On March 3, 2025 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a clinical-stage precision oncology company, reported financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Repare Therapeutics, MAR 3, 2025, View Source [SID1234650839]).

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"Our recently implemented re-structuring and the re-prioritization of our clinical portfolio meaningfully extends our cash runway into late 2027. We are now focused on three ongoing Phase 1 clinical trials with readouts expected in 2025: the LIONS trial evaluating our RP-1664 PLK4 inhibitor; the POLAR trial evaluating our RP-3467 Polθ ATPase inhibitor; and our ongoing MYTHIC trial evaluating lunresertib in combination with Debiopharm’s WEE1 inhibitor, Debio 0123," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "Our progress with RP-3467 Polθi is particularly promising. We believe we are leading the field with helicase Polθi – PARPi clinical combinations and look forward to sharing initial data by Q3 this year."

Fourth Quarter 2024 and Recent Portfolio Highlights:

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RP-3467: Potential best-in-class, oral Polθ ATPase/helicase inhibitor
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Repare initiated the Phase 1 clinical trial of RP-3467 (POLAR) in the fourth quarter of 2024, dosing patients alone and in combination with the poly-ADP ribose polymerase (PARP) inhibitor, olaparib. The POLAR clinical trial is a multicenter, open-label, dose-escalation Phase 1 clinical trial designed to investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of RP-3647 alone or in combination with olaparib in adults with locally advanced or metastatic epithelial ovarian cancer, metastatic breast cancer, metastatic castration-resistant prostate cancer, or pancreatic adenocarcinoma.
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Upcoming expected milestones:
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Q3 2025: Topline safety, tolerability and early efficacy data from the POLAR trial in monotherapy and in combination with olaparib.
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RP-1664: First-in-class, oral selective PLK4 inhibitor
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Repare is currently evaluating RP-1664 as a monotherapy in the Phase 1 LIONS clinical trial in adult and adolescent patients with TRIM37-high solid tumors. The LIONS clinical trial is a first-in-human,

multicenter, open-label Phase 1 clinical trial designed to investigate safety, pharmacokinetics, pharmacodynamics and the preliminary efficacy of RP-1664.
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Upcoming expected milestones:
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Q3 2025: Initiation of a Phase 1/2 expansion trial in pediatric neuroblastoma
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Q4 2025: Initial topline safety, tolerability and early efficacy data from the LIONS trial
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Mid-2026: Trial completion and final trial readout of proof-of-concept from the LIONS trial
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Lunresertib (RP-6306) in combination with Debio 0123
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Repare is evaluating lunresertib in combination with Debio 0123, a highly selective brain-penetrant, clinical WEE1 inhibitor, in patients with advanced solid tumors harboring CCNE1 amplification or FBXW7 or PPP2R1A deleterious alterations as part of an ongoing 50/50, cost-sharing collaboration with Debiopharm.
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Upcoming expected milestones:
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Q2 2025: Enrollment completion of MYTHIC trial evaluating lunresertib in combination with DEBIO 0123 (WEE1 inhibitor).
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Lunresertib (RP-6306) and Camonsertib (RP-3500)
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Repare reported positive efficacy and safety data from the Phase 1 MYTHIC gynecologic expansion clinical trial evaluating the combination of lunresertib and camonsertib (Lunre+Camo) at the recommended Phase 2 dose (RP2D) in patients with endometrial cancer (EC) and platinum-resistant ovarian cancer (PROC) in December 2024. Nearly half of patients with gynecologic cancers in the trial maintained progression-free survival (PFS) at 24 weeks, comparing favorably to PFS for current standard of care. Repare intends to seek partnering opportunities for this program as a condition to further advancement of the program into pivotal development and will not continue to develop lunresertib or camonsertib in other studies.
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Other Highlights
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Repare announced a re-alignment of resources and a re-prioritization of its clinical portfolio to focus on the continued advancement of its Phase 1 clinical programs, RP-1664 and RP-3467. In connection with the re-alignment, the Company is reducing its workforce by approximately 75% to extend its cash runway into late-2027.
Fourth Quarter and Full Year 2024 Financial Results:

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Cash, cash equivalents and marketable securities: Cash, cash equivalents and marketable securities as of December 31, 2024 were $152.8 million, as compared to $223.6 million as of December 31, 2023. The Company believes that its cash, cash equivalents, and marketable securities, along with the expected cost-savings from the re-alignment, are sufficient to fund its current operational plans into late-2027.
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Revenue from collaboration agreements: Revenue from collaboration agreements was nil and $53.5 million for the three- and twelve-month periods ended December 31, 2024, respectively, as compared to $13.0 million and $51.1 million for the three- and twelve-month periods ended December 31, 2023, respectively.

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Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $24.5 million and $115.9 million for the three- and twelve-month periods ended December 31, 2024, respectively, as compared to $35.3 million and $133.6 million for the three- and twelve-month periods ended December 31, 2023, respectively.
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General and administrative (G&A) expenses: G&A expenses were $6.3 million and $29.7 million for the three- and twelve-month periods ended December 31, 2024, respectively, as compared to $8.6 million and $33.8 million for the three- and twelve-month periods ended December 31, 2023, respectively.
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Net loss: Net loss was $28.7 million, or $0.67 per share, and $84.7 million, or $2.00 per share, in the three- and twelve-month periods ended December 31, 2024, respectively, and $28.0 million, or $0.67 per share, and $93.8 million, or $2.23 per share, in the three- and twelve-month periods ended December 31, 2023, respectively.