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Repare Therapeutics has three cancer drug candidates in the clinic and another one expected to enter Phase 1 by the end of this year. The biotech aims to ensure it has enough cash to support these programs, including the most advanced of them which recently lost its big pharma partner, so it’s implementing a corporate restructuring that cuts out preclinical and discovery work. The corporate shakeup will cut about 25% of Repare’s workforce, mostly those involved in preclinical work, the company said in its announcement after Wednesday’s market close. Repare is headquartered in Montreal and also maintains operations in Cambridge, Massachusetts. Of Repare’s 179 total employees as of February of this year, 143 are involved in R&D, according to the company’s annual report. Repare develops drugs that leverage a concept called synthetic lethality, in which a deficiency in a gene pair leads to cell death. A deficiency in one gene is not enough to kill a cell. Repare’s small molecule drugs target the other gene in a pair to trigger cell death. The most advanced Repare program is camonsertib, a drug designed to inhibit the DNA damage response protein ATR. presented by Health IT Accelerating Claim Processing: Strategies to Shorten the Life of a Claim These strategies and practices can significantly shorten the life cycle of claims, leading to quicker resolutions and improved financial outcomes. By Greenway Health Two years ago, Roche paid $125 million up front for global rights to camonsertib, which at the time had reached Phase 1/2 testing in a range of tumor types. Repare won’t be getting the up to $1.2 billion in milestone payments laid out in that deal. In February, Repare disclosed the pharma giant had decided to terminate the alliance after “a review of Roche’s pipeline and evolving external factors.” A separate collaboration with Bristol Myers Squibb is ongoing. The Roche termination was effective in May. Camonsertib is still in Phase 1/2 clinical testing. A study of the drug as a monotherapy for non-small cell lung cancer is enrolling patients with ATR-inhibitor sensitizing mutations; preliminary data are expected in 2025. The Repare pipeline also includes lunresertib, which blocks a target called PKMYT1. A Phase 1 test of lunresertib in combination with camonsertib is underway at the recommended Phase 2 dose in patients with ovarian and endometrial cancers. The company said it expects to report data from this study in the fourth quarter of this year, which could set the stage for a registrational study in 2025. Meanwhile, RP-1664, an inhibitor of PLK4, is in Phase 1 testing. The company expects to advance this drug to a Phase 1/2 clinical trial enrolling pediatric patients with high-risk, recurrent neuroblastoma. RP-3647, Repare’s polymerase theta ATPase inhibitor, is on track to begin a Phase 1 dose-finding study in the fourth quarter of this year. In its report of second quarter 2024 financial results on Aug. 6, Repare said its cash position was $208.1 million, which it expected would be sufficient to fund operations into mid-2026. The board of directors approved the strategic reprioritization on Aug. 1, according to an Aug. 28 Repare regulatory filing. No mention of this corporate shake-up was made in the quarterly report. Repare expects to record a one-time cash charge of $1.5 million to $2 million for termination benefits. The restructuring will save an estimated $15 million annually, which extends Repare’s cash runway into the second half of 2026, the company said in the filing. Sponsored Post What Healthcare Can Learn from Costco The path forward is clear: employers must evaluate their health plan the same way they do their Saturday shopping excursion. By Jeff Bak, Imagine360 CEO and President “We acknowledge today the extraordinary contributions and productivity of our discovery team, who have enabled the development of our deep, innovative clinical portfolio,” Repare President and CEO Lloyd Segal said in a prepared statement. “In our mission to rapidly develop new, practice-changing therapies, we will more fully dedicate our resources to our most promising and advanced precision oncology programs to maximize value for patients and for our shareholders.” Illustration: Getty Images

