On November 8, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended September 30, 2021 (Press release, ORIC Pharmaceuticals, NOV 8, 2021, View Source [SID1234594732]).
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!
"We are proud of the ongoing steady advancement of our broad pipeline" said Jacob Chacko, M.D., president and chief executive officer. "In October, we announced initial trial data from our ORIC-101 combination with enzalutamide in prostate cancer, which demonstrated a safe and tolerable profile and encouraging early antitumor activity in a key patient population; in November, we submitted a CTA filing for ORIC-114, our brain penetrant EGFR/HER2 exon 20 inhibitor. In the fourth quarter, we also expect to initiate a Phase 1 trial with our CD73 inhibitor ORIC-533 as a single agent in multiple myeloma and to file an IND for ORIC-944, our allosteric PRC2 inhibitor."
Third Quarter 2021 and Other Recent Highlights
Data Presentations at AACR (Free AACR Whitepaper)-NCI-EORTC:
ORIC-101: The Phase 1b clinical trial of ORIC-101 in combination with enzalutamide is a single arm, multicenter, open-label study conducted in two parts, intended to establish the recommended Phase 2 dose (RP2D), safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the combination when administered in patients with metastatic prostate cancer progressing on enzalutamide. Following the completion of the Part I dose escalation portion of the trial, the RP2D was determined to be 240 mg of ORIC-101 and 160 mg of enzalutamide once daily. In the Part II dose expansion portion of the trial, up to 48 patients with metastatic prostate cancer progressing on enzalutamide are expected to be enrolled and treated with the combination at the RP2D. Patients are enrolled independent of GR status, with retrospective analysis of AR variants and GR expression and other potentially predictive biomarkers. Enrollment continues in the Part II dose expansion cohorts at nine clinical sites across the United States.
As of the August 20, 2021, data cut-off date, the key findings of the initial data presented included:
Preliminary Safety Analyses:
25 patients were enrolled across Parts I/II of the study, which included 7 patients treated at non-RP2D doses and 18 patients treated at the RP2D.
RP2D was well tolerated; treatment-related adverse events were primarily Grade 1 or 2, with only four Grade 3 events, which all resolved with dose interruption.
Tolerability profile for the combination was generally consistent with that of single agent enzalutamide.
Preliminary PK and Biomarker Analyses:
Plasma concentrations exceeded the threshold for GR inhibition at all dose levels, with GR target gene suppression observed after one dose of ORIC-101 in peripheral blood mononuclear cells from 22 of 23 patients.
ORIC-101 exposure increased with dose.
No evidence observed of drug-drug interaction impacting enzalutamide levels.
Translational efforts identified a key patient population, in line with published literature, consisting of the ~60% of patients with tumors lacking biomarkers of AR resistance (e.g., ARv7 splice variant, AR L702H point mutation) and AR independence (e.g., lineage switching).
Preliminary Antitumor Activity:
Within the key patient population (n=8), 75% (6 of 8) of patients’ tumors expressed moderate to high GR and 25% (2 of 8) of patients’ tumors expressed low GR.
The two patients with low GR came off treatment at less than two months. In contrast, the six patients with moderate to high GR demonstrated prolonged time on treatment (with two patients on treatment for over seven months, and another four patients still ongoing at varying durations at the time of the data cut).
ORIC-114: A brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. Key findings of the preclinical presentation included:
ORIC-114 demonstrated greater cell potency on HER2-positive breast cancer cell lines relative to non-amplified cell lines and was more potent than lapatinib and tucatinib, two approved tyrosine kinase inhibitors for the treatment of HER2-positive breast cancer.
ORIC-114 demonstrated robust tumor regressions in a HER2-positive breast cancer in vivo model without significant body weight loss.
ORIC-114 demonstrated superior brain exposure compared to other EGFR exon 20 and HER2 targeted agents.
Corporate: In August 2021, the company appointed Steven L. Hoerter to its board of directors. Mr. Hoerter is currently CEO of Deciphera Pharmaceuticals and has more than twenty-five years of experience in sales, marketing, commercial and public company leadership roles.
In July 2021, ORIC raised gross proceeds of $50.0 million through the sale of approximately 2.6 million shares under its ATM offering, with participation based on unsolicited interest received from a healthcare specialist fund. The company sold the shares at a purchase price per share of $19.25, a premium to the market price at the time of the sale.
Anticipated Milestones
ORIC anticipates the following milestones in the fourth quarter of 2021:
ORIC-533:
Present update on oral CD73 inhibitor program at the ASH (Free ASH Whitepaper) Annual Meeting
Initiate single agent Phase 1 trial in patients with multiple myeloma
ORIC-944: File IND
Third Quarter 2021 Financial Results
Cash, Cash Equivalents and Investments: As of September 30, 2021, cash, cash equivalents, and investments totaled $296.5 million, which the company expects will fund its current operating plan into 2024.
R&D Expenses: Research and development expenses were $12.9 million for the three months ended September 30, 2021, compared to $8.8 million for the three months ended September 30, 2020, an increase of $4.1 million. For the nine months ended September 30, 2021, R&D expenses were $40.1 million compared to $23.8 million for the same period of 2020, an increase of $16.3 million. The increases for the 2021 periods were primarily driven by an increase in external expenses related to the advancement of ORIC-101 and other product candidates of $2.8 million and $12.8 million for the three and nine months ended September 30, 2021, respectively, as well as higher personnel costs, including additional non-cash stock-based compensation of $0.7 million and $2.2 million for the three and nine months ended September 30, 2021, as compared to the same periods in 2020, respectively.
G&A Expenses: General and administrative expenses were $5.6 million for the three months ended September 30, 2021, compared to $3.8 million for the three months ended September 30, 2020, an increase of $1.8 million. For the nine months ended September 30, 2021, G&A expenses were $16.0 million compared to $9.1 million for the same period of 2020, an increase of $6.8 million. The increases were primarily due to higher personnel costs, including additional non-cash stock-based compensation of $1.1 million and $3.6 million for the three months and nine months ended September 30, 2021, as compared to the same periods in 2020, respectively, as well as higher professional services and related costs to operate as a public company.