Buloxibutid (C21/VP-01): A Comprehensive Monograph on a First-in-Class AT2R Agonist for Idiopathic Pulmonary Fibrosis

Executive Summary

Buloxibutid is an investigational, first-in-class, orally available small molecule that functions as a potent and highly selective agonist of the Angiotensin II Type 2 Receptor (AT2R).[1] Developed by Vicore Pharma, it is primarily being evaluated for the treatment of Idiopathic Pulmonary Fibrosis (IPF), a chronic, progressive, and ultimately fatal lung disease characterized by an irreversible decline in lung function.[3] The current standard of care for IPF, comprising the antifibrotic agents nintedanib and pirfenidone, offers only a modest benefit by slowing the rate of disease progression and is frequently associated with significant tolerability issues that lead to treatment discontinuation.[5]

Buloxibutid represents a paradigm shift in the therapeutic approach to IPF. Its novel, upstream mechanism of action targets the protective arm of the renin-angiotensin system, which is highly expressed on alveolar epithelial type 2 cells (AEC2s), the progenitor cells critical for lung repair.[7] By stimulating these cells, Buloxibutid promotes a multimodal cascade of effects, including the inhibition of pro-fibrotic signaling, the resolution of existing scar tissue, and the active repair of the alveolar structure.[7]

This unique mechanism provides a strong biological rationale for the unprecedented clinical results observed in the Phase IIa AIR trial. In this study, treatment with Buloxibutid over 36 weeks resulted not in a slowing of functional decline, but in a statistically significant mean improvement in Forced Vital Capacity (FVC), the primary measure of lung function in IPF.[11] This remarkable efficacy signal was coupled with an excellent safety and tolerability profile, notably a lack of the severe gastrointestinal side effects that plague current therapies.[11]