation with its own challenges for the vaccination infrastructure. That’s why we’re doing this with Pfizer as a global partner.

EuroBiotech_Where do you stand?

Lingelbach_We are in the Phase III trial,

and we will see first data in about a year.

I assume that we will need an annual vaccination for good protection. If this vaccine is a success, Valneva will become a different company.

EuroBiotech_What do you mean by that?

Lingelbach_We will simply be playing in

a different league. Our previously authorised vaccines serve niche markets. With travel vaccines in particular, market entry is not immediately a great success; it can easily take ten years for such vaccines to become established as a useful prophylaxis. Lyme disease is simply different. It represents a huge unmet medical need (475,000 reported Lyme cases annually in the US) and we are the only company with a vaccine in Phase III. EuroBiotech_Has the world changed for your company since COVID-19 and are these changes still noticeable?

Lingelbach_For us, the development of a

corona vaccine was a success. Not commercially, not in any ranking and perhaps not in the public eye either. But we received the first non-conditional marketing authorisation for a COVID-19 vaccine worldwide. Others have then asserted themselves more strongly, we got caught in the wheels of European politics a little.

But as a company, as a vaccine manufacturer covering the whole value chain from research and development to production and authorisation, we have learned an incredible amount. The belief that everything is now easier and faster after the pandemic because the authorities have also learnt a lot and upgraded is unfortunately a misconception. On the contrary, the requirements have become more demanding. Speed is no longer an issue, regulation has regained the upper hand.

INTERVIEW

EuroBiotech_Have you learnt any technological or other lessons from this?

Lingelbach_We developed an inactivated

vaccine during the COVID-19 pandemic, and as I said, it was successful. The vaccine is authorised and works very well.

But then nobody wanted to buy it because others were faster and their market power was greater. For us, there was no financial loss and no gain, so all that remains is the learning curve that all our employees have completed there and two brand new manufacturing facilities.

And we have no problem with the inactivated vaccine technology. In certain cases this is a good choice, our Zika vaccine is also based on this process and can now utilise the entire process chain that we set up for COVID-19 in the same way.

EuroBiotech_What is the reason for your cooperation with the Swiss company Limmatech? Their toolbox?

Lingelbach_No. It’s all about the indica-

tion. We are used to polyvalent active substances ourselves. The special expertise in relation to Shigella and the development of a joint vaccine against this pathogen was the decisive factor for us in this partnership. This can also be categorised as a ‘travel vaccine’, and it also addresses regions where we already have partners or are about to, and no one else is doing Shigella. All these factors fit perfectly with our overall strategy. We are currently starting Phase II and could be in Phase III in two to three years.

EuroBiotech_The pandemic is history, infectious diseases only get the spotlight if the bird flu comes closer to humans or to the farmers. Are investors or pharmaceutical partners still interested at all?

Lingelbach_Of course, awareness has de-

creased after the pandemic. But most people around the world don’t die from cancer or cardiovascular disease, but from infectious diseases. Many of these can be prevented prophylactically with a vaccination, or the serious consequences of the disease can be greatly mitigated.

The medical need is huge and that’s why L we are in it. g.kaeaeb@biocom.eu

21

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STOCK MARKETS

European Biotechnology | Winter Edition | Vol. 23 | 2024

Trump’s win will affect the biotechnology sector PETER THILO HASLER – SPHENE CAPITAL During the conference calls on the latest quarterly

reports, several recurring questions emerged: What consequences do you anticipate if Trump is to be re-elected? How will tariffs affect supply chains and operating profits?

What about FDA, IRA, the healthcare system, or the bioeconomy strategy?

The answers from biotech executives showed that they are not particularly well prepared for the economic policy measures of the Trump administration. Probably also because Trump has not yet presented a finalised concept for the healthcare sector. However, he has pointed out some options, such as giving an avowed vaccine sceptic like Robert F. Kennedy Jr. a leading role in healthcare policy. This shows that his health policy – as we have come to expect from him – could also include unorthodox or disruptive ideas. “I’m going to let him go wild on health,” Trump said in a campaign speech in New York. He has already hinted at what Kennedy means by this. He wants to rid the regulatory authorities of corruption, return them to evidence-based sci-

ence, and end what he described as an epidemic of chronic diseases.

The pharmaceutical industry is arguably the most heavily regulated industry in the world – next to banking – and not a playing field for amateurs or politicians.

In principle, it is up to the federal states to ban vaccinations and health protection measures. But states are usually guided by standards set by authoritative national institutions: the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Environmental Protection Agency (EPA), and the National Institutes of Health. While more than 60% of Republicans have little or no trust in these institutions, according to a recent article in the New England Journal of Medicine, Trump is likely to weaken

these state institutions significantly, for example, by providing these authorities with less funding and staffing than before. And since some of these institutions – such as the CDC – are globally active organisations, these cuts could also have worldwide repercussions.

The revival of the ‘Most Favoured Nation’ policy in medicine pricing may also not benefit biotech/pharma stock performance, especially as the presidential candidate – who is typically positioned as business-friendly – has repeatedly criticised ‘Big Pharma’ in his election campaigns for high drug costs. Kennedy confirmed in a commentary in the Wall Street Journal that legislators should cap drug prices so that companies cannot charge Americans much more than Europeans. L

News from the floor You can win an FDA approval but nothing happens on your stock? Autolus Therapeutics plc. (NASDAQ: AUTL) got approval of obe-cel, Autolus’ cell therapy product, which was the first of its kind to be approved without a risk monitoring programme and represents a significant milestone in the field of cell therapies. Optimism about the business’s potential followed, with Redburn-Atlantic upgrading the stock’s rating from Neutral to Buy and setting a new price target of $13.00, signalling confidence in

Autolus’s future performance. RedburnAtlantic was enthusiastic about the Autolus product and its market potential, particularly for the treatment of autoimmune diseases. But the stock did not follow, so that rumours about a sale of the whole business at low prices emerged, even though shareholder German BioNTech SE would have to be consulted first.

The last in the European stock market alphabet is Zealand Pharmaceutical A/S from Søborg. However, year-to- date performance positions the company,

which specialises in obesity and insulin disorders, as one of the leading listed biotech companies. Strongly overshadowed by Novo, Zealand is its strongest competitor when it comes to the next wave of diet drugs focussing on Amylin. This year, the share price has risen by 125%, and recruitment for Phase II with an Amylin analogue, following well-received Phase I data, has started. Additionally, the collaboration with Boehringer Ingelheim on MASH has received FDA breakthrough status and is also entering Phase II. L

FINANCIAL MARKETS

European Biotechnology | Winter Edition | Vol. 23 | 2024

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45,860k

Abionyx Pharma SA

1.23

42,900k

Abivax SA

8.23

520,910k

Ablivia AB

0.00

2,260k

AC Immune SA

3.11

312,500k

Acticor Biotech SA

0.27

4,440k

52 WEEKS INDICATOR low high

       

Active Biotech AB

0.01

4,990k

Adaptimmune Therapeutics plc

0.57

168,790k

ADC Therapeutics SA

1.85

179,095k

Addex Therapeutics Ltd

0.07

6,481k



ADL Bionatur Solutions SA

0.24

15,540k

Adocia SAS

7.99

125,630k

Advicenne SA

2.12

25,670k

  

Aelis Farma SAS

2.82

40,570k

Affimed NV

2.49

38,980k

Akari Therapeutics plc

1.20

21,060k

ALK-Abelló A/S

20.82

4,220,000k

Alkermes plc

26.40

4,270,000k

Allarity Therapeutics A/S

1.18

5,240k

Alligator Bioscience AB

0.04

33,280k

Altamira Therapeutics Ltd

0.39

1,489k

Alvotech SAS

11.70

3,530,000k

Alzinova AB

0.29

25,720k

Annexin Pharmaceuticals AB

0.03

10,740k

Aprea Therapeutics AB

2.68

14,567k

Aqua Bio Technology ASA

0.16

10,980k

Arctic Zymes Technologies ASA

1.13

57,510k

Arecor Therapeutics plc

0.89

33,410k

Argenx BV

570.40

34,430,000k

Arocell AB

0.03

5,250k

Arterra Bioscience SpA

1.90

12,650k

Ascelia Pharma AB

0.16

15,320k

Ascendis Pharma A/S

122.00

747,000,000k

Autolus Therapeutics plc

2.70

750,390k

Avacta Group plc

0.56

197,580k

Avadel Pharmaceuticals plc

11.10

1,070,000k

Axichem AB

0.06

3,580k

Basilea Pharmaceutica AG

42.54

515,667k

Bavarian Nordic A/S

25.92

2,010,000k

BB Biotech

39.10

2,120,000k

Bergenbio ASA

0.91

35,570k

BICO Group B

3.05

206,120k

Bicycle Therapeutics plc

19.40

908,280k

Bioarctic AB

16.24

1,170,000k

Biocartis NV

0.29

27,240k

Bioextrax AB

0.28

9,440k

Biofrontera AG

2.74

16,500k

Biogaia AB

9.09

882,490k

Bioinvent International AB

3.88

256,640k

Biomed-Lublin SA

0.85

60,580k

Biomérieux SA

97.15

11,460,000k

BioNTech SE

103.60

23,730,000k

Biophytis SA

0.27

1,470k

Bioporto Diagnostics A/S

0.22

96,030k

BioSenic SA

0.01

1,670k

Biosergen AB

0.05

7,010k

Biotage Sweden AB

13.07

1,050,000k

  

COMPANY

QUOTE

M-CAP

Bioventix plc

44.20

227,580k

Biovica International AB

0.12

10,510k

Bioxxmed AG

2.65

6,570k

Bivictrix Therapeutics plc

0.10

8,210k

Brain AG

3.12

69,480k

C4X Discovery Holdings plc

0.12

29,260k

Calliditas Therapeutics AB

35.20

980,710k

Camurus AB

48.52

2,850,000k

Cantargia AB

0.13

23,400k

Carbios SAS

7.39

126,010k

Cellectis SA

1.74

125,440k

Celon Pharma SA

5.70

324,750k

52 WEEKS INDICATOR low high

           

  

European Biotech Stocks

                   

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

COMPANY

                   

M-CAP

52 WEEKS INDICATOR low high

 

Celyad Oncology SA

0.65

25,270k

Centessa Pharmaceuticals plc

17.40

210,000k

Centogene NV

0.07

2,030k

Circio Holding

0.05

2,100k

Co.don AG

0.01

267k

Coegin Pharma AB

0.32

8,010k

CombiGene AB

0.22

4,710k

Cosmo Pharmaceuticals NV

67.00

1,070,000k

CRISPR Therapeutics AG

44.57

3,806,972k

CSL Ltd

171.00

81,980,000k

Curevac NV

2.44

546,860k

Cyxone AB

0.00

75k

DBV Technologies SA

0.51

52,380k

Destiny Pharma plc

0.04

3,740k

Diagonal Bio AB

0.00

Diamyd Medical AB



QUOTE

          

 1,000k 

1.07

107,970k

Diasorin SpA

104.45

5,570,000k

DMS Imaging

0.02

25,030k

Elicera Therapeutics AB

0.12

4,330k

Ellen AB

0.09

389k

Enzymatica AB

0.15

25,310k

Epigenomics AG

1.10

877k

Erytech Pharma SA

1.60

15,240k

e-Therapeutics plc

0.09

53,170k

Eurobio Scientific SA

25.60

262,370k

Eurocine Vaccines AB

0.00

1,650k

Eurofins Scientific SE

46.84

8,850,000k

Evaxion Biotech A/S

1.39

8,191k

Evgen Pharma plc

0.00

214k

Evolva N

0.88

6,369k

Evotec SE

9.81

1,790,000k

               

23

24

FINANCIAL MARKETS

COMPANY

QUOTE

European Biotechnology | Winter Edition | Vol. 23 | 2024

M-CAP

Expres2ion Biotech Holding AB

1.72

3,620k

Faron Pharmaceuticals Oy

1.66

179,750k

Fermentalg SA

0.30

25,160k

Flerie AB

3.96

309,140k

Fluicell

0.00

481k

Formycon AG

45.80

821,390k

Fusion Antibodies plc

5.10

489,663k

Gabather AB

0.04

536k

Galapagos NV

24.02

1,580,000k

Genedrive PLC

0.02

12,760k

Geneuro SA

0.06

1,920k

Genfit SA

3.98

199,720k

Genflow Biosciences plc

0.02

6,990k

GENinCode plc

0.04

7,960k

Genmab A/S

195.50

12,380,000k

0.00

694,595k

Genovis AB

2.37

153,840k

Genoway SA

3.73

33,940k

Gensight Biologics SA

0.32

36,930k

Gentian Diagnostics AS

3.48

53,670k

Genus plc

19.70

1,290,000k

Global Bioenergies SA

0.78

13,840k

Glycorex Transplantation AB

2.68

189,170k

Guard Therapeutics International AB

1.64

20,040k

Hansa Biopharma AB

2.47

171,840k

Genomic Vision SA

HBM Healthcare Investments AG

164.80

1,150,000k

Heidelberg Pharma AG

2.29

101,590k

Hemogenyx Pharmaceuticals plc

0.01

16,820k

Herantis Pharma Oyj

1.23

24,800k

Hofseth Biocare ASA

0.11

43,660k

HOOKIPA Pharma

2.13

20,533k

Hybrigenics SA

0.01

4,870k

Idorsia Ltd

0.81

146,100k

Immatics NV

7.40

864,140k

Immunic AG

1.06

93,680k

Immunovia AB

0.03

4,240k

ImmuPharma plc

0.01

8,950k

Infant Bacterial Therapeutics AB

3.36

40,360k

InflaRx NV

1.96

117,410k

Innate Pharma SA

1.53

124,200k

Integragen SA

0.45

2,960k

Intervacc AB

0.20

15,450k

Inventiva SA

2.37

212,470k

IO Biotech Inc.

0.66

43,413k

IRLAB Therapeutics AB

1.10

53,860k

Isofol Medical AB

0.27

43,040k

ISR Holding AB

0.19

13,350k

Kancera AB

0.09

10,390k

Kuros Biosciences AG

24.27

911,762k

Lipigon Pharmaceuticals AB

0.02

1,340k

Lipum AB

1.44

13,428k

Lytix Biopharma AS

0.52

26,790k

MaaT Pharma SA

7.56

111,350k

Mabion Ltd

2.67

38,790k

Magle Chemoswed Holding AB

2.82

51,890k

Mainz Biomed BV

0.20

4,430k

Marinomed Biotech AG

8.34

14,170k

MDxHealth SA

3.08

15,220k

Medesis Pharma SA

0.38

2,160k

52 WEEKS INDICATOR low high

                                           

  

     

M-CAP

1.54

11,380k

Medincell SA

17.04

501,170k

Medivir AB

0.20

23,980k

Mendus AB

0.71

36,610k

Merus BV

42.40

2,900,000k

Metabolic Explorer SA

0.12

6,160k

Mithra Pharmaceuticals SA

1.44

14,429k

Modus Therapeutics Holding AB

0.11

3,810k

Molecular Partners AG

5.19

191,367k

Morphosys AG

67.05

2,550,000k

Nabriva Therapeutics plc

0.67

2,150k

Nanobiotix SA

3.49

162,610k

Newron Pharmaceuticals SpA

7.88

154,110k

Nextcell Pharma AB

0.11

7,930k

NFL Biosciences SA

1.91

18,930k

Nicox SA

0.22

12,970k

Niox Group plc

0.73

294,510k

NLS Pharmaceutics AG

3.19

3,742k

Novacyt SA

0.57

40,120k

Novozymes Biopharma DK A/S

55.72

22,580,000k

NuCana ADR

1.21

2,700k

Nykode Therapeutics ASA

0.20

67,860k

ObsEva SA

0.00

54k

Okyo Pharma Ltd

1.07

36,260k

Oncimmune Holdings plc

0.17

19,000k

Oncoarendi Therapeutics SA

2.34

42,760k

Oncopeptides AB

0.11

10,710k

OncoZenge AB

0.33

4,310k

Open Orphan plc

0.25

172,810k

0.13

14,010k

120.00

5,110k

Oryzon Genomics SA

1.54

100,230k

OSE Immuno SA

8.68

188,290k

Ovoca Bio plc

0.01

1,150k

Oxford Biodynamics plc

0.00

4,560k

Oxford Biomedica plc

4.82

510,550k

Oxurion NV

0.31

616k

Paion AG

0.00

44,228k

Pangaea Oncology SA

1.79

61,600k

PCI Biotech Holding ASA

0.12

4,760k

Orphazyme A/S

 

QUOTE

Medigene AG

Optibiotix Health plc

 

 

COMPANY

Pentixapharm Holding AG

3.07

76,000k

Pharma Mar SA

72.95

1,340,000k

Pharming Group NV

0.70

487,060k

Pharnext SA

0.00

1,190k

Photocure ASA

4.29

116,480k

Physiomics plc

0.00

1,320k

Pieris Pharmaceuticals Inc.

11.25

14,850k

Plant Advanced Technologies SA

11.50

12,700k

PMD Device Solutions AB

0.08

2,350k

PolyPeptide Group SF

29.63

977,140k

Poolbeg Pharma plc

0.08

41,750k

Poxel SA

0.23

9,500k

Predilife SA

4.08

15,250k

Probi AB

30.30

344,100k

ProQR Therapeutics BV

3.45

356,050k

Prostatype Genomics AB

0.43

2,230k

Proteome Sciences plc

0.03

9,300k

Prothena Corporation plc

13.80

742,560k

Pure Biologics SA

3.91

14,660k

52 WEEKS INDICATOR low high

                                                          

FINANCIAL MARKETS

European Biotechnology | Winter Edition | Vol. 23 | 2024

COMPANY

QUOTE

M-CAP

Qiagen NV

40.63

8,920,000k

Q-Linea AB

0.10

11,720k

Quantum Genomics SAS

0.07

4,740k

Redx Pharma plc

0.17

64,960k

Relief Therapeutics Holding AG

5.22

65,489k

Reneuron Group plc

0.03

1,940k

Ryvu Therapeutics SA

9.73

226,810k

Saniona AB

0.23

25,730k

Santhera Pharmaceuticals AG

8.36

101,260k

Sareum Holdings plc

0.32

39,420k

172.40

5,750,000k

Scancell Holdings plc

0.14

134,790k

Scandion Oncology A/S

0.01

1,620k

Selvita SA

12.02

220,630k

Sensorion SA

0.63

197,730k

SenzaGen AB

0.61

17,820k

Shield Therapeutics plc

0.03

31,280k

Silence Therapeutics plc

6.35

320,570k

Simris Group AB

0.01

1,810k

Skinbiotherapeutics plc

0.17

39,290k

Softox Solutions AS

0.00

1,950k

Sophia Genetics SA

3.00

197,430k

Spexis AG

0.05

3,461k

Sartorius AG

Sprint Bioscience AB

0.11

7,710k

Stayble Therapeutics AB

0.05

2,040k

Summit Therapeutics Inc.

18.21

13,426,311k

Swedish Orphan Biovitrum AB

25.12

8,940,000k

SynAct Pharma AB

0.78

27,440k

52 WEEKS INDICATOR low high

                           

COMPANY

QUOTE

M-CAP

Synairgen Research Ltd

0.03

6,080k

Theranexus SA

0.49

3,820k

Thor Medical ASA

0.33

53,670k

Tissue Regenix Group plc

0.65

46,050k

Tiziana Life Sciences plc

0.93

102,360k

TME Pharma NV

0.14

6,020k

Transgene SA

0.78

76,150k

Trinity Biotech plc

2.07

14,010k

Ultimovacs ASA

0.20

6,530k

uniQure NV

5.58

271,890k

Valbiotis SAS

1.22

19,140k

Valerio Therapeutics

0.08

9,740k

Valirx plc

0.02

2,050k

Valneva SE

2.02

332,530k

Verici Dx plc

0.04

9,340k

Verona Pharma plc

36.60

3,180,000k

Vicore Pharma Holding AB

0.66

155,290k

Virax Biolabs Group Ltd

1.87

8,126k

Virogates A/S

2.21

15,940k

Vita 34 AG

4.20

73,210k

Vivoryon Therapeutics AG

1.97

51,610k

WntResearch AB

1.08

9,310k

X4 Pharmaceuticals Inc.

0.35

56,790k

Xbrane Biopharma AB

0.02

30,590k

Xintela AB

0.03

17,120k

Xlife Sciences AG

29.59

169,906k

Xspray Pharma AB

3.52

98,020k

Zealand Pharmaceuticals A/S

94.65

6,690,000k

25

52 WEEKS INDICATOR low high

                           

All quotes are listed in Euro. All data is provided without guarantee. The effective date is 25th November 2024.

These Europe-based biotech companies are traded on European stock markets.

Focussing Europe as business location For biotechnologists, Europe is a collaborative research area. For the biotech industry it is a huge common market with almost 500 million potential customers. The 14th edition of the European Biotechnology Guide presents an attractive cross-section of companies and institutions from 16 nations.

164 pages, available in all bookshops and at biospheria.shop/en ISBN 978-3-928383-91-2

19.80 Euro

BIOCOM Interrelations GmbH | www.biocom.eu

ECONOMY

European Biotechnology | Winter Edition | Vol. 23 | 2024

Trouble: Novartis writes down Morphosys deal The acquisition of Morphosys by the Swiss company Novartis AG in January this year for US$ 2.7bn and its subsequent delisting put an end to the 30-year development of the company, headquartered in Planegg south of Munich. But the story isn’t over yet.

The drug asset faces significant FDA delays, prompting many questions.

TAKEOVER

royalties from a psoriasis antibody that partner Johnson&Johnson had brought to market (Tremfya), as well as from the company‘s only internally marketed antibody, Monjuvi.

All on one card

Pipeline asset of Morphosys under investigation. Novartis and the FDA have more questions about pelabresib.

Novartis had just celebrated a successful third quarter, raising its full-year forecast by several percentage points. The Swiss company‘s optimism stems from a pipeline that appears well stocked with blockbusters and annual sales that promise low double-digit growth on a conservative estimate of around US$50bn.

The fact that the purchase of Munichbased Morphosys AG with its drug pelabresib is now on the books as a multimillion-dollar ‘write-off’ could almost go unnoticed.

Long story not yet finished?

Morphosys AG, part of the Munich bio­ technology cluster, initially based in

Martinsried and later in Planegg, is history. The takeover by the Swiss company Novartis AG in January this year for US$2.7bn and the subsequent delisting of the company put an end to the 30-year development of the company, which for many years was considered a beacon for the region and the German biotechnology scene as a whole.

Turning away from antibodies The small-molecule myelofibrosis drug pelabresib, acquired through the takeover of US-based Constellation Pharmaceuticals, cost the Munich-based company around US$1bn in 2021. This amount was raised from the sale of expected

To save money, the new CEO, Jean-Paul Kress, implemented a strict cost-cutting programme, closed down preclinical development, laid off a good 70 employees in Munich, and raised additional funds through capital measures on the stock exchange. None of this helped the share price. All too often, industry experts had witnessed companies betting on a single horse in the stable, only to crash and burn.

From over €100 per share at the start of 2020, the biotech´s share price plummeted to around €15 over the next three years.

Hope gradually returned to Morphosys in 2023, however, as data from the pivotal pelabresib trial was due to be presented at the end of the year.

