Cheryl Barton is director of PharmaVision, 

Cheryl Barton

Advancing Healthcare with CAR T-Cell Therapy: A New Frontier in Medicine | Image Credit: ©Funny – stock.adobe.com

In the past two decades, significant advances in immunology have improved our understanding of immune checkpoint mechanisms and the role of T-cell receptors (TCRs) recognizing tumour antigens and tumour cell eradication (1). This knowledge has led to the development of several immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) treatments. Although ICIs have cured many cancer patients, some patients fail to respond to ICIs due to the limited presence of tumour-specific effector T cells (2).

This article was published in the April 2025 issue of 

Adoptive T-cell therapies (ACTs), which include chimeric antigen receptor T cells (CAR-T), tumour-infiltrating lymphocytes (TILs), and engineered T-cell receptor-T cells (TCR-Ts), have the potential to overcome these shortfalls. To date, six CAR-T therapies targeting CD19 or B cell maturation antigen have been approved by the regulators and have shown encouraging results in haematological cancers; however, their clinical impact on solid tumours has been modest due to antigen scarcity, tumour heterogeneity, and immunosuppression within the tumour microenvironment (TME) (3–4). Thus, companies have been exploring other ACT approaches to overcome these issues (5–6).

Engineered T-cell receptor-T cell therapies

TCR-T increases the flexibility for targeting solid tumours, particularly those with a high mutational burden (HMB). Unlike TILs, one does not need access to the primary tumour, which allows the use of upstream sources of material, for example, peripheral blood. Importantly, TCR-T cells can target inside the cell surface and recognize a broader range of epitopes than CAR-T cells and up to 90% of cellular proteins, including:

tumour-associated antigens (TAAs) that are over-expressed in cancer cells compared with normal tissues. For example, tissue differentiation antigens (TDAs) such as melanoma antigen recognized by T 1 (MART-1) and gp100, and cancer germline antigens (CGAs) such as melanoma-associated antigen A (MAGE-A) protein family, New York oesophageal squamous cell carcinoma-1 (NY-ESO-1), and preferentially expressed antigen in melanoma (PRAME)

tumour-specific antigens (TSAs) or neoantigens (NAs) that are exclusively expressed in tumour cells. For example, TP53 and Kirsten rat sarcoma virus (KRAS)

viral antigens, for instance, antigens stemming from viral-induced cancers such as Epstein-Barr virus (EBV), human papillomavirus (HPV), hepatitis B virus (HBV), and Merkel cell polyomavirus (MCPyV).

Importantly, TCR-T cells exhibit high antigen sensitivity that could result in improved tumour cell detection and removal, and they are associated with a high level of T cell persistence (7). More than 30 clinical trials are underway exploring the potential of TCR-T cells in haematological and solid tumours (

Table I. TCR-T cell therapies in clinical development.

Allogeneic “off-the-shelf” solutions are emerging

The use of gene editing in autologous (patient-derived) CAR-T and TCR-T cell therapies is dictated by the compatibility of the highly polymorphic HLA molecules between donors and recipients, which can lead to graft-versus-host disease (GVHD) and rejection. Academic researchers and biotechs are looking at ways to generate “off-the-shelf” or allogeneic (universal) solutions using virus-specific T cells, lipid-restricted (CD1) T cells, MR1-restricted T cells, and γδ-TCR T cells (8). This approach could enable TCR-T therapies to be produced more cost-effectively and be made available to a broader patient population. For instance, researchers at Princess Máxima Center for Paediatric Oncology, Utrecht, The Netherlands, have engineered allogeneic cord blood-derived CD8+ T cells with a specific TCR targeting the tumour-associated antigen WT1 to achieve high efficiency and potent cytotoxicity against AML cells (9).

European biotech investing in TCR-T therapies

Several European biotechs are leading the way in TCR-T therapies, including the following.

 The biopharma company was co-founded by CEO Reagan Jarvis in 2014 to develop TCR-T therapies to treat solid tumours and other difficult-to-treat diseases, including infectious and autoimmune diseases. Its proprietary TCR discovery platform systematically maps cancer targets to build TCR libraries and generate personalized TCR-T treatments. To date, the company has raised US$120 million (€111 million) in three funding rounds, attracting investment from AMF, Danske Bank, European Investment Bank, Melby Gard, and others (10). In May 2024, Anocca teamed up with Shinobi Therapeutics to co-develop “off-the-shelf” allogeneic TCR-induced pluripotent stem cell (iPS)-T-cell therapies for the treatment of solid tumours (11). In March 2025, Anocca received authorization for its Clinical Trial Application (CTA) to initiate a Phase I/II, VIDAR-1 trial with ANOC-001, a non-viral gene-edited TCR-T therapy targeting mutant KRAS G12V in advanced pancreatic cancer. Anocca aims to initiate the study in the second quarter of 2025 and enrol 20 patients with HLA and KRAS mutations at leading medical centres in Sweden, Denmark, Germany, and the Netherlands (12).

