ORIC® Pharmaceuticals Provides Early Phase 1b Combination Data for ORIC-944, Operational Highlights for 2024, and Anticipated Upcoming Milestones

Rhea-AI Summary

ORIC Pharmaceuticals has reported encouraging early Phase 1b combination data for ORIC-944 in treating metastatic castration-resistant prostate cancer (mCRPC). The trial showed deep PSA decreases, with 3 of 6 patients achieving confirmed PSA50 responses and 2 achieving PSA90 responses. The treatment demonstrated favorable safety with primarily Grade 1 and 2 adverse events.

The company entered a clinical collaboration with Johnson & Johnson to evaluate ORIC-114 combined with amivantamab for first-line NSCLC treatment. ORIC expects seven data readouts across its clinical programs over the next 18 months, with potential registrational trials starting in 2H25 and early 2026.

Following a $125 million private placement financing, ORIC's cash position stood at $282.4 million as of September 30, 2024, expected to fund operations into late 2026.

Positive

• Strong early Phase 1b data showing PSA90 responses in 2 of 6 patients
• Strategic collaboration with Johnson & Johnson for ORIC-114 development
• Robust cash position of $282.4 million funding operations through late 2026
• Seven clinical data readouts planned over next 18 months

Negative

• Small patient sample size (n=6) in initial Phase 1b trial
• Extended timeline to potential registrational trials (2H25/early 2026)

Insights

Oncology Research Analyst

The early Phase 1b data for ORIC-944 shows promising efficacy signals in metastatic castration-resistant prostate cancer (mCRPC). The 50% PSA response rate (3 out of 6 patients) and notably 2 patients achieving PSA90 responses with durability up to 38 weeks represents encouraging clinical activity. The favorable safety profile with mainly Grade 1-2 adverse events suggests potential for combination therapy.

The clinical collaboration with Johnson & Johnson for ORIC-114 plus amivantamab in first-line EGFR exon 20 NSCLC is strategically significant, as this combination could address an important unmet need. With $282.4 million in cash providing runway into late 2026 and seven planned data readouts over 18 months, ORIC is well-positioned to advance both programs toward registrational trials.

The reported drug properties of ORIC-944, including ~20-hour half-life and lack of CYP autoinduction, differentiate it from first-generation PRC2 inhibitors. This could translate to improved clinical outcomes compared to existing options.

Financial Analyst

The $125 million PIPE financing from healthcare specialist funds significantly strengthens ORIC's financial position. With $282.4 million in cash and investments as of September 2024, the extended runway into late 2026 provides ample cushion to reach multiple value-inflecting clinical milestones.

The strategic collaborations with major pharmaceutical companies (Johnson & Johnson and Bayer) validate ORIC's platform and reduce development risks. These partnerships could potentially lead to future licensing or M&A opportunities. The planned seven data readouts through mid-2026 create multiple catalysts that could drive stock performance.

The expansion into commercial planning with the hiring of a SVP of Commercial and Medical Affairs indicates confidence in the clinical programs and preparation for potential market entry. The company's focus on therapeutic resistance mechanisms in oncology addresses high-value market opportunities in both prostate cancer and NSCLC.

Announces encouraging early safety and efficacy data in ongoing dose escalation trial for ORIC-944 in combination with apalutamide in patients with mCRPC

Entered into clinical trial collaboration and supply agreement with Johnson & Johnson to evaluate ORIC-114 in combination with subcutaneous amivantamab for the first-line treatment of NSCLC patients with EGFR exon 20 insertion mutations

Expects to report seven data readouts across ORIC-114 and ORIC-944 clinical programs over the next 18 months, with potential initiation of registrational trials in 2H25 and early 2026

Cash and investments expected to fund operating plan into late 2026

SOUTH SAN FRANCISCO and SAN DIEGO, Jan. 13, 2025 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today provided early Phase 1b combination data for ORIC-944, operational highlights for 2024, and anticipated upcoming milestones.

“We made strong progress on multiple fronts in 2024, most notably with the initiation of multiple cohorts for ORIC-114 in NSCLC and ORIC-944 in mCRPC. We also forged three strategic collaborations with leading pharma partners, strengthened our leadership team to expand functional capabilities, and completed a $125 million PIPE financing, extending our cash runway into late 2026,” said Jacob M. Chacko, M.D., president and chief executive officer. “These accomplishments position us well for 2025 and beyond, with seven anticipated data readouts over the next 18 months as we advance toward potentially initiating registrational studies for ORIC-114 in the second half of 2025 and for ORIC-944 in early 2026.”

Updated Phase 1b Combination Data for ORIC-944

ORIC-944 is a potent and selective allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via allosteric targeting of the embryonic ectoderm development (EED) subunit. ORIC-944 was initially evaluated as a single agent in a Phase 1b trial in patients with advanced prostate cancer and demonstrated potential best-in-class drug properties, including a clinical half-life of approximately 20 hours, robust target engagement, and a favorable safety profile.

In mid-2024, the Company initiated once daily dosing of ORIC-944 in combination with 240 mg QD apalutamide or with 600 mg BID darolutamide, as part of the ongoing Phase 1b trial in patients with metastatic castration resistant prostate cancer (mCRPC). As of the December 10, 2024 data cut-off, the Company completed the first two ORIC-944 dose escalation cohorts (n=6 patients) for the apalutamide combination. This initial experience demonstrated:

• Deep prostate-specific antigen (PSA) decreases across both the 600 mg and 800 mg dose cohorts; 3 of 6 patients achieved confirmed PSA50 responses, of which 2 achieved confirmed PSA90 responses. All the PSA responses were maintained at ≥12 weeks, including a durable confirmed PSA90 response ongoing at 38 weeks.

