ORIC® Pharmaceuticals Announces Focused Registrational Clinical Development Plans for Lead Programs, Extended Cash Runway, and Updated Corporate Milestones

Rhea-AI Summary

ORIC Pharmaceuticals has announced focused registrational clinical development plans for its lead programs ORIC-944 and ORIC-114, along with an extended cash runway into 2027. The company plans to initiate its first Phase 3 trial for ORIC-944 in metastatic castration resistant prostate cancer (mCRPC) in 1H 2026, while ORIC-114's registrational development will focus on first-line non-small cell lung cancer (NSCLC) with anticipated initiation in 2026.

Key milestones include combination dose escalation data for ORIC-944 expected in 1H and 2H 2025, and comprehensive NSCLC data for ORIC-114 in 2H 2025. The company reported $256 million in cash and investments as of December 31, 2024, extending their projected cash runway from late 2026 to 2027 under the refined operating plan.

Positive

• Extended cash runway into 2027 with $256M cash position
• Accelerated timeline for ORIC-944 dose optimization data
• Favorable enrollment trends in clinical trials
• Multiple data readouts expected throughout 2025-2026

Negative

• Phase 3 trials won't start until 2026
• Discontinued pursuit of 2L EGFR and 2L+ HER2 exon 20 NSCLC trials
• Capital markets constraints affecting development decisions

Insights

Financial Analyst

ORIC Pharmaceuticals has implemented a strategic pipeline refinement that sharpens focus on its most promising clinical opportunities while extending its financial runway. This calculated narrowing of development priorities represents a significant shift in the company's capital allocation strategy and clinical development timeline.

For ORIC-944 (PRC2 inhibitor), the acceleration of data readouts to 1H 2025 and 2H 2025 for combination trials with AR inhibitors in metastatic castration-resistant prostate cancer (mCRPC) suggests stronger-than-expected enrollment and potentially encouraging preliminary efficacy signals. The decision to advance directly to Phase 3 by 1H 2026 indicates high confidence in the mechanism of action, particularly significant given recent clinical validation of PRC2/AR inhibitor combinations in this indication. This approach targets a substantial market opportunity in mCRPC, where resistance to existing therapies remains a critical unmet need.

For ORIC-114 (brain-penetrant EGFR/HER2 inhibitor), the strategic pivot to focus exclusively on first-line NSCLC settings rather than pursuing second-line indications represents classic pipeline prioritization. First-line treatment settings typically offer 3-4x larger commercial potential due to broader patient eligibility, longer treatment durations, and higher reimbursement rates. The brain-penetrant properties of ORIC-114 could provide a meaningful differentiation in EGFR exon 20 and HER2 exon 20 patient populations, where CNS metastases remain a significant clinical challenge.

The extension of cash runway into 2027 (from previous guidance of late 2026) with $256 million in reserves as of December 2024 is particularly noteworthy in the current biotech financing environment. This extension, coupled with accelerated clinical milestones, suggests the company has optimized its operational efficiency while potentially accelerating its path to pivotal data. The refined strategy effectively balances clinical advancement with fiscal discipline, potentially postponing dilutive financing events while maintaining momentum in key programs.

This strategic refinement reflects an increasingly common approach among mid-stage oncology companies: concentrating resources on programs with the strongest clinical validation and highest commercial potential rather than advancing broader pipelines with more uncertain outcomes. For investors, this represents a more focused risk profile with potentially clearer value inflection points in 2025-2026.

Oncology Expert

ORIC Pharmaceuticals' strategic refinement of its oncology pipeline represents a scientifically sound approach targeting two critical resistance mechanisms in advanced cancers with significant unmet needs.

For ORIC-944, the focus on PRC2 inhibition in combination with AR pathway blockade in mCRPC addresses a fundamental resistance mechanism in prostate cancer progression. PRC2 overexpression drives lineage plasticity and neuroendocrine transdifferentiation, allowing tumor cells to escape AR-targeted therapy. Recent clinical evidence with other PRC2 inhibitors has validated this approach, showing that dual inhibition of both pathways can potentially restore sensitivity to AR-targeted therapies in patients who have developed resistance. The accelerated reporting of combination data in 1H 2025 and 2H 2025 suggests encouraging preliminary signals that warrant expedited development.