When the results were presented in the autumn, there was a very mixed response. Initially, the achievement of the primary endpoint was celebrated, but soon there was a debate about the secondary endpoint, which was not significantly met, and the occurrence of adverse side effects. Instead of jumping for joy, the share price fell again. Only after some delay did the company reverse its view that the drug would be a candidate for approval after all. This was probably not entirely altruistic. Discussions with the Swiss company Novartis AG appear to have intensified since the summer of

Picture: © freepik.de/maniacvector

26

European Biotechnology | Winter Edition | Vol. 23 | 2024

2023 on whether this compound could be added to the Basel-based company‘s pipeline. While Novartis initially only wanted to add the compound to one of its own drugs already approved in this indication, Kress and his management team insisted that the entire Morphosys AG would have to be acquired in a deal.

All or nothing.

At the turn of the year 2023/24, the share price was just over €30. Novartis‘ offer to acquire Morphosys for €68 per share and a total of around US$2.7bn looked like a welcome doubling to all shareholders at the time. The company, whose antibody development platform had made it a successful drug supplier, had actually been trading well above €50 for most of the time since 2014, but the multi-billion euro sale was hailed in many industry reports as a success and a good deal for Morphosys shareholders.

Unexpected delay However, rumours began to circulate in late spring that the expected and almost certain approval of pelabresib would be delayed. The FDA could not be convinced so quickly, the data would have to be analysed more thoroughly and a rapid approval within a few weeks or months was no longer on the table. Another striking development in the first half of the year was that at Morphosys´ last annual general meeting, chaired by the new interim CEO Heinrich Moisa (head of Novartis Deutschland GmbH), former CEO Jean-Paul Kress, who left Morphosys in June, and another member of the Executive Committee were refused discharge by the current majority shareholder. Was it clear then that the clinical development of pelabresib was far from optimal?

The current, thinly veiled information from Novartis in the context of the quarterly results says little: ‘Following Novartis‘ review of the 48-week data from the Phase III MANIFEST-2 study, a longer follow-up period is required to determine the regulatory pathway for pelabresib in myelofibrosis in consultation with health authorities. Industry

publication EndpointsNews has identified a write-down of around US$800m for the current financial year. This is likely to rise further next year to the same amount if development of the drug is discontinued altogether. There are likely to be concerns about the emergence of new malignancies in the course of clinical trials. STAT News reported such new malignancies in pelabresib-treated patients earlier this year, casting doubt on the acquisition. Now, Novartis is willing to look at the data in more detail “over the next year and assess the potential need for additional studies,” said CEO Vas Narasimhan during the third-quarter media conference call.

A quick approval, as the story was told while the acquisition was in preparation, is therefore no longer to be expected. It remains to be seen whether Novartis will go to the trouble of starting from scratch.

One question that remains unanswered – despite repeated requests to Novartis – is why Novartis did not take a closer look at the clinical data in its original assessment of pelabresib.

Morphosys had to evolve its business model as the antibodies of their platform had kind of gone out of fashion, and other new variations were gaining attention, such as ADCs, which Morphosys had simply missed. However, the complete abandonment of these molecules left a whole workforce out in the cold, having to deal with bought-in small molecules whose exact pharmaceutical effect – and possible side effects – had to be validated in a very different way from the antibody assays that had been introduced.

The battering the Morphosys story has now taken, Novartis may be able to cope with. Setbacks in the drug pipeline are not uncommon, and easily balanced with the blockbusters that are currently generating big revenues in Basel. Even at the same time as the shaky Morphosys deal, Novartis‘ own hopeful XXB750, an anti-hypertension antibody, was fasttracked from the earliest Phase of a study in healthy volunteers directly into a Phase II trial, but is now discontinued. For Novartis,  this is a normal process. g.kaeaeb@biocom.eu

ECONOMY

Radiopharma TREND A biotech acquisition trend is still

ongoing in the area of radiopharmaceuticals this year. These radioactive drugs can be used for the diagnosis and, increasingly, for the therapy of diseases (depending on the type of radiation that those radioisotopes produce). The applications range from imaging of many different organs to the treatment of cancer and hyperthyroidism.

A decade ago, Bayer (Germany) started the acquisition trend in 2013 with the purchase of Norwegian Algeta for US$2.9bn. In 2017, Novartis entered the space with a twin acqusition of Francebased AAA (US$3.9bn) and US-based Endocyte in October 2018 (US$2.1bn), leading to the bestseller drugs Lutathera and Pluvicto, the latter of which was approved by the FDA in 2022. Taking advantage of this uptick in market interest, RayzeBio went public on NASDAQ in September 2023, raising US$340m.

Shortly after the IPO, Bristol Myers Squibb (BMS) bought RayzeBio off the stock exchange for US$3.1bn. Also Eli Lilly got on the moving train and acquired Point BioPharma for US$1.4bn at the end of last year.

The story continues in 2024: In March, it was announced that AstraZeneca would acquire Canadian Fusion Pharmaceuticals for US$2.5 bn. And most recently, Novartis announced that it was stepping back into the market to acquire Mariana Oncology for US$1bn upfront and up to US$750m in potential milestone payments. Boston-based Mariana was founded in 2021 by Atlas Venture and RA Capital Management, and has raised additional funding from other top investors, including DeepTrack Capital and Forbion. It is developing a pipeline of peptide-based radiopharmaceuticals designed to maximise tumour penetration in solid tumours while minimising toxicity.

Adrian Toutoungi of Taylor Wessing comments: “This is clearly a big pharma land grab, as we have seen with ADCs and before that with tyrosine kinase in hibitors.”

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RUBRIK

European Biotechnology | Spring Edition | Vol. 23 | 2024

Celebrating ABBA style Celebrating 30 years of pioneering partnerships in the life sciences, this year’s BIO-Europe programme was inspired by the Swedish approach: an openness to collaboration to drive innovation in the life sciences industry. “Money, Money, Money” and other songs by famous Swedish and international musicians set the frame in panel discussions on how to explore strategies that strengthen the European venture ecosystem to support future life science breakthroughs. The EBD Group celebrated its own invention: the mother of all partnering events.

BIO EUROPE

Pictures: © xxx

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EVENT

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Pictures: #BIO-Europe

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artnering was again rapidly in full swing, with meeting requests and scheduled meetings up on the very first day compared to last year’s conference. 61 nations compiled in the BioEurope arena, the 10 strongest nations were the US, Germany, UK, South Korea, Switzerland, Japan, France, Sweden, the Netherlands and China (in this order). Sweden showed the strongest growth over the last year, not too surprisingly, as the host country.

In numbers: 5,700 attendees from over 61 countries travelled to Stockholm to come together in 30,506 one-to-one meetings where 4,023 licensing opportunities could be discussed. 3,038 companies where represented by the participants. In addition to the one-to-one meetings, the event was set to cater to the needs of the entire value chain with workshops and panels, innovative compa-

ny showcases, an active exhibition and a variety of networking opportunities.

Song titles set the agenda The first day covered “Money, Money”: venture capital representatives and corporate ventures discussed the financing in times when interest rates are going down and everybody is waiting for signals of resurrection after a difficult year in 2023. The second day kicked off with “Keep This Fire Burning: Innovate or Acquire?” The famous patent cliff of Big Pharma is still the predominantly used phrase to picture the end of many blockbusters. Strategic choices for these large companies to navigate patent expirations, and innovation gaps were discussed, and different approaches to filling their pipelines were presented: Do they focus on internal innovation or pur-

sue acquisitions? Leading pharmaceutical companies such as Chiesi, Novartis, Bayer, Ipsen and Johnson & Johnson provided insights into the decision-making processes that drive partnerships, M&A and innovation strategies.

Innovation topics In continuation under the motto “I’ve Been Waiting for You”, speakers showcased the rise of novel cardiometabolic therapies as transformative developments in a major global health challenge.

Discussions focused on breakthrough innovations in the treatment of age-related and cardiometabolic diseases, with insights from key industry players.

Subsequently, the anniversary partnering event also reflected on the rich history of past partnerships, deals and innovations over the last three decades.

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EVENT

European Biotechnology | Winter Edition | Vol. 23 | 2024

The organisers are used to the crowd that shuffles into every new location the BioEurope is stopping by. This leads to another very practical factor that plays an important role in the selection of the event location: the several thousand participants need a venue for the get togethers that does not look like an exhibition hall or an airport hangar for an evening event in a relaxed atmosphere.

The setting is important This consideration significantly narrows down the number of suitable venues across Europe, especially when the selection process also takes into account a critical mass of local pharma and biotech activity. The conditions for these side events have to meet with BioEurope attendees, who love to party. This was very well met in the birthplace of ABBA.

Claire Macht, Director, European Portfolio, EBD Group, stated: “Over the past 30 years BIO-Europe has grown with the biotech industry, in size, in sophistication, and in global reach. We understand that collaboration is central to the success of the industry and so we strive to keep every element of BIO-Europe focused on bringing people together, whether that is in a partnering booth, a pitch competition, or at a lunch table.” And the founder of BioEurope, Carola Schropp, today President of Hayim Holding LLC, said: “In the 1990s the world was not yet connected. Phones, faxes – those were your options. It was very hard for biotech companies to meet pharma. The conference gave people a way to get to know each other, to start a community. People became friends, opened up – yes, it was about business but also about so much more. We learned that partnerships and collaborations only worked when people trusted each other and both parties felt that the deal was fair. Our meetings helped the industry create billions of dollars of value. Not that we knew this in the beginning nor was it our goal … but L we helped as accelerators.”

Pictures: © xxx

A long history to harvest from

Pictures: #BIO-Europe

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NEWS IMoono-boost In mid-November, inflammation specialist MoonLake Immunotherapeutics AG started US enrolment of patients for its global Phase III programme to evaluate its antiIL-17A/A, anti-IL-17A/F, and anti-IL17F/F dimer nanobody sonelokimab with active psoriatic arthritis. In the split Phase III IZAR-1 and -2 study, Moonlake is going to enrol about 1,500 adult patients to evaluate the efficacy and safety of 60mg and 120mg doses of sonelokimab over 52 weeks. IZAR-1 will enrol biological-naïve patients while IZAR-2 will enrol patients refractive to TNF-IR) and will include the IL-23 blocker risankizumab in the reference arm.

The primary endpoint (ACR-50) versus placebo, and secondary endpoints for both trials are expected to read out at week 16. The readout of the primary endpoint for both IZAR-1 and IZAR-2 is anticipated in H1/26.

Sleepless in Tokyo Tokyo-based Nxera Pharma Co. Ltd’s (formerly Sosei Group) partner Centessa Pharmaceuticals Ltd has initiated a Phase II study with its oral orexin receptor 2 agonist ORX750 to treat patients with the sleep/wake disorders narcolepsy type 1 and 2, and idiopathic hypersomnia. The trial initiation triggered a US$3.5m milestone payment to Nxera. ORX750, which originated from a strategic co-investment between Nxera and Medicxi, is designed to target the pathophysiology of orexin neuron loss in NT1, with potential applicability to NT2, idiopathic hypersomnia, and other sleep-wake disorders with normal orexin levels.

European Biotechnology | Winter Edition | Vol. 23 | 2024

Update of ongoing clinical trials SOLID TUMOURS

In November, PPF Group subsidiary SOTIO Biotech has given an update on two attempts to prevent immune cell exhaustion with its PD-1 blocking immunocytokine SOT-201 and its CAR-T cell therapy BOXR-1030 targeting PD-1 resistant solid tumours and GPC3-expressing tumours, respectively. At the 2024 Society for Immunotherapy of Cancer Meeting (November 6–10, Houston), the first four patients enrolled in the open-label dose-escalation Phase I trial VICTORIA showed good tolerability of SOT-201. SOT-201 is a humanised, Fc-silenced cis-acting immunocytokine consisting of a monoclonal antibody against PD-1 fused to a covalent RLI15 complex that activates innate immune responses through an attenuated human IL-15 mutein and the high-affinity binding site of the IL-15Ralpha, the sushi+ domain. According to preclinical data, the activity of SOT201 is based on spatiotemporal reinvigoration of PD-1+ CD8 + tumour-infiltrating lymphocytes (TILs) via cis activation and concomitant activation of innate immunity by IL15-mediated signalling via the IL-2/IL-15 betagamma receptor. In MC38 mouse models, the immunocytokine showed higher cytotoxicity, lower exhaustion and immune checkpoint transcriptional signatures in comparison to mPD1IL-2v. SOTIO CSO Martin Steegmaier, Ph.D., commented, “SOT201 demonstrates a superior ability to reinvigorate exhausted tumoural CD8 + T cells with a high cytotoxicity and minimal cellular exhaustion compared to the related cytokine PD1-IL2v. These data demonstrate SOT201’s reduced off-target interactions and more durable anti-tumour efficacy in vivo, underscoring its potential to address current limitations in anti-PD-1 therapies.”

In addition, the company showed preclinical data of an approach to advance efficacy of its BOXR CAR-T cell therapy platform. For this purpose, SOTIO co-expressed the PGC-1alpha transgene with

a ROR1-targeted CAR in human T cells and compared in vitro and in vivo data to CAR alone. According to Steegmaier, “chimeric PGC-1alpha enhanced CAR T anti-tumour efficacy with no overt signs of toxicity, suggesting that co-expression of CAR and the chimeric PGC-1alpha could be a promising approach to improving CAR T cell efficacy in solid tumours.”

At the ESMO conference in mid-September, Immatics NV has presented first interim Phase I data from an ongoing adaptive dose escalation study (6,6µg2,500 µg) with its bispecific T cell engager (TCE) IMA401 – a novel, nextgeneration, half-life extended bispecific T cell engager directed against an HLAA*02-presented peptide that is derived from MAGEA4 and MAGEA8 with high target copy numbers on various solid tumour entities. According to the company, interim data from the study, enrolling 35 heavily pre-treated patients across 16 solid tumour types, demonstrate initial anti-tumour activity and a manageable therapeutic index for IMA401 monotherapy (secondary endpoints). The confirmed objective response rate was low for a TCE – only 25%. However, in responders, IMA402 achieved a disease control rate of 53% and a tumour shrinkage rate of 53%. The objective responses that were observed in head and neck squamous cell carcinoma, neuroendocrine tumour, as well as cutaneous and mucosal melanoma included durable ongoing partial responses of up to 13 months and a tumour shrinkage of sometimes more than 50%. Pharmacokinetics data indicated a median terminal half-life of 16.9 days, justifying the current bi-weekly dosing schedule and the exploration of potential dosing schedules of up to once in every four weeks.

Immatics further announced it is to regain full clinical development and commercialisation rights to IMA401 from its commercialisation partner Bristol Myers Squibb, who is defining new portfolio priorities for its pipeline.

REGULATORY AFFAIRS

European Biotechnology | Winter Edition | Vol. 23 | 2024

is designed to demonstrate that treatment with semaglutide 2.4 mg in adults with MASH and moderate to advanced liver fibrosis reduces the risk of liver-related clinical events compared to placebo after 240 weeks.

IMA401 is a 2 x 1 bispecific T cell engager that was selected as the most effective from seven bispecific antibody formats.

Picture: Data ESMO 2022

OBESITY

Despite lower Q3/24 sales than expected by analysts, new clinical data relating to Novo NordiskA/S’ obesity blockbuster semaglutide suggest that the GLP1-receptor agonist is set to get a lucrative FDA label extension. In liver fibrosis as well as metabolic dysfunction-associated steatohepatitis (MASH), semaglutide delivered convincing preliminary results in the two-part pivotal Phase III ESSENCE study that will enrol 1,200 adults with MASH and moderate to advanced liver fibrosis (stage 2-3). In part I of the study, the effect of a onceweekly 2.4 mg dose of semaglutide in addition to standard treatment on liver histology was investigated in 800 pa-

tients over a period of 72 weeks. Semaglutide met all primary endpoints. At week 72, 37% of people treated with semaglutide achieved improvement in liver fibrosis without worsening steatohepatitis compared to 22.5% in the placebo group. Additionally, 62.9% of people treated with semaglutide 2.4 mg achieved resolution of steatohepatitis without worsening of liver fibrosis, compared to 34.1% in the placebo group. There occurred no unknown side effects. The Danish pharma giant expects to submit marketing authorisation applications in the US and EU in the first half of next year. Part 2 of the ESSENCE study will continue and is expected to be completed in 2029. Part II

In June, Eli Lilly announced Phase II results of its SYNERGY-NASH trial in which 54.9% of patients on its dual GLP-1/GIP receptor agonist tirzepatide 5 mg, 51.3% of patients on tirzepatide 10 mg and 51% of patients on tirzepatide 15 mg saw their fibrosis decrease by at least one stage without their metabolic dysfunction-associated steatohepatitis (MASH) worsening. That compared with just 29.7% of MASH patients in the placebo group who saw their fibrosis improve, according to a latebreaking abstract published ahead of the EASL International Liver Congress.

Results of Lilly and Novo are better than those obtained with the approved treatment, resmetirom (Rezdiffra), from Madrigal Pharmaceuticals Inc. At the end of October, Italian obesity gene therapy developer Resalis Therapeutics srl has gained an equity investment from French pharma major Sanofi SA sufficient to finance its miRNA-22 antisense blocker RES-010 through Phase II testing. According to CEO Antonio Toniolo, Resalis will start enrolment of

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REGULATORY AFFAIRS

a Phase I trial very soon. No details of the transaction and its impact on later M&A or drug licencing were disclosed.

Though Sanofi did not publish financial details, as the programme is to be financed up to Phase II proof-of-concept, an investment in the region of €50m to €150m can be assumed.

NSCLC

Daiichi Sank yo Co Ltd’s potential blockbuster lung cancer antibody drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd), which was licenced to AstraZeneca plc, has failed in the pivotal Phase III trial TROPION-Lung01. The engineered TROP2-directed antibody linked to four topoisomerase I inhibitors as toxic payloads showed no significant improvement in overall survival versus docetaxel, the current standard of care in adult patients, according to the Journal of Clinical Oncology (10.1200/ JCO.24.009). The partners are now focussing on a subgroup of patients with non-squamous NSCLC who experienced a clinically meaningful improvement in overall survival.

SARCOMA

French Valneva SE and its licensor Swiss Limma­Tech Biologics AG started a Phase IIb human challenge study of their tetravalent Shigella Vaccine Candidate S4V2 in mid-November. In the CHIM study S4V03 (NCT06615375), S4V2 will be tested for safety and preliminary efficacy in approximately 120 healthy Shigella-naïve volunteers aged 18 to 50 years at three sites in the United States. The parallel-group, randomised, double-blind, multicenter, placebo-controlled study includes two steps: confirmation of the vaccine dose, and challenge of the study population with the Shigella sonnei strain 53G one month after injection of S4V2 or placebo, in order to assess the ability of S4V2 to protect against the Shigella infection. The infection rate of shigellosis caused by Shigella sonnei 53G in the group vaccinated with S4V2 will then be compared to the group of participants who received placebo injections.

European Biotechnology | Winter Edition | Vol. 23 | 2024

According to Thomas Lingelbach, Chief Executive Officer of Valneva (see p. 20) “human challenge studies are unique in their ability to investigate and understand the onset and development of disease in a safe and highly controlled environment. This CHIM study […] should provide the first results on efficacy before potentially advancing to further CHIM and Phase III studies.” In addition to the CHIM study, LimmaTech will conduct a Phase II paediatric study in low- and middle-income countries expected to begin this year.

British Adaptimmune Ltd nears a second approval for a TCR-T cell therapy.

After meeting the primary endpoints of a pivotal Phase II trial in mid-November, Oxford-based Adaptimmune Ltd has announced to submit a Biologics License Application to the FDA for its autologous T-cell receptor therapy (TCR-T) Lete-cel (letetresgene autoleucel) next year.

In the pivotal Phase II trial IGNYTEESO, Adaptimmune’s TCR-T cell therapy Lete-cel, which is directed against the tumour antigen NY-ESO-1, achieved an objective response rate of 42% in 64 evaluable patients with NY-ESO-1-positive advanced or metastatic synovial sarcoma or with myxoid/round cell liposarcoma (MRCLS). Six complete and 21 partial remissions were achieved.

The UK company plans to submit its second marketing authorisation application (rolling BLA) after afami-cel for a second-line TCR-T cell therapy in solid tumours to the US Food and Drug Administration (FDA) by the end of 2025.

The primary data analysis showed a response rate of 14/34 (41%) in patients with synovial sarcoma and 13/30 (43%) in patients with MRCLS. The median response duration was 12.2 months (95% CI 6.8, 19.5). In synovial sarcoma, the median response duration was 18.3 months (95% CI 3.3, -). In MRCLS, the median response duration was 12.2 months (95% CI 5.3, -). The median progression-free survival (PFS) was 5.3 months (95% CI 4.0, 8.0). Side effects such as cytopenias and cytokine release

syndrome, which can prevent paediatric use, occurred most frequently, but are common and manageable with this class and generation of drugs. In August this year, Adaptimmune received the world’s first accelerated FDA approval for its genetically engineered TCR-T cell therapy afami-cel (afamitresgene autoleucel) against solid tumours – more precisely: inoperable synovial sarcomas – on the basis of response rate, which must be confirmed by further clinical data. Afami-cel is also directed against the cancer testis antigen Mage-4. Following Roche’s withdrawal from a US$3bn licence agreement, Adaptimmune was only able to obtain marketing authorisation for afamicel and pay the costs of the IGNYTE-ESO trial because Galapagos NV stepped in as a partner. The Belgians licensed a third British IND-stage TCR-T candidate, uza-cel (uzatresgene autoleucel), which recognises the MAGE-4A antigen on tumour cells, for an upfront payment of US$100m.

SJÖGREN’S DISEASE

In mid-November, Johnson & Johnson subsidiary Janssen-Cilag International NV presented results from a Phase II DAHLIAS study that assesses the safety and efficacy of nipocalimab in adult patients with moderate-to-severe Sjögren’s disease (SjD). Patients (n=54) who received the investigational FcRn blocker showed a significant improvement in the ClinESSDAIa score at 24 weeks versus placebo. The key secondary endpoints of the study were met, indicating reduced disease activity both systemically and across multiple organ systems, as well as positive physician assessments and composite SjD assessment tools. Results also showed a significant reduction in IgG (77%), including autoantibody levels among patients receiving 15 mg/kg (n=54) nipocalimab every two weeks versus placebo. Improvements in ClinESSDAI were greatest in participants with high baseline levels of anti-Ro and anti-La autoantibodies.

Nipocalimab did not show severe safety issues during the period of administraL tion.

ECONOMY

European Biotechnology | Winter Edition | Vol. 23 | 2024

Unified Patent Court: quo vadis?

The Unified Patent Court is up and running for more than one year. It’s time for a brief resume. The court is not overly patentee friendly but is applying strict standards to patent validity. Further, litigation in Europe with the new court is at present far more complex and costly than previously thought.

IP

› Dr Ute Kilger, Boehmert & Boehmert, Germany

Picture: © Boehmert & Boehmert

The Unified Patent Court (UPC) started on 1 June 2023. The UPC was created to enable enforcement and revocation of a European patent in one central court instead of having litigation before national courts throughout Europe. At present a European patent may be effective in 27 EU member states and in 12 other European states. After the central granting procedure before the European Patent Office, the European patent must be dealt with before the national courts of the member states of the European Patent Convention (EPC). It was argued that litigation before ONE court instead of 39 national courts would facilitate litigation and be less costly. To be honest, however, there were not many examples of European patents that were litigated before 39 national courts throughout Europe. Mostly, European patents were litigated in Germany, in the Netherlands, and maybe in the UK, and then the parties settled. 80% of all European litigation took place in Germany, and German litigation is by far less costly than litigation before the UPC. Also, the UPC is not effective in all 39 EPC member states.

It is effective only in 18 EU member states (not in the UK). This puts the cost argument and the complexity argument into perspective.

Some statistics The Court of First Instance has received a total number of 503 cases until September 2024. From 192 infringement actions,

significant cases – also bring parallel patent infringement actions from their patent portfolio before the German patent infringement courts in parallel to UPC actions.

