Slides
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Company Overview September 2026
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Forward-Looking Statements 2 This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding ORIC Pharmaceuticals, Inc.’s (“ORIC”, “we”, “us” or “our”) future financial condition, results of operations, business strategy and plans, and objectives of management for future operations, as well as statements regarding industry trends, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potentially,” “predict,” “should,” “will” or the negative of these terms or other similar expressions. Forward-looking statements contained in this presentation also include, but are not limited to, statements regarding: our development plans and timelines; the potential advantages of, and commercial opportunities for, our product candidates and programs; plans for the clinical trials and development of enozertinib (ORIC- 114) and rinzimetostat (ORIC-944); enozertinib and rinzimetostat clinical outcomes, which may materially change as patient enrollment continues or more patient data becomes available; the expected timing of reporting data from our clinical trials; our anticipated milestones and clinical updates; and the period over which we estimate our existing cash and investments will be sufficient to fund our current operating plan. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: the timing of the initiation, progress and results of our preclinical studies and clinical trials; risks associated with the process of developing and commercializing drugs that are safe and effective for use in humans and operating as an early clinical stage company; negative impacts of health emergencies, economic instability or international conflicts on our operations, including clinical trials; the potential for current or future clinical trials of product candidates to differ from preclinical, initial, interim, preliminary or expected results; our ability to advance product candidates into, and successfully complete, clinical trials; the timing or likelihood of regulatory filings and approvals; changes in our plans to develop and commercialize our product candidates; our estimates of the number of patients who suffer from the diseases we are targeting and the number of patients that may enroll in our clinical trials; the commercializing of our product candidates, if approved; our ability to successfully manufacture and supply our product candidates for clinical trials and for commercial use, if approved; potential benefits and costs of strategic arrangements, licensing and/or collaborations; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of our license or collaboration agreements; our estimates regarding expenses, future revenue, capital requirements and needs for financing and our ability to obtain capital; the sufficiency of our existing cash and investments to fund our future operating expenses and capital expenditure requirements; our ability to retain the continued service of our key personnel and to identify, hire and retain additional qualified professionals; the implementation of our business model and strategic plans for our business and product candidates; the scope of protection we are able to establish and maintain for intellectual property rights, product candidates and our pipeline; our ability to contract with third-party contract research organizations, suppliers and manufacturers and their ability to perform adequately; the pricing, coverage and reimbursement of our product candidates, if approved; developments relating to our competitors and our industry, including competing product candidates and therapies; regulatory developments in the United States and foreign countries; general economic and market conditions; and the other risks, uncertainties and assumptions discussed in the public filings we have made and will make with the Securities and Exchange Commission (“SEC”). These risks are not exhaustive. New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Except as required by law, we undertake no obligation to update any statements in this presentation for any reason after the date of this presentation. We have filed Current Reports on Form 8-K, Quarterly Reports on Form 10-Q, Annual Reports on Form 10-K, and other documents with the SEC. You should read these documents for more complete information about us. You may obtain these documents for free by visiting EDGAR on the SEC website at www.sec.gov. This presentation discusses our product candidates that are under preclinical or clinical study, and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of our product candidates for the therapeutic use for which they are being studied.
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ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer 3 Validated Targets in High Unmet Need Populations Late-Stage Clinical Pipeline Strong Financial Position Experienced Management Team • Potential best-in-class PRC2 inhibitor for prostate cancer • Potential best-in-class TKI for NSCLC with EGFR exon 20 insertion and EGFR atypical mutations • Heritage of discovering, developing, and commercializing oncology therapies at Ignyta, Medivation, Aragon, Pharmacyclics, Deciphera, and Genentech • Rinzimetostat: first Phase 3 initiated in post-abiraterone mCRPC • Enozertinib: rapidly advancing towards potential Phase 3 initiation(s) in 1L EGFR-mutant NSCLC Anticipated Milestones • Rinzimetostat for mCRPC: Announced combination dose optimization data with AR inhibitor Initiated first global Phase 3 registrational trial in post-abiraterone mCRPC ─ 2H26: Program update • Enozertinib for NSCLC: ─ Oct 2026: 1L EGFR atypical monotherapy data to be presented at ESMO Congress 2026 ─ 2H26: 1L EGFR exon 20 monotherapy data and combination data with SC amivantamab (1) Note: Cash and investments as of June 30, 2026. Abiraterone refers to abiraterone acetate. (1) Clinical collaboration with Johnson & Johnson to evaluate enozertinib in combination with amivantamab and hyaluronidase-lpuj subcutaneous injection (SC amivantamab) in patients with first -line NSCLC with EGFR exon 20 mutations. • Cash and investments of $388 million expected to fund company into 2H 2028 • Funding through primary endpoint readout from first Phase 3 trial of rinzimetostat Two potential best-in-class programs in or approaching Phase 3; cash runway into 2H28, beyond rinzimetostat Phase 3 data
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Executive Team with Expertise in Building Leading Oncology Companies 4 • Previously CFO at Ignyta (acquired by Roche), raised >$500m in capital • TPG Capital (completed $10bn of aggregate acquisitions) and McKinsey & Company • Board member of 4D Molecular and Board Chair of Bright Peak; previously Turning Point, Bonti, RentPath, EnvisionRx, Par Pharma, IMS and Quintiles Jacob Chacko, MD Chief Executive Officer Pratik Multani, MD Chief Medical Officer Matt Panuwat Chief Business Officer • Previously SVP of Business Development at Prothena, established Celgene collaboration for up to $2.2bn • Head of Business Development at Medivation (acquired by Pfizer) • Global Healthcare Investment Banking at Merrill Lynch • Previously CMO of Ignyta; led development and regulatory for ROZLYTREK (entrectinib) • CMO of Fate; previously at IDEC, Salmedix, Dana Farber and MGH • Board member of Erasca and Chimerix Lori Friedman, PhD Chief Scientific Officer • Previously Head of Translational Oncology at Genentech; advanced >20 drug candidates into development • Director of Signal Transduction at Exelixis Christian Kuhlen, MD General Counsel • Previously General Counsel at Synthorx (acquired by Sanofi), completed $151 million IPO • General Counsel at Ignyta and Genoptix Dominic Piscitelli Chief Financial Officer • Previously CFO at AnaptysBio, raised >$500m in capital • VP of Finance, Strategy and IR at Medivation and OSI Pharmaceuticals • Board member of Alterome Therapeutics and Celyad Oncology Edna Chow Maneval, PhD EVP Clinical Development • Previously SVP at Ignyta; clinical lead for ROZLYTREK, led transition team through global filings • VP of Clinical Development at Seragon and Aragon, clinical lead for ERLEADA (apalutamide) Keith Lui SVP Commercial & Medical Affairs • Previously SVP of Business Development, Commercial and Medical Affairs at DURECT • Led commercial strategy and launch-readiness at Pharmacyclics, Genentech, Prothena, and Oncopeptides Kevin Brodbeck, PhD Chief Technical Officer • Previously Chief Technical and Development Operations Officer at Deciphera Pharmaceuticals; led pharmaceutical sciences (CMC) and supply chain operations • SVP of Technical Operations at Nektar Therapeutics; led the global CMC development and manufacturing organization
