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EXTERNAL NON-CONFIDENTIAL Corporate Presentation December 2024 | Nxera Pharma Co., Ltd. (TSE: 4565)
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The material that follows is a presentation of general background information about Nxera Pharma Co., Ltd and its subsidiaries (collectively, the “Company”) as of the date of this presentation. This material has been prepared solely for informational purposes and is not to be construed as a solicitation or an offer to buy or sell any securities and should not be treated as giving investment advice to recipients. It is not targeted to the specific investment objectives, financial situation or particular needs of any recipient. It is not intended to provide the basis for any third-party evaluation of any securities or any offering of them and should not be considered as a recommendation that any recipient should subscribe for or purchase any securities. The information contained herein is in summary form and does not purport to be complete. Certain information has been obtained from public sources. No representation or warranty, either express or implied, by the Company is made as to the accuracy, fairness, or completeness of the information presented herein and no reliance should be placed on the accuracy, fairness, or completeness of such information. The Company takes no responsibility or liability to update the contents of this presentation in the light of new information and/or future events In addition, the Company may alter, modify or otherwise change in any manner the contents of this presentation, in its own discretion without the obligation to notify any person of such revision or changes. This presentation contains “forward looking statements, ” as that term is defined in Section 27 A of the U S Securities Act of 1933 as amended, and Section 21 E of the U S Securities Exchange Act of 1934 as amended. The words “ believe” , “ expect” , “ anticipate” , “ intend” , “ plan” , “ seeks” , “ estimates” , “ and “ and similar expressions identify forward looking statements. All statements other than statements of historical facts included in this presentation, including, without limitation, those regarding our financial position, business strategy, plans and objectives of management for future operations (including development plans and objectives relating to our products), are forward looking statements. Such forward looking statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by such forward looking statements. Such forward looking statements are based on numerous assumptions regarding our present and future business strategies and the environment in which we will operate in the future The important factors that could cause our actual results, performance or achievements to differ materially from those in the forward looking statements include, among others, risks associated with product discovery and development, uncertainties related to the outcome of clinical trials, slower than expected rates of patient recruitment, unforeseen safety issues resulting from the administration of our products in patients, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. These factors include, without limitation, those discussed in our public reports filed with the Tokyo Stock Exchange and the Financial Services Agency of Japan. Although the Company believes that the expectations and assumptions reflected in the forward-looking statements are reasonably based on information currently available to the Company’s management, certain forward-looking statements are based upon assumptions of future events which may not prove to be accurate. The forward-looking statements in this document speak only as at the date of this presentation and the company does not assume any obligations to update or revise any of these forward statements, even if new information becomes available in the future. This presentation does not constitute an offer, or invitation, or solicitation of an offer, to subscribe for or purchase any securities. Neither this presentation nor anything contained herein shall form the basis of any contract or commitment whatsoever. Recipients of this presentation are not to construe the contents of this summary as legal, tax or investment advice and recipients should consult their own advisors in this regard. This presentation and its contents are proprietary confidential information and may not be reproduced, published or otherwise disseminated in whole or in part without the Company’s prior written consent. These materials are not intended for distribution to, or use by, any person or entity in any jurisdiction or country where such distribution or use would be contrary to local law or regulation. This presentation contains non-GAAP financial measures. The non‐GAAP financial measures contained in this presentation are not measures of financial performance calculated in accordance with IFRS and should not be considered as replacements or alternatives profit, or operating profit, as an indicator of operating performance or as replacements or alternatives to cash flow provided by operating activities or as a measure of liquidity (in each case, as determined in accordance with IFRS). Non-GAAP financial measures should be viewed in addition to, and not as a substitute for, analysis of the Company’s results reported in accordance with IFRS. (c) Nxera Pharma Co, Ltd, 2024. Nxera and the Nxera logos are trademarks of Nxera Pharma Co. Ltd. 2 Disclaimer
