On August 9, 2023 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported financial results for the second quarter ended June 30, 2023 (Press release, Repare Therapeutics, AUG 9, 2023, View Source [SID1234634090]).

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"During the second quarter we made great progress advancing our clinical programs and presenting novel findings from our ongoing clinical trials, including reporting on camonsertib’s combination with three PARP inhibitors and initial clinical proof of concept for lunresertib," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "While these clinical programs move towards Phase 2 studies, we continue to support our preclinical pipeline, for example with the designation of our Polθ inhibitor, RP-3467. We look forward to reporting initial combination data of lunresertib with camonsertib in the fourth quarter of this year as we continue advancing our differentiated, synthetic lethal-based oncology pipeline."

Second Quarter 2023 Review and Operational Updates:

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Advancing camonsertib, a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase) for the treatment of tumors with specific synthetic lethal genomic alterations in partnership with Roche.
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Roche has included a camonsertib-based arm in its Phase 2, global, multicenter, open-label, multi-cohort TAPISTRY study (NCT04589845) and its Phase 1/2 study of multiple immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (Morpheus Lung; NCT03337698). Repare is eligible to receive a milestone payment of $40 million upon dosing of the first patient with camonsertib in the TAPISTRY study and could be eligible for an additional $15 million milestone if this study becomes registrational.

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Repare is continuing to conduct 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. In April 2023, we received a payment of $4 million from Roche for additional revisions to the clinical development plan under the Roche Agreement. Repare is eligible to receive further milestone payments upon the initiation of registrational trials or the transition of existing trials to become registrational for camonsertib in specific tumor types.
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Published data in Nature Medicine from the ongoing Phase 1/2 TRESR clinical trial evaluating camonsertib monotherapy in 120 patients (NCT04497116). The article, entitled "Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results" can be accessed at View Source
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Announced initial clinical data from the Phase 1/2 TRESR and ATTACC trials evaluating camonsertib 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) (Free AACR Whitepaper) Annual Meeting.
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Camonsertib-PARP inhibitor combinations appeared to be well tolerated and 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), including overall response of 32%, CBR of 58% and median progression-free survival of approximately 7 months with treatment greater than 16 weeks and ongoing in 9 patients, as of the 2023 AACR (Free AACR Whitepaper) Annual Meeting data cutoff of February 27, 2023. The molecular response rate (MRR) of circulating tumor DNA was significantly higher in patients with clinical benefit (83%) compared to those without (48%; p=0.015) and significantly higher than seen in the camonsertib monotherapy trial in which camonsertib was administered at higher doses (66% vs. 43%; p=0.02). Molecular responses were also observed in patients with prior PARP inhibitor exposure (57%) and platinum resistance (64%).
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Advancing lunresertib (RP-6306), a first-in-class, oral PKMYT1 inhibitor, for the treatment of molecularly select advanced solid tumors as a monotherapy and in combinations in multiple clinical studies.
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Announced clinical proof of concept for lunresertib, including monotherapy data from the Phase 1 MYTHIC clinical trial and early insights from ongoing combination trials in June 2023. Achieved primary endpoints of safety and tolerability and proposed dose and schedule. The tolerability profile of lunresertib monotherapy appears favorable and differentiated from other clinical cell cycle inhibitors, as lunresertib treatment does not result in significant myelotoxicity nor diarrhea. No grade 4 toxicity was observed with lunresertib, while grade 3 treatment emergent adverse events of interest included rash (7.9%), anemia (6.3%) and nausea or vomiting (1.6%). The dose limiting toxicity was reversible rash, alleviated with dose modifications and simple supportive measures. Two proposed dose/schedules were identified – 240mg daily continuously and 80-100mg BID intermittent weekly – to offer maximum flexibility in combination studies.
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Preliminary anti-tumor activity was observed for monotherapy, including moderate tumor shrinkages and a confirmed partial response per RECIST 1.1 criteria in a patient with metastatic recurrent uterine carcinosarcoma.

