Alveus Therapeutics Inc., a clinical-stage biotech with operations in Boston and Copenhagen, has dosed its first patient in a Phase II study of ALV-100, its bifunctional glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist and glucagon-like peptide-1 receptor (GLP-1R) agonist fusion protein, positioning the company to generate controlled evidence on whether this class of molecule can sustain weight loss after patients transition off semaglutide.
The PRESERVE trial is a randomized, double-blind, placebo-controlled study enrolling approximately 220 adults across multiple US sites who have lost at least 10% of body weight and reached a stable weight on semaglutide. Participants will be randomized to one of four ALV-100 dose regimens or placebo for 24 weeks, with the primary endpoint measuring percentage change in body weight from randomization. The design is explicitly a maintenance study — not an induction trial.
ALV-100 combines GLP-1 receptor agonism with GIPR antagonism, a mechanism Alveus believes could support durable weight control with less frequent treatment. The GIPR antagonist component differentiates ALV-100 from semaglutide and from Eli Lilly's tirzepatide, which activates rather than inhibits GIPR. PRESERVE is not designed to compare the two GIP strategies directly; instead, it will test whether monthly ALV-100 can maintain weight loss after patients discontinue semaglutide.