Slide 1: R&D Meeting February 22, 2024
R&D Meeting February 22, 2024
Slide 2: Cautionary Notes
Cautionary Notes Forecasts and other forward-looking statements included in this document are based on information currently available and certain assumptions that the Company deems reasonable. Actual performance and other results may differ significantly due to various factors. Such factors include
Slide 3: Agenda
Agenda Introduction（13:00-13:10） President, Representative Director, and CEO Gyo Sagara ONO-4578 Development Status（13:10-13:30） • ONO-4578-01 Part C • ONO-4578-01 Part D Corporate Officer / Deputy Executive Director, Clinical Development Tatsuya Okamoto Updates of Open Innovation and ONO-8250 Intro
Slide 4: Change in Representative Directors
Change in Representative Directors Details of the change in directors as of April 1, 2024 Name New Role Current Title Representative Director, Chairman of the Board Gyo Sagara Representative Director, President and Chief Exective Officer Representative Director, President and Chief Director, Senior
Slide 5: Future growth strategies - Aggressively invest in R&D for growth
Future growth strategies - Aggressively invest in R & D for growth - Investment allocation (FY 2022 to FY 2026) Leverages abundant R & D capabilities R & D investment Strategic Investment Accelerate global business development investment Shareholder to increase 600 billion yen 250 Returns corporate
Slide 6: ONO-4578 Development Status
ONO-4578 Development Status
Slide 7: ONO-4578
ONO-4578 Compound ONO-4578（In-house, Small molecule） Mechanism Prostagrandin receptor (EP4) antagonist Formulation Tablet Phase2：GC*（JP・KR・TW） Phase1：Colorectal cancer*, Pancreatic cancer*, Stage NSCLC*, Hormone receptor-positive, HER2-negative breast cancer（JP） （* : Combination with OPD） 6 / 63
Slide 8: ONO-4578 Mechanism of Action
ONO-4578 Mechanism of Action ▪ Prostaglandin E2 (PGE2) is produced from arachidonic acid through cyclooxygenase-2 (COX-2) ▪ COX-2 is overexpressed in solid cancer1). PGE2 has been reported to induce myeloid-derived suppressor cells (MDSC) and M2 macrophages in the tumor microenvironment through one
Slide 9: ONO-4578 Non-clinical data
ONO-4578 Non-clinical data Fig 1. Time course of median tumor volume in syngeneic mouse colorectal cancer MC38 tumor-bearing model Vehicle αPD-1 αPD-1+4578（0.1 mg/kg） αPD-1+4578（0.3 mg/kg） ▪ In syngeneic mouse tumor-bearing model, αPD-1+4578（1 mg/kg） αPD-1+4578（3 mg/kg） ONO-4578 improved immunosuppr
Slide 10: ONO-4578 Development stage
ONO-4578 Development stage 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 Phase1（FIH）：Solid cancer★ Phase1b：GC, Colorectal cancer ★ ONO-4578-01 Phase1b ： Colorectal cancer ★ ONO-4578-02 Phase1b ： Rectal cancer NAC ★ ONO-4578-03 Phase1b ： Pancreatic cancer ★ ONO-4578-04 Phase1b ：NSCLC★ ONO-45
Slide 11: ONO-4578-01 Part C Results
ONO-4578-01 Part C Results Safety, efficacy, and biomarkers for ONO-4578 plus nivolumab in unresectable advanced or recurrent gastric or gastroesophageal cancer Hidekazu Hirano1, Akihito Kawazoe2, Kensei Yamaguchi3, Tetsuya Hamaguchi4, Yukiya Narita5, Shogen Boku6, Takashi Oshima7, Hiroki Hara8, Yas
Slide 12: Methods
Methods Study Design ◼ Part C of the ONO-4578-01 phase 1 study (NCT03155061) was an open-label, uncontrolled study, conducted at 22 sites in Japan ◼ Recruited patients were categorized into three parts (C1, C2, C3) on the basis of prior anti-PD-1/ ◼ PD-L1 therapy and UGT1A1 genotype (Figure 2) ◼ All
Slide 13: Efficacy Results
Efficacy Results C1 (n=30) C2 (n=30) Objective Response Rate, % [90% CI] 10.0 [2.8–23.9] 16.7 [6.8–31.9] Disease Control Rate, % [90% CI] 73.3 [57.0–86.0] 40.0 [25.0–56.6] Best Overall Response, n (%) [90% CI] Complete Response 0 (0) [0.0–9.5] 0 (0) [0.0–9.5] Partial Response 3 (10.0) [2.8–23.9] 5 (