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Early clinical responses per RECIST 1.1 criteria have been observed with lunresertib and combinations with gemcitabine, camonsertib, and FOLFIRI in multiple tumor types and genotypes.
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Repare is collaborating with Princess Margaret Cancer Center to initiate clinical testing, as part of an investigator-sponsored trial (IST) of a fourth lunresertib combination with carboplatin and paclitaxel for the treatment of recurrent gynecological malignancies, with first patient dosing expected this year.
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Repare is also collaborating with the Canadian Cancer Trials Group in an ongoing basket Phase 2 IST that is enrolling patients with selected, advanced cancers receiving lunresertib as combination with gemcitabine (NCT05605509), and in a second active study that will evaluate lunresertib in combination with gemcitabine in patients with CDK4/6 inhibitor treated ER+/HER2- metastatic breast cancer (NCT05601440).
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In August 2023, the U.S. Food and Drug Administration (FDA) granted Fast Track designation (FTD) to lunresertib in combination with camonsertib for the treatment of adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A mutated endometrial cancer previously treated with a platinum-containing regimen and immune checkpoint inhibitor when indicated. FTD is intended to facilitate the development and expedite the review of drugs to treat serious conditions and fulfill an unmet medical need, enabling drugs to reach patients earlier.
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The Company expects to present further Phase 1 MYTHIC Module 2 combination data with camonsertib at a medical conference in the fourth quarter of this year.
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Advancing preclinical programs into clinical development.
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RP-1664 IND-enabling studies, which began in the first quarter of 2023, remain ongoing with potential for the program to enter the clinic in early 2024.
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Initiated IND-enabling studies for the newly designated Polθ inhibitor RP-3467 in June 2023. RP-3467 has shown greater potency in preclinical studies compared to RP-2119, our first Polθ inhibitor designated in 2022, and has potential to enter the clinic in 2024. The research term of our Polθ collaboration with Ono Pharmaceutical Company Ltd., as previously extended, expired on July 31, 2023. With the termination of the agreement with Ono Pharmaceutical Company Ltd., Repare’s Polθ program, including RP-3467, is wholly-owned by Repare.
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The Company intends to host an R&D day focused on its ongoing pre-clinical programs and its overall pipeline in the fourth quarter of this year.
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In May 2023, Bristol Myers Squibb exercised its option for a third druggable target and separately triggered a $1 million payment for a previously exercised druggable target option.
Second Quarter 2023 Financial Results:

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Cash and cash equivalents and marketable securities: Cash and cash equivalents and marketable securities as of June 30, 2023 were $280.7 million, which Repare believes will be sufficient to fund its planned operations into 2026.
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Revenue from collaboration agreements: Revenue from collaboration agreements were $30.2 million and $35.9 million for the three and six months ended June 30, 2023, respectively, as compared to $0.7 million and $1.1 million for the three and six months ended June 30, 2022. The increase in revenue for the three- and six-month periods were primarily due to revenue recognized from our collaboration and license agreement with BMS and our collaboration agreement with Ono.

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Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $33.8 million and $65.6 million for the three and six months ended June 30, 2023, respectively, as compared to $31.5 million and $57.9 million for the three and six months ended June 30, 2022. The increase in Net R&D expenses for the three- and six-month periods was primarily due to higher personnel-related costs and direct external costs related to the advancement of preclinical programs into IND-enabling studies.
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General and administrative (G&A) expenses: G&A expenses were $8.7 million and $17.2 million for the three and six months ended June 30, 2023, respectively, compared to $7.9 million and $16.7 million for the three and six months ended June 30, 2022. The increase in G&A was primarily due higher personnel related costs, offset by lower D&O insurance premiums.
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Net loss: Net loss was $11.9 million, or $0.28 per share, and $46.9 million, or $1.11 per share, in the three and six months ended June 30, 2023, respectively, and $38.1 million, or $0.91 per share, and $72.9 million, or $1.74 per share, in the three and six months ended June 30, 2022, respectively.