POLQ

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 .

Event featuring Fiona Simpkins, M.D. and Timothy A. Yap, MBBS, PhD, FRCP to take place on October 31, 2023 at 11:00 am ETDOYLESTOWN, Pa., Oct. 24, 2023 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical stage biopharmaceutical company focused on precision oncology through synthetic lethality, today announced it will host a KOL event on Tuesday, October 31, 2023 at 11:00 am ET. The program will feature Dr. Fiona Simpkins, Perelman School of Medicine, University of Pennsylvania, and Dr. Timothy A. Yap, University of Texas MD Anderson Cancer Center, who will discuss the current landscape of treatments and investigational drugs for patients with advanced solid tumors and their role in tumor suppression. The Aprea Therapeutics team will discuss the Phase 1/2a study evaluating its lead program of a highly potent and selective macrocyclic inhibitor of ataxia telangiectasia and Rad3-related (ATR), ATRN-119, in patients with advanced solid tumors having mutations in defined DDR genes. The event will also highlight Aprea’s pre-clinical WEE1 inhibitor, ATRN-1051, with IND filing anticipated by the end of 2023, including the clinical development strategy for the study of ATRN-1051 A live question and answer period will follow the presentations. The session will be available for replay on the News and Events portion of the Investor Relations section of the company’s website. To register for the event, please click here. About Fiona Simpkins, M.D.Dr. Fiona Simpkins is a Professor in the Division of Gynecology Oncology and Department of OB-GYN at the University of Pennsylvania. She is Director of Preclinical Drug Development for the Ovarian Cancer Research Center and a member on the Phase I/Developmental Therapeutics Committee for Gynecological Cancers for the NRG Cooperative Group. Dr. Simpkins completed her OB-GYN residency at Johns Hopkins University and Gynecology Oncology Surgical fellowship at the Cleveland Clinic Foundation. She is board certified in GOB-GYN and Gynecology Oncology. a surgeon and specializes in gynecological cancer surgeries. Her laboratory’s focus is developing strategies to circumvent drug resistance in gynecological cancers. Dr. Simpkins completed a Cancer Research Training in basic science focusing on ovarian cancer signal transduction at the National Cancer Institute. She completed a post-doctoral fellowship at the University of Miami studying ant-estrogen resistance in ovarian cancer. Dr. Simpkins is also a principal investigator for early phase ovarian cancer clinical trials evaluating novel therapies emanating from her laboratory. About Timothy A. Yap, MBBS, PhD, FRCPDr. Timothy Yap is a Medical Oncology Physician-Scientist and Professor based at the University of Texas MD Anderson Cancer Center. He is a Professor in the Department for Investigational Cancer Therapeutics (Phase I Program), and the Department of Thoracic/Head and Neck Medical Oncology. Dr. Yap is Vice President and Head of Clinical Development in the Therapeutics Discovery Division, a drug discovery biopharmaceutical division where drug discovery and clinical translation are seamlessly integrated. He is also the Associate Director of Translational Research in the Institute for Personalized Cancer Therapy, which is an integrated research and clinical trials program aimed at implementing personalized cancer therapy and improving patient outcomes. Dr. Yap’s main research focuses on the first-in-human and combinatorial development of molecularly targeted agents and immunotherapies, and their acceleration through clinical studies using novel predictive and pharmacodynamic biomarkers. His main interests include the targeting of the DNA damage respons (DDR) with novel therapeutics, such as ATR, PARP1, WEE1, POLQ, USP1, PARG, CHK1, ATM, and DNA-PK inhibitors, next generation CDK4 and CDK1-selective inhibitors, YAP/TEAD inhibitors, as well as the development of novel immunotherapeutics. Prior to his current position, Dr. Yap was a Consultant Medical Oncologist at The Royal Marsden Hospital in London, UK and National Institute for Health Research BRC Clinician Scientist at the Institute of Cancer Research, London, UK. About ApreaAprea Therapeutics, Inc. is a clinical stage biopharmaceutical company headquartered in Doylestown, Pennsylvania, focused on precision oncology through synthetic lethality. The Company’s lead program is ATRN-119, a clinical-stage small molecule ATR inhibitor in development for solid tumor indications. Our oral, small molecule WEE1 inhibitor is being advanced to IND submission. For more information, please visit the company website at www.aprea.com. The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Forward-Looking Statement Certain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended related to our study analyses, clinical trials, regulatory submissions, and projected cash position. We may, in some cases use terms such as “future,” “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team and on information currently available to management that involve risks, potential changes in circumstances, assumptions, and uncertainties. All statements contained in this press release other than statements of historical fact are forward-looking statements, including statements regarding our ability to develop, commercialize and achieve market acceptance of our current and planned products and services, our research and development efforts, including timing considerations and other matters regarding our business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are submits to risks and uncertainties including, without limitation, risks related to the success, timing and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials, futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results including, without limitation, any preclinical results or data, which are not necessarily indicative of the final results of our ongoing clinical trials, and the other risks, uncertainties, and other factors described under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we file with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to update such forward-looking statement for any reason, except as required by law. Investor Contact: Mike MoyerLifeSci Advisorsmmoyer@lifesciadvisors.com

