On November 15, 2023 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported polo-like kinase 4 (PLK4) as the target of its RP-1664 development program and provided comprehensive preclinical data for both RP-1664 and the Company’s Polq inhibitor, RP-3467 (Press release, Repare Therapeutics, NOV 15, 2023, View Source [SID1234637708]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

RP-1664 is a potential first-in-class, selective, oral PLK4 inhibitor that is synthetic lethal with TRIM37 amplification or overexpression in solid tumors. Tumors rely on PLK4 for survival in the presence of high levels of TRIM37. Preclinical studies demonstrate RP-1664 drives potent synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. Elevated TRIM37 is a feature found across a range of solid tumors and in nearly all high-grade neuroblastomas.

RP-3467 is a potential best-in-class inhibitor of DNA polymerase theta, or Polq. Polq is a synthetic lethal target associated with homologous recombination deficiency (HRD) tumors, including those with BRCA1/2 mutations or other genomic alterations. Data suggest that RP-3467 works synergistically with therapies that result in double stranded DNA breaks, such as PARP inhibition, radioligand therapy and multiple chemotherapies and antibody-drug conjugates (ADCs). Additionally, initial data suggest that Polq inhibition may interfere with mechanisms central to the development of PARPi resistance.

"We are excited to announce the initial clinical approach for RP-1664 based on highly compelling preclinical data supporting its potential for treating TRIM37-high tumors," said Lloyd M. Segal, President and CEO of Repare. "We are also pleased to share preclinical data from our RP-3467 program supporting its significant potential across multiple high-value therapeutic opportunities. These programs represent our third and fourth internally developed clinical candidates and provide further confirmation of Repare’s powerful discovery platform. We look forward to advancing both RP-1664 and RP-3467 into Phase 1 clinical trials in 2024."

RP-1664 Highlights

•
RP-1664 is a highly potent, selective and bioavailable PLK4 inhibitor that is synthetic lethal with TRIM37 gain of function.

•
RP-1664 demonstrated robust and dose-dependent monotherapy activity in multiple TRIM37-high preclinical models across a variety of tumor types, including breast cancer, non-small cell lung cancer (NSCLC) and neuroblastoma.

•
The Company plans to initiate a Phase 1 dose escalation study of RP-1664 in adult and adolescent patients with TRIM37-high solid tumors in the first half of 2024.

RP-3467 Data Highlights

•
RP-3467 is a highly potent and selective inhibitor of the Polq helicase domain.

•
RP-3467 demonstrates synergy with PARP inhibitor activity, resulting in durable, complete tumor regressions in multiple preclinical models.

•
Preclinical studies also show combination potential with multiple other modalities, including RLT, chemotherapy and ADCs.

•
The Company plans to initiate a Phase 1 dosing finding clinical trial of RP-3467 in the second half of 2024.

"Preclinical data for RP-1664 demonstrate early and promising activity in TRIM37-high tumors, including breast cancer, NSCLC and neuroblastoma," said Michael Zinda, Ph.D., EVP, Chief Scientific Officer of Repare. "The durable, complete regressions observed in the preclinical RP-3467 and PARPi combination studies are also extremely exciting and demonstrate the broad combination potential of our potent and selective Polq helicase inhibitor. Repare plans to investigate RP-3467 with a focus on its potential as a combination partner across agents that induce double stranded DNA breaks, including RLT, ADCs, and a range of chemotherapies."

Conference Call and Webcast

Repare will host a conference call and webcast today, November 15, 2023, at 8:00 a.m. ET. To access the call, please dial (877) 870-4263 (U.S. and Canada) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined to the Repare Therapeutics call. A live webcast will be available in the Investor section of the Company’s website at View Source A webcast replay will also be archived for at least 30 days.