On February 28, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported financial results for the fourth quarter and full year ended December 31, 2023 (Press release, Repare Therapeutics, FEB 28, 2024, View Source [SID1234640631]).
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"2023 was a year of substantial progress for Repare. We advanced each of the four programs in our portfolio and set the stage for meaningful data readouts and new clinical trial starts this year," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "In particular and as leaders and innovators in PKMYT1 inhibition, we look forward to data readouts across all ongoing lunresertib clinical trials in 2024 and are excited to begin a lunresertib and WEE1 combination clinical trial in partnership with Debiopharm."
2023 and Recent Portfolio Highlights:
Lunresertib
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 American Association for Cancer Research (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 ten patients with heavily pre-treated gynecological tumors at the preliminary recommended Phase 2 dose.
Announced a partnership with Debiopharm to explore the potential clinical synergy of Debio 0123, a highly selective clinical WEE1 inhibitor, and lunresertib, with dosing of the first patient expected to occur in the first half of 2024 and for which the companies have developed substantial pre-clinical validation. Repare will sponsor the global clinical trial as a new arm in the ongoing MYTHIC trial, with costs being shared equally by Debiopharm and Repare.
Camonsertib
Presented initial clinical data from the Phase 1/2 TRESR and ATTACC trials evaluating camonsertib (RP-3500) in combination with three poly (ADP-ribose) polymerase (PARP) inhibitors in a Clinical Trials Plenary Session at the 2023 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.
Upon dosing of the first patient with camonsertib in Roche’s Phase 2 TAPISTRY trial (NCT04589845), Repare earned a $40 million milestone payment from its collaboration with Roche, which was subsequently received in February 2024. 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).
Since inception of the Roche camonsertib collaboration, Repare has earned a cumulative total of $182.6 million pursuant to the Roche collaboration agreement, including the upfront payment, the milestone payment, as well as additional reimbursements from Roche. In February 2024, Repare received written notice from Roche of their election to terminate the Roche collaboration agreement. The termination will become effective in May 2024, at which time Repare will regain global development and commercialization rights for camonsertib from Roche.
RP-1664
Dosed the first patient in the multicenter, open-label Phase 1 dose escalation trial of RP-1664 in adult and adolescent patients with TRIM37-high solid tumors in February 2024. Repare disclosed polo-like kinase 4 (PLK4) as the target of the RP-1664 development program and reported that RP-1664 demonstrated potent and selective inhibition of PLK4 and synthetic lethality in TRIM37-high tumor cells in preclinical studies.
RP-3467
Reported comprehensive preclinical data for RP-3467, a potential best-in-class Polθ ATPase inhibitor. RP-3467 demonstrated complete, sustained regressions preclinically in combination with PARP inhibitors, and compelling anti-tumor activity in combination with radioligand therapy and chemotherapy.
2024 Outlook:
Initiate a Phase 1/1b clinical trial of lunresertib and Debio 0123, a WEE1 inhibitor, in the first half of 2024 as a fourth arm of the ongoing MYTHIC clinical trial.
Report initial data from the Phase 1 MINOTAUR trial evaluating lunresertib in combination with FOLFIRI for the treatment of advanced solid tumors in the first half of 2024.
Disclose additional camonsertib clinical development plans beyond the TRESR and ATTACC clinical trials sponsored by Repare in the second quarter of 2024.
Report data from the dose expansion cohorts of the Phase 1 MYTHIC trial evaluating lunresertib in combination with camonsertib in selectively advanced solid tumors in the second half of 2024.
Report initial data from the Phase 1 MAGNETIC trial evaluating lunresertib in combination with gemcitabine for the treatment of advanced solid tumors in the second half of 2024. Enrollment in this trial is now closed.
Initiation of a Phase 1 dose finding trial of RP-3467 in the second half of 2024.
Fourth Quarter and Full Year 2023 Financial Results:
Cash, cash equivalents, and marketable securities: Cash, cash equivalents, and marketable securities as of December 31, 2023 were $223.6 million. In February 2024, Repare received a $40 million milestone payment from Roche upon dosing of the first patient with camonsertib in Roche’s TAPISTRY trial. The Company believes that its cash, cash equivalents, and marketable securities are sufficient to fund its operations into mid-2026.
Revenue from collaboration agreements: Revenue from collaboration agreements was $13.0 million and $51.1 million for the three- and twelve-month periods ended December 31, 2023, respectively, as compared to $18.2 million and $131.8 million for the three- and twelve-month periods ended December 31, 2022, respectively. The decrease in revenue for the three-month period was due to lower deferred revenue recognized from the Roche collaboration and the BMS collaboration. The decrease in revenue for the twelve-month period was primarily due to a decrease in revenue recognized under the Roche collaboration mainly as a result of the $108.0 million revenue recognized in 2022 pursuant to the satisfaction of the Company’s performance obligations for the issuance of the combined licenses and the clinical trial materials transferred. The decrease in the twelve-month period was partially offset by higher deferred revenue recognized from the BMS collaboration and the Ono collaboration.
Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $35.3 million and $133.6 million for the three- and twelve-month periods ended December 31, 2023, respectively, as compared to $29.9 million and $119.1 million for the three- and twelve-month periods ended December 31, 2022, respectively. The increase in Net R&D expenses for the three- and twelve-month periods were primarily due to higher personnel-related costs and direct external costs related to the progress of our lunresertib clinical program, as well as the advancement of preclinical programs into IND-enabling studies.
General and administrative (G&A) expenses: G&A expenses were $8.6 million and $33.8 million for the three- and twelve-month periods ended December 31, 2023, respectively, compared to $7.9 million and $32.6 million for the three- and twelve-month periods ended December 31, 2022, respectively. The increase in G&A expenses was primarily due to higher personnel-related costs, partially offset by lower D&O insurance premiums and reduced professional fees associated with the Roche collaboration agreement.
Net loss: Net loss was $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, and $31.7 million, or $0.75 per share, and $29.0 million, or $0.69 per share, in the three- and twelve-month periods ended December 31, 2022, respectively.
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.