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Business Overview Strategic Roadmap Our Pipeline Japan/APAC Business Our NxWaveTM Platform Financial Results Appendix 3 Agenda 01 02 03 04 05 06 07
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Business Overview 01
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5 Leading the Next Era of Medicine. From Japan, for Japan, and the world World-leading NxWave platform (UK), coupled with Japan’s most effective development and commercial organization Our Mission Our Vision To lead the next era of medicine. From Japan, for Japan, and the world. Our Values • Patients come first • Innovation and teamwork • Focus • Speed and agility • Operational excellence To accelerate the development of life-changing medicines, by investing in science and technology. OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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We are Nxera Pharma 6 A technology-powered biopharma in pursuit of new specialty medicines to improve the lives of patients Cutting-edge Science Programs by Design Real Human Outcomes WORLD-LEADERS IN GPCR STRUCTURE-BASED DRUG DESIGN 30+ ACTIVE PROGRAMS PROTECTING LIVES EVERYDAY 5 Global Locations Tokyo, Cambridge, London, Seoul & Basel Strong focus on GPCR targets – solved 375+ molecular structures Revenue-Generating $350m+ Cash in hand (Dec-2023) 350+ FTE EmployeesTSE: 4565 Tokyo Stock Exchange Prime 15,000+ patients have received PIVLAZ® (Japan and shortly South Korea) +4 other partnered marketed products CNS 39% IMM 9% GI 33% Other 18% OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Global Corporate Structure 7 Over 350 team members employed across Japan, South Korea, UK and Switzerland Nxera Pharma (formerly “Sosei Group”) Group Operations | ~60 people Nxera Pharma Japan (NPJ) (formerly “Idorsia Pharma Japan” and “Sosei Co. ”) Tokyo | ~140 staff Nxera Pharma UK (NPU) (formerly “Heptares”) Cambridge | ~170 staff Nxera Pharma Korea (NPK) (formerly “Idorsia Pharma Korea”) Seoul | ~7 staff Research & Early Clinical Development • NxWaveTM – SBDD Platform • Drug Discovery • Translational Medicine • Early Clinical Development • Business Development Drug Development & Commercial Operations • Clinical Development • Regulatory Affairs • Marketing Authorisation Holder • Commercial Sales (direct and via partners) Drug Development & Commercial Operations • Clinical Development • Regulatory Affairs • Marketing Authorisation Holder • Commercial Sales (via partners) OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Chris Cargill Chief Executive Officer Agile and decisive leadership team 8 Shinichi Tamura Chairman Tomohiro Toyama Legal David Roblin Clin Dev Rolf Soderstrom Finance Kuniaki Kaga Clin Dev Noriaki Nagai Compliance Miwa Seki Tech/ESG Chris Cargill CEO Eiko Tomita Reg Affairs BOARD OF DIRECTORS UK Research & Development Operations Japan Development & Commercial Operations Research & Early Development Discovery / Preclinical / Phase I Development & Commercialization Phase II / III / IV Group Operations Tokyo / London Kieran Johnson Chief Accounting Officer Candelle Chong Chief of Staff Hironoshin Nomura Chief Financial Officer Kazuhiko Yoshizumi Chief Compliance Officer Matt Barnes President of Nxera Pharma UK Makoto Sugita President of Nxera Pharma Japan Toshihiro Maeda Chief Operating Officer EXECUTIVE MANAGEMENT OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Strategic Roadmap 02
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Launched new corporate branding: Nxera Pharma Co With a vision to lead the next era of medicine. From Japan, for Japan, and the world. Our History 10 Strategic steps taken to build Nxera over the last two decades Elevated our status in the Tokyo Stock Exchange, improving access to institutional investors ✓ Promotion to TSE (PRIME) segment in 2023 ✓ First public healthcare investment by the Japan Investment Corporation in 2023 JAPAN KOREA Acquired a commercial-stage pharmaceutical company which provided an integrated platform for even greater sustainable revenue growth ✓ $466m acquisition of Idorsia Pharmaceuticals Japan and Korea ✓ Rapidly growing revenues from sales of PIVLAZ® Invested in research-focused companies that could generate a continuous pipeline of new medicines ✓ $400m acquisition of Heptares Therapeutics Limited in 2015 Out-licensed several programs to global pharma to generate profit, a cash reserve and a larger market valuation ✓ 15+ partnered programs that generate upfront and milestone revenue (plus future royalties) Launched a public company dedicated to bringing innovation to Japan ✓ IPO on TSE (MOTHERS) in 2004 Made strategic acquisitions to bring steady revenue through groundbreaking medicines ✓ $186m acquisition of Arakis Limited in 2005 ✓ Royalty revenues from Breezhaler® medicines from 2012 to present 2000s 2015 2023 2024 OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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To make our mission happen… 11 Accelerate the development of life-changing medicines Focusing on these three areas is how we plan to make our mission happen as fast as possible 1 Acquire or in-license multiple de-risked medicines for Japan 2 Invest in our NxWaveTM platform to seed programs 3 Build a first-class technology environment OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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12 …building a fully integrated biopharma from Japan JAPAN KOREA Discovery / Preclinical Approved Commercialized Medicines Clinical Trials Phase 1 Phase 2 Phase 3 United Kingdom Japan 2000s 2015 2023 2024 Accelerating growth to achieve our mission by leveraging business platform in Japan and UK Acquire or in-license multiple de-risked medicines for JapanInvest in our NxWaveTM platform to seed programs2 1 Build a first-class technology environment3 OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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13 Priority objectives for FY2024 JPY 16 billion+ NHI sales for PIVLAZ® JNDA approval for daridorexant in Japan Acquire/in-license at least one late-stage medicine for Japan/AP AC (ex-China) Execute at least one new major partnership, and initiate at least one new in-house Ph.1 study PMI investment in new brand concept, plus systems and applications for efficiency and scalability 01 02 03 04 05 EP4 ag. SLIGHTLY BEHIND ON-TRACK ON-TRACK P P P Sep. 2024 New target is JPY 15-16Bn OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Our Pipeline Programs by Design 03
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Major Pipeline Overview Note: Pref. ag. : Preferring agonist Respiratory Portfolio = Seebri®, Ultibro®, Enerzair® and Breezhaler® which is registered trademarks of Novartis AG. *APAC (ex-China) territory includes Japan, South Korea, Australia, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, New Zealand, Philippines, Singapore, Taiwan, Thailand and Vietnam 15 PARTNERED 15+ PROGRAMS IN-HOUSE 10+ PROGRAMS Discovery – Preclinical Phase 2 FiledPhase 3 Commercial GPR52 ag. NXE’149 Schizophrenia EP4 ag. NXE’744 IBD PIVLAZ® Cerebral vasospasm QUVIVIQTM Insomnia EP4 ant. NXE’732 Advanced solid tumours Cenerimod Systemic lupus erythematosus Lucerastat Fabry disease Respiratory Portfolio COPD Asthma M4 ag. NBI’568 Schizophrenia M1M4 ag. NBI’570 Neurology OX2 ag. ORX750 Narcolepsy MC4 ant. PF’669 Malnutrition CCR6 ant. PF’894 IBD mGlu5 NAM TMP-301 Substance abuse GLP-1 ag. PF’522 Type 2 Diabetes M1 pref. ag. NBI’567 Neurology M4 pref. ag. NBI’569 Neurology : Exclusive opt-in right : Exclusive license-out option Previous and ongoing discovery collabs. GI Diabetes/Metabolic Multiple Multiple Neurology Phase 1 A A A A J A J : Nxera have Japan rights : Nxera have APAC* rights OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC On-going Technology collabs. AI-driven AI-driven PAR2 peptide Gut-brain axis Neurology & Autoimmune
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Major Pipeline Overview (with future projection) 16 IN-HOUSE 10+ PROGRAMS Discovery – Preclinical Phase 2 Phase 3 Commercial GPR52 ag. NXE’149 Schizophrenia EP4 ag. NXE’744 IBD PIVLAZ® Cerebral vasospasm EP4 ant. NXE’732 Advanced solid tumours Cenerimod Systemic lupus erythematosus Lucerastat Fabry disease Respiratory Portfolio COPD Asthma MC4 ant. PF’669 Malnutrition M1 pref. ag. NBI’567 Neurology M4 pref. ag. NBI’569 Neurology Phase 1 2025 (current Ph1/2a study will expand Ph2a cohort in 2025) 2026 (current trial complete in 2025) 2026 (current trial complete in 2025) 1H 2025 End of 2024 : Exclusive opt-in right : Exclusive license-out option A J : Nxera have Japan rights : Nxera have APAC* rights A A A J Note: Pref. ag. : Preferring agonist Respiratory Portfolio = Seebri®, Ultibro®, Enerzair® and Breezhaler® which is registered trademarks of Novartis AG. *APAC (ex-China) territory includes Japan, South Korea, Australia, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, New Zealand, Philippines, Singapore, Taiwan, Thailand and Vietnam OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC PARTNERED 15+ PROGRAMS Previous and ongoing discovery collabs. GI Diabetes/Metabolic Multiple Multiple Neurology On-going Technology collabs. AI-driven AI-driven PAR2 peptide Gut-brain axis Neurology & Autoimmune M4 ag. NBI’568 Schizophrenia M1M4 ag. NBI’570 Neurology OX2 ag. ORX750 Narcolepsy CCR6 ant. PF’894 IBD mGlu5 NAM TMP-301 Substance abuse GLP-1 ag. PF’522 Type 2 Diabetes QUVIVIQTM Insomnia A Filed