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5 Note: ARi – androgen receptor inhibitor. (1) Clinical collaboration with Johnson & Johnson to evaluate enozertinib in combination with SC amivantamab in patients with fi rst-line NSCLC with EGFR exon 20 mutations. Clinical Pipeline Focused on Advancement of Rinzimetostat and Enozertinib Program Indication PRODUCT CANDIDATES Enozertinib EGFR inhibitor Rinzimetostat PRC2 inhibitor Discovery / IND Enabling Phase 1/2 Pivotal / Phase 3 Clinical Collaboration Phase 3 Initiations • Post-abiraterone and post-ARi • Combination with darolutamide • 1L monotherapy • 1L combination with SC amivantamab (1) • 1L combination with chemotherapy • Post-abiraterone and post-ARi • Combination with apalutamide • 1L monotherapy Prostate Cancer NSCLC EGFR atypical NSCLC EGFR exon 20 Potential Redwood-1 in 2027 • Post-abiraterone • Combination with darolutamide Potential Himalayas-2 in 2027 Himalayas-1 Initiated Diversified, late-stage pipeline includes two potential best-in-class programs addressing large solid tumor market opportunities
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Combination of Rinzimetostat + Darolutamide Compares Favorably to Competitor PRC2 Combination and to AR Inhibitor Monotherapy In Post-Abiraterone mCRPC Rinzimetostat Dose Optimization Update (March 2026) PSA50 SAFETY (All Grade / Grade ≥3) Rinzimetostat 400 mg QD + Darolutamide Mevrometostat 1250 mg BID Fasted + EnzalutamideEnzalutamide • Fatigue (39% / 0%) • Diarrhea (22% / 0%) • Nausea (22% / 0%) • Blood creatinine increased (17% / 0%) • Decreased appetite (11% / 0%) • Anemia (11% / 0%) • AE cutoff of ≥10% • Diarrhea (78% / 17%) • Dysgeusia (59% / 0%) • Decreased appetite (59% / 0%) • Fatigue (56% / 5%) • Anemia (49% / 5%) • Nausea (42% / 0%) • Alopecia (39% / 0%) • Thrombocytopenia (29% / 2%); 2% Gr 4 • Neutropenia (22% / 7%); 2% Gr 4 • Vomiting (22% / 0%) • Arthralgia (22% / 0%) • Rash (20% / 2%) • AE cutoff of ≥20% • Fatigue (43% / 3%) • Nausea (25% / 0%) • Anemia (23% / 3%) • Diarrhea (18% / 0%) • Decreased appetite (18% / 0%) • Dysgeusia (8% / 0%) 6 Source: ORIC data on file. Enzalutamide and mevrometostat + enzalutamide data from Schweizer et al. ASCO GU (2025) and Matsubara et al. ASCO (2025). AEs <30% estimated from Matsubara et al. ASCO (2025). Note: Competitor rPFS percentages estimated from published data. PSA50 represents confirmed responses. Cross -trial comparison in previously treated mCRPC patients shown. Rinzimetostat + darolutamide efficacy data as of March 6, 2026, and TRAE data as of January 16, 2026. Enzalutamide AEs represent TEAE cutoff >30% across both mevrometostat 1250 mg BID + enzalutamide and enzalutamide monotherapy. Rinzimetostat + ARi safety profile compatible with long-term dosing, with the majority of AEs Grade 1, and no Grade 4/5 events 5-Month rPFS 33%34%15% 4-Month rPFS 3-Month rPFS 84% 84% 93% 80% 86% 92% 60% 70% 78%
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Enozertinib Phase 1b Data Establishes Potential Best-in-Class Profile in EGFR Exon 20 and PACC Mutated NSCLC 7 2L EGFR Exon 20 40% 45% Benchmark ORR ORR 22% 36% Benchmark ORR ORREnozertinib Enozertinib Ongoing development of enozertinib is focused on 1L, where preliminary data demonstrated potential best-in-class systemic and intracranial activity Enozertinib Updated Phase 1b Data Highlights (ESMO Asia 2025) Previously Treated Median 3L EGFR PACC Source: John et al. ESMO Asia (2025), Hong et al. ESMO Asia (2025), and ORIC data on file. Benchmark ORR: Piotrowska et al. J Clin Oncol (2025) and Udagawa et al. WCLC (2025). Note: All data in previously treated patients represent confirmed ORR. All data in 1L patients represent best ORR, due to prelim inary nature of data. 1L EGFR exon 20 intracranial ORR data in all patients with measurable CNS disease by BICR-RANO and 1L EGFR PACC intracranial ORR data in all patients with measurable CNS disease by investigator assessment using RECIST. PACC – P-loop and alpha C-helix compressing. 100% 67% Intracranial ORR ORR 100% 80% Intracranial ORR ORR Enozertinib Treatment- Naïve (1L) 1L EGFR Exon 20 (Preliminary Data) 1L EGFR PACC (Preliminary Data) Enozertinib Enozertinib Enozertinib
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8 Both Rinzimetostat and Enozertinib Have Multibillion Dollar Commercial Opportunities in the US Alone Rinzimetostat mCRPC Post-Abiraterone mCRPC Post-AR Inhibitor mCSPC Enozertinib NSCLC EGFR exon 20 NSCLC EGFR atypical Estimated Initial US Market Opportunity >$3.5bn Opportunity Annual US Incidence: 17,000 >$3.5bn Opportunity Annual US Incidence: 20,000 >$1bn Opportunity Annual US Incidence: 4,000 >$2.5bn Opportunity Annual US Incidence: 6,000 Program Initial Focus Source: ©DRG 2025, Raval et al. J Clin Oncol (2025), Gebrael et al. J Clin Oncol (2025), American Cancer Society Cancer Facts & Figures 2025, Heymach et al. WCLC (2018), Robichaux et al. Nature (2021), SEER Cancer Stat Facts: Female Breast Cancer Subtypes, and ORIC data on file. Note: Market opportunity assumes current price of ARPIs for prostate cancer and current price of tyrosine kinase inhibitors for NSCLC for illustrative purposes. EGFR atypical includes PACC + select classical-like mutation. Est. Annual US Incidence NSCLC (KRASi Combo) 45,000 Future Development Opportunities CRC (KRASi Combo) 65,000 Adjuvant NSCLC EGFR exon 20 Adjuvant NSCLC EGFR atypical Rinzimetostat and enozertinib are initially targeting multiple blockbuster commercial opportunities with substantial future upside Breast Cancer (ERi Combo) 220,000 >$10bn Opportunity Annual US Incidence: 33,000 mCRPC (RLT, TCE, ADC Combo) 37,000
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Rinzimetostat Allosteric PRC2 Inhibitor
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Rinzimetostat: Potential Best-In-Class PRC2 Inhibitor for Prostate Cancer 10 KEY LIMITATIONS of approved and investigational PRC2-directed agents • Poor in vitro and in vivo potency across preclinical prostate cancer models • Inadequate clinical drug exposures due to short half-life and/or CYP autoinduction • Suboptimal tolerability potentially from variability in pharmacokinetic profiles RINZIMETOSTAT may address these limitations • Selectively targets PRC2 through allosteric inhibition of the EED subunit • Superior in vitro and in vivo activity across preclinical prostate cancer models • Synergistic activity with AR inhibitors across preclinical prostate cancer models • Strong drug properties including a 20-hour clinical half-life FIRST PHASE 3 INITIATED • Highly competitive emerging efficacy profile with landmark rPFS substantially better than SOC therapies in mCRPC • Highly differentiated safety profile • First Phase 3 trial initiated in post-abiraterone mCRPC evaluating 400 mg QD rinzimetostat in combination with darolutamide • Additional Phase 3 trials under consideration Rinzimetostat is a potential best-in-class therapy for development with AR inhibitors in prostate cancer, demonstrating superior drug properties and favorable combination efficacy & safety Rinzimetostat Overview
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11 PRC2 Plays a Pivotal Role in Transcriptional Regulation and Cancer Evolution PRC2 is a validated oncogenic target across several cancers with substantial therapeutic potential in prostate cancer • PRC2 regulates gene expression by modifying chromatin, and is implicated in tumor evolution and cell fate (1) • PRC2 is clinically validated in prostate cancer ─ Decreased expression of PRC2 target genes is associated with poor prognosis in prostate cancer (2) ─ Randomized data with second-generation PRC2 inhibitor demonstrated significant PFS improvement in mCRPC (3) • PRC2 dysfunction has been linked to multiple cancers ─ PRC2 inhibitors approved in follicular lymphoma, epithelioid sarcoma and T cell leukemia/lymphoma ─ Emerging scientific rationale in breast, colon and prostate cancers Tri-methylation of histone H3K27 Polycomb Repressive Complex 2 (PRC2) PRC2 Introduction Closed chromatin Gene silencing Open chromatin Gene transcription PRC2 Is a Clinically Validated Target in Multiple CancersPRC2 Is an Epigenetic Modifier EZH2EED PRC2 inhibition Note: EZH2 – enhance of zeste homolog 2. EED – embryonic ectoderm development. H3K27 – histone H3 at lysine 27. (1) Schade et al. Nature (2024), Loi et al. Cancer Discovery (2024), Daemen et al. AACR (2024 and 2025), and Friedman AACR Presentation (2024). (2) Yu et al. Cancer Res. (2007). (3) Schweizer et al. ASCO GU (2025).
