Repare Therapeutics Inc.

We are a clinical-stage precision oncology company focused on discovering and developing new treatments using our proprietary synthetic lethality approach. Synthetic lethality (SL) is a clinically proven method in drug development where a deficiency in either of two genes is tolerated, but simultaneous deficiencies in both genes cause cell death. Cancer cells with a mutation in one gene of an SL pair are vulnerable to therapies targeting the other gene. We utilize our proprietary, genome-wide, CRISPR-enabled SNIPRx platform to identify and develop highly targeted cancer therapies that specifically treat cancers due to genomic instability mechanisms, including DNA damage repair. In January 2025, we realigned resources and reprioritized our clinical portfolio to focus on advancing our Phase 1 clinical programs, RP-3467 and RP-1664. We also intend to seek partnering opportunities for our portfolio, including lunresertib and camonsertib, before starting pivotal development. On February 24, 2025, we reduced our workforce by approximately 75%, with remaining employees primarily focused on RP-3467 and RP-1664. Using our SNIPRx platform, we internally developed four clinical therapeutic candidates. RP-3467 is a potential best-in-class inhibitor of adenosinetriphosphatase (ATPase) activity on the helicase domain of DNA polymerase theta (Polθ). Polθ is a synthetic lethal target linked to homologous recombination deficiency (HRD) tumors, including those with BRCA1/2 mutations or other genomic alterations. Data suggest RP-3467 works effectively and synergistically with therapies causing double-stranded DNA breaks, such as PARP inhibition, radioligand therapy (RLT), and various chemotherapies and antibody-drug conjugates (ADCs). Initial data suggest Polθ inhibition may interfere with mechanisms central to PARPi resistance, potentially relevant to marketed PARP 1/2 inhibitors and emerging PARP1-selective inhibitors. In November 2023, we reported preclinical data for RP-3467, showing complete, sustained regressions in combination with PARP inhibitors and compelling anti-tumor activity with RLT and chemotherapy.