 Immunocore was founded by Bent Jakobsen and James Noble in 2008 as a spinout of MediGene AG. The core TCR technology was developed at Oxford University in 1999. The company has raised more than US$574 million (€531 million) and undertook an IPO in February 2021. Immunocore’s proprietary TCR technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) that enable the immune system to recognize and eliminate virally infected cells. ImmTACs recognize intracellular cancer antigens and selectively kill haematological and solid tumour cells via an anti-CD3 immune-activating effector function. In January 2022, the US Food and Drug Administration (FDA) approved Kimmtrak (tebentafusp), a bispecific gp100 peptide-HLA-directed CD3 T cell engager, for the treatment of metastatic uveal melanoma (13). Kimmtrak generated global sales of US $310 million (€280 million) in 2024. Tebentafusp is currently being evaluated in two Phase III trials (TEBE-AM and ATOM) in additional melanoma indications. Immunocore is evaluating brenetafusp (IMC-F106C) targeting PRAME-A02 in the Phase III PRISM-MEL-301 in first-line advanced cutaneous melanoma and a Phase I/II trial of brenetafusp combinations in ovarian cancer and NSCLC. In addition, the company is evaluating an IMC-P115C targeting PRAME-A02-HLE in a Phase I trial for colorectal and other gastrointestinal cancers (14). The company is also evaluating the ImmTAC technology in infectious diseases (HIV and HBV) and autoimmune diseases (type 1 diabetes and dermatology) (15).

 Medigene is an immuno-oncology platform company developing TCR-T therapies. Its End-to-End Platform aims to generate and optimize TCRs for multiple therapeutic modalities, including TCR-guided T cell engager therapies (TCR-TCEs), TCR-natural killer (TCR-NK) cell therapies, and TCR-T cell therapies. The company has codeveloped an allogeneic TCR-TCE therapy, MDG3010, with WuXi Biologics that targets KRAS G12V in solid tumours. It is also developing autologous TCR-T therapies, including MDG1015 (NY-ESO01/LAGE-1a), MDG2011 (KRAS G12V), MGD2021 (KRAS G12D), and MDG2012 (KRAS G12V) (16). Medigene has forged partnerships with BioNTech and Regeneron where it is codeveloping a PRAME TCR-T and MAGE-A4 TCR-T therapy, respectively (17). In February 2025, the company partnered with EpimAb Biotherapeutics to develop MCD3020, an allogeneic TCR-TCE for the treatment of solid tumours and immune-related disorders (18).

Biotechs in the US and the Asian Pacific are active in the TCR-T space

In the United States, Adaptimmune Therapeutics and Iovance Biotherapeutics have received regulatory approval for ACTs. In March 2024, FDA approved Iovance’s Amtagvi (lifileucel), the first TIL therapy for advanced melanoma following anti-PD1 and targeted therapy (19). In clinical studies, the overall response rate for pooled data in 153 patients was 31.4%, the median duration of response (mDOR) was 21.5 months, and the four-year pooled analysis mDOR was not reached at 48.1 months. In August 2024, FDA approved Adaptimmune’s Tecelra (afamitresgene autoleucel), the first MAGE-A4-targeted TCR-T therapy for unresectable or metastatic synovial sarcoma (20). Among the 44 patients in the trial who received Tecelra, the overall response rate was 43.2%, and the median duration of response was six months.

Several other US biotech companies are evaluating TCR-T therapies in the clinic, including BioNTech, Cartesian Therapeutics, Immatics, and Regeneron. Immatics has developed three proprietary platforms: an autologous ACTengine, an allogeneic ACTallo platform, and an antibody-like TCR bispecific platform or T cell engaging receptors (TCER). Its lead programme, IMA203, uses ACTengine technology and is currently being evaluated in the Phase III SUPRAME targeting PRAME in heavily pretreated metastatic melanoma patients (21).

In January 2025, BioNTech published proof-of-concept data from Phase I trials with BNT221, a personalised, neoantigen-specific autologous T-cell product derived from peripheral blood (22). The infused T cells were highly specific, polyfunctional, and cytotoxic and expressed TCRs with a wide range of avidities in patients with advanced melanoma. The treatment was well-tolerated, and the vast majority of adverse events observed were attributed to the lymphodepletion chemotherapy preceding BNT221 infusion.

Other US biotechs working in this field include Alaunos Therapeutics, Affini-T Therapeutics, BlueSphere Bio, and TScan Therapeutics.

In the Asian-Pacific region, HRYZ Biotech, Neowise Biotechnology, Precision Biotech, and TCRCure Biological Technology in China; Lion TCR and SCG Cell Therapy in Singapore; and Takara Bio in Japan all have products in early clinical development.

Advances in TCR-T applications and the clinical approval of novel ACTs have paved the way for a new generation of T-cell therapies targeting solid tumours (23). Despite the promising clinical results, the total time to manufacture the cell product still limits the broader use of ACT therapies. Like CAR-T therapies, TCR-T cell therapy requires cellular expansion; however, the CAR-T field is moving towards in-vivo approaches. Further work is needed to enhance the potency, expansion, and persistence of T-cells; this may be achieved by combining products such as PD-1 inhibitors/TCR-T or cancer vaccine/TCR-T therapy (24).

Alternatively, the development of allogeneic TCR-T therapies could provide a cost-effective “off-the-shelf” solution, enabling patients broader access to these innovative therapies. Several large pharma companies, AstraZeneca, Galapagos, GlaxoSmithKline, and Shionogi, have TCR-T programmes in clinical development, and this field is likely to attract further investment from biopharma and private investors as proof-of-concept studies report out.

