Next-Generation Anti-Obesity Medicines

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 (Table I). 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).

Table I. 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 (Figure 1). 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.

Figure 1. Anti-obesity agents in clinical development. [Image courtesy of author.]

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

Table II. Anti-obesity medicines in clinical development from European biotechs.

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

Antag Therapeutics, Denmark. 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, Denmark. 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, UK. 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).

Zealand Pharma, Denmark. 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).

Future directions

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.

References

1. Dolgin, E. A History of Drugs on the Weight List. Nat. Med. 2012 6 Jun.
2. Melson, E.; Ashraf, U.; Papamargaritis, D.; et al. What is the Pipeline for Future Medications for Obesity? Int. J. Obes. 2024. https://doi.org/10.1038/s41366-024-01473-y
3. IQVIA. A Look at the R&D Landscape in Obesity, Led by GLP-1s. Fiercebiotech, 19 March 2024.
4. Garza, M. FDA Approves Mounjaro (Tirzepatide) for Diabetes Treatment. diaTribe. 13 May 2022.
5. Müller, T.D.; Blüher, M.; Tschöp, M.H.; et al. Anti-obesity Drug Discovery: Advances and Challenges. Nat. Rev. Drug Discov. 2022, 21, 201–223.
6. Quarta, C.; Cota, D. Anti-obesity Therapy with Peripheral CB1 Blockers: From Promise to Safe(?) Practice. Int. J. Obes. 2020, 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. Mol. Metab. 2024, 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. Nat. Commun. 2025, 16(1), 229.

About the author

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

Article details

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

Citation

When referring to this article, please cite it as Barton, C. Next-Generation Anti-Obesity Medicines. Pharmaceutical Technology Europe, 2025, 37 (1), 16–17.