Ono Pharmaceutical Co., Ltd. · TSE:4528
Ono Pharmaceutical — Technical Presentation (February 2023)
51 slides from Ono Pharmaceutical's technical presentation, Feb 24, 2023
Slide 1: R&D Meeting
R&D Meeting February 24, 2023 0/49
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 Research and Development Strategy of ONO President, Representative Director, and Chief Executive Officer Gyo Sagara Drug Discovery Strategy & Alliance Updates Senior Executive Officer, Executive Director of Discovery and Research Toichi Takino Itolizumab (Anti-CD6 antibody) Executive Officer,
Slide 4: Research and Development Strategy of ONO
Research and Development Strategy of ONO President, Representative Director, and Chief Executive Officer Gyo Sagara 3/49
Slide 5: Investment strategy over the next 5 years
Investment strategy over the next 5 years Aggressive R&D investment to overcome patent cliff and further growth Sources of cash Allocation of Investments （2022-2026） （2022-2026） R&D Priority investments in Newly generated cash ¥600B oncology, immunology, neurology, and specialty areas Strategic inve
Slide 6: Global pipeline expansion
Global pipeline expansion Global development（medium to long term） VELEXBRU （BTK inhibitor / PCNSL ONO-4578 （EP4 antagonist / Solid tumor, Gastric cancer, etc） Oncology ONO-7475 （Axl / Mer inhibitor / Acute leukemia, etc） ONO-4685 （PD-1×CD3 bispecific antibody / T cell Lymphoma） ONO-7018 （MALT1 inhib
Slide 7: Drug Discovery Strategy & Alliance Updates
Drug Discovery Strategy & Alliance Updates Senior Executive Officer/Executive Director Discovery & Research Toichi Takino 6/49
Slide 8: Corporate Philosophy
Corporate Philosophy ” Dedicated to the Fight against Disease and Pain” 7/49
Slide 9: Focused Areas of Drug Discovery Research
Focused Areas of Drug Discovery Research 8/49
Slide 10: Drug Discovery Strategy
Drug Discovery Strategy 「Open Innovation」×「Technology」 allows us create unique & innovative new drugs 9/49
Slide 11: Open Innovation x Technology
Drug Discovery Strategy 「Open Innovation」×「Technology」 allows us create unique & innovative new drugs 「Open Innovation」×「Technology」 10/49
Slide 12: Recent Updates of Discovery Alliances (2021~)
Recent Updates of Discovery Alliances (2021～) Anti-GPCR Autoimmune Jan Jan Sponsorship Antibodies Diseases Feb Agreement Mar DNA Damage Jan Cancer Response Mar Apr Modified Autoimmune Feb Cytokine Diseases Jun Cancer Mar Large-scale Aug Transcriptome undisclosed Aug Analysis Antibody/Imm Cancer Nov
Slide 13: Our Focus on Drug Discovery Platform and Modalities
Our Focus on Drug Discovery Platform and Modalities Technology Cell Small Molecule Peptide Protein/Antibody Platform Therapy 2021 2023 2022 2022 Oncology Immunology expanded in 2021 2022 Vanderbilt Univ. 2022 Expanding Neurology 2022 Biologics 2022 2023 Specialty 2023 2021 2021 2022 2021 2021 2021 O
Slide 14: Drug Discovery Strategy
Drug Discovery Strategy 「Open Innovation」×「Technology」 allows us create unique & innovative new drugs 13/49
Slide 15: Exploratory of the original drug discovery seeds
Drug Discovery Strategy 「Open Innovation」×「Technology」 allows us create unique & innovative new drugs Exploratory of the original drug discovery seeds 14/49
Slide 16: Sponsorship Agreements with LabCentral and MBC BioLabs
Sponsorship Agreements with LabCentral and MBC BioLabs （2021.02.26） “Investment to the start-up Biotech companies” 2021～ San Francisco 2021～ Boston Access to the latest information and exploration of future collaborators Weatherwax Biotechnologies https://labcentral.org/news-events/press-releases/on
Slide 17: Joins the University of California Drug Discovery Consortium