Opting out

Dr Ute Kilger, Partner, Boehmert & Boehmert

151 infringement actions have been filed before German local division. 212 counterclaims for revocation have been filed with the Court’s local and regional divisions, wherein 204 counterclaims for revocation come from 103 individual infringement actions.

In comparison In 2023 alone, 601 new patent infringement suits were filed before German courts (not UPC), whereas the UPC had 192 infringement actions from June 2023 until September 2024, and most of them were filed before German local divisions of the UPC. And it should be noted that almost all UPC plaintiffs – especially in more

Thus, it seems that Germany has become a UPC heavyweight from the start, which is no surprise given the well-established patent case law in Germany over the past 100 years.

Is opting out of the UPC a good option? Many patentees have opted out of the UPC system. At the end of 2023 there were well over 500,000 opt-out declarations, which must be regarded as a high number. It should also be noted that whenever national proceedings of any kind (infringement or invalidity) have been conducted for the European patent in the past (before the opt-out), opting back in is not possible. On the other hand, an opt-out declaration is not required to be able to bring an action before a national infringement court. Both court systems – UPC and national patent jurisdiction – are, in principle, competent in parallel without an opt-out declaration. If the European patent falls under the jurisdiction of the UPC, there is, however, the risk that one single revocation action may invalidate the patent in all 39 EPC member states. With the UPC system, the patentee has “all eggs in one basket” – a risk that some patentees may not be willing to take.

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ECONOMY

Let’s look at the first cases and what lessons are learned. The most spectacular case was the 10x Genomics vs Nanostring. Local Division (LD) of the UPC Munich issued preliminary injunction against Nanostring with effect in all UPC countries. By order of February 26, 2024, the UPC Court of Appeal overturned the order of the LD, rejected 10x Genomics‘ request to issue a preliminary injunction, and ordered that 10x Genomics, being the losing party, has to bear the procedural costs. The reason for the appeal court's different assessment: The appeal court came to the conclusion that it is overwhelmingly likely that the patent will be declared invalid in the main proceedings due to lack of inventive step. The plaintiff was very unhappy with this decision and argued that the taking of evidence cannot be replaced by the technical opinion of a member of the panel, and even less so if this opinion has not even been documented in writing or has become the subject of the proceedings and the parties have not had a meaningful opportunity to comment on it. On April 24, 2024, the plaintiff 10x Genomics filed a motion for retrial. The President of the Court of Appeal referred the matter to the Second Panel and ordered that the judges of the Court of Appeal involved in the decision are not allowed to sit on the review jury. The Second Panel of the Court of Appeal ruled that the request was inadmissible because the decision did not suffer from a fundamental procedural error. Let’s wait and see for the main proceedings.

European Biotechnology | Winter Edition | Vol. 23 | 2024

This case is, however, also interesting because of the principles that were used to interpret the claims. Firstly, the UPC Court of Appeal confirms the basic principle that the principles for the interpretation of a patent claim must apply equally to the assessment of infringement and the legal validity of a European patent. This was different in the German bifurcated system, where the patentee could argue in infringements proceedings that the scope of the claim must be interpreted broadly thereby catching the alleged infringer, whereas the patentee could argue before the BPatG that the claim was very small and far from the prior art. So, the patentee could argue a “mouse claim” before the BPatG, and an “elephant claim” before the infringement court. This is not possible before the UPC. Secondly, in the above case, the appeal court made clear that the interpretation of a patent claim does not depend solely on its exact wording in the linguistic sense. Rather, the description and the drawings must always be considered as explanatory aids for the interpretation of the patent claim and not only be used to eliminate any ambiguities in the patent claim. When applying these principles, it seems that appropriate protection for the patent proprietor can be combined with sufficient legal certainty for third parties.

Looking further, the initial judgements indicate a tendency of UPC to restrict patents. One of the most interesting questions was how plaintiff-friendly the court would be. Although it isn't possible

to compile statistics from the few published judgments, initial rulings show that the divisions are analysing patents critically. So far, the majority of patents have been restricted or nullified, and only a few plaintiffs have been successful.

Conclusions What are the preliminary conclusions? For the foreseeable future, the UPC will operate alongside national courts, likely resulting in an overall increase in litigation across Europe. National courts will remain important, in particular German and Dutch courts.

The UPC merges the procedural features of many European jurisdictions, providing new strategic options alongside existing strategies and tools. With a timeframe of one year to a first instance judgment, the UPC will provide quicker outcomes than many existing European court systems. The front-loaded nature of UPC proceedings implies greater preparation by the claimant, with significant time pressures on the defendant. This will require more resources from claimants and defendants, which will make the proceedings more costly. While it may simplify European patent litigation in the long-term, the UPC will give rise to significantly greater complexity in the short-term. Thus, at present, the UPC may not be the right playground for small and medium companies but will be extensively tested by those L with deeper pockets.

Picture: © Andrii - stock.adobe.com

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SPECIAL

European Biotechnology | Winter Edition | Vol. 23 | 2024

New antibody formats need custom research Biotech CSOs, CDMOs, CROs, lab specialists and AI developers gave an in-depth insight into next-generation protein-based therapies to about 1,500 attendees at the 16th PEGS Europe in Barcelona. Several new formats are expected to enter the market in the next few years that might significantly reduce the side effects of CAR-Ts, bispecific antibodies, ADCs, and improve their efficacy.

As the innovators are SMEs or virtual companies, they depend on support with tools and services.

Picture: © BIOCOM

PEGS EUROPE

At US$230.87bn, monoclonal antibody therapies accounted for the majority of the US$416.65bn global market for biologics and biosimilars at the end of 2023. However, at the 16 th PEGS Europe in Barcelona, drug hunters from a new Venture Capitalist that has already raised US$1bn told European Biotechnology that "the golden age of antibodies is still to come". New formats such as bispecific antibodies, antibody drug conjugates (ADCs), multispecific T-cell engagers activated in their target tissue to prevent off-target toxicities as well as further engineered modalities such as bispecific 4th and 5th generation CAR-Ts, TCR-Ts and protein degraders presented by biotech start-ups at PEGS Europe are not only emerging from the development pipelines but also from partnerships with tool, service and AI providers (see p. 39).

For instance, British Nuclera Ltd announced a partnership with French CRO Domainex – the first of its kind – that is going to use its eDiscovery platform for custom protein production.

Though Yumab CSO André Frenzel told European Biotechnology that developers have become careful in selecting AI partners, they announced a partnership with Japan's MOLCURE Inc to use the AI specialist’s platform for in silico de novo design of antibody sequences based on antigen sequences and/or target structures.

About 150 sponsors and exhibitors presented their results, products and services at the 16th PEGS Europe 2024 in Barcelona.

Many presentations at PEGS Europe demonstrated that the approval of newly engineered bispecific antibodies, ADCs, and CAR-T cell therapies has picked up immensely since 2021. "To date, 13 ADCs and 17 bispecific antibodies have been approved, representing global sales of US$10bn and US$8bn, respectively,” said protein engineering expert Dr Christian Klein, who recently moved from Roche to early-stage investor Curie.Bio (see short interview).

"ADCs and bispecifics are the fastest

growing class of therapeutic antibodies. This is also reflected in the current deal activity."

Growing with new markets As targeting, toxicity and affinity challenges have to be overcome, drug developers were seeking for the next-gen solutions at the PEGS Europe exhibition, particularly in the fastest moving field of bispecific antibodies. With nine marketing authorisations from 2021 to 2023

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SPECIAL

alone, bispecifics are a particularly attractive antibody format, not least because of their potential to demonstrate completely novel mechanisms of action for the treatment of various diseases that cannot be achieved with monospecific antibodies. The antibodies presented at PEGS included tumour-eliminating T-cell engagers with reduced toxicity, which was achieved by switching target affinity, NK-cell engagers, and macrophage cell engagers. Furthermore, dual-targeted specific ADCs with selectivity for defined cancer types were presented, along with the cis-targeting of T-cell subsets using dual checkpoint inhibitors or cytokines. Further developments invvolved degraders of cell surface proteins, formats that pass the blood-brain barrier and those that can switch bsAbs on/off in the tumour microenvironment to prevent undesired peripheral toxicities, cytokine and coagulation factor mimetics, and many more (see p. 12). Specialised service providers and sponsors also present-

European Biotechnology | Winter Edition | Vol. 23 | 2024

ed novel methods such as single-cell sequencing, proteomics, cryo-EM, machine learning, and AI and ML solutions that promise to overcome development challenges such as a narrow therapeutic index, premature protein aggregation, unselective release of toxic payloads of ADCs and radiopharmaceuticals, biomanufacturing issues and a lack of selectivity for target sites.

In lectures, exhibitors presented innovations including microfluidic technologies (Lightcast, Sphere Fluidics), tag technologies to scale and automate protein production/expression (IBA Bio­logics, Absolute Bio­tech, BioRAD), high-throughput screening of tumourselective T-cell engagers and other antibody formats through combination of machine learning and cell-based functional assays (LabGenius plc, Genscript Inc., Biointron, Cradle), and ML-driven screening of antibodies for difficult targets (Yumab, Ailux Biologics, PipeBio, BioMap). Other technologies or services covered included in ­v itro antibody

libraries (Specifica/an IQVIA company), protein expression/contract manufacturing (Fuji, Asymbio, GTP Bioways, Excellgene, ThermoFisher), and preclinical modelling (GemPharma­tech, ­Bioneer, The Jackson Laboratory).

Successful exhibition "Participants discussed all aspects of protein and antibody engineering with expanded coverage of AI/ML, drug targets, multi-specific antibodies, immunotherapy, analytical characterisation and developability, protein expression, oncology, and much more," the conference organisers of the 16th Annual PEGS Europe Summit from Cambridge Healthtech Institute told European Biotechnology Magazine.

In the end, the CHI management was pleased with "nearly 1,500 attendees from 38 countries, including 300 speakers and more than 150 sponsorL ing companies from industry." t.gabrielczyk@biocom.eu

Getting started effecively Getting seed and Series A financing while minimising long-term dilution, but getting all essential functions of a large biotech company – how does that sound? At PEGS Europe, E uropean Biotechnology spoke with Nina Kreymborg, SVP, CSO Partner Team at the VC specialist Curie.Bio. EuroBiotech_W hat is unique about what Curie offers?

Kreymborg_Curie.Bio is designed to improve founders’ probability of success in creating impactful medicines while also helping them maintain ownership in their company. We invest and leverage our large team of experienced drug hunters and biotech oper-

ators to help founders design and execute optimal research and operational plans. We co-pilot alongside the founders and provide proprietary access to world-class experts, external vendors, and future investors. We help founders to create not only scientifically exciting but also financially profitable and operationally sound companies to succeed in their journey of turning their ideas into actual medicines.

EuroBiotech_What is your typical investment and which companies do you support?

Kreymborg_We invest around US$712m into each therapeutics start-up.

We must be excited by their science and

believe they can deliver a drug that competitively addresses a major unmet medical need. We are agnostic to therapeutic modalites and indications and give support to companies across various geographies.

EuroBiotech_Why did you join Curie.

Bio? Kreymborg_I am excited to be part of Curie.Bio because of the value Curie sees in exciting science, because of the emphasis Curie puts on reliable and trustworthy interactions with founders and partners, and because of the outstanding team of professionals. “It takes a village to raise a child” and a team of experienced, creative, knowledgeable, and truly collaborative experts to develop a drug or build a company. That team is Curie.Bio. L

Picture: © Curie.Bio

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SPECIAL

European Biotechnology | Winter Edition | Vol. 23 | 2024

Getting to the next stage in ADC development ANTIBODY DRUG CONJUGATES Toxicity problems due to unstable linkers limit the therapeutic index of

­ ntibody-Drug Conjugates (ADCs). Shortly before the PEGS Europe summit, Chinese BigHat and Lonza A subsidiary Synaffix BV signed an agreement for the production of ADCs using machine learning (ML).

Here is the background.

Machine Learning (ML) was a hot topic at PEGS Europe Summit, organised by CHI, with many AI/ML companies exhibiting and reporting how their latest algorithms could help bioengineers to optimise their antibodies and constructs. "Optimisation with the help of AI is years away because we don't have enough clinical data to feed AIs for antibody or even ADC development," experts told E urope an B iotechnology at the must-attend meeting for European protein engineers. "It makes no sense to take preclinical data and feed them to an algorithm", another said, "because in vitro is so poorly predictive for in vivo and preclinical in vivo is so poorly predictive for clinical in

vivo." However, experts agreed that AI can help in rational design. Financings, such as that of Dutch-Swiss ML startup Cradle NV, which announced a €69.5m Series B financing led by IVP and existing investors after the Summit, documented a high interest to integrate AI/ML in development or QS processes. A number of either antibody or ADC developers no longer want to sleep through the development and thus have set up partnerships.

Partnering with algorithms One expample is German antibody development CRO Yumab GmbH, which seeks synergies with Japanese ML

start-up Molcure Inc. Another one was announced right before PEGS Europe

by ADC specialist Synaffix BV. Synaffix’ collaboration with Chinese BigHat Bioscience Co. Ltd was the first after Lonza Group took over the Belgian company this May for €100m upfront + €60m in milestones. It combines Lonza Group's end-to-end ADC development and manufacturing platform with Synaffix’s clinical-stage platform technology for the development of antibody-drug conjugates (ADCs) with best-in-class therapeutic index. Because Lonza as a huge CDMO was interested in Synaffix’ know-how, aka its people, but not its huge proprietary and partnered (around US$10bn biobucks)

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SPECIAL

pipeline, the Belgians spun off three proprietary ADC assets into the startup KIVU Bioscience Inc, which closed a US$92m Series A financing led by Novo Holdings at the end of October. Insiders told E uropean Biotechnology, Synaffix’ deal with BigHat Bioscience was only possible because the Chinese were attracted by both; Lonza’s expertise in contract manufacturing under a single quality system encompassing all critical development and manufacturing activities, including the production of the antibody, bioconjugation, and drug product filling plus Synaffix’ GlycoConnect™, Hydra­Space® and toxSYN® ADC technologies.

According to the agreement, BigHat w ill combine Sy naf fix technolog y with its proprietary ML antibody design platform for the development of a new ADC programme which is at IND-enabling stage and is on track to be BigHat's first clinical stage programme. BigHat’s AI/ML-powered antibody design platform, Milliner™, integrates a synthetic biology-based high-speed wet lab with state-of-theart ML technologies into a full-stack antibody discover y and engineering platform, to engineer antibodies with more complex functions and better biophysical properties.

European Biotechnology | Winter Edition | Vol. 23 | 2024

mal drug-like properties. The incorporation of Synaffix's ADC technologies aims to further improve the safety and efficacy of BigHat’s next-generation ADCs by making them more durable, with greater on-target toxicity and, consequently, a larger therapeutic index—similar to the preclinical ADC trio spun out into KIVU Bioscience.

Hype towards ADCs Lectures on ADCs were a major focus at PEGS Europe. According to Floris van Delft, former CSO of Synaffix and now Head of Research at Lonza, the transition rate of ADCs is above 15% in oncology, while antibodies and small molecule drugs had a success rate of 10% and 5%, respectively. That is probably the reason why so many companies at PEGS Europe go for ADCs. According to Chinese scientists who published a global database called ADCdb last year, there were 6,572 projects ongoing, 346 of which were clinical. However, most of them suffer from a low therapeutic index, they simply show too much off-target toxicity due to systemic release before reaching their target(s).

Early-generation ADCs from Daiichi and others experienced significant

r­ elease of linker-payload outside the tumour, resulting in less pronounced on-target toxicity, while off-target toxicity became the dose-limiting factor.

At PEGS Europe, it became clear that the challenge for the sector currently is to add stability to linkers and enhance tumour selectivity and on-target tox­icity with less toxic new payloads, as reported by several companies (see p. 14) in Barcelona.

New generation of payloads Experts told E urope an B iotechnology what's needed to write ADC success stories: "We need a new generation of payloads for ADCs that are less potent than PBDs and have a lower drug-toantibody ratio (DAR) to reduce toxicity or broaden the therapeutic index.

For tubulin inhibitors such as MMEA, a DAR of 4 limits the maximum tolerated dose to 1.8-2.2 mg/kg. However, for good biodistribution, a higher dose is better." Good biodistribution means a MTD as high as 5 to 10mg/kg, according to pharmacologists. Thus, the current credo is: if the DAR goes down, the dose can go up. Many current clinical or approved ADCs could be dosed up to 3 mg/kg but have a DAR of 8.  t.gabrielczyk@biocom.eu

What ML can improve?

BioHat's approach – similar to that of Cradle, UK-based Labgenius and other players that seek to combine wetlab data, automation and ML/AI to find candidates with optimised attributes – promise to reduce the time for candidate discover y and validation in a sector where time to patent expiry is cash. However, as mentioned in some PEGS lectures and round tables, wet lab data sometimes only comprise 700 to 800 datapoints per screening cycle, which might be not enough for algorithms to learn from.

BigHat’s next-gen ADC candidate was optimised on its Milliner platform for maximum payload delivery to tumour cells (= linker stability) and opti-

Global CDMO Lonza AG announced to build a new bioconjugation production site with 800 m² of manufacturing space at Lonza’s Ibex® Biopark in Visp, in October.

Pictures: BioAlps Association/Lonza

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European Biotechnology | Winter Edition | Vol. 23 | 2024

SCIENCE & TECHNOLOGY

Precision oncology starts with precision insights Successful drug discovery relies on tumor and matched normal tissue samples that preserve tumor biology as close to its original state as possible. This integrity, combined with analytical, computational, and biochemical expertise, enables the discovery of novel therapeutic targets and drug candidates.

D RUG DISCOVERY

› Prof. Dr. Hartmut Juhl, Founder & CEO, Indivumed Therapeutics

The journey to developing novel, effective cancer therapies begins with the collection of tissue samples that ­a ccurately reflect the true biology of the ­tumour. However, such high-quality samples alone are not enough. To truly harness the potential of these samples, cutting-edge computing, and biomathematical and laboratory approaches are required.

Our recent research, published in Cell Death & Disease1, highlights how quickly sample quality declines. Within just ten minutes after surgical removal, molecular markers start to degrade.

Indivumed Therapeutics has pioneered a proprietary approach to sample collection, storage, and processing, which minimises ischemia time to under 12 minutes for more than 75% of samples. This innovative approach, combined with their advanced molecular and multivariate analyses, enables the transformation of high-quality ­samples into high-quality insights, facilitating the identification of novel therapeutic ­targets.

Picture: © Indivumed

Identifying novel targets Indivumed’s unique and proprietary database integrates genomics, transcriptomics, proteomics, and phosphoproteomics, providing a truly multi-omic view of cancer biology. Indivumed’s comprehensive approach uses advanced biomathematics, biophysics, and artificial intelligence (AI) for multi-

rate functional target validation, adding the ­characterisation of identified targets by protein type, biochemical characteristics, cellular location, and biological function.

The future demands quality

Prof. Dr. Hartmut Juhl, Founder & CEO, Indivumed Therapeutics

variate analysis. These proprietary tools analyse complex data patterns and interaction networks, allowing researchers to identify novel and precise targets that are both relevant and highly specific to cancer biology.

Unique holistic process What sets the holistic process apart from the rest of the field is the additional b ­ io­chemical validation of these targets. Samples stored in Indivumed’s biospecimen inventory allow for deeper tissue analyses and, most importantly, the cultivation of 2D and 3D patientderived tumour models – which are as close as possible to the functional reality of the tumour. This enables an accu-

Since its founding, Indivumed has made sample quality the bedrock of its work.

Combined with cutting-edge molecular analyses, this approach uncovers targets otherwise not even found, and this with a higher probability of ­successful therapeutic development ­further down the pipeline.

With 20 years of experience, Indivumed is a trusted partner offering novel, validated, and characterised target packages, grounded in real biology, and develops novel therapies in partnership with phar ma companies.

Scan to read the full publication here:

1

von der Heyde, S., Raman, N., Gabelia, N. et al. Tumor specimen cold ischemia time impacts molecular cancer drug target discovery | nature, Cell Death & Disease 15, 691 (2024) https:// www.nature.com/articles/s41419 -024-07090-x

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EVENT

European Biotechnology | Winter Edition | Vol. 23 | 2024

CPHI Milan 2024 unites the global pharma industry CPHI Milan 2024 became the epicentre of the global pharma supply chain, show­casing unprecedented networking, collaboration, and innovation, from 8th to 10 th October in ­Milan, Italy. With record-breaking attendance of circa 60,000 attendees and 2,838 exhibitors, the event captured the pulse of the industry, setting the stage for future ­advancements and partnerships in pharma.

EVENT

› Tara Dougal, Content and Brand Director – Pharma, Informa Markets

Celebrating its 35th anniversary, CPHI Milan once again proved to be the ultimate gathering for pharma professionals worldwide. The energy of the event resonated far beyond the show floor, as our global community engaged actively onsite and online through CPHI Milan.

With participants from 108 countries, CPHI Milan created a truly international stage, showcasing strong representation from Europe (61%), Asia (24%), and the Americas (12%).

The event featured 68 content sessions, including 41 talks focused on product innovation, and brought together 186 expert speakers. Highlights included Elisabeth Stampa’s insights on the future of pharma manufacturing, Michael Schorpp’s exploration of AI-driven knowledge management at Boehringer Ingelheim, and David Rakowski’s discussion on sustainability in pharma.

Innovation & sustainability At the heart of CPHI Milan’s innovation showcase was the vibrant Startup Market, where 89 pioneering startups from 29 countries took centre stage. This dynamic platform offered a fresh perspective on pharma’s future, with cuttingedge ideas and solutions that energised the event. It became a launchpad for invaluable networking and collaboration, sparking connections that could fuel partnerships and open doors to future opportunities – offering both startups

and established companies the chance to meet their unique needs and expand their horizons together.

This year saw the launch of the Mentorship Program at CPHI Milan, a transformative initiative where seasoned professionals shared their insights with emerging talent. This program offered mentees invaluable opportunities to grow their skills and contribute to sectorwide progress. Sustainability took centre stage as a collective focus, with dedicated hubs fostering vital discussions on eco-friendly practices and meaningful change within the pharma industry.

Awards celebration The CPHI Milan celebration brought together over 1,400 participants from 75+ countries for an evening honouring innovation. The 21st annual Pharma Awards

featured 300+ entries across 14 categories, celebrating breakthroughs in drug development, manufacturing, delivery, and sustainability. Two new award categories – Woman of the Year and Future Leader – highlighted outstanding achievements and rising talent in ­pharma.

CPHI Frankfurt 2025 coming soon Building on the success of CPHI Milan, plans for CPHI Frankfurt 2025 are already underway. Set for 28–30 October, the next event promises to continue the tradition of bringing together industry leaders, innovations, and global partnerships for another milestone gathering.

We look forward to welcoming you in Frankfurt!

Visit CPHI Frankfurt 2025 to learn more  and register today!

Picture: © Informa/CPHI

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Euro BioFairs Compass 1st half-year 2025

©Ezps - Freepik.com

II Guide to Life Sciences Events

SPECIAL

EURO BIOFAIRS COMPASS

European Biotechnology | Winter Edition | Vol. 23 | 2024

17–19 March 2025 Milan Italy

BIO-Europe Spring 2025 ®

BIO-EUROPE SPRING BIO-Europe Spring connects Europe’s top innovation centers with the global life sciences industry to cultivate thriving, strategic partnerships.

Access the next wave of innovation at BIO-Europe Spring – the event connecting companies from the top innovation centers around Europe with the global life science community to cultivate strategic partnerships. The 19 th annual BIO-Europe Spring® will take place March 17-19, 2025, in Milan.

