Comprehensive Report on BHV-2100

I. Executive Summary

BHV-2100 is an orally administered, first-in-class, selective Transient Receptor Potential Melastatin 3 (TRPM3) antagonist currently under development by Biohaven Pharmaceuticals. The compound targets the TRPM3 ion channel, a novel mechanism implicated in neuroinflammatory pain signal transmission and the pathophysiology of migraine.[1] Preclinical investigations have demonstrated BHV-2100's capacity for potent pain reversal across various animal models, including models of neuropathic pain and chemotherapy-induced pain, as well as its ability to inhibit the release of Calcitonin Gene-Related Peptide (CGRP), a key mediator in migraine.[1]

Phase 1 clinical trials involving healthy volunteers have established that BHV-2100 is safe and well-tolerated. These studies also revealed favorable pharmacokinetic properties, characterized by rapid absorption and sustained plasma concentrations, which support its advancement into patient populations.[3] Notably, BHV-2100's pharmacological profile is distinguished by its peripheral restriction, aiming to minimize central nervous system (CNS) side effects, and it has not been associated with sedation or the thermoregulatory issues that have complicated the development of other TRP channel modulators.[4]