Joins the University of California Drug Discovery Consortium （2021.03.16） Access to undiscovered top scientists Explore collaboration opportunities based on unverified and unpublished ideas Bridging academia's drug discovery seeds to pharma UC 8 Universities Research Plan Funding 16/49
Slide 18: Collaborative research with knowledge palette
Collaborative research with knowledge palette to build a data- driven new drug discovery platform using large-scale transcriptome analysis technology （2022.08.10） Treatment with many different compounds Mapping Perturbations such as inhibition of gene function Database Elucidation of new target mole
Slide 19: Multi Target R&D Collaboration Agreement with PrecisionLife
Multi Target R&D Collaboration Agreement with PrecisionLife to identify novel therapeutic targets in CNS disorders （2022.12.14） Identification of Therapeutic Target Patient Bioinformatics Analysis Targets and Biomarkers Disease-related Genes in Target Patients Unique Combinatorial Patient Dataset Va
Slide 20: Acquisition of Oncology Programs from KSQ Therapeutics
Acquisition of Multiple Research-Stage Oncology Programs from KSQ Therapeutics（2023.01.25） Acquisition of multiple research-stage DNA damage response programs identified by KSQ’s CRISPRomics® platform technology 19/49
Slide 21: Utilization of Therapeutic Modalities
Drug Discovery Strategy 「Open Innovation」×「Technology」 allows us create unique & innovative new drugs Utilization of Therapeutic Modalities 20/49
Slide 22: Alliances on Multispecific Antibodies
Alliances on Multispecific Antibodies Biclonics® technology platform OmniRat®, OmniMouse® and OmniFlic® Holland The US 2014～ 2016～ Highly flexible multispecific format, MATCH LassoGraft Technology® Switzerland Japan 2017～ 2021～ 21/49
Slide 23: ONO-4685: PD-1×CD3 Bispecific Antibody
ONO-4685：PD-1×CD3 Bispecific Antibody • PD-1×CD3 Bispecific Antibody generated by Biclonics® PD-1 arm CD3 arm Discovery Platform T cell lymphoma （USA, Phase 1） Autoimmune Diseases（Japan・EU, Phase1） Suppression of activated T cell Cytotoxicity on activated T cells T cell PD-1 expressing cell （Activat
Slide 24: Antibody Discovering Partnership with MEMO Therapeutics
Antibody Discovering Partnership for Immuno-oncology with MEMO Therapeutics（2022.11.01） B cells Entire repertoire Repertoire High throughput (Entire repertoire) library copied in HEK Functional Screening Maximizing antibody repertoire against target antigens Therapeutic Antibody for Immuno-oncology
Slide 25: Antibody Drug Discovery Collaboration with Neurimmune AG
Antibody Drug Discovery Collaboration with Neurimmune AG in the Field of Neurodegenerative Diseases（2022.01.17） Healthy Elder Donors Non-Clinical Studies Candidate Antibodies Creating Selective High Affinity Antibodies Using the Reverse Translational Medicine™ Technology Platform Based on Immune Res
Slide 26: Research Collaboration with Monash University
Research Collaboration with Monash University in the Autoimmune and Inflammatory Diseases（2023.01.13） Monash University’s sophisticated technologies for antibody discovery which enables the creation of therapeutic antibodies using monoclonal antibodies against two GPCRs traditionally hard to targe
Slide 27: Strategic Collaboration with Fate Therapeutics on iPSC-derived CAR-T
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 Tumors（2022.11.07） Appropriate activation signal to escape exhaustion HER2CAR＋1xx CXCR2 T-cell receptor (TCR） deletion Improvement of migra
Slide 28: ONO-8250: Anti-tumor effect on HER2+ tumor bearing model
