We target the next generation of genomic alterations in cancer, focusing on specific genetic alterations with application to multiple tumor types.

The first generation of approved targeted therapies were predominately directed at driver mutations, which target specific types of receptor tyrosine kinases, such as BCR-ABL, EGFR and HER2. Since then, a rapid evolution in the understanding of tumor biology coupled with an improved ability to segment subsets of tumors based on genomic alterations have led to the development of new generations of targeted cancer therapies for a variety of additional tumor-specific genomic abnormalities.

Targeting DNA repair genes and specifically loss-of-function alterations is an emerging area of research in precision oncology, with PARP inhibitors pioneering the field. Synthetic lethality (SL) represents a clinically-validated approach to drug development that also targets genomic instability lesions caused by mutations in mechanisms that govern DNA damage repair.

SL arises when a deficiency in either of two genes is tolerated in cells, but simultaneous deficiencies in both genes cause cell death. Cancer cells that contain an inactivating mutation in one gene of a SL pair are susceptible to therapeutic intervention targeting the other gene pair.

SL is a powerful approach and opportunity in oncology drug development that combines two key principles in treating patients with cancer through precision oncology: (1) identifying and selecting patient subgroups with specific genomic alterations in tumors that are most likely to benefit from these therapies and (2) improving tolerability and reducing toxicity by not affecting normal, non-cancerous cells.

Using our SNIPRx platform, we are developing our pipeline of SL product candidates, including our lead product candidate, camonsertib (RP-3500), a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase) for the treatment of solid tumors with specific DNA damage repair-related genomic alterations, including those in the ATM gene (ataxia telangiectasia mutated kinase). We announced our worldwide license and collaboration agreement with Roche for camonsertib (RP-3500) on June 1, 2022. We are also developing another product candidate, RP-6306, a PKMYT1 SL inhibitor, in advanced solid tumors.