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Rinzimetostat: Next-Generation PRC2 Inhibitor Designed for Best-in-Class Drug Properties 12 Rinzimetostat is a potential best-in-class PRC2 inhibitor that addresses the limitations of earlier generation PRC2 inhibitors PRC2 Inhibitor Landscape in Prostate Cancer Key Features CPI-1205 (1st gen) Tazemetostat (1st gen) Mevrometostat (2nd gen) Rinzimetostat (3rd gen) Cellular Potency In Vivo Activity Strong Drug Properties (PK, solubility, no CYP autoinduction) Long Clinical Half-Life Cellular Potency In Vivo Activity Strong Drug Properties Long Clinical Half-Life Development Status Discontinued Discontinued Phase 3 trials ongoing First Phase 3 initiated Superior potency vs. 1st gen programs across prostate cancer models Improved single agent and combination activity across prostate cancer models Higher and more consistent clinical exposures Sustained target coverage and QD dosing (~20-hour half-life) Potential Best-in-Class Source: Friedman et al. AACR (2024), Vaswani et al. J Med Chem (2016), Motwani et al. and Bradley et al. AACR -EORTC-NCI (2019), Schweizer et al. ESMO (2022), Italiano et al. Lancet (2018), and Harb et al. TAT (2018). Note: Drug properties include absorption, CYP profile and metabolism, pharmacokinetic (PK) and solubility profile.
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Rinzimetostat Demonstrates Superior In Vitro Potency vs. First-Gen PRC2 Inhibitors In Vitro Potency in Prostate Cancer Cells 0.01 1 100 10000 0.0 0.5 1.0 1.5 CWR22PC (AR+ Cells) Cell Viability Concentration (nM) CPI-1205 Tazemetostat Mevrometostat Rinzimetostat 0.01 1 100 10000 0.0 0.5 1.0 1.5 LNCaP (AR+ Cells) Cell Viability Concentration (nM) CPI-1205 Tazemetostat Mevrometostat Rinzimetostat Rinzimetostat demonstrates potency in AR+ prostate cancer cell lines comparable to mevrometostat and superior to tazemetostat and CPI-1205 13 LNCaP (AR-Positive Prostate Cancer Cells) Note: Head-to-head in vitro cell viability analysis with CellTiterGlo assay. CWR22PC (AR-Positive Prostate Cancer Cells)
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AR targeted therapies 14 Heterogeneous Lineage changeCastration sensitive Castration resistant PRC2 inhibitors Therapeutic potential of PRC2 inhibitors in prostate cancer is maximized in combination with AR inhibitors AR Dependent Prostate Cancer AR Independent Prostate Cancer • Prostate cancer cells evade therapies by cellular reprogramming to an AR independent state • PRC2 inhibition can reverse or prevent this process, such that prostate cancer cells regain or maintain AR dependency • Randomized data with PRC2 inhibitor + AR inhibitor demonstrated significant PFS improvement Luminal cell state, reflects tissue of origin Pluripotent Lineage Change Source: Mu et al. Science (2017), Dardenne et al. Cancer Cell (2016), Davies et al. Nat Cell Biol (2021), Nouruzi et al. Nat Com mun (2022), Goel et al. Semin Cancer Bio (2022), and Schweizer et al. ASCO GU (2025). PRC2 Role in Prostate Cancer PRC2 Epigenetic Dysregulation Plays a Key Mechanistic Role During the Progressive Reprogramming of Prostate Cancers Treated with AR Inhibitors
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Rinzimetostat Increases Progression-Free Survival in Combination with Darolutamide in Prostate Cancer Xenograft Tumors 15 Progression-Free Survival in Prostate Cancer Xenografts Rinzimetostat combination with darolutamide improves progression-free survival in CRPC and CSPC settings in vivo Note: C4-2 CRPC model (left) grown in castrated mice and LNCaP CSPC (fast-growing clone) model (right) grown in intact mice. Darolutamide 50 mg/kg BID, mevr ometostat 100 mg/kg BID, and rinzimetostat 100 mg/kg QD. No drug-related tolerability issues. Progression event for either tumor volume >800 mm3 or morbidity. 0 10 20 30 40 0 50 100 Days Progression-Free Survival (%) Vehicle Darolutamide Rinzimetostat + Darolutamide Mevrometostat + Darolutamide Vehicle Daro Mevro Rinzi Mevro + Daro Rinzi + Daro Median PFS (days) 11 12.5 15.5 27 24.5 Not Reached Vehicle Daro Mevro Rinzi Mevro + Daro Rinzi + Daro Median PFS (days) 18 25 21 19.5 28 Not Reached 10 20 30 40 0 50 100 Days Progression-Free Survival (%) Vehicle Darolutamide Rinzimetostat + Darolutamide Mevrometostat + Darolutamide CRPC Model CSPC Model
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Mevrometostat Randomized Data Provides Clinical Validation of the Combination of PRC2 Inhibitor and AR Inhibitor in Prostate Cancer Mevrometostat plus enzalutamide demonstrated improved rPFS, PSA50 and ORR versus enzalutamide in mCRPC patients previously treated with abiraterone, with a manageable (and potentially improvable) AE profile Mevrometostat Plus Enzalutamide Randomized Dose Expansion Results (ASCO GU 2025) • All patients previously treated with abiraterone and 44% previously treated with chemotherapy • Mevrometostat plus enzalutamide vs enzalutamide: – rPFS of 14.3 months vs. 6.2 months (HR=0.51), – cPSA50 of 34.1% vs 15.4%, uPSA50 of 53.7% vs 17.9% Source: Schweizer et al. ASCO GU Presentation (2025). 16
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Rinzimetostat Is Being Explored in Combination with Darolutamide and Apalutamide in Metastatic CRPC 17 Key Eligibility • Patients with mCRPC • Previously treated with an ARPI (e.g., abiraterone, enzalutamide, apalutamide, or darolutamide) • May have received up to 1 line of chemotherapy • Allows other prior therapies Phase 1b, Multicenter, Open-Label Trial (in Collaboration with Bayer and Johnson & Johnson) Candidate RP3Ds Rinzimetostat Combination Dose OptimizationRinzimetostat Combination Dose Exploration Note: ClinicalTrials.gov identifier: NCT05413421. Rinzimetostat dosed in combination with approved doses of darolutamide (600 mg BID) and apalutamide (240 mg QD). RP3D – recommended Phase 3 dose; rPFS – radiographic progression free survival; ORR – objective response rate; DOR – duration of response: PSA – prostate-specific antigen; ctDNA – circulating tumor DNA. Primary endpoints: Safety and Recommended Phase 3 Dose Key secondary endpoints: rPFS, ORR, and DOR Exploratory endpoints: PSA, ctDNA, H3K27 trimethylation, PRC2 target gene expression, and genomics Prior enza, apa, daro Prior abiraterone Prior enza, apa, daro Rinzimetostat (QD) + apalutamide Rinzimetostat (QD) + darolutamide Rinzimetostat (QD) + apalutamide Prior abirateroneRinzimetostat (QD) + darolutamide Dose optimization data reported and first Phase 3 trial initiated in post-abiraterone mCRPC; ORIC continuing to evaluate rinzimetostat in combination with darolutamide and apalutamide in mCRPC patients March 2026 Update
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-100 -75 -50 -25 0 25 50 Rinzimetostat in Combination with Darolutamide Continues to Demonstrate Strong Clinical Activity in Post-Abiraterone mCRPC Patients 18 PSA Response Data of Rinzimetostat 400 mg QD Plus Darolutamide • Rinzimetostat at 400 mg QD plus darolutamide demonstrated strong clinical activity ─ Multiple patients remain on treatment with potential for deepening of responses Broad and deep PSA responses observed for 400 mg QD rinzimetostat in combination with darolutamide u50 Best % Change in PSA from Baseline * ** Response Unconfirmed Confirmed PSA50 7/15 (47%) 5/15 (33%) PSA90 2/15 (13%) 1/15 (7%) 5090505050u50 Notations: * denotes >50% increase; 50 – confirmed PSA50 response; 90 – confirmed PSA90 response; u50 – unconfirmed PSA50 response. Source: ORIC data on file as of March 6, 2026. Note: All patients treated with 600 mg BID of darolutamide. Excludes three patients without post -baseline PSA assessments. Patients were previously treated with a median of two prior therapies, including abiraterone, up to one prior chemotherapy, and a variety of other approved or investigational agents. This median does not include background androgen deprivation therapy or first-generation AR inhibitors that the patients may have received.
