Touting an “exceptional” gastrointestinal safety profile for its oral obesity drug candidate in a study of healthy volunteers, Enveda plans to test the asset in people stopping GLP-1 treatment.
A Phase 1 trial has supported the gastrointestinal safety profile of Enveda’s “exercise in a tablet” asset, encouraging the biotech to assess if the drug candidate can maintain the benefits of GLP-1 medicines.
Many patients experience steep weight loss on GLP-1 receptor agonists such as Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy. However, gastrointestinal side effects are common, preventing some people from fully realizing the effects of the drugs. Furthermore, studies have shown that patients regain weight and lose the metabolic benefits of the medicines after stopping treatment.
Enveda designed ENV-308 to address unmet needs around GLP-1 treatment. The drug candidate mimics N-lactoyl-phenylalanine (Lac-Phe), a hormone that is elevated after exercise. In 2022, Stanford University researchers found Lac-Phe suppresses feeding and obesity in mice.
Because the body quickly clears Lac-Phe, Enveda engineered ENV-308 to provide the hormone’s effects while being suitable for daily oral dosing. The biotech received FDA clearance to test the drug candidate in humans last year, leading to Tuesday’s release of topline data from a Phase 1 clinical trial of healthy volunteers.
The 88 healthy adult volunteers enrolled to date tolerated ENV-308 well across the full dose range, the biotech said. Enveda called the gastrointestinal safety profile “exceptional,” though the biotech has yet to share the data behind its tolerability claims. Nevertheless, Enveda said the study suggests the molecule is differentiated from GLP-1 medicines that cause nausea, vomiting and other gut-based side effects. There were no serious adverse events, discontinuations or dose interruptions.
Although the study was not designed to generate evidence of ENV-308’s effect on body weight or other metabolic endpoints, a biomarker endpoint provided early evidence on the molecule’s mechanism of action. Levels of leptin, an appetite-control hormone that can be chronically elevated in people with obesity, fell in study participants, with the steepest declines seen in people with higher baseline levels. The decreases in leptin replicate the results of animal studies.
Encouraged by the data, Enveda will run a Phase 2 trial to test whether ENV-308 can maintain weight loss and other metabolic benefits in people stopping GLP-1 therapy. The biotech plans to assess changes in weight, body composition and other metabolic health markers.
The obesity study is part of a potentially broader development program for ENV-308. Enveda is mulling development of the asset in multiple conditions where exercise may be beneficial, including migraine, inflammatory bowel disease (IBD) and polyendocrine metabolic ovarian syndrome.
A series of financing rounds equipped Enveda to explore the benefits of ENV-308. After closing a $150 million series C round in early 2025, Enveda raised a further $150 million in series D funding six months later. The rounds brought Enveda’s total funding up to $517 million, empowering the biotech to advance ENV-308 alongside assets including eczema prospect ENV-294 and IBD candidate ENV-6946.