Building and nurturing relationships is an essential part of the progression of successful business partnerships. BIOEurope Spring will offer a vibrant onsite event and a fusion of innovative digital solutions to facilitate these connections.

BIO-Europe Spring will bring together over 3,700 life science executives from around the world. The more than 20,000 partnering meetings held onsite will connect leaders from academia, start-ups, and scaling-up biotech

› QUICK FACTS Registration www.bioeuropespring.com Save €700 when you register before January 31, 2025

companies with pharma companies and forward-thinking investors. Along with world-class workshops and panels, innovative company presentations, and an active exhibition, the variety of networking opportunities make this event an unrivalled forum for companies across the biotech value chain to meet and do business.

Partnering at BIO-Europe Spring is powered by partneringONE®, the goldstand platform for licensing professionals to forge connections that lead to impactful collaborations. With a single login, delegates can schedule oneon-one meetings, access on-demand content, and stay updated on conference activities.

Together with the Biotechnology Innovation Organization (BIO), EBD Group is thrilled to welcome you to this “mustattend” partnering event for innovators L and business leaders.

Come to Milan GREETING Unite with delegates from across the globe at BIO-Europe Spring, Eu r o p e's p r e m i e r event for networking and partnership opportunities with upand-coming companies.

Over the years EBD Group has redefined how the biopharma community connects, collaborates, and creates opportunities. Join us in Milan for the nineteenth annual BIO-Europe Spring, taking place March 17–19, 2025, to discover the latest industry insights and rekindle old connections and create new ones through one-to-one partnering meetings and dedicated networking activities. In 2025, the networking receptions will be hosted in some of Milan’s most iconic venues, ensuring unforgettable opportunities to build meaningful connections.

Start planning to join us in Milan this March to propel the new wave of innovation.

Claire Macht EBD Group

Pictures: EBD Group

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EURO BIOFAIRS COMPASS

European Biotechnology | Winter Edition | Vol. 23 | 2024

8 - 9 April 2025 Wiesbaden Germany

GMP in practice This industry meeting brings together representatives from authorities and the (bio)pharma industry to discuss latest issues and developments – with a focus on challenges and solutions in daily practice, allowing delegates to directly benefit from lectures and from personal exchange.

PHARMACONGRESS & PHARMATECHNICA EXPO

Traditionally, the PharmaCongress conferences offer a broad spectrum of current GMP topics, from which congress participants can put together their individual congress programmes.

As Artificial Intelligence (AI) is finding its way into pharmaceutical manufacturing, and other modern forms of automation and digitalisation, such as IOT and Industry 4.0, are increasingly playing a role, this year’s congress offers two tracks dedicated to these

topics: "Digitisation & Artificial Intelligence" and "Trends in Barrier Systems & Robotics". In addition, the promising application opportunities of automation, digitalisation, AI and robotics will also be addressed, as well as explored in case studies, in the other six conference tracks: Aseptic Technologies/Annex 1, Cleanroom Challenges, Sustainability/Green GMP, Single-Use Systems, ATMPs, and Medical Cannabis. Moreover, as part of the conferences, Phar-

Meet the sector

pert speakers from authorities, industry and service providers who will share their wealth of experience with you. On 8/9 April, you will be able to benefit from insights gained from dayto-day practice, exchange ideas in the eight conference tracks, and expand your network at the Expo and during the popular social event on the first evening.

GREETING For the 27 th time, we are excited to welcome attendees, visitors and exhibitors to the PharmaCongress & PharmaTechnica Expo – taking place for the third time at the RheinMain CongressCenter Wiesbaden. Join us along with around 100 ex-

Axel H. Schroeder Operations Director, Concept Heidelberg

maTechnica Expo exhibitors will provide insights into their technologies with almost 15 live demonstrations, presenting them 'in action'.

On 8th April, the Congress will kick off with a keynote lecture on AI in Manufacturing and Quality at Sanofi, presented

by Dr Maite Durrenbach, Chief Quality Officer at Sanofi and responsible for R&D, Industrial Affairs and Commercial Activities.

At the PharmaTechnica Expo, delegates and expo visitors are invited to learn more about product innovations and to discuss the latest technology advances with nearly 120 exhibitors.

Further, at the expo, the latest winner of the Professor Wallhäußer Innovation Award will be presented in a special ceremony. The eight two-day conference tracks, the large expo, the award ceremony, and a social event make the GMP PharmaCongress with its GMP PharmaTechnica Expo a mustL attend.

› QUICK FACTS Contact www.pharma-congress.com Content

› 8 parallel Conference Tracks › Live Demonstrations › Wallhäußer Innovation Award Ceremony

› Expo with 120 Exhibitors › Social Event

Pictures: © Concept Heidelberg

46

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ECONOMY

European Biotechnology | Winter Edition | Vol. 23 | 2024

Italy goes bold in start-ups: pension funds have to invest Italian pension funds are being urged to take a leading role in the country’s innovation ecosystem. To benefit from an exemption on capital gains tax, a portion of the fund's portfolio must also be allocated to alternative investment funds, which are, amongst others, venture capital funds investing in tech startups.

INNOVATION ECOSYSTEMS

Italian pension funds are being urged to take a leading role in the country’s innovation ecosystem. A recent amendment to the Decreto Concorrenza, agreed upon by the government by the end of November and set to be voted on in Parliament shortly thereafter, introduces a new condition for pension funds to benefit from an exemption on capital gains tax (currently set at 26%).

The key condition is that a portion of the funds' portfolio must be allocated to the real economy – including productive enterprises, infrastructure, and, crucially, venture capital funds investing in tech start-ups. Specifically, pension funds must invest 10% of their total assets each year in such funds.

Picture: © Government of Italy

Italy takes the forefront This measure, developed by the Italian Ministry for Business and Made in Italy under Adolfo Urso (Fratelli d’Italia), with support from experts such as Gianmarco Carnovale, a counselor for the global startup organisation Allied for Startups, positions Italy at the forefront of European efforts to channel pension savings into sectors that drive technological advancement and industrial competitiveness.

To qualify for the capital gains tax exemption, pension funds must allocate a portion of their portfolio – starting at 5% in 2025 and increasing to 10% thereafter – into venture capital funds. These funds, in turn, will invest in scale-ups and latestage start-ups, expanding their presence in the registry from 5 to 9 years. New selection criteria will be introduced start-

Adolfo Urso, Minister of Business and Made in Italy

ing in the third year, alongside tax incentives of up to 65% for investments in innovative start-ups from 2025 onwards.

This new legislation has sparked significant enthusiasm within the Italian startup community. Pablo Docimo, an industry veteran and CEO of 20Ventures, a pre-seed investment firm, commented: "We’re witnessing a transformative moment in Italy’s start-up ecosystem. The recently approved reform represents more than just policy changes – it’s a bold statement about Italy’s commitment to becoming a leading innovation hub."

Better risk-reward equation From the perspective of an investor focused on pre-seed opportunities, Docimo sees these reforms as addressing critical challenges within the ecosystem: › First, the risk-reward equation for early-stage investments has been significantly improved. The maintained tax benefits, even in failure scenarios, create a more balanced environment, en-

couraging capital flow into innovative ventures › Second, the mandatory allocation of pension funds into venture capital will help build a sustainable funding pipeline, potentially transforming Italy’s historically undercapitalised start-up landscape › Third, the inclusion of incubators and accelerators in the incentive framework strengthens the support infrastructure that is vital for early-stage start-ups Docimo sees the reform as a key step in Italy’s effort to compete with established innovation hubs like London, Paris, and Berlin. “This reform isn’t just about tax benefits,” he explains. “It’s about creating a sustainable, competitive ecosystem capable of nurturing world-class start-ups.” The message is clear: Italy is no longer watching from the sidelines. "The pieces are finally in place for our ecosystem to compete on the global stage," Docimo concludes. 

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RUBRIK

Things got busy around the cubicles for partnering at BIO-Europe 24.

European Biotechnology | Winter Edition | Vol. 23 | 2024

Pictures: © xxx

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ECONOMY

European Biotechnology | Winter Edition | Vol. 23 | 2024

Scandinavia’s gangbuster biotech It was the 30 th anniversary for the largest ­pharmaceutical sector partnering event on the European continent, and this year’s programme saw a colourful mix of veterans, first-timers and absolute newcomers. The Nordic countries and host Sweden in particular made quite a splash.

B IO-EUROPE

Picture: © EBD Group, Ludwig Schedl

W

hat began three decades ago as the mother of all partnering events has turned both participants and organisers into professionals and veterans. BIO-Europe is all about the repetition of participation and routine reunions for relationships that may have been established years ago. It’s about the friendly handshake hinting that unfortunately you have to leave immediately for the next meeting, or really lingering over small talk. Maybe followed by a lunch appointment at a less draughty location in the exhibition hall in Stockholm or elsewhere in the city, because there are so many interesting topics to discuss. Those and many other ways of approaching people in the industry are all part of the job.

MC Services – a communications agency and long-time partner in crime with the organisers – collected examples of necessary, cultivated small talk into a little booklet called “The Stockholm Pocket Phrase Book”, with the standard introductory chit-chat in Swedish. It also revealed that about five questions are sufficient to sail through the event without peril. The first should be:

What’s new in your drug pipeline?

Veteran observer Mike Ward, a true trendsetter who was himself celebrating 40 years in the communications indus-

try, echoed the ‘Groundhog Day’ feeling that the event at times inspires: a kind of ‘been there, done that, got the t-shirt’ attitude. Like Donald Trump’s re-election after four years out of office, which dominated discussions on the second day of the fair, but also the industry’s ritualised annual meeting to find partners in general. Repetition is a constant companion at BioEurope, and no one is particularly bothered by it, regardless of where the event’s entourage sets up camp. This time it took place in Stockholm, outside the German-speaking core of Europe. The choice was a nod to Nordic dynamism, which has given the world league of large pharmaceutical players a new North Star with Copenhagen-based pharma heavyweight Novo Nordisk.

Sweden and Denmark can also be mentioned in one breath and considered together, as industry savants in Copenhagen refer to the Øresund region as Medicon Valley, which includes nearby Lund (Sweden) across a watery border.

While the Danes make waves around the world and have a giant pharmaceutical tanker at anchor with Novo, Sweden likes to present more as a hotbed of innovation benefiting both neighbouring countries and Europe as a whole. Both regularly top the innovation and patent league tables in the life sciences, especially in relation to their populations. But even without that kind of caveat, Sweden

is second only to Switzerland in global innovation rankings. In early October and then again at their presentation in December, the country radiates scientific excellence with the Nobel Prizes, still viewed as the top global award for the international research elite.

Considered a partnership?

At this year’s showcase event, Sweden didn’t just want to bask in the glow of other successes, it also wanted to highlight its own strengths. With around 4,000 life sciences companies in a country of around 10.5 million, there is plenty to brag about. By comparison, Austria – which has a similar population – is home to just over 1,000 life sciences companies (biotech, pharma and medtech).

In Sweden, medical technology is the largest sector within the life sciences in terms of number of companies, while lab technology and diagnostics are the smallest sectors. Swedish companies though are often active in several different industries. For example, there is a large overlap between laboratory equipment and diagnostics and medical technology. The Swedish innovation agency Vinnova tried to illustrate these overlaps in a very unique 3D graphic.

In 2022, the Swedish life sciences sector employed around 52,400 people in 3,838 companies. These companies gen-

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ECONOMY

erated net sales of around SEK474bn in 2022, an increase of SEK257bn since 2014. Larger life science companies saw the largest increase in absolute terms, increasing net sales by SEK175bn (138%) between 2009 and 2022.

The cumulative value of exported goods by life science companies in Sweden in 2022 was approximately SEK 186bn. The level of goods exports by life science companies was relatively stable between 2009 and 2014, but has increased steadily since 2014. Between 2009-2022, life sciences companies will account for between 7-11% of the country’s total exports of goods.

A deeper dive into Sweden According to Vinnova’s “Statistics for Swedish Life Sciences Companies”, such businesses had a production value of SEK 324bn in 2020, an increase of 99% compared to 2009. During the same period, value added increased by 39%, and in 2022, life science companies had a total value added of SEK121bn (€10,5bn).

Compared to the total number of companies in Sweden, production and processing value in the life sciences decreased between 2009 and 2017, and then increased again between 2017 and 2022. The contribution to Sweden’s GDP follows the same trend. In 2022, life sciences companies will contribute around 2% of Sweden’s GDP.

European Biotechnology | Winter Edition | Vol. 23 | 2024

The Scandinavian frontrunner regularly tops the Global Innovation Index together with Switzerland, and is proud of the fact that foreign venture capitalists are increasingly pumping cash into Swedish companies. In 2023, Swedish firms received SEK52bn in total from both Swedish and foreign venture capital investments. A large part of that money – about 70% in total – went to the information and communication technology (ICT) and general products and services sectors. However, the overall strong increase in venture capital investments has exploded since 2017, and had already more than doubled from a total of about SEK 10bn to more than SEK40bn before the pandemic. In its first year (2020), information technology made a huge leap in investment from 8 to almost SEK20bn.

After a slight delay in 2021, bio­t ech jumped from around SEK2bn to SEK14bn (2021) and SEK13bn (2022) respectively, only to subside significantly to around 4bn last year. As in many other European countries, the healthcare sector as a whole has experienced strong investment, and was still at almost SEK20bn last year. That was ahead of information technology, which peaked in Sweden in 2022.

The “Professor’s Privilege” In Sweden, researchers have retained the right to commmercialise their results, a

Minister for Education Johan Pehrson (L), Minister for Energy and Business Ebba Busch (KD), Minister for Health Acko Ankarberg Johansson (KD) and Minister for Social Affairs Jakob Forssmed (KD) presented the updated Swedish Life Sciences Strategy.

privilege that most other countries abolished years ago. That’s why there are so many spin-offs in Sweden, and why around 58% of the country’s life science companies have their origins in academia. Swedish researchers make very intensive use of this “professor’s privilege” and have to some extent prioritized patenting over publishing. This is one of the reasons why the Nordic country is well out in front in the global patent rankings – even ahead of the US in terms of patents per head of population.

This year’s BIO-Europe offered an opportunity to step out of the shadows with these innovation messages, along with Swedish folklore, modern musical highlights, and many seafood culinary delights.

Hidden strengths Sweden is often overlooked as a European player when it comes to drug development. This is partly due to how it keeps statistics. While the ‘Pharma­ projects’ database for the Swedish pharmaceutical R&D pipeline currently counts 351 drugs in active development, the organisation SwedenBio counts more than 500 such drug development projects in its triennial compilation, as it is ‘closer’ to researchers and lists not only the publicly known projects, but also early-stage discovery projects.

According to SwedenBio’s latest statistics for 2022, 159 companies are involved in a total of 506 projects. Of these, 221 are in clinical Phase I, II or III. The majority of projects are in early phases. The 506 projects describe 340 unique drugs being investigated for multiple indications. 54% of the projects are in the discovery or pre-clinical phase. Of the clinical phases, 16% are in Phase I, 23% in Phase II and 4% in Phase III. These figures put Sweden in fifth place in Europe. When compared in tandem with its Nordic neighbours, the region as a whole only trails the UK and Switzerland – a very impressive contribution, especially when compared with the economic size of the traditional EU5. And don’t forget: Sweden is just 10.5 million people.

Picture: © LifeScience Sweden, Lotta Naesenius

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Oncology

The better way to DNA!

Percent of projects

Neurology/CNS

Plasmid & Minicircle DNA

Infection Autoimmune / Im mu nol og y Endocrinology/Metabolism Cardiovascular

other

2006

2007

2008

2009

2010

2011

2012

2014

2015

2016

2020

2022

87

110

142

125

107

86

67

91

107

367

419

506

From Research to GMP grade

Picture: © The Swedish Drug Discovery and Development Pipeline 2023, SwedenBio

The Swedish drug pipeline holds candidates for a very wide variety of indications.

A strong uptick in projects in 2016 is due to first-time inclusion of discovery projects in the statistics (numbers on the bottom-most line).

Among its peers, Sweden also has one of the highest proportions of preclinical drug candidates. Such candidates are less likely to develop into approved medicines for patients because of the risks involved in R&D. However, the growing presence of early-stage bio­tech research is a positive indicator of the country’s innovation ecosystem. Domestic companies are filling their pipelines with compounds discovered in Sweden. These in turn will become the therapeutic breakthroughs of the future as cutting-edge science advances. It’s a contrast to mature pharma-led countries, such as Switzerland and Denmark, which rely more on external innovation and in-­licensing.

Sweden’s pipeline is characterised by diversity, led by a large number of smaller biotechs with a collective broad research focus (see figure above). In total, the Pharmaprojects database identifies 128 separate Swedish biopharma companies actively engaged in R&D. Again, Sweden ranks fifth on this measure, and the gaps to Germany (135), Switzerland (162) and France (166) are not unbridgeable. No single Swedish-based company has more than 12 publicly disclosed assets in active development, with cell therapy pioneer Anocca and antibody specialist BioArctic jointly leading the domestic charge. And these two companies account for just 7% of Sweden’s total pipeline, compared

with 22-40% for the top two in the other major European countries.

Updating strategy The ‘new’ Swedish life sciences strategy is actually an old one that has been in place since December of 2019, with a time horizon of 2030 – one reason why even Swedish industry representatives are now wagging fingers and warning that more concrete measures need to be defined. Just before BIO-Europe took place, Sweden’s national life sciences strategy was updated by a new government. Four ministers presented the updated approach during a presentation in Stockholm.

“With this Life Science Strategy, we want to establish Sweden as a leading life science nation,” said Ebba Busch (KD), Minister for Energy and Industry, stressing that this is not a position Sweden can take for granted. She pointed to entrepreneurs as the key to success, mentioning well-known names in the industry such as KTH professor Mathias Uhlén and bio­ tech entrepreneur Evelina Vågesjö.

The updated strategy focuses on clinical trials, national digital infrastructure, medical technology and precision health.

“The focus on supporting clinical trials and ensuring that the results benefit the whole country is positive. Basic research

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ECONOMY

is equally important, because without early ideas we have nothing to develop,” writes Jenny Nyström, Dean of Sahlgrenska Academy at the University of Gothenburg, commenting on the new strategy for Life Science Sweden. The strategy also emphasises collaboration between universities, healthcare and industry, which Nyström believes is crucial for the country’s life sciences sector. “The emphasis on infrastructure is also positive, but equally important is the competence to use it,” she writes.

Presented early last week, the Danish Life Science Strategy set a target of doubling exports from that country’s sector to DKK350bn (€ 46,9bn) by 2030. However, after the presentation in Forskaren, Minister Busch said in comments to Life Science Sweden that the Swedish strategy does not include such a target: “No, we have not set an exact number. Too few people are aware that the life science sector today accounts for 10% of our total exports. We want it to grow and reach as much potential as possible, but it is difficult for politicians to set an exact target.”

A focus on therapeutic areas Taking the innovation and science into account – as well as the country’s somewhat hidden pipeline – the choice of Stockholm as the 2024 venue for BIO­

European Biotechnology | Winter Edition | Vol. 23 | 2024

Europe is therefore more than understandable. An example of the worldwide recognition of Swedish drug development comes from BioArctic (see p. 14) and its Alzheimer’s antibody (lecanamab), developed in collaboration with Eisai/Biogen and brought to approval first in the US and – just a few weeks ago – in the EU. The partnership started between Bio­Arctic and Esai in 2005, with Biogen entering into the collaboration in 2014. This success can be chalked up to the company’s founders, Prof. Lars Lannfelt and Dr. Pär Gellerfors, and the combined efforts from research and clinical teams in the three companies.

Founded in 2003, BioArctic AB was set up to explore academic discoveries made at the Karolinska Institutet involving the Arctic mutation, which causes an auto­somal dominant disease with a clinical picture of typical Alzheimer’s disease. Discovery and preclinical research were performed during the years 20052012 followed by clinical trials from 2013-2022. Oncology is another main focus of Swedish pipelines.

Gene editing in the spotlight The timing of the event, which took place during US election week, had a slightly negative impact. It led to a perceived lack of US participation, which was not confirmed by the organisers, the

EBD Group. According to sources within the organisation, about the same number of Americans came to Stockholm in November as generally come to other BIOEuropes. But perhaps this time it was not the ‘right’ people for partnering, as one repetetive refrain heard in conversations in the exhibition area was that ‘the Americans are not here’. However, perhaps that gave the Europeans on hand a little more time to get to know each other better, or to interact with the numerous representatives from Asia.

Restraint prevails But what was the mood? What were the fresh new topics? That’s where the apparent lack of US representatives seemed telling. There were very few new topics beyond the progress of individual drug programmes. The most notable exceptions were targeted base editing in the clinic or – at an even earlier stage, but with remarkable progress – the targeted integration of entire genome segments, as is being pursued by Seamless Therapeutics in Dresden. Other buzzwords, such as ADC, radioligands, click chemistry, degraders and glues, as well as of course AI in drug discovery, are likely to remain topics of great interest, but can’t really be described as new.

What is novel, however, are technology platforms that can show drug inter­

European Biotechnology | Winter Edition | Vol. 23 | 2024

actions with target molecules in narrow time windows in the cell, which are challenging some postulated interactions, even in established drug pipelines. Austrian company Quantro Therapeutics has received a lot of attention for its ultra-fast transcriptome analysis, and has already impressed partners Boehringer Ingelheim and Evotec after in-house testing. Never­ theless, Quantro’s disruptive approach will probably require a very thick layer of skin. After all, it’s not easy for research project managers to have their pipelines questioned at a fundamental level.

Under the spell of US elections It was difficult to really pin down the general atmosphere at BIO-Europe this time with a single word or phrase. Of course, those who had good meetings with the right people were in a more positive mood than those who were unable to land appointments for partnering meetings. This is always the case at events of this kind, however, and this time it felt like there were actually fewer complaints than usual about not being able to get an appointment. On the contrary, European companies even seemed to be making more time for the less popular service providers, so that this important group also strode the aisles in seemingly good spirits. But is this positive willingness to have a chat enough to

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brighten up the entire economic sector within the global political framework?

Anyone expecting or hoping for a clear signal will have to be patient for a few more months, maybe even a year, some industry experts said with a shrug. After all, no one really knows what kind of impact Donald Trump’s election to a second term will have. Case in point – the much-discussed BioSecure Act, which practically declares China an enemy of US trade and production. Will this remain the case during the next four years?

Will it be strengthened or weakened?

Should Europe now press China more, or proclaim a “Europe for the Europeans”?

Will the leash on the FDA be shortened?

The price pressure on pharmaceuticals increased or lifted? Will healthcare systems promoted and streamlined, or drift more in the direction of being only affordable for the wealthy? Nobody knows, and any­one who turned on the television after returning from the conference saw even more question marks in breaking news broadcasts from all over the world.

Investors self-centred The investors who attend BIO-Europe events are most interested in talking to pharma companies directly themselves, and recommending their own port­folios for pipeline strategies. These investors leave practically no time for start-ups or

ECONOMY

new projects. The ceremonial presentation of a few start-up awards is a nice sideline at the conference, but not the focus. At BIO-Europe, the few European investors who are on the road are not looking for early-stage projects. They can learn more about those at the umpteen incubator and accelerator events taking place somewhere in Europe practically every week. They are also unlikely to find investor partners for a later round of financing here, unless it’s someone they already know, who they can quickly sound out for mutual interest.

See you again – in Vienna In this respect, the community meeting in Stockholm fulfilled exactly the expectations it was supposed to fulfill. It was a kind of self-confirmation, a reassurance that (almost) everyone is still there, that cooperation and partnership are a prerequisite for innovation. Many European regions made it clear that they are planning to up their game in the future.