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PROGRAM PARTNER TIMING EVENT EP4 Ag Achieved (Mar. 2024) Ph.1 start GPR35 Ag Achieved (Mar. 2024) Program reversion GPR52 Ag Achieved (Mar. 2024) Option-to-license agreement NBI-568 (M4 Ag) Achieved (Apr. 2024) Long-term TOX study completed NBI-567 (M1 pref. Ag) Achieved (May 2024) Ph.1 start ORX750 (Ox2 Ag) Achieved (May 2024) Ph.1 start NBI-568 (M4 Ag) Achieved (Aug. 2024) Ph.2 topline data ORX750 (Ox2 Ag) Achieved (Sep. 2024) Ph.1 completion & POC data ORX750 (Ox2 Ag) Achieved (Nov. 2024) Ph.2 start Daridorexant (Japan) Achieved (Sep.&Dec. 2024) NDA Approval & Launch Daridorexant (Sth Korea) Achieved (Dec. 2024) New Partnership&Ph.3 start (Achieved) Cenerimod 4Q 2024 Exclusive opt-in decision Lucerastat 4Q 2024 Exclusive opt-in decision TMP-301 (mGlu5 NAM) End of 2024 Ph.2 start Achievements and several potential catalysts in 2024 17 Potential catalysts of in-house and out-licensed programs (excluding new business development transactions) P P P P P P P OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC P P P P
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Major Pipeline Overview (with business categories) 18 IN-HOUSE 10+ PROGRAMS Discovery – Preclinical Phase 2 FiledPhase 3 Commercial GPR52 ag. NXE’149 Schizophrenia EP4 ag. NXE’744 IBD PIVLAZ® Cerebral vasospasm EP4 ant. NXE’732 Advanced solid tumours Cenerimod Systemic lupus erythematosus Lucerastat Fabry disease Respiratory Portfolio COPD Asthma MC4 ant. PF’669 Malnutrition M1 pref. ag. NBI’567 Neurology M4 pref. ag. NBI’569 Neurology Phase 1 : Exclusive opt-in right : Exclusive license-out option A J : Nxera have Japan rights : Nxera have APAC* rights A A A J Note: Pref. ag. : Preferring agonist Respiratory Portfolio = Seebri®, Ultibro®, Enerzair® and Breezhaler® which is registered trademarks of Novartis AG. *APAC (ex-China) territory includes Japan, South Korea, Australia, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, New Zealand, Philippines, Singapore, Taiwan, Thailand and Vietnam Acquire or in-license for Japan OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC NxWaveTM platform driven PARTNERED 15+ PROGRAMS Previous and ongoing discovery collabs. GI Diabetes/Metabolic Multiple Multiple Neurology On-going Technology collabs. AI-driven AI-driven PAR2 peptide Gut-brain axis Neurology & Autoimmune M4 ag. NBI’568 Schizophrenia M1M4 ag. NBI’570 Neurology OX2 ag. ORX750 Narcolepsy CCR6 ant. PF’894 IBD mGlu5 NAM TMP-301 Substance abuse GLP-1 ag. PF’522 Type 2 Diabetes QUVIVIQTM Insomnia A
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Key strategy for each business category 19 Maximize the value of each business and demonstrate synergies by conducting integrated development in future Acquire or in-license for Japan NxWaveTM platform driven Organic Growth Strategic Growth ◼ Collaborate with existing partner to help them to progress pipeline licensed from us ◼ Execute at least one new high value collaboration and/or co-investment per year ◼ Maximize and optimize sales and profit for two major products (PIVLAZ®/QUVIVIQTM) ◼ Collaborate/invest in new technologies with synergies ◼ In-license late-stage products for clinical development and commercialization in Japan and APAC OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Japan/APAC Business Deliver innovation to patients in Japan/APAC 04
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Commercial Japan will serve as our base to expand across APAC markets 21 Japan is an attractive, established market with strong volumes Japan is the second largest pharma market (ex-China) Tailwinds from near- term regulatory changes High quality clinical and regulatory environment APAC is the second highest growth pharma market 169 85 65 42 US China Japan Germany France 0 50 100 150 200 (2021) 580 Market size (USD bn) Source: IQVIA Market Prognosis, Sep 2022; IQVIA Institute, Nov 2022. APAC (ex-China) territory includes South Korea, Australia, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, New Zealand, Philippines, Singapore, Taiwan, Thailand and Vietnam 8.5% 7.0% 6.0% 5.5% 4.0% Latin America APAC Africa & Middle East Europe North America 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% (2019 - 2027)Market growth (CAGR %) Japan Phase 1 Drug Clinical Trials No Longer Needed for Global Clinical Trials “ ” ✓ Excellent access to Doctors/HCPs who evaluate novel drugs ✓ Typically achieve strong patient uptake ✓ Reduces drug loss and drug lag for Japan patients OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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34% 57% 66% 0% 20% 40% 60% 80% 100% 120% 0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000 2022 2023 2024 NHI sales Market share (patient base) Our product: PIVLAZ® Our first commercially available medicine is penetrating the market and protecting lives every day. Source: MDV DPC hospital data *: Comparison of 2-4Q of 2022 and 2023, **: Estimation from previous trend PIVLAZ® is rapidly spreading and becoming standard of care in prevention of cerebral vasospasm 22 1,846 2,365 3,326 2,322 3,477 3,071 4,537 2,752 3,747 3,587 21% 39% 42% 51% 53% 62% 64% 62% 64% 10% 20% 30% 40% 50% 60% 70% 80% 0 500 1,000 1,500 2,000 2,500 3,000 3,500 4,000 4,500 5,000 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 NHI sales Market share (patient base) Quarterly PIVLAZ® Sales (NHI-based) Yearly PIVLAZ® sales and its growth 2022 2023 2024 (YTD) 15,000~16,000 13,407 7,537 +47%* +16% ** ✓ Target sales changed from previous plan ✓ Keeping strong sales growth (2023 - 2024 growth (1Q-3Q): +14%) OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Commercial (million JPY) (million JPY)
