Rain has built a precision oncology pipeline that’s focused on genetically selecting the patients most likely to benefit from treatment.
The recent advancements in cancer research and drug development allow for an unprecedented degree of insight into the critical drivers of cancer growth and its associated signaling networks and vulnerabilities. We believe this knowledge, combined with our leveraging of widely available, comprehensive next generation sequencing-based companion diagnostics and biomarkers to identify relevant patients, gives us a key advantage as we endeavor to identify and develop novel, targeted therapies.
Rain’s lead product candidate, RAIN-32 (milademetan), a small molecule, oral inhibitor of mouse double minute 2 (MDM2) is being developed in patients with MDM2 amplified or overexpressed cancers. MDM2 is a critical regulator of tumor protein 53 (p53), which is known as the “guardian of the genome.” p53 regulates the cell cycle, and in that role is essential for tumor suppression. If MDM2 is overexpressed, p53 can be inactivated, leading to tumor growth and cancer progression. By inhibiting MDM2, RAIN-32 is expected to reactivate p53, which can resume its role in controlling cancer growth. RAIN-32’s differentiated profile enables a rationally-designed dosing schedule that we believe has the potential to reduce toxicities while preserving activity.
Rain is initially evaluating RAIN-32 for the treatment of well-differentiated (WD)/de-differentiated (DD) liposarcoma. Nearly 100% of WD/DD liposarcoma patients exhibit MDM2 gene amplification. The incidence of WD/DD liposarcoma is estimated at approximately 2,000 patients annually in the U.S. for which there are few effective treatment options. Rain commenced a pivotal Phase 3 trial for RAIN-32 in liposarcoma patients in July 2021.
Rain also plans to commence two additional Phase 2 trials for RAIN-32 in late 2021 with an open-label MDM2-amplified tumor-agnostic basket trial and in early 2022 with an open-label trial in patients with intimal sarcoma, a rare sarcoma also exhibiting MDM2-amplification.
RAD52 Research Program
RAD52 plays a central role in the DNA Damage Response (DDR) pathway. Targeting RAD52 represents a novel strategy for patients that may exhibit homologous recombination deficiencies (HRD+), or a loss of function, of several pathway constituents including BRCA1/2, PALB2 or several others in tumor types frequently characterized by these deficiencies. These tumors include breast, prostate, pancreatic, ovarian and possibly other cancers. Current approaches to treating these cancers include PARP inhibitors, however, patients often relapse to PARP inhibitors and are left with few options.
In cancer patients with BRCA1/2 deficiencies, or in patients relapsed to PARP inhibitor therapies, RAD52 may provide an alternative strategy. Rain anticipates selecting a lead clinical candidate for its RAD52 program in 2022.