And not just the Scandinavian countries, which had particularly elaborate presentations, but also Eastern European countries, Switzerland and Austria, to name but a few. The last will host the next BIO-Europe partnering event in L Vienna in November of 2025. georg.kaeaeb@biocom.eu (see also page 29f about BioEurope)

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BIOPEOPLE

Experienced CMO on board DIOGENX In mid-November, Marseille-

based DiogenX SA announced the appointment of Dr Klara Owen as new Chief Medical Officer. The French biotech start-up, founded in 2020, focuses on the regeneration of insulin-producing beta cells for the treatment of diabetes. Owen brings a broad experience in the field of diabetes and metabolic disorders from a clinical and entrepreneuriKlara Owen al perspective. She has spent the last ten years in senior positions at Novo Nordisk and Zealand Pharma. She received her medical degree and PhD from Charles University in Prague (Czech Republic) and furthered her education with an MSc in Drug Development Science at King’s College London. L

New CEO and Chair of Board CALLUNA PHARMA Norwegian Calluna

Pharma AS strengthened its management with the appointment of Mark Gaffney as new CEO and Mark Altmeyer as Chair of the Board. John Montana, who has been acting as the Company’s interim CEO, will return to his role as an Operating Partner at Forbion. Gaffney brings over 20 years of experience in corporate strategy, business development, Mark Gaffney and operations in private and public biotechnology companies. Prior to Calluna, he was CEO of Ox-

European Biotechnology | Winter Edition | Vol. 23 | 2024

ular Limited, a company developing novel drug delivery and formulation technologies to treat retinal disorders, where he remains a strategic advisor and member of the Board. The newly appointed independent Chair of the Calluna Board, Mark Altmeyer, brings extensive leadership experience, havMark Altmeyer ing served on the boards and as an advisor to several pharma and biotech companies. He is currently Chair of AMPharma and also serves on the boards of Novaremed, Merz Therapeutics, Aculys, and Alector, all focusing on the CNS and neurological treatments. Previously, he was President and CEO of Arvelle Therapeutics, Chief Commercial Officer at Axovant Sciences, and held senior roles at Otsuka L America and Bristol-Myers Squibb.

Old business acquaintance HALIX Leiden-based CDMO Halix B.V. has a new CEO: Dr Lutz Hilbrich took over the position in September. Until June 2024, he was CEO of ProBioGen AG and CEO/CMO of MiGenTra GmbH, b ot h companie s based in Berlin. Hilbrich has started his career at Boehringer Ingelheim and Sanofi, where he Lutz Hilbrichr worked for many years. During this time, he gained extensive knowledge in the areas of strategic leadership, operational excellence and innovation in biopharmaceutical development and manufacturing. Hilbrich succeeds Alex Huybens, who has successfully built and led the activities of HaL lix over the past years.

New Chief Scientific Officer MOSAIC THERAPEUTICS Former Astra-

Zeneca Senior Director, Dr Barry Davies, started in October as Chief Scientific Officer at Mosaic Therapeutics (Cambridge, UK). He joins Mosaic with over 25 years of experience in drug discovery, including 19 years at AstraZeneca where he most recently held the position of Senior Director, Global Project Leader. During his time with AstraZeneca, he led multiple projects across phases from lead optimisation to Phase-IIb proofof-concept clinical Barry Davies trials, mainly in the cell signalling, apoptosis and DNA damage response areas, and led preclinical work on multiple drug discovery programmes. Prior to this, he held other senior leadership roles at AstraZeneca, including Senior Director, Clinical and Translational Scientific AlliL ances.

New President in California BECKMAN COULTER In October, Joe Fox

joined Beckman Coulter Life Science (USA), a subsidiary of Danaher Corp., as new President. In the past 13 years, he held positions of increasing responsibility at SCIEX, most recently as President. Prior to that, Fox assumed both technical and commercial roles at Bruker and ShimadL Joe Fox zu.

Pictures: © DiogenX/Calluna Pharma/Halix/Mosaic Therapeutics

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NORTHERN EUROPE

Kancera’s pivot

European Biotechnology | Winter Edition | Vol. 23 | 2024

Bio meets AI

Hanging on

FUNDING Artificial intelligence (AI) developments in the life sciences are moving at breakneck speed. The Knut and Alice Wallenberg Foundation is investing SEK600m (around €51.7m) in data-driven life sciences with the goal to recruit and train the next generation of researchers and create globally leading competencies in computational and data science for life sciences in Sweden. The funding expansion follows a 2020 commitment of SEK3.1bn.

PIPELINE For struggling BerGenBio ASA, the hits keep coming. Following mixed clinical trial results and a stalled COVID-19 drug initiative, investor confidence in the Bergen-based biotech has steadily eroded. Now, the company must find new leadership to guide it toward recovery, as erstwhile CEO Martin Olin has stepped down. The share price, already down over 99% over the past three years, fell an additional 10% following news of Olin’s departure. Meanwhile, the company has opted to discontinue all activities related to tilvestamab, an anti-AXL monoclonal antibody in Phase I development for fibrotic diseases, including out-licensing efforts.

Now, BerGenBio is focusing on treatments for non-small cell lung cancer (NSCLC), particularly its Phase II AXL inhibitor bemcentinib. In collaboration with MSD, BerGenBio recently concluded a Phase II study evaluating bemcentinib in combination with Keytruda for recurrent NSCLC. Additionally, bemcentinib is under investigation in a Phase I trial combined with chemo-immunotherapy, a study set to continue through Q3/2025. L

STRATEGY Kancera AB, originally

focused on cancer treatments, is shifting its focus to cardiovascular diseases. After positive Phase IIa results, the company will focus on its fractalkine-blocking candidates, KAND567 and KAND145, with an initial target of treating ST-elevation myocardial infarction (STEMI), a severe type of heart attack.

The strategic pivot is driven by pragmatism as much as potential. While CEO Peter Selin sees opportunities in cancer, focussing on one therapeutic area will up Kancera’s changes of success, Selin believes. He points to the high unmet medical need, promising data, and payer willingness as reasons for zeroing in on STEMI. In the FRACTAL study, KAND567 showed promise in reducing intramyocardial hemorrhage – an often overlooked complication strongly linked to worse outcomes. With no treatments currently available, Kancera is eyeing a spot in the standard-of-care toolkit for high-risk STEMI patients undergoing primary percutaneous coronary intervention.

Whether the bet pays off will depend on how well the company can carve out its place in the competitive cardiovascular space. ”Considering the huge potential of this project, we believe that there is a significant upside in keeping the commercial rights in selected markets, such as the US,” explains Selin, justifying the decision to potentially keep development and commercialisation in-house.

“At the same time, we are initiating the process to seek specialist investors who L want to embark on this journey.”

The new funds will support recruitment and infrastructure, with SEK200m for 11 new research recruitment packages and SEK100m for advanced microscopy equipment at Science for Life Laboratory. The Foundation is also channeling SEK270m into “Alpha Cell,” an AI-driven project aimed at mapping fundamental functions in human cells. The initiative is intended to build on existing projects such as the Data-Driven Life Science programme, which has brought hundreds of early-career researchers to Sweden. Finally, SEK30m is allocated to extend the Human Protein Atlas programme until 2030.

“These investments are crucial for Sweden’s national competence and expertise in this fast-evolving sector,” says foundation chair Peter Wallenberg. The Knut and Alice Wallenberg Foundation, established in 1917, supports Swedish basic research and education, primarily in medicine, technology and the natural sciences by awarding grants to excellent researchL ers and projects.

Betting big COLLABOR ATION Novo Nordisk A/S is putting its weight behind Ascendis Pharma’s TransCon technology, signing a deal worth up to US$362m to develop a once-monthly GLP-1 receptor agonist. Reducing dosing frequency is a clear priority for Novo Nordisk, the company said. The agreement grants Novo exclusive rights to leverage TransCon for metabolic and cardiovascular diseases, including obesity and type 2 diabetes. Ascendis will receive up to US$285m in upfront and milestone payments for the lead programme, with additional milestones and royalties tied to future projects. While Ascendis leads early development, Novo will handle clinical trials, manufacturing, and global commerL cialisation.

Picture: © Bild von freepik

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European Biotechnology | Winter Edition | Vol. 23 | 2024

Making strides in foodtech SUSTAINABILITY Finland is emerging as a significant R&D player in the bioeconomy sector, with Finnish foodtech companies leading the way in Europe and beyond. Business Finland has allocated €10m in R&D funding to two Finnish projects – FoodID and FinBioFAB – which focus on alternative proteins and lipids, and biodegradable plastics and protein-based materials, respectively. Both projects were selected for the Global Centers research programme, led by the US National Science Foundation, which seeks innovative solutions to global challenges. Notably, Finland is the only EU country chosen to participate.

Going public Solar Foods, the biotech company behind the Solein protein, has taken its next big step by listing its shares on Nasdaq First North Growth Market Finland.

Solein, produced by feeding microbes

Picture: © Solar Foods (Solein), Iiro Muttilainen (PEKILO), Onego Bio (Bioalbumen)

Solein powder

with gases (carbon dioxide, hydrogen, and oxygen) and small amounts of nutrients, offers a groundbreaking solution for food production without the need for arable land. With Solein-based products already on the market in Singapore, Solar Foods is scaling up its operations with the opening of Factory 01, its first commercial-scale production facility for Solein.

NEWS Biosimilar agreement

Enifers’ PEKILO

PEKILO. This nutrient-rich, neutral-tasting mycoprotein powder is produced through a specialised fermentation process using a unique strain of fungus. Earlier this year, Enifer secured funding for a €33m production facility, which is expected to be completed by 2025. The facility will have the capacity to produce 3,000 tons of mycoprotein annually, meeting the rising demand for sustainable, plant-based food ingredients.

Going overseas Finnish foodtech company Onego Bio has made a major move into the US market with the opening of a 450m 2 commercial headquarters in the US. The facility will serve as a hub for food manufacturing partners, where Onego Bio will showcase its flagship ingredient, Bioalbumen – an animal-free egg protein powder. Bioalbumen mimics the taste, nutrition, and functionality of traditional eggs, but with an environmental footprint more than 90% smaller. This expansion follows a successful €14m (US$15.2m) funding round, secured from the European Innovation Council (EIC) Accelerator L Programme and Series A investors.

Going to market In October, biotech scale-up Enifer Bio­ tech made history as the first Nordic company to apply for Novel Food approval for its mycoprotein ingredient,

NORTHERN EUROPE

Bioalbumen, produced by Onego Bio

Xbrane Biopharma AB and Intas Pharmaceuticals Ltd have signed a global licensing agreement to co-develop a nivolumab biosimilar referencing Opdivo, a cancer drug with US$9bn in global sales in 2023. Intas, via Accord Healthcare, will oversee development, regulatory approval, and commercialisation.

Xbrane will receive €10m upfront, €3m in milestones, and double-digit royalties post-launch.

Power-to-X acceleration BioInnovation Institute and Villum Foundation are collaborating in power-to-X technology, which produces sustainable fuels and materials using green hydrogen. In 2025 and 2026, Villum Foundation will donate ­DKK20m to support four promising Power-to-X projects from the Villum P2X Accelerator, integrating them into BII’s Venture Lab. The initiative aims to support projects that can turn innovative ideas into scalable, practical applications with the potential for global impact on the green transition, while also being commercially viable.

Antibiotic alternative Immunotherapy might be as effective in treating infection as antibiotics, a recent study by Hamlet BioPharma AB suggests. The Lundbased company, which explores immunotherapy to bolster the body’s antibacterial defenses, said the Phase II study showed comparable clinical outcomes between antibiotic treatment and anakinro, an Interleukin1 receptor antagonist for recurrent acute cystitis.

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WESTERN EUROPE

European Biotechnology | Winter Edition | Vol. 23 | 2024

Stress pattern

UCB starts 2nd programme

CANCER French Brenus Pharma SA has raised €22.2m (US$25m) to accelerate clinical trials of two precision cancer vaccines derived from tumour cell banks representing about 200 tumour antigens.

The Series A round was led by UI Investissement/Kreaxi, Crédit Agricole Centre-France and Crédit Agricole CentreEst, as well as Belgian funds Noshaq and Investsud. According to the Lyon-based company, the proceeds will be mainly used to fund a multicentre Phase I/IIA trial of STC-1010 in immune therapy-refractory patients with metastatic colorectal cancer and an undisclosed indication. Both programmes are based on the patented Stimulated Tumour (ghost) Cell (STC) platform invented by Brenus Pharma’s CSO and co-founder Benoît Pinteur. It enables dendritic cells to detect and anticipate escape and resistance mechanisms in cold tumours. STC is the first platform to generate cancer vaccines based on cells that are stimulated to reproduce antigenic signatures of recurrent tumours and haptenised to train the immune system against resistant tumours.

Specifically, the company uses nonproliferative haptenised allogeneic tumour ghost cells as a vaccine to evade the therapy resistance and escape mechanisms of tumours. The tumour ghost cells carry exactly the same haptenised stress protein pattern on their surface that the individual patient’s tumour produces when exposed to chemotherapy, radio- or cancer immunotherapy, as well as metabolic, oxidative L or other types of stress.

CANCER Belgian UCB SA and British Cancer UK have started a second clinical trial within their multi-year partnership launched in March 2023. In a multi-centre Phase I study the Brits will evaluate the safety and optimal dose of UCB4594 in patients with advanced cancers. UCB4594 is an antibody that targets human leukocyte antigen G (HLA-G), which mediates maternal-foetal tolerance in the placenta. Tumours overexpressing HLA-G take advantage of the effect of this protein to supress the normal immune response to foreign antigens. Thus, blocking HLA-G might be a way to prime the immune system to attack cancer cells overexpressing HLA-G. “Targeting immune processes involving HLA-G could show promise as an approach for beating certain cancers,” said chief investigator Fiona Thistlethwaite from The University of Manchester. Under

the collaboration, Cancer Research UK is responsible for the trial, while UCB will manufacture and provide drug lots. UCB retains exclusive rights to further develop and commercialise UCB4594 and will receive a licence to the results of the clinical trials from Cancer Research UK in return for undisclosed milestones and royalties.

UCB SA is not the only company focusing on (cancer) antigens expressed by the placenta. Harbinger Health Inc, which was spun-out of the MPI for Molecular Genetics in Berlin, is currently testing whether a CpG methylation signature found in placental tissue is suitable for the early diagnosis of the 10 most important types of cancer. According to academic founder Alexander Meissner, the signature is found exclusively in placental tissue and in the blood from patients with stage I or II tumours. A study involving 10,000 volunL teers is ongoing.

Money, money money …

FINANCING Dutch venture capitalist Forbion (Naarden) has announced its largest fundraising to date, with Forbion’s Growth Opportunities Fund III raising €1.2bn and Forbion Ventures Fund VII raising €890m.

According to Forbion, the fundraising will allow an increase of the number of investments and the average size of future portfolio company financings, reflecting the opportunities the VC spe-

cialist sees for superior returns in development-stage life sciences companies.

It is anticipated that the Forbion Growth Opportunities Fund III and Forbion Ventures Fund VII will each invest in approximately 15 portfolio companies. Most recently, Forbion expanded its pharma life sciences focus by a fund investing in bioeconomy, bringing all assets under management at Forbion to L €5bn.

Picture: © Thierry du Bois

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European Biotechnology | Winter Edition | Vol. 23 | 2024

Promise of TGF-beta CANCER Strategies to destroy the immunological camouflage mode of solid tumours induced by their secretion of TGF-beta are currently booming among pharma majors. TGF-beta creates an anti-inflammatory milieu in the tumour microenvironment and also plays a role in other conditions that puts immune cells to sleep. In mid-October, Belgian start-up Agomab Therapeutics NV raised US$89m in a Series D funding.

New investors Sanofi and Invus joined the bandwagon of blocking the TGFbeta receptor or TGF-beta/SMAD signaling, alongside existing investors.

As of 2023, 26 small molecule candidates, 16 anti-TGF beta-antibodies, 34 TGF-beta ligand traps, two blockers of latent TGF-beta complexes and 16 anti-sense RNAs that block TGF-beta synthesis have

been undergoing clinical testing (10.1016/ j.omto.2023.100755).

Agomab Therapeutics has several organ restricted ALK5 (TGFbeta1 receptor) inhibitors in its pipeline. Agomab plans to advance the ongoing Phase IIa development of AGMB-129, a gut-restricted small molecule inhibitor of ALK5, in patients with fibrostenosing Crohn’s Disease. Interim data are set to be announced in Q1/2025.

The proceeds will also be used to advance Phase I development of AGMB447, a lung-restricted, inhaled small molecule Alk5 inhibitor in healthy volunteers and patients with idiopathic pulmonary fibrosis (IPF), as well to push development of AGMB-101, a MET agonistic antibody in pre-IND stage to be developed L as a treatment for liver cirrhosis.

WESTERN EUROPE

NEWS Genes to cure brains In return for an investment of US$20m and an upfront payment of US$30m to British gene therapy specialist AviadoBio Ltd in mid-October, Tokyo-headquartered Astellas Pharma receives the option to licence the AVR-01 gene therapy candidate that is currently in Phase I development in patients with frontotemporal dementia with progranulin mutations (FTDGRN).

Down to earth In October, Luxembourg Institute of Health announced that it is part of the Genome of Europe (GoE) initiative, a project aligning 48 institutes in Europe to sequence and annotate a representative European reference genome for epidemiological studies based on whole-genome data from 100,000 European volunteers by early 2028. The project is a downgraded version of a proposal of the One Million Genomes consortium that originally suggested in 2022 to build a federated human population study reference based on national whole genome sequencing data of at least 500,000 Europeans.

More cell models

Royal opening at Avantium Avantium NV has taken a major step towards reducing the carbon footprint of the plastics industry by replacing fossil PET with the plant-based PEF. In late October, Queen Maxima inaugurated the company’s commercial furandicarboxylic acid (FDCA) production facility with CEO Tom van Aken in Delfzijl in front of 250 invited guests. Avantium uses the plant-based monomers FDCA and mono-ethylene glycol for the polycondensation of polyethylene furanoate, which, unlike PET, can be processed in a single layer and has better barrier properties, but is just as non-biodegradable as fossil plastics. L

Picture: © RZeemering/Avantium NV

FDCA

Cambridge-based iSCP specialist Axol Bioscience Ltd has acquired French Phenocell SAS. The acquisition extends Axol’s portfolio of iPSC-derived cell models, adding skin and human retinal iPSC-derived cell lines to its neuroscience, pain and touch, and cardiovascular portfolio to accelerate drug discovery. The amount of the transaction was kept confidential.

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CENTR AL EUROPE

European Biotechnology | Winter Edition | Vol. 23 | 2024

Evotec: in a rollercoaster of emotions

ADC in Bavaria EXPANSION With a symbol-

ic ground-breaking ceremony, Bavaria’s Minister-President Dr Markus Söder marked the start of the construction of a building at the production and development site of the Japanese pharmaceutical company Daiichi Sankyo in Pfaffenhofen (north of Munich) at the end of November. Here, so-called antibody drug conjugates (ADCs) will be produced in the future. Earlier this year, Daiichi Sankyo announced plans to invest around €1bn over the next few years to transform the site into an innovation and manufacturing centre. The new building is an important milestone in this endeavour.

With this construction site, Daiichi Sankyo is significantly expanding its global oncology manufacturing capacity, with it being one of the largest production and development sites the Japanese company is running globally. It is quite a change though. Until now, the site has mainly been used to package millions of pills a year. In future, the production of ADCs will be a very different gamble. But Daiichi is not gambling at all, being a leading player in the field of ADCs (see p. 16), those monoclonal antibody molecules combined with a cytotoxic agent for the targeted treatment of patients with certain types of cancer. Daiichi Sankyo Europe currently employs more than 800 experts at the Pfaffenhofen site and plans to hire up to 350 additional employees by 2030 for current and future expansion.

In the Munich area, there are other ADC-players like Tubulis, who built a whole ecosystem of biopharmaceutics. 

PRECLINICAL At first, the 9-month figures were received in mixed ways – from positive to disappointing. Then a takeover bidder comes forward, then another with a concrete price – but a week later it’s all smoke and mirrors. The share price jumped north, but the crash followed immediately. What’s going on at Evotec?

No sooner had Hamburg-based Evotec received the first takeover bid from the hedge fund Triton than the US company Halozyme Therapeutics came forward shortly afterwards with a much more concrete offer and a real purchase price.

Since then, €11 per share has been on the table. Evotec’s Management Board and Supervisory Board wanted to analyse this in more detail.

Before this, the very high revenues of around €575m (a decrease of around one per cent compared to the same period in 2023; at that time around €580m) were announced, which were largely generated by partnered projects (around €447m) and increasingly from the highly automated production environment at Evotec’s Just Biologics sites (around €127m). Both of these factors speak in favour of the high market acceptance and relevance of the technology platforms that Evotec can bring to such partnerships. Long-term partner Bris-

Headquarter of Evotec SE in Hamburg

tol Myers Squibb (BMS) alone has already transferred a high three-digit million euro amount in milestone payments to Hamburg and only recently extended the partnership for many more years.

Although analysts are divided in their assessments of the business in a difficult year of management change at Evotec, word of the attractiveness of this business model – regarded by some industry observers as the archetypal biotechnology business model, excellently executed

by Evotec – has ssemingly reached hedge fund circles, likely due to the company’s low valuation.

As the management has now clearly rejected Halozyme’s offer (a spokesperson said they want to remain independent in any case), it was hardly surprising that the US company Halozyme officially withdrew its non-binding offer of €11 per share. The company valuation at €2bn was perhaps not a good basis for discussion either. In addition, the company’s other major shareholders, Novo Nordisk and the Abu Dhabi sovereign wealth fund Mubadala Investment, each of which probably hold around 8% of the shares, have not been put off by Triton’s similarly high commitment. Conclusion: These days in autumn were a rollercoaster ride for the shareholders too. 

Picture: © Evotec SE

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Somagenetix: CHF10m series A FINANCING With the completion of preclinical work in the field of stem cell gene therapy for the hereditary immune disease septic granulomatosis, the Swiss company Somagenetix AG has found a consortium of investors to finance the Series A round with SFR10m. With the help of lentiviral particles (LNP), a stem cell construct that can be used for all patients should eliminate the current lack of treatment options.

Septic granulomatosis (CGD) is a rare hereditary disease of the immune system.

The phagocytes (neutrophils and monocytes) are unable to fight bacteria and fungi. Affected patients are therefore susceptible to severe, potentially life-threatening bacterial and fungal infections. However, the immune defence against viruses is intact. Patients also show symptoms that are

associated with chronic inflammation and are often ‘granulomatous’ (nodular accumulation of cells).

In CGD patients, neutrophils show no increase in oxygen metabolism, which is normally associated with phagocytosis (the ‘eating’ of germs). This is due to a missing component of the enzyme NADPH oxidase, which occurs in phagocytes. NADPH oxidase catalyses the formation of superoxide, a precursor of potent reactive oxygen compounds, by the transmembrane passage of electrons from NADPH oxidase to molecular oxygen.

The funding will enable Somagenetix to advance its lead gene therapy candidate SGX-001 for the treatment of the p47-deficient subtype of septic granulo matosis into clinical trials.

CENTR AL EUROPE

NEWS Brain in a petri dish Brain organoids are the core competence of a:head from Vienna, Austria. Now the startup could close a series A round above the one-million-benchmark. a:head’s technology utilises sophisticated models of the human brain – miniature brains in a petri dish – to mitigate the problems in drug development at the crossroads of preclinical and clinical testing. It provides more accurate preclinical findings and thus increases the likelihood of clinical success.

