Cheryl Barton is director of PharmaVision, 

Cheryl Barton

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.

1. Dolgin, E. A History of Drugs on the Weight List. 

 6 Jun.
2. Melson, E.; Ashraf, U.; Papamargaritis, D.; et al. What is the Pipeline for Future Medications for Obesity? 

. https://doi.org/10.1038/s41366-024-01473-y
3. IQVIA. A Look at the R&D Landscape in Obesity, Led by GLP-1s. 

, 19 March 2024.
4. Garza, M. FDA Approves Mounjaro (Tirzepatide) for Diabetes Treatment. 

. 13 May 2022.
5. Müller, T.D.; Blüher, M.; Tschöp, M.H.; et al. Anti-obesity Drug Discovery: Advances and Challenges. 

, 21, 201–223.
6. Quarta, C.; Cota, D. Anti-obesity Therapy with Peripheral CB1 Blockers: From Promise to Safe(?) Practice. 

, 44 (11), 2179–2193.
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. 

Articles

European biopharma companies are looking beyond GLP-1s.

Next-Generation Anti-Obesity Medicines

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

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).

Since 2019, the number of active clinical trials for PD has remained relatively consistent, with more than 136 trials per year. However, the proportion of disease-modifying to symptomatic therapies has been increasing during the past five years, and the diversity of drug targets across both symptomatic and disease-modifying drugs has also increased. Interestingly, the number of trials investigating drugs aiming to improve non-motor symptoms has expanded and several drugs are now being developed to target inflammation, a key driver of PD progression (23). But despite these significant advances, many drugs still fail to transition from Phase II to Phase III.

National and international organizations and foundations, such as Cure Parkinson’s, the American and European Parkinson’s Disease Association, Michael J. Fox Foundation, National Parkinson’s Foundation, and Parkinson’s UK, have an important role in raising awareness, supporting patients, and funding PD research. Pharma companies including Bayer, Biogen, Genzyme, GlaxoSmithKline, Sanofi, and Pfizer have made multi-million-dollar strategic investment investments, and several life-changing therapies, including CGTs, are steadily progressing through the clinic. If successful, these therapies could help rewire the PD brain circuits and fundamentally change the way patients are treated over the next decade (24).

1. Elsworth, J.D. Parkinson’s Disease Treatment: Past, Present, and Future. 

 May;127(5):785-791.
2. Pajares. M.; Rojo, A.I.; Manda, G.; Boscá, L.; Cuadrado, A. Inflammation in Parkinson’s Disease: Mechanisms and Therapeutic Implications. 

 Jul 14;9(7):1687.
3. Abeliovich, A.; Hefti, F.; Sevigny, J. Gene Therapy for Parkinson‘s Disease Associated with GBA1 Mutations. 

 11(s2): S183-S188.
4. Westenberger, A.; Skrahina, V.; Usnich, T.; et al. Relevance of Genetic Testing in the Gene-targeted Trial Era: The Rostock Parkinson’s Disease study. 

. 147(8) 2652-2667.
5. Centogene. Introducing the ROPAD Consortium: Unlocking Real-world Genetic Insights to Accelerate Treatment Access for Parkinson’s Disease. Webinar. October 2024.
6. Parkinson’s Foundation. Statistics. 

 (accessed 30 Oct. 2024).
7. BBC News. New Parkinson’s Drug Produodopa to be Available on NHS. 16 Feb. 2024.
8. NeuroDerm Ltd. ND0612 (accessed 30 Oct. 2024).
9. Cerevel Therapeutics. Cerevel Therapeutics Announces Positive Topline Results for Tavapadon in Phase 3 Adjunctive Trial for People Living with Parkinson’s Disease | Cerevel Therapeutics. News Release. 18 Apr. 2024.
10. Contera Pharma A/S. Contera Pharma Reports Topline Results from its Phase IIb Clinical Trial ASTORIA, evaluating JM-010 for the Treatment of Parkinson’s Disease Dyskinesia. News Release. 21 May 2024.
11. AbbVie. U.S. FDA Approves VYALEV (foscarbidopa and foslevodopa) for Adults Living with Advanced Parkinson’s Disease. News Release. 17 Oct. 2024.
12. AbbVie. AbbVie Launches PRODUODOPA (foslevodopa/foscarbidopa) for People Living with Advanced Parkinson’s Disease in the European Union. News Release. 9 Jan. 2024.
13. Bial. Bial launches Kynmobi in Germany. News Release. 3 May 2024.
14. Bial. BIA 28-6156. 

