ChemDiv’s Discovery Platform Enables Differentiated, Reversible Pan-EGFR Kinase Inhibitors for GFR-Mutant Lung Cancer

ChemDiv has enhanced its discovery platform to support the development of differentiated, reversible pan-EGFR kinase inhibitors specifically for EGFR-mutant non-small cell lung cancer (NSCLC)12.

The platform now incorporates AI-guided chemical-biological design, kinome-wide selectivity modeling, and parallel synthesis targeting broad coverage across both classical and resistance EGFR mutations while sparing wild-type EGFR12.

The upgrades enable partners to achieve molecules with improved safety and tolerability by minimizing wild-type EGFR inhibition, which is essential for next-generation EGFR therapy12.

Programs have advanced from late lead-optimization to process route scouting and multi-gram scale-up, with early CMC (Chemistry, Manufacturing, and Controls) activities such as solid-form assessment, analytical method development, and pre-formulation now underway12.

Innovations include mutant-centric design loops (with AI/ML prioritizing mutant potency and wild-type sparing), reversible chemistry toolkits for tunable non-covalent EGFR binding, and kinome-wide off-target risk modeling12.

Rapid synthesis and learning cycles, as well as CMC-aware discovery approaches, facilitate more efficient progression toward pre-IND (Investigational New Drug) readiness12.

Recent results have shown broad mutant activity with wild-type sparing in cellular assays and favorable pharmacokinetics in preclinical models2.

Multi-gram scale-up, route scouting, solid-form screening, and pre-formulation work are ongoing to support future non-GLP and GLP toxicology and maintain flexibility for combination studies2.

Sources:

1. https://www.biospace.com/press-releases/chemdivs-discovery-platform-enables-differentiated-reversible-pan-egfr-kinase-inhibitors-for-gfr-mutant-lung-cancer

2. https://www.prnewswire.com/news-releases/chemdivs-discovery-platform-enables-differentiated-reversible-panegfr-kinase-inhibitors-for-gfrmutant-lung-cancer-302599522.html