Repare Therapeutics Inc. (NASDAQ: RPTX) witnessed a notable surge of 6.57%, reaching $5.35 in the extended trading session on Friday. This ascent marked a robust recovery for Repare stock, which had experienced a discouraging decline of 9.71% during the regular session, concluding at $5.02. The elevation in RPTX stock during the extended session followed the revelation of two forthcoming programs slated for entry into clinical trials.
In the preceding week, Repare divulged the identification of polo-like kinase 4 (PLK4) as the focal point of its RP-1664 developmental initiative. RPTX presented comprehensive preclinical data encompassing both RP-1664 and the Company’s Polθ inhibitor, RP-3467.
RP-1664 stands as Repare’s potential pioneering, discerning, oral PLK4 inhibitor designed to induce synthetic lethality with TRIM37 amplification or overexpression in solid tumors. Tumors heavily rely on PLK4 for survival in the presence of elevated TRIM37 levels. Preclinical investigations indicate that RP-1664 instigates robust synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. Elevated TRIM37 manifests as a characteristic in various solid tumors and nearly all high-grade neuroblastomas.
RP-3467, Repare’s potential foremost inhibitor of DNA polymerase theta, or Polθ, presents itself as a synthetic lethal target linked to homologous recombination deficiency (HRD) tumors, including those harboring BRCA1/2 mutations or other genomic alterations. Data suggests that RP-3467 synergizes with therapies inducing double-stranded DNA breaks, such as PARP inhibition, radioligand therapy, and various chemotherapies and antibody-drug conjugates (ADCs).
Preliminary data also indicate that Polθ inhibition may disrupt mechanisms integral to the emergence of PARPi resistance. Repare unveiled the initial clinical strategy for RP-1664, grounded in highly compelling preclinical data supporting its efficacy in treating TRIM37-high tumors. RPTX also disseminated preclinical data from its RP-3467 program, affirming its substantial potential across diverse high-value therapeutic opportunities.
These initiatives signify Repare’s third and fourth internally conceived clinical candidates, underscoring the potency of Repare’s discovery platform. Repare is poised to advance both RP-1664 and RP-3467 into Phase 1 clinical trials in 2024.
