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"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
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in this presentation also include, but are not limited to, statements regarding: our development plans and timelines; the potential advantages of our product candidates and programs; plans for the clinical trials and development of ORIC-114 and
ORIC-944; ORIC-114 and ORIC-944 clinical outcomes, which may materially changes 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 discovering, 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. 2
ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer
Potential best-in-class TKI targeting NSCLC with EGFR exon 20, HER2 exon 20, and EGFR atypical mutations Lead Programs Advancing toward Pivotal Studies Potential best-in-class PRC2 inhibitor targeting mCRPC Pipeline built
from internal R&D and external business development Dual Engine for Pipeline Expansion Targeting one new IND candidate every 18 months Heritage of discovering, developing, and commercializing oncology therapies Experienced
Management Team at Ignyta, Medivation, Aragon, Pharmacyclics, and Genentech (1) Strong Financial Position Cash and investments of $282 million expected to fund company into late 2026 ORIC-114 (NSCLC): 1H25: 2L EGFR exon 20
and 2L+ HER2 exon 20 2H25: 2L+ EGFR atypical 1H26: 1L EGFR exon 20 Anticipated Data Milestones Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical ORIC-944 (mCRPC): 4Q25 / 1H26:
Combination with AR inhibitors Two potential best-in-class programs expected to enter pivotal studies in 2H25 (ORIC-114) and early 2026 (ORIC-944) (1) Unaudited balance as of September 30, 2024. 3
Executive Team with Expertise in Building Leading Oncology Companies
Jacob Chacko, MD Previously CFO at Ignyta (acquired by Roche), raised >$500m in capital Chief Executive Officer 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 Previously Head of Translational Oncology at Genentech; advanced >20 drug candidates into development Lori
Friedman, PhD Chief Scientific Officer Director of Signal Transduction at Exelixis Board member of NextRNA Therapeutics Pratik Multani, MD Previously CMO of Ignyta; led development and regulatory for ROZLYTREK (entrectinib)
Chief Medical Officer CMO of Fate; previously at IDEC, Salmedix, Dana Farber and MGH Board member of Erasca and Chimerix Matt Panuwat Previously SVP of Business Development at Prothena, established Celgene collaboration for
up to $2.2bn Chief Business Officer Head of Business Development at Medivation (acquired by Pfizer) Global Healthcare Investment Banking at Merrill Lynch Dominic Piscitelli Previously CFO at AnaptysBio, raised >$500m in
capital Chief Financial Officer VP of Finance, Strategy and IR at Medivation and OSI Pharmaceuticals Board member of Alterome Therapeutics and Celyad Oncology Christian Kuhlen, MD Previously General Counsel at Synthorx
(acquired by Sanofi), completed $151 million IPO General Counsel General Counsel at Ignyta and Genoptix Edna Chow Maneval, PhD Previously SVP at Ignyta; clinical lead for ROZLYTREK, led transition team through global filings EVP
Clinical Development VP of Clinical Development at Seragon and Aragon, clinical lead for ERLEADA (apalutamide) Keith Lui Previously SVP of Business Development, Commercial and Medical Affairs at DURECT SVP Commercial & Medical
Affairs Led commercial strategy and launch-readiness at Pharmacyclics, Genentech, Prothena, and Oncopeptides 4
Clinical Pipeline Focused on Advancement of ORIC-114 and ORIC-944
Discovery / Clinical Anticipated Program Indication IND Enabling Phase 1/2 Pivotal / Phase 3 Collaboration Data Milestones PRODUCT CANDIDATES Mid-2026 1L combination with SC amivantamab EGFR exon 20 1L monotherapy 1H26 (1) NSCLC
2L monotherapy 1H25 1L monotherapy Mid-2026 Atypical EGFR ORIC-114 NSCLC 2L+ monotherapy 2H25 EGFR/HER2 inhibitor HER2 exon 20 2L+ monotherapy 1H25 NSCLC Combination with apalutamide 4Q25 / 1H26 ORIC-944
Prostate Cancer PRC2 inhibitor Combination with darolutamide 4Q25 / 1H26 DISCOVERY RESEARCH PROGRAMS Multiple programs targeting Solid tumors resistance mechanisms (1) Clinical collaboration with Johnson & Johnson to evaluate ORIC-114
plus subcutaneous (SC) amivantamab in patients with first-line NSCLC with EGFR exon 20 insertion mutations. 5
Substantial Progress in 2024: Well Positioned to Build Value in 2025 and
Beyond 2024 Accomplishments and Next Steps Completed dose escalation, selected provisional RP2Ds, and initiated multiple dose expansion cohorts Executed clinical supply agreement with JNJ to evaluate ORIC-114 in combination with
ORIC-114 EGFR/HER2 inhibitor SC amivantamab in 1L NSCLC EGFR exon 20 Presented data further supporting potential best-in-class profile of ORIC-114 versus competitors Phase 1b single agent data demonstrated potential best-in-class drug
properties and favorable safety, supporting advancement into combination development in prostate cancer Executed clinical supply agreements with JNJ and Bayer to evaluate ORIC-944 in combination with ORIC-944 PRC2 inhibitor apalutamide and