• Well-tolerated safety, with primarily Grade 1 and Grade 2 treatment related adverse events (TRAE), consistent with PRC2 and androgen receptor (AR) inhibition, and one Grade 3 TRAE of fatigue (patient remains on treatment without dose modification). The first two dose levels cleared without dose limiting toxicities or treatment discontinuations related to safety. Dose escalation is ongoing.
  

Dose escalation for the combination of ORIC-944 with darolutamide is also ongoing with the first dose cohort completed and the second enrolling. Preliminary clinical activity seen to date is consistent with the apalutamide combination cohort.

2024 Key Accomplishments

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

• Entered into a clinical trial collaboration and supply agreement with Johnson & Johnson to evaluate ORIC-114 in combination with subcutaneous (SC) amivantamab for the 1L treatment of NSCLC patients with EGFR exon 20 insertion mutations.
• Initiated a cohort to evaluate ORIC-114 monotherapy for the treatment of patients with 1L treatment-naïve EGFR exon 20 insertion NSCLC.
• Announced the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 and the selection of two provisional recommended phase 2 doses; after which, first patients were dosed across three expansion cohorts in the Phase 1b trial of ORIC-114 in patients with mutated non-small cell lung cancer (NSCLC), including 2L EGFR exon 20 insertion (EGFR exon 20 inhibitor naïve), 2L+ HER2 exon 20 insertion, and 2L+ EGFR atypical mutations.
• Presented preclinical data demonstrating potential best-in-class properties, including potency and selectivity, of ORIC-114 to treat NSCLC harboring EGFR exon 20 insertions and other atypical EGFR mutations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.

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

• Initiated dosing of ORIC-944 in combination with ERLEADA^® (apalutamide) and in combination with NUBEQA^® (darolutamide) in mid-2024 in the ongoing Phase 1b trial for prostate cancer.
• Entered into clinical trial collaboration and supply agreements with Johnson & Johnson and Bayer to support the ongoing Phase 1b trial of ORIC-944 in combination with AR inhibitors for the treatment of prostate cancer.
• Reported initial Phase 1b single agent data for ORIC-944 in metastatic prostate cancer supporting advancement into combination development and demonstrating the potential as a best-in-class PRC2 inhibitor, including a clinical half-life of ~20 hours, robust target engagement, no signs of CYP autoinduction that was observed with first-generation PRC2 inhibitors, and a generally well-tolerated safety profile.
• Presented preclinical data at the 2024 AACR Annual Meeting demonstrating superior drug properties and synergy data in prostate cancer models, reinforcing the promise of ORIC-944 as a potential best-in-class treatment for combination with AR inhibitors.

Corporate Highlights:

• Strengthened cash position and runway with a $125 million private placement financing from new and existing healthcare specialist funds.
• Expanded the leadership team with the appointment of industry veteran Keith Lui as Senior Vice President of Commercial and Medical Affairs.

Anticipated Program Milestones

ORIC anticipates the following upcoming data milestones:

• ORIC-114 (NSCLC):
  • 1H 2025: 2L EGFR exon 20 and 2L+ HER2 exon 20
  • 2H 2025: 2L+ EGFR atypical
  • 1H 2026: 1L EGFR exon 20
  • Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical
• ORIC-944 (mCRPC):
  • 4Q 2025 / 1H 2026: Combination with AR inhibitors
    

Financial Guidance
As of September 30, 2024, cash, cash equivalents and investments totaled $282.4 million, which the company expects will be sufficient to fund its operating plan into late 2026.

Presentation and Webcast

Jacob M. Chacko, M.D., president and chief executive officer, will present a company overview at the 43rd Annual J.P. Morgan Healthcare Conference on Tuesday, January 14, 2025, 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.

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-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, and (2) ORIC-944, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the EED subunit, being developed for prostate cancer. 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-114 and ORIC-944; statements regarding the potential best-in-class properties of ORIC-114 and ORIC-944; clinical outcomes from combination studies with ORIC-944, which may materially change as patient enrollment continues or more patient data become available; the development plans and timelines for ORIC-114, ORIC-944 and ORIC’s other product candidates; the potential advantages of ORIC-114, ORIC-944 and ORIC’s other product candidates and programs; plans underlying ORIC’s clinical trials and development; anticipated program milestones, including timing of program and data updates and the initiation of registrational studies; the period over which ORIC estimates its existing cash, cash equivalents and investments will be sufficient to fund its current operating plan; 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 Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on November 12, 2024, 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

What were the key results from ORIC-944's Phase 1b combination trial in mCRPC?

The trial showed deep PSA decreases with 3 of 6 patients achieving PSA50 responses and 2 achieving PSA90 responses. The treatment was well-tolerated with mainly Grade 1 and 2 adverse events.

When does ORIC Pharmaceuticals expect to start registrational trials for ORIC-114 and ORIC-944?

ORIC expects to initiate registrational trials for ORIC-114 in the second half of 2025 and for ORIC-944 in early 2026.

How long will ORIC's current cash position last?

ORIC's cash position of $282.4 million as of September 30, 2024, is expected to fund operations into late 2026.

What is the new collaboration between ORIC and Johnson & Johnson for?

The collaboration is to evaluate ORIC-114 in combination with subcutaneous amivantamab for first-line treatment of NSCLC patients with EGFR exon 20 insertion mutations.

How many data readouts does ORIC expect in the next 18 months?

ORIC anticipates seven data readouts across their ORIC-114 and ORIC-944 clinical programs over the next 18 months.