Repare Therapeutics Doses First Patient in Phase 1 Clinical Trial of RP-3467, a Polθ ATPase Inhibitor

Rhea-AI Summary

Repare Therapeutics (Nasdaq: RPTX) has dosed the first patient in its Phase 1 POLAR clinical trial for RP-3467, a Polθ ATPase inhibitor. The trial will evaluate RP-3467 alone and in combination with the PARP inhibitor olaparib. RP-3467 is Repare's fourth clinical program and has shown promising preclinical results, including complete and durable tumor regressions when combined with olaparib, without additional toxicities.

The POLAR trial (NCT06560632) aims to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of RP-3467. It will enroll approximately 52 patients with advanced solid tumors, including ovarian, breast, prostate, and pancreatic cancers. The study's primary objectives are to evaluate safety and tolerability, and determine a recommended Phase 2 dose for the combination therapy.

Positive

• First patient dosed in Phase 1 POLAR clinical trial for RP-3467
• RP-3467 showed complete and durable tumor regressions in preclinical studies when combined with olaparib
• No additive toxicities observed in preclinical combination studies
• Potential to mitigate PARP inhibitor resistance, addressing an unmet medical need
• RP-3467 is Repare's fourth clinical program, demonstrating pipeline progress

Negative

• None.

Insights

Medical Research Analyst

The initiation of the Phase 1 POLAR trial for RP-3467 is a significant milestone for Repare Therapeutics. This Polθ ATPase inhibitor represents a novel approach in precision oncology, targeting a mechanism that could potentially overcome PARP inhibitor resistance. The trial's design, combining RP-3467 with olaparib, is particularly noteworthy as it addresses a critical unmet need in cancer treatment.

Key points to consider:

• The trial targets advanced solid tumors, including ovarian, breast, prostate and pancreatic cancers, which are often challenging to treat.
• Preclinical data showing complete and durable tumor regressions with no additive toxicities is promising, but clinical validation is crucial.
• The potential to improve efficacy and limit toxicity in combination with radioligand therapy and ADCs expands the drug's possible applications.
• As Repare's fourth clinical program, RP-3467 demonstrates the company's growing pipeline and commitment to innovative oncology treatments.

While this news is positive for Repare's development pipeline, investors should note that Phase 1 trials primarily focus on safety and dosing. Efficacy signals, if any, will be preliminary. The 136 million market cap suggests the market is cautiously optimistic but awaiting more concrete clinical data.

CAMBRIDGE, Mass. & MONTREAL--(BUSINESS WIRE)-- Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today announced the first patient has been dosed in the Company’s Phase 1 (POLAR) clinical trial evaluating RP-3467, a Polθ ATPase inhibitor, alone and in combination with the poly-ADP ribose polymerase (PARP) inhibitor, olaparib. RP-3467 is Repare’s fourth clinical program.

“RP-3467, our potential best-in-class Polθ ATPase inhibitor, has demonstrated highly compelling preclinical results, including complete and durable tumor regressions in combination with olaparib, the leading PARP inhibitor, with no additive toxicities. This combination is designed to meaningfully improve patient outcomes by mitigating PARP inhibitor resistance, a significant area of high unmet medical need,” said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. “In addition, Repare’s previously reported data established the potential for RP-3467 to improve efficacy and limit toxicity in combination with radioligand therapy and chemotherapy-bearing antibody drug conjugates (ADCs), and we look forward to exploring those areas.”

The POLAR clinical trial (NCT06560632) is a multicenter, open-label, dose-escalation Phase 1 clinical trial to investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of RP-3467 alone or in combination with the PARP inhibitor, olaparib, in adults with molecularly selected advanced solid tumors. The study is expected to enroll approximately 52 patients with locally advanced or metastatic epithelial ovarian cancer, metastatic breast cancer, metastatic castration-resistant prostate cancer, or pancreatic adenocarcinoma. The primary objectives of the study are to assess the safety and tolerability of RP-3467 alone and in combination with olaparib, and to define a preliminary recommended Phase 2 dose of RP-3467 in combination with olaparib.

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 1/2 clinical development; camonsertib (also known as RP-3500), a potential leading ATR inhibitor currently in Phase 1/2 clinical development; RP-1664, a Phase 1 PLK4 inhibitor; RP-3467, a Phase 1 Polθ ATPase inhibitor; as well as additional, undisclosed preclinical programs. For more information, please visit reparerx.com and follow @Reparerx on X (formerly Twitter) and LinkedIn.

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, progress and results of the Phase 1 clinical trial of camonsertib in combination with radiotherapy treatment for genotypically-selected cancers; and the Company’s future plans for clinical development of camonsertib; and the tolerability, efficacy and clinical progress of the Company’s product candidates, including camonsertib; 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: the potential that 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 conflict in Ukraine and the conflict in the Middle East, heightened 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; the Company’s ability to realize the benefits of its collaboration and license agreements; 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 Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 filed with the Securities and Exchange Commission (“SEC”) and the Québec Autorité des Marchés Financiers ("AMF") on August 6, 2024, 2024. 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 https://www.linkedin.com/company/repare-therapeutics/.

View source version on businesswire.com: https://www.businesswire.com/news/home/20241014582242/en/

Investor Relations & Media:

Robin Garner

Vice President and Head of Investor Relations

Repare Therapeutics Inc.

investor@reparerx.com

Source: Repare Therapeutics Inc.

FAQ

What is the purpose of Repare Therapeutics' POLAR clinical trial for RP-3467 (RPTX)?

The POLAR clinical trial aims to investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of RP-3467 alone and in combination with olaparib in patients with advanced solid tumors.

How many patients are expected to enroll in Repare Therapeutics' Phase 1 POLAR trial for RP-3467 (RPTX)?

The POLAR clinical trial is expected to enroll approximately 52 patients with locally advanced or metastatic solid tumors, including ovarian, breast, prostate, and pancreatic cancers.

What were the preclinical results of RP-3467 in combination with olaparib for Repare Therapeutics (RPTX)?

Preclinical studies showed that RP-3467 in combination with olaparib demonstrated complete and durable tumor regressions without additive toxicities, suggesting potential for improved patient outcomes and mitigation of PARP inhibitor resistance.

What are the primary objectives of Repare Therapeutics' Phase 1 POLAR trial for RP-3467 (RPTX)?

The primary objectives are to assess the safety and tolerability of RP-3467 alone and in combination with olaparib, and to define a preliminary recommended Phase 2 dose for the combination therapy.