darolutamide in mCRPC and initiated combination cohorts mid-2024 Presented data demonstrating potential best-in-class drug properties and data supporting mechanistic rationale for combination with AR inhibitors Raised $125 million from
healthcare specialist funds, extending cash runway into late 2026 Corporate Expanded leadership team with appointment of SVP of Commercial and Medical Affairs Two potential best-in-class programs expected to enter pivotal studies in 2H25
(ORIC-114) and early 2026 (ORIC-944) 6
ORIC-114 Brain Penetrant EGFR/HER2 Inhibitor
ORIC-114: Potential Best-in-Class TKI to Overcome Limitations of
Approved and Investigational Agents for EGFR and HER2 Mutated NSCLC KEY LIMITATIONS of approved and investigational agents Lack of CNS activity in populations with high rate of CNS metastases leads to suboptimal clinical outcomes
Tolerability issues with high rates of treatment discontinuations due to on- and off-target toxicity ORIC-114 may address these limitations Selectively targets EGFR and HER2 with high potency against exon 20 insertion and atypical mutations
Multiple confirmed responses observed in heavily pretreated NSCLC patients with EGFR and HER2 exon 20 Demonstrated CNS activity including first ever confirmed CNS complete response in an EGFR exon 20 patient with untreated brain
metastases Well-tolerated with mostly Grade 1-2 TRAEs, low rates and severity of on-target rash and diarrhea, and minimal off- target toxicities STATUS of development Enrolling three cohorts in 2L NSCLC: EGFR exon 20, HER2 exon
20, and EGFR atypical mutations Initiating three cohorts in 1L NSCLC: EGFR atypical, EGFR exon 20 monotherapy and in combination with SC amivantamab (1) (in collaboration with Johnson & Johnson) Six Phase 1b data readouts
expected through mid-2026 ORIC-114 is a potential best-in-class therapy for NSCLC with excellent selectivity and brain penetrance that has demonstrated promising clinical proof-of-concept in heavily pretreated patients with active CNS metastases (1)
Clinical collaboration with Johnson & Johnson to evaluate ORIC-114 plus subcutaneous (SC) amivantamab in 1L NSCLC patients with EGFR exon 20. 8
ORIC-114 Selectively Targets EGFR and HER2 with High Potency Against
EGFR Exon 20 Insertion, HER2 Exon 20 Insertion and EGFR Atypical Mutations Kinome Selectivity Comparison ORIC-114 Firmonertinib Zipalertinib Lazertinib BDTX-1535 Off-target Kinases Inhibited 80% at 1 M ORIC-114 Firmonertinib Zipalertinib
Lazertinib BDTX-1535 0 4 7 14 25 ORIC-114 has demonstrated an exquisitely clean kinome panel, mitigating the potential for off-target toxicities Source: Junttila et al. ESMO (2023) and ORIC data on file. Note: Kinase binding profiles across 468
kinases at 1 M 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. 9
ORIC-114 Demonstrates Potent In Vivo Activity in EGFR Exon 20 Insertion
Models In Vivo Efficacy - NSCLC EGFR Exon 20 Insertion Models EGFR Exon 20 insNPH EGFR Exon 20 insASV EGFR Exon 20 insG Vehicle Vehicle Vehicle ORIC-114 (4 mg/kg QD) ORIC-114 (4 mg/kg QD) ORIC-114 (4 mg/kg QD) 112% TGI 127% TGI 110% TGI
ORIC-114 demonstrates potent tumor regression in multiple NSCLC EGFR exon 20 insertion models without significant body weight loss Source: Junttila et al. AACR (2021). 10
Drugs Lacking CNS Activity Often Have Worse Clinical Outcomes in NSCLC
Case Study on NSCLC Targeted Therapy without CNS Activity: Mobocertinib In mobocertinib's phase 1/2 trial, ~35% of patients had CNS metastases at baseline Patients WITHOUT 8.1 CNS Metastases at Baseline Patients with CNS
metastases at baseline had markedly worse outcomes Brain was the first site of progression in 68% of patients with CNS metastases at baseline and in 38% of all patients Patients WITH 3.7 CNS Metastases at Baseline ORR was 25% in
patients with CNS metastases at baseline compared to 43% in all patients 0.0 2.0 4.0 6.0 8.0 10.0 Median Progression Free Survival (Months) Approximately 35% of EGFR exon 20 NSCLC patients have CNS metastases at baseline and the brain is a frequent
site of progression in patients with and without CNS metastases at baseline, leading to shorter PFS with therapies lacking CNS activity Source: Janne et al. ASCO (2019) and Ramalingam et al. ASCO (2021). 11
Superior Brain Penetration of ORIC-114 Differentiates from Comparator
Exon 20 Targeted Agents ORIC-114 Properties Allowed ORIC-114 Exhibits High Ratio of Free (Unbound) Optimization of Brain Exposure Brain/Plasma Exposure in Mice Minimal pump engagement Key pumps that limit brain penetration, PGP and
BCRP drug transporters, have minimal impact on ORIC-114 in cell assays Suitable physicochemical properties LogP, LogD, TPSA, MW, HBD/HBA, pKa High free unbound exposure in brain tissue Mouse Kp,uu 0.5 Dog
Kp,uu 1.5 * * Extensive preclinical profiling demonstrates superior CNS properties of ORIC-114 versus competitors; Excellent free brain exposure across species for ORIC-114 as exhibited by Kp,uu Source: Junttila et al. AACR (2021), Junttila et al.
