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Forward-Looking Statements 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 our product candidates and programs; plans for the clinical trials and development of ORIC-114,
ORIC-944 and ORIC-533; 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 the COVID-19 pandemic 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; 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
Two potential best-in-class programs advancing towards pivotal studies Broad Pipeline of Potential First-in-Class and Best-in-Class Programs Additional preclinical programs targeting novel and validated targets Precision Oncology
Expertise Enables Rapid timelines enabled by biomarker-driven, patient-selected clinical Accelerated Clinical Timelines trials and translational expertise Track record of building pipeline via internal R&D and business
development Dual Engines for Pipeline Expansion Targeting one new IND candidate every 18 months Heritage of discovering and developing multiple approved oncology medicines at Experienced Management Team Ignyta, Medivation, Aragon and
Genentech (1) Strong Financial Position Cash and investments of $235 million expected to fund company into 2026 ORIC-944 initiation of combination study with AR inhibitor(s): 1H 2024 ORIC-944 program update: mid-2024
Anticipated Milestones ORIC-114 initiation of dose expansion in multiple cohorts: 1H 2024 ORIC-114 updated Phase 1b data: 1H 2025 (1) Approximate unaudited balance as of December 31, 2023. 3
Executive Team with Expertise in Building Leading Oncology Companies
Previously CFO of Ignyta (acquired by Roche), raised over $500mm in capital Jacob Chacko, MD Chief Executive Officer TPG Capital (completed $10bn of aggregate acquisitions) and McKinsey Board member of 4D Molecular
Therapeutics and Board chair of Bright Peak Therapeutics; previously Turning Point, Bonti, RentPath, EnvisionRx, Par Pharma, IMS and Quintiles Previously Head of Translational Oncology at Genentech; advanced over 20 drug candidates into Lori
Friedman, PhD development, two approvals to date Chief Scientific Officer Director of Signal Transduction at Exelixis; led new target discovery collaboration with BMS Inventor on 28 issued patents and author on 99 peer-reviewed
publications Board member of NextRNA Therapeutics Previously CMO of Ignyta, led development and regulatory for entrectinib Pratik Multani, MD Chief Medical Officer CMO of Fate Therapeutics; contributed to development of
Rituxan and Zevalin at Idec, and Treanda at Salmedix; earlier at Dana Farber and MGH Board member of Erasca and Chimerix Previously SVP of Business Development at Prothena, established Celgene collaboration for up to $2.2bn Matt
Panuwat Chief Business Officer Head of BD at Medivation (acquired by Pfizer), led M&A including the acquisition of talazoparib Global Healthcare Investment Banking at Merrill Lynch Previously CFO of AnaptysBio, raised
over $500mm in capital (IPO and follow-on financing) Dominic Piscitelli Chief Financial Officer VP of Finance, Strategy and Investor Relations at Medivation VP of Treasury and Finance at OSI Pharmaceuticals (acquired by Astellas)
Board member of Celyad Oncology Previously General Counsel at Synthorx (acquired by Sanofi), completed $151 million IPO Christian Kuhlen, MD General Counsel General Counsel at Ignyta and Genoptix (acquired by Novartis),
executed multiple financings and M&A Attorney at Cooley LLP Edna Chow Maneval, PhD Previously SVP at Ignyta; clinical lead for entrectinib, led transition team through global filings SVP Clinical Development VP of
Clinical Development at Seragon and Aragon, clinical lead for apalutamide Led pivotal Phase 3 study in RCC for Sutent at Pfizer 4
Clinical Pipeline Focused on Advancement of ORIC-114 and ORIC-944 Lead
Lead Program Indication Identification Optimization IND Enabling Phase 1 Phase 2 Phase 3 Key Differentiation PRODUCT CANDIDATES NSCLC, Breast & CNS active ORIC-114 Phase 1b: ORIC-114 single agent Tumor agnostic Well tolerated
EGFR/HER2 exon 20 inhibitor Potential best-in-class ORIC-944 Phase 1b: ORIC-944 single agent Prostate Cancer drug properties PRC2 inhibitor OUT-LICENSING CANDIDATE Single agent activity ORIC-533 Phase 1b: ORIC-533 combination
ready Clean safety profile Multiple Myeloma CD73 inhibitor Immune activation DISCOVERY RESEARCH PROGRAMS ORIC-613 Breast cancer First-in-class potential PLK4 inhibitor Solid tumors Multiple programs targeting resistance
mechanisms Solid tumors 5
Substantial Progress in 2023: Well Positioned to Build Value in 2024 and
Beyond 2023 Accomplishments and Next Steps Phase 1b dose escalation data presented at ESMO 2023 demonstrated potential best-in-class profile, ORIC-114 with favorable safety and both systemic and CNS activity in heavily pre-treated NSCLC
patients EGFR/HER2 exon 20 inhibitor Initiating multiple dose expansion cohorts in 1H 2024 Phase 1b dose escalation data demonstrated potential best-in-class drug properties and favorable ORIC-944 safety, supporting advancement