Slide 14: Efficacy Results
Efficacy Results Waterfall Plot by Best Overall Response ESMO 2023: Poster #1546 13 / 63
Slide 15: Study schedule of ONO-4578-01 Part C (3rd or later line, GC)
Study schedule of ONO-4578-01 Part C (3rd or later line, GC) Pre Post Baseline Day1 6 weeks 12 weeks X weeks End of treatment Treatment ONO-4578 + Nivolumab Efficacy CT scan Every 6 weeks Biomarkers Tumor Blood 14 / 63
Slide 16: Results of Biomarker Analysis
Results of Biomarker Analysis T-cell Gene Signature and M1/M2 Macrophage Gene Signature in Tumor Biopsies Signature score was calculated as mean of log-transformed expression value BOR, best overall response; PD, progressive disease; PR, partial response; SD, stable disease Scr, Screening period; C2
Slide 17: Results of Biomarker Analysis
Results of Biomarker Analysis ◼ Baseline urine PGEM, the potential surrogate marker of tumor PGE2, was found to be higher in patients with partial response or stable disease than in patients with progressive disease Baseline Urine PGEM Levels PD, progressive disease; PGEM, prostaglandin E2 metabolit
Slide 18: Safety Results
Safety Results ESMO 2023: Poster #1546 17 / 63
Slide 19: ONO-4578-01 Part D Results
ONO-4578-01 Part D Results Safety And Efficacy Of ONO-4578 Plus Nivolumab In Metastatic Colorectal Cancer Akihito Kawazoe1, Atsuo Takashima2, Hiroshi Matsuoka3, Yasuo Hamamoto4, Tatsuya Okuno5, Tetsuya Hamaguchi6, Kensei Yamaguchi7, Eiji Oki8, Naotoshi Sugimoto9, Yasushi Tsuji10, Shogen Boku11, Tomo
Slide 20: Methods
METHODS Study Design •Part D (CRC cohort) of the ONO-4578-01 phase 1 study (NCT03155061) was an open-label, uncontrolled study, conducted at 12 sites in Japan •Key eligibility criteria were as follows ─ Age ≥20 years ─ Unresectable and metastatic CRC that progressed on/after standard treatment or co
Slide 21: Efficacy Results
Efficacy Results Best Overall Response (BOR) n (%) [90% CI] CR 0 (0.0) [0.0–5.7] PR 2 (3.9) [0.7–11.8] SD 18 (35.3) [24.2– 47.7] PD 30 (58.8) NE 1 (2.0) ORR (CR+PR) 2 (3.9) [0.7–11.8] DCR (CR+PR+SD) 20 (39.2) [27.7–51.7] CR, complete response; DCR, disease control rate; NE, not evaluable; ORR, objec
Slide 22: Efficacy Results
Efficacy Results Spider Plot for Best Overall Response Waterfall Plot by Best Overall Response Treatment ongoing Best overall response follows RECIST guidelines version 1.1 PD, progressive disease; PR, partial response; SD, stable disease ASCO-GI 2024: Poster #93 21 / 63
Slide 23: Results of studies in colorectal cancer
Results of studies in colorectal cancer 試験 ORR, DCR（%） PFS（month） OS（month） CORRECT, CRC 3L, P3 1) ORR: 1.0 vs 0.4 Median: 1.9 vs 1.7 Median: 6.4 vs 5.0 Regorafenib vs Placebo DCR: 41 vs 15 HR: 0.49 HR: 0.77 RECOURSE, CRC 3L, P3 2) ORR: 1.6 vs 0.4 Median: 2.0 vs 1.7 Median: 7.1 vs 5.3 TAS102 vs Plac
Slide 24: Efficacy Results
Efficacy Results Subgroup Analysis by PD-L1 (CPS) PD-L1 CPS=0 PD-L1 CPS≥1 (n=22) (n=25) n (%) [90% CI] n (%) [90% CI] ORR (CR+PR) 1 (4.5) [0.2–19.8] 1 (4.0) [0.2–17.6] DCR (CR+PR+SD) 8 (36.4) [19.6–56.1] 12 (48.0) [30.5–65.9] CPS, combined positive score; CR, Complete Response; DCR, Disease Control
Slide 25: Efficacy Results
Efficacy Results Duration of Treatment by PD-L1 Status •The proportion of patients continuing treatment for 6 months was 4.5% (1/22) in those with CPS of 0 vs 20% (5/25) in those with CPS ≥1 PD-L1 CPS=0 PD-L1 CPS≥1 26 25 25 * 24 24 23 * 23 22 22 21 21 20 20 19 19 18 * Treatment ongoing 18 17 17 16 1
Slide 26: Efficacy Results
