On January 11, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported program updates and announced key milestones for 2021, which are expected to substantially expand and advance the company’s clinical pipeline (Press release, ORIC Pharmaceuticals, JAN 11, 2021, View Source [SID1234573783]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"2020 was a transformational year for ORIC during which we significantly broadened the pipeline via internal discovery and business development efforts, expanded the team, and strengthened the balance sheet with the completion of an IPO and follow-on financing," said Jacob Chacko, M.D., president and chief executive officer. "These efforts have positioned us for a dynamic 2021, with our first data from two ongoing trials of our lead program ORIC-101 and three INDs/CTAs for our other product candidates, which represents a tremendous amount of development activity for a company at our stage."
Program Updates and 2021 Milestones
ORIC-101: Glucocorticoid Receptor (GR) Antagonist
ORIC-101 is a potent and selective GR antagonist, with two distinct mechanisms of action being evaluated in two Phase 1b trials in combination with: (1) Xtandi (enzalutamide) in metastatic prostate cancer and (2) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors.
The company announced today the completion of the Part I dose escalation portion of the Phase 1b trial of ORIC-101 in combination with enzalutamide in metastatic prostate cancer, by identifying the provisional recommended Phase 2 dose (RP2D) that will be used in the Part II expansion portion of the trial. The selection of the provisional RP2D was based upon the totality of safety, pharmacokinetic, and pharmacodynamic data demonstrating a well-tolerated regimen that achieved ORIC-101 exposures leading to demonstrable target engagement and GR inhibition. In the Part I dose escalation portion of the trial, patients were enrolled to evaluate daily dosing of ORIC-101 with doses ranging from 80 to 240 mg, in combination with daily dosing of 160 mg of enzalutamide. In the Part II dose expansion portion of the trial, up to 48 patients are expected to be enrolled and treated at the RP2D of 240 mg of ORIC-101 and 160 mg of enzalutamide on a continuous daily dosing schedule. Patients will be enrolled independent of GR status, with retrospective analysis of GR expression and other potentially predictive biomarkers. The company expects to report interim safety, efficacy, and translational data from this trial in the second half of 2021.
The Phase 1b trial of ORIC-101 in combination with nab-paclitaxel is now enrolling patients in the Part II dose expansion portion. In December 2020, the company announced the completion of the Part I dose escalation portion of ORIC-101 in combination with nab-paclitaxel in solid tumors, the selection of the RP2D, and the initiation of the dose expansion portion of the trial. For the Part II dose expansion portion of the trial, up to 132 patients are expected to be enrolled across four cohorts, including pancreatic ductal adenocarcinoma, ovarian cancer, triple negative breast cancer, and other advanced solid tumors. Patients in Part II of the trial will be treated at the RP2D of 160 mg of ORIC-101 continuous once daily dosing and 75 mg/m2 of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, without requirement for prophylactic granulocyte colony-stimulating factor. Eligible patients must have previously progressed on a taxane-containing regimen and will be enrolled independent of baseline GR status, with retrospective analysis of GR expression and other potentially predictive biomarkers. The company expects to report interim safety, efficacy, and translational data from this trial in the first half of 2021.
ORIC-533: CD73 Inhibitor
ORIC-533 was designed to be a highly potent, orally bioavailable CD73 inhibitor and has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule CD73 inhibitors. ORIC-533 continues to progress in Investigational New Drug (IND) enabling studies and the company expects to file an IND with the Food and Drug Administration (FDA) in the first half of 2021. Having conducted a preclinical collaboration with an academic key opinion leader that generated compelling single agent activity in patient derived model systems in an undisclosed tumor type, the company plans to pursue a single agent clinical development path in this indication.
ORIC-944: PRC2 Inhibitor
ORIC-944, in-licensed in August 2020, is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2), that targets its regulatory embryonic ectoderm development (EED) subunit and has demonstrated single agent efficacy in multiple enzalutamide-resistant prostate cancer models in preclinical studies. The company plans to conduct IND enabling studies and then file an IND with the FDA in the second half of 2021, with initial clinical development as a single agent in treatment-resistant prostate cancer.
ORIC-114: EGFR/HER2 Inhibitor
ORIC-114, in-licensed in October 2020, is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. ORIC-114 has demonstrated greater brain exposure in preclinical studies compared to other compounds being developed against exon 20 mutations and has shown strong antitumor activity in an EGFR-driven intracranial lung cancer model. The company plans to conduct IND enabling studies and then file a Clinical Trial Application (CTA) in South Korea in the second half of 2021.
Discovery Pipeline
In addition to the four product candidates, the company is leveraging its resistance platform in pursuit of multiple discovery research programs that focus on its expertise in precision oncology, hormone-dependent cancers, and key tumor dependencies. These programs highlight the company’s medicinal chemistry and structure-based drug design proficiency to target drivers of resistance in solid tumors like prostate, breast, and lung cancer that relapse with innate, acquired or bypass mechanisms of resistance. The company recently advanced one of these programs into lead optimization.
Anticipated 2021 Milestones
ORIC anticipates the following milestones in 2021:
ORIC-101: Report interim safety, efficacy, and translational data from ongoing combination trial with nab-paclitaxel in the first half of 2021
ORIC-101: Report interim safety, efficacy, and translational data from ongoing combination trial with enzalutamide in the second half of 2021
ORIC-533: File an IND in the first half of 2021
ORIC-944: File an IND in the second half of 2021
ORIC-114: File a CTA in the second half of 2021
Present additional preclinical and translational research data on ORIC-101, ORIC-533, ORIC-944, and ORIC-114 at scientific conferences in 2021
Financial Guidance
Cash, cash equivalents and marketable securities totaled $293.6 million as of December 31, 2020, which included gross proceeds of $133.3 million from the follow-on financing completed in November 2020. The company expects its cash, cash equivalents and marketable securities will be sufficient to fund its current operating plan into the second half of 2023.
Presentation and Webcast
Jacob Chacko, M.D., president and chief executive officer, will present a corporate overview at the 39th J.P. Morgan Healthcare Conference beginning at 12:40 p.m. PT on Tuesday, January 12, 2021. A live webcast will be available through the investor section of the company’s website at View Source A replay of the webcast will be available for 90 days following the event.