ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC) has announced encouraging early Phase 1b combination data for ORIC-944 in metastatic castration-resistant prostate cancer (mCRPC) and a clinical trial collaboration with Johnson & Johnson for ORIC-114 in non-small cell lung cancer (NSCLC). These developments mark significant progress in ORIC's efforts to develop treatments addressing therapeutic resistance in cancer.
ORIC-944: Early Phase 1b Data in mCRPC
ORIC-944, a potent and selective allosteric inhibitor of the polycomb repressive complex 2 (PRC2), is being evaluated in an ongoing Phase 1b trial in combination with androgen receptor inhibitors apalutamide and darolutamide for patients with mCRPC. Initial data from the apalutamide combination arm (n=6) showed:
- Deep prostate-specific antigen (PSA) decreases in both the 600 mg and 800 mg dose cohorts.
- Confirmed PSA50 responses were achieved in 3 of 6 patients, with 2 patients achieving confirmed PSA90 responses.
- All PSA responses were maintained for at least 12 weeks, with one durable confirmed PSA90 response ongoing at 38 weeks.
- The combination was well-tolerated, with primarily Grade 1 and Grade 2 treatment-related adverse events (TRAEs), consistent with PRC2 and androgen receptor (AR) inhibition. One Grade 3 TRAE of fatigue was reported, but the patient remained on treatment without dose modification.
Dose escalation for the combination of ORIC-944 with darolutamide is ongoing, with preliminary clinical activity consistent with the apalutamide combination cohort. These early findings suggest that ORIC-944 may offer a valuable addition to existing AR inhibitors for mCRPC treatment.
ORIC-114: Collaboration with Johnson & Johnson in NSCLC
ORIC has entered into a clinical trial collaboration and supply agreement with Johnson & Johnson to evaluate ORIC-114 in combination with subcutaneous amivantamab for the first-line treatment of NSCLC patients with EGFR exon 20 insertion mutations. ORIC-114 is a brain-penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor.
Jacob M. Chacko, M.D., president and chief executive officer of ORIC Pharmaceuticals, stated, "We made strong progress on multiple fronts in 2024, most notably with the initiation of multiple cohorts for ORIC-114 in NSCLC and ORIC-944 in mCRPC. We also forged three strategic collaborations with leading pharma partners..."
ORIC expects to initiate the combination Phase 1b trial in the first quarter of 2025, with initial data anticipated in mid-2026. The primary objectives are to determine the provisional recommended Phase 2 dose for the combination, assess efficacy, and further characterize the safety profile.
Anticipated Milestones and Financial Position
ORIC anticipates reporting seven data readouts across the ORIC-114 and ORIC-944 clinical programs over the next 18 months. The company expects to potentially initiate registrational trials for ORIC-114 in the second half of 2025 and for ORIC-944 in early 2026.
As of December 31, 2024, ORIC's cash, cash equivalents, and investments totaled $256 million, which is expected to fund its operating plan into late 2026.