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-100 -75 -50 -25 0 25 50 19 ctDNA Molecular Response Data of Rinzimetostat 400 mg QD Plus Darolutamide 50 90 Source: ORIC data on file as of March 11, 2026. Note: All patients treated with 600 mg BID of darolutamide. Excludes one patient without evidence of ctDNA at baseline, and three patients without ctDNA data available. Likely germline variants and clonal hematopoiesis variants were excluded from ctDNA analysis. Molecular response (MR) defined as decrease in ctDNA fraction relative to baseline. Best percent change in ctDNA fraction from baseline assessed at the start of cycle 2, cycle 7, or end of treatment. • ctDNA molecular responses across a breadth of genotypes including AR mutations, AR amplified, AR wildtype • Deep ctDNA reductions for the vast majority of patients treated with 400 mg QD rinzimetostat, with 71% of patients demonstrating >50% ctDNA reduction Notations: 50 – MR50 response; 90 – MR90 response. MR50 10/14 (71%) MR90 4/14 (29%) 5050 50 50 50 90 90 90 High molecular response rate observed in post-abiraterone patients treated with 400 mg QD rinzimetostat Best % Change in ctDNA Fraction from Baseline Rinzimetostat in Combination with Darolutamide Demonstrates Impressive ctDNA Molecular Response in Post-Abiraterone mCRPC Patients
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Radiographic Progression-Free Survival Data Are Immature, but Early Landmark Analyses Are Promising in Post-Abiraterone mCRPC Patients 20 Rinzimetostat 400 mg QD Plus Darolutamide Dose Optimization: Time on Treatment Many patients remain on treatment with few reports of radiographic progression Source: ORIC data on file as of March 6, 2026. Note: Abi – abiraterone; D – docetaxel; IO – immune therapy; P – PARP inhibitor; R –- radium 223; O – other; rPD – radiographic progressive disease. 0 1 2 3 4 5 6 7 8 9 10 11 12 Time on Treatment (Months) Ongoing rPD Prior Treatments Abi + IO + R Abi + IO + P + O Abi + D Abi + D + R Abi + D Abi Abi + IO Abi Abi + D Abi Abi Abi Abi Abi + D Abi + R Abi + D Abi + D Abi Landmark % rPFS (Median Follow-up of 4.9 Months) 3-Month 93% 4-Month 84% 5-Month 84%
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Rinzimetostat 400 mg QD in Combination with Darolutamide Has been Generally Well Tolerated in Post-Abiraterone mCRPC Patients 21 TEAEs Attributed to Rinzimetostat Plus Darolutamide (≥10% Total Incidence) Rinzimetostat 400 mg QD + Darolutamide Post-Abiraterone mCRPC (n=18) Preferred Term, n (%) Grade 1 Grade 2 Grade 3 All Grade Fatigue 3 (17) 4 (22) – 7 (39) Diarrhea 3 (17) 1 (6) – 4 (22) Nausea 4 (22) – – 4 (22) Blood creatinine increased 2 (11) 1 (6) – 3 (17) Decreased appetite 1 (6) 1 (6) – 2 (11) Anemia 1 (6) 1 (6) – 2 (11) In post-abiraterone patients, rinzimetostat in combination with darolutamide is generally well-tolerated, with almost all TRAEs Grade 1 or 2 in severity Source: ORIC data on file as of January 16, 2026. Note: Severity grade according to NCI CTCAE v5.0. Adverse Events: • 6% Grade 3 • No Grade 4 or 5 Dose Modifications: • 6% Dose Interruptions • No Dose Reductions • 6% Treatment Discontinuations
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80% 60% 40% 20% 0% 20% 40% 60% 80% Diarrhea Thrombocytopenia Decreased Appetite Dysgeusia Nausea Anemia Fatigue/Asthenia Alopecia Rash Blood Creatinine Increased Weight Decreased Arthralgia Rinzimetostat in Combination with Darolutamide in Post-Abiraterone mCRPC Demonstrates a Clearly Differentiated Safety Profile 22 Source: ORIC data on file as of January 16, 2026. Mevrometostat 1250 mg BID data represents 41 post -abiraterone mCRPC patients from Matsubara et al. ASCO (2025) and mevrometostat 875 mg BID data represents 29 post -ARPI mCRPC patients from Matsubara et al. ASCO GU (2026). Note: Severity grade according to NCI CTCAE v5.0. Rinzimetostat in combination with darolutamide demonstrates a clearly differentiated safety profile, with the majority of adverse events Grade 1, enabling long-term dosing and sustained patient adherence Mevrometostat 1250 mg BID (Fasted) + Enzalutamide Grade 1 Grade 2 Grade 3 Grade 4 80% 60% 40% 20% 0% 20% 40% 60% 80% Diarrhea Fatigue/Asthenia Dysgeusia Decreased Appetite Anemia Nausea Alopecia Weight Decreased Thrombocytopenia Vomiting Arthralgia Neutropenia Rash Blood Creatinine Increased Rinzimetostat Adverse Event Comparison to Mevrometostat ? ? ? ? TEAEs <20% not disclosed TEAEs <20% not disclosed TEAEs <20% not disclosed TEAEs <20% not disclosed Rinzimetostat 400 mg QD + Darolutamide Grade 1 Grade 2 Grade 1 Grade 2 Rinzimetostat 400 mg QD + Darolutamide Grade 1 Grade 2 Grade 3 Mevrometostat 875 mg BID (Fed) + Enzalutamide
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Rinzimetostat Demonstrates Competitive Early Landmark rPFS in Post- Abiraterone mCRPC and Does So with a Highly Differentiated Safety Profile 23 Landmark rPFS and Safety Benchmark Comparisons Median Follow-up 3-Month rPFS 4-Month rPFS 5-Month rPFS Grade ≥3 TRAEs Dose Reductions / Discontinuations Mevrometostat 875 mg BID Fed + Enzalutamide (n=14) 9.2 Months 36% 7% / 7% Mevrometostat 1250 mg BID Fasted + Enzalutamide (n=41) 11.7 Months 49% 37% / 2% Enzalutamide Monotherapy (n=40) 9.0 Months 23% 8% / 5% Rinzimetostat 400 mg QD + Darolutamide (n=18) 4.9 Months 6% None / 6%93% 78% 92% 92% 84% 70% 86% 92% 84% 60% 80% 84% Source: ORIC data on file, Schweizer et al. ASCO GU (2025), and Matsubara et al. ASCO GU (2026). Note: Competitor rPFS percentages estimated from published data. Preliminary rinzimetostat rPFS landmark analysis, albeit early, compares favorably to competitor benchmarks with a far cleaner safety profile, despite more heavily pretreated patients
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Himalayas-1: Global Phase 3 Trial of Rinzimetostat in Combination with Darolutamide in Patients with mCRPC Previously Treated with Abiraterone 24 • Patients with mCRPC • Prior abiraterone in mCSPC or mCRPC setting • Up to 1 prior chemotherapy in mCSPC setting R Physician’s Choice (AR inhibitor or chemotherapy) (n=300) Rinzimetostat + Darolutamide (n=300) 1:1 Rinzimetostat’s first global registrational Phase 3 trial is designed to evaluate combination with darolutamide compared to AR inhibitor and chemotherapy • Primary Endpoint: ─ Radiographic progression-free survival (rPFS) • Key Secondary Endpoint: ─ Overall survival (OS) • Other Secondary Endpoints: ─ PSA response rate ─ ORR (RECIST 1.1 and PCWG3) ─ Patient reported outcomes Rinzimetostat Global Phase 3 mCRPC Trial Note: ClinicalTrials.gov identifier: NCT07723248. Rinzimetostat 400 mg QD dosed in combination with approved dose of darolutamide (600 mg BID). PSA – prostate-specific antigen; ORR – objective response rate.
