ALV-100
Alveus' lead program ALV-100 - a GIPR antagonist/GLP-1R agonist fusion protein - is a novel approach validated by human genetics showing that GIPR loss-of-function variants are associated with lower BMI and improved cardiometabolic traits.
ALV-100 is designed to harness the synergistic effects of these mechanisms to deliver sustainable weight loss resulting in a reduced treatment burden for patients.
Importantly, this durable dual approach aims to address counterregulatory metabolic mechanisms that drive weight regain and to improve long-term outcomes. We anticipate entering Phase 3 trials in 2027.
ALV-200
Amylin agonism is a clinically validated biology for weight loss. Amylin signals through the calcitonin receptor CTR and the amylin receptors AMYR1, AMYR2 and AMYR3.
Most amylin analogues in clinical development are dual amylin-calcitonin receptor agonists (DACRAs). As with GLP-1R agonists, gastrointestinal adverse effects reduce the tolerability of DACRAs.
The main beneficial metabolic effects of amylin, including lean mass preservation, are suggested to be driven by AMYR3, while gastrointestinal adverse effects such as nausea and aversion are likely due to CTR activation.
In preclinical models, ALV-200 demonstrated selectivity over CTR whilst maintaining weight loss efficacy. Preclinical data suggest a once-weekly dosing profile. ALV-200 is currently in IND-enabling development.
GLP-1 receptor agonism
Drives appetite suppression and initiates weight loss. A well-validated mechanism with a strong body of clinical evidence. ALV-100's GLP-1 component is designed to support weight loss induction as part of its bifunctional approach.
GIPR antagonism
The mechanism the market has not fully solved. Human loss-of-function genetics show GIPR variants may protect against obesity independently of GLP-1. ALV-100's GIPR antagonist antibody is designed with an extended half-life intended to support the infrequent dosing intervals Alveus is investigating in clinical development.
ALV100
Why it matters
The scientific rationale behind ALV-100 is grounded in human genetics: targeting both mechanisms is designed to support weight loss and help address the biology that drives weight regain.
ALV-100 is now enrolling for the Phase 2 long-term maintenance study. Learn more about participation and eligibility.