Slides
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Company Overview January 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-l ooking 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 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 and EGFR PACC mutations • Heritage of discovering, developing, and commercializing oncology therapies at Ignyta, Medivation, Aragon, Pharmacyclics, Deciphera, and Genentech • Rinzimetostat (ORIC-944) and enozertinib (ORIC-114) rapidly advancing towards potential Phase 3 initiations Anticipated Milestones • Rinzimetostat for mCRPC: ─ 1Q26: Combination dose optimization data with AR inhibitor ─ 1H26: Initiate first global Phase 3 registrational trial in mCRPC ─ 2H26: Program update • Enozertinib for NSCLC: ─ 2H26: 1L EGFR exon 20 monotherapy data and combination data with SC amivantamab (2) ─ 2H26: 1L EGFR PACC monotherapy data Note: PACC – P-loop and alpha C-helix compressing. (1) Represents cash and investments of approx imately $413 million as of September 30, 2025. (2) Clinical collaboration with Johnson & Johnson to evaluate enoz ertinib in combination with amivantamab and hyaluronidase-lpujsubcutaneous injection (SC amivantamab) in patients with first-line NSCLC with EGFR exon 20 mutations. • Cash and investments of $413 million expected to fund company into 2H 2028 (1) • Funding through primary endpoint readout from first Phase 3 trial of rinzimetostat Two potential best-in-class programs approaching Phase 3 initiation; 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 Program Indication PRODUCT CANDIDATES Enozertinib (ORIC-114) EGFR inhibitor Rinzimetostat (ORIC-944) PRC2 inhibitor Discovery / IND Enabling Phase 1/2 Pivotal / Phase 3 Clinical Collaboration Anticipated Data Milestones •Combination with apalutamide •1L monotherapy •1L combination with SC amivantamab (1) •1L combination with chemotherapy •Combination with darolutamide •1L monotherapy Prostate Cancer NSCLC EGFR PACC NSCLC EGFR exon 20 Note: PACC – P-loop and alpha C-helix compressing. (1) Clinical collaboration with Johnson & Johnson to evaluate enoz ertinib in combination with amivantamab and hyaluronidase-lpujsubcutaneous injection (SC amivantamab) in patients with first-line NSCLC with EGFR exon 20 mutations. Clinical Pipeline Focused on Advancement of Rinzimetostat and Enozertinib Clinical-stage pipeline includes two potential best-in-class programs addressing large solid tumor market opportunities; Both programs approaching initiation of registrational trials 2H 2026 2H 2026 1Q and 2H 2026
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6 ORIC’s Two Programs Are Approaching Registrational Trials and Each Have Multibillion Dollar Commercial Opportunities in the US Alone mCRPC Post-Abiraterone Rinzimetostat mCRPC Post-AR Inhibitor mCSPC NSCLC EGFR exon 20 Enozertinib NSCLC EGFR PACC 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 >$2bn Opportunity Annual US Incidence: 5,000 Program Initial Focus Source: ©DRG 2025, Raval et al. J Clin Onco l (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. Abiraterone refers to abiraterone acetate.2 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 PACC 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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2025 Was Transformative and Highly Productive as ORIC Prepares for Phase 3 Rinzimetostat Reported potentially best-in-class data in EGFR exon 20 & EGFR PACC mutated NSCLC: • Systemic ORRs at or above competitor benchmarks • 100% intracranial ORR in patients with measurable brain metastases • Well-tolerated safety profile with no significant off-target tox Selected Phase 3 monotherapy dose 7 Enozertinib Reported potentially best-in-class data in mCRPC: • Confirmed PSA response rates compare favorably to competitor PRC2 inhibitors • ctDNA clearance rate superior to SOC therapies • Clearly differentiated safety profile compatible with long-term dosing Selected provisional RP2Ds and initiated dose optimization in combination with AR inhibitors Corporate Raised $244 million from new and existing top-tier healthcare specialist funds Cash runway into 2H 2028, past Phase 3 readout for rinzimetostat Rinzimetostat & enozertinib continue to exhibit potential best-in-class profiles and are approaching initiation of registrational trials Key 2025 Accomplishments
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Rinzimetostat (ORIC-944) Allosteric PRC2 Inhibitor
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Rinzimetostat: Potential Best-In-Class PRC2 Inhibitor for Prostate Cancer 9 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 and well-tolerated profile as single agent and in combination with AR inhibitors PHASE 3 INITIATION expected 1H 2026 • Conducting dose optimization combination trial with apalutamide and with darolutamide in collaboration with Johnson & Johnson and Bayer • Promising combination data of rinzimetostat + AR inhibitors compares favorably to competitor PRC2 inhibitors 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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10 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 Prese ntation (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 11 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 PotencyCellular Potency In Vivo ActivityIn Vivo Activity Strong Drug Properties Strong Drug Properties Long Clinical Half-Life Long Clinical Half-Life Development Status Discontinued Discontinued Phase 3 trials ongoing Phase 3 initiation 1H 2026 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 metabo lism, pharmacokinetic (PK) and solubility profile. Tazemetostat is approved for follicular lymphoma and epithelioid sarcoma, but development in prostate cancer has been discontinued.
