InnovationTherapeutic Taking Gut Hormone Discovery to a $10 Billion Obesity Therapeutics Platform

Obesity drives type 2 diabetes, cardiovascular disease, cirrhosis and cancer. In our first BRC, Imperial researcher, Professor Sir Stephen Bloom demonstrated that a hormone produced in the gut, glucagon-like peptide-1 (GLP-1) not only plays a role
in blood sugar control, but directly suppresses appetite through activity in the brain, now recognised as a key scientific foundation of GLP receptor agonists (GLP-1RAs) which have transformed obesity management worldwide. However, significant needs remained, addressing extreme obesity, improving obesity-related diseases and reducing side-effects.

Supported by the NIHR Imperial BRC, the team built a research platform to develop new combination treatments and improve existing treatments. They demonstrated that combined administration of GLP-1, along with 2 other gut
hormones, oxyntomodulin and PYY (collectively called GOP infusion) improved control of blood glucose and reduced body weight in obese patients with prediabetes/diabetes. The results were better than patients who had gastric bypass
and very low-calorie diets and was one of the first demonstrations that GOP infusion could be an alternative treatment for diabetes and obesity. The team further showed that small alterations in the shape of GLP-1RAs could enhance their blood sugar lowering effects and, importantly, that continuous infusion of these new drug combinations (GLP-1/glucagon receptor co-agonist) was safe, well tolerated and gave significant weight loss within shorter timeframes than currently available
therapies.

From this work, the team amassed a library of approximately 20,000 gut hormonemimicking peptides, and for many, initial laboratory and clinical studies had been conducted within the BRC and the NIHR Imperial Clinical Research Facility. This
library was licensed to an Imperial spinout, Zihipp, which was acquired by Metsera in 2023, with Professor Bloom appointed Head of Research and Development. Metsera developed two key new drug candidates, MET-097i, a biased GLP-1 agonist
reducing injection frequency, and MET-233i, an analogue of a gut hormone called amylin which had strong combination potential. Clinical trials (Phase 2b) showed MET-097i was well tolerated, giving an average weight loss of 14.1% at 28 weeks
with no plateau — raising the prospect of continued loss with longer treatment. This sparked an intense bidding war between NovoNordisk and Pfizer, with Pfizer ultimately acquiring Metsera for $10bn in 2025 to enable a broader reach of Imperial developed technology.