On January 8, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported a corporate update and highlighted key milestones anticipated in 2024 (Press release, Repare Therapeutics, JAN 8, 2024, View Source [SID1234639218]).

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"We significantly advanced our pipeline in 2023 and presented strong data from key programs, notably for lunresertib in combination with camonsertib, and for camonsertib in combination with PARP inhibitors. In addition, we presented compelling preclinical data sets for RP-3467, which we’re developing as a potential best-in-class Polq inhibitor, and for RP-1664, a potential first- and best-in-class PLK4 inhibitor," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "2024 will be a substantial year for Repare as we aim to expand our pipeline to four clinical-stage programs by the second half of 2024, and we expect to share data readouts from ongoing studies of lunresertib combinations."

Recent Accomplishments:

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Presented initial clinical data from the Phase 1/2 TRESR and ATTACC trials evaluating camonsertib (RP-3500/RG6526, now partnered globally with Roche) in combination with three poly (ADP-ribose) polymerase (PARP) inhibitors in a Clinical Trials Plenary Session at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Camonsertib, a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase), showed 48% overall clinical benefit rate in patients with advanced solid tumors across tumor types regardless of choice of PARP inhibitor or platinum resistance, with a favorable safety and tolerability profile. Data from the TRESR trial were also published in Nature Medicine highlighting the clinical benefit of camonsertib in advanced solid tumors.

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Presented initial positive data from its ongoing Phase 1 MYTHIC trial evaluating lunresertib (RP-6306) alone and in combination with camonsertib in patients with advanced solid tumors harboring CCNE1 amplification or FBXW7 or PPP2R1A deleterious alterations at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). Initial combination data included an overall RECIST response rate of 50% in patients with heavily pre-treated gynecological tumors at the preliminary recommended Phase 2 dose.

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Disclosed polo-like kinase 4 (PLK4) as the target of its RP-1664 development program and reported comprehensive preclinical data for both RP-1664 and the Company’s Polq inhibitor, RP-3467, both of which we expect to enter clinical trials in 2024. RP-1664 demonstrated potent and selective inhibition of PLK4 and synthetic lethality in TRIM37-high tumor cells in preclinical studies. RP-3467 demonstrated complete, sustained regressions preclinically in combination with PARP inhibitors, and compelling anti-tumor activity in combination with radioligand therapy (RLT) and chemotherapy.

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Announced a partnership with Debiopharm to explore the potential clinical synergy of Debio 0123, a highly selective clinical WEE1 inhibitor, and lunresertib in a trial expected to start in H1 and for which the companies have developed substantial pre-clinical validation. Repare will sponsor the global study as a new arm in the ongoing MYTHIC study with costs being shared equally by Debiopharm and Repare.

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Enrollment of patients is ongoing in the camonsertib arm of Roche’s TAPISTRY trial ( NCT04589845), a Phase 2, global, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy in patients with unresectable, locally advanced or metastatic solid tumors determined to harbor specific oncogenic genomic alterations. With multiple patients in advanced stages of screening, dosing of the first patient with camonsertib is expected in the near term, which would result in the achievement of a $40 million milestone payment from Roche to Repare. In October 2023, Roche also dosed the first patient in a camonsertib-based arm in its Phase 1b/2 clinical trial of multiple immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (Morpheus Lung; NCT03337698).

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Announced the appointment of Susan M. Molineaux, Ph.D., to its Board of Directors. Dr. Molineaux currently serves as President and Chief Executive Officer at Para Therapeutics and previously served as Chief Executive Officer of Calithera Biosciences and of Proteolix. Additionally, Repare expanded its senior leadership team with the appointment of Daniel Bélanger as EVP of Human Resources.

Anticipated Key Milestones in 2024:

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Initiation of a Phase 1 dose escalation study of RP-1664, a potential first-in-class, oral PLK4 inhibitor, in adult and adolescent patients with TRIM37-high solid tumors in the first half of 2024.

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Initiation of a Phase 1/1b study of lunresertib and Debio 0123, a WEE1 inhibitor, in the first half of 2024.

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Report initial data from the Phase 1 MINOTAUR study evaluating lunresertib in combination with FOLFIRI for the treatment of advanced solid tumors in the first half of 2024.

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Report data from the dose expansion cohorts of the Phase 1 MYTHIC study evaluating lunresertib in combination with camonsertib in selectively advanced solid tumors in the second half of 2024.

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Repare has closed enrollment in the Phase 1 MAGNETIC study evaluating lunresertib in combination with gemcitabine for

the treatment of advanced solid tumors. The Company expects to report initial data from this study in the second half of 2024.

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Initiation of a Phase 1 dose finding study of RP-3467, a potential best-in-class Polq inhibitor, in the second half of 2024.

Cash Position and Financial Guidance

Repare ended 2023 with approximately $223 million in cash, cash equivalents and marketable securities, which is anticipated to fund planned operations into mid-2026.

About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.