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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) Concentration (nM) CPI-1205 Tazemetostat Mevrometostat Rinzimetostat Cell Viability Rinzimetostat demonstrates potency in AR+ prostate cancer cell lines comparable to mevrometostat and superior to tazemetostat and CPI-1205 12 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 13 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 this process, such that prostate cancer cells regain 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 Commun (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 AR Inhibitor in Prostate Cancer Xenograft Tumors 14 Progression-Free Survival in Prostate Cancer Xenografts Rinzimetostat combination with darolutamide improves progression-free survival in a treatment refractory setting in vivo Note: C4-2 prostate model grown in castrated mice. Darolutamide 50 mg/kg BID, mevrometostat 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. Progression-Free Survival (%) Rinzimetostat + Darolutamide Mevrometostat + DarolutamideRinzimetostatMevrometostatDarolutamideVehicleC4-2 (castrated) Not reached24.52715.512.511Median PFS (days)
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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). Note: Abiraterone refers to abiraterone acetate. 15
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Rinzimetostat Single Agent Trial Confirms Potential Best-in-Class Drug Properties 16 Key Eligibility • Metastatic prostate cancer • Progressed: ─ ≥1 AR inhibitor(s) ─ ≤2 chemo regimens • ECOG 0-1 Phase 1b, Multicenter, Open-Label Trial Single Agent Dose Escalation Rinzimetostat • Single agent • i3+3 design • Oral once daily dosing Screening / Enrollment Single Agent Objectives Phase 1b confirmed rinzimetostat differentiated single agent profile and positioned rinzimetostat as a potential best-in-class PRC2 inhibitor for combination development in prostate cancer Strong drug properties Long half-life Dose proportional exposures No CYP autoinduction Robust target engagement Well tolerated
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Rinzimetostat Advanced into Combination Development with AR Inhibitors 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 Phase 1b, Multicenter, Open-Label Trial (in Collaboration with Johnson & Johnson and Bayer) Candidate RP2Ds Rinzimetostat Combination Dose OptimizationRinzimetostat Combination Dose Exploration Note: ClinicalTrials.gov identifier: NCT0541 3421. RP2D – recommended Phase 2 dose; rPFS – radiographic progression free survival; ORR – objective response rate; DOR – duration of response: PSA – prostate-specific antigen. Abiraterone refers to abiraterone acetate. Primary endpoints: Safety and Recommended Phase 2 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) + darolutamide (600 mg BID) Rinzimetostat (QD) + apalutamide (240 mg QD) Rinzimetostat (QD) + darolutamide (600 mg BID) Prior abiraterone Rinzimetostat (QD) + apalutamide (240 mg QD) Ongoing Dose exploration completed, with data update provided in November 2025; Dose optimization ongoing, with data update expected in 1Q 2026
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-100 -50 0 50 Rinzimetostat Continues to Demonstrate Strong Clinical Activity with Apalutamide and with Darolutamide in Post-Abiraterone mCRPC Patients 18 PSA Response Data of Rinzimetostat Plus Apalutamide or Darolutamide (N=20) ConfirmedUnconfirmedResponse 8/20 (40%) (1)11/20 (55%)PSA50 4/20 (20%)4/20 (20%)PSA90 400 mg QD 600 mg QD Rinzimetostat Dose 800 mg QD 1,200 mg QD • Rinzimetostat plus AR inhibitor combination demonstrates strong clinical activity ─ PSA responses across all dose levels ─ Comparable PSA responses in combination with apalutamide or with darolutamide ─ PSA90 response ongoing >1 year • Dose exploration with apalutamide and with darolutamide complete • Dose optimization ongoing with preliminary data expected 1Q26 Broad and deep PSA responses observed for rinzimetostat in combination with apalutamide and with darolutamide at all dose levels 909090 9050505050p50 Notations: * denotes >50% increase in PSA; 50 – confirmed PSA50 response; 90 – confirmed PSA90 response; p50 – unconfirmed pending PSA50 response; u50 – unconfirmed PSA50 response. Note: Data as of September 22, 2025. All patients treated with either 240 mg QD of apalutamide or 600 mg BID of darolutamide. Ex cludes three patients previously treated with lutetium 177, one of which achieved a PSA50 response. Abiraterone refers to abiraterone acetate. Patients were previously treated with a median of three prior therapies, including abiraterone acetate, 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. (1) One additional PSA50 response pending confirmation (denoted by p50); patient had dose hold due to ankle fracture. One patien t developed bone progression and PSA50 was not confirmed. One patient came off drug due to TRAE of G1 diarrhea / G2 nausea and lost opportunity to confirm PSA50 response. u50 u50 Best % Change in PSA from Baseline **