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25 Rinzimetostat Is Initially Pursuing a Significant Addressable Market in Post- Abiraterone mCRPC Rinzimetostat Total Addressable Market in Post-Abiraterone mCRPC Meaningful Market Share Best-In-Disease Safety Profile Equivalent Efficacy Leadership Market Share Best-In-Disease Safety and Efficacy Profile Post-abiraterone mCRPC is a large addressable market with limited effective therapeutic options that are oral and well-tolerated; Rinzimetostat is positioned to capture substantial share with its potential best-in-disease profile Potential Rinzimetostat Share Price 14 Months Duration ~17,000 US Annual Incidence >$3.5B US Addressable Market ~$7B Global Addressable Market Source: ©DRG 2025, Swami et al. J Clin Oncol (2025), Raval et al. J Clin Oncol (2025), Gebrael et al. J Clin Oncol (2025), Schweizer et al. ASCO GU (2025), and ORIC data on file. Note: Addressable market assumes current price of ARPIs for illustrative purposes. Total Addressable Market in Post-Abiraterone mCRPC
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PRC2 Inhibitors Have the Potential to Expand the ARPI Market, which Currently Represents $11B and Growing Despite Significant Generic Usage 26 PRC2 inhibitors have the potential to be combined with ARPIs to significantly improve clinical benefit, and expand the already significant commercial opportunity in prostate cancer Source: Company filings for Astellas, Johnson & Johnson and Bayer. Sales converted to USD using the Federal Reserve annual average exchange rate for applicable year. ©DRG 2025. Note: Major markets include US, Japan, UK, Germany, France, Italy, Spain. Market share by patients. ~$12.6B (+19% YoY) $6.3B (+7% YoY) $3.6B (+19% YoY) $2.7B (+64% YoY) Zytiga or Generic Abiraterone (47%) Nubeqa Xtandi Erleada Worldwide Sales and Market Share for Androgen Receptor Pathway Inhibitors Worldwide Sales (2025) Market Share in Major Markets (2024) (First Approval 2012) (First Approval 2018) (First Approval 2019)
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Rinzimetostat Is Being Explored in Other Patient Populations that Could Form the Basis of Future Phase 3 Trials, Including Post-AR Inhibitor mCRPC 27 Rinzimetostat 400 mg QD Plus Darolutamide in Post-ARi mCRPC: Time on Treatment Preliminary data in second mCRPC population, albeit early, are promising Source: ORIC data on file as of March 6, 2026 from dose optimization trial. Note: rPD – radiographic progressive disease. 0 1 2 3 4 5 6 7 8 9 10 11 12 Time on Treatment (Months) Landmark % rPFS (Median Follow-up of 4.8 Months) 3-Month 93% 4-Month 85% 5-Month 85% Rinzimetostat 400 mg QD + Darolutamide (n=19) Ongoing rPD Death
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PRC2 Inhibitors Are Associated with Significant Radiographic Progression-Free Survival in Post-AR Inhibitor mCRPC, Comparing Favorably to Available Therapies 28 Therapies for 1L+ mCRPC (Post-AR Inhibitor) PRC2 inhibitors in combination with an AR inhibitor have demonstrated much longer rPFS (key regulatory primary endpoint) than what has been reported with other approved and emerging therapies Treatment Status 5-Month rPFS Median rPFS (months) Enzalutamide (Xtandi®) Approved N/A N/A Abiraterone (Zytiga®) Approved Cabazitaxel (Jevtana®) Approved Mevrometostat + Enzalutamide N/A Rinzimetostat + Darolutamide Phase 1b Not mature Source: de Wit et al. N Engl J Med (2019), Schweizer et al. ASCO GU (2025), Schweizer et al. ASCO (2024), and Matsubara et al. ASCO GU ( 2026). Note: Androgen receptor pathway inhibitor (ARPI) represents abiraterone, enzalutamide, apalutamide and darolutamide. Competitor rPFS percentages estimated from published data. All trademarks are the property of their respective registered owners. 85% 68% 65% 41% 11.7 8.2 3.4
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Rinzimetostat Commercial Opportunity Is Significant in Each Segment of the Prostate Cancer Treatment Continuum 29 PRC2 Inhibitor Commercial Opportunity in Prostate Cancer (US Only) Near term development of rinzimetostat will focus on previously treated mCRPC populations that represent a $7B+ addressable market in the US; future development in earlier disease settings represents an even more significant opportunity nmCSPC mCSPC nmCRPC mCRPC ARPI-Naïve Prior Abiraterone Prior AR Inhibitor US Incidence (Estimated) 118,000 33,000 12,000 16,000 17,000 20,000 ARPI Efficacy Benchmarks (rPFS) >85 months >33 months >36 months >16 months 4-6 months 3 months ARPI + PRC2i Efficacy Potential (rPFS) TBD TBD TBD TBD 14 months 12 months Rinzimetostat Opportunity $7B+ Addressable US MarketFuture Development Opportunities Initial Focus Source: US Incidence from ©DRG 2025, Raval et al. J Clin Oncol (2025), Gebrael et al. J Clin Oncol (2025). US incidence for nmCSPC includes biochemical recurrent and newly diagnosed, high risk patients only. ARPI Efficacy Benchmarks based on Attard et al. Lancet (2022) and Armstrong et al. N Engl J Med (2024) for nmCSPC, Fizazi et al. N Engl J Med (2017) and Armstrong et al. J Clin Oncol (2022) for mCSPC, Smith et al. N Engl J Med (2018) and Fizazi et al. N Engl J Med (2019) for nmCRPC, Ryan et al. N Engl J Med (2012) and Beer et al. Eur Urol (2017) for ARPI-Naïve mCRPC, Powles et al. Nat Med (2022) and Schweizer et al. ASCO GU (2025) for Prior Abiraterone mCRPC, and de Wit et al. N Engl J Med (2019) for Prior AR Inhibitor mCRPC. ARPI + PRC2i Efficacy Potential based on Schweizer et al. ASCO GU (2025) and Schweizer et al. ASCO (2024). Note: Addressable market assumes current price of ARPIs for illustrative purposes.