AACR-NCI-EORTC (2021) and ORIC data on file. * Brain exposures were below quantification limit. 12 Free Brain/Plasma Ratio (@ 4 hr)
First-In-Human Phase 1b Study of ORIC-114 Phase 1b, Multicenter,
Open-Label Study Dose Expansion (Part II) Accelerated Approval Dose Escalation (Part I) All Patients +/- CNS mets Cohorts (Ph 2) Key Eligibility EGFR ex20 NSCLC +/- CNS Advanced solid tumors na ve to EGFR ex20 therapy RP2D 1
EGFR exon 20 ORIC-114 HER2 exon 20 Single agent EGFR atypical mutated HER2+ NSCLC +/- CNS i3+3 design EGFR atypical Active CNS Oral QD/BID daily dosing RP2D 2 Candidate metastases allowed RP2Ds
HER2 ex20 NSCLC +/- CNS Prior EGFR exon 20 Selected treatment allowed Primary endpoints: Part I: Safety and candidate RP2Ds; Part II: Dose expansion (RP2D selection) and ORR (per RECIST v1.1) Key secondary endpoints: Part I: PK; Part II:
Safety; DOR, CBR and PFS, including intracranial ORR/PFS Initial safety, PK/PD, and preliminary antitumor data from dose escalation (part I) presented at ESMO 2023 Note: ClinicalTrials.gov identifier: NCT05315700. Dose expansion may include QD and
BID dosing, fed/fasted dosing. RP2D, recommended Phase 2 dose 13 Screening / Enrollment
ORIC-114 Phase 1 Patient Disposition and Baseline Characteristics
Patient Disposition and Baseline Characteristics EGFR Ex20 HER2 Ex20 HER2+ Total (n=21) (n=24) (n=5) (N=50) 63 (31,80) 63 (25,86) 66 (48,68) 63 (25,86) Age, years, median(range) 50 patients were treated with 10 (48) 11 (46) 3 (60) 24 (48)
Females, n (%) increasing doses of ORIC-114 ECOG performance score, n (%) Of the NSCLC patients with 1 (5) 10 (42) 3 (60) 14 (28) 0 EGFR exon 20 20 (95) 14 (58) 2 (40) 36 (72) 1 12 (57) 16 (68) 3 (60) 31 (62) Non-smoker, n (%)
1 prior EGFR ex20: 81% 2 (1,6) 2 (0,7) 4 (1,7) 2 (0,7) Prior lines of therapies, median (min, max) 2 prior EGFR ex20: 19% Prior therapies, n (%) 21 (100) 23 (96) 5 (100) 49 (98) Chemotherapy CNS mets at baseline: 86% 18
(86) 1 (4) - 19 (38) EGFR targeted agents Of the NSCLC patients with EGFR exon 20 targeted agents 17 (81) - - 17 (34) HER2 exon 20 Amivantamab 15 (71) - - 15 (30) Mobocertinib 4 (19) - - 4 (8)
1 prior HER2 agent: 30% Other (CLN-081, BLU-451) 2 (10) - - 2 (4) CNS mets at baseline: 38% HER2 targeted agents - 7 (30) 3 (60) 10 (20) 18 (86) 9 (38) 1 (20) 28 (56) CNS metastases at baseline, n (%) Phase
1b enrolled heavily pretreated patients with exceptionally high rates of prior exon 20 targeted therapy and CNS metastases at baseline Note: All data as of the data cut-off on September 26, 2023. 14
ORIC-114 Has Been Generally Well Tolerated Despite More
Heavily-Pretreated Patients and Less Stringent Enrollment Criteria for Prior Therapy and CNS Disease Treatment Related Adverse Events Occurring in 10% of Patients <45 mg TDD 45 - 60 mg TDD 75 mg TDD Total (n=18) (n=23) (n=9)
(N=50) Well tolerated safety profile Preferred Term, n (%) Gr1 Gr2 Gr3 Gr4 Gr1 Gr2 Gr3 Gr4 Gr1 Gr2 Gr3 Gr4 All Grades with mostly Grade 1-2 Rash* 6 (33) 4 (22) - - 6 (26) 6 (26) - - 4 (44) 1 (11)
- - 27 (54) TRAEs Diarrhea 2 (11) 2 (11) - - 7 (30) 2 (9) 2 (9) - 2 (22) 2 (22) 1 (11) - 20 (40) Minimal EGFR-wt related or other toxicities Stomatitis 4 (22) 2 (11) - - 2 (9) 2 (9) 1 (4)
- 2 (22) 2 (22) - - 15 (30) Paronychia 1 (6) 2 (11) - - 4 (17) 4 (17) - - 2 (22) 1 (11) - - 14 (28) Low rates and severity of rash and diarrhea Pruritis 2 (11) - - - 4