. (accessed 30 Oct. 2024).
15. Cavion. Cavion to Present Results of Phase 2 Essential Tremor Clinical Trial in Platform Presentation at the American Academy of Neurology. News Release. 24 Apr. 2019.
16. Neurolixis. Successful NLX-112 Clinical Results were Discussed in an Interview with the Parkinson’s UK Foundation. 15 Jan. 2024.
17. AC Immune. ACI-7104: Updates on Clinical Progress. 2024.
18. AskBio. AskBio Phase Ib Trial of AB-1005 Gene Therapy in Patients with Parkinson’s Disease Meets Primary Endpoint. News Release. 4 Jan. 2024.
19. MeiraGTx. MeiraGTx Announces Positive Data from Randomized, Sham-controlled Clinical Bridging Study of AAV-GAD for the Treatment of Parkinson’s Disease. News Release 15 Oct. 2024.
20. Cai M.; Wei, J.; Ren, X.; et al. NouvNeu001, A Phase 1 Stage Chemically Induced Human Dopaminergic Progenitor Cell Therapy for the Treatment of Mid- to Late-stage Parkinson’s Disease. 2024 International Conference. Abstract Number 700.
21. BlueRock Therapeutics. BlueRock’s Phase I Study with Bemdaneprocel in Patients with Parkinson’s Disease Meets the Primary Endpoint. News Release. 28 Aug. 2023.
22. LCT. NTCELL. Accessed 30 Oct. 2024.
23. Cure Parkinson’s. Parkinson’s Drug Therapies in the Clinical Trial Pipeline: 2024 Update. News Release. August 2024.
24. Kingwell, K. Gene Therapy Zeroes in on Parkinson’s Disease Brain Circuits. 


Vol. 36, No. 10
November/December 2024
Pages: 16–18

When referring to this article, please cite it as Barton, C. European Biotechs Unlocking Parkinson’s Disease. 

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

European Biotechs Unlocking Parkinson’s Disease

On 15 Oct. 2024, the European Federation of Pharmaceutical Industries and Associations (EFPIA) published an article to raise industry awareness that the European Union (EU) is developing a roadmap to advance precision oncology at the country level to address the growing burden of cancer in Europe (1). Cancer remains the second biggest cause of death in Europe. In 2024, the predicted mortality cancer rates are forecast to fall by 6.5% in men and by 4.3% in women in the EU (based on data from the five most populous countries and the United Kingdom). However, the number of deaths is still rising, with a total of 1,270,800 predicted deaths in 2024 in the EU and 172,900 in the UK, due to population growth and ageing (2).

New therapies, along with advances in prevention, screening, radiotherapy, and surgery are helping to save lives, but further collaboration, and partnership are needed. The “#WeWontRest until we beat cancer” campaign is underway (3). On 13 Nov. 2024, the EFPIA Oncology Platform organized a stakeholder roundtable in Brussels to bring together EFPIA member companies—AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Ipsen, Johnson & Johnson, Lilly, Novartis, MSD, Menarini, Pfizer, Roche, Sanofi, Servier, and Takeda—to help define future legislative and policy directions to improve the provision of personalized treatment for cancer patients (4).

The event was hosted by the Committee of the Regions, with scientific support from the European Regional and Local Health Authorities (EUREGHA) and Cancer Patients Europe, and aims to bring together stakeholders—policymakers, regional health authorities, patient advocates, and healthcare providers—to explore the challenges to improve access to precision oncology to ensure optimal and timely treatment and overcome healthcare disparities across Europe.

The EU has been developing policies to move toward personalized medicine (PM) and has made significant investments starting in 2010. As of 2017, €3.2 billion was invested in PM research across the medical innovation cycle ‘from bench to bedside’ from the research framework programs FP7 and Horizon 2020 (5).

