China-based generative artificial intelligence (AI)-driven biotech Insilico Medicine has entered into an exclusive license agreement with US firm Exelixis Inc., (NASDAQ: EXEL), granting Exelixis global rights to develop and commercialize ISM3091, a potentially best-in-class small molecule inhibitor of USP1. USP1 has been identified as a synthetic lethal target in the context of BRCA-mutated tumors.
Financial Terms and Milestones of the Agreement
Under the terms of the agreement, Insilico will receive an upfront payment of USD 80 million, to be made during Q3 2023. Additionally, Insilico is eligible to receive future development, commercial, and sales-based milestone payments, as well as tiered royalties on net sales of ISM3091 and other USP1-targeting compounds.
The Role of USP1 in DNA Damage Repair and the Potential of ISM3091
USP1 plays a critical role in DNA damage repair by removing ubiquitin from multiple substrates, including proteins that stabilize the replication fork. ISM3091, discovered using Insilico Medicine’s generative AI platform with extensive multiparameter optimization capabilities, is designed to inhibit the activity of USP1. Preclinical experiments have demonstrated ISM3091’s potent efficacy against multiple tumor cell lines and in vivo models with BRCA mutations, as well as in homologous recombination DNA repair (HRR)-proficient models. The compound shows promise both as a single agent and in combination with PARP inhibitors.-Fineline Info & Tech
