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Be a Game Changer March 19, 2020 Shionogi & Co., Ltd Research and Development at Shionogi Be a Game Changer March 19, 2020 Shionogi & Co., Ltd. Agenda 1. Introduction – Isao Teshirogi, Ph.D., President and CEO 2. Research – Ryuichi Kiyama, Ph.D., Corporate Officer, Senior Vice President, Pharmaceutical Research Division 3. Development – Toshinobu Iwasaki, Ph.D., Senior Executive Officer, Senior Vice President, Global Development Division 4. CMC – Yasuyoshi Isou, Ph.D., Corporate Officer, Senior Vice President, CMC R&D Division 5. Summary – Isao Teshirogi, Ph.D., President and CEO 6. Q&A 2 1. Introduction - Research and Development in SGS2020 ~ Overview ~ - Isao Teshirogi, Ph.D., President and CEO Cited from presentation material of FY2013 R&D, Selection of Therapeutic Area partially modified in SGS2020 ⚫ Core Therapeutic Areas: Capitalize on our strengths Infectious Diseases Pain/Neuropathy ⚫ Expand anti-HIV drug discovery ⚫ Strengthen R&D for treatment of pain platform into other anti-viral discovery ⚫ Enter neurology/psychiatric areas, areas starting with Alzheimer’s disease and ⚫ Accelerate research and development ADHD for multi-drug-resistant bacteria ⚫ Pursue discovery of neuro-regeneration ⚫ Pursue drug discovery for emerging and drugs that may improve synapse and re-emerging infectious disease neural function ⚫ Innovative Frontier Medicines: Establish our next core therapeutic areas Obesity/Geriatric Metabolic Disease Oncology/Immunological Disease ⚫ Progress R&D for anti-obesity drugs ⚫ Progress cancer peptide vaccines ⚫ Pursue research for complicated ⚫ Pursue research into novel immuno- /refractory/geriatric condition modulating therapies ➢ Make the most of our know-how and assets in our areas of strength and evolve into leadership positions ➢ Leverage modalities and alliances to cultivate new areas that contribute to medium- to long- term growth 4 Cited from presentation material of Updates to SGS2020 Growth Strategy for 2020 Grow sustainably as a drug discovery-based pharmaceutical company contributing to a more vigorous society through improved healthcare Region to grow Keys to growth Japan/US Addressing society’s Development in EU/Asia needs Infectious disease Balance of innovation and health economic Pain/CNS efficiency 5 Cited from presentation material of Updates to Pursuing More Efficient R&D with SGS2020 Small Molecule Drug Discovery Contribute throughout the healthcare value chain by leveraging our capabilities in small molecule drug discovery, creating novel drugs whose innovation brings both health and economic benefits Drug discovery Development Open innovation engine design • Effective and efficient drug • New SAR* platforms • Identify novel research pre-registration and post- • Expand platform to include concepts marketing product peptides development Biomarker R&D pursuing synergies with our pipeline Utilization of big data * Structure-Activity Relationship 6 R&D vision and KPI for SGS2020 R&D vision Research: Innovation in drug 研究：社会に応える創薬イノベーション discovery to meet societal needs CMC: Research and Development CMC：Benefit for Allの製品開発 of original CMC technology Development: Advance reliability 開発：効率的かつ着実な開発 and innovation together KPI of Efficiency: Original pipeline ratio*: Over 50% Shionogi-origin achieved Research- 67% collaboration [as of Mar. 2020 In-licensed * Proprietary origin compounds in the development pipeline（Includes development candidates and results from joint research with partners） 7 Cited from presentation material of FY2018 Financial Results Strategic Investment in FY2018 Obtained pipeline and new technology through strategic investment Drug candidates for mycobacterial・S- disease600918 (Hsiri) Collaborative research on anti・-SRS -virus637880 drug (Ube) Promote research on the world‘s top Disease Collaborative research on prophylaxis and 3 infectious diseases, and other treatment for Malaria (Nagasaki Univ.) refractory infectious diseases Nitric Oxide inhaled antimicrobial ⇒Establish a global presence in drug candidates (Vast) infectious disease area Technology for Antimicrobial Resistance (Nemesis) Infectious Anti-depressant candidate, S-812217(Sage) Obtained new pipeline assets Drug candidate for cognitive and memory deficits, BPN-14770 (Tetra) ⇒Provide new treatment options based on ・S-770108 novel mechanisms Pain/CNS Digital medicine candidate AKL-T01, AKL-T02(Akili) PDC* technology (PeptiDream) Obtain new modalities Regenerative medicine product candidate, ⇒Meet unmet needs that small molecule Modality ADR-001 (Rohto) drugs cannot solve Collaborated with 10 new partners for beyond 2020 * Peptide drug conjugates 8 Enhance Assets and Maximize Value Through Alliances Overcoming drug discovery hurdles, expanding product Advancing development, indications and pipeline maximizing product value