In 2021, the European Commission (EC) published its cancer plan for Europe outlining several goals to reverse the rising trend of cancer across the EU (

). Europe’s Beating Cancer Plan was the EU’s response to medical needs and aims to tackle the entire disease pathways from prevention, early detection, diagnosis, and treatment, as well as the quality of life of the cancer patients and survivors (6).

EU initiatives in precision medicine in Europe

Many EU initiatives are underway to advance precision medicine in Europe. On 11. Sept. 2024, the Thematic Network on Advancing Precision Medicine for Europe’s Cancer Patients with artificial intelligence (AI)-powered Imaging held a webinar led by the European Society of Radiology to discuss with health stakeholders how AI-powered cancer care can improve personalized treatment strategies and reduce the burden of cancer (7).

Meanwhile, the Digital Oncology Network for Europe (DigiONE) pilot is underway in Europe. An amount of €3 million has been allocated for technology investment in a proof-of-concept learning health system in a precision oncology platform that aims to identify optimal cancer treatments by learning from every patient, not just those in clinical trials, through privacy-preserving interrogation of their standardized routine electronic health records (8,9).

Roadmap for a European cancer data management and precision medicine infrastructure

Aside from the goals laid out in Europe’s Beating Cancer Plan stakeholders recognize that for European citizens to have access to innovative precision medicines there is a need to develop a gold-standard cancer data management system. This will rely on three key elements: adopting standardized data formats; ensuring robust data privacy; educating professionals about the infrastructure’s benefits and leveraging cutting-edge technologies to transform cancer care (10).

Further work is needed to refine the EU roadmap on precision oncology but significant steps have already been taken to put in place the framework to reverse the rising trend of cancer across the EU. Stakeholders should keep abreast of the situation and can access details of the advancing precision oncology agenda in the EU online, via the EFPIA (11).

1. EFPIA. Advancing the Precision Oncology Agenda in the EU: Developing a Roadmap at Country Level to Address the Growing Burden of Cancer in Europe. Guest Blog. 15 Oct. 2024.
2. Santucci, C.; Mignozzi, S.; Malvezzi, M.; et al. European Cancer Mortality Predictions for the Year 2024 with a Focus on Colorectal Cancer. 

35 (3) 308–316.
3. EFPIA. #WeWontRest Until We Beat Cancer. 

Accessed 22 Oct. 2024.
4. EFPIA. Advancing the Precision Oncology Agenda in the EU. Brussels, Belgium. 13. Nov. 2024.
5. Nimmesgern, E.; Norstedt, I.; Draghia-Akli, R. Enabling Personalized Medicine in Europe by the European Commission‘s Funding Activities. 

 14 (4) 355–365.
6. European Commission. 

. Communication Paper, 2021.
7. Nikolski, M.; Hovig, E.; Al-Shahrour, F.; et al. Roadmap for a European Cancer Data Management and Precision Medicine Infrastructure. 

5, 367–372.
8. Mahon, P.; Chatzitheofilou, I.; Dekker, A.; 

 A Federated Learning System for Precision Oncology in Europe: DigiONE. 

 30, 334–337.
9. Nahon. P. Building a Digital Oncology Network for Europe (DigiOne) The Digital Institute for Cancer Outcome Research (DigiCore). 

Accessed 22 Oct. 2024.
10. European Commission. Recording—EUHPP Live Webinar—How to Advance Precision Medicine for Europe’s Cancer Patients with AI-powered Imaging (11 September 2024). News Announcement, 11 Sep. 2024.
11. EFPIA. Advancing the Precision Oncology Agenda in the EU. 13 Nov. 2024


Vol. 36, No. 10
November/December 2024
Pages: 9–10

When referring to this article, please cite it as Barton, C. Advancing the Precision Oncology Agenda in Europe. 

The European Commission has developed a roadmap aimed at reversing the rising trend of cancer across the European Union. 

Advancing the Precision Oncology Agenda in Europe

cosmetic molecule and chromosome background | Image Credit: ©Thongden_studio - stock.adobe.com

Over the past century, life expectancy has dramatically increased in most parts of the world, but humans are spending more years in poor health than at any point in history (1). However, technological and scientific advances have increased our understanding of the ‘hallmarks of ageing’ resulting in molecular and cellular changes that lead to the modulation of mitochondrial dysfunction, inflammation, and cellular senescence (2).

