Company: RPTX
Filing Date: 2025-03-03
Form Type: 10-K
Source: 0000950170-25-030405
Chunk: 10

Company: Repare Therapeutics Inc.
Filing Date: 2025-03-03
Form: 10-K
Item: Item 1
Chunk 10
---
 we further presented our preclinical findings in a plenary session at the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities. We initiated the Phase 1 clinical trial of RP-3467 (POLAR) in the fourth 

5

quarter of 2024, as well as dosed the first patient in the POLAR trial with the combination of RP-3467 and olaparib. Upcoming expected milestones include topline safety, tolerability and early efficacy data from the POLAR trial in monotherapy and in combination with olaparib in the third quarter of 2025.

(b)RP-1664 is a potential first-in-class, highly selective, oral PLK4 inhibitor designed to harness the synthetic lethal relationship with TRIM37 amplification or overexpression in solid tumors. Tumors rely on PLK4 for centriole biogenesis in S-phase of the cell cycle when TRIM37, an E3 ligase that reduces pericentriolar material, is high. Preclinical studies demonstrate that RP-1664 selectively inhibits PLK4 and 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 approximately 80% of high-grade neuroblastoma. RP-1664 is the only selective PLK4 inhibitor known to be in the clinic.

We reported comprehensive preclinical data for RP-1664 in November 2023, including deep tumor growth inhibition and regressions in multiple TRIM37-high solid tumor or neuroblastoma xenograft models. The preclinical in vivo animal model evaluations were performed both internally and in collaboration with Children’s Hospital of Philadelphia (CHOP). In February 2024, we dosed the first patient in the LIONS (PLK4 Inhibitor in Advanced Solid Tumors) clinical trial, a multicenter, open-label Phase 1 clinical trial to investigate safety, pharmacokinetics, pharmacodynamics, and the preliminary efficacy of RP-1664. After evaluating safety in adult patients with recurrent solid tumors in the LIONS clinical trial, we expect to move into a Phase 1/2 clinical trial in high risk, recurrent pediatric neuroblastoma, in which children have limited treatment options and high prevalence of TRIM37-altered tumors. Upcoming expected milestones include initiation of a Phase 1/2 expansion trial in pediatric neuroblastoma in the third quarter of 202