– First patient dosed in a first-in-human study to assess safety and tolerability of MOMA-313 in patients with cancers carrying mutations in DNA repair genes – – MOMA-313 is a highly potent and selective oral polymerase theta helicase inhibitor, displaying best-in-class potential – – MOMA selects MOMA-341, a potentially best-in class Werner helicase inhibitor, as development candidate for second program; IND application filing anticipated in Q1 2025 – CAMBRIDGE, MA, USA I August 19, 2024 I MOMA Therapeutics , a clinical-stage biopharmaceutical company discovering and developing a new generation of precision therapeutics, today announced that the first patient has been dosed in its Phase 1 clinical trial to assess the safety and tolerability of MOMA-313, a novel, highly potent and selective oral polymerase theta helicase inhibitor. MOMA-313 is initially being developed in combination with a PARP inhibitor for patients with solid tumors harboring alterations in certain DNA repair genes, including subgroups of prostate cancer, pancreatic cancer and breast cancer. In parallel, MOMA announced the selection of a development candidate for its second lead program, MOMA-341, an oral potent and selective covalent Werner helicase inhibitor for treatment of cancers with microsatellite instability. An IND application filing with the FDA is anticipated in the first quarter of 2025. “We are excited to be progressing two molecules with best-in-class potential toward the benefit of cancer patients in need in such close proximity,” said Asit Parikh, M.D., Ph.D., chief executive officer of MOMA. “The advance into clinical development for a company founded as an idea on paper a few years back is humbling. This progress serves as a testament to the excellence and unwavering commitment of the entire MOMA team.” “Advancing two highly potent and selective drug candidates derived from our proprietary KNOMATIC platform toward the clinic is a unique privilege,” added Peter Hammerman, M.D., Ph.D., chief scientific officer of MOMA. “The goal with each candidate is to translate groundbreaking science into life-altering medicine.” About MOMA-313 and the Phase 1 Trial MOMA-313 is a potent and selective oral polymerase theta (Polθ) helicase inhibitor. Polθ is involved in the repair of DNA double-strand breaks that arise during DNA replication. The Phase 1 trial ( NCT06545942 ) is a multi-center, open-label study designed to evaluate the safety and tolerability of MOMA-313 as monotherapy and in combination with the PARP inhibitor olaparib for patients where a PARP inhibitor would be expected to provide benefit. Response to PARP inhibitors can be short-lived due to primary and acquired resistance. Pre-clinical studies suggest that combining a PARP inhibitor with a Polθ inhibitor could afford unique mechanistic potential to deepen and prolong that response. About MOMA-341 MOMA is developing MOMA-341 as an oral, potent and selective covalent inhibitor of Werner helicase with a novel chemical scaffold as monotherapy and in combination with chemotherapy and immunotherapy in tumors with microsatellite instability (e.g., colorectal, gastric, endometrial cancers). About the KNOMATIC platform The KNOMATIC platform integrates deep structural insights, advanced hit-finding technologies, and computation-enabled lead optimization to accelerate discovery of novel therapeutics targeting families of highly dynamic proteins, such as ATPases and GTPases. MOMA-313 and MOMA-341 were discovered and developed through the application of the KNOMATIC platform. About MOMA Therapeutics MOMA Therapeutics is a clinical-stage, next-generation precision medicine company dedicated to targeting highly dynamic proteins that underlie human disease via a small molecule approach, utilizing its proprietary KNOMATIC platform. The platform was designed to exploit key vulnerabilities inherent to all dynamic proteins, namely their dependence on well-coordinated, stepwise changes in protein conformation. By focusing on genetically validated targets with high translation potential, MOMA is rapidly advancing its pipeline toward responses in the clinic. In January 2024, MOMA announced a five-year discovery collaboration with Roche focused on critical cancer dependencies. SOURCE: MOMA Therapeutics

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 PARPi, and compelling anti-tumor activity in combination with radioligand therapy (RLT) and chemotherapy Company expects to initiate clinical trials of RP-1664 in 1H 2024 and RP-3467 in 2H 2024 Repare to host conference call and webcast today at 8:00 a.m. ET CAMBRIDGE, Mass. & MONTREAL--(BUSINESS WIRE)-- Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today 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 Polθ 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 Polθ. Polθ is a synthetic lethal target associated with homologous recombination deficiency (HRD) 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 (ADCs). Additionally, initial data suggest that Polθ inhibition may interfere with mechanisms central to the development of PARPi resistance. "We are excited to announce the initial clinical approach for RP-1664 based on highly compelling preclinical data supporting its potential for treating TRIM37-high tumors,” said Lloyd M. Segal, President and CEO of Repare. "We are also pleased to share preclinical data from our RP-3467 program supporting its significant potential across multiple high-value therapeutic opportunities. These programs represent our third and fourth internally developed clinical candidates and provide further confirmation of Repare’s powerful