Efficacy Results Kaplan-Meier Plot for Overall Survival, Overall and by PD-L1 Status •The overall survival rate at 12 months was numerically better in those with CPS ≥1 (59.5%) than those with CPS of 0 (36.4%) •Specifically, median (90% CI) overall survival was 9.4 months (5.65–12.06) in those with
Slide 27: Safety Results
Safety Results ASCO-GI 2024: Poster #93 26 / 63
Slide 28: Summary
Summary ✓ The results were presented here, the domestic phase I study (ONO-4578-01, Part C and Part D) of combination therapy with ONO-4578 and nivolumab in patients with gastric cancer or colorectal cancer that was refractory or intolerant to standard therapy. These are excerpts of the contents rep
Slide 29: Updates of Open Innovation and ONO-8250 Introduction
Updates of Open Innovation and ONO-8250 Introduction
Slide 30: INDEX
１ Drug Discovery Strategy & Priority Areas ２ Updates of Open Innovation ３ ONO-8250 Introduction INDE X 29 / 63
Slide 31: Drug Discovery Strategy & Priority Areas
01 Drug Discovery Strategy & Priority Areas 30 / 63
Slide 32: Drug Discovery Strategy
Drug Discovery Strategy Promoting open innovation in multiple fields and aiming to create innovative new drugs that meet medical needs ONO focuses on the areas of oncology, immunology, neurology and specialties; all of which include diseases with high medical needs. In each of these areas, we are wo
Slide 33: Priority Areas of Drug Discovery Research
Priority Areas of Drug Discovery Research "developing original and innovative new drugs." 32 / 63
Slide 34: Updates of Open Innovation
02 Updates of Open Innovation 33 / 63
Slide 35: Updates of Open Innovation (2021～)
Updates of Open Innovation (2021～) NEW NEW explained at the R & D Day on Feb 24th, 2023 34 / 63
Slide 36: Updates of Open Innovation (2021～)
Updates of Open Innovation (2021～) Biologics Biologics Seeds NEW Biologics Biologics Seeds AI Biologics AI Biologics Biologics Biologics 2023～ NEW Biologics Open Innovation Updates Seeds AI Discovery Biologics Seeds AI Biologics AI explained at the R & D Seeds 10 5 4 Day on Feb 24th, 2023 Seeds 35 /
Slide 37: Discovery Technology and Therapeutic Modalities
Discovery Technology and Therapeutic Modalities Biologics collaborations Tech & Seeds Small Molecule Peptide Protein & Antibody Cell Therapy AI Oncology ONO-8250 ONO-7018 ONO-4685 Immunology Neurology Vanderbilt Univ. AI Specialty AI AI AI AI AI Undisclosed 2023~ 36 / 63
Slide 38: Updates of Open Innovation: Biologics Collaboration
02 Updates of Open Innovation ◆ Biologics Collaboration 37 / 63
Slide 39: 5 Key Features of Biologics Collaborations
5 Key Features of Biologics Collaborations 1 Antibody Libraries 2 AI・Digital 3 Multispecific Abs 4 Advanced PJ Introduction Bifunctional Fusion Proteins Multi-specific Macrophage Engager Macrophage modulating antibodies Cancer Immunotherapy Anti-GPCR Abs 5 Diversified Modalities CAR-T Cell Therapy M
Slide 40: Drug Discovery Collaboration with Macomics
Drug Discovery Collaboration with Macomics to Develop Macrophage- targeting Antibody for the Treatment of Cancer（2023.03.23） 【Tumor-associated macrophage (TAM)】 Bladder Type of cancer Breast TAM： Bowel Macrophages represent the major population infiltrating Stomach most human cancers. Lung Luca Cass
Slide 41: Option and Collaboration Agreement with Numab (NM49)
•. Option and Collaboration Agreement with Numab to Develop Multi-specific Antibody NM49 (2024.02.14) Next-generation Plug & Play Novel Multispecific Therapeutic Platform Various Multivalent Antibody Format Generation Technologies Based on Optimized Humanized scFv (Hu-Fv) CDR Ultra-high throughput a
Slide 42: Drug Discovery Collaboration Agreement with Twist Bioscience
