TIDES USA Day 1: Chugai LUNA18 Kilogram-Scale GMP Production Paper — Oral Cyclic Peptide KRAS Inhibitor Cleared Through 24-Step Liquid-Phase Synthesis
TIDES USA 2026 opens in Boston May 11-14 with a featured presentation on Chugai's LUNA18 (paluratide), an N-alkyl-rich cyclic undecapeptide oral KRAS inhibitor. The corresponding paper in Organic Process Research & Development describes a convergent 24-step liquid-phase synthesis route delivering kilogram-scale GMP material at >98.5% purity and >30% overall yield. LUNA18 binds KRAS, NRAS, and HRAS mutants plus wildtype, inhibiting the inactive-state RAS-GEF protein-protein interaction; it achieves 21-47% oral bioavailability without special formulation. The molecule is in Phase 1 monotherapy and combination-with-cetuximab dose escalation. LUNA18's chemistry is a milestone for the oral-cyclic-peptide-against-intracellular-targets thesis that Bicycle Therapeutics, Circle Pharma, and Unnatural Products are advancing through different platform architectures.