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30 Rinzimetostat Has the Potential to Address Multiple Large Market Opportunities in Prostate Cancer, with Several Development Opportunities in Other Solid Tumors 17,000 patients 20,000 patients 33,000 patients 0 10,000 20,000 30,000 40,000 50,000 60,000 70,000 80,000 90,000 mCRPC Post-Abiraterone mCRPC Post-AR Inhibitor mCSPC Estimated Annual Incidence in the US Potential Rinzimetostat Commercial Opportunity (US Only) >$3.5 billion US opportunity >$3.5 billion US opportunity >$10 billion US opportunity Est. Annual US Incidence NSCLC (KRASi Combo) 45,000 Future Development Opportunities CRC (KRASi Combo) 65,000 Breast Cancer (ERi Combo) 220,000 mCRPC (RLT, TCE, ADC Combo) 37,000 Rinzimetostat has the potential to address ~70,000 patients in the US with prostate cancer annually Source: ©DRG 2025, Swami et al. J Clin Oncol (2025), Raval et al. J Clin Oncol (2025), Gebrael et al. J Clin Oncol (2025), SEER Cancer S tat Facts: Female Breast Cancer Subtypes, and ORIC data on file. Note: Addressable market assumes current price of ARPIs for illustrative purposes. RLT – radioligand therapy; TCE – T-cell engager; ADC – antibody-drug conjugate.
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Enozertinib Brain-Penetrant EGFR Inhibitor
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Enozertinib: Potential Best-in-Class TKI for EGFR Exon 20 and EGFR Atypical NSCLC 32 KEY LIMITATIONS of approved and investigational agents • Lack of CNS activity: ~50% of patients develop brain metastases and derive limited benefit with non- CNS-active drugs • Tolerability issues: high rates of treatment discontinuations due to on- and off-target toxicity PRIORITIZING 1L for future development • Selected Phase 3 monotherapy dose: 80 mg once-daily • Enrollment and follow-up continues in 1L cohorts – EGFR exon 20: monotherapy, combination with SC amivantamab(1), and combination with chemotherapy – EGFR atypical: monotherapy • Data expected 2H26, ahead of potential initiation of Phase 3 trial(s) Enozertinib is a potential best-in-class therapy with excellent selectivity and brain-penetrance that has demonstrated highly competitive clinical data in EGFR exon 20 and EGFR PACC (1) Clinical collaboration with Johnson & Johnson to evaluate enozertinib in combination with SC amivantamab in patients with fi rst-line NSCLC with EGFR exon 20 mutations. CLINICAL DATA establishes enozertinib’s potential best-in-class profile • Competitive systemic activity: response rates at or above competitor benchmarks • Convincing CNS activity: 100% intracranial ORR in patients with measurable disease • Well-tolerated safety profile: no significant off-target toxicity, resulting in low rate of discontinuations Enozertinib Overview
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33 High Burden of CNS Disease in NSCLC Patients with EGFR Mutations Leads to Disease Progression and Limited Survival with Current Therapies An effective, brain-penetrant therapy can potentially drive long-term outcomes and extend survival through durable CNS control CNS Disease Highly Prevalent in EGFR Mutated NSCLC… ~30% of patients have known CNS disease at diagnosis (1) ~50% of patients eventually develop brain metastases, often as the first site of progression (2) Initial Diagnosis Disease Progression on Treatment …And Patients With CNS Metastases Derive Limited Benefit From Non-CNS-Active Drugs Mobocertinib (3) Amivantamab + Chemotherapy (4) Patients Without History of Brain Mets (1) Patil et al. Clin Lung Cancer (2021). (2) Wilcox et al. Ann Oncol. (3) Janne et al. ASCO (2019) and Ramalingam et al . ASCO (2021). (4) Girard et al. ESMO Presentation (2023). Patients With History of Brain Mets 67% Risk Reduction 37% Risk Reduction Patients Without Baseline CNS Mets Patients With Baseline CNS Mets 8.1 months 3.7 months Risk of Progression or Death vs. Control ArmMedian Progression Free Survival
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Enozertinib Was Designed to Selectively Target EGFR with High Potency Against Exon 20 and Atypical Mutations Source: Junttila et al. Cancer Research 2025. Note: Kinase binding profiles across 468 kinases at 1 μM assessed using KINOMEscan. Red circles indicate kinases impacted within 10% of control. Table reports the number of off -target (non-EGFR/HER2) wildtype kinases inhibited 80% or more. Kinome Selectivity Comparison Enozertinib has demonstrated an exquisitely clean kinome panel, mitigating the potential for off-target toxicities 34 Off-target Wildtype Kinases Inhibited ≥80% at 1 µM Enozertinib Zipalertinib Firmonertinib Silevertinib 0 7 4 25 SilevertinibFirmonertinibEnozertinib Zipalertinib
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Phase 1b Trial of Enozertinib in NSCLC Patients 35 Key Eligibility • Advanced NSCLC ─ EGFR exon 20 ─ EGFR atypical • Untreated, stable, asymptomatic brain metastases allowed Phase 1b, Multicenter, Open-Label Trial Primary endpoints: Safety and candidate RP2Ds, dose expansion (RP2D selection) and ORR (per RECIST v1.1) Key secondary endpoints: PK, safety, DOR, CBR and PFS, including intracranial ORR/PFS (per RECIST v1.1 and RANO-BM) Robust clinical activity demonstrated in 1L and 2L+ NSCLC patients with EGFR exon20 and EGFR PACC mutations Monotherapy Combination with chemotherapy Combination with SC amivantamab (1) Monotherapy EGFR exon 20 EGFR atypical Note: ClinicalTrials.gov identifier: NCT05315700. Dose expansion may include QD and BID dosing, fed/fasted dosing. RP2D – recommended Phase 2 dose. PACC – P-loop and alpha C-helix compressing. (1) In a dedicated dose exploration trial via clinical collaboration with Johnson & Johnson to evaluate enozertinib in combination w ith SC amivantamab in patients with first-line NSCLC with EGFR exon 20 mutations.