Ono Enters into a Drug Discovery Collaboration Agreement with Twist Bioscience to Discover Novel Antibodies for Autoimmune Diseases（2023.08.31） 【Library of Libraries】 an expansive collection of synthetic antibody libraries based on naturally occurring sequences High probability of obtaining function
Slide 43: Drug Discovery Collaboration Agreement with Adimab
Ono Enters into a Drug Discovery Collaboration Agreement with Adimab to Discover Novel Antibody Drugs in the Oncology Field（2023.09.27） 【Adimab’s platform technology】 Yeast Library Rich experiences of multi-specific antibodies Adimab will discover novel therapeutic antibodies against multiple target
Slide 44: Collaboration Agreement with EME for VHH Antibodies
Ono Enters into Collaboration Agreement with EME to Generate Novel VHH Antibodies against Multiple Therapeutic Targets（2024.02.21） 【What is VHH】 【HTS Platform “The Month”】 Camelid HcAb it only takes approximately a month for obtaining hit VHH to a drug target VHH抗体が分かる絵 Front. Immunol., 21 August 20
Slide 45: Collaboration and Option Agreement with Shattuck Labs
A Collaboration and Option Agreement with Shattuck Labs for Bifunctional Fusion Protein（2024.02.13） Agonist Redirected Checkpoint (ARC) Platform Target 1 Target 2 Fc Region ◼ Shattuck Labs has proprietary technology for creating modified proteins, enabling the development of functional proteins for
Slide 46: Updates of Open Innovation: AI・Digital Collaboration
02 Updates of Open Innovation ◆ AI・Digital Collaboration 45 / 63
Slide 47: Collaboration Agreement with EVQLV
Ono Enters into Collaboration Agreement with EVQLV to Generate Novel Antibodies against Multiple Targets Utilizing EVQLV’s AI-powered Antibody Design Engine for Development of Innovative Antibody Drugs（2023.12.19) 【EVQLV Platform】 AI-powered Antibody Design Engine The platform designs and modifies a
Slide 48: Drug Discovery Collaboration Agreement with MOLCURE
Ono Enters into a Drug Discovery Collaboration Agreement with MOLCURE to Discover and Develop Innovative Antibody Drugs for Multiple Targets Utilizing MOLCURE’s AI-driven Platform Technology（2023.03.23） For more details, please refer to Molcure website (https://molcure.com/). Utilize MOLCURE's propr
Slide 49: Research Collaboration with Turbine
Research Collaboration with Turbine to Identify and Validate Novel Therapeutic Targets in Oncology (2023.10.24) 【Simulated Cell Platform】 The virtual cells capture cancer biology and are used for in silico cell simulation. Leveraging Turbine’s AI-driven cell simulation, we are committed to identify
Slide 50: Research Collaboration Agreement with InveniAI
Ono Enters into a Research Collaboration Agreement with InveniAI to Identify Novel Therapeutic Targets（2024.02.19） 【AlphaMeld】 InveniAI's proprietary AI platform technology based on machine learning, advanced natural language processing and large language models Data Source（Big Data） AI technology •
Slide 51: Accelerating AI Drug Discovery with the Supercomputer 'Tokyo-1'
Accelerating AI Drug Discovery with the Supercomputer 'Tokyo-1’ (2024.02.01) Vast amounts of genetic information data Assessment of the value of proprietary seeds Image analysis, video analysis, natural language processing supercomputer dedicated to drug discovery Significantly reduce time and effor
Slide 52: Strategic Investment and Research Grants by Foundations
02 Updates of Open Innovation ◆ Strategic Investment by Ono Venture Investment ◆ Research Grants by Foundations 51 / 63
Slide 53: Open Innovation That Supports Drug Discovery
Open Innovation That Supports Drug Discovery https://www.ono-pharma.com/en/company/rd/open_innovation.html 52 / 63
Slide 54: Investment in the start-up Bio-Ventures
