On March 22, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the discontinuation of ORIC-101 and also reported financial results and operational updates for the quarter and year ended December 31, 2021 (Press release, ORIC Pharmaceuticals, MAR 22, 2022, View Source [SID1234610602]). The company conducted planned interim analyses of two Phase 1b studies and concluded that ORIC-101 did not demonstrate sufficient clinical activity to warrant further development.
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"We are disappointed in the outcome of the ORIC-101 studies in combination with nab-paclitaxel in various solid tumors and in combination with enzalutamide in metastatic prostate cancer, two late-line patient populations for whom limited treatment options exist today. We believe both studies were well designed, allowing us to thoroughly and efficiently answer an important clinical question. With this decision to discontinue ORIC-101 development, we would like to thank the investigators, site staff, the ORIC team, and most importantly, patients and families who participated in the trials," said Pratik S. Multani, MD, chief medical officer.
"We’ve always been committed to rapid, data driven decision making and allocating resources efficiently and prudently," said Jacob M. Chacko, MD, chief executive officer, "We intentionally built a diverse pipeline of differentiated programs, which includes our Phase 1b single agent trials for ORIC-533, our orally bioavailable CD73 inhibitor, ORIC-114, our brain penetrant EGFR/HER2 inhibitor, and ORIC-944, our embryonic ectoderm development (EED) inhibitor. We expect to report initial data from each study in the first half of 2023. As a result of the ORIC-101 discontinuation, we project our cash runway to extend into the second half of 2024, well beyond the planned initial data disclosures from these three clinical programs."
Fourth Quarter 2021 and Other Recent Highlights
ORIC-101: Glucocorticoid Receptor Antagonist
Based on interim analyses from the two Phase 1b studies, ORIC-101 did not demonstrate sufficient clinical activity and, therefore, the company has discontinued further development.
The dose expansion portion of the Phase 1b clinical trial of ORIC-101 in combination with enzalutamide enrolled 28 patients at the recommended phase 2 dose (RP2D) with metastatic prostate cancer progressing on enzalutamide. The RP2D was well tolerated with a safety profile consistent with previously reported results. ORIC-101 in combination with enzalutamide did not translate into a meaningful clinical benefit, with a median progression-free survival (PFS) in the target patient population of 3.7 months.
The dose expansion portion of the Phase 1b clinical trial of ORIC-101 in combination with nab-paclitaxel enrolled 61 patients at the RP2D across four cohorts: pancreatic ductal adenocarcinoma (PDAC), ovarian cancer, triple negative breast cancer (TNBC), and other advanced solid tumors. The RP2D was well tolerated with a safety profile consistent with previously reported results. There were no objective responses in the PDAC cohort (n=21) and there was one confirmed partial response in the ovarian cancer cohort (n=13). There was no meaningful clinical benefit based on median PFS across all cohorts (PDAC: 1.9 months, and ovarian cancer: 2.2 months).
ORIC-533: CD73 Inhibitor
ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73 and has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule inhibitors of the adenosine pathway.
Ex vivo human data supporting the therapeutic potential of single agent ORIC-533 in multiple myeloma were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.
Single agent activity in an autologous bone marrow mononuclear assay system from multiple myeloma patients showed CD73 inhibition compared favorably to approved therapies for the treatment of multiple myeloma, including lenalidomide, bortezomib and daratumumab.
A Phase 1b trial with ORIC-533 as a single agent in multiple myeloma is enrolling patients and initial data are expected to be reported in the first half of 2023.
ORIC-114: EGFR/HER2 Inhibitor
ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations.
Compelling brain exposure and antitumor activity of ORIC-114 in preclinical studies of HER2-positive breast cancer were presented at AACR (Free AACR Whitepaper)-NCI-EORTC.
Head-to-head data in an EGFR exon 20 NSCLC xenograft model were disclosed demonstrating good tolerability and improved efficacy, including a 90% complete response rate, with ORIC-114 versus multiple clinical stage exon 20 inhibitors.
The Clinical Trial Application (CTA) for ORIC-114 was filed in the fourth quarter of 2021 and was cleared by the regulatory authorities of the Republic of Korea in the first quarter of 2022.
A Phase 1b trial with ORIC-114 as a single agent has been initiated and will enroll patients with advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplification and will allow patients with CNS metastases that are either treated or untreated but asymptomatic. The company expects to report initial Phase 1b data from this trial in the first half of 2023.
ORIC-944: PRC2 Inhibitor
ORIC-944 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 IND for ORIC-944 was cleared by the FDA in the fourth quarter of 2021.
A Phase 1b trial with ORIC-944 as a single agent will enroll patients with metastatic prostate cancer. The company expects to report initial Phase 1b data from this trial in the first half of 2023.
PLK4 Inhibitor Program
In March, the company announced a small molecule therapeutic program intended to address a mechanism of innate resistance found in a subset of breast cancers, specifically a synthetic lethal interaction of polo-like kinase 4 (PLK4) inhibition in tumors bearing a TRIM37 DNA amplification. Breast cancer models as well as other tumor models with this TRIM37 amplification have a key tumor dependency on PLK4 and our therapeutic approach is to selectively inhibit this enzyme.
Corporate
In November 2021, the company appointed Angie You, PhD, to its board of directors. Dr. You was most recently CEO of Amunix Pharmaceuticals, which was acquired by Sanofi, and brings broad experience spanning venture capital, business development and public company leadership roles.
Anticipated Program Milestones
ORIC anticipates the following upcoming milestones:
ORIC-533: Initial Phase 1b data in 1H 2023
ORIC-114: Initial Phase 1b data in 1H 2023
ORIC-944: Initial Phase 1b data in 1H 2023
Fourth Quarter and Full year 2021 Financial Results
Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $280.4 million as of December 31, 2021, and with the discontinuation of ORIC-101, the company expects its cash runway to be extended into the second half of 2024.
R&D Expenses: Research and development (R&D) expenses were $16.7 million for the three months ended December 31, 2021, compared to $12.1 million for the three months ended December 31, 2020, an increase of $4.6 million. For the year ended December 31, 2021, R&D expenses were $56.9 million compared to $35.9 million for the same period of 2020, an increase of $20.9 million. The increases for the 2021 periods were primarily driven by an increase in external expenses related to the advancement of ORIC-101, ORIC-533 and our other product candidates, as well as higher personnel costs, including additional non-cash stock-based compensation of $0.7 million and $2.9 million for the three and twelve months ended December 31, 2021, as compared to the same periods in 2020, respectively.
G&A Expenses: General and administrative (G&A) expenses were $6.1 million for the three months ended December 31, 2021, compared to $4.3 million for the three months ended December 31, 2020, an increase of $1.8 million. For the year ended December 31, 2021, G&A expenses were $22.0 million compared to $13.4 million for the same period in 2020, an increase of $8.6 million. These increases were primarily due to higher personnel costs, including additional non-cash stock-based compensation of $1.1 million and $4.6 million for the three and twelve months ended December 31, 2021, as compared to the same periods in 2020, respectively, and higher costs related to operating as a public company.
Webcast and Conference Call
ORIC will host a conference call and webcast today at 5:00 p.m. ET. To participate in the conference call, please dial (833) 651-0991 (domestic) or (918) 922-6080 (international) and refer to conference ID 8637367. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.