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Enozertinib Phase 1b Data Establishes Potential Best-in-Class Profile in EGFR Exon 20 and PACC Mutated NSCLC 36 2L EGFR Exon 20 40% 45% Benchmark ORR ORR 22% 36% Benchmark ORR ORREnozertinib Enozertinib Ongoing development of enozertinib is focused on 1L, where preliminary data demonstrated potential best-in-class systemic and intracranial activity Enozertinib Updated Phase 1b Data Highlights (ESMO Asia 2025) Previously Treated Median 3L EGFR PACC Source: John et al. ESMO Asia (2025), Hong et al. ESMO Asia (2025), and ORIC data on file. Benchmark ORR: Piotrowska et al. J Clin Oncol (2025) and Udagawa et al. WCLC (2025). Note: All data in previously treated patients represent confirmed ORR. All data in 1L patients represent best ORR, due to prelim inary nature of data. 1L EGFR exon 20 intracranial ORR data in all patients with measurable CNS disease by BICR-RANO and 1L EGFR PACC intracranial ORR data in all patients with measurable CNS disease by investigator assessment using RECIST. PACC – P-loop and alpha C-helix compressing. 100% 67% Intracranial ORR ORR 100% 80% Intracranial ORR ORR Enozertinib Treatment- Naïve (1L) 1L EGFR Exon 20 (Preliminary Data) 1L EGFR PACC (Preliminary Data) Enozertinib Enozertinib Enozertinib
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Event, n (%) 80 mg (n=18) 120 mg (n=15) TRAEs Grade ≥3 4 (22) 9 (60) Dose reduction due to TRAE 3 (17) 12 (80) Discontinued due to TRAE 2 (11) 0 • Well tolerated safety profile with TRAEs predominantly Grades 1-2 • No significant off-target toxicities (e.g., myelosuppression, QTc prolongation, hepatotoxicity) • Low rate of discontinuations due to TRAEs • Higher rate of dose reductions at 120 mg (80%) vs 80 mg (17%) – 58% of reductions at 120 mg dose by ~8 weeks (2 cycles) Event, n (%) 80 mg (n=18) 120 mg (n=15) Preferred term, n (%) Grade 1-2 Grade 3 Grade 1-2 Grade 3 Diarrhea 15 (83) 2 (11) 9 (60) 1 (7) Paronychia 8 (44) 0 11 (73) 1 (7) Stomatitis 7 (39) 1 (6) 4 (27) 0 Dermatitis acneiform 5 (28) 0 4 (27) 6 (40) Rash 4 (22) 1 (6) 2 (13) 1 (7) Nausea 6 (33) 0 3 (20) 0 Pruritis 4 (22) 0 3 (20) 0 Mucosal inflammation 4 (22) 0 5 (33) 1 (7) Dry skin 1 (6) 0 6 (40) 0 Alopecia 1 (6) 0 8 (53) 0 Rash maculo-papular 5 (28) 0 2 (13) 0 37 Enozertinib Has Been Generally Well Tolerated Despite Less Stringent Enrollment Criteria for Baseline CNS Disease Source: John et al. ESMO Asia (2025). Note: Data as of August 29, 2025. Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients High rate of dose reductions in 120 mg cohort led to subsequent cohort of patients being dosed at 80 mg QD 1L EGFR exon 20 NSCLC
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-100 -80 -60 -40 -20 0 20 Change From Baseline in Target Lesions, % * ** ** ** * • Initial cohort of efficacy evaluable patients were treated at 120 mg; given 80% dose reduction rate, most patients effectively received 80 mg • Subsequent cohort of patients were treated at 80 mg; follow-up is still in progress Evaluable Population (1) 120 mg (n=15) Best ORR,† % [95% CI] 67 [38, 88] Confirmed ORR, % [95% CI] 60 [32, 84] Partial response, n (%) 9 (60) Stable disease, n (%) 5 (33) Progressive disease, n (%) 1 (7) Disease control rate (CR + PR + SD), % [95% CI] 93 [68, 100] Systemic Objective Response Rate Best % Change in Lesions in Patients Receiving 120 mg Dose (n=15) Patients with brain metastases at trial entry, including active brain metastases 38 Enozertinib Achieved Strong Antitumor Activity, Including in Patients with CNS Disease at Baseline * Enozertinib demonstrates strong ORR and disease control in 1L NSCLC patients with EGFR exon 20 mutations Source: John et al. ESMO Asia (2025). Note: Data as of August 29, 2025. CR – complete response; PR – partial response; SD – stable disease. (1) Reported in the evaluable population which includes participants who have received ≥1 dose, have ≥1 measurable lesion at baselin e, and have had the opportunity for ≥3 postbaseline scans. † Best objective response rate includes both confirmed and unconfirmed responses. 1L EGFR exon 20 NSCLC
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CNS Response† 120 mg (n=7) (1) Best ORR,‡ % [95% CI] 71 [29, 96] Confirmed ORR, % [95% CI] 71 [29, 96] Complete response, n (%) 2 (29) Partial response, n (%) 3 (43) Stable disease, n (%) 0 Progressive disease, n (%) 2 (29) Disease control rate (CR + PR + SD), % [95% CI] 71 [29, 96] 39 Enozertinib Achieved Strong CNS Antitumor Activity as Measured by BICR-RANO -100 -80 -60 -40 -20 0 20 Change From Baseline in Target Lesions, % Best % Change in CNS Lesions in Patients Receiving 120 mg Dose (n=7) Strong CNS ORR (100% in measurable CNS disease by BICR-RANO), including in patients with active brain metastases, showcases enozertinib’s CNS activity and positions it favorably for future clinical development in 1L NSCLC patients with EGFR exon 20 Patients with measurable CNS disease Patients with active brain metastases ** ** ** CNS non-target lesions with PD # # # ## • 3 patients with measurable CNS disease: – 100% confirmed intracranial ORR • 4 patients with non-measurable CNS disease: – 2 confirmed complete responses Source: John et al. ESMO Asia (2025). Note: Data as of August 29, 2025. Percentages in the table may not total 100% due to rounding. CR – complete response; PR – partial response; SD – stable disease. Measurable disease includes patients with target lesions ≥1 cm in diameter. (1) One patient was deemed not evaluable by blinded independent central review (BICR). † Per RANO by BICR. ‡ Best objective response rate includes both confirmed and unconfirmed responses. ** CNS non-target lesions with CR 1L EGFR exon 20 NSCLC
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Baseline Baseline End of Cycle 1 End of Cycle 1 40 Source: John et al. ESMO Asia (2025). Note: Data as of August 29, 2025. Complete Intracranial and Partial Systemic Responses in a Treatment-Naïve EGFR Exon 20 Mutant NSCLC Patient With Active CNS Metastases Patient: 60-year-old female Prior Therapy: None CNS Metastases at Baseline: 5 active non-target lesions (no prior radiation or surgery) Enozertinib Dose: 120 mg oral, once-daily Systemic Response: Partial response after Cycle 1 (47% reduction) CNS Response: Complete response after Cycle 1 (disappearance of all 5 CNS lesions) Treatment-Related Adverse Events: Grade 1 paronychia, Grade 2 mucositis, dose reduced to 80 mg for Grade 3 palmar erythrodysesthesia Duration of Treatment: Cycle 6 (ongoing at data cutoff) Enozertinib demonstrated robust systemic activity and complete intracranial response in a patient with active brain metastases
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0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 £ £ ££ ££ ££ £ ££ Time on Treatment, wks * * CNS Disease at Baseline Confirmed PR Start Unconfirmed PR Start Treatment Ongoing£ * ** **** • Responses generally occur by 4 weeks, but tumor regression continues over time, with late responses seen after 4+ months on treatment • Median follow-up of 32.6 weeks; 80% (8 of 10) of responders are still on treatment 41 120 mg QD (n=15) Source: John et al. ESMO Asia (2025). Note: Data as of August 29, 2025. Tumor Responses on Enozertinib Were Generally Achieved Early and the Vast Majority of Patients Remain on Treatment • Initial cohort of efficacy evaluable patients were treated at 120 mg; given 80% dose reduction rate, most patients effectively received 80 mg • Subsequent cohort of patients were treated at 80 mg; follow-up is still in progress 80% of responders are still on therapy, most at a reduced 80 mg dose; all subsequent enrollment was at 80 mg, with follow-up in progress 1L EGFR exon 20 NSCLC