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QUVIVIQTM *: A Novel Dual Orexin Receptor Antagonist (DORA) 23 DORA is rapidly establishing its position in insomnia treatment 26%14%25%16%19%Jul. 2022 22%11%17%12%37%Apr. 2024 0 20 40 60 80 (JPY Bn) 12% 28.7 2019 14% 33.1 1.4 2020 17% 33.3 11.3 2021 19% 29.4 27.6 2022 22%** 26.4 41.5 2023 DORA share (patient base) Lemborexant (Dayvigo) Suvorexant (Belsomra) Zolpidem Eszopiclone Others DORA Sales and market share (NHI-base) Prescription share (Most frequently prescribed sleeping pills) Source: Nikkei Medical (2022/7/23, 2024/4/13),IQVIA, Encise, Eisai’s website * Discovered by Idorsia ** Estimation ✓ DORAs are rapidly penetrating the insomnia treatment market in Japan ✓ Japan is one of the largest DORA markets OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Commercial
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QUVIVIQTM Business scheme change 24 SHIONOGI to Exclusively Handle Distribution and Sales Activities in Japan Old Scheme (Sold by 3 companies / 2 channels) New Scheme (Sold by 1 company / 1 channel) Originator Sales & Distribution * Mochida will remain exclusively responsible for manufacturing of QUVIVIQTM in Japan OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Cultivating part of markets at the company's own cost Royalty income from entire market without any costs Market Royalty Commercial * Marketing Authorization Holder
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In-house pipeline: QUVIVIQTM 25 JNDA approval received in Sep. 2024 and launched in Dec. 2024. Aim to be the best-in-class drug Source: 1 ESRS Home | European Sleep Research Society, 2 Lancet Neurol 2022; 21: 125–39. About QUVIVIQTM Dual Orexin Receptor Antagonist Alleviates excessive wakefulness through strong inhibition of orexin receptors European Guideline Recommended in the 2023 European Insomnia Guidelines as the only orexin receptor antagonist that can be used 1 PK profile Significant improvement in next-day sleepiness and daytime functioning confirmed in global phase 3 trials 2 T½: about 6-9 hour Tmax: about 0.5-1.4 hour Unmet needs in insomnia Rapid sleep onset Nocturnal awakenings Carry-over effects to the next day after medication zZ Aim to be the Best-in-class drug in DORA class OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Commercial
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Our NxWaveTM Platform Cutting-edge Science 05
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NxWave platform is focussed on drugging GPCRs GPCRs are the largest family of drug discovery targets – comprising 1/3 of all FDA approved drugs Soruce: 1 “Unexplored opportunities in the druggable human genome”, Nature Reviews, 2016 ; 2 “Trends in GPCR in Drug Discovery – new agents, targets and indications”, Nature Reviews, 2017, GPCRs as targets for approved drugs: How many targets and how many drugs? (2018), Evaluate Pharma, The IUPHAR/BPS Guide to PHARMACOLOGY GPCRs are active in a wide range of disease areas, and offer broad therapeutic potential ~400 GPCR targets active in diseases2 ~34% of FDA approvals target GPCRs1 27 19% 17% 2021 17% 2020 2022 19% 2023 19% 2024 20% 2025 19% 2018 2026 19%19% 2027 19% 2019 2028 134 19% 145 155 159 172 140 207 222 237 251 191 Drugs that target GPCRs account for 20% of the entire pharmaceutical market (Billion USD) Market share of GPCR-targeting drug Market size of GPCR-targeting drug Actual Prediction NEUROLOGICAL DISORDERS GASTROINTESTINAL DISEASES IMMUNOLOGY/ONCOLOGY METABOLIC DISORDERS CARDIOVASCULAR RESPIRATORY OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Platform
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ADORA2A ADRA2A ADRB2 CHRM1 DRD1 DRD3 HTR2A HTR4 OPRD1 OPRM1 P2RY12 PTGER2 GHRHR TSHR ADORA2B ADRB3 CHRM2 GLP1R HTR1B HTR1F MTNR1A PTGER3 PTGIR S1PR5 GCGR GIPR MC4R RXFP1 SCTR AVPR1A C5AR1 CCR5 CXCR4 DRD4 EDNRB GNRHR HCRTR2 HTR2B TACR1 CALCRL P2RY2 TACR3 ADRA1B ADRA2B AVPR1B DRD5 GABBR2 SSTR1 SSTR3 ACKR1 ACKR3 ADCYAP1R1 ADGRA2 ADGRB1 ADGRB3 ADGRD2 ADGRE2 ADGRE4P ADGRF1 ADGRF3 ADGRF5 ADGRG2 ADGRG4 ADGRG6 ADGRL1 ADGRL3 ADGRV1 BDKRB1 C3AR1 CCKBR CCR10 CCR3 CCR6 CCR8 CCRL2 CELSR2 CHRM4 CMKLR1 CRHR1 CX3CR1 CXCR2 CXCR5 CYSLTR2 F2RL2 FFAR2 FFAR4 FPR2 FZD1 FZD2 FZD4 FZD6 FZD8 GALR1 GALR3 GPBAR1 GPR1 GPR107 GPR12 GPR135 GPR139 GPR142 GPR146 GPR149 GPR150 GPR152 GPR156 GPR158 GPR161 GPR17 GPR173 GPR176 GPR18 GPR183 GPR20 GPR22 GPR26 GPR3 GPR32 GPR34 GPR37 GPR39 GPR42 GPR50 GPR55 GPR61 GPR63 GPR68 GPR78 GPR82 GPR84 GPR87 GPRC5A GPRC5C GPRC6A GRM2 GRM4 GRM6 GRM8 HCAR1 HCAR3 HTR1E HTR5BP KISS1R LGR5 LPAR1 LPAR3 LPAR5 LTB4R MAS1 MC1R MC5R MCHR2 MRGPRD MRGPRF MRGPRX1 MRGPRX3 NMBR NMUR2 NPBWR2 NPFFR2 NPY1R NPY4R