Zhao, X.; Shao, S.; Hu, L. The Recent Advancement of TCR-T Cell Therapies for Cancer Treatment. 

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Tracxn. Anocca - Raised $120M in Funding from 8 Investors. 

Anocca. Anocca AB and Shinobi Therapeutics Announce Strategic Partnership to Develop Allogeneic TCR-T Cell Therapies in Oncology. Press Release. 30 May 2025.

Anocca. Anocca Announces Authorisation of Clinical Trial Application to Start First In-Human Trial in Advanced Pancreatic Cancer. Press Release. 17 Mar. 2025.

OncoDaily. KIMMTRAK (Tebentafusp) Uses in Cancer: Dosages, Indications, Expectations and More. 23 Feb. 2025.

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FDA. FDA Approves First Cellular Therapy to Treat Patients with Unresectable or Metastatic Melanoma. Press Release. 16 Feb.2024.

FDA. FDA Approves First Gene Therapy to Treat Adults with Metastatic Synovial Sarcoma. Press Release 2 Aug. 2024.

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Cheryl Barton is founder and director of PharmaVision, Pharmavision.co.uk.

When referring to this article, please cite it as Barton, C. Engineered T Cell Receptor-T Cell Therapies. 

Articles

New TCR-T cell therapies look promising in the treatment of haematological and solid tumours.

Engineered T Cell Receptor-T Cell Therapies

Landkarte *** Europa | Image credit: ©beugdesign - Stock.adobe.com

On 11 Mar. 2025, the European Commission (EC) proposed the Critical Medicines Act, setting out a plan to improve medicine procurement, provide subsidies for drug production, and improve supply chains to reduce the risk of drug shortages (1). The European Union (EU) relies heavily on medical supplies outside the EU, particularly India and China (2). The COVID-19 pandemic exposed significant vulnerabilities in the EU’s pharmaceutical supply chain.

Access to medicines varies considerably from Member State to Member State. According to a recent survey conducted by the EU4Health programme-funded Joint Action of Member States on shortages (CHESSMEN), over 50% of reported shortages in 2022 and 2023 were caused by manufacturing issues, in particular, shortages in APIs (see Table I [3–4]).

The European Medicines Agency (EMA) regularly updates its list of critical medicines to ensure it can take proactive measures to avoid medicine shortages (5). It has set up the European Shortages Monitoring Platform (ESMP) to gather information about medicine availability, supply, and demand to prevent, detect, and manage human medicine shortages in the EU and European Economic Area (EEA). As per Regulation (EU) 2022/123, a ‘shortage’ is defined as “a situation in which the supply of a medicinal product that is authorized and placed on the market in a Member State […] does not meet the demand for that medicinal product […] at a national level, whatever the cause” (6). However, there is currently no harmonized definition on the EU level for a potential shortage.

Recommendations from the Critical Medicines Alliance

In January 2024, the EC launched the Critical Medicines Alliance (CMA) to “identify challenges resulting from vulnerabilities and the most appropriate actions and instruments to address the vulnerabilities in the supply chains of critical medicines, with the primary public health goal of reducing the risk of shortages of those critical medicines” (7). In February 2025, the Alliance published its Strategic Report laying out a set of recommendations (8).

The Critical Medicines Act aims to address the issues raised by:

strengthening Europe’s manufacturing capacity

The EC’s proposal aims to overhaul procurement rules allowing EU Member States to prioritize the security of supply based not only on price but on additional criteria including stockholding obligations, the number of diversified suppliers, monitoring of supply chains, transparency, and performance clauses. Where appropriate, preference will be given to suppliers that manufacture a significant proportion of critical products in Europe and EU Member States or the EC may undertake joint procurement of critical medicines (2).

EU countries can provide financial support for ‘strategic projects’ to improve and expand the EU’s manufacturing capabilities of critical medicines, APIs, or starting materials. These funds are not available for non-critical medicines. EU funding will be accessible through the Strategic Technologies for Europe Platform (9).

A Critical Medicines Coordination Group, composed of representatives from each Member State, will be established to provide information on manufacturing capabilities, identify strategic projects for state support, and pinpoint areas of vulnerability in the supply chains (2).

Given the turbulent geopolitical landscape, it is paramount that the EU has access to a stable and reliable supply chain for essential medicines. The Critical Medicine Act complements the revised pharmaceutical legislation and will help the EU to improve its preparedness and resilience, strengthen its overall security, and increase the EU’s competitiveness within the global pharmaceutical arena (10). 

EC. Proposal for a Critical Medicines Act.

O’Neill, R. EU Plans to Boost Medicines Manufacturing in Drug Shortages Bill. 

 Identifying the Root Causes of Observed Shortages of Medicines

EMA. European Shortages Monitoring Platform (ESMP) Frequently Asked Questions (FAQs). 

CMA. Strategic Report of the Critical Medicines Alliance. 

EU. Strategic Technologies for Europe Platform (STEP). 

EC. Reform of the EU Pharmaceutical Legislation. 

Cheryl Barton, PhD, is founder and director of PharmaVision, Pharmavision.co.uk.

When referring to this article, please cite it as Barton, C. Critical Medicines Act Plans to Improve Supply Chain. 

The Act is the European Union’s plan to avert drug shortages.

