On October 30, 2025 ChemDiv, a global provider of integrated drug discovery solutions, reported kinase inhibitor design enhancements to its discovery platform. The new capabilities strengthen support for partners developing reversible pan‑EGFR inhibitors for EGFR‑mutant NSCLC (non‑small cell lung cancer). This upgrade integrates AI‑guided chem‑bio design, kinome‑wide selectivity modeling, and parallel synthesis to deliver candidates with broad coverage across driver and on‑treatment resistance mutations while minimizing inhibition of wild‑type (WT) EGFR—a profile aimed at improving therapeutic window, safety, and tolerability.
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As a result of these upgrades, a partner collaboration has progressed from late lead‑optimization into process route scouting and multi‑gram scale‑up, with early CMC (solid‑form assessment, analytical method development, and pre‑formulation) now underway.
"Wild‑type sparing is the needle to thread in next‑generation EGFR therapy," said Ilya Baimetov, COO/CTO at ChemDiv. "Our platform brings together structure‑enabled, reversible chemistry space exploration and kinome selectivity risk‑mitigation to help partners design pan‑EGFR molecules that hit the right mutants—and leave WT EGFR largely alone—so the safety margin moves in the right direction."
What’s new in ChemDiv’s pan‑EGFR support
Mutant‑centric design loops: AI/ML and physics‑based engines prioritize potency against classical and resistance mutations while penalizing WT EGFR liabilities. Integrated ADME/DMPK prediction balances potency with exposure and brain/lung distribution targets as defined by program strategy.
Reversible chemistry toolkits: Focused make‑on‑demand libraries and scaffold families for non‑covalent EGFR binding—engineered for tunable residence time, metabolic stability, and efflux navigation.
Kinome‑wide selectivity modeling: Early off‑target risk scoring against a broad kinase panel to drive SAR decisions toward cleaner profiles that support tolerability and combination potential.
Rapid synthesis + learn cycles: Parallel synthesis and micro‑scale PK accelerate SAR hypotheses; "success criteria" dashboards track mutant coverage, WT‑sparing index, and developability in each sprint.
CMC‑aware discovery: Route‑scouting heuristics, green‑chemistry flags, and salt/solid‑form optionality are considered during hit‑to‑lead to de‑risk later manufacturing.
"By aligning mutant coverage, selectivity index, and developability from day one, we’re seeing cleaner, faster paths into scale‑up and CMC." said Roman Timakhov, Research Director at ChemDiv.
Collaboration progress toward scale‑up and CMC
Following demonstration of a differentiated reversible pan‑EGFR profile in lead series (broad mutant activity with WT sparing in cellular assays; favorable PK in preclinical models), ChemDiv and its partner have initiated:
Multi‑gram scale‑up with route scouting and solvent/impurity risk assessment;
Solid‑form and salt screening to support stability and formulation flexibility;
Phase‑appropriate analytical methods (purity, potency, related substances); and
Pre‑formulation to enable non‑GLP and GLP toxicology material supply.
These activities are designed to support pre‑IND readiness while maintaining optionality for combination studies.
(Press release, ChemDiv, OCT 30, 2025, View Source [SID1234657176])