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ctDNA Analysis Reveals Impressive Molecular Response for Rinzimetostat Plus Apalutamide or Darolutamide in Post-Abiraterone mCRPC Patients 19 ctDNA Response Data of Rinzimetostat Plus Apalutamide or Darolutamide (n=17) (1) Note: Data as of September 22, 2025. Waterfall plot displays patients previously treated with abiraterone. Abiraterone refers to abiraterone acetate. Germline, predicted clonal hematopoiesis, and synonymous somatic variants were excluded from ctDNA analysis. (1) From the 20-patient data-cut, ctDNA data are included for 17 patients, with 2 patients lacking samples for ctDNA assessment and 1 patient without evidence of ctDNA at baseline. • Patients denoted by asterisk had a ctDNA fraction <0.5% at baseline, which cleared by C2D1. Rapid and deep ctDNA reductions observed for rinzimetostat in combination with darolutamide and with apalutamide, across breadth of AR mutations and other tumor alterations • Impressive ctDNA responses across all dose levels and at comparable rates in combination with apalutamide or with darolutamide • Deep ctDNA reductions for the vast majority of patients, with 76% of patients demonstrating >50% ctDNA reduction • ctDNA responses in breadth of genotypes including tumors with: ─ AR mutations, AR amplified, AR wildtype ─ Tumor suppressor and oncogene mutations, e.g., p53, SPOP, PI3K, BRCA Rinzimetostat Dose 400 mg QD 600 mg QD 800 mg QD 1,200 mg QD Best % Change in ctDNA Fraction from Baseline
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ctDNA Clearance with Rinzimetostat Plus Apalutamide or Darolutamide Is Superior to Standard of Care Therapies 20 Source: ORIC data as of September 22, 2025. Sweeney et al. CCR (2024) and Sumanasuriya et al. EAU (2021). Note: ctDNA response was assessed at C2D1 in ORIC Phase 1b, at C3D1 in IMbassador250 and at C4D1 in FIRSTANA/PROSELICA. For rinz imetostat, from the 20 patients previously treated with abiraterone as of the data-cutoff, ctDNA data were available for 17 pat ients, with 2 patients lacking samples for ctDNA assessment and 1 patient without evidence of ctDNA at baseline. Abiraterone refers to abiraterone acet ate. rPFS – radiographic progression free survival. (1) PROSELICA included patients previously treated with docetaxel, and in those patients two doses of cabazitaxel were tested. F IRSTANA included chemo-naïve patients with comparison of docetaxel vs cabazitaxel. ORIC Phase 1bFIRSTANA / PROSELICAIMbassador250Trial Rinzimetostat + AR inhibitor Docetaxel or cabazitaxelEnzalutamideTreatment n=17n=135n=171Size 88%73%80% % Patients with Detectable ctDNA at Entry • Prior abiraterone • Chemo allowed • Prior ARPI allowed • Chemo allowed (1) • Prior abiraterone • Chemo allowedPrior Therapies D to ND 59% ND to ND 12% D to D 29% D: Detected ctDNA ≥0.5% ND: Non-detected ctDNA <0.5% Rinzimetostat ctDNA Clearance Rate Versus Trials in Comparable mCRPC Populations Rinzimetostat Phase 1b ctDNA (Baseline to On-Treatment) 12% 32% 59% 0% 15% 30% 45% 60% ctDNA Clearance Rate (% Detected to Not Detected on Tx) ctDNA clearance is associated with prolonged rPFS and overall survival in mCRPC; rinzimetostat plus apalutamide or darolutamide demonstrated a higher ctDNA clearance rate than observed in precedent trials with standard of care therapies D to ND: 59% (10/17) D to D: 29% (5/17) ND to ND: 12% (2/17) ND to D: 0% (0/17)
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Rinzimetostat in Combination with Apalutamide and with Darolutamide Has Been Generally Well Tolerated to Date 21 Total (N=20)1200 mg (n=3)800 mg (n=5)600 mg (n=9)400 mg (n=3)Dose Level (QD) Grade 3Grade 1-2Grade 3Grade 1-2Grade 3Grade 1-2Grade 3Grade 1-2Grade 3Grade 1-2Preferred Term, n (%) 1 (5%)11 (55%)–3 (100%)–4 (80%)1 (11%)3 (33%)–1 (33%)Diarrhea –9 (45%)–1 (33%)–3 (60%)–4 (44%)–1 (33%)Fatigue –7 (35%)–1 (33%)–2 (40%)–3 (33%)–1 (33%)Nausea –5 (25%)–1 (33%)–1 (20%)–2 (22%)–1 (33%)Dysgeusia –4 (20%)–––1 (20%)–3 (33%)––Vomiting –4 (20%)–1 (33%)–1 (20%)–2 (22%)––Hypothyroidism (1) –3 (15%)–––1 (20%)–2 (22%)––Constipation –3 (15%)–1 (33%)–1 (20%)–––1 (33%)Blood creatinine increased TEAEs Attributed to Rinzimetostat Plus Apalutamide or Darolutamide (≥15% of Total Patients) Rinzimetostat in combination with AR inhibitors has been generally well tolerated with the vast majority of adverse events Grade 1 or 2 and consistent with PRC2 and AR inhibition • No Grade 4 or Grade 5 TEAEs attributed to rinzimetostat with apalutamide or with darolutamide Note: Data as of September 22, 2025. Includes all treatment-emergent adverse events (TEAEs) attributed to rinzimetostat plus apalutamide or rinzimetostat plus darolutamide. Severity grade according to NCI CTCAE v5.0. All patients treated with either 240 mg QD of apalutamide or 600 mg BID of darolutamide. (1) The occurrence of hypothyroidis m is consistent with the known safety profile of apalutamide.