Investment in the start-up Bio-Ventures Company Location Notes Company Location Notes Bio-Venture for developing Bio-Venture for development of South San Boston, MA, innovative genetic medicines to new drugs for the treatment of Francisco, USA transform the treatment of CNS fibrosis CA, USA diseases
Slide 55: Research Grants Through Foundations and Donated Courses
Research Grants Through Foundations and Donated Courses ONO Medical Research Foundation (FY1988~) The Foundation provides grants for research activities in the field of lipid metabolism disorders and also aims to promote research and treatment in that field through various projects, thereby contribu
Slide 56: ONO-8250 Introduction
03 ONO-8250 Introduction 55 / 63
Slide 57: Off the Shelf iPSC-derived HER-2 CAR-T incorporate 7 Functional Edits
Strategic Collaboration with Fate Therapeutics to Develop iPSC-derived CAR-T （2018.09.18） Exercise Option to HER2-targeted CAR-T Cell Product Candidate for Solid Tumor（2022.11.07） 1. Preference of killing activity on HER2-expressing tumor cells and optimal killing signaling to avoid T cell exhaustio
Slide 58: Novel binder incorporated into ONO-8250
Novel binder incorporated into ONO-8250 “The preclinical data for FT825 / ONO-8250 indicate a highly-differentiated therapeutic profile across a broad range of solid tumors, with the novel HER2- targeted antigen binding domain demonstrating selective targeting of cancer cells expressing HER2 includi
Slide 59: Preferential targeting of HER2 on tumor cells by H2CasMab-2 binder
Preferential targeting of HER2 expressed on tumor rather than normal cells is uniquely enabled by the novel H2CasMab-2 binder HER2high tumor cells （SKOV3） VS HER2+ normal cells Trastuzumab H2CasMab-2 （MCF10A） CAR-T CAR-T HER２high tumor cells HER2+ normal cells （SKOV3） （MCF10A） Trastuzumab CAR-T Cyto
Slide 60: ONO-8250: Multiplex-engineered CAR T for solid tumors
ONO-8250：Multiplex-engineered CAR T designed to address and overcome challenges currently faced by cell therapies in solid tumors Promote tumor trafficking Resistance to TME Suppression Multi-antigen Targeting （CXCR2） （TGFbR-IL18） （hnCD16a） HER２High tumor cells HER２Low EGFR High （SKOV3） PCA（PC3） HER
Slide 61: ONO-8250: Robust HER2 Targeting Across Antigen Expression Density
ONO-8250：Robust HER2 Targeting Across a Wide Range of Antigen Expression Density HER２high OVCA HER２Low PCA （SKOV3） （PC3） Target cells ONO-8250 ONO-8250 Cytotoxicity（％） Cytotoxicity（％） ONO-8250 VS CAR-T : Target cells Target cells Target cells = 10:1 Tine（h） Time（h） Hosking Ｍ, et al. SITC 2023 #268 O
Slide 62: ONO-8250: Anti-tumor effect on HER2+ tumor bearing model
ONO-8250: Anti-tumor effect on HER2+ tumor bearing model ONO-8250 ＋／－ HER2+ tumor aHER2mAb hnCD16a Combination effect with other therapeutic antibody ONO-8250 Tumor Volume（mm3） aHER2mAb ONO-8250 ＋aHER2mAb Hosking Ｍ, et al. SITC 2022 #304 ONO-8250 showed anti-tumor effect in HER2+ tumor bearing model
Slide 63: Discovery Technology and Therapeutic Modalities
Discovery Technology and Therapeutic Modalities Biologics collaborations Tech & Seeds Small Molecule Peptide Protein & Antibody Cell Therapy AI Cancer ONO-8250 ONO-7018 ONO-4685 Immunology Neurology Vanderbilt Univ. AI Specialty AI AI AI AI AI Undisclosed 2023~ 62 / 63
Slide 64: Main Status of Development Pipelines
Main Status of Development Pipelines Therapy Development Area Phase Target Indication Area Code Solid Tumor, Gastric Cancer, Pancreatic Cancer, Colorectal ONO-4578 Japan I cancer, non-small cell lung cancer, Hormone receptor-positive, HER2-negative breast cancer ONO-7475 Japan I Solid Tumor, EGFR mu
Slide 65: Dedicated to the Fight against Disease and Pain
Dedicated to the Fight against Disease and Pain