Critical Medicines Act Plans to Improve Supply Chain  

On 30 Jan. 2025, the European Commission (EC) launched a new Biotech and Biomanufacturing Hub to help European Union (EU) businesses, particularly small and medium enterprises (SMEs), to access support, expand, and grow (1).

The Hub offers access to EU funding for research and development (R&D), business development tools to market products on a global scale, regulatory guidance on product approval, and compliance and support for intellectual property rights to protect innovative products (1).

The Hub is accessible on the EC’s Your Europe portal to EU nationals, nationals of European Arenas Association (EAA) countries, family members of EU/EEA nationals, non-EU nationals that enjoy EU rights, and businesses with headquarters in a EU country (2). A task force of advisors will guide the continuous development of the portal (3).

In June 2023, the EC proposed a regulation to establish a new platform for Strategic Technologies for Europe Platform (STEP) (4). STEP aims to support the development and manufacturing of critical technologies and to address any shortage of labour and skills. Several proposals were outlined in STEP to boost biotechnology and biomanufacturing in the EU, these are summarized in 

Figure 1. Proposals outlined in the European Commission’s Strategy to boost biotechnology and biomanufacturing in the EU. Figure courtesy of the author

On 1 March 2024, the STEP Regulation (Regulation (EU) 2024/795) came into force (6). The STEP platform has access to €160 billion in funds to invest in strategic projects that develop or manufacture critical technologies namely:

biotechnologies—molecular biotechnology, pharmaceuticals, crop biotechnology.

clean and resource-efficient technologies—capture and storage technologies, and heat pumps.

digital technologies and deep technology innovation—artificial intelligence (AI), advanced connectivity, and quantum technologies (4).

STEP stakeholders include governments, regulatory bodies, industry leaders, research institutions, and the public. The STEP Task Force coordinates and cooperates with stakeholders to address funding challenges and identify new opportunities.

The EU aims to bolster its industrial competitiveness, enhance its strategic autonomy and resilience, and boost its economic security through investment in biotech and biomanufacturing, and the Hub is a key element of the EC’s strategy (7).

STEP has invested in 11 EU programmes including:

Digital Europe Programme (DEP): Provides funding for projects including advanced digital skills AI, cybersecurity, supercomputing, and ensuring the wide use of digital technologies across the economy and society (8).

European Defence Fund (EDF): This supports collaborative research and development (R&D) of defence capabilities with the EU budget (9).

EU4Health: Established in response to COVID-19’s impact on medical and healthcare staff, patients, and health systems in Europe. It aims to improve and foster health in the EU (10).

Horizon Europe (HE): Aims to tackle climate change and helps to achieve the United Nations’ (UN’s) Sustainable Development Goals and boosts the EU’s competitiveness and growth (11).

Innovative Fund (IF): One of the world’s largest funding programmes for the demonstration of innovative low-carbon technologies (12).

Additional funding has been provided by STEP to the European Regional Development Fund (ERDF), Cohesion Fund, European Social Fund+ (ESF+), InvestEU, Just Transition Fund (JTF), and Recovery and Resilience Facility (13).

The EC continues to strengthen the competitiveness and resilience of the European economy through investment in transformational technologies. The investment in the Biotech and Biomanufacturing Hub will not only support innovative European biotechs but also sends a clear message to the rest of the world that Europe means business (14).

EC. New Biotech Hub to Support Companies. ec.europa.eu. 20 Jan 2025.

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EC. Regulation (EU) 2024/795 of the European Parliament and of the Council of 29 February 2024 Establishing the Strategic Technologies for Europe Platform (STEP) and Amending Directive 2003/87/EC and Regulations (EU) 2021/1058, (EU) 2021/1056, (EU) 2021/1057, (EU) No 1303/2013, (EU) No 223/2014, (EU) 2021/1060, (EU) 2021/523, (EU) 2021/695, (EU) 2021/697 and (EU) 2021/241. ec.europa.eu. 29 Feb. 2024.

EC. Building the Future with Nature: Boosting Biotechnology and Biomanufacturing in the EU. EC.europa.eu. 20 Mar 2024.

EC. Digital Europe Programme. ec.europa.eu (accessed 14 Feb. 2025).

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EC. STEP Strategic Technologies For Europe Platform. June 2024.

Yadav, R. European Commission Launches Biotech and Biomanufacturing Hub. The Bioeconomy. 31 Jan. 2025.

When referring to this article, please cite it as Barton, C. Launching the New Biotech and Biomanufacturing Hub. 

The Biotech and Biomanufacturing Hub will help European companies access funding, navigate regulations, and speed up market access.

Launching the New Biotech and Biomanufacturing Hub  

Two dosing pens of a fictitious semaglutide drug (GLP-1) on a scale facing a dumbbell. Concept for alternative ways to loose weight. | Image Credit: © Andreas Prott - Stock.adobe.com

Obesity is a major public health threat and is associated with an increased risk of obesity-related complications and mortality. It has proved a challenging target for pharmaceutical intervention, and early strategies using amphetamine-based appetite suppressants resulted in significant side effects and high-profile lawsuits against manufacturers (1).

