London and San Francisco-based Verdiva Bio Limited has dosed the first patient in a Phase I single ascending dose study of VRB-103, a once-weekly oral amylin peptide analog selective for the amylin receptor subtypes AMY1 and AMY3. The randomized, double-blind, placebo-controlled trial will assess safety and tolerability in healthy participants with elevated body mass index, evaluating VRB-103 both as monotherapy and in combination with VRB-101 (oral ecnoglutide), Verdiva's once-weekly oral GLP-1 analog currently in Phase II. Initial data are anticipated by the end of 2026. If successful, VRB-103 could become the first once-weekly oral amylin peptide, potentially combining the efficacy associated with peptide amylin agonists with the convenience of oral dosing.
VRB-103 is described by Verdiva as the first once-weekly oral amylin peptide analog to enter clinical development. Both molecules rely on the company's proprietary oral peptide delivery platform, an absorption enhancer that enables weekly dosing of peptides that would otherwise require injection. Preclinical data, presented at the American Diabetes Association 86th Scientific Sessions in June 2026, indicated strong potency and high AMY1/AMY3 receptor selectivity relative to the calcitonin receptor, with a pharmacokinetic profile comparable to VRB-101.
Amylin is co-secreted with insulin and promotes satiety, suppresses glucagon and delays gastric emptying. Unlike GLP-1, preclinical studies suggest amylin signaling may also help preserve energy expenditure during weight loss, potentially improving the durability of obesity treatment.
VRB-103's selectivity for AMY1 and AMY3 over the bare calcitonin receptor is pharmacologically deliberate. The calcitonin receptor mediates bone and cardiovascular effects, and non-selective agonism carries off-target liability.
The non-incretin mechanism positions amylin agonism as both a standalone alternative for patients who do not respond to or cannot tolerate GLP-1 receptor agonists, and as a complementary pathway for combination regimens. Preclinical and clinical data indicate that amylin and GLP-1 pathways engage partially overlapping but distinct neural circuits, producing additive weight loss — the rationale behind Verdiva's combination development strategy with VRB-101.