RP-2119 / Repare Therap - LARVOL DELTA

The Discovery of RP-2119: A Potent, Selective, and Orally Bioavailable Polθ ATPase Inhibitor. (PubMed, J Med Chem) - "Further optimization of potency and ADME properties led to the identification of RP-2119 with robust in vitro cellular activity in a wide range of HR-deficient cancer cell lines. In HR-deficient cell line- and patient-derived mouse xenografts, RP-2119 demonstrated strong synergy with the PARP inhibitor, olaparib, without exacerbating its hematological toxicity."

Journal • Hematological Disorders • Oncology • BRCA1 • BRCA2 • POLQ

Repare Therapeutics Provides Business Update and Reports First Quarter 2023 Financial Results (Businesswire) - "Advancing preclinical programs into clinical development: (i) 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; (ii) Repare is also pursuing development of an inhibitor of polymerase theta (Polθ) that is expected to enter the clinic in 2024."

New trial • Pipeline update • Oncology

Repare Therapeutics Receives $1.5 Million (¥200 million) Payment from Ono Pharmaceuticals (Businesswire) - "Repare Therapeutics Inc...announced that the Company has received an approximately $1.5 million (¥200 million) research service payment from Ono Pharmaceutical Co., Ltd. ('Ono'). The payment reflects achievement of a specified research trigger, under the companies’ 2019 Strategic Partnership Agreement ('Ono Agreement'). Under the terms of the Ono Agreement, Repare is primarily responsible for carrying out research activities for its Polθ program, now known as RP-2119, until the first submission of an IND in the U.S. or Japan."

Financing • Licensing / partnership • Oncology • Solid Tumor

Repare Therapeutics Provides Business Update and Reports Third Quarter 2022 Financial Results (Businesswire) - "Initial Phase 1 clinical data readout for RP-6306 is expected in the first half of 2023. Based on promising preclinical data released at the 34th EORTC-NCI-AACR Symposium in October 2022, Repare is working with clinical investigators to initiate clinical testing of a new carboplatin combination with RP-6306 in 2023....Advancing IND-enabling studies for RP-2119, Repare's Polθ inhibitor, and plan to initiate clinical trials in the summer of 2023. Repare also expects to initiate IND-enabling studies in the first half of 2023 for an additional small molecule against an undisclosed target."

IND • P1 data • Oncology • Solid Tumor

Identification of RP-6685, an Orally Bioavailable Compound that Inhibits the DNA Polymerase Activity of Polθ. (PubMed, J Med Chem) - "A high-throughput screening campaign of 350,000 compounds identified an 11 micromolar hit, giving rise to the N2-substituted fused pyrazolo series, which was validated by biophysical methods. Structure-based drug design efforts along with optimization of cellular potency and ADME ultimately led to the identification of RP-6685: a potent, selective, and orally bioavailable Polθ inhibitor that showed in vivo efficacy in an HCT116 BRCA2 mouse tumor xenograft model."

Journal • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA2 • POLQ