Novartis climbs Mt. Rosa Novartis is partnering with USbased, but Swiss-sounding company Monte Rosa Therapeutics. The deal starts with an upfront payment of US$150m and up to US$2.1bn if milestones, approval and several revenue thresholds will be reached.

The interest of Novartis in partnering with Mt. Rosa Thx is based on their clue/degrader technology platform.

Techpark listing Spherical Staphylococcus aureus bacteria (yellow) during phagocytosis of a neutrophil white blood cell

Picture: © Callista Images - stock.adobe.com

Immatics: jumpstart to Phase III IMMUNOTHERAPY Tübingenbased Immatics NV has published updated Phase Ib clinical data on ACTengine ® IMA203, targeting PRAME in melanoma, which showed more details compared to the last data update in May 2024. The data on progression-free survival (PFS) and overall survival (OS) were so convincing that the company was allowed by the FDA to proceed directly with a

pivotal Phase III trial on this basis. And Immatics was using the tailwind to place new shares at US$150m. “I would like to highlight that a subset of 12 of the 26 patients showed a reduction in tumour lesion size of more than 50% and a median PFS of 13.4 months”, said Dr Cedrik Britten, Chief Medical Officer at Immatics. Now a trial with up to 360 patients is planned, with data expected in 2026. 

In 2021 and 2022, there was a large increase in construction projects for technology parks and laboratory buildings in Germany. The pandemic was to blame. Although construction activity subsequently declined due to the more difficult financial environment, it remains at a higher level than before the upturn. With a list of technology parks in Germany, Austria and Switzerland, Biocom provides an overview of lab buildings as well as expansion plans for the coming years: transkript.de/tech-parks

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Italy in gene therapy fever

On the map STRATEGY At the beginning of Sep-

tember, the Slovenian Government in Ljubljana has signed a memorandum of understanding with the newly established biotech business accelerator Biotech Hills Institute supported by Novartis Pharmaceutical Production doo, Lek Pharmaceuticals dd/Sandoz, lab specialist Labena doo and the American Chamber of Slovenia doo. The key objective is the preparation of a development strategy for the biotech and pharma sectors up to 2030, accompanied by an action plan for short-term measures by 2026 to establish an advanced biotech ecosystem, focused on › developing specialised educational programmes and additional laboratory spaces to attract biofuels and bio­ methane production. › encouraging the development of the biotechnology and pharmaceutical sector. › establishing a legislative framework with minimal administrative burden to attract talent and innovation. › encouraging investments in public research institutions and utilising all available financial mechanisms to support biotech as a key industry. › reducing tax burdens on labour while providing tax benefits to attract highly qualified professionals and boost productivity and competitiveness in the biotechnology sector. › attracting new investors.

No financial commitments regarding the action plan and strategy were disclosed. 

FINANCING Two Italian gene therapy developers have raised significant amounts of money: Genespire srl and Resalis Therapeutics srl. In the first week of October, Milan-based Genespire raised €46.6m in a Series B round to advance GENE202, its paediatric in-vivo gene therapy for the rare metabolic disorder methyl­malonic acidemia (MMA), to Phase I/II testing. It was one of the largest private financings of an Italian company to date, co-led by Sofinnova Partners, XGEN Venture and CDP Venture Capital as well as Indaco SGR. MMA is associated with high mortality and morbidity, and manifests clinically through symptoms such as muscular weakness, seizures, developmental delays and organ damage. Using its proprietary Immune Shielded Lentiviral Vector (ISLV) platform, which utilises an MHCI restricted lentiviral vector expressing the baculovirus-derived GP64 envelope protein to target the RNA encoding functional methylmalonyl-CoA mutase (MUT) to hepatocytes and liver sinusoidal endothelial cells (LSEC), the company aims to prevent immunological neutralisation. The financing will enable the development of GENE202 up to a Phase I/ II clinical trial.

Promising obesity therapy At the end of October, Resalis Therapeutics srl gained an equity investment from French pharma major Sanofi SA sufficient to finance its miRNA-22 antisense

blocker RES-010 through Phase II proofof-concept. No financial details were given. However, experts estimate the Phase II cost to be somewhere between €50m and €150m. Previously, the LNA-specialist raised €10m in a Series A round to finance Phase I safety testing and dosefinding that will start this year, according to CEO Alessandro Toniolo.

RES-010 is the first locked nucleic acid targeting miR-22(-3p), which plays a key role in the molecular pathways underlying obesity, obesity-related metastasis, metabolic-associated fatty liver disease (MALFLD) and its progressive disease state, metabolic-associated steatohepatitis (MASH), with an antisense mechanism. MiR-22 orchestrates multiple prolipogenic programmes modulating both direct and indirect gene targets.

A comparison of obese and normalweight individuals showed that miR-22-3p was significantly overexpressed in obese human adipose tissue (p-value: 0.0078; q-value: 0.0373). Its expression also correlated positively with different anthropometric and metabolic characteristics, such as waist–hip ratio, body-mass index, serum triglycerides, serum ApoB, HOMAIR, serum alanine aminotransferase and serum C-reactive protein. Also, miR-22-3p levels correlated negatively with muscle mass, serum adiponectin and serum HDL cholesterol, and several metabolic pathways were predicted to be under the control of mi­R-22, indicating that the role of miR-22 in metabolic homeostasis is conserved in mice and humans. 

Picture: © Dr_Microbe - stock.adobe.com

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SOUTHERN EUROPE

NEWS Green label

New Asabys fund closed VC In mid-September, Spain’s Asabys closed its Sabadell Asabys II Fund at €180m, €30m over the initial target. According to co-founders Clara Campàs and Josep Ll. Sanfeliu (in front), similar to Sabadell Asabys Fund I, which closed with €117m in commitments, SAHII II is investing across biopharma, medtech and digital health companies. SAHII II will invest in 12 to 15 companies in line with Asabys’ core strategy of funding companies that develop novel solutions for unmet medical needs building on solid sciL entific evidence and a clear benefit for patients.

Picture: © Asabys

Huge boost for biofuels FINANCING US investor KKR has bought a 25% stake worth €2.94bn in Italian Eni srl’s green mobility and biofuel business, Enilive. Enilive produces biofuels and biomethane from waste such as used cooking oil, animal fat and other biomass.

The Eni subsidiary launched last year aims at producing 3 million tonnes hydrotreated vegetable oil (HVO) per year by 2026.

Compared to diesel, HVO biofuels reduce CO2eq emissions, depending on the feedstock used, by between 60% and 90%. Eni stopped supplying palm oil to its Venice and Gela biorefineries in October 2022 with the goal of offering integrated services and products that are progressively decarbonised by 2050. This includes converging the company’s mobility activities, including its biorefining and biometh-

ane assets, and smart mobility solutions, as well as the distribution of mobility energy carriers through its more than 5,000 Enilive Stations in Europe. Eni has announced plans for Enilive to more than double its bio­refining capacity from 2023 to 2026, and to reach more than 5 million tons per year by 2030. Eni also announced to invest €2bn into the transformation of its chemical business Versalis to reduce emissions by 1 million tonnes of CO2 by 2027.

KKR is making the investment through its Global Infrastructure Strategy. The acquisition follows KKR’S recognition in December 2023 of decarbonisation and the large scale “brown-to-green” transition in asset-heavy sectors, in particular, as a key “mega-theme” driving investment opportunities. 

At the end of October, Italybased pharma packaging specialist Bormioli Pharma announced a partnership with Chiesi Group to supply carbon-capture PET bottles for packaging an allergic rhinitis medicine.

The companies said it was the first time a CO2-reducing PET bottle was used to provide a 21.9% decrease in kg of CO2eq compared to traditional PET. As the ccPET produces the same amount of microplastics as fossil PET, it is not a solution that is completely free of greenwashing.

Silver jubilee To mark its 25th anniversary, the Spanish biotech industry association AseBio has captured the impressive growth of the Spanish bio­p harma sector in an infographic that can be downloaded from the association’s website. The number of companies has risen from 54 at its founding in 1999 to more than 300 in 2023.

Spain is the European champion regarding the number of clinical trials conducted, and AseBio has recently launched an initiative to appoint a High Commissioner to promote strategic technologies in Spain.

Precise cuts Vilnius-based genome editing specialist Caszyme (Vilnius) and advanced therapies expert Integra Therapeutics (Barcelona) announced a €40m licensing deal for the use of Caszyme’s novel Cas12l nucleases to develop safer and more efficient gene and cell therapies at BioEurope.

Cas12l will be integrated in Caszymes gene writing platform.

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Tregs to fight autoimmunity

Hungarian ban CULTURED FO OD The EU’s 2015/1535 procedure is intended to prevent barriers from being created in the internal market before they actually arise.

This is precisely why, at the end of October, the EU Commission issued a warning to Hungary’s government, which, following Italy’s example from last year, was planning a trade ban on meat substitutes produced in fermenters or by cell culture. The EU Commissioner for Health and Food Safety, Stella Kyriakides, drew the Hungarian government’s attention to the six-month standstill obligation, which expires in mid-January 2025, following a detailed opinion from the Commission and its obligation to respond. Kyriakides also threatened to take Hungary to the European Court of Justice under the TFEU if, like Italy, it imposed a marketing ban on its own. Poland takes over the EU Council Presidency from Hungary at the beginning of January.

In mid-July, Hungary had notified a ‘Draft act prohibiting the production and placing on the market of laboratory-grown meat’ notified via the so-called TRIS procedure, citing potential health risks and the threat to the livelihood of its agricultural sector posed by meat substitutes as reasons for a national marketing ban. The Commission pointed out that there was currently no approved product on the EU internal market and that product safety would also be guaranteed because the products would have to be approved in accordance with the EU Novel Food Regulation. 

CLINICAL TRAIL PolTREG SA (Warsaw) has launched a Phase II trial with its Treg cell therapy PTG-007 in children with presymptomatic type 1 diabetes (T1D) in November. In the study, the company is going to evaluate safety and efficacy of the polyclonal autologous Treg cell therapy in 150 patients aged between 6 and 16 years who are at high genetic risk of developing T1D, but who have not yet shown any symptoms.

Clinical sites for the study have started to open, and patient recruitment and randomisation will follow later this year.

The hope is to prevent disease manifestation by administering PTG-007 at an early stage of the disease, so that the number of viable islets is sufficient to prevent symptoms from occurring.

The company has received a grant of €7.3m from Poland’s Medical Research Agency for the study. The company has completed a total of five clinical trials in T1D, multiple sclerosis (MS) and graft vs host disease.

Its lead product, PTG-007, is ready for Phase II/III testing, but the company is L still seeking a partnership.

EVEREST coming next year EXOSOME RESEARCH In November, Pharmahungary Group announced it will be participating in the ambitious EU EVEREST project. The €1.3m project aims to set up standardised methods that allow comparable analyses of the intercellular and interorgan communication via extracellular vesicles – the next big thing in the diagnosis and therapy of cancer and cardiovascular diseases.

Although the initial budget of the EU EVEREST project is small, its impact could be huge. Extracellular vesicles enclose DNAs, RNAs, lipids, and proteins triggering specific cellular responses in a cell-to-cell communication process, and

Exosomes

are thus of high interest for ultra-targeted therapies. Coordinated by Professor Breandán Kennedy, UCD School of Biomolecular and Biomedical Science in Dublin, the research project brings together 21 institutions from 11 countries to standardise methods for isolating and characterising these vesicles, facilitating their use to improve the precision and effectiveness of treatments for complex diseases such as cancer and cardiovascular conditions. The project, funded through the Marie Skłodowska-Curie Actions (MSCA) programme under Horizon Europe, will run for 48 months, starting in January 2025. 

Picture: © Qiagen NV

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SCIENCE & TECHNOLOGY

Researchers find genetic cause for yoyo effect Researchers at ETH Zürich have proven the existence of an obesogenic memory in mouse adipocytes. These largely stable epigenetic changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic ‘yo-yo’ effect often seen with dieting. However, it may be a new target for drug developers.

CELL THERAPY

Diets often feel pointless due to the yoyoeffect. Given that previous metabolic states have been shown to induce reversible changes in the epigenome – altering the accessibility of DNA-sequences to transcription factors – researchers at ETH Zürich investigated whether certain parts of the epigenome could undergo lasting silencing, potentially creating an obesogenic memory.

Picture: © Bigplankton - en.wikipedia.org

Discovery with health impact The team, headed by Ferdinand von Meyenn, found that tissue indeed retains a ‘memory’ of obesity through cellular transcriptional and epigenetic changes that persist after weight loss, which might increase the likelihood of regaining weight, as their experiments in mouse and human cells suggest. The findings may help to explain the problematic ‘yoyo’ effect often seen with dieting or other weight loss strategies where individuals regain the lost weight, and might inform future weight management strategies (10.1038/s41586-024-08165-7 y).

A primary goal in treating obesity and improving health is to reduce body weight to prevent secondary complications, such as type-2 diabetes, fatty liver disease, and hypertension-triggered co-morbidities.

Both strategies focusing on diet and lifestyle changes, as well as pharmaceutical approaches, often lead only to short-term weight loss, with body fat returning once obesity drugs are discontinued – the yoyo effect. This issue seems to be driven by a memory of obesity, but its mechanisms are unclear. Using single-nucleus

Obese mouse

RNA sequencing (snRNA-seq) of biopsies from subcutaneous and omental fatty tissue from individuals that had never been overweight, and those living with obesity before and after significant weight loss, von Meyenn and colleagues demonstrated for the first time that cells from human and mouse adipose tissue display transcriptional changes retained even after substantial weight loss. Their results from a pilot study with only 18 non-obese and 20 obese individuals, who experienced at least a 25% reduction in BMI following bariatric surgery, need to be confirmed by a larger study population.

Preclinical read-out Similar analyses were carried out in lean, obese and formerly obese mice that had lost weight. In mice, the ETH researcher team also found epigenetic changes besides transcriptional changes which ap-

pear to be associated with impairments to metabolic processes that persist after weight loss such as fatty acid biosynthesis or the formation of white fat cells, which may contribute to rebound weight gain after dieting, and an inflammatory phenotype. Transcriptional deregulation was most pronounced in adipocytes, adipocyte progenitor cells (APCs), and endothelial cells. In feeding experiments, notably during obesity, the numbers of lipid-associated macrophages (LAM) and nonperivascular macrophages increased in adipose tissue with the epigentic pattern of former obesity, altering the macrophage population composition persistently.

Targeting these changes in fat cells through hit-and-run epigenome editing (Chroma Medicine srl) using CRIPR, TALENs, and ZFNs holds promise for targeting epigenome remodelling (10.1038/s41586 024-07087-8 d). t.gabrielczyk@biocom.eu

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INTERVIEW

European Biotechnology | Winter Edition | Vol. 23 | 2024

Biotechnological climate rescue While investigating the substrate selectivity of nitrogenases from phototrophic bacteria, microbiologists have discovered an enzyme that paves the way for the fossil-free synthesis of hydrocarbons. European Biotechnology spoke with Dr Johannes Rebelein about the industrial feasibility and tech transfer.

DECARBONISATION

chain hydrocarbons through directed evolution. We are also trying to make iron nitrogenase even more selective for CO2, i.e. to limit the proportion of nitrogen fixation by the enzyme.

EuroBiotech_ Dr Rebelein, you have found a new way to produce hydrocarbons enzymatically from carbon dioxide (CO2). How does this work?

Rebelein _We are researching nitroge-

nases, the enzymes that use large ironsulphur clusters to fix atmospheric nitrogen and make it biologically available.

However, nitrogen is not the only substrate. After showing that nitrogenases can also fix carbon monoxide, our group has demonstrated that these enzymes can also fix the greenhouse gas CO2 – not only in vitro under special conditions and with purified enzymes, but surprisingly also under physiological conditions (doi: 10.1126/sciadv. ado7729).

We have shown that iron nitrogenase catalyses the conversion of CO2 to formate, but also to methane gas, without the need for CO2 enrichment. We are interested in using these nitrogenases biotechnologically for decarbonisation and optimising them for this purpose.

The task is to e­ ngineer the enzyme in such a way that fewer electrons flow into the formate synthesis, i.e. more electrons are used for the synthesis of methane or longer-chain hydrocarbons such as ethylene or propylene.

We have already shown that this works with a vanadium nitrogenase. However, this is not as selective for CO2 as our iron nitrogenase, which therefore appears to be more suitable for the technical use we are aiming for later.

EuroBiotech_What is the current ratio of nitrogen to CO2 fixation?

Rebelein_When we enrich the CO2, two

thirds of the electrons flow into the reduction of CO2. One goal would be to make nitrogenase even more selective for this process.

JOHANNES REBELEIN, PHD, is Emmy Noether Research Group Leader at the Max Planck Institute for Terrestrial Microbiology in Marburg, ­Germany. In June 2024, he was awarded the prestigious VAAM Research Prize.

EuroBiotech_Does this mean that you have created the basis for a climateneutral combustion fuel based on bacterial enzymes?

Rebelein_That’s right, the next step for

us now is to further develop iron nitrogenases. We are currently trying to shift the product profile towards longer-

EuroBiotech_In your opinion, is it more promising to influence the electron flow in the desired direction or to use cha ssis microorganisms with optimised metabolic pathways to achieve the goal?

Rebelein_Good question. We are actual-

ly working on accelerating the flow of electrons. There is already some evidence showing that this can be achieved.

Nitrogenase consists of two components, a reductase and a catalytic component. Electron transport always requires 2 moles of ATP per mole of electrons, which are transferred from the reductase to the catalytic component. It has a­ lready been shown that the reductase component can be replaced by using strong reducing agents, for example europium-II-diethylenetriaminepentaacetic acid, which transfers the electrons directly to the catalytic component. The advantage here is that ATP

Picture: © Chris Kettner, MPI for terrestrial Micro biology, Marburg, Germany

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is no longer required. In another example, photosensitisers were used on the surface of the nitrogenase to transfer the electrons. This all works in vitro but is not so easily possible in vivo because a certain redox potential prevails in the cell.

However, I assume that it merely is a technical issue to get rid of the reductase component in vivo as well, because in vivo the electron transfer from the reductase to the catalytic component is the slowest step in substrate conversion. This is exactly what we are trying to improve.

EuroBiotech_What turnover rates do you see and what do you need for industrial use?

Rebelein _ One thing must be clear:

nitro­genases, similar to ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo), are among the slowest enzymes in nature, with a turnover rate of one to two molecules per second. Compared to formate dehydrogenase, which also catalyses this reaction, nitrogenases have the advantage that the reaction is irreversible. This reaction is too ineffective to be used for formate.

That is why we are concentrating on hydrocarbons such as ethylene, where there is a market with an annual turnover of US$160bn and therefore a great deal of interest from the industry in new processes.

Of course, we cannot currently compete with fossil natural gas in terms of price. And turnover would also have to be at least 150 times higher than it is today.

However, we have only just started engineering and are hoping that, with the trend towards a circular economy and further optimisation, we will be able to produce ethy­lene competitively in around ten years’ time. Companies like the US gas fermentation specialist Lanzatech Inc are also trying to do this. Ultimately, however, a price of US$100 per tonne of CO2 emissions will be necessary to make bio­technological processes worthwhile. Including the large increase in the CO2 price by the German govern-

INTERVIEW

ment, we are currently at €45 per ton. As of the end of October the EU ETS price stood at US$65.56. So there is still a lot to do.

patents will follow. In the current paper we have worked with wild-type enzymes so there is nothing to file a patent application on.

EuroBiotech_What is the advantage of your process over Lanzatech’s Acetogens’ process, which is the most advanced in industrial implementation?

Rebelein_Our process in Rhodobacter

EuroBiotech_Will there be a spin-out at some point or would you prefer to ­licence the patent?

Rebelein_ At the moment, I favour the

capsulatus has the advantage that, in contrast to acetogens, it is light-driven, i.e. it carries out anoxygenic photosynthesis and thus produces ATP, which we currently still need for our process.

Another advantage of nitrogenase-producing aerobic bacteria such as Azotobacter vinelandii, which we could use as an alternative, is that they survive aerobically.

This offers considerable advantages in process control compared to the obligate anaerobic acetogens commercialised by Lanzatech. Compared to the ­Fischer-Tropsch process: We do not have to concentrate the CO2 and aerobic diazotrophic bacteria can tolerate oxygen in the process.

idea of making the process patents ­licensable through a spin-off.

However, science is difficult to plan and so is the time horizon until the enzyme technology is finalised. As we will still need some chemical raw materials such as ethylene or propylene in 20 or 30 years, I am confident that there will also be a market for our inventions.

EuroBiotech_ In addition to creating good conditions for technology transfer, what do you see as an important political task?

Rebelein_I think politicians need to pe-

nalise greenwashing so that truly sustainable processes that have a positive effect on our environment are developed.

EuroBiotech_ Are there also advantages over approaches in which oil-containing auxotrophic green algae are simply propagated and the biodiesel content is then separated?

Rebelein_The advantage of our process

EuroBiotech _ So you don’t think it makes sense that Lanzatech produces CO 2 -neutral ethylene, which L’Oréal then uses to produce disposable packaging?

Rebelein_Exactly, this packaging should

is that a finished product for the chemical industry is simply outgassed and ready for use without any further processing steps. This is a general advantage over biomass-based processes, including those based on RuBisCo, the key enzyme of the photosynthetic dark reaction: While the CO2 must first be incorporated in the biomass, our process directly forms and releases the final product. This is precisely the advantage.

also be recycled. Furthermore; poli­ t i c i a ns co u l d s t e e r d eve l o p m e n t through appropriate regulations to control the development without interfering with the economy, for example by promoting higher recycling rates, tax incentives and market-based measures.

EuroBiotech_How do you want to commercialise your research?

Rebelein _ A patent for CO and CO 2

conversion by nitrogenases has been granted. If our genetically modified ­nitrogenases work well, further process

EuroBiotech_What’s next for you scientifically?

Re b e l e i n _ To date, t here is no re ­

cognised reaction mechanism for nitrogenases. We are trying to tackle this by analysing homologous enzymes with metal clusters and then using this improved understanding for new applicaL tions. t.gabrielczyk@biocom.eu

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European Biotechnology | Winter Edition | Vol. 23 | 2024

Multispecific attack on blood cancer cells BISPECIFIC ANTIBODIES In the search for strategies to overcome the disadvantages of T-cell

engagers, such as cytokine storms (CRS) or neurotoxicity (ICANS), Innate Pharma has found what they were looking for. Their tetravalent NK-cell engager IPH6501, directed against the BCMA tumour antigen, was preclinically more effective with less proinflammatory cytokine production.

Antibody-engineering Marseille-based Innate Pharma SA has presented promising preclinical data of its tetraspecific antibody-based B and NK cell engager IPH6501, a novel approach to treat Bcell non-Hodgkin lymphoma (B-NHL).

The therapeutic landscape for relapsed or refractory (R/R) B-cell nonHodgkin lymphoma (B-NHL) is evolving toward targeted T-cell based immunotherapies, including CD19-targeted CART and CD3xCD20 T-cell engaging (TCE) bispecific antibodies. Yet, there remains an unmet medical need for patients who are refractory to, or ineligible for these treatments. Leveraging natural killer NK cells emerges as a promising strategy in hematological malignancies.

Better than other engagers?