The mCRPC treatment landscape remains challenging despite recent advances, with most patients eventually developing resistance to available therapies. A successful PRC2/AR inhibitor combination could potentially address the approximately 34,000 patients who progress annually on current standard-of-care treatments in the U.S. alone, representing a significant therapeutic advance.

For ORIC-114, the prioritization of first-line NSCLC with EGFR exon 20, HER2 exon 20, and atypical EGFR mutations targets molecular subsets with particularly poor prognoses. The brain-penetrant properties of ORIC-114 address a critical unmet need, as approximately 30-40% of these patients develop CNS metastases, which remain poorly controlled with current therapies. The combination with subcutaneous amivantamab is particularly noteworthy, as this bispecific antibody targets both EGFR and MET, potentially addressing multiple resistance pathways simultaneously.

The decision to focus on first-line settings aligns with the evolving treatment paradigm in precision oncology, where more effective targeted therapies are increasingly moving into frontline settings to maximize duration of disease control and impact on overall survival. For patients with these molecular alterations, effective first-line options with CNS activity could significantly improve outcomes and quality of life.

From a clinical development perspective, the accelerated timelines suggest robust enrollment and potentially promising early efficacy signals. The comprehensive data update for ORIC-114 expected in 2H 2025 will be particularly informative, as it will include data across multiple molecular subtypes and could potentially demonstrate differentiation from existing therapies in terms of CNS penetration, tolerability, and durability of response.

These focused development plans address critical resistance mechanisms and treatment gaps in oncology, potentially offering new options for patient populations with effective therapies.

Anticipated registrational development plans for ORIC-944 and ORIC-114 prioritized to focus on indications with strongest clinical validation and highest unmet need

ORIC-944 initiation of first Phase 3 trial in mCRPC expected in 1H 2026; ORIC-114 registrational development plans to focus on 1L NSCLC with anticipated initiation in 2026

Favorable enrollment across both programs allows for accelerated/augmented corporate milestones, including combination dose escalation data in mCRPC expected in 1H 2025 and 2H 2025, and comprehensive NSCLC data expected in 2H 2025 that includes 1L EGFR exon 20

Projected cash runway extended into 2027 under refined operating plan

SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, Feb. 25, 2025 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today announced focused registrational clinical development plans for its two lead programs, an extension of projected cash runway into 2027 (from previous guidance of late 2026), and accelerated/augmented corporate milestones.

"Based on the initial data we have generated with ORIC-944 and ORIC-114 and recent clinical data reported with other programs in mCRPC and NSCLC, we have refined our registrational plans to focus on the most promising opportunities for both programs," stated Jacob M. Chacko, M.D., president and chief executive officer. "For ORIC-944, based on both internal and external data that validate the combination of PRC2 inhibitors with AR inhibitors in mCRPC, we intend to initiate our first Phase 3 trial in 1H 2026. For ORIC-114, we intend to initiate registrational trial(s) in 2026 with a focus on areas of highest unmet need in first-line NSCLC settings. With these focused registrational plans, we have extended our projected cash runway into 2027."

Registrational Clinical Development Plans and Updated Corporate Milestones:

ORIC-944: a potent and selective allosteric inhibitor of PRC2

• Given the recently reported encouraging early safety and efficacy data from an ongoing dose escalation trial for ORIC-944 in combination with apalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) and favorable enrollment trends, ORIC now expects to report dose escalation data of ORIC-944 both in combination with apalutamide and in combination with darolutamide in 1H 2025, followed by an additional update in 2H 2025.
• Expected timing for the previously communicated milestone of ORIC-944 dose optimization data in combination with AR inhibitor(s) has been accelerated/narrowed to 4Q25 or 1Q26 (previously 4Q25 or 1H 2026).
• ORIC expects to initiate its first Phase 3 trial for ORIC-944 in mCRPC in 1H 2026.
  