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15% 18% 0% 20% 40% 60% 80% cPSA50 uPSA50 34% 54% 0% 20% 40% 60% 80% cPSA50 uPSA50 8% 8% 0% 20% 40% 60% 80% cPSA90 uPSA90 12% 17% 0% 20% 40% 60% 80% cPSA90 uPSA90 Combination of Rinzimetostat + AR Inhibitors Compares Favorably to Competitor PRC2 Inhibitor + AR Inhibitor and to AR Inhibitor Monotherapy Rinzimetostat Phase 1b Update (November 2025) PSA50 PSA90 SAFETY (All Gr / Gr ≥3) Rinzimetostat + Apalutamide or Darolutamide Mevrometostat + EnzalutamideEnzalutamide • Diarrhea (60% / 5%) • Fatigue (45% / 0%) • Nausea (35% / 0%) • Dysgeusia (25% / 0%) • Vomiting (20% / 0%) • Hypothyroidism (20% / 0%) • Constipation (15% / 0%) • Blood creatinine increased (15% / 0%) • AE cutoff of ≥15% • 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 in (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%) 22 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: Cross-trial comparison in previously treated mCRPC patients shown. Rinzimetostat + apalutamide or darolutamide data as of September 22, 2025. (1) One additional PSA50 response pending confirmation; patient had dose hold due to ankle fracture. One patient developed bone progression and PSA50 was not confirmed. One patient came off drug due to TRAE of G1 diarrhea/G2 nausea and lost opportunity to confirm PSA50 response. Rinzimetostat + ARi safety profile compatible with long-term dosing, with the vast majority of AEs Gr 1 or 2, and no Gr 4/5 events 40% (1) 55% 20% 20%
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Next Steps and Expansion Opportunities for Rinzimetostat in Prostate and Beyond 23 Rinzimetostat has the potential to be a meaningful addition to therapeutic strategies across multiple solid tumors Initiate First Phase 3 Trial in Prostate Cancer • Conduct dose optimization (Project Optimus) and select RP2D • Finalize Phase 3 trial design, solicit regulatory input, and initiate first global Phase 3 Evaluate Additional Prostate Cancer Indications • Continue evaluating other mCRPC indications (e.g., post-AR Inhibitor, ARPI-naïve) • Explore potential in mCSPC • Design trial, solicit regulatory input, and initiate second potential global Phase 3 Maximize Potential of PRC2 Beyond Prostate Cancer • Extend rationale for PRC2 in lung, breast, and colorectal cancers • Design proof-of-concept clinical trials for one or more new solid tumor indications • Initiate potential clinical trial(s) for new solid tumor indication(s)
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PRC2 Inhibitors Have the Potential to Expand the ARPI Market, which Currently Represents $11B and Growing Despite Significant Generic Usage 24 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. ©DRG 2025. Note: Major markets include US, Japan, UK, Ge rmany, France, Italy, Spain. Market share by patients. Abiraterone refers to abiraterone acetate. ~$11B (>25% YoY) $5.9B (+16% YoY) $3.0B (+26% YoY) $1.6B (+75% YoY) Zytiga or Generic Abiraterone (47%) Nubeqa Xtandi Erleada Worldwide Sales and Market Share for Androgen Receptor Pathway Inhibitors (2024) Worldwide Sales Market Share in Major Markets
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Rinzimetostat Commercial Opportunity Is Significant in Each Segment of the Prostate Cancer Treatment Continuum 25 PRC2 Inhibitor Commercial Opportunity in Prostate Cancer (US Only) Source: US Incidence from ©DRG 2025, Raval et al. J Clin Oncol (2025), and 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. Abiraterone refers to abiraterone acetate. 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 mCRPC nmCRPCmCSPCnmCSPC Prior AR InhibitorPrior AbirateroneARPI-Naïve 20,00017,00016,00012,00033,000118,000US Incidence (Estimated) 3 months4-6 months>16 months>36 months>33 months>85 months ARPI Efficacy Benchmarks (rPFS) 12 months14 monthsTBDTBDTBDTBD ARPI + PRC2i Efficacy Potential (rPFS) Rinzimetostat Opportunity $7B+ Addressable US MarketFuture Development Opportunities Initial Focus
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Potential for Rinzimetostat (ORIC-944) in Additional Cancer Indications and Combinations Based on Shared Reliance on PRC2 Mechanism Prostate cancer Breast cancer Lung cancer Colorectal cancer Lineage of origin Lineage change luminal lung epithelial luminal colon epithelial Lineage Oncogene AR ER KRAS AR inhibitors ER inhibitors KRAS inhibitors PRC2 Activity Enables Lineage Plasticity that Underlies Therapeutic Resistance Treatment KRAS KRAS inhibitors Therapeutic potential of PRC2 inhibitors may be maximized in combination with oncogene-directed inhibitors in prostate, breast, colon, and lung cancers 26 Source: Mu et al. Science (2017), Dardenne et al. Cancer Cell (2016), Davies et al. Nat Cell Biol (2021), Nouruzi et al. Nat Commun (2022), Goel et al. Semin Cancer Bio (2022), Loi et al., Cancer Disc (2024), Quintanal-Villalonga et al. Nat Clin Can Rev (2020), Liang et al. Nat Cancer (2025), Schade et al. Nature (2024), Jones et al. Scientific Reports (2025), Yu et al. Cancer Res. (2007), Yomtoubian et al. Cell Reports (2020), and Ni et al. ENA (2025).