discovery platform. We look forward to advancing both RP-1664 and RP-3467 into Phase 1 clinical trials in 2024." RP-1664 Highlights RP-1664 is a highly potent, selective and bioavailable PLK4 inhibitor that is synthetic lethal with TRIM37 gain of function. RP-1664 demonstrated robust and dose-dependent monotherapy activity in multiple TRIM37-high preclinical models across a variety of tumor types, including breast cancer, non-small cell lung cancer (NSCLC) and neuroblastoma. The Company plans to initiate a Phase 1 dose escalation study of RP-1664 in adult and adolescent patients with TRIM37-high solid tumors in the first half of 2024. RP-3467 Data Highlights RP-3467 is a highly potent and selective inhibitor of the Polθ helicase domain. RP-3467 demonstrates synergy with PARP inhibitor activity, resulting in durable, complete tumor regressions in multiple preclinical models. Preclinical studies also show combination potential with multiple other modalities, including RLT, chemotherapy and ADCs. The Company plans to initiate a Phase 1 dosing finding clinical trial of RP-3467 in the second half of 2024. “Preclinical data for RP-1664 demonstrate early and promising activity in TRIM37-high tumors, including breast cancer, NSCLC and neuroblastoma,” said Michael Zinda, Ph.D., EVP, Chief Scientific Officer of Repare. “The durable, complete regressions observed in the preclinical RP-3467 and PARPi combination studies are also extremely exciting and demonstrate the broad combination potential of our potent and selective Polθ helicase inhibitor. Repare plans to investigate RP-3467 with a focus on its potential as a combination partner across agents that induce double stranded DNA breaks, including RLT, ADCs, and a range of chemotherapies.” Conference Call and Webcast Repare will host a conference call and webcast today, November 15, 2023, at 8:00 a.m. ET. To access the call, please dial (877) 870-4263 (U.S. and Canada) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined to the Repare Therapeutics call. A live webcast will be available in the Investor section of the Company’s website at . A webcast replay will also be archived for at least 30 days. 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 pro 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. About Repare Therapeutics Inc. Repare Therapeutics is a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics. The Company utilizes its genome-wide, CRISPR-enabled SNIPRx® platform to systematically discover and develop highly targeted cancer therapies focused on genomic instability, including DNA damage repair. The Company’s pipeline includes lunresertib (also known as RP-6306), a PKMYT1 inhibitor currently in Phase 1 clinical development; camonsertib (also known as RP-3500 or RG6526), a potential leading ATR inhibitor currently in Phase 1/2 clinical development and partnered with Roche; RP-3467, a preclinical Polθ inhibitor program; RP-1664, a preclinical PLK4 inhibitor; as well as several additional, undisclosed preclinical programs. For more information, please visit and follow @Reparerx on X (formerly Twitter) and LinkedIn. SNIPRx® is a registered trademark of Repare Therapeutics Inc. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 and securities laws in Canada. All statements in this press release other than statements of historical facts are “forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the design, objectives, initiation, timing, progress and results of the Company’s current and future preclinical studies and clinical trials, including specifically the clinical development of RP-1664 and RP-3467 programs; the tolerability, efficacy and clinical progress of RP-1664 and RP-3467; the potential of RP-1664 as a first-in-class oral PLK4 inhibitor and RP-3467 as a best-in-class Polθ inhibitor; and the benefits and ability to discover further targets and clinical candidates from the Company’s discovery platform. These forward-looking statements are based on the Company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause the Company’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate; the impacts of macroeconomic conditions, including the COVID-19 pandemic, the conflict in Ukraine and the conflict between Israel and Hamas, rising inflation, and uncertain credit and financial markets on the Company’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled "Risk Factors" in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022 filed with the Securities and Exchange Commission (“SEC”) and the Québec Autorité des Marchés Financiers ("AMF") on February 28, 2023, and its other documents subsequently filed with or furnished to the SEC and AMF including the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 filed with the SEC on November 9, 2023. The Company expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. For more information, please visit reparerx.com and follow Repare on Twitter at @RepareRx and on LinkedIn at .