ORIC Pharmaceuticals Announces Clinical Collaborations for Prostate Cancer Trial

ORIC Pharmaceuticals, Inc., a clinical-stage oncology company specializing in treatments aimed at overcoming therapeutic resistance, has announced the initiation of dosing for its drug candidate ORIC-944. This potent and selective allosteric inhibitor of PRC2 is being tested in combination with two androgen receptor (AR) inhibitors: darolutamide and apalutamide. The dosing began in the first half of 2024 as part of an ongoing Phase 1b trial targeting patients with metastatic castration-resistant prostate cancer (mCRPC).

The trial's design includes separate cohorts for each combination, each featuring a dose escalation phase followed by an expansion phase. These cohorts will evaluate the safety and efficacy of ORIC-944 in combination with either NUBEQA® (darolutamide) or ERLEADA® (apalutamide).

In conjunction with the trial, ORIC Pharmaceuticals has entered into clinical trial collaboration and supply agreements with Bayer and Janssen Research & Development, LLC, a Johnson & Johnson company. These agreements stipulate that ORIC will continue sponsoring and conducting the ongoing Phase 1b trial, while Bayer and Johnson & Johnson will supply darolutamide and apalutamide, respectively. Despite these collaborations, ORIC retains full global development and commercial rights for ORIC-944.

Jacob M. Chacko, M.D., the president and CEO of ORIC Pharmaceuticals, expressed enthusiasm about the collaborations. He highlighted preclinical findings and emerging clinical data that suggest the combination of ORIC-944 with AR inhibitors could be particularly effective. Chacko pointed out that data presented at the AACR Annual Meeting indicated that ORIC-944 and AR inhibitors work synergistically in multiple prostate cancer models by reprogramming the cancer to revert to an AR-dependent state. This mechanism, combined with ORIC-944's superior clinical half-life, robust target engagement, and favorable safety profile as a monotherapy, suggests significant potential for this combination therapy to become a new treatment paradigm for prostate cancer patients.

ORIC-944, being an allosteric inhibitor of PRC2 via its EED subunit, was first evaluated as a single agent in a Phase 1b trial involving patients with advanced prostate cancer. The drug displayed promising attributes, including a clinical half-life of approximately 20 hours, effective target engagement, and a strong safety profile.

ORIC Pharmaceuticals is dedicated to improving cancer patients' lives by overcoming resistance mechanisms in cancer. Apart from ORIC-944, the company's clinical-stage product candidates include ORIC-114, a brain-penetrant inhibitor targeting EGFR and HER2 mutations, and ORIC-533, a small molecule inhibitor of CD73 designed to address resistance to chemotherapy and immunotherapy in multiple myeloma. Additionally, ORIC is developing several precision medicines targeting other cancer resistance mechanisms.

The company operates offices in South San Francisco and San Diego, California.