Comprehensive Intelligence Report: BLU-808, a Novel Wild-Type KIT Inhibitor for Mast Cell-Mediated Diseases

Executive Summary

BLU-808 is an investigational, oral, once-daily small molecule being developed by Blueprint Medicines, a company recently acquired by Sanofi. It is engineered as a highly potent and selective inhibitor of wild-type KIT, a receptor tyrosine kinase that serves as the master regulator of mast cell survival and activation. This positions BLU-808 as a potential first-in-class oral therapy for a broad range of mast cell-mediated inflammatory and allergic diseases, with an initial focus on chronic urticaria and allergic rhinoconjunctivitis.

The therapeutic rationale for BLU-808 is to address the root cause of these conditions by modulating mast cell activity, a more fundamental approach than targeting downstream mediators or activation pathways. This strategy represents a significant expansion for Blueprint Medicines, leveraging its deep expertise in KIT biology—honed through the development of the mutant KIT inhibitor avapritinib for oncology—into the much larger immunology market.

Preclinical data demonstrate a best-in-class profile, characterized by sub-nanomolar potency against wild-type KIT and exceptional selectivity, thereby avoiding off-target kinases associated with the toxicities of earlier-generation inhibitors. This profile translated into a completed Phase 1 study in healthy volunteers that established an exceptionally wide therapeutic window. The trial showed that BLU-808 was remarkably well-tolerated, with no adverse events greater than Grade 1, and demonstrated robust, dose-dependent target engagement, evidenced by serum tryptase reductions exceeding 80%. The pharmacokinetics support a convenient once-daily oral dosing regimen.