Day 2: Wednesday, September 17Wednesday, 17 September 2025

• Obesity drugs (GLP-1s, ...) decrease food intake & lower metabolic rate. Agents that boost metabolic rate are needed for lasting efficacy
• Adult humans have abundant thermogenic (brown) adipocyte stem cell reservoir in the skeletal muscle vasculature
• Energesis is developing first-in-class small molecules & biologics unlocking brown adipose stem cell differentiation
• Development candidates boost resting metabolic rate, drive selective fat loss, improve glucose control & synergize with GLP-1s

Exploring an innovative beaded oral glucose formulation which reactivates the body's natural nutrient-sensing enteroendocrine cells in the gastrointestinal tract to restore the release of multiple endogenous hormones including GLP-1 and PYY for improved glucose tolerance and weight management

- Gordian's mosaic screening platform enables the parallelized interrogation of genetic targets within living animals, including visceral adipocytes, which are typically challenging to culture.
- Transcriptomic analysis accurately predicted adiposity and insulin sensitivity phenotypes of multiple interventions.
- A novel target has been identified that is suggested to increase adipocyte futile cycling. This target was confirmed to induce weight loss in a preclinical model of obesity.

-NHBE and ACVR1C encode a ligand-receptor pair in the TGF-beta superfamily

-Human genetic loss-of-function of either gene is associated with reduced visceral fat and improvements in other cardiometabolic traits

-Preclinical obesity models support the role of siRNAs targeting these members of the activin pathway can enhance total weight loss, weight loss quality, and prevent weight regain

• RES-101, a first-in-class miR-22 inhibitor, restores lipid biosynthesis and drives adipose browning for sustained reduction of unhealthy fat and improved body composition.

• RES-010 as a disease-modifying backbone that can be synergistically combined with other therapeutic modalities.

• Review of preclinical data supporting ARO-INHBE and ARO-ALK7 as a monotherapy

• Exploring a combination of siRNA targeting ALK7 and Gene X for greater body weight reduction and lean mass preservation
• Exploring a new combination of siRNA targeting Gene A and Gene B for potential improvement in lean mass while limiting weight gain

• Reviewing the impact of the obesity therapeutics on consumer behaviour
• Discussing future changes to the food industry as anti-obesity drugs progress, from ingredient sourcing to retail dynamics

• Discussing the influence of the obesity therapeutics on full patient health and addressing global demand

• How is GLP-1R modulation being harnessed to treat broader diseases?

• What next steps must be taken to better predict wider beneficial health outcomes of obesity therapeutics?

• How is the industry working together to manage the global surge in GLP-1/ obesity drug products?