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Repare Therapeutics' PLK4, Pol Theta Inhibitor Programs to Enter Phase I Trials Next Year

NEW YORK – Repare Therapeutics on Wednesday disclosed two synthetic lethality product candidates, the PLK4 inhibitor RP-1664 and the pol theta inhibitor RP-3467, both of which it expects to move into clinical trials in 2024.

The PLK4 inhibitor is a synthetic lethal therapy for solid tumors harboring TRIM37 amplification or that otherwise overexpress TRIM37. In preclinical studies, Repare found that RP-1664 drove synthetic lethality in TRIM37-high tumor models. High TRIM37 expression is found in a range of solid tumors and in nearly all high-grade neuroblastomas, according to Repare.

Meanwhile, Repare plans to develop the pol theta inhibitor as a treatment for tumors with homologous recombination deficiency (HRD), including those with BRCA1/2 mutations. Preclinical studies have suggested that RP-3467 has combination activity with other treatments for these tumors, including with PARP inhibitors, radioligand therapy, chemotherapy, and antibody-drug conjugates. The preclinical data also indicate that pol theta inhibition can address tumor resistance to PARP inhibitors.

Repare expects to begin a Phase I study of RP-1664 in adult and adolescent patients with TRIM37-high solid tumors in the first half of 2024. It aims to launch a Phase I study for RP-3467 in the second half of next year.

Last year, Repare out-licensed its lead candidate, the ATR inhibitor camonsertib, to Roche in a deal worth up to $1.2 billion. The Montreal-based company is also developing a PKMYT1 inhibitor as a treatment for tumors with CCNE1 amplifications and FBXW7 alterations and has two other undisclosed discovery programs.