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Early Enozertinib Data in 1L EGFR PACC Patients Demonstrated Impressive Antitumor Activity, Including in Patients with CNS Disease at Baseline 42 -100 -80 -60 -40 -20 0 20 40 Change From Baseline in Target Lesions, % ** * ** * Patients with brain metastases at trial entry, including active brain metastases * Best % Change in Lesions in Patients Receiving 80 mg Dose (n=10) Preliminary Response Assessment 80 mg (n=10) Best ORR,‡ % 80 Partial response, n (%) 8 (80) Stable disease, n (%) 2 (20) Progressive disease, n (%) 0 (0) Disease control rate (CR + PR + SD), % 100 Early enozertinib data in 1L NSCLC patients with EGFR PACC mutations shows impressive responses, with additional data expected in 2H 2026 Source: ORIC data on file as of November 18, 2025. Note: PACC – P-loop and alpha C-helix compressing. ‡ Best ORR presented due to preliminary nature of data, and includes confirmed and pending unconfirmed responses. • Safety profile to date in line with 80 mg dose level in other cohorts 1L EGFR PACC NSCLC
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Early Enozertinib Data in 1L EGFR PACC Patients Demonstrated Strong CNS Antitumor Activity 43 -100 -80 -60 -40 -20 0 20 40 Change From Baseline in Target Lesions, % Best % Change in CNS Lesions in Patients Receiving 80 mg Dose (n=5)Preliminary CNS Response 80 mg (n=5) (1) Best ORR,‡ % 80 Complete response, n (%) 1 (20) Partial response, n (%) 3 (60) Stable disease, n (%) * 1 (20) Progressive disease, n (%) 0 (0) Disease control rate (CR + PR + SD), % 100 Source: ORIC data on file as of November 18, 2025. Note: PACC – P-loop and alpha C-helix compressing. (1) Excludes one patient with no post-baseline CNS assessment. ‡ Best ORR (investigator assessed using RECIST) presented due to preliminary nature of data and includes confirmed and pending u nconfirmed responses. * CNS non-target disease with best response of non-CR / non-PD. Early enozertinib data in 1L NSCLC patients with PACC mutations shows impressive CNS antitumor activity (100% ORR in measurable CNS disease), including in patients with active brain metastases, with additional data expected in 2H 2026 Patients with measurable CNS disease Patients with active brain metastases # # # # # • 4 patients with measurable CNS disease: – 100% intracranial ORR, including 1 complete response • 1 patient with non-measurable CNS disease: – Best response of non-CR / non-PD CNS non- target disease with non- CR/non-PD* ** ** ** **** # 1L EGFR PACC NSCLC
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Baseline Baseline BOR Timepoint BOR Timepoint 44 Source: ORIC data on file as of November 18, 2025. Note: PACC – P-loop and alpha C-helix compressing. Partial Intracranial and Systemic Responses in a Treatment-Naïve EGFR PACC Mutant NSCLC Patient with Active CNS Disease Patient: 67-year-old male PACC Mutation: G719A Prior Therapy: None CNS Metastases at Baseline: 1 target lesion (no prior radiation or surgery) Enozertinib Dose: 80 mg oral, once-daily Systemic Response: Partial response after Cycle 1 (43% reduction) CNS Response: Partial response after Cycle 1 (66% reduction); complete response after Cycle 4 Treatment-Related Adverse Events: Grade 1 acneiform rash Duration of Treatment: Cycle 5 (ongoing at data cutoff) Enozertinib demonstrated robust systemic activity and complete intracranial response in a patient with active brain metastasis
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45 2026 2027+ Ongoing Phase 1b Trials Potential Phase 3 Trial(s) 1L EGFR Exon 20 Monotherapy and/or Combination 1L EGFR Atypical Monotherapy Multiple Potential Registrational Paths for 1L Approvals Additional data expected in 2H 2026, ahead of potential initiation of Phase 3 trial(s) Enozertinib Next Steps Enozertinib Development Is Focused on First-Line NSCLC Patients with EGFR Exon 20 and EGFR Atypical Mutations 1L EGFR Exon 20 Monotherapy 1L EGFR Exon 20 Combination with chemotherapy 1L EGFR Atypical Monotherapy 1L EGFR Exon 20 Combination with SC amivantamab (1) (1) Clinical collaboration with Johnson & Johnson to evaluate enozertinib in combination with SC amivantamab in patients with fi rst-line NSCLC with EGFR exon 20 mutations.
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46 Enozertinib Is Pursuing a Significant Commercial Opportunity Across Patient Populations that Lack an Approved CNS Active Agent Enozertinib has the potential to address ~10,000 patients with NSCLC annually, representing a commercial opportunity of ~$3.0 to $4.0 billion in the US alone 4,000 patients 6,000 patients 0 2,000 4,000 6,000 8,000 10,000 12,000 1L EGFR Exon 20 1L EGFR Atypical Estimated Annual Incidence in the US Potential commercial opportunity of ~$3.0 to $4.0 billion in the US annually Potential Enozertinib Commercial Opportunity (US Only) Source: American Cancer Society Cancer Facts & Figures 2025, Heymach et al. WCLC (2018), and Robichaux et al. Nature (2021). Note: Estimated addressable market assumes 11.4-month treatment duration for EGFR exon 20 based on Girard et al. N Engl J Med (2023), 16.0- month treatment duration based on Le et al. WCLC (2025), and current price of tyrosine kinase inhibitors for NSCLC. EGFR atypical includes PACC + select classical-like mutation. • ~10,000 patients (~5% of NSCLC) diagnosed annually • EGFR exon 20 mutant NSCLC: no approved CNS-active therapies • EGFR atypical NSCLC: no approved therapies>$1.0 billion US opportunity >$2.5 billion US opportunity
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Key Takeaways
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48 Note: ARi – androgen receptor inhibitor. (1) Clinical collaboration with Johnson & Johnson to evaluate enozertinib in combination with SC amivantamab in patients with fi rst-line NSCLC with EGFR exon 20 mutations. Clinical Pipeline Focused on Advancement of Rinzimetostat and Enozertinib Program Indication PRODUCT CANDIDATES Enozertinib EGFR inhibitor Rinzimetostat PRC2 inhibitor Discovery / IND Enabling Phase 1/2 Pivotal / Phase 3 Clinical Collaboration Phase 3 Initiations • Post-abiraterone and post-ARi • Combination with darolutamide • 1L monotherapy • 1L combination with SC amivantamab (1) • 1L combination with chemotherapy • Post-abiraterone and post-ARi • Combination with apalutamide • 1L monotherapy Prostate Cancer NSCLC EGFR atypical NSCLC EGFR exon 20 Potential Redwood-1 in 2027 • Post-abiraterone • Combination with darolutamide Potential Himalayas-2 in 2027 Himalayas-1 Initiated Diversified, late-stage pipeline includes two potential best-in-class programs addressing large solid tumor market opportunities
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ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer 49 Validated Targets in High Unmet Need Populations Late-Stage Clinical Pipeline Strong Financial Position Experienced Management Team • Potential best-in-class PRC2 inhibitor for prostate cancer • Potential best-in-class TKI for NSCLC with EGFR exon 20 insertion and EGFR atypical mutations • Heritage of discovering, developing, and commercializing oncology therapies at Ignyta, Medivation, Aragon, Pharmacyclics, Deciphera, and Genentech • Rinzimetostat: first Phase 3 initiated in post-abiraterone mCRPC • Enozertinib: rapidly advancing towards potential Phase 3 initiation(s) in 1L EGFR-mutant NSCLC Anticipated Milestones • Rinzimetostat for mCRPC: Announced combination dose optimization data with AR inhibitor Initiated first global Phase 3 registrational trial in post-abiraterone mCRPC ─ 2H26: Program update • Enozertinib for NSCLC: ─ Oct 2026: 1L EGFR atypical monotherapy data to be presented at ESMO Congress 2026 ─ 2H26: 1L EGFR exon 20 monotherapy data and combination data with SC amivantamab (1) Note: Cash and investments as of June 30, 2026. Abiraterone refers to abiraterone acetate. (1) Clinical collaboration with Johnson & Johnson to evaluate enozertinib in combination with amivantamab and hyaluronidase-lpuj subcutaneous injection (SC amivantamab) in patients with first -line NSCLC with EGFR exon 20 mutations. • Cash and investments of $388 million expected to fund company into 2H 2028 • Funding through primary endpoint readout from first Phase 3 trial of rinzimetostat Two potential best-in-class programs in or approaching Phase 3; cash runway into 2H28, beyond rinzimetostat Phase 3 data