In late November, Innate Pharma SA published preclinical results of IPH6501, the company’s first tetra-specific NK cell engager to engage activating receptors (NKp46 and CD16), a tumour associated antigen (CD20) and an interleukin-2 receptor (via an IL-2 variant, IL-2v) via a single molecule (10.1126/sciimmunol.adp3720), using Innate’s proprietary multispecific antibody format ANKET (Antibody-based NK cell Engager Therapeutics). IPH6501 was bound to both, cancerous B cells and natural killer (NK) cells, activating the immune cells of the innate immune system to target blood cancer cells. The treatment showed higher efficacy and lower toxicity than T-cell engager-based existing B-NHL therapies in mouse models and non-human pri-

Schematic drawing of the binding sites of Innate Pharma‘s tetravalent NK cell engager

mates, and is currently undergoing Phase I evaluation in relapsed or unresponsive human B-NHL patients.

Novel NHL treatments such as T-cell engagers (TCEs) have shown clinical promise but often cause serious toxicities. Recent research has suggested that NK cell-based treatments may offer effective and safer alternatives to some T cell therapies. Building on these findings, Olivier Demaria and colleagues developed IPH6501, which can activate NK cells through three different receptors while also targeting the tumour-associated antigen CD20 on B-NHL tumours.

Notably, the molecule was designed to include an IL-2 variant that could trigger NK cell proliferation without activating regulatory T cells (Tregs) but did not show IL-2-related side effects – a common phenomenon in TCE treatments that can cause therapy resistance.

The team headed by CSO Eric Vivier also produced a variant of the molecule, named CD20-NKCE-IL2v, with a key change in one domain to enable testing in mice. IPH6501 promoted NK cell

activation in vitro, and exhibited higher anti-tumour efficacy and lower toxicity than CD20-targeting TCEs. Demaria et al. demonstrated that CD20-NKCE-IL2v and IPH6501 elicited NK cell expansion and migration to tumour sites in mouse models and non-human primates, respectively. IPH6501 also induced proliferation and efficient anti-tumour activity in NK cell samples from relapsed or unresponsive B-NHL patients.

Furthermore, IPH6501 could activate NK cells to target CD20-negative tumour cells, indicating its broad therapeutic potential against varied lymphomas.

IPH6501 showed strong antitumour efficacy in a tumour model resistant to rituximab and obinutuzumab and post-Car-T cell therapy.

Clinial update Currently, IPH6501 is in a Phase I/II dose-escalation trial with a study design presented at this year’s ASCO conferL ence. t.gabrielczyk@biocom.eu

Pictures: Innate Pharma SA

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Targeted macrophage therapy

Synthetic life

CANCER So-called M2 tumour-associated macrophages (TAMs) in the tumour microenvironment (TME) are known to be associated with worse outcomes across tumour types. However, not all TAMs are created equal. Swedish researchers reported in November that patients with the deadliest form of brain cancer, glioblastoma multiforme (GBM), have unusual immune cells called tumour-associated foam cells (TAFs) which correlate with poor outcomes. The team led by Mattias Belting from the Universities of Lund and Uppsala demonstrated that these lipid droplet-carrying cells can be targeted to suppress tumour formation in mouse models of GBM. Their data suggest a potential new therapeutic strategy for glioblastoma, a disease with a five-year survival rate of only circa 5%.

these turncoat immune cells: TAFs, a type of macrophage that takes up lipid droplets secreted by human glioblastoma tumour cells. They examined biopsies from patients with glioblastoma and observed that these samples harboured high amounts of TAFs. These cells were linked to hypoxia, and their numbers correlated with more aggressive tumours and poorer survival outcomes in a group of 36 patients. Further experiments showed that the cells exhibited many tumour-supporting qualities, such as fostering angiogenesis, boosting mesenchymal transition or blocking of phagocytosis, and formed when macrophages scavenged lipids from vesicles secreted by glioblastoma cells.

AI Bioengineers and AI experts from the

Complex TME

As the researchers blocked key enzymes involved in lipid droplet formation, such as diacylglycerol O-acyltransferase or long-chain acyl-CoA synthetase, TAFs lost their proliferation-promoting functions in mice. Governa et al. conclude such compounds could offer viable targeted therapies. To materialise this direction “for GBM therapy, it will be critical to tailor lipid-inhibiting agents with improved blood-brain barrier penetrance, allowing increased tumour bioavailability,” the researchers conclude.

“Although such strategies could eradicate tumour cells, it may prove more beneficial to convert protumourigenic L TAFs into antitumourigenic TAMs.”

Merged

Nuclei LDs

CD45 Nuclei

Picture: © Governa, et al., Sci. Trans. Med., 16 eadk1168 (2024)

Glioblastoma multiforme is usually treated with a combination of surgery and radiation or chemotherapy, but the highly invasive, growing tumours almost always recur, and most patients live only 12-18 months after diagnosis. These tumours are tricky to eliminate in part because of their complex tumour microenvironment (TME), in which tumour-associated macrophages can make up 50% of stromal cells, and their TME’s ability to reprogramme immune cells to support tumour growth.

First author Valeria Governa and colleagues focused on one category of

Potential strategy

Immune cells (CD45-positive) constitute up to half of lipid droplet loaded cells in human glioblastoma multiforme (GBM). Examining protumourigenic tumourassociated foam cells (TAFs), Governa et al. found that 40% of tumour-associated macrophages were TAFs in GBM.

University of California in Berkeley have designed a high-performance machine learning (ML) model dubbed Evo that is going to revolutionise synthetic biology. Evo is capable of decoding and designing DNA, RNA sequences of up to 1 megabase in length, and the protein sequences encoded therein. According to experts in the field, EVO’s ability to predict the effects of mutations across all layers of regulation in the cell and to design DNA sequences to manipulate cell function would have tremendous diagnostic and therapeutic implications for disease. In contrast to current generative ML models that tend to focus on individual molecules or DNA segments, the scope of EVO is on capturing broader genomic interactions necessary for understanding complex biological processes. The new foundation model is equipped with seven billion parameters and designed to generate DNA sequences up to whole-genome scale. Built on the StripedHyena architecture, Evo was trained on a dataset of 2.7 million evolutionary diverse microbial genomes, excelling in both predictive and generative biological tasks, and achieving high accuracy in zero-shot evaluations for predicting mutation impacts on bacterial proteins and RNA, as well as in modeling gene regulation. Evo also grasps the intricate co-evolution between coding and noncoding sequences, supporting the design of complex systems like CRISPR-Cas complexes and transposable elements. 

Test of function HTS Using a combination of base ed-

iting and prime editing, researchers at ETH Zurich have introduced 50,000 variants of the EGFR gene into cells and functionally tested them. The approach can be applied to all cancer gene variants with unclear function (10.1038/ s41587-024-02439-1). 

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European Biotechnology | Winter Edition | Vol. 23 | 2024

Breakthroughs honoured: 2024 Nobel Prizes The 2024 Nobel Prize Week will take place from December 6 to 12 in ­Stockholm, during which the prestigious awards will be presented. These include the Nobel Prize in Medicine or Physiology for the discovery of microRNAs as a new class of regulatory molecules, and the Nobel Prize in Chemistry for AI-supported methods in protein design and the rapid calculation of their structures.

S TOCKHOLM

The Nobel Prize Award Ceremony at the Stockholm Concert Hall (2022)

The Nobel Prizes stem from the foundation established by Swedish entrepreneur and inventor of dynamite, Alfred Nobel, and include a certificate, a medal, and a monetary award of 11 million Swedish kronor (approximately €950,000). The prizes will be presented by King Carl XVI Gustaf of Sweden in the Stockholm Concert Hall on December 10, the anniversary of Nobel’s death. First awarded in 1901, this year marks the 115th occasion.

The ceremony will be accompanied by concerts, art exhibitions, and the Nobel lectures given by the laureates. Among the speakers will be the US researchers Victor Ambros and Gary Ruvkun, who are awarded the Nobel Prize in Medicine or Physiology for their discovery of

microRNA, as well as David Baker, Demis Hassabis, and John M. Jumper, who share the Nobel Prize in Chemistry for their work on computational protein design and AI-driven predictions of protein folding from amino acid sequences.

MicroRNA – a therapeutic target The Nobel Assembly at the Karolinska Institute in Stockholm has honoured groundbreaking basic research with this year’s Nobel Prize in Medicine or Physiology, which are already influencing clinical drug development. In their laudatory address, the jury described the discovery of the first regulatory microRNAs carried out by developmental biologist Victor

Ambros (71, University of Massachusetts Medical School, Worcester) and geneticist Gary Ruvkun (72, Massachusetts General Hospital and Harvard Medical School, Boston) as a “new dimension of gene regulation”. Today, microRNAs represent promising therapeutic targets for conditions such as heart failure, cancer, and metabolic disorders.

Rewriting gene regulation The discovery of microRNAs challenged the prevailing belief at the time that genes could only be regulated by proteins. At the time, both Ambros and Ruvkun were postdoctoral researchers in the laboratory of Nobel laureate Rob-

Picture: © Nanaka Adachi/ Nobel Prize Outreach

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European Biotechnology | Winter Edition | Vol. 23 | 2024

ert Horvitz at the Massachusetts Institute of Technology (MIT), studying two mutated genes in the nematode Caenorhabditis elegans. Ambros demonstrated that the lin-4 gene inhibits the activity of lin-14 and does not code for a protein, but rather a microRNA that is just 22 nucleotides long. As Ruvkun found, this microRNA binds to the lin-14 mRNA through an antisense mechanism, blocking its translation. Their 1993 findings were initially met with little attention, but this changed with the discovery of the highly conserved microRNA let-7 in Ruvkun’s lab. It was soon clear that this newly discovered universal mechanism had been in existence for over 500 million years in all multicellular organisms.

The advent of AI The Nobel Prize in Chemistry has also been deemed groundbreaking by the Nobel Committee of the Royal Swedish Academy of Sciences. It marks a milestone in the rapid adoption of Artificial Intelligence in research and drug development. David Baker (62, University of Washington and Howard Hughes Medical Institute) enabled the rapid and reliable prediction of protein structures using AI algorithms, providing an alternative to time-consuming methods like X-ray crystallography. His Rosetta algorithm could predict 3D protein structures that were previously known. By having the software predict the appropriate amino acid sequence for a desired structure, Baker was able to design an entirely new range of proteins. The freely available version, Rosetta@home, theoretically allows anyone to become a protein designer. The de novo design of proteins, enhanced by AI, enables nearly unlimited new creations – including the development of innovative therapies.

Protein folding 2.0 The foundation for the accurate prediction of protein folding was laid by British scientist Demis Hassabis (48) and US researcher John M. Jumper (39) at Google DeepMind.

Hassabis, a neuroscientist, chess player, and former video game developer, founded his own development studio and later DeepMind Technologies in London, which was acquired by Google Health for around US$400m in 2014.

There, he trained the AI model AlphaFold using a vast protein database and, together with Jumper, developed the impressive successor AlphaFold2, which delivered protein structures with accuracy comparable to X-ray crystallography and was followed more recently by a third version. This breakthrough ­allowed the two AI researchers to predict the structure of all known single proteins. Today, millions of users worldwide use the AI model, expanding the known range of protein structures.

When combined with Baker’s research, AlphaFold even facilitates the simulation of protein interactions, paving the way for the design of biologics.

These are already being commercialised by companies, heralding a new era in therapeutic development.

Physics and beyond The 2024 awards in other categories will also be presented at the Nobel Prize Week. The Nobel Prize in Physics was granted jointly to John J. Hopfield (91) and Geoffrey E. Hinton (76) for their groundbreaking work on machine learning with artificial neural networks.

The Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel was awarded jointly to Daron Acemoglu (57), Simon Johnson (61) and James A. Robinson (64) for their research on how institutions are formed and influence prosperity. The Japanese organisation Nihon Hidankyo (founded 1956) will receive the Nobel Peace Prize for its efforts towards a nuclear weapon-free world and its testimonies against their use.

The Nobel Prize in Literature will be given to South Korean author Han Kang (53), the only woman among the laureates, for her poetic prose, which addresses historical traumas and highlights the  fragility of human life. c.kaehler@biocom.eu

RUBRIK

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SCIENCE & TECHNOLOGY

European Biotechnology | Winter Edition | Vol. 23 | 2024

One in a billion: Basel Institute of Immune Engineering GROUNDBREAKING A billion-euro donation caused a stir in Basel. The Swiss Botnar Foundation

donated US$1bn for a new immunology research institute, which is to be located in Basel after a worldwide search for a site. Over the next 15 years, this money will be used to set up the Botnar Institute for Immune Engineering (BIIE), and for research into cost-effective immunotherapies.

The so-called Main Campus of the Life Sciences Mile in Basel Allschwil continues to grow. At the end of October, the foundation stone was laid for the construction of the laboratory building with the abbreviation ALL. The 20,500 square metre complex with laboratory and office space is also being developed and built by real estate investors Senn together with architects Herzog & de Meuron, who have already constructed two other buildings in the neighbourhood. The anchor tenant in ALL will be the Botnar Institute for Immune Engineering (BIIE), which was newly founded with a billioneuro donation, with its new CEO Stephen Wilson, who was poached from La Jolla, California.

From the sea to the river Rhine Stephen Wilson, long-time research director at the La Jolla Institute in California, has been in Basel since the summer and is already working in other rooms on an interim basis to conceptualise the structure and research focus of the new institute. For the time being, the BIIE is

Architectural highlight in the Switzerland Innovation Park in Basel, the new BIIE in the so called ALL-complex of Herzog&deMeuron built by Senn Group.

housed in the building of the Department of Biosystems Science and Engineering (D-BSSE) at ETH Zurich in Basel, where the Scientific Director of the BIIE, Sai Reddy, is also in charge. The building, whose foundation stone was laid in the immediate vicinity as part of the Switzerland Innovation Park Basel Area Main Campus, marking the official start of construction, is expected to be ready for occupancy in 2027.

Fondation Botnar

Foundation stone ceremony in October

The Fondation Botnar is a Swiss philanthropic foundation that is committed to improving the health and well-being of young people in low-income countries.

The BIIE is now benefiting from this and has also been given the task of making the possibilities of immunotherapy accessible and affordable for low-income countries by optimising the processes.

Basel was not simply chosen as the location because the foundation is based there. The city held its own in an open, global competition between leading international research centres. "We were looking for a location for our institute that would fully meet the high demands of the world's best researchers in the field of immune engineering", comments Stephen Wilson. "The Main Campus is located in one of the best life sciences ecosystems in Europe and has proven to be the best global location for us."

The engineering field of manufacturing immunotherapies has not yet been sufficiently addressed in order to be able to spread these therapy options beyond Western countries. "We will really have the low-income countries in mind", says Wilson. "This requires excellent research, an outstanding ecosystem and openess for L technological interdisciplinarity." georg.kaeaeb@biocom.eu

Pictures: ©Herzog&deMeuron; Senn & Partner Holding AG

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ASSOCIATIONS

European Biotechnology | Winter Edition | Vol. 23 | 2024

Position paper BIO DEUTSCHLAND In its position pa-

per, Driving the Economy through the Power of Biology, BIO Deutschland highlights industrial biotechnology as essential for transitioning to a sustainable, biobased economy. The paper advocates for clear regulatory frameworks, stronger government support, and market incentives like CO2 taxes to drive innovation and adoption. It also highlights the need for funding pre-competitive pilot plants, building value chains for bio-based products, and creating tax incentives to attract venture capital. Public engagement and transparency are also prioritised to ensure biotechnology’s role in achieving national and international sustainability goals is  clearly understood.

European Biotechnology is published in co-operation with the following organisations: European Biotechnology Net work

Young European Biotech Network

Europe: european-biotechnology.net

Europe: yebn.eu

Austria: lifescienceaustria.at

Austria: biotechaustria.org

Open letter MEDTECH EUROPE MedTech Europe,

alongside 39 national associations, has called on European Health Commissioner Stella Kyriakides to address the challenges posed by the EU’s medical technology regulations. In an open letter, the group emphasised the urgent need for reforms to prevent the exodus of innovation from Europe and ensure the availability of life-saving devices. They stressed that the current regulatory framework threatens patient safety, industry competitiveness, and public health. The industry proposed a three-point plan to address these challenges. First, it advocates legislative reforms by 2025 to make the regulations efficient, innovation-friendly, and well-governed. Second, it urges immediate “bridging measures” to reduce certification costs, streamline assessments, and accelerate pathways for breakthrough technologies. Lastly, MedTech Europe calls for ongoing improvements in regulation implementation, including reducing documentation burdens and adopting global standards. Without swift action, they warn, Europe risks falling behind in medical tech nology innovation and patient care.

United States: slas.org

Europe: medicinesforeurope.com

Ireland: ibec.ie/ibia

Denmark: danskbiotek.dk

The Netherlands: hollandbio.nl

Germany: gasb.de

Portugal: www.p-bio.org

UK: biopartner.co.uk

France: france-biotech.org

Italy: assobiotec.federchimica.it

Sweden: swedenbio.com

Hungary: hungarianbiotech.org

Europe: cebr.net

Spain: asebio.com

Norway: bioteknologiradet.no

Finland: suomenbioteollisuus.fi

Belgium: bio.be

Switzerland: swissbiotech.org

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

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European Biotechnology | Winter Edition | Vol. 23 | 2024

Join the YEBN biotech community on slack UPCOMING EVENTS The Young European Biotech Network (YEBN) is thrilled to introduce a dynamic new space for connection, learning, and collaboration: the YEBN Community on Slack! Our Slack community will be a central hub across the European biotech landscape.

ONLINE COLLABORATION

After months of preparations, we launch the YEBN Community on Slack. YEBN has been setting the stage for members to engage in a lively, ongoing exchange that extends far beyond our traditional events. Imagine a space where all our member associations can interact, share insights, and keep the conversation going no matter where they are in Europe.

From engaging discussions on biotech trends to expert advice, peer support, and shared resources, this community is built to bring out the best of YEBN’s collaborative spirit and drive for innovation.

In this space, all of our institutions associated with YEBN will play a key role in shaping this community, offering expertise, resources, and perspectives that make YEBN a truly multidisciplinary network. In dedicated channels, members can explore specialized topics, receive updates and event news, and connect around shared interests and goals. It’s an invaluable opportunity to bring together diverse perspectives and approaches from across

Europe, creating a foundation for crossborder collaborations and transformative projects. The Slack community brings everyone closer, with daily interactions that fuel the excitement of our in-person events while adding a new layer of connectivity and continuity.

Our Slack community is open for everyone in the bioscience field, whether you’re a student exploring career possibilities, a young professional building your network, or an experienced researcher interested in sharing your expertise, the YEBN Slack community provides opportunities for engagement at every level. Our platform is designed to be easy to navigate, making it simple for members to find discussions that resonate, gain insights, and contribute to conversations that spark new ideas and collaborations. This isn’t just a digital space – it’s a launchpad for professional growth, community-building, and knowledge exchange that strengthens the biotech ecosystem in Europe. So do not hesitate to become part of this project, we set

› February 5, 2025, Online BioHorizons research jobs › March 12, 2025, Online CV Workshop

the platform so you can launch your professional career to new heights.

Besides being in touch with peers, members will also have the chance to attend exclusive online meetups, participate in Q&A sessions with industry leaders, and join collaborative projects hosted within the community. Our Slack community is buzzing with activity every day, featuring daily conversations and vibrant discussions.

These initiatives ensure that YEBN’s network continues to grow and evolve in response to the needs and interests of our members, creating an inclusive and supportive environment where biotech enthusiasts at all career stages can thrive.

As YEBN embarks on a semester full of events, learning, and connection, our Slack community promises to keep the energy going long after each event concludes. By bridging the distance between our member associations, this platform is a testament to YEBN’s commitment to innovation, networking, and growth within Europe’s biotech community. If you’re interested in becoming part of this journey and aligning with our core values, reach out to us at contact@yebn.eu to learn more about how you can get involved. Together, let’s inspire, collaborate, and create lasting impact.  FIND OUT MORE! For more details about the association and upcoming activities, visit our website at yebn.eu

Pictures: © yebn

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European Biotechnology | Winter Edition | Vol. 23 | 2024

ASSOCIATIONS

UPCOMING EVENTS › December 18, 2024, Vienna Networking-Punsch › April 10, 2025, Vienna 4th BIOTECH CIRCLE AUSTRIA

Seed to succeed

Picture: © BIOTECH AUSTRIA

BIOTECH SUMMIT AUSTRIA 2024 The BIOTECH SUMMIT AUSTRIA 2024 in Innsbruck brought together leaders, innovators and investors to network, interact and to enjoy being part of the booming Austrian biotech community. It showcased science, funding and collaboration opportunities, setting the stage for 2025 in Graz.

Austria’s biotechnology sector was in focus at the second BIOTECH SUMMIT AUSTRIA 2024, held in Innsbruck from October 9–11. Organized by ­BIOTECH AUSTRIA, Standortagentur Tirol, and Human.technology Styria, the event brought together over 250 participants, cementing its role as a key forum for Austrian life science.

Renowned speakers, including Patrick Trojer (TRIANA Biomedicines), Nicole Schlautmann (MSD Austria), Josef Penninger (Helmholtz Centre for Infection Research), Alexander von Gabain (Valneva) and Severin Schwan (Roche), shared insights on founding companies, securing funding and advancing groundbreaking science. Panels explored biotechnology trends in science, venture capital’s role and interaction with entrepreneurs and strategies for successful exits and collaborations. Participants from 13 countries included leading Pharma companies like Pfizer, Novartis, MSD and Roche, alongside investors such as MIG Capital and Wellington Partners, reflecting the sum-

mit’s growing international stature. Local and national governmental players in the industry such as xista, LISA, aws, ABA, FFG amongst universities and institutes from across Austria showed the strong interest and support for the biotech sector.

A hub for co-operation The event also offered vibrant networking opportunities and a dynamic start-up area where biotech innovators pitched ideas to investors. A 1:1 partnering program facilitated connections, further emphasizing the summit’s reputation also as a hub for co-operation.

Peter Llewellyn-Davies, President of BIOTECH AUSTRIA, emphasised its significance: “The summit has solidified its position as a vital platform for Austria’s growing biotech sector. The high turnout and engagement highlight the importance of collaboration and innovation in driving the industry forward. Presenting our strategic packages and measures to

improve vital prerequisites for success in our industry was key.”

Innsbruck, with its strong research environment and thriving biotech community, served as an optimal venue. Dr. Klaus Weinberger, CEO at Health Hub Tirol, commented on the event: “Thanks to its excellent research environment and strong local biotech community, Innsbruck was an ideal location for this year’s conference. We are delighted that together with BIOTECH AUSTRIA and Human.technology Styria we were able to host such a forward-looking and impressive event that enabled productive discussions and new contacts in an inspiring setting.”

Building on this success, the BIOTECH SUMMIT AUSTRIA 2025 will take place in Graz from October 23–24. Lejla Pock, CEO of Human.technology Styria, shared her excitement: “Given the repeated success of this event and the positive feedback, we are already looking forward to continuing the exchange and driving innovation in biotechnology even further with the Summit’s return to Graz and its dynamic biotech community in 2025.”

Austria continues, also through initiatives like the BIOTECH SUMMIT AUSTRIA, to strengthen its global presence and impact in biotechnology, advancing scientific innovation and fostering impactful connections. At the heart of these efforts, BIOTECH AUSTRIA unites key players and drives the industry’s progress, ensuring a dynamic future for Austrian biotech. 

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European Biotechnology | Winter Edition | Vol. 23 | 2024

Revolutionising research The Society for Laboratory Automation and Screening (SLAS) is transforming the global life sciences community by uniting interdisciplinary researchers and technology providers to drive innovation in laboratory automation and research.