This article was published in the October 2024 print issue of 

Ageing is emerging as a druggable condition with multiple pharmaceuticals able to alter the pace of ageing in model organisms. Anti-ageing activity has been demonstrated in some US Food and Drug Administration (FDA)-approved drugs such as the immunosuppressant rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, and the anti-diabetic agent, metformin, an AMP-activated protein kinase (AMPK) activator (3). US-based Aeovian Pharmaceuticals and Amplifier Therapeutics are looking to develop next-generation AMPK and mTOR inhibitors in age-related diseases (4,5).

Many biopharmaceutical companies are now prioritizing ageing research for early-stage discovery or therapeutic pipeline development. BioAge Labs, Fauna Bio, and Insilico Medicine are deploying artificial intelligence (AI)-enabled multi-omic platform technologies to identify novel anti-ageing targets. Several experimental drugs—dasatinib, fisetin, navitoclax, and quercetin—have demonstrated senolytic activity, and inhibitors targeting Bcl-2, HSP, tyrosine kinase or P53, are now being evaluated by biopharma as potential senolytics (6). One of the most advanced programmes is Unity Biotechnology’s UBX1325 (foselutoclax), a Bcl-2 inhibitor in Phase II development for the treatment of age-related macular degeneration (AMD) (7).

Several European start-ups are actively pursuing anti-ageing research including Swiss-based Vandria and UK-based clook.bio and Genflow Biosciences.

Vandria mitochondrial therapeutics look promising in neurodegenerative disease models

Vandria is developing novel mitophagy inducers that rejuvenate cells to treat age-related and chronic diseases. The decline in mitochondrial function has been implicated in many age-related diseases including mild cognitive impairment (MCI), neurodegenerative diseases, and muscular disorders. Vandria has demonstrated that removing damaged mitochondria via mitophagy can rejuvenate cells leading to an improvement in cellular functions and the generation of energy or ATP (adenosine triphosphate) (8).

 screening platform and generated a novel pipeline of small-molecule mitophagy inducers to target different tissues and address specific unmet medical conditions. Its lead programme, VNA-318, has completed investigational new drug (IND) studies for central nervous system (CNS) indications including MCI, Alzheimer’s, and Parkinson’s diseases, and other forms of dementia. Its other preclinical programmes include VNA-052 for sporadic inclusion body myositis, VNA-438 for Metabolic Dysfunction Associated Steatohepatitis (MASH), VNA-710 for idiopathic pulmonary fibrosis (IPF), and VNA-897 for an undisclosed target (9).

In February 2024, Vandria was awarded a CHF 2.5 million (US$2.8 million) research grant from the Swiss Innovation Agency Innosuisse to help advance the development of VNA-318 (10). The funds will be matched with CHF 4.6 million from the company initiative to progress VNA-318 into Phase I/IIb clinical trials in 2025. In preclinical animal models, VNA-318, has been shown to improve memory and learning. Additionally, VNA-318 has strong disease-modifying effects in Alzheimer’s and Parkinson’s disease models and has a wide safety window. The company has been issued a composition of matter patent by the US Patent Office covering VNA-318 and other compounds (10).

The company is also advancing the development of another mitophagy lead candidate, VNA-052, for muscle diseases. This clinical programme was awarded a research grant, totaling €1.1 million (US$1.2 million) from Eurostars, a programme co-funded by the European Union (10). In August 2024, Vandria announced the second closing of its Series A financing raising CHF 28.3 million (US$30.7 million). The funds will be used to support its clinical development programmes (11).

Pioneering gene therapies to decelerate the ageing process

Recent advances in gene editing and delivery have allowed scientists to partially reprogramme cells and reverse the effects of ageing (12). Two UK start-ups, clock.bio and Genflow Biosciences, are leveraging human inducible pluripotent stem cells (hiPSC) to prevent and treat age-related diseases:

 was founded in 2020, by Mark Kotter and has attracted more than US$4 million (€3.6 million) in funding (13). The company has developed an ageing model that force-ages hiPSCs to trigger self-rejuvenation. The company deploys unbiased clustered regularly interspaced short palindromic repeats (CRISPR) screens to identify gene candidates that are causally linked to cell rejuvenation. Clock.bio aims to decode the biology of human rejuvenation across the entire human genome and generate a comprehensive atlas of disease and rejuvenation targets for clinical translation (14).