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27 Rinzimetostat Is Initially Pursuing Significant Addressable Markets in Prostate Cancer, With Several Additional Development Opportunities Rinzimetostat has the potential to address ~70,000 patients in the US with prostate cancer annually 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 mCRP C Post-AR Inhibitor mCSPC Estimated Annual Incidencein the US Potential Rinzimetostat Commercial Opportunity (US Only) Source: ©DRG 2025, Raval et al. J Clin Oncol (2025), Gebrael et al. J Clin Oncol (2025), SEER Cancer Stat Facts: Female Breast Cancer Subtypes, and ORIC data on file. Note: Addressable market assumes current price of ARPIs for illustrative purposes. Abiraterone refers to abiraterone acetate. >$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
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Enozertinib (ORIC-114) Brain-Penetrant EGFR Inhibitor
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Enozertinib: Potential Best-in-Class TKI for EGFR exon 20 and EGFR PACC NSCLC 29 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 PACC: 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 Note: PACC – P-loop and alpha C-helix compressing. (1) Clinical collaboration with Johnson & Johnson to evaluate enoz ertinib in combination with amivantamab and hyaluronidase-lpujsubcutaneous injection (SC amivantamab) in patients with first-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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30 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 31 Off-target Wildtype Kinases Inhibited ≥80% at 1 M Silevertinib FirmonertinibZipalertinibEnozertinib 25 470 Silevertinib FirmonertinibEnozertinib Zipalertinib
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Phase 1b Trial of Enozertinib in NSCLC Patients 32 Key Eligibility • Advanced NSCLC ─ EGFR exon 20 ─ EGFR PACC • 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 PACC Note: ClinicalTrials.gov identifier: NCT0531570 0. 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 collaborati on 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.
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Enozertinib Phase 1b Data Establishes Potential Best-in-Class Profile in EGFR Exon 20 and PACC Mutated NSCLC 33 2L EGFR Exon 20 40% 45% Benchmark ORR ORR 22% 36% Benchmark ORR ORR 100% 67% Intracranial ORR ORR 100% 80% Intracranial ORR ORR Enozertinib Enozertinib Enozertinib Enozertinib data in previously treated patients with EGFR exon 20 and PACC mutations exceed competitor benchmarks; preliminary 1L systemic and intracranial activity establishes potential best-in-class profile Enozertinib Updated Phase 1b Data Highlights (ESMO Asia 2025) Previously Treated Treatment- Naïve (1L) 1L EGFR Exon 20 (Preliminary Data) Median 3L EGFR PACC 1L EGFR PACC (Preliminary Data) 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 preliminary 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. Enozertinib Enozertinib Enozertinib
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120 mg (n=21) 80 mg (n=24)Event, n (%) 7 (33)10 (42)TRAEs Grade ≥3 12 (57)8 (33)Dose reduction due to TRAE 03 (13)Discontinued due to TRAE • Well tolerated safety profile with TRAEs predominantly Grades 1-2 • One Grade 4 TRAE (pneumonitis at 120 mg); no Grade 5 TRAEs • No significant off-target toxicities (e.g., cardiac, hematologic and liver) • Low rate of discontinuations due to TRAEs 120 mg (n=21) 80 mg (n=24)Event, n (%) Grade 3Grade 1-2Grade 3Grade 1-2Preferred term, n (%) 5 (24)12 (57)2 (8)19 (79)Diarrhea 014 (67)020 (83)Paronychia 1 (5)12 (57)010 (42)Stomatitis 04 (19)1 (4)9 (38)Dermatitis acneiform 1 (5)12 (57)1 (4)9 (38)Rash 09 (43)08 (33)Nausea 06 (29)06 (25)Decreased appetite 03 (14)06 (25)Mucosal inflammation 05 (24)06 (25)Alopecia 02 (10)08 (33)Dysgeusia 34 Enozertinib Has Been Generally Well Tolerated Despite Enrolling Heavily-Pretreated Patients and a Less Stringent Enrollment Criteria for Baseline CNS Disease 2L EGFR exon 20 NSCLC Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients Enozertinib was generally well tolerated with mainly Grade 1 or 2 adverse events and no significant off-target toxicities; 80 mg cohort experienced lower rate of dose reductions compared to 120 mg cohort Source: John et al. ESMO Asia (2025). Note: Data as of August 29, 2025.