NPY6R NTSR2 OPN4 OPRL1 OXER1 P2RY1 P2RY11 P2RY14 P2RY6 PRLHR PROKR2 PTGDR2 QRFPR RXFP4 S1PR3 SSTR4 TAAR2 TAAR4P TAAR6 TAAR9 TAS1R1 TAS1R3 TAS2R10 TAS2R14 TAS2R19 TAS2R3 TAS2R31 TAS2R39 TAS2R40 TAS2R42 TAS2R45 TAS2R5 TAS2R60 TAS2R8 TPRA1 UTS2R VIPR2 GPCR: Large unmet needs and FIC opportunities 28 >650 First-in-class opportunities in GPCR-targeting drug Marketed drugs only, *27 GPCRs×2 (ago. and ant.) Sources: GPCRs as targets for approved drugs: How many targets and how many drugs? (2018), Evaluate Pharma, The IUPHAR/BPS Guide to PHARMACOLOGY First-in-class opportunities ~680 • ~310 GPCRs: NO agonists nor antagonists (620 opportunities) • ~60 GPCRs: Either agonists or antagonists (60 opportunities) Total ~800 drug opportunities (~400 GPCRs are thought to be drug targets) Best-in-class opportunities（~120）: Drugs are available ago. & ant. (54*) ago. (31) ant. (26) OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Platform
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NxWave platform enables faster, cheaper and more precise drug discovery 29 World-leading science and platform enables efficient drug discovery against difficult targets 1 HTS/High Throughput Screening is a method to find drug candidates by reacting tens of thousands to millions of compounds with drug targets using large machines and human hands. 2 The period from target selection to preclinical testing. For conventional drug discovery, figures are taken from NATURE REVIEWS Drug Discovery (MARCH 2010). 3 Precise drug design make clear the binding site of target, make easier to improve compound, create backups and redo – potentially increase the success rate. GPCR is most popular drug target which account for 30% of current drug target. Conventional drug discovery Our drug discovery Approach Empirical design Rational design (computer-based) Method High Throughput Screening (HTS1) Proprietary NxWave Platform Period2 4.5 years on average 3.0 years on average Costs2 $15 million $5 million Features 3 Difficult to design drugs precisely – high development attrition rate Execute more precise drug design – lower development attrition rate Target 3 Difficult for GPCRs with unstable structures Best for GPCRs with unstable structures OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Platform
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Our platform enables precise design of GPCR models 30 Only by performing detailed structural analysis can we design great drugs. Imprecise GPCR model: Standard Medicine Precise GPCR model: Optimized Medicine Target- GPCR Off-target Off-target Target- GPCR Off-target Off-target Efficacy Unintended side effects Poorly understood GPCRs (locks) led to suboptimal drugs (keys) being designed High selectivity enables to optimize efficacy and minimize side effects Optimal Efficacy No/minimal side effects Drug Drug OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Platform
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0 200 400 600 800 1,000 1,200 0 2,000 4,000 6,000 8,000 10,000 12,000 FY15/3 FY16/3 FY17/3 FY18/3 FY18/12 FY19/12 FY20/12 FY21/12 FY22/12 FY23/12 FY24/12 Commercial milestone(left axis) Development milestone(left axis) Received upfront and milestone(right axis/cumulative) 0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 Voyager Therapeutics Exscientia Poseida Therapeutics Nurix Therapeutics Sichuan Kelun-Biotech Kelun Group Precision Biosciences CytomX Therapeutics Galapagos Sangamo Therapeutics PeptiDream Arcturus Therapeutics Nxera Pharma Ionis Pharmaceuticals AstraZeneca Daiichi Sankyo Our track record of major licensing transactions speaks for itself… 31 Income from licensing provides a great source of non-dilutive financing to support our growth 5,000+ 5,000+ (USD million)(USD million) Top 15 pharmaceutical/biotech companies by license value2 (cumulative total since 2015) 4th out of 3,843 (USD million) Balance of potential milestone income from existing license agreements1 1 Balance as of the end of the fiscal year of only those currently under contract. TEVA and AbbVie (formerly Allergan), for which compounds were returned, are excluded from the balances from FY2018 and FY2021, respectively. 2 The figures are based on ‘Licensing’ category on third party's (EvaluatePharma's) proprietary database and therefore do not completely match the amounts shown in the LHS chart. Source: Company’s data (LHS) and EvaluatePharma (as of 2024/10/17) (RHS) OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Platform