 was founded in 2020 and has R&D facilities in Belgium. Its lead compound, GF-1002, a suspension of an adeno-associated virus vector-based (AAV-based) gene therapy that delivers the centenarian variant of the sirtuin 6 (SIRT6) gene, a gene intricately linked to cellular stress responses that can promote longevity in mice. GF-1002 has demonstrated promising preclinical results and is due to enter clinical development in 2025 for the treatment of MASH (15). In January 2024, Genflow established two technological innovation partnerships with Revatis SA and with EXO Biologics to develop advanced therapy medicinal products (ATMPs) in sarcopenia and Werner Syndrome, respectively (16). In April 2024, Genflow raised £715,000 (US$959,000) through the placing and subscription for new stock organized by Capital Plus Partners (17). Genflow has been awarded a European Patent with the University of Rochester, New York, for SIRT6 in the prevention and treatment of age-related diseases (18).

In the United States, numerous companies are also pursuing cellular reprogramming strategies including Altos Labs, Longeveron, Retro Biosciences, Rejuvenate Bio, and Turn Biotechnologies (19–23).

Great strides have been made in anti-ageing longevity research, numerous drug targets have been identified, and several agents are progressing steadily through the clinic. In 2021, venture capitalists invested $9.26 billion (€8.3 billion) in this area, with cellular reprogramming and rejuvenation attracting the most attention (24). Pharma has announced several partnerships in this space including Eli Lilly/Fauna Bio, Sanofi/Insilico Medicine, and Pfizer/VitaDAO. While US biotechs dominate the scene, European and UK start-ups are gaining traction, and there are significant opportunities for pharma to expand their foothold and take a more proactive approach in the treatment of chronic age-related diseases.

We’re Spending More Years in Poor Health than at Any Point in History. How Can We Change This?

Hallmarks of Aging: An Expanding Universe

Faragher, R. Anti-ageing Treatments: These Two Drug Types are Being Investigated. 

Aeovian Pharmaceutical doses first participants in Phase 1 Clinical Trial, Strengthens Leadership Team, and Raises Additional $50 million Financial

Amplifier Therapeutics. Amplifier Therapeutics, a Cambrian Bio Pipeline Company, Doses the First Patients in the Phase 1B Clinical Trial and Closes New Financing fromFuture Ventures and RA Capital Management. New Release, 17 Oct. 2023.

Senolytics: from Pharmacological Inhibitors to Immunotherapies, a Promising Future for Patients’ Treatment

Lobo, A. Parkinson’s Grant will Advance VNA-318 for Parkinson’s, Age-related Diseases. 

Hevolution Foundation and Dolby Family Ventures join Vandria’s 2nd Series A closing, bringing the total round to $30.7M (CHF 28.3M) to Progress the Mitophagy Inducer VNA-318 into CNS Clinical Development

Cellular Rejuvenation: Molecular Mechanisms and Potential Therapeutic Interventions for Diseases

Clock. bio Launches to Decode Rejuvenation Biology Across the Human Genome

A White Paper for Rejuvenation Therapies and Blueprint for Clock.bio

Secures Two Research Grants from Belgium’s New Technological Innovation Partnership

Genflow Biosciences Plc Successful Placing and Subscription To Raise £715,000, Grant of Warrants and PDMR Notifications

Genflow Biosciences Plc Announced the Publication of a Key European Patent in Partnership with the University of Rochester, New York

Altos Labs Launches with the Goal to Transform Medicine through Cellular Rejuvenation Programming

Longeveron Announces Second Quarter 2024 Financial Results and Provides Business Update

Rejuvenate Bio Announces New Preclinical Research Evaluating Cellular Reprogramming for Age Reversal

Turn Biotechnologies Reports Historic Skin Cell Rejuvenation Breakthroughs at ESDR this Week

Longevity Investment Hits 3.01 Billion in Full Year 2023

Cheryl Barton, PhD,is director of PharmaVision.


Vol. 36, No. 9
October 2024
Pages: 14–15, 18

When referring to this article, please cite it as Barton, C. European Biotech Targeting Anti-ageing. 

Novel mitophagy inducers and gene therapies that restore cellular function and decelerate the ageing process.

