Quartet is discovering and developing novel small molecule modulators of the de novo BH4 synthesis pathway for the treatment of chronic pain and inflammation.
Quartet’s lead program focused on inhibitors of sepiapterin reductase is in advanced lead optimization with development candidate selection expected in 2H15.
The company’s drug discovery efforts are fully structurally enabled and are focused on demonstrating changes in BH4-related biomarkers that correlate with drug pharmacokinetics and efficacy in preclinical animal models.
• Structure-based drug design – Quartet has built on published crystal structures of the BH4 synthesis enzymes by solving numerous proprietary x-ray co-crystal structures with advanced drug candidates. This structural information continues to be a key driver in our drug discovery efforts.
• Biomarker for target engagement – Having a peripheral measure of target engagement is unusual for a chronic pain program. The ability to nucleate an R&D strategy around correlating drug exposure with a reduction in BH4 in the peripheral nerve tissue and immune system before advancing compounds into preclinical efficacy models is at the core of our research and development strategy. The BH4 biomarker approach will continue to be a valuable tool for assessing target engagement as the program advances into clinical development.
The BH4 synthesis pathway has been implicated in a range of chronic human pain and inflammatory conditions. Quartet is using human genetic and biomarker tools, along with preclinical disease models, to select the ideal early clinical proof-of-concept indications for a modulator BH4 synthesis pathway. In addition, we’re developing a translational biomarker strategy for clearly establishing human target engagement early in Phase 1 clinical trials. This dual indication discovery and translational biomarker-based approach will help de-risk our lead program as it advances through early clinical development.