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… hundreds of millions of dollars received, billions of dollars in potential to come 32 New collaboration and exclusive option to license agreement executed with Boehringer Ingelheim Partner Execution Program Therapeutic Area(s) Upfront and Initial Milestones Potential Total Milestone1 March 2024 Collaboration and exclusive option-to- license agreement for GPR52 agonist Schizophrenia €25m €670m December 2022 Multi-target Collaboration Diabetes and Metabolic $37m $800m August 2022 Multi-target Collaboration Neurological disorders $80m $1.2bn December 2021 Collaboration and license agreement for M4, M1 and M1/M4 dual agonist Neurological disorders $100m $2.6bn December 2020 Collaboration and license agreement for GPR 35 Gastrointestinal, immunology $44m $480m December 2020 Collaboration and license agreement for CGRP portfolio Neurology $10m $380m June 2020 Discovery Collaboration and Option to License2 Inflammatory and Autoimmune $32m $400m August 2019 Multi-target Collaboration Multiple; Initial focus on Gastrointestinal $26m $1.2bn July 2019 Multi-target Collaboration Multiple $26m $1.0bn November 2015 Multi-target Collaboration Multiple - $1.8bn 1Potential option fees, development, regulatory and commercial milestone payments agreed at the time of transaction. Nxera is also eligible to receive tiered royalties ranging from high single digit to mid-teen percentage on future net sales of any products developed under the partnership. 2 AbbVie has the option to expand the collaboration by an additional three targets OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Platform
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M4 ago. (NBI’568) demonstrated competitive positive phase 2 data 33 Once-daily 20 mg dose showed efficacy, and good safety / tolerability profile for schizophrenia patients. Source: Presentation of Neurocrine Sciences (Aug.28 2024), KarXT for Schizophrenia draft evidence report (Nov. 28, 2023) OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC Clinically meaningful and statistically significant efficacy (Once-daily 20 mg dose) ➢ PANSS total score change -18.2 Met primary and additional endpoints and demonstrated efficacy on both positive and negative symptoms ➢ PANSS total score change vs. Placebo -7.5 (p = 0.011) ➢ Effect size 0.61 ➢ Marder Factor score change vs Placebo: • Positive -3.0 (p=0.004) • Negative -1.9 (p=0.028) Generally safe and well-tolerated across all doses tested ➢ Treatment discontinuation rate due to adverse events across all NBI’568 arms 5.0% (placebo: 4.3%) NBI’568 showed safety and tolerability for all doses➢ GI and CV adverse event frequency (Cobenfy (BMS/Karuna): 3-5x (GI), ~4x (CV) vs. placebo) Similar to placebo Rapidly advancing to Phase 3 development ➢ Received successful milestone of Ph2 trial US$ 35 m Expanding potential of muscarinic agonist portfolio ➢ Ph3 clinical trial begin in 1H 2025 ➢ Evaluating additional indication for NBI’568 ➢ Advancing follow-on compounds in muscarinic agonist portfolio Platform
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Financial Results 06
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80 2,408 8,440 2,269 2,614 2,092 1,594 1,366 4,665 974 10,557 1,282 1,392 3,590 8,641 5,474 21,983 0 5,000 10,000 15,000 20,000 25,000 3Q FY21 3Q FY22 3Q FY23 3Q FY24 (4,225) (615) (7,992) (2,846)(2,658) 1,300 (3,919) 4,425 (9,000) (6,000) (3,000) 0 3,000 6,000 3Q FY21 3Q FY22 3Q FY23 3Q FY24 OP Core OP Key financial indicators 35 1 Upfront fee revenue recognised at deal inception 2 Milestone revenue recognised at milestone event + deferred revenue releases Revenue (JPY million) (JPY million) 3Q result Operating Profit / Loss Explanation for 1Q-3Q 2024 Full impact of NPJ/NPK product sales and cost base reflected in FY2024 Upfront1 ◼ New option-to-license deal signed with Boehringer. (March) Milestone2 ◼ $15m M4 development milestone from Neurocrine (April). ◼ $4.6m milestone from Centessa (May). ◼ $10m milestone from AbbVie (June). ◼ $35m M4 Ph2 succusses milestone from Neurocrine (Sept). Royalty / Other ◼ Royalty from Respiratory Portfolio from Novartis decreased. Product Sales ◼ PIVLAZ® sales are increasing and fully impact for 2024. R&D ◼ Increase investment in R&D activities for clinical trial. ◼ Inclusion of NPJ/NPK related R&D costs. Cost of Sales ◼ Inclusion of PIVLAZ® product supply costs. ◼ Additional non-cash CoS charge relating to PIVLAZ® inventory. G&A ◼ Inclusion of NPJ/NPK related G&A costs. ◼ Integration costs (incl. company name change). ◼ Amortization of intangible assets (PIVLAZ®). OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Breakdown of 3Q 2024 result 36 Impact of Non-cash/Non-recurring costs on full-year result is more significant in 2024 due to the inclusion of Idorsia businesses (JPY million) Consolidated P&L (Core)NPC / NPU*1 Consolidated P&L (IFRS) Non-recurring CostsNon-cash costsNPJ / NPK*2 (2,401) PIVLAZ® inventory adjustment (1,022) Amortization - Product IP (836) Integration Revenue Cost of Sales + SG&A Other income 13,613 (4,823) 933 8,370 (6,100) (39) 21,983 (10,923) 894 21,983 (17,206) R&D (6,553) (976) (7,529) (8,517) 894 OP/Core OP 3,170 1,255 Core OP 4,425 OP (2,846) A B Additional CoS charge for PIVLAZ® stock which completed by 3Q 2024. This will no longer be recurring from 4Q 2024.A Amortization of intangible assets (currently relates to PIVLAZ®). Annual charge to increase to c. JPY 1,800mper year from 2025.B ＋＋ = =＋ Integration related costs (988) Other Amortization of other intangible assets (e.g. IP), depreciation (e.g. laboratory equipment), share-based payments and other restructuring costs.D