LAB AUTOMATION

SL AS is gearing up for it s flagship ­I nternational Conference and Exhibition which brings thousands of global life sciences community members together in San Diego from January 25-29, 2025, for an exploration of life sciences discovery and technology. This leading event promises exceptional opportunities for professional growth with hands-on courses, in-depth technology demonstrations, and networking and exposure to groundbreaking innovations, making it a must-attend for scientists, engineers and technology providers. With the theme of “Curiosity Igniting Innovation,” there’s an unlimited number of ways that attendees can feed their curiosities through multiexperiential explorations.

Feeding your curiosity

Picture: © SLAS

The SLAS2025 Short Course Program empowers individuals with comprehensive instruction on key topics, issues and techniques vital to the laboratory science and technology community. Attendees can select from 18 expertly curated short courses designed to deepen practical knowledge and elevate transferable skills – all before the conference kicks off.

Two extraordinary keynote speakers will be centerstage to spark curiosity: Ahmar Zaidi, M.D., from Agios Pharmaceuticals and Jesse Boehm, Ph.D., from Break Through Cancer and MIT. Endless opportunities to learn with 150 podium presentations spanning eight scientific tracks: › Assay Development and Screening › Automation Technologies › Cellular Technologies › Data Science and AI › Micro- and Nano-Technologies › New Modalities › Omics and Spatial Omics › Screening Applications and Biomarker Diagnostics Hundreds of additional presentations, including posters, Innovation AveNEW start-up companies vying for the SLAS Ignite Award and SLAS New Product Award finalists, will showcase curiosity that will drive innovation and discoveries – and the educational experience doesn’t stop there.

The new NexusXp™ – a groundbreaking exhibition pavilion that shows how laboratory automation connects the pillars of the Design-Make-Test-Analyze cycle. This exclusive space showcases cutting-edge integration scenarios, live

UPCOMING EVENTS › January 25-29, 2025, San Diego SLAS2025 International Conference and Exhibition › May 20-22, 2025, Hamburg SLAS Europe 2025 Conference & Exhibition

demonstrations and success stories from leading technology providers.

Global community get-together Networking at SLAS2025 is a highlight in itself. First-timers can explore the show floor with experienced guides to navigate the bustling space of up to 400 leading exhibitors, while students and early-career professionals can connect at dedicated gatherings.

The SLAS Booth is a hub of activity, offering Recruiter Hours, Mentor Match meetings and a celebration of SLAS Journals: SLAS Discovery and SLAS Technology. For SLAS members, the conference provides exclusive benefits to amplify their experience. This year, attendees can participate in the SLAS Meet-Up Hub, which will provide a space to delve into specialized subjects and exchange insights with peers. SLAS2025 is more than just a conference; it’s a transformative experience that advances careers, fuels innovation, rewards sustainability and social responsibility and fosters lifelong profes sional connections.

FIND OUT MORE! slas.org Sign up for Pointto-point, our weekly e-newsletter, to stay in touch.

European Biotechnology | Winter Edition | Vol. 23 | 2024

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COMPANY INDEX

10x Genomics (USA) . . . . . . . . . . . . . . . . 36 A a:head (AT). . . . . . . . . . . . . . . . . . . . . . . . 63 Accord Healthcare AB (SE). . . . . . . . . . . . 59 AC Immune SA (CH). . . . . . . . . . . . . . . . . 23 Adaptimmune Ltd (GB). . . . . . . . . . . . . . . 34 AgomAb Therapeutics N.V. (BE). . . . . . . . 61 Akeso Biopharma Co. Ltd. (CN). . . . . 14, 15 Algeta ASA (N). . . . . . . . . . . . . . . . . . . . . 27 Alzinova AB (SE). . . . . . . . . . . . . . . . . . . . 23 Amgen Inc. (USA). . . . . . . . . . . . . . . . . . . 14 Ansell Alpha Tec (DE). . . . . . . . . . . . . . . . 79 Araris Biotech AG (CH). . . . . . . . . . . . . . . 18 Asabys Partners (ES) . . . . . . . . . . . . . . . . . 65 Ascendis Pharma A/S. . . . . . . . . . . . . . . . 58 Astellas Pharma (JP) . . . . . . . . . . . . . . . . . 61 AstraZeneca (GB/SE). . . . . . . . 14, 27, 34, 56 ATB Therapeutics BV (BE). . . . . . . . . . . . . 18 Atlas Venture (USA) . . . . . . . . . . . . . . . . . 27 Autolus Therapeutics Ltd. (GB). . . . . . . . . 22 Avantium Life Sciences BV (NL). . . . . . . . 61 AvioadoBio Ltd. (GB). . . . . . . . . . . . . . . . 61 Axol Bioscience Ltd. . . . . . . . . . . . . . . . . 61 B Bayer AG (DE) . . . . . . . . . . . . . . . . . . 27, 29 Beckman Coulter Life Sciences (USA). . . . 56 BerGenBio AS (N). . . . . . . . . . . . . . . . . . . 58 Berlin Partner f. Wirtschaft und Tech (DE). 55 BioArctic Neuroscience AB (SE). . . . . 14, 54 BIOCOM (DE) . . . . . . . . . . . . 49, 57, 73, 79 Biogen Idec (USA) . . . . . . . . . . . . . . . . . . 54 Biomunex SA (F). . . . . . . . . . . . . . . . . . . . 15 BioNTech SE (DE). . . . . . . . . . . . . 15, 22, 82 Biotheus Inc. (CN) . . . . . . . . . . . . . . . . . . 15 Boehmert & Boehmert (DE) . . . . . . . . . . . 35 Boehringer Ingelheim (DE). . . . . . . . . 22, 55 Bormioli Pharma (IT) . . . . . . . . . . . . . . . . 65 Brenus Pharma SA (F). . . . . . . . . . . . . . . . 60 Bristol-Myers Squibb (USA) . . . . . 18, 27, 62 C Calluna Pharma SA (NO). . . . . . . . . . . . . 56 Cancer Research UK. . . . . . . . . . . . . . . . . 60 Caszyme LLC (LT). . . . . . . . . . . . . . . . . . . 65 Catalent (USA). . . . . . . . . . . . . . . . . . . . . 11 CDP Venture Capital. . . . . . . . . . . . . . . . . 64 Celonic AG (CH) . . . . . . . . . . . . . . . . . . . 82 Centessa Pharmaceuticals Ltd (GB). . . . . . 32 Chiesi Farmaceutici S.p.A. (IT) . . . . . . 29, 65 Chiron B.V. (NL). . . . . . . . . . . . . . . . . . . . 20 CN Bio (GB). . . . . . . . . . . . . . . . . . . . . . . 79 Concept Heidelberg / GMP PharmaCongress 2025 (DE). . . . . . . 47 Constellation Pharmaceuticals (USA). . . . 26 Crossfire Oncology BV. . . . . . . . . . . . . . . 16 Curie.Bio . . . . . . . . . . . . . . . . . . . . . . . . . 13 D Daiichi Sankyo (JP). . . . . . . . . . . . . . . 34, 62 Danaher Group (USA) . . . . . . . . . . . . . . . 56 DASGIP GmbH an Eppendorf Company DE). . . . . . . . . . . . . . . . . . . . . . 19 DeepTrack Capital ( . . . . . . . . . . . . . . . . . 27 DiogenX SA (F). . . . . . . . . . . . . . . . . . . . . 56 E EBD Group (USA). . . . . . . . . . . . . . . . . . . 45 Eisai Co. Ltd. (JP) . . . . . . . . . . . . . . . . . . . 54 Eli Lilly & Co Ltd (USA) . . . . . . . . . . . 27, 33

European Biotechnology | Winter Edition | Vol. 23 | 2024

Elicit Plant (F). . . . . . . . . . . . . . . . . . . . . . 82 Endocyte Inc. (USA). . . . . . . . . . . . . . . . . 27 Eni srl (IT). . . . . . . . . . . . . . . . . . . . . . . . . 65 Enifer Biotech (FI). . . . . . . . . . . . . . . . . . . 59 Enilive (IT) . . . . . . . . . . . . . . . . . . . . . . . . 65 Epigenomics AG (DE). . . . . . . . . . . . . . . . 23 European Biotechnology Network (BE). . CP3 Evotec AG (DE). . . . . . . . . . . . . . . . . . 55, 62 F FGK Clinical Research GmbH (DE). . . . . . 39 Forbion Capital Partners (NL) . . . . . . . 27, 60 Fosun Pharma (CN). . . . . . . . . . . . . . . . . . 18 Fusion Pharmaceuticals (CDN). . . . . . . . . 27 G Galapagos NV (BE). . . . . . . . . . . . . . . . . . 34 Genespire srl (IT) . . . . . . . . . . . . . . . . . . . 64 Google Inc. (USA) . . . . . . . . . . . . . . . . . . 73 H Halix B.V. (NL). . . . . . . . . . . . . . . . . . . . . 56 Halozyme Therapeutics Inc. (USA). . . . . . 62 Hamlet BioPharma AB (SE). . . . . . . . . . . . 59 Hangzhou Jiuyuan Gene Engineering (CN).11 Harbinger Health Inc. (USA). . . . . . . . . . . 60 I IBA Lifesciences GmbH (DE) . . . . . . . . . . . 7 Iksuda Therapeutics Ltd.. . . . . . . . . . . . . . 16 Immatics NV (DE). . . . . . . . . . . . . . . . 32, 63 Indaco SGR . . . . . . . . . . . . . . . . . . . . . . . 64 Indivumed GmbH (DE). . . . . . . . . . . . . . . 41 Informa Markets B.V. | CPHI (GB). . . . . . . 42 Innate Pharma SAS (F) . . . . . . . . . . . . 15, 70 Integra Therapeutics (ES). . . . . . . . . . . . . . 65 Invus S.A.S. (F). . . . . . . . . . . . . . . . . . . . . 61 Ipsen S.A. (F) . . . . . . . . . . . . . . . . . . . . . . 29 J Janssen-Cilag International NV (BE) . . . . . 34 Jazz Pharmaceuticals plc (IRL) . . . . . . . . . 14 Johnson & Johnson (USA). . . . . . . . . . 26, 29 Just Biologics (USA) . . . . . . . . . . . . . . . . . 62 K Kancera AB (SE) . . . . . . . . . . . . . . . . . . . . 58 KKR & Co. L.P. (USA). . . . . . . . . . . . . . . . 65 L L'Oréal (F) . . . . . . . . . . . . . . . . . . . . . . . . 69 Labena d.o.o. (SL). . . . . . . . . . . . . . . . . . . 64 LaNova Medicines (CN). . . . . . . . . . . . . . 15 Lanzatech Inc. (USA) . . . . . . . . . . . . . . . . 69 Lek Pharmaceuticals dd (SL). . . . . . . . . . . 64 LimmaTech Biologics AG (CH). . . . . . . . . 34 Lindis Biotech GmbH (DE). . . . . . . . . . . . 14 M Mabswitch Inc. (USA). . . . . . . . . . . . . 13, 15 Madrigal Pharmaceuticals Inc. (USA). . . . 33 Mariana Oncology (USA). . . . . . . . . . . . . 27 Medicxi Ventures (CH/GB). . . . . . . . . . . . 32 Merck Sharp & Dohme Ltd (USA). . . . . . . 15 Merus BV (NL). . . . . . . . . . . . . . . . . . . . . 24 Molecular Partners AG (CH). . . . . . . . . . . 18 Monte Rosa Therapeutics (USA). . . . . . . . 63 MoonLake Immunoltherapeutics AG (CH). 32 MorphoSys AG (DE). . . . . . . . . . . . . . 26, 27 Mosaic Therapeutics (GB). . . . . . . . . . . . . 56 MSD Sharp & Dohme GmbH (USA). . . . . 58

Mylan Pharmaceuticals (NL). . . . . . . . . . . 11 N Nabriva Therapeutics plc (IRL) . . . . . . . . . 24 Nanostring Technologies Inc (USA). . . . . . 36 Novartis AG (CH). . . . . . . 20, 26, 27, 29, 63 Novartis Pharmaceutical Production (SL) . 64 Novo Nordisk A/S (DK). . . 11, 33, 51, 58, 62 NürnbergMesse GmbH | POWTECH 2025 (DE) . . . . . . . . . . . . . . CP2 Nxera Pharma Co. Ltd (JP) . . . . . . . . . . . . 32 O Onego Bio Ltd. (FI). . . . . . . . . . . . . . . . . . 59 P Pfizer (USA). . . . . . . . . . . . . . . . . . . . . . . 20 Pharmahungary Group. . . . . . . . . . . . . . . 66 PharmaMar SA (ES). . . . . . . . . . . . . . . . . . 24 Pharmanovia (GB) . . . . . . . . . . . . . . . . . . 14 Phenocell SAS (F). . . . . . . . . . . . . . . . . . . 61 PlasmidFactory GmbH & Co.KG (DE). 53, 54 Point Biopharma Inc. (USA) . . . . . . . . . . . 27 PolTREG SA (PL). . . . . . . . . . . . . . . . . . . . 66 PPF Group (NL) . . . . . . . . . . . . . . . . . . . . 32 Q Quantro Therapeutics (AT) . . . . . . . . . . . . 55 R RA Capital Management (USA). . . . . . . . . 27 RayzeBio Inc. (USA). . . . . . . . . . . . . . . . . 27 Regeneron Pharmaceuticals Inc. (USA). . . 14 Rentschler Biopharma SE (DE) . . . . . . . . . 17 Resalis Therapeutics srl. (IT) . . . . . . . . 33, 64 Richter Biologics (DE). . . . . . . . . . . . . . . CP4 Roche AG (CH). . . . . . . . . . . . . . . . . . 14, 34 S Sandoz AG (CH). . . . . . . . . . . . . . . . . . . . 64 Sanofi SA (F). . . . . . . . . . . . . . . . . 33, 61, 64 Seamless Therapeutics (DE). . . . . . . . . . . . 54 Sino Biological Europe GmbH (DE) . . . . . . 9 SixPeaks Bio AG (CH). . . . . . . . . . . . . . . . 14 Sofinnova Partners (F). . . . . . . . . . . . . . . . 64 Somagenetix AG (CH). . . . . . . . . . . . . . . . 63 Sophia Genetics SA (CH) . . . . . . . . . . . . . 25 Sosei Group (JP). . . . . . . . . . . . . . . . . . . . 32 Sotio a.s. (CZ). . . . . . . . . . . . . . . . . . . . . . 32 Stayble Therapeutics AB (SE). . . . . . . . . . . 25 Summit Therapeutics plc (IRL). . . . . . . 14, 15 SystImmune Co. Ltd. (CN) . . . . . . . . . . . . 18 T Trion Pharma GmbH (DE). . . . . . . . . . . . . 14 U UAB BiotechPharma (LT) . . . . . . . . . . . . . 31 UCB Pharma SA (BE) . . . . . . . . . . . . . . . . 60 V Valneva SE (F). . . . . . . . . . . . . . . . . . . 20, 34 Vetter Pharma InternationalGmbH (DE). . 33 X Xbrane Biopharmaceuticals AB (SE) . . . . . 59 XGEN Venture (IT) . . . . . . . . . . . . . . . . . . 64 Z Zealand Pharmaceuticals A/S (DK). . . . . . 22 Zymeworks Inc. (CDN). . . . . . . . . . . . 14, 16

EVENTS

European Biotechnology | Winter Edition | Vol. 23 | 2024

BIO-Europe Spring 17.–19.03.2025 MILAN BIO-Europe Spring brings together Europe’s top innovators and the global life sciences industry to build strategic partnerships.

Alongside partnering opportunities, the event offers a carefully curated programme to inform attendees about the latest trends, challenges and opportunities in the sector. https://informaconnect.com/bioeurope-spring/

11.-13.3.25

4.-5.6.25

12.-13.3.25

16.-20.6.25

EFIB at BIOKET 2025, Brussels (BE) Info: EuropaBio https://www.europabio.org/

Cellulose Fibres Conference 2025, Cologne (DE)/online Info: nova Institut www.cellulose-fibres.eu

18.-20.3.25

Bioprocessing Summit Europe, Barcelona (ES)/ +++ online +++ Info: Cambridge Healthtec Institute www.bioprocessingeurope.com/

2.-3.4.25

CEBioForum 2025, Warsaw (PL) Info: Association of Biotechnological Companies BioForum https://cebioforum.com/

28.-29.4.25

BioVaria 2025, Munich (DE) Info: Rebecca Engels, Ascenion GmbH www.biovaria.org/

Chemspec Europe 2025, Cologne (DE) Info: Reed Exhibitions https://www.chemspeceurope.com/

EuPA 2025, Saint-Malo (F) Info: European Proteomics Association https://eupa.org

Life Sciences Baltics 17. –18 .0 9. 2025 VILNIUS Decision-makers and the next generation of founders and talents from the Baltics will meet in Vilnius. In addition, CEOs, tech scouts and researchers from all over the world will come together for collaboration. https://lifesicencesbaltics.com/

12.-15.5.25 12.1.25

New Horizons Forum in Biologics and Bioprocessing, Stockholm (SE) Info: Life Science Sweden http://www.bioprocessing.se

15.-18.1.25

Global Forum for Food and Agriculture, Berlin (DE) Info: Federal Ministry of Food and Agriculture https://www.gffa-berlin.de

22.-23.1.25

Pharmapack 2025, Paris (F) Info: INFORMA www.pharmapackeurope.com

Pictures: mouradb4 / Duernsteiner / Peggy und Marco Lachmann-Anke (alle auf Pixabay)

25.-29.1.25

SLAS2025, San Diego (USA) Info: Society for Lab Automation and Screening – SLAS https://www.slas.org

26.-27.1.25

DxPx Conference 2025, Munich (DE) Info: SLS Partnering GmbH https://dxpx-conference.com/eu/

17.-21.2.25

Barcelona Health Innovation Week 2025, Barcelona (ES) Info: biocat https://www.biocat.cat/en

18.-19.2.25

CLIB International Conference CIC2025, Düsseldorf (DE) Info: Cluster Industrial Biotechnology, CLIB https://www.clib-cluster.de

BioProcess International Europe, Hamburg (DE) Info: Informa Connect https://informaconnect.com/bpieurope/

14.-15.5.25

8 th European Symposium on Biomaterials and Related Areas – BioMAT 2025, Weimar (DE), +++ online +++ Info: Deutsche Gesellschaft für Materialkunde e.V. DGM https://dgm.de/biomat

SLAS Europe 2025 20.–22.05.2025 HAMBURG The

event offers workshops from tech providers, scientific conferences, networking opportunities, and more than 100 demonstrations on laboratory automation and life sciences as part of the exhibition. It is the perfect place to connect with experts and discover innovative technologies. www.slas.org

16.-19.6.25

BIO International Convention, Boston (USA) Info: BIO – Biotechnology Innovation Organization https://www.bio.org

19.-20.6.25

World Bio Markets – Driving the commercialisation of the bioeconomy, Le Hague (NL) Info: Paul McDonald, TNP Media Ltd. https://www.worldbiomarkets.com

7.-9.9.25

BIOSPAIN 2025, Barcelona (ES) Info: ASEBIO https://asebio.com

16.-18.9.25

ILMAC 2025, Basel (CH) Info: MCH Group https://www.ilmac.ch/de

30.9.-2.10.25

Festival of Biologics 2025, Basel (CH) Info: Terrapinn https://www.terrapinn.com

6.-8.10.25

BioTechX Europe, Basel (CH) Info: Terrapinn, https://www.terrapinn.com/

81

ENCORE

European Biotechnology | Winter Edition | Vol. 23 | 2024

Plant growth

I’m in biotechnology because ...

BIONTECH has left its phase as a vaccine developer behind and has credibly transformed itself into an AI company. This is what the company had always wanted to do: cure cancer with data science. Now it’s back on track with oncology in the spotlight.

AGRITECH Elicit Plant, a French agri-bio-

FDA With an anti-vacci-

nation activist like R.F. Kennedy at the helmet of the newly appointed US Department of Health and Human Services, it will also be difficult for the FDA to maintain its composure. The background noise from the new Trump administration is likely to throw a spanner in the works, as RFK feels himself in charge to work against the ‘corrupt’ FDA system. MASA: Make America sick again? 

DR SAMANTA CIMITAN, CEO, Celonic Group, Basel/Heidelberg

“I want to solve complex problems and advance life-changing therapies.

Innovation in biotherapeutics and next-gen bioprocessing enable more targeted and affordable treatments.”

Antibiotics: still growing Global antibiotic consumption continues to rise despite a brief decrease during the COVID-19 pandemic, according to a study. Eili Klein, Arindam Nandi, and colleagues used pharmaceutical sales data to estimate trends in antibiotic consumption in 67 high-income (HIC) and middleincome countries between 2016 and 2023 and projected future global antibiotic consumption through 2030. From 2016 to 2023, total estimated antibiotic consumption in the examined countries increased by 16.3% to 34.3 billion defined daily doses (DDDs) dispensed in 2023. 

tech company specialising in biosolutions for broadacre crops, has raised €45m to accelerate its global expansion as farmers face increasing climate challenges.

The investment round was led by Carbyne with participation from existing investors Sofinnova, European Circular Bioeconomy Fund (ECBF) and BPI France. The primary net proceeds to the company will be used to increase commercialisation of existing products and support further development of new solutions to provide farmers worldwide with effective products to combat climate uncertainties that impact their yields and ability to feed populations.

Elicit is using extragenous phytosterols to elicit (sic!) natural stress resistance mechanisms like closing stromata and increasing root growth. The products are already widley used in Europe, Brazil and USA. 

HIC 20 LMIC 16 MIC 12 UMIC 8 2016

2018

2020

2022

The really very last word

Next issue 2025

One thing has to be said: there is a lot going on politically in the northern hemisphere. Most of the governments from the coronavirus years in the democracies have now actually been replaced or are as good as replaced. Whether the new ones will be better remains to be seen. But, as we all know, there is magic in every new beginning – and the people under the warmongering would-be tsar, the crocodile

SPRING EDITION Our next issue comes

in the Middle Kingdom or the fat dictator in the starving part of Korea can only dream of this. It’s just a pity that these and other obscurantists are holding us back from the two huge challenges of this century: the fight against climate catastrophe and the global decline in biodiversity. Is anyone else besides us drumming up support for the biologisation of our ‘civilisations’? Does really everything have to get absolutely bad before it can get better?

Bernardo Glavo 

with three specials: Legal, Tax & Accounting, Oligonucleotides & Peptides and automation/organoids/microscaling. Players in these fields are invited to present their offering in our special in European Biotechnology. Want to participate? Just contact Christian Böhm (+49-30-264921-49), Oliver Schnell (-45), Andreas Macht (-35) or mail: marketing@biocom.de. Publishing date is 27 March 25; deadline for ads is 14 March 25. 

Data source: PNAS, Nov 18 2024, Eili Y.Klein et al., Global trends in antibiotic consumption, https://doi.org/10.1073/pnas.241191912 © kora_ra_123 - stock.adobe.com (Icon) , Picture: © Celonic Group

Winners & losers

DDDs per 1,000 inhabitants per day

82

European Biotechnology Net work

Let’s save the planet!

Join the European Biotechnology Network!

Find out about (free) membership on our website www.european-biotechnology.net ©master24 - stock.adobe.com

C O R P O R AT E M E M B E R S 12 / 24

Biodiversity loss, climate apocalypse, billions of people in turmoil. New strategies are desperately needed. Biotechnology creates confidence and solutions. The European Biotechnology Network is a non-profit organisation that aims to facilitate cooperation between all professionals in biotechnology and life sciences on the European continent.

European Biotechnology Network AISBL Avenue Louise 65, Box 11 | 1050 Brussels Belgium | Tel: +32 (0)2 588 70 71 www.european-biotechnology.net info@european-biotechnology.net

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