Better understanding has fuelled product development

A better understanding of the gut-brain axis has led to the development of oral glucagon-like peptide-1 (GLP-1) receptor agonists (RA) and glucose-dependent insulinotropic polypeptide (GIP) RAs for the treatment of type 2 diabetes (T2D) and weight management (

). These include Novo Nordisk’s oral Ozempic/Wegovy (semaglutide) and Saxenda (liraglutide) and Eli Lillys’ once-weekly GIP/GLP-1 dual agonist Mounjaro (tirzepatide), which was approved by the European Medicines Agency (EMA) in 2202 to manage weight (2,3).

Regulatory-approved anti-obesity medicines.

Next-generation anti-obesity medicines are emerging

GLP-1 agonists and GIPs are not without their side effects, so companies are researching new drug targets, combinations, and formulations to overcome these shortfalls and provide safer, more robust, and sustainable body weight loss (3-6). According to IQVIA, 116 new anti-obesity medicines (AOMs) are in clinical development (

). Several of the agents modulate novel targets such as amylin, cannabinoid receptor type 1 (CB-1), diacylglycerol O-acyltransferase 1 (DGAT1), monoacylglyceroltransferase (MGAT2), and solute carrier 6 (SLC6) transporters.

 Anti-obesity agents in clinical development. 

European biotechs active in the AOM space

The AOM space has attracted a lot of attention from pharma and biopharma leading to some high-profile acquisitions during 2024 including US-based Carmot Therapeutics by Roche and US-based Versanis Bio by Eli Lilly and UK Biotech Zihipp by Metsera (7–9). Several European biotechs are making headway in this arena (

), and private investors are keen to get in on the act.

Anti-obesity medicines in clinical development from European biotechs.

European companies worth watching out for in the AOM space include the following.

The company’s lead programme, AT-7687, is a once-weekly subcutaneously administrated GLP-1 receptor peptide antagonist that binds strongly to albumin circulating in the blood to extend its half-life (10). In December 2024, Antag gained US Food and Drug Administration (FDA) investigational new drug (IND) clearance to advance to Phase I in early 2025. The company is evaluating AT-7687 as a monotherapy and in combination with Novo Nordisk’s Ozempic/Wegovy (semaglutide) (11). Antag recently completed an €80 million (US$82.4 million) Series A financing round backed by Versant Ventures and Novo Holdings, and the funds will be used to drive the development of AT-7687 (12). In January 2025, Antag announced that Joerg Moeller formerly of Bayer would succeed Alexander Sparre-Ulrich as chief executive officer, who will move to the chief operating officer role to drive the GLP-1 programme forward.

 Gubra is a pre-clinical contract research organization (CRO)/biotech founded in 2008 and focusing on peptide-based therapies. Its lead program, GUBamy, is a long-acting amylin analogue that is well-tolerated and significantly increased weight loss during the six-week Phase I study (13). Gubra is developing four anti-obesity agents in conjunction with Boehringer Ingelheim (BI) including two clinical progammes with a long-acting neuropeptide Y receptor type 2 (NPY2R) agonist, BI 1820237, and a triple agonist. In October 2024 BI discontinued its development of BI 1820237, and no further details were released (14). In December 2024, Gubra announced a new collaboration with Amylyx Pharmaceuticals to develop a novel long-acting GLP-1 receptor agonist (15). Under the agreement, Gubra will receive upfront and research payments and may receive more than US$50 million (€48 million) on milestones payments and royalties on worldwide net sales. In January 2025, Gubra announced it had appointed Anne-Marie Levy Rasmussen as the company’s new chief operating officer (previously at GlaxoSmithKline and Bavarian Nordic) to help grow and optimize the company (16).

 Verdiva Bio is a private cardiometabolic health company founded in 2024 and headed up by Khurem Farooq, Farooq, formerly chief executive of Aiolos Bio, and Gyroscope Therapeutics before their respective acquisitions by GlaxoSmithKline and Novartis, respectively. In January 2025, Verdiva Bio completed a US$411 million (€391 million) Series A financing co-led by Forbion and General Atlantic, with additional participation from RA Capital Management, OrbiMed, Logos Capital, Lilly Asia Ventures, and LYFE Capital (17). In January 2025, Verdiva acquired global development and commercialization rights outside of greater China and South Korea to their industry-leading portfolio from Sciwind Biosciences in 2024. The partnered portfolio includes:

VRB-101, a Phase II-ready, once-weekly oral GLP-1

VRB-103, a once-weekly, oral dual-acting amylin and calcitonin receptor against (DACRA) agent in preclinical development for use as monotherapy or in combination with VRB-101

VRB-102, once-weekly injectable DACRA for use in combination with VRB-101 in pre-clinical development (18).

 The biopharma company was founded by Bjarne Due Larsen, Lars Hellerung Christiansen, Leif Helth Jensen, Dan Buxbom, and Florian Schönharting in 1997 as Peptide Probe Technologies ApS, focused on the design and development of peptide-based medicine. In June 2024, Zealand Pharma completed an upsized equity offering of 8.35 million new ordinary shares raising DKK 7 billion (US$1 billion) to fund the development of its pipeline (19). The company is developing several AOMs including a long-activating amylin analogue, petrelintide (ZP8396), and GLP-1/GLP-2 receptor dual agonist, dapiglutide. In the first half of 2025, the company expects to initiate a Phase IIb trial with petrelintide in overweight or obese patients without T2D, and a Phase Ib combination trial with petrelintide and dapiglutide (20–21). In January 2025, the company appointed Steven R. Smith, MD as senior global medical advisor in Obesity to help advance Zealand’s peptide-based assets (22).