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80 mg (n=20)Evaluable Population (1) 45 [23, 69]Best ORR,† % [95% CI] 45 [23, 69]Confirmed ORR, % [95% CI] 9 (45)Partial response, n (%) 11 (55)Stable disease, n (%) 0Progressive disease, n (%) 100 [83, 100]Disease control rate (CR + PR + SD), % [95% CI] 40 (8)With CNS disease at baseline,‡ % (n) 38 [9, 76]Best ORR,† % [95% CI] 38 [9, 76]Confirmed ORR, % [95% CI] 3 (38)Partial response, n (%) 5 (63)Stable disease, n (%) 0Progressive disease, n (%) 100 [63, 100]Disease control rate (CR + PR + SD), % [95% CI] 35 Enozertinib Achieved Strong Antitumor Activity, Including in Patients with CNS Disease at Baseline Enozertinib demonstrates strong systemic and CNS antitumor activity in 2L NSCLC patients with EGFR exon 20 mutations Source: John et al. ESMO Asia (2025). Note: D ata 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. (1) Reported in the evaluable population which includes participants who have received ≥1 dose, have ≥1 measurable lesion at baseline, and have had the opportunity for ≥3 postbaseline scans. † Best objective response rate includes both confirmed and unconfirmed responses. ‡ CNS disease at baseline includes patients with brain metastases at study entry, including active brain metastases. -100 -80 -60 -40 -20 0 20 Change From Baseline in Target Lesions, % ******** 80 mg (n=20) Patients with brain metastases at study entry, including active brain metastases * • Median follow-up of 30.3 weeks; 67% (6/9) of responders remain on treatment 2L EGFR exon 20 NSCLC
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120 mg (n=15) 80 mg (n=18)Event, n (%) 9 (60)4 (22)TRAEs Grade ≥3 12 (80)3 (17)Dose reduction due to TRAE 02 (11)Discontinued due to TRAE • 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) 120 mg (n=15) 80 mg (n=18)Event, n (%) Grade 3Grade 1-2Grade 3Grade 1-2Preferred term, n (%) 1 (7)9 (60)2 (11)15 (83)Diarrhea 1 (7)11 (73)08 (44)Paronychia 04 (27)1 (6)7 (39)Stomatitis 6 (40)4 (27)05 (28)Dermatitis acneiform 1 (7)2 (13)1 (6)4 (22)Rash 03 (20)06 (33)Nausea 03 (20)04 (22)Pruritis 1 (7)5 (33)04 (22)Mucosal inflammation 06 (40)01 (6)Dry skin 08 (53)01 (6)Alopecia 02 (13)05 (28)Rash maculo-papular 36 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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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 120 mg (n=15)Evaluable Population (1) 67 [38, 88]Best ORR,† % [95% CI] 60 [32, 84]Confirmed ORR, % [95% CI] 9 (60)Partial response, n (%) 5 (33)Stable disease, n (%) 1 (7)Progressive disease, n (%) 93 [68, 100]Disease control rate (CR + PR + SD), % [95% CI] Systemic Objective Response Rate Best % Change in Lesions in Patients Receiving 120 mg Dose (n=15) Patients with brain metastases at study entry, including active brain metastases 37 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 baseline, 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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120 mg (n=7) (1)CNS Response† 71 [29, 96]Best ORR,‡ % [95% CI] 71 [29, 96]Confirmed ORR, % [95% CI] 2 (29)Complete response, n (%) 3 (43)Partial response, n (%) 0Stable disease, n (%) 2 (29)Progressive disease, n (%) 71 [29, 96]Disease control rate (CR + PR + SD), % [95% CI] 38 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). (1) One patient was deem ed not evaluable by blinded independent central review (BICR). † Per RANO by BICR. ‡ Best objective response rate includes both confirmed and unconfirmed responses. 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. ** 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 39 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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• 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 40 120 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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• Well tolerated safety profile with TRAEs predominantly Grades 1-2 • No Grade 4 or 5 TRAEs • No significant off-target toxicities (e.g., myelosuppression, QTc prolongation, hepatotoxicity) • No discontinuations due to TRAEs • Higher rate of dose reductions at 120 mg (68%) vs. 80 mg (20%) – 80% of dose reductions at 120 mg dose down to 80 mg occurred before ~8 weeks on treatment (2 cycles) 120 mg (n=22) 80 mg (n=25)Event, n (%) 8 (36)7 (28)TRAEs Grade ≥3 15 (68)5 (20)Dose reduction due to TRAE 00Discontinued due to TRAE 120 mg (n=22) 80 mg (n=25)Event, n (%) Grade 3Grade 1-2Grade 3Grade 1-2Preferred term, n (%) 3 (14)14 (64)2 (8)12 (48)Diarrhea 1 (5)13 (59)012 (48)Paronychia 1 (5)10 (45)010 (40)Stomatitis 08 (36)08 (32)Dermatitis acneiform 04 (18)08 (32)Rash 07 (32)03 (12)Nausea 05 (23)1 (4)5 (20)Pruritis 2 (9)4 (18)04 (16)Mucosal inflammation 41 Enozertinib Has Been Generally Well Tolerated Despite More Heavily-Pretreated Patients and Less Stringent Enrollment Criteria for Prior Therapy and Baseline CNS Disease Previously treated EGFR Atypical NSCLC Source: Hong et al. ESMO Asia (2025). Note: Data as of August 29, 2025. Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients 80 mg dose generally well tolerated; given high rate of dose reductions at 120 mg dose, most patients received an effective dose of 80 mg QD
