BOULDER, Colo. — Enveda reported positive Phase 1 results for ENV-308, an investigational oral small molecule designed to mimic Lac-Phe, a hormone released by the body during high-intensity exercise.
The company said ENV-308 was well tolerated across 88 healthy adult volunteers, with no serious adverse events, discontinuations or dose interruptions reported. Enveda is now planning additional clinical studies, including a Phase 2 trial evaluating whether the drug can help people maintain weight loss and other metabolic benefits after discontinuing GLP-1 therapies.
ENV-308 was discovered using PRISM, Enveda’s proprietary artificial intelligence platform for identifying naturally occurring biologically active molecules. The drug was engineered to reproduce the effects of Lac-Phe, which is released during intense exercise and after meals and has been associated with appetite and metabolic regulation.
“Many of the benefits of exercise can be traced back to chemical messengers that are released in the body. Until Lac-Phe was characterized, almost none of that chemistry was available to us as a potential path towards a viable medicine. ENV-308 is our attempt to put the chemistry of exercise into a daily tablet, and to offer a sustainable and convenient solution that synergizes with people’s daily habits and supports them on the path to long-term health,” said Viswa Colluru, Ph.D., Founder and CEO of Enveda.
The Phase 1 study was designed primarily to assess safety, tolerability and the behavior of ENV-308 in the body. Enveda said participants tolerated the drug across the tested dose range and that it showed a favorable gastrointestinal safety profile. Gastrointestinal side effects such as nausea and vomiting are among the reasons some patients discontinue GLP-1 medicines.
The study also assessed circulating levels of leptin, a hormone produced by fat cells that helps regulate appetite and energy balance. Enveda said ENV-308 reduced circulating leptin, with the largest reductions occurring among participants who had higher baseline leptin levels relative to their sex.
Because the trial involved healthy volunteers, it was not designed to evaluate changes in body weight or other metabolic outcomes. Enveda said upcoming studies will assess weight, body composition and additional metabolic health markers.
“There is now compelling data in preclinical models indicating that Lac-Phe is involved in regulating several aspects of metabolic, brain, and inflammatory health. The possibility that ENV-308 may mimic these effects in a daily oral tablet in humans is an extremely exciting potential scientific breakthrough,” said Jonathan Long, Ph.D., Associate Professor of Pathology and Institute Scholar at Stanford ChEM-H and an advisor to Enveda.
In animal studies, ENV-308 preserved lean muscle during weight loss and maintained weight loss after weight-loss treatment was withdrawn, according to Enveda. The company said preclinical studies also suggested the drug could complement GLP-1 therapies and potentially allow less frequent dosing, findings that will require confirmation in human trials.
“Unraveling the chemistry of exercise through the lens of AI presents a new frontier for the discovery of the next generation of metabolic medicines. The tolerability profile of ENV-308 observed in the Phase 1 trial, together with the observed effects on leptin, gives strong encouragement for further development of ENV-308 as a potential new class of medicine targeting long-term metabolic health: before, during and after the use of other interventions,” said Nadeem Sarwar, Global Head of Metabolic Strategy & Disease Prevention at Enveda.
Enveda plans to evaluate ENV-308 in people who have discontinued or plan to discontinue GLP-1 therapy, with a Phase 2 trial expected to examine whether the drug can maintain weight loss and other metabolic benefits.
The company is also evaluating ENV-308 for other conditions in which exercise may provide benefits, including migraine, inflammatory bowel disease and polyendocrine metabolic ovarian syndrome, formerly known as polycystic ovary syndrome.
ENV-308 remains investigational and has not been approved for commercial use.
