ACHIEVE · ACHIEVE: Development of an oral ACG-based treatment to combat obesity, maintain long-term dieting success and improve metabolic health

Obesity constitutes an alarming global epidemic, exposing billions of individuals to a multitude of metabolic, infectious, & neoplastic health ramifications. While weight reducing interventions of the GLP-1 family are transforming medical weight reductive therapy, long-term weight loss maintenance remains a daunting unmet challenge, with most medically treated individuals rebounding to obesity. In our project, we will generate a first-of-its kind solution to this global need that will involve oral human utilization of microbiome-modulated weight-regulating interventions. In our ERC-funded project (Fluhr et al., Nature 2021), we discovered that depletion of several microbiome-modulated metabolites drives weight gain in smoking-cessation-induced weight gain. Oral supplementation of several of these molecules has led to a generalizable & significant weight reduction across multiple obesogenic conditions.Building on these findings, the ERC-PoC will develop a commercial metabolite-based treatment or supplement, that will safely attenuate weight gain, maintain long-term weight reducing impacts, and improve metabolic functions. The project includes four work packages:(1) Development and production of metabolite-based drugs and/or medical foods (following a rigorous market study in a dual path approach). (2) Testing these molecules for efficacy, mechanism and safety in obese/lean mice. (3) performing a first-in-human trial (using the most efficacious formulation) in obese/GLP-1-treated individuals (4) in parallel, conducting an extensive commercialization effort to translate our findings into a NewCo, based on 1-2 new products. Notably, there is currently no such orally administered long-term solution complementing weight-reducing therapies in maintaining weight over time. As such, our ERC-PoC project will provide a proof-of-concept product/s for prevention & treatment intervention, providing a unique and commercially scalable solution to an important unmet global problem.