ONO-8250：Anti-tumor effect on HER2+ tumor bearing model ONO-8250 ＋／－ HER2+ tumor αHER2mAb hnCD16a Combination effect with other therapeutic antibody ONO-8250 αHER2mAb ONO-8250 +αHER2mAb Tumor Volume (mm3) Vehicle ONO-8250 showed anti-tumor effect in HER2+ tumor bearing model. Combo with anti HER2mAb
Slide 29: Collaboration and Option Agreement with Cue Biopharma
Collaboration and Option Agreement with Cue Biopharma for CUE-401, a Bispecific Protein （2023.02.22） CUE-401 Tregs induced by CUE-401 IL-2 moiety Diversity：Generated from vastly diverse T cells Phenotype：Regulatory phenotype can be achieved and sustained Disease impact：Conversion of pathogenic
Slide 30: License agreement with PeptiDream on Peptide Discovery Platform
License agreement with PeptiDream Inc. on automated Peptide Discovery Platform System (2021.03.01) Characteristics of Specialty Cyclicpeptide Drug Discovery Small Specialty Cyclic Antibody molecule peptide （Large （Middle molecule） molecule) MW <500 500 - 2000 150000 Specificity Low High High Oral ad
Slide 31: Collaboration with Captor Therapeutics on Protein Degraders
Drug Discovery Collaboration with Captor Therapeutics to Develop Protein Degraders for Treatment of Neurodegenerative Diseases（2022.11.14） Druggable Proteins Undruggable Proteins* Functional Inhibition Degradation Receptor Antagonists Target Protein Degraders *70-80% of all proteins Enzyme Inhibitor
Slide 32: Digital/AI/Robotics
Drug Discovery Strategy 「Open Innovation」×「Technology」 allows us create unique & innovative new drugs Digital/AI/Robotics 31/49
Slide 33: Collaboration agreement with Iktos using AI
Collaboration agreement with Iktos to discover and develop a novel small molecule using AI technology.（2022.03.30） (2017.12.19～) Auto-synthesis AI design・MPO Design Make Analysis Test Auto-analysis Auto- testing AＩ design・automation enables major productivity gains in upstream pharmaceutical researc
Slide 34: Collaboration agreement with Curreio on Cryo EM
Collaboration agreement with Curreio to access to structual analysis technology using Cryo EM.（2022.05.23） 「Visualization of interaction mode between target protein and compound」 X-ray analysis X-ray analysis CryoEM soluble proteins Membren proteins Kinase/protease GPCR Target X 2005～ 2011～ 2022～ Ar
Slide 35: Making full use of Human disease modeling
Making full use of Human disease modeling iPS cell technology Humanoid robot×Digital technology 2020. 08 - Joint research （Academia） Japan6・Overseas10 Alliance （Biotech venture/CRO) Japan and Overseas8 （2023.03） Drug discovery research based on human disease biology through active utilization of hum
Slide 36: Creation of PET for Bioimaging of α-synuclein
Creation of PET for Bioimaging of Abnormal Protein "α- synuclein" in the Neurodegenerative Disease（2022.08.31） α-synuclein accumulation Captures α-synuclein accumulation (Multiple System Atrophy) Co-Development of Radiopharmaceuticals Ref.： Tokyo Medical Research Institute Neuropathology Database He
Slide 37: Create unique and innovative new drugs
Drug Discovery Strategy 「Open Innovation」×「Technology」 allows us create unique & innovative new drugs Create unique and innovative new drugs 36/49
Slide 38: Promotion System to Support Open Innovation Driven Drug Discovery
Promotion System to Support Open Innovation Driven Drug Discovery Ono Pharma Discovery Research Alliance & Foundation Business Development Ono Venture Investment, Inc. 37/49
Slide 39: Investment to the start-up Bio-Venture
Investment to the start-up Bio-Venture Start-up Outline Cambridge, • Bio-Venture for development of new drugs for the MA, USA treatment of fibrosis • Bio-venture for drug discovery based on detailed Tokyo, Japan protein structure information by cryo-electron microscopy Waltham, • Bio-Venture Committ