 January/February2025 digital issue. It was later published in 

The pharma and biotech industry continues to explore new modalities and targets that modulate the brain-gut axis. Late in 2024, Sanofi strategically invested in Italy-based Resalis Therapeutics to gain access RES-010, a first-in-class antisense oligonucleotide targeting miR-22, that plays a pivotal role in the molecular pathways underlying obesity (23). Meanwhile, scientists at the National Cancer Research Centre (CNIO), USA have identified a new mitochondrial protein (MCJ/DnaJC15) involved in brown fat thermogenesis that may present promising new targets for obesity and related metabolic disorders (24). There is still significant room in the multi-billion AOM market to make a mark.

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7. Carmot Therapeutics. Carmot Therapeutics Announces Completion of Acquisition by Roche. News Release. 29 Jan. 2024.
8. Eli Lilly. Lilly to Acquire Versanis to Improve Patient Outcomes in Cardiometabolic Diseases | Eli Lilly and Company. News Release. 14 July 2024.
9. Taylor, P. Metsera Lands with $290m to Take on Obesity Giants. Pharmaphorum. 19 April 2024.
10. Jensen, M.H.; Sanni, S.J.; Riber, D.; et al. AT-7687, a Novel GIPR Peptide Antagonist, Combined with a GLP-1 Agonist, Leads to Enhanced Weight Loss and Metabolic Improvements in Cynomolgus Monkeys. 

, 88, 102006.
11. Antag Therapeutics Antag Therapeutics Announces €80 Million Series A Financing. News Release. 4 Dec. 2024.
12. Antag Therapeutics. Antag Therapeutics Announces FDA Clearance of Investigational New Drug (IND) Application for Lead Molecule, AT-7687. News Release. 9 Oct. 2024.
13. Gubra. Gubra announces positive GUBamy Phase 1 SAD data (correction). News Release. 13 Nov. 2024.
14. Gubra. Gubra Announces New Collaboration with Amylyx Pharmaceuticals to Develop a Novel Long-acting GLP-1 Receptor Antagonist. News Release. 30. Dec. 2024.
15. Gubra. Gubra Announces Discontinuation of Development of NPY2R in Obesity with Boehringer Ingelheim. News Release. 31 Oct. 2024.
16. Gubra. Gubra Appoints New Chief Operating Officer. News Release. 15 Jan. 2025.
17. Verdiva Bio. Verdiva Bio. News Release. 9 Jan. 2024.
18. Scimind Biosciences. Sciwind Biosciences Announces Global Licensing and Collaboration Agreement for Metabolic Disease Portfolio. 10 Jan. 2025.
19. Zealand Pharma. Zealand Pharma Announces Completion of an Upsized Equity Offering of 8.35 million New Ordinary Shares Raising Proceeds of USD 1 billion/DKK 7 billion. News Release. 25 Jun. 2024.
20. Zealand Pharma. Zealand Pharma Announces the First Participant Enrolled in People with Overweight or Obesity. News Release. 10 Dec. 2024.
21. Zealand Pharma. Zealand Pharma Announces Positive Topline Results From 13-Week Phase 1b Multiple Ascending Dose Clinical Trial With GLP-1/GLP-2 Receptor Dual Agonist Dapiglutide. News Release.
22. Zealand Pharma. Steven R. Smith, MD, joins Zealand Pharma as Senior Global Medical Advisor in Obesity. 7 Jan. 2025.
23. Resalis Therapeutics. Resalis Therapeutics Gains Strategic Equity Investment from Sanofi. News Release. 28 Oct. 2024.
24. Cicuéndez, B.; Mora, A.; López, J.A.; et al. Absence of MCJ/DnaJC15 Promotes Brown Adipose Tissue Thermogenesis. 

Cheryl Barton is director of Pharmavision, info@pharmavision.co.uk.


Vol. 37, No. 1
January/February 2025
Pages: 16–17

When referring to this article, please cite it as Barton, C. Next-Generation Anti-Obesity Medicines. 

European biopharma companies are looking beyond GLP-1s.

Next-Generation Anti-Obesity Medicines

On 1 Jan. 2025, the European Medicines Agency (EMA) introduced a new legal framework, fees, and charges for its regulatory activities and services to medicine developers (1). The New Fee Regulation (NFR) is governed by Regulation (EU) 2024/568 which amended Regulations (EU) 2017/745 and (EU) 2022/123 of the European Parliament and the Council (EPC) and repealed Regulation (EU) No 658/2014 and Regulation (EC) No 297/95 (2–5).

Since the EMA became operational in 1995, it has depended on “fees payable” to offset the cost incurred for providing a range of activities and services listed in the Council Regulation (EC) No 297/95. EMA and the National Competent Authorities (NCA) need to receive efficient funding to carry on their activities and “ensure an efficient, responsive, and innovative regulatory system in Europe for human and veterinary medicines,” according to Jean-Michel Mastio, head of the Finance Department at EMA (6). The EMA budget is currently around €0.5 billion, and a large part of this budget is used to support the NCAs; more than 95% of the budget is generated from fees, and the remainder is contributed by the European Union (EU).

