Repare Therapeutics and Debiopharm Partner to Explore the Synthetic Lethal Combination of PKMYT1 and WEE1 Inhibition in Cancer

Rhea-AI Summary

Repare Therapeutics Inc. (RPTX) collaborates with Debiopharm to investigate the combination of lunresertib, a PKMYT1 inhibitor, and Debio 0123, a WEE1 inhibitor, in a new arm of Repare’s ongoing global MYTHIC study. The Phase 1/1b clinical trial is anticipated to initiate in the first half of 2024. The collaboration aims to explore the synergy between the two compounds and share all costs equally. The combination has shown highly synergistic and promising preclinical data, demonstrating potential transformative benefit to patients with high unmet medical need.

Oncology Clinical Research Analyst

The strategic collaboration between Repare Therapeutics and Debiopharm to evaluate the combination of lunresertib and Debio 0123 is a significant step in the advancement of cancer treatments. The decision to combine these two agents is based on the concept of synthetic lethality, where the concurrent inhibition of PKMYT1 by lunresertib and WEE1 by Debio 0123 could potentially lead to catastrophic cell death in cancer cells, which rely on these pathways for survival.

This approach, if successful, could open up new avenues for treating cancers with high unmet medical needs. The shared costs and collaborative design of the trial arm indicate a strong commitment from both companies to the research, which could accelerate the development process. The retention of commercial rights for each company's respective compounds provides a clear path for monetization if the clinical outcomes are positive.

The preclinical data suggesting a high level of synergy between these compounds is promising, but the transition from preclinical to clinical efficacy is not guaranteed. Investors should monitor the progression of the MYTHIC study closely, as positive clinical results could have a substantial impact on the companies' valuations and on the future treatment landscape for difficult-to-treat cancers.

Market Research Analyst

The oncology market is highly competitive, with numerous companies seeking to develop novel therapies that can provide clear benefits over existing treatments. The collaboration between Repare and Debiopharm has the potential to position both companies as leaders in the DNA damage response (DDR) space, a key area in precision oncology.

From a market perspective, the successful development of a combination therapy that can address hard-to-treat cancers could capture significant market share and offer competitive differentiation. The equal cost-sharing arrangement also suggests a balanced risk profile for both companies, which may be viewed favorably by investors. The anticipation of clinical trial initiation in the first half of 2024, while not immediate, gives stakeholders a timeline for evaluating the potential impact on the stock market.

It is crucial to consider that the outcome of the Phase 1/1b trial will be closely watched by competitors, as it may set a precedent for similar combination strategies. The market response to this news will likely be tied to investor confidence in the therapeutic potential of the combination and the companies' ability to execute the clinical study effectively.

Pharmaceutical Legal Expert

In the pharmaceutical industry, collaboration agreements such as the one between Repare and Debiopharm are critical for sharing the high costs and risks associated with drug development. From a legal standpoint, the clear stipulation that each company retains commercial rights to their compounds, both as monotherapy and in combination, is crucial. This ensures that irrespective of the collaboration's outcome, both entities maintain autonomy over their intellectual property.

Furthermore, the agreement to share all costs equally reflects a balanced legal and financial arrangement that may mitigate potential disputes over investment and revenue sharing. However, the complexity of such agreements requires careful navigation of regulatory landscapes, especially when dealing with global clinical trials. The adherence to international clinical trial standards and intellectual property laws will be essential in the execution of the MYTHIC study and the subsequent commercialization of the therapy.

For stakeholders, the legal robustness of the agreement provides a layer of security, underpinning the potential long-term benefits and commercial viability of the collaboration. It will be important to monitor how the legal framework adapts to the evolving nature of the partnership and any future regulatory challenges that may arise.

Collaborative clinical study will investigate a novel combination of lunresertib, Repare’s first-in-class PKMYT1 inhibitor, and Debio 0123, Debiopharm’s potent, brain-penetrant inhibitor of WEE1

MONTREAL & LAUSANNE, Switzerland--(BUSINESS WIRE)-- Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today announced that it has entered into a clinical study and collaboration agreement with Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standards of care to cure cancer and infectious diseases. This clinical collaboration aims to explore the synergy between lunresertib, a first-in-class, selective and potent oral, small molecule inhibitor of PKMYT1 with demonstrated anticancer activity, and Debio 0123, a potential best-in-class, brain-penetrant and highly selective WEE1 inhibitor.

Under the clinical study and collaboration agreement, the combination of lunresertib and Debio 0123 will be evaluated in a new arm of Repare’s ongoing global MYTHIC study (NCT04855656) under Repare’s sponsorship. The Phase 1/1b clinical trial is anticipated to initiate in the first half of 2024. Repare and Debiopharm will collaborate on the design of the trial arm for the development of the combination and will share all costs equally. Repare and Debiopharm will each supply their respective drugs, and each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.

“Combining with Debiopharm’s highly selective WEE1 inhibitor is the ideal strategy to further extend our leadership in PKMYT1 inhibitor development,” said Lloyd M. Segal, CEO of Repare. “The compelling mechanistic rationale and preclinical data Repare and Debiopharm have each generated for this combination give us confidence in its potential to deliver transformative benefit to patients with high unmet medical need.”