GSK101 (IDE705) is being developed as a potential first-in-class Pol Theta Helicase Inhibitor in combination with niraparib in GSK-sponsored Phase 1/2 clinical trial GSK101 and niraparib combination development will focus on advanced solid tumors with HR mutations or HRD, pursuant to the clinical protocol IDEAYA to receive a $7 million milestone payment upon IND acceptance, and potential future aggregate milestones of up to $950 million related to GSK101 Pol Theta inhibitors SOUTH SAN FRANCISCO, Calif., Aug. 21, 2023 /PRNewswire/ -- IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, announced the clearance of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for initiation of a GSK-sponsored Phase 1/2 clinical trial to evaluate GSK101 (IDE705), a small molecule inhibitor of Pol Theta Helicase, in combination with niraparib, the GSK small molecule inhibitor of poly-(ADP-ribose) polymerase (PARP), for the treatment of patients having tumors with BRCA or other homologous recombination (HR) mutations or homologous recombination deficiency (HRD). "There remains an unmet medical need for patients having tumors with homologous recombination mutations, such as BRCA1/2 mutations. Based on Pol Theta's critical role in microhomology-mediated end joining and BRCA reversions, a central mechanism of resistance to PARP inhibitors, we view the niraparib and GSK101 combination as having potential to improve depth and duration of tumor responses that could potentially impact longer-term outcomes for these cancer patients," said Dr. Ramon Kemp, Vice President, Global Head of Oncology Early Development, GSK. "We are pleased to have our fourth potential first-in-class program advance into the clinic with GSK101, and we believe GSK is well-positioned to maximize the value of GSK101 by creating a potential best-in-class combination with niraparib to treat solid tumors. We are also targeting the Werner Helicase development candidate nomination later this year with GSK, which represents our fifth potential first-in-class program," said Yujiro S. Hata, Chief Executive Officer, IDEAYA Biosciences. GSK101 is a potential first-in-class small molecule inhibitor of the helicase domain of DNA Polymerase Theta (Pol Theta). The Pol Theta enzyme facilitates DNA repair through microhomology-mediated end joining (MMEJ), an enzymatic function that enables reversion of BRCA mutations. Approximately 30% of patients who progress following treatment with PARP inhibitors have tumors with MMEJ signatures at reversion sites, reflecting a significant medical need and potential commercial opportunity for GSK101 in combination with niraparib. GSK101 was discovered and preclinically evaluated by IDEAYA in collaboration with GSK. In preclinical studies, the GSK101 and niraparib combination resulted in deeper and more durable regressions or efficacious responses relative to either single agent in BRCA mutant models. GSK is targeting first-in-human studies for GSK101 in the fourth quarter of 2023. GSK is the sponsor of the IND application and plans to develop GSK101 in combination with niraparib in a Phase 1/2 clinical trial for patients with advanced solid tumors who have exhausted standard of care options and who may benefit from a PARP or POLQ inhibitor, pursuant to the clinical protocol. Enrollment may include patients harboring tumors with BRCA or other homologous recombination (HR) mutations or homologous recombination deficiency (HRD). GSK will lead clinical development for the Pol Theta program pursuant to its global, exclusive license to develop and commercialize the Pol Theta Helicase Inhibitor DC (GSK Pol Theta License). GSK is responsible for all research and development costs for the program. IDEAYA is eligible to receive a $7 million milestone payment upon acceptance of the IND by the U.S. Food and Drug Administration (FDA), and a potential additional $10 million milestone payment upon initiation of Phase 1 clinical dose expansion. IDEAYA may potentially also receive further aggregate later-stage development and regulatory milestones of up to $465 million. Upon potential commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones and tiered royalties on global net sales by GSK, its affiliates and their sublicensees ranging from high single digit to sub-teen double-digit percentages, subject to certain customary reductions. About IDEAYA Biosciences IDEAYA is a precision medicine focused oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its early research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets. Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to (i) the clinical focus for and enrollment in the GSK101 Phase 1/2 clinical trial, (ii) the receipt of development and regulatory milestones, (iii) the potential therapeutic benefits of IDEAYA and GSK therapeutics, (iv) the ability to maximize the value of GSK101, (v) the timing of selection of a development candidate for a Werner Helicase inhibitor, and (vi) the timing of first-in-human studies for GSK101. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's Quarterly Report on Form 10-Q filed on August 10, 2023 and any current and periodic reports filed with the U.S. Securities and Exchange Commission. Investor and Media Contact IDEAYA Biosciences Paul A. Stone Senior Vice President and Chief Financial Officer [email protected] SOURCE IDEAYA Biosciences, Inc.