CAMBRIDGE, Mass. & MONTREAL–(BUSINESS WIRE)–Repare Therapeutics Inc. (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today reported financial results for the first quarter ended March 31, 2023.
“We continue to execute clinically and across our pipeline programs, including presenting initial clinical data of camonsertib in combination with various PARP inhibitors from the ongoing TRESR and ATTACC trials at this year’s AACR conference,” said Lloyd M. Segal, President and Chief Executive Officer of Repare. “These findings are consistent with our preclinical data demonstrating that low, intermittent dosing of the camonsertib and PARP inhibitor combinations appears well tolerated and exhibited antitumor activity, most notably in advanced ovarian cancer. In addition, we are on track to present initial Phase 1 monotherapy data for RP-6306 in June.”
First Quarter 2023 Review and Operational Updates:
- Announced initial clinical data from the Phase 1/2 TRESR and ATTACC trials evaluating camonsertib (RP-3500/RG6526, partnered with Roche), a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase), in combination with three poly (ADP-ribose) polymerase (PARP) inhibitors in a Clinical Trials Plenary Session at the 2023 American Association for Cancer Research (AACR) Annual Meeting.
- Camonsertib combinations appear to be well tolerated. Dose limiting toxicity in 68 patients treated with the proposed combination doses were related to myelotoxicity (Grade 3+ anemia 3%, thrombocytopenia 6%, neutropenia 7%, and febrile neutropenia 3%). No prophylactic growth factors were required when administering the PARP inhibitors at evaluated doses.
- Camonsertib combination resulted in durable clinical benefit across tumor types and genomic alterations, regardless of choice of PARP inhibitor and presence of platinum resistance. Overall clinical benefit rate (CBR) for all patients was 48%. Patients with platinum-resistant tumors had an overall response rate (ORR) of 12% and CBR of 49% and benefited similarly to non-platinum-resistant tumors (ORR 13%, CBR 46%).
- Compelling results were observed particularly in patients with advanced ovarian cancer (n = 19). In these patients, overall response was 32%, CBR was 58% and median progression-free survival was approximately 7 months with treatment greater than 16 weeks and ongoing in 9 patients.
- Early circulating tumor DNA molecular responses in 66% (31/47) of evaluable patients confirm antitumor activity of low dose, intermittent PARP inhibitor + ATR inhibitor therapy. The molecular response rate (MRR) was significantly higher in patients with clinical benefit (83%) compared to those without (48%; p=0.015) and significantly higher than camonsertib monotherapy that was also administered at higher doses (43% or 27/63; p=0.02). Molecular responses were also observed in patients with prior PARP inhibitor exposure (57%) and platinum resistance (64%).
- Repare is conducting dose optimization and efficacy assessments in tumor specific expansions in the ATTACC study in collaboration with Roche to support future clinical development plans for camonsertib combinations with PARP inhibitors.
- Evaluating RP-6306, a first-in-class, oral PKMYT1 inhibitor as a monotherapy and in combinations in multiple early clinical studies.
- Repare presented two poster presentations for RP-6306 at the 2023 AACR Annual Meeting regarding the co-mutation landscape in CCNE1 amplifications and the tumor heterogeneity of copy number in ovarian and uterine cancers. Additionally, several collaborators presented preclinical findings on the potential benefits of combining a Wee1 inhibitor with RP-6306 and the effect of RP-6306 in triple negative breast cancer.
- Repare expects to report initial Phase 1 monotherapy clinical data for RP-6306 for the treatment of molecularly selected advanced solid tumors (MYTHIC) in June 2023. The Company expects to report initial Phase 1 combination therapy clinical data for RP-6306 for the treatment of molecularly selected advanced solid tumors in the fourth quarter of the year.
- Repare is working with clinical investigators to initiate clinical testing, as part of an investigator-sponsored trial (IST), of a fourth RP-6306 combination with carboplatin, with first patient dosing expected this year.
- Repare is collaborating with the Canadian Cancer Trials Group for a basket Phase 2 IST to evaluate RP-6306 in patients with selected, advanced cancers receiving standard agents that is expected to begin this year. A sub-study under the master clinical trial protocol will evaluate RP-6306 in combination with gemcitabine in patients with CD4/6i-resistant ER+/HER2- metastatic breast cancer.
- Advancing preclinical programs into clinical development.
- Repare initiated IND-enabling studies in the first half of this year for a small molecule, now designated RP-1664, against an undisclosed target with potential to enter the clinic in late 2023 or early 2024.
- Repare is also pursuing development of an inhibitor of polymerase theta (Polθ) that is expected to enter the clinic in 2024.
- In April 2023, Repare announced the appointment of Susan Molineaux, Ph.D., to its Board of Directors, effective as of the date of the Company’s upcoming annual meeting of shareholders in June 2023. Concurrent with Dr. Molineaux’s appointment as of the date of the annual meeting, Jerel Davis, Ph.D., Managing Director at Versant Ventures and a founding member of Repare’s Board of Directors, will step down from the Board. Additionally, Repare has expanded the senior leadership team with the appointment of Daniel Belanger as EVP Human Resources in May 2023.
First Quarter 2023 Financial Results:
- Cash and cash equivalents and marketable securities: Cash and cash equivalents and marketable securities as of March 31, 2023 were $314.1 million.
- Revenue from collaboration agreements: Revenue from collaboration agreements were $5.7 million and $0.4 million for the three months ended March 31, 2023 and 2022, respectively. The year-over-year increase in revenue was due to revenue recognized from our collaboration and license agreement with Roche.
- Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $31.8 million and $26.5 million for the three months ended March 31, 2023 and 2022, respectively. The year-over-year increase in Net R&D expenses was primarily due to higher personnel related costs from headcount in support of our development activities, and direct external costs related to the advancement of preclinical programs into IND-enabling studies.
- General and administrative (G&A) expenses: G&A expenses were $8.6 million and $8.8 million for three months ended March 31, 2023 and 2022, respectively. The year-over-year decrease in G&A was primarily due to lower professional fees associated with our collaboration and license agreement with Roche and lower D&O insurance premiums, offset by higher personnel related costs.
- Net loss: Net loss was $34.9 million, or $0.83 per share, in the three months ended March 31, 2023, and $34.8 million, or $0.83 per share in the three months ended March 31, 2022.
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.
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 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; a preclinical Polθ inhibitor program; as well as several undisclosed preclinical programs, including RP-1664. For more information, please visit reparerx.com.