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

• Given favorable enrollment for ORIC-114 in the 1L EGFR exon 20 monotherapy cohort and the 2L+ atypical EGFR cohort, ORIC now expects to provide a comprehensive data update during 2H 2025 that will include these two cohorts along with cohorts for 2L EGFR exon 20 and 2L+ HER2 exon 20.
• ORIC-114 in combination with subcutaneous (SC) amivantamab in patients with 1L EGFR exon 20 has recently been initiated. Initial data from this trial in addition to ORIC-114 data as a monotherapy in 1L EGFR atypical mutations are expected in mid-2026.
• ORIC expects to initiate Phase 3 trial(s) for ORIC-114 in 1L NSCLC in 2026, in EGFR exon 20, HER2 exon 20, and/or atypical EGFR mutations. ORIC does not currently plan to pursue registrational trials of ORIC-114 in 2L EGFR and 2L+ HER2 exon 20 NSCLC given the more significant commercial opportunity in first-line settings and the current state of capital markets.
  

Corporate Highlights:

• Cash, cash equivalents and investments totaled $256 million as of December 31, 2024; based on the refined operating plan, projected cash runway has been extended into 2027.
  

About ORIC Pharmaceuticals, Inc.
ORIC Pharmaceuticals is a clinical stage biopharmaceutical company dedicated to improving patients’ lives by Overcoming Resistance In Cancer. ORIC’s clinical stage product candidates include (1) ORIC-944, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the EED subunit, being developed for prostate cancer, and (2) ORIC-114, a brain penetrant inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, being developed across multiple genetically defined cancers. Beyond these two product candidates, ORIC^® is also developing multiple precision medicines targeting other hallmark cancer resistance mechanisms. ORIC has offices in South San Francisco and San Diego, California. For more information, please go to www.oricpharma.com, and follow us on X or LinkedIn.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the continued clinical development of ORIC-944 and ORIC-114; statements regarding the potential of ORIC-944 and ORIC-114; clinical outcomes, which may materially change as patient enrollment continues or more patient data become available; the development plans and timelines for ORIC-944, ORIC-114 and ORIC’s other programs; the potential advantages of ORIC-944, ORIC-114 and ORIC’s other programs; plans underlying ORIC’s clinical trials and development; anticipated program milestones, including timing of program and data updates and the initiation of Phase 3 or registrational studies; ORIC’s projected cash runway; and statements by the company’s chief executive officer. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon ORIC’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company; ORIC’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in ORIC’s plans to develop and commercialize its product candidates; the potential for clinical trials of ORIC’s product candidates to differ from preclinical, initial, interim, preliminary or expected results; negative impacts of health emergencies, economic instability or international conflicts on ORIC’s operations, including clinical trials; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of ORIC’s license and collaboration agreements or its clinical trial collaboration and supply agreements; the potential market for ORIC’s product candidates, and the progress and success of competing therapeutics currently available or in development; ORIC’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; ORIC’s reliance on third parties, including contract manufacturers and contract research organizations; ORIC’s ability to obtain and maintain intellectual property protection for its product candidates; the loss of key scientific or management personnel; competition in the industry in which ORIC operates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section titled “Risk Factors” in ORIC’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (the “SEC”) on February 18, 2025, and ORIC’s future reports to be filed with the SEC. These forward-looking statements are made as of the date of this press release, and ORIC assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.

Contact:
Dominic Piscitelli, Chief Financial Officer
dominic.piscitelli@oricpharma.com
info@oricpharma.com

FAQ

When will ORIC Pharmaceuticals initiate Phase 3 trials for ORIC-944 in mCRPC?

ORIC plans to initiate its first Phase 3 trial for ORIC-944 in mCRPC in the first half of 2026.

What is the current cash position of ORIC Pharmaceuticals (ORIC) as of December 2024?

ORIC reported $256 million in cash, cash equivalents and investments as of December 31, 2024.

When will ORIC release comprehensive NSCLC data for ORIC-114?

ORIC expects to provide comprehensive NSCLC data for ORIC-114 during the second half of 2025.

What are the target indications for ORIC-114's registrational trials?

ORIC-114's registrational trials will focus on first-line NSCLC settings, specifically in EGFR exon 20, HER2 exon 20, and/or atypical EGFR mutations.

How long will ORIC's current cash runway last according to their refined operating plan?

ORIC's refined operating plan extends their projected cash runway into 2027, extended from previous guidance of late 2026.