Infectious diseases Pain/CNC Frontier areas Generating operational IT reform, pursuit of great Acquiring new modalities synergies efficiency Middle-sized molecules drug discovery Vaccine, diagnosis Creation of novel innovation Regenerative medicine 9 Growth Drivers Discovered/Acquired in SGS2020 Disease area Research Pre-clinical development Clinical development Launched Xofluza® Infectious Drug discoveryneeds unmet challenge to program (Influenza) diseases cefiderocol* (Multidrug resistant Gram- three major S-540956 S-648414 negative bacterial infection) infections, severe (HIV) (HIV) Juluca® infections, influenza, (HIV) and emerging/re- ® merging infectious Dovato (HIV) diseases etc. BPN14770 S-812217[zuranolone] Psycho- (Alzheimer’s (Depression) naldemedine** disease etc.) (Opioid-induced S-600918 constipation) neurological S-874713 (refractory diseases (Psycho-neurological chronic cough etc.) Intuniv® diseases) S-637880 （ADHD） S-109802 (Pain etc.) ® depression, ADHD, [botulinus toxin] Vyvanse dementia, (Post-stroke spasticity) SDT-001 [app.] (ADHD) autism, and pain etc. (ADHD) New growth S-723595 S-005151[Redasemtide] (NASH) [HMGB1 peptide] areas (Epidermolysis bullosa, Infectious disease S-540956 ischemic stroke) Psycho-neurological immuno-oncology, (Cancer) S-770108 disease guided regeneration, Regulatory T cell [Pirfenidone inhalation] and fibrotic disease inhibitor (IPF) New growth area etc. (Cancer) Growth Drivers Created from FY2014 to present ADHD: attention deficit hyperactivity disorder * brand name in US: Fetroja®, brand name in EU: Fetcroja®, details are shown in p.117 10 ** brand name in Japan and US: Symproic®, brand name in EU: Rizmoic® Today’s Topic The World We Envision Based on Our Core Pipeline Paradigm shift of cancer treatment with synergy with existing products Regulatory Changing the regenerative T cell medicine paradigm inhibitor S-005151 [redasemtide] Improve a wide range of psycho- S-874713 neurological diseases, such as A platform that improves the addictions, with a new mechanism efficacy of immunotherapy of action for a wide range of diseases. Paradigm ✓ Cancer: A booster of immune shift of checkpoint inhibitors disease ✓ HIV: Paradigm shift to functional cure BPN14770 treatment S-540956 Game New option for treating Changer Alzheimer’s through Paradigm shift in treatments improving cognitive function for many diseases S-812217 S-600918 ✓ Refractory chronic cough [zuranolone] ✓ Sleep apnea ✓ Chronic pain, etc. S-637880 Efficacy that changes existing concepts of depression treatment A new key mechanism for psycho-neurological diseases (Pain, depression, and multiple sclerosis) Create products and services for diseases with no satisfactory treatment options, and contribute to solving social issues 11 Biggest Management Issue Facing Shionogi Transpiring around 2028 Overcoming the “HIV Product Patent Cliff” for Sustainable Growth 12 Research Ryuichi Kiyama, Ph.D. Corporate Officer Senior Vice President Pharmaceutical Research Division R&D Vision Beyond 2020 R&D vision Create innovations beyond the borders of medical/pharmaceutical fields, unbound from existing concepts, showing every consideration for social issues • Create solutions that go beyond existing concepts via expanded modalities and flexible disease area strategies – To further enhance our strength in small molecule drug discovery and establish a presence in peptide drug discovery and nucleic acid drug discovery. – To further enhance/extend approaches to drug discovery through alliances – To pursue what patients really suffer from through flexible disease area strategies • Collaboration with a wide range of business partners – To flexibly adapt to changes in external environments through collaboration with other companies • Realize high-level business operations – To expand multi-level preparations for the HIV patent cliff with a keen focus on timelines Establish new platforms combining the strengths of our company with those of our business partners 14 Therapeutic Area Strategies Beyond 2020 Therapeutic Area While focusing on infectious and psycho-neurological diseases Strategies as our core fields, we will pursue other therapeutic areas with high social and medical need, while establishing a research management system that enables flexible and clear prioritization. Protecting the world from the threat of infectious Infectious diseases as a leader in the area ✓ To provide new benefits to HIV/influenza patients diseases ✓ To contribute to global health by dealing with the three major infectious diseases and AMR Paradigm shift in the treatment of psycho- Psycho‐ neurological diseases neurological ✓ To realize optimal therapy through objective diagnosis/stratification diseases ✓ To provide a wide range of treatment options through discovery of innovative
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