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Effective Dose 80 mg (n=22)Efficacy Evaluable Population (1) 36 [17, 59]Best ORR,‡ % [95% CI] 36 [17, 59]Confirmed ORR, % [95% CI] 8 (36)Partial response, n (%) 12 (55)Stable disease, n (%) 2 (9)Progressive disease, n (%) 91 [71, 99]Disease control rate (CR + PR + SD), % [95% CI] 59 (13)With CNS disease§ at baseline, % (n) 31 [9, 61]Best ORR,‡ % [95% CI] 31 [9, 61]Confirmed ORR, % [95% CI] 4 (31)Partial response, n (%) 7 (54)Stable disease, n (%) 2 (15)Progressive disease, n (%) 85 [55, 98]Disease control rate (CR + PR + SD), % [95% CI] Best % Change in Lesions in Patients Receiving 80 mg Effective Dose (n=22) 42 Enozertinib demonstrates strong systemic and CNS antitumor activity in a median 3L EGFR PACC mutant NSCLC patient population, 59% of which had brain metastases at study entry Enozertinib Achieved Strong Antitumor Activity, Including in Patients with CNS Disease at Baseline Previously treated (median 3L) EGFR Atypical NSCLC Patients with brain metastases at study entry, including active brain metastases* Source: Hong 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 efficacy evaluable population which includes participants who have received ≥1 dose, have ≥1 measurable lesion at baseline, and have had the opportunity for ≥3 postbaseline scans. † 22 patients were efficacy evaluable and received an effective dose of 80 mg: in the 80 mg cohort n=12 patients were efficacy evaluable; of the efficacy evaluable patients in the 120 mg cohort, 77% (n=10) required an early dose reduction to 80 mg. ‡ Best objective respon se rate includes both confirmed and unconfirmed responses. § CNS disease at baseline includes patients with brain metastases at study entry, including active brain metastases. PACC – P-loop and alpha C-helix compressing. • Median follow-up of 32.6 weeks; 75% (6/8) of responders remain on treatment
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Early Enozertinib Data in 1L EGFR PACC Patients Demonstrated Impressive Antitumor Activity, Including in Patients with CNS Disease at Baseline 43 Patients with brain metastases at study entry, including active brain metastases* Best % Change in Lesions in Patients Receiving 80 mg Dose (n=10) 80 mg (n=10)Preliminary Response Assessment 80Best ORR,‡ % 8 (80)Partial response, n (%) 2 (20)Stable disease, n (%) 0 (0)Progressive disease, n (%) 100Disease control rate (CR + PR + SD), % 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 prelimi nary 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 44 Best % Change in CNS Lesions in Patients Receiving 80 mg Dose (n=5) 80 mg (n=5) (1)Preliminary CNS Response 80Best ORR,‡ % 1 (20)Complete response, n (%) 3 (60)Partial response, n (%) 1 (20)Stable disease, n (%) * 0 (0)Progressive disease, n (%) 100Disease control rate (CR + PR + SD), % 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 RE CIST) presented due to preliminary nature of data and includes confirmed and pending unconfirmed 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 45 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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ORIC Entered into a Clinical Collaboration with Johnson & Johnson to Evaluate Enozertinib Plus Amivantamab in 1L NSCLC Patients with EGFR Exon 20 Mutations • Enozertinib plus SC amivantamab to be evaluated in 1L NSCLC with EGFR exon 20 insertions (1) ─ Phase 1b combination trial initiated in 1Q25 • ORIC to conduct the initial trial and Johnson & Johnson to provide SC amivantamab • ORIC retains development and commercialization rights to enozertinib 46 ORIC and Johnson & Johnson are evaluating the potential of enozertinib plus SC amivantamab in 1L NSCLC with EGFR exon 20; initial data from the combination trial expected in 2H26 Collaboration Overview Combination Rationale Potential for deeper and more durable clinical activity than either agent alone ─ Enozertinib provides CNS exposure to treat and/or prevent brain metastases ─ Amivantamab provides activity against potential TKI resistance mechanisms (e.g., cMET, C797S) ─ Combination may provide more potent and comprehensive coverage across exon 20 insertions Proof of concept established with lazertinib plus amivantamab in classical EGFR mutations (2) Chemotherapy free regimen (1) Clinical collaboration with Johnson & Johnson to evaluate enoz ertinib in combination with amivantamab and hyaluronidase-lpujsubcutaneous injection (SC amivantamab) in patients with first-line NSCLC with EGFR exon 20 mutations. (2) Cho et al. N Engl J Med (2024).