European Biotech Targeting Anti-ageing

On 5 Sept. 2024, the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) published high-level principles and recommendations for staff across the European Medicines Regulatory Network (EMRN) regarding the use of generative artificial intelligence (AI), namely large language models (LLMs) (1).

This article was published in the October 2024 issue of

LLMs are widely used by regulatory staff in various daily tasks including education and tutoring, language translation, search and summarizing information, writing assistance, and providing coding language support (2). However, the deployment of LLMs may result in variable results and inaccurate responses, and they can present potential data security risks in terms of confidential information, data protection, and privacy (2). Thus, the guidelines and principles lay the foundation for the safe and responsible use of LLMs so users “avoid pitfalls and risks” (1).

The EMA/HMA’s guiding principles aim to ensure users to do the following:

take appropriate measures to ensure safe input of data, apply critical thinking, and cross-check outputs continuously learn how to use LLMs effectively know who to consult when facing concerns and report issues (2). In addition, the organizational principles:

define governance that helps users have a safe and responsible use, specifying permitted use cases, providing training, and monitoring risks

Overall, the guiding principles provide a working framework to ensure LLMs are used safely and ethically and are effectively implemented in regulatory science and for medicines regulatory activities.

HMA-EMA multiannual AI workplan 2023-2028

The guiding principles represent one of the deliverables from the HMA/EMA 

 published in December 2023 (3). This workplan guides EMA and EMRN in their use of AI, maximizing the benefits while managing the risks and facilitating information sharing. The first version of the Multi-annual AI Workplan focuses on four critical dimensions—guidance, policy and product support; tools and technologies; collaboration and change management; and experimentation—and will be regularly updated under the oversight of the HMA-EMA Big Data Steering Group (BDSG) (3).

Over the coming months and years, EMA’s Committee for Medicinal Products for Human Use (CHMP) Methodology Working Party (MWP) will help to develop the 

document, which will include domain-specific guidance on pharmacovigilance and other areas. From mid-2024 work was initiated on preparations for the European Artificial Intelligence Act (AI Act), which came into force in August 2024, and an observatory will be created to monitor the impact of AI and the emergence of novel systems and approaches (3,4).

The EMRN will survey its capabilities to analyse data including the use of AI, and this survey will be used to inform collaborative efforts to enhance the analytics capability of the ERMN to ensure all parties are compliant with data protection legislation. In addition, a Network Tools policy will be published to help foster collaboration, integration, and reusability of tools and models within the EMRN (3).

The EMRN will continue to work with partners on AI on an international scale including the International Coalition of Medicines Regulatory Authorities and other agencies in the European Union, as well as with academia and the devices sector. Furthermore, the European Specialised Expert Community of the EMA MWP, will establish a Special Interest Area on AI to provide a forum for collaboration and knowledge sharing, and the EU-Network Training Centre will provide a framework and platform to upskill staff on AI and Data Analytics and support the development and delivery of BDSG Data Science Curriculum (3).

EMA and HRA recognize that AI is a rapidly moving field, and it is essential for regulatory personnel to be provided with a structured approach to integrate these tools in their daily tasks while safeguarding information and maintaining trust. EMA is leading by example and has promptly responded to the implementation of the AI Act, which aims to ensure that AI developed and used in the EU is trustworthy and that there are sufficient safeguards in place to protect people’s fundamental rights. Pharma should take heed as the AI ACT will impact all industries, and it will be essential that companies work closely with the AI Office and other relevant authorities to ensure the safe deployment of AI solutions that will be beneficial to society and drive future innovation in the European pharmaceutical industry (5).

Harnessing AI in Medicines Regulation: Use of Large Language Models (LLMs)

Guiding Principles on the Use of Large Language Models in Regulatory Science and for Medicines Regulatory Activities

Multi-Annual Artificial Intelligence Workplan 2023-2028: HMA-EMA Joint Big Data Steering Group

European Artificial Intelligence Act Comes into Force

Barton, C. European Artificial Intelligence Act Comes into Force. 

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

When referring to this article, please cite it as Barton, C. Responding to the Increased Use of Generative AI. 

Regulators, EMA and HMA, have published principles and recommendations 
on the use of LLMs, which are being increasingly used for daily tasks.