The fees were introduced in 1995 and recognize 23 different basic procedural fees including those associated with applications for certificates, marketing authorization applications (MAA), scientific advice (SA), inspections, as well as supplemental authorization of additional strengths and pharmaceutical forms (7). Other fee-related regulations include Regulation (EU) No 658/2014 regarding pharmacovigilance inspection activities, and Regulation (EC) No 2049/2005 for reduced fees associated with non-orphan medicinal products submitted by small and medium-sized businesses (SMEs), medicinal products with orphan designation (OD) or paediatric use, advanced therapy medicinal products (ATMPs), and medicinal products for preparedness against biological agents (8–11).

Since 2015, the European Commission (EC) has been working on reviewing the EMA fee system. The EMA’s user fee system was evaluated in 2019 to assess if the fees were in alignment with the underlying activity cost of the EMA and NCAs, to identify areas for improvement, and to reduce the complexity of the fee system (12). EMA previously amended fees in 1999 and 2005 to ensure there was adequate provision for the services it provides. Fees increase on an annual basis to adjust for inflation, with the last adjustment having been published in April 2022, which resulted in an increase in the fee level by 0.3% for 2020 and 5.3% for 2021 (13).

In December 2022, the EC published a proposal for the revised EMA Fee Regulation, and the EPC agreed on the revised EMA Fee Regulation in September 2023. It was adopted and formally published on 7 Feb. 2024 (6). In 2024, EMA published a working arrangements document that clarified the requirements and terminology of the new regulation, established fee reductions for certain types of services, and provided further details on payment modalities; the working arrangements were adopted by EMA’s Management Board in June 2024 (11). The key principles and objectives for the NFR are: harmonization, flexibility, alignment, and sustainability. The new fees are “proportionate” instead of the previous “standard” or flat-rate fees.

The provisions outlined in Regulation (EU) 2024/568 will apply to all requests validated and starting in January 2025 and will impact human and veterinary medicines. A few examples of the new fees compared with previous fees (2024) are summarized in 

 (14). Applications with OD or drugs for use in paediatrics will be exempt from fees; however, there are some special circumstances where administrative fees will be applicable. Namely, if an applicant submits the application and withdraws it after 24 hours or EMA rejects the application during the validation phase (15). If an applicant applies for certificates, parallel distribution, or SA, EMA will issue an invoice, and once the payment is received it will deliver the service. The application will be cancelled if EMA does not receive payment within 30 days (15).

A few examples of fees payable under New Fee Regulation (NFR) versus previous regulation. MAA is marketing authorization applications.

For veterinary medicine, EMA has adopted a single framework to deliver a streamlined fee system, and the fees payable to EMA will be proportionate to the work carried out based on the complex evaluation, workload, and actual costs for the services delivered by EMA and NCA (6). The key changes to the fee regulations for veterinary medicines are summarized in 

. EMA will charge a fee for certificates, SA, and MAAs, and the amount payable will be dependent on the type of active substance (i.e., new active substance or known active substance). The fee will be calculated after the submission of the application in conjunction with the related fee reductions. For more details, see Annex I, Section 2, or Annex II, Section 1, of the Fee Regulation and Chapter 1.1 of the Fee Regulation Working Arrangements (11,16,17).

High-level changes to fees based on new fee regulation from 1 Jan. 2025.

Overhauling of the EMA fees legislation is long overdue and should provide EMA and NCAs with sufficient funds to ensure they can continue to deliver high-quality services and adapt to future market demands. The simplified proportionate fee structure should be easier to navigate but may lead to significant increases in the fees payable for medicine developers particularly when obtaining or maintaining MAAs from January 2025 onwards (14).

1. EMA. Fees Payable to the European Medicines Agency. 

. 1 Jan. 2025.
2. EMA. Regulation (EU) 2024/568. 

. 4 Feb. 2024.
3. EMA. Regulations (EU) 2017/745. 

. 5 April 2017.
4. EMA. Regulation (EU) 2022/123. 

. 25 Jan. 2022.
5. EMA. Regulation (EU) No 658/2014. 

. 15 May 2014.
6. EMA. New Fee Regulation. Webinar. 20 June 2024.
7. EMA. Council Regulation (EC) No 297/95. 

. 10 Feb 1995.
8. EMA. Regulation (EU) No 658/2014. 

. 15 May 2014.
9. EMA. Regulation (EC) No 2049/2005. 

. 15 Dec. 2005.
10. EMA. Regulation (EC) No 141/2000. 

. 22 Jan. 2000.
11. EMA. Fee Regulation working arrangement. 

. 13 June 2024.
12. EC. Evaluation of the European Medicine Agency’s Fee System. 18 Sep. 2019.
13. AgencyIQ. What You Need to Know about the Status of the Proposed EMA Fees Regulation. 

. 3 Nov. 2023.
14. DLCR. EMA Updated Fees: What Does This Mean for My Applications? 9 Aug. 2024.
15. Vignol, C. EMA – New Fee Regulation (NFR). RPN Group.com. 9 Aug. 2024.
16. EMA. Annex I to Regulation (EU) 2024/568; Q&As. 

. 14 Nov. 2024.
17. EMA. Annex II to Regulation (EU) 2024/568; Q&As. 