At the AACR-NCI-EORTC conference held in Boston in October 2023, Repare presented data showing that the combination of lunresertib and Debio 0123 is highly synergistic, and drives rapid and deep tumor regressions (Gallo et al., Poster #A023). Unpublished data independently generated by Debiopharm confirmed the dramatic synergy of the Debio 0123/lunresertib combination in vivo, further supporting the rationale for this clinical collaboration. In addition, several recent preclinical studies published by Repare and its collaborators have demonstrated proof-of-concept for the combination of WEE1 and PKMYT1 inhibition in relevant cancer cell lines and animal models of cancer (Sokhi et al. “Investigating Wee1 and Myt1 combined inhibition as a potential cancer therapeutic strategy”, AACR 2023, Poster #5511; Benada et al., 2023).

“We are delighted to enter into this clinical collaboration with Repare, the leader in PKMYT1 inhibition, to reinforce our commitment to the DDR space with our potential best-in-class WEE1 inhibitor. We believe this synthetic lethality approach will bring an innovative precision medicine therapy to patients,” said Bertrand Ducrey, CEO of Debiopharm. “This is the first time that Debiopharm has initiated a collaboration to combine two investigational compounds, demonstrating our excitement by the potential of this therapeutic approach in hard-to-treat cancers.”

About Lunresertib

Lunresertib (RP-6306) is a first-in-class, selective and potent oral small molecule inhibitor of PKMYT1, a cancer target Repare discovered and identified as synthetic lethal with CCNE1 amplification, FBXW7 and PPP2R1A alterations in solid tumors. Lunresertib is currently the sole PKMYT1 inhibitor known to be in clinical trials and is being evaluated alone and in combinations across several studies in the US, EU and Canada. Repare has presented positive initial Phase 1 data from its ongoing Phase 1 MYTHIC trial (NCT04855656) demonstrating proof of concept for lunresertib alone and in combination. In addition to being well tolerated and having a compelling safety profile, Repare presented anti-tumor activity for lunresertib in combination with camonsertib, an ATR inhibitor developed by Repare and partnered with Roche, expanded clinical studies for which are ongoing.

About Debio 0123

Debio 0123 is a brain-penetrant, highly selective WEE1 kinase inhibitor. WEE1 is a key regulator of the G2/M and S phase checkpoints, activated in response to DNA damage, allowing cells to repair their DNA before resuming their cell cycle. WEE1 inhibition, particularly in combination with DNA damaging agents, induces an overload of DNA breaks. In conjunction with abrogation of other checkpoints such as G1, the compound pushes the cells through cell cycle without DNA repair, promoting mitotic catastrophe and inducing apoptosis of cancer cells. Currently in research for solid tumors in monotherapy and combination, Debio 0123 is being developed to respond to high unmet needs of patients living with the burden of difficult-to-treat cancers.

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 or RG6526), a potential leading ATR inhibitor currently in Phase 1/2 clinical development and partnered with Roche; RP-1664, a preclinical PLK4 inhibitor program; RP-3467, a preclinical Polθ inhibitor program; as well as additional, undisclosed preclinical programs. For more information, please visit reparerx.com.

SNIPRx® is a registered trademark of Repare Therapeutics Inc.

Debiopharm's Commitment to Patients

Debiopharm aims to develop innovative therapies that target high unmet medical needs in oncology and bacterial infections. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy, and then hand stewardship to large pharmaceutical commercialization partners to maximize patient access globally.

For more information, please visit www.debiopharm.com

We are on Twitter. Follow us @DebiopharmNews at http://twitter.com/DebiopharmNews

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 Company’s clinical collaboration with Debiopharm including the benefits and results that may be achieved through the collaboration; the potential therapeutic benefits of lunresertib in combination with Debio 0123; and the anticipated timing, patient enrollment, outcomes or associated costs of the Phase 1/1b clinical trial of lunresertib in combination with Debio 0123. 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 impacts of macroeconomic conditions, including the COVID-19 pandemic, the conflict in Ukraine, the Hamas-Israel conflict, 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 risk that Repare may not realize the potential benefits of this collaboration with Debiopharm; the discovery, development and potential commercialization of potential product candidates using Repare’s SNIPRx® platform technology , including the development of lunresertib under the clinical study and collaboration agreement; 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 https://www.linkedin.com/company/repare-therapeutics/.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240104723197/en/

Repare Contact:

Robin Garner

Vice President and Head of Investor Relations

Repare Therapeutics Inc.

investor@reparerx.com

Investors:

Matthew DeYoung

Argot Partners

repare@argotpartners.com

Media:

David Rosen

Argot Partners

david.rosen@argotpartners.com

212-600-1902

Source: Repare Therapeutics Inc.

FAQ

What is the collaboration between Repare Therapeutics Inc. and Debiopharm about?

Repare Therapeutics Inc. (RPTX) has entered into a clinical study and collaboration agreement with Debiopharm to explore the synergy between lunresertib, a PKMYT1 inhibitor, and Debio 0123, a WEE1 inhibitor, in a new arm of Repare’s ongoing global MYTHIC study.

When is the Phase 1/1b clinical trial expected to initiate?

The Phase 1/1b clinical trial is anticipated to initiate in the first half of 2024.

What are the aims of the collaboration between Repare Therapeutics Inc. and Debiopharm?

The collaboration aims to explore the synergy between lunresertib and Debio 0123, share all costs equally, and develop a potential best-in-class precision medicine therapy for patients with high unmet medical need.

What has the preclinical data shown about the combination of lunresertib and Debio 0123?

The preclinical data has shown that the combination of lunresertib and Debio 0123 is highly synergistic and has demonstrated potential transformative benefit to patients with high unmet medical need.