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47 2026 2027+ Ongoing Phase 1b Trials Potential Phase 3 Trial(s) 1L EGFR Exon 20 Monotherapy and/or Combination 1L EGFR PACC 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 PACC Mutations 1L EGFR Exon 20 Monotherapy 1L EGFR Exon 20 Combination with chemotherapy 1L EGFR PACC Monotherapy 1L EGFR Exon 20 Combination with SC amivantamab (1) (1) Clinical collaboration with Johnson & Johnson to evaluate enoz ertinib in combination with amivantamab and hyaluronidase-lpujsubcutaneous injection (SC amivantamab) in patients with first-line NSCLC with EGFR exon 20 mutations.
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48 Enozertinib Is Pursuing a Significant Commercial Opportunity Across Patient Populations that Lack an Approved CNS Active Agent Enozertinib has the potential to address ~9,000 patients with NSCLC annually, representing a commercial opportunity of ~$3.0 to $3.5 billion in the US alone 4,000 patients 5,000 patients 0 2,000 4,000 6,000 8,000 10,000 12,000 1L EGFR Exon 20 1L EGFR PACC Estimated Annual Incidencein the US Potential commercial opportunity of ~$3.0 to $3.5 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. PACC – P-loop and alpha C-helix compressing. • ~9,000 patients (~5% of NSCLC) diagnosed annually • EGFR exon 20 mutant NSCLC: no approved CNS-active therapies • EGFR PACC mutant NSCLC: no approved therapies>$1.0 billion US opportunity >$2.0 billion US opportunity
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Key Takeaways
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50 Program Indication PRODUCT CANDIDATES Enozertinib (ORIC-114) EGFR inhibitor Rinzimetostat (ORIC-944) PRC2 inhibitor Discovery / IND Enabling Phase 1/2 Pivotal / Phase 3 Clinical Collaboration Anticipated Data Milestones •Combination with apalutamide •1L monotherapy •1L combination with SC amivantamab (1) •1L combination with chemotherapy •Combination with darolutamide •1L monotherapy Prostate Cancer NSCLC EGFR PACC NSCLC EGFR exon 20 Note: PACC – P-loop and alpha C-helix compressing. (1) Clinical collaboration with Johnson & Johnson to evaluate enoz ertinib in combination with amivantamab and hyaluronidase-lpujsubcutaneous injection (SC amivantamab) in patients with first-line NSCLC with EGFR exon 20 mutations. Clinical Pipeline Focused on Advancement of Rinzimetostat and Enozertinib Clinical-stage pipeline includes two potential best-in-class programs addressing large solid tumor market opportunities; Both programs approaching initiation of registrational trials 2H 2026 2H 2026 1Q and 2H 2026
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ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer 51 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 and EGFR PACC mutations • Heritage of discovering, developing, and commercializing oncology therapies at Ignyta, Medivation, Aragon, Pharmacyclics, Deciphera, and Genentech • Rinzimetostat (ORIC-944) and enozertinib (ORIC-114) rapidly advancing towards potential Phase 3 initiations Anticipated Milestones • Rinzimetostat for mCRPC: ─ 1Q26: Combination dose optimization data with AR inhibitor ─ 1H26: Initiate first global Phase 3 registrational trial in mCRPC ─ 2H26: Program update • Enozertinib for NSCLC: ─ 2H26: 1L EGFR exon 20 monotherapy data and combination data with SC amivantamab (2) ─ 2H26: 1L EGFR PACC monotherapy data Note: PACC – P-loop and alpha C-helix compressing. (1) Represents cash and investments of approx imately $413 million as of September 30, 2025. (2) Clinical collaboration with Johnson & Johnson to evaluate enoz ertinib in combination with amivantamab and hyaluronidase-lpujsubcutaneous injection (SC amivantamab) in patients with first-line NSCLC with EGFR exon 20 mutations. • Cash and investments of $413 million expected to fund company into 2H 2028 (1) • Funding through primary endpoint readout from first Phase 3 trial of rinzimetostat Two potential best-in-class programs approaching Phase 3 initiation; Cash runway into 2H28, beyond rinzimetostat Phase 3 data