Instead of initially targeting CBP/p300, TOLREMO used a phenotypic, target-agnostic screen to find molecules addressing transcriptional addiction. This indirect discovery path led to a chemically distinct drug with a better safety profile than first-generation inhibitors, a key competitive advantage.
First-generation CBP inhibitors are limited by severe thrombocytopenia. TOLREMO's drug has shown no such toxicity in 45 patients, enabling a strategy to pursue the larger, more commercially attractive solid tumor market, rather than being confined to the initial validated indication of multiple myeloma.
The drug's mechanism is to block cancer's stress response. When a primary therapy like an EGFR inhibitor attacks a tumor, the cancer cells use CBP to reprogram and survive. By inhibiting CBP simultaneously, TOLREMO aims to prevent this escape, leading to deeper and more durable patient responses.
The company's Phase 1 trial began as an 'all-comers' study for solid tumors. However, after observing anti-tumor activity at the very first dose level, the team quickly adapted the protocol to enrich for lung cancer patients, demonstrating an agile, data-driven approach to accelerate proof-of-concept.