Slide 40: Research Grant Activities by the Ono Pharma Foundation
Research Grant Activities by the Ono Pharma Foundation in the United States Ono Pharma Breakthrough Science Initiative Awards Program： is the embodiment of the Foundation’s commitment to focus on and accelerate researcher-driven open innovation by supporting high-risk and high-reward science researc
Slide 41: Itolizumab (Anti-CD6 antibody)
Itolizumab(Anti-CD6 antibody) Executive Officer/Executive Director Clinical Development Kiyoaki Idemitsu 40/49
Slide 42: Itolizumab
Itolizumab Ono and Equillium Announce Exclusive Option and Asset Purchase Agreement for the Development and Commercialization of Itolizumab（5 Dec, 2022） Partner Equillium, Inc（CA, USA） Compound Itolizumab Name Mechanism Anti-CD6 antibody Highly safe FIC drug that change T-cell status to treat autoim
Slide 43: CD6 Drives Pathogenic T Cell Activity & Trafficking
CD6 Drives Pathogenic T Cell Activity & Trafficking Co-stimulation = Activation Proliferation Differentiation/Survival Trafficking Suppression of regulatory pathways 42 42/49
Slide 44: Itolizumab inhibits pathogenic T Cell Activity & Trafficking
Itolizumab inhibits pathogenic T Cell Activity & Trafficking Co-stimulation = Activation Proliferation Differentiation/Survival Trafficking Itolizumab Restoration of regulatory pathways 43/49
Slide 45: aGvHD treatment guideline in the US
aGvHD treatment guideline in the US aGvHD：Complications After Hematopoietic Stem Cell Transplantation, a Treatment for Hematologic Cancer aGvHD 4,500 【Abbreviations】 Approx. ATG： Antithymocyte globulin, CSP： Cyclosporine, MMF： Mycophenolate mofetil, patients in the US mPSL： Methylprednisolone, MTX：
Slide 46: Phase 1b study - EQUATE study
Phase 1b study - EQUATE study Evaluate the clinical activity and safety of Itolizumab on top of steroids, as 1st line treatment for aGvHD mPSL, i.v., ~2mg/kg prednisolone, p.o., （i.v.p.o.［Dose tapering］） Steroids Itolizumab D1 D15 D29 D43 D57 0.4 , 0.8 , 1.6 mg/kg, q2w, i.v. • Scoring of skin, li
Slide 47: High Response Rates to Itolizumab + Steroids
High Response Rates to Itolizumab + Steroids Itolizumab treatment (≤3 days of steroids) Day 15 Day 29 100% 100% 20% 80% 75% 77% 80% 急性GvHD Response 69% 64% 65% 20% 23% 60% 25% 23% 50% 13% 5% 21% 4% 40% 8% 80% 60% 50% 50% 50% 48% 20% 38% 43% 0% 0.4 mg/kg 0.8 mg/kg 1.6 mg/kg TOTAL TOTAL 0.4 mg/kg 0.8
Slide 48: Phase 3 Study for aGvHD (EQUATOR study)
Phase 3 Study for aGvHD（EQUATOR study） Itolizumab: IV 1.6 mg/kg loading dose followed by 0.8 mg/kg Q2W x 6 doses (n=100) Grade III-IV patients & Grade II patients with lower GI R Steroid tapering recommendation Concomitant within 72 hours of high-dose corticosteroids Placebo: (2 mg/kg) (n=100) Day D
Slide 49: P1b Study for Lupus Nephritis (EQUALISE study)
P1b Study for Lupus Nephritis （EQUALISE study） Evaluate the efficacy and safety of Itolizumab as an add- on to Steroids + Mycophenolate mofetil Target Steroids Tapering to ≤10mg/d@10weeks Class III/IV (with V) on renal biopsy Mycophenolate mofetil (MMF)：2～3g/day UPCR > 1 g/g Itolizumab：1.6mg/kg,
Slide 50: P1b Study for Lupus Nephritis: UPCR reduction in all cases
P1b Study for Lupus Nephritis Cut off：2022/09/02 ※ CR : ≧ 50% UPCR reduction + <0.5g/g PR : ≧ 50% reduction UPCR UPCR reduction in all cases （Urine protein／Creatinine ratio） CR ≧ 50% UPCR reduction + <0.5g/g PR ≧ 50% reduction UPCR CR ≧ 50% UPCR reduction + 0.5-0.7g/g No Response < 50% reduction or
Slide 51: Dedicated to the Fight against Disease and Pain
Dedicated to the Fight against Disease and Pain
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