Vol. 37, No. 1
January/February 2025
Pages: 6–7

When referring to this article, please cite it as Barton, C. Introducing a New Legal Framework, Fees, and Charges. 

EMA introduced its New Fee Regulation in January 2025, but what impact will the new fees and charges have on medicine developers? 

Introducing a New Legal Framework, Fees, and Charges

Human head shape made from a large grid of pins connected with string. Communication technology and mental health concept | Image Credit: © ink drop - Stock.adobe.com

Over the past decade, researchers have developed a greater understanding of the relative contributions of the environment, genetic, and epigenetic influences on the onset and progression of Parkinson’s disease (PD). New strategies have emerged that seek to modulate inflammatory cellular mediators, mitochondrial function, and/or halt the accumulation of synuclein and neuromelanin (1–3).

In August 2024, German-based Centogene NV released new data from the landmark Rostock International Parkinson’s Disease (ROPAD) Consortium Study which aimed to characterize the genetics of PD to better understand disease progression, diagnosis, and treatment for patients (4). The study identified that approximately 15% of 12,580 patients studied harboured genetic variants that present new opportunities for genetic testing and the development of innovative therapies such as cell and gene therapies (CGTs) (5).

New formulations and novel non-biological drugs

More than 10 million people worldwide are living with PD, and it is now classed as the fastest-growing neurological condition in the world (6,7). Several companies such as NeuroDerm (a Tanabe Pharma company), Cerevel (an AbbVie company), and Swiss-based Contera Pharma A/S are working on non-biological agents with immediate or long-duration action to improve the symptoms of PD (8–10) (

). In October 2024, the US Food and Drug Administration (FDA) finally approved AbbVie’s Vyalev (foscarbidopa and foslevodopa), the first 24-hour infusion of levodopa-based therapy for motor fluctuations in adults with advanced PD (11). This single infusion helps reduce the pill burden whereby PD patients may take more than 20 tablets a day to control their symptoms. AbbVie gained approval for the drug, under the trade name Produodopa, from the European Commission (EC) in January 2024 (12). In May 2024, Portuguese BIAL Holding S/A launched a novel sublingual film formulation Kynmobi (apomorphine hydrochloride) in Germany, for the intermittent treatment of off episodes in adult patients with PD who are not sufficiently controlled by oral anti-Parkinson medication (13).

Pharma companies are actively pursuing the development of drugs that target novel pathways involved in the underlying mechanism of PD (

). These include BIAL’s BIA 28-6156, a small-molecule activator of glucocerebrosidase (GCase), a lysosomal enzyme involved in the breakdown of glycosphingolipids and UK-based Neurolixis’ NLX-112 (befiradol), a novel 5-HTA1A receptor agonist that has completed a Phase IIa proof-of-concept trial for dyskinesia in PD (14–16).

Innovative non-biological drugs under clinical development for Parkinson’s disease (PD).

Innovative biological therapies are progressing through trials

Several companies are looking to harness biologics to halt the accumulation of detrimental proteins such as alpha-synuclein (a-syn), which has been implicated in the pathology of PD (

). US-based AC Immune is evaluating ACI-7104 in Phase II, a monoclonal antibody (mAb) that has been shown to inhibit the accumulation of a-syn aggregates in preclinical animal models and the brain tissue of PD patients (17). An alternative approach is the use of adeno-associated virus (AVV) vectors to deliver genes that selectively modulate the production of proteins such as glutamic acid decarboxylase (GAD) to increase gamma-aminobutyric acid (GABA) levels, or glial cell line-derived neurotrophic factor (GDNF) to boost dopamine levels. In January 2024, Asklepios BioPharmaceuticals (AskBio, a subsidiary of Bayer AG) released positive data with its AAV2-GDNF showing that the one-time bilateral delivery of AB-1005 gene therapy was well-tolerated, and no serious adverse events (AEs) were observed (18). In October 2024, US-based MeiraGTx Holdings released positive top-line data from its clinical bridging study with MGT-GAD-025, an AAV-GAD, resulted in a significant and clinically meaningful improvement in Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) from baseline to Week 26 in patients with idiopathic PD (IPD) (19).

Cell and gene therapies under clinical development for the treatment of Parkinson’s disease (PD).

Cell-based therapy is expected to provide an alternative route to treat PD through the surgical injection of autologous induced pluripotent stem cell (iPSC)-derived dopamine neurons into the putamen, the brain region affected in PD. Denmark/China-based iRegene is evaluating chemically induced human dopaminergic neuron precursors derived from iPSCs to treat moderate to severe PD; the company entered clinical development with its gene therapy NouvNeu001 in the second half of 2023 (20). Similarly, Massachusetts-based BlueRock Therapeutics (a subsidiary of Bayer AG) has released promising Phase I follow-up data from its safety trial with its cell-based therapy bemdaneprocel (MSK-DA01) (21). Alternatively, Australia-based Living Cell Technologies (LCT) is developing an alginate-coated capsule containing clusters of neonatal porcine choroid plexus cells that contains a range of factors that support nerve cell functions and protective enzymes that are crucial for nerve growth and healthy functioning in PD patients (22).

Centogene NV and ROPAD consortium publish data from a landmark study identifying genetic variants that may respond to innovative cell and gene therapies.