Repare to advance RP-1664 and RP-3467 into Phase 1 clinical trials in 2024

Repare Therapeutics disclosed polo-like kinase 4 or PLK4 as the target of its RP-1664 development program and reported comprehensive preclinical data for both RP-1664 and the Company’s Pol inhibitor, RP-3467. RP-1664 is a potential first-in-class, selective, oral PLK4 inhibitor that is synthetic lethal with TRIM37 amplification or overexpression in solid tumors. Tumors rely on PLK4 for survival in the presence of high levels of TRIM37. Preclinical studies demonstrate RP-1664 drives potent synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. Elevated TRIM37 is a feature found across a range of solid tumors and in nearly all high-grade neuroblastomas. RP-3467 is a potential best-in-class inhibitor of DNA polymerase theta, or Pol. Pol is a synthetic lethal target associated with homologous recombination deficiency tumors, including those with BRCA1/2 mutations or other genomic alterations. Data suggest that RP-3467 works synergistically with therapies that result in double stranded DNA breaks, such as PARP inhibition, radioligand therapy and multiple chemotherapies and antibody-drug conjugates . Additionally, initial data suggest that Pol inhibition may interfere with mechanisms central to the development of PARPi resistance….We look forward to advancing both RP-1664 and RP-3467 into Phase 1 clinical trials in 2024.”