into combination development in prostate cancer PRC2 inhibitor Initiating combination development with AR inhibitor(s) in 1H 2024 Phase 1b dose escalation data presented at ASH 2023 demonstrated favorable safety and clinical
ORIC-533 activity in heavily pre-treated multiple myeloma patients CD73 Inhibitor Pursuing strategic partnership for combination studies Presented preclinical data confirming therapeutic potential of highly selective PLK4
inhibitors as synthetic lethal for TRIM37 amplified breast cancer Discovery Research Advanced ORIC-613, a novel, highly selective PLK4 inhibitor, through IND enabling studies Strengthened balance sheet with $85 million financing
from healthcare specialist funds Corporate Extended cash runway into 2026 ORIC-114 and 944 rapidly advancing, with potential registrational studies for both programs expected to initiate in 2025 6
ORIC-114 Brain Penetrant EGFR/HER2 Exon 20 Inhibitor
ORIC-114 Is a Promising Candidate for Patients with Tumors Harboring
EGFR and HER2 Exon 20 Insertion Mutations, Including Those with Brain Metastases ORIC-114 Target Product Profile Selectively targets EGFR and HER2 with high potency against exon 20 insertion mutations Exquisite kinome selectivity
with limited potential Selective and Potent for off-target activity 800 600 Significant tumor regression in multiple exon 20 400 insertion models 200 Promising Phase 1b Results 0 0 5 10 15 20 25 Days After Treatment Superior
therapeutic index in vivo with improved efficacy and tolerability than competitor molecules Well tolerated safety profile Robust In Vivo Efficacy Systemic activity post-amivantamab CNS activity High unbound (free)
brain exposures in vivo Substantial tumor regression in intracranial efficacy studies Highly Brain Penetrant ORIC-114 is a potentially best-in-class EGFR and HER2 exon 20 inhibitor with excellent selectivity and brain penetrance 8 3 Mean
ORIC-114 Was Designed to Selectively Target EGFR and HER2 with High
Potency Against Exon 20 Insertion Mutations Kinome Selectivity Comparison CLN-081 Furmonertinib BLU-451* Mobocertinib ORIC-114 Off-target Wildtype (WT) Kinases Inhibited 80-100% at 1 M ORIC-114 CLN-081 Furmonertinib BLU-451 Mobocertinib 0 7
4 7* 7 ORIC-114 has demonstrated an exquisitely clean kinome panel, which is especially important for covalent inhibitors Source: Junttila et al. ESMO Poster (2023) and Murray et al. AACR Poster (2022). Note: ORIC-114,
mobocertinib, CLN-081, data conducted head-to-head in 468 kinases at 1 M. Top 10% shown. *BLU-451 data not conducted head-to-head in 409 kinases at 1 M. 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 3000 800 800 Vehicle Vehicle Vehicle ORIC-114 (4 mg/kg QD) ORIC-114 (4 mg/kg QD) ORIC-114 (4 mg/kg QD) 600 600 2000 400 400
1000 200 200 112% TGI 127% TGI 110% TGI 0 0 0 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 Days After Treatment Days After Treatment Days After Treatment ORIC-114 demonstrates potent tumor regression in multiple NSCLC EGFR exon 20 insertion
models without significant body weight loss Source: Junttila et al. AACR Poster (2021). 10 3 Mean Tumor Volume (mm ) 3 Mean Tumor Volume (mm ) 3 Mean Tumor Volume (mm )
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 Presentation (2019) and Ramalingam et al. ASCO Poster (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 10 Key pumps that limit brain penetration, PGP
and BCRP drug transporters, have minimal impact on 1 ORIC-114 in cell assays Suitable physicochemical properties 0.1 LogP, LogD, TPSA, MW, HBD/HBA, pKa High free unbound exposure in brain tissue 0.01 Mouse Kp,uu 0.5
Dog Kp,uu 1.5 * * 0.001 ORIC-114 Mobocertinib CLN-081 BDTX-189 Osimertinib 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 Poster (2021), Junttila et al. AACR-NCI-EORTC Presentation (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) EGFR ex20 NSCLC +/- CNS Key Eligibility na ve to EGFR ex20 therapy Advanced solid tumors RP2D 1
EGFR exon 20 EGFR ex20 NSCLC +/- CNS ORIC-114 HER2 exon 20 post-amivantamab Single agent HER2+ i3+3 design EGFR atypical EGFR atypical mutated NSCLC +/- CNS Active CNS Oral QD/BID daily dosing
RP2D 2 Candidate metastases allowed RP2Ds Prior EGFR exon 20 Selected HER2 ex20 NSCLC +/- CNS 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 15 (71) - - 15 (30) Amivantamab 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 Stomatitis 4 (22) 2 (11) - - 2 (9) 2 (9) 1 (4) - 2 (22) 2 (22)
- - 15 (30) other toxicities 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 (17) 2
(9) 1 (4) - 1 (11) 1 (11) - - 11 (22) No Grade 3 rash Nausea 1 (6) - - - 2 (9) 2 (9) - - 1 (11) 1 (11) 1 (11) - 8 (16) Low rate of Grade 3 Decreased appetite - 1 (6)
- - 5 (22) 1 (4) - - - - - - 7 (14) diarrhea (6%) Vomiting 2 (11) - - - 2 (9) - - - 1 (11) 1 (11) 1 (11) - 7 (14) Infrequent dose reduction Dose