On January 8, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported initial data for its PRC2 inhibitor ORIC-944, operational highlights for 2023, and anticipated upcoming milestones (Press release, ORIC Pharmaceuticals, JAN 8, 2024, View Source [SID1234639099]).

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"2023 was a landmark year for ORIC with both ORIC-114 and ORIC-944 generating clinical proof of concept data that position them as potential best-in-class therapies for NSCLC and prostate cancer, respectively. Additionally, with the completion of an $85 million PIPE financing from top tier new and existing funds, we extended our cash runway into 2026," said Jacob M. Chacko, M.D., president and chief executive officer. "In 2024, we are focused on initiating multiple dose expansion cohorts for ORIC-114 in NSCLC as well as combination studies with one or more AR inhibitors in prostate cancer for ORIC-944, all in anticipation of both programs potentially entering pivotal studies in 2025."

Initial Phase 1b Data for ORIC-944

As of December 10, 2023, the initial Phase 1b monotherapy data for ORIC-944, a potent and selective allosteric inhibitor of PRC2, in patients with metastatic prostate cancer demonstrated:
Potential best-in-class drug properties, including clinical half-life consistent with preclinical prediction of >10 hours, which is superior to other PRC2 inhibitors and supports QD dosing;
No signs of CYP autoinduction that is seen with first-generation PRC2 inhibitors;
Robust target engagement with maximal decrease (≥75%) in H3K27me3 in monocytes from peripheral blood samples at doses as low as 200 mg QD, with low inter-patient variability; and
Favorable safety with only grade 1 and 2 treatment-related adverse events at dose levels corresponding with strong target engagement.
Emerging profile with superior drug properties support advancement into combination development in prostate cancer with AR inhibitor(s).
2023 Key Accomplishments

ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Presented initial data from the ongoing Phase 1b dose escalation trial for patients with EGFR or HER2 exon 20 mutated non-small cell lung cancer (NSCLC) at the ESMO (Free ESMO Whitepaper) Congress 2023. Initial data demonstrated potential best-in-class profile, with favorable safety and both systemic and CNS activity in heavily pretreated patients, with 81% of patients having received prior EGFR exon 20 targeted agents and 86% having CNS metastases at baseline.
Presented preclinical data for ORIC-114 at ESMO (Free ESMO Whitepaper) Congress 2023, demonstrating potent activity across atypical mutations in EGFR, thus expanding the potential patient population.
ORIC-944: a potent and selective allosteric inhibitor of PRC2

Presented preclinical data highlighting a comprehensive biomarker strategy for the ongoing Phase 1b trial in metastatic prostate cancer at the 2023 AACR (Free AACR Whitepaper) Annual Meeting.
Demonstrated via preclinical studies the potential for ORIC-944 to synergize with enzalutamide and other AR inhibitors in prostate cancer.
ORIC-533: a highly potent, orally bioavailable small molecule inhibitor of CD73

Presented initial data from Phase 1b trial of ORIC-533 in patients with relapsed/refractory multiple myeloma at the 2023 ASH (Free ASH Whitepaper) Annual Meeting. Initial data demonstrated preliminary evidence of clinical antimyeloma activity and immune effects, as well as a clean safety profile, with only grade 1 and 2 treatment-related events in heavily pre-treated patients.
Expect to complete dose escalation for the Phase 1b trial of ORIC-533 in the first quarter of 2024, and company plans to pursue strategic partnership for combination studies.
Discovery Pipeline:

Presented preclinical data confirming the therapeutic potential of highly selective PLK4 inhibitors as a synthetic lethal therapy for TRIM37 amplified breast cancers at the 2023 AACR (Free AACR Whitepaper) Annual Meeting.
Advanced ORIC-613, a novel, highly selective PLK4 inhibitor, through IND enabling studies.
Corporate Highlights:

Strengthened cash position with $85 million private placement financing from new and existing healthcare specialist funds in the second quarter of 2023.
Anticipated Program Milestones

ORIC-944 initiation of combination study with AR inhibitor(s): 1H 2024
ORIC-944 program update: mid-2024
ORIC-114 initiation of dose expansion in multiple cohorts: 1H 2024
ORIC-114 updated Phase 1b data: 1H 2025
Financial Guidance

As of September 30, 2023, cash, cash equivalents and investments totaled $256.2 million, which the company expects will be sufficient to fund its operating plan into 2026.

Presentation and Webcast
Jacob M. Chacko, M.D., president and chief executive officer, will present a company overview at the 42nd Annual J.P. Morgan Healthcare Conference on Tuesday, January 9, 2024, at 11:15 a.m. PT. A live webcast will be available through the investor section of the company’s website at www.oricpharma.com. A replay of the webcast will be available for 90 days following the event.