D (2,024) Other C D C Integration costs including IT system integration and Corporate rebranding. Will significantly decrease in 2025. *1 = Nxera Pharma Co. Ltd. (formerly Sosei Group Corporation) + Nxera Pharma UK Ltd (formerly Heptares Therapeutics Ltd.) + Sosei K.K *2 = Nxera Pharma Japan (formerly Idorsia Pharmaceuticals Japan) + Nxera Pharma Korea (formerly Idorsia Pharmaceuticals Korea) Total : 7,271 OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Full year cost guidance 37 Incremental investment designed to deliver greater returns over the medium to long term (JPY million) (JPY million) 3,793 5,931 7,454 10,075 11,000 0 5,000 10,000 15,000 FY20 FY21 FY22 FY23 FY24 3,435 3,940 4,377 9,965 14,000 0 5,000 10,000 15,000 20,000 FY20 FY21 FY22 FY23 FY24 1. Nxera Pharma Japan 2. Nxera Pharma Korea R&D expenses (IFRS) ¥11,000 ~ ¥13,000m Major points on FY24 ◼ Investment in discovery and translational medicine capabilities. ◼ 1 clinical trial initiated for in-house program (EP4 ag.) ◼ Advancing in-house programs further through the clinic will deliver higher out-licensing revenues ¥12,000 ~ ¥14,000m NewOld - ¥1,000m SG&A expenses (IFRS) ¥14,000 ~ ¥16,000m Major points on FY24 ◼ Includes NPJ1/NPK2 SG&A costs for a full year. ◼ Increase in support for PIVLAZ® to drive growth. ◼ Increase in amortization charge for PIVLAZ® and QUVIVIQTM(c. ¥1,600m) ◼ PMI relating costs for NPJ/NPK (c. ¥1,000m) ¥18,000 ~ ¥20,000m NewOld - ¥4,000m LATEST GUIDANCE 13,000 ~ 16,000 ~ OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Cost expenses guidance gap vs. beginning of FY24 38 We expect downward trend in SG&A expenses to continue through optimization in 2025 SG&A expenses (IFRS) guidance * The median of range is given as an example Assumed exchange rate: 140 JPY/USD | 172 JPY/GBP (old guidance), 152 JPY/USD | 193 JPY/GBP (latest guidance) R&D expenses (IFRS) guidance 2,000 500 Old guidance Cost saving through integration Others -1,500 FX impact Latest guidance 13,000 12,000 2,500 800 1,000 Old guidance Cost saving through integration QUVIVIQ sales strategy change Others -300 FX impact Latest guidance 19,000 15,000 OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC * * * * - ¥1,000m - ¥4,000m (JPY million) (JPY million)
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PIVLAZ® sales guidance update 39 Updated sales guidance due to SAH occurrence decrease and cancellation of inventory adjustment plan 34% 57% 66% 0% 20% 40% 60% 80% 100% 120% 0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000 2022 2023 2024 NHI sales Market share (patient base) 15,000~16,000 13,407 7,537 * Sales guidance of PIVLAZ® Background of sales guidance update Updated sales guidance though PIVLAZ’s market share is continuously growing SAH occurrence decrease in 2024 0 800 1,000 1,200 Mortality cases of SAH in Japan (patients) Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 2022 2023 2024 Mortality cases of SAH in 2024 (Jan-May) was 4-6% lower than past 2 years Optimization of year-end inventory 2023 In anticipation of increasing demand over the year-end and New Year period, the inventory for distributor was adjusted (excess of c. JPY 200 million than monthly forecast) 2024 Inventory adjustment was cancelled based on the track records in 2022-2023 OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC c. JPY200m c. JPY800m * Estimation from previous trend
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07 Appendix
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Exclusive Opt-in Rights And ROFN/ROFR1 41 Option to develop up to seven clinical programs for Japan and APAC (ex-China) from Idorsia 1 ROFN/ROFR - Right of first negotiation / Right of first refusal 2 Territories include Japan, South Korea, Australia, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, New Zealand, Philippines, Singapore, Taiwan, Thailand and Vietnam * Global Phase Program Indication Stage Region APAC (ex-China)2 Mechanism of Action Exclusive Opt-in Right ROFR /ROFN1 Lucerastat Cenerimod ACT-1004-1239 ACT-1014-6470 IDOR-1117-2520 ACT-777991 Fabry disease Systemic lupus erythematosus Multiple sclerosis and other demyelinating diseases Immune-mediated disorders Immune-mediated disorders Recent-onset Type 1 diabetes Phase 3 Phase 3 Phase 2* Phase 1* Phase 1* Phase 1* Glucosylceramide synthase inhibitor S1P1 receptor modulator ACKR3 / CXCR7 antagonist C5aR1 antagonist Undisclosed CXCR3 antagonist OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Core Operating Profit - Definition 42 Core Operating Profit/Loss – a financial indicator closer to the reality of our business Cash Non-cash (Material) Recurring Non-recurring (Material) Operating Profit “IFRS” ◼ Financial results recorded and prepared in accordance with International Financial Reporting Standards (IFRS) Operating Profit “Core” ◼ Core Operating Profit/ Loss is a key financial indicator that highlights the underlying recurring cash generating capability of our business. ◼ Core Operating Profit/Loss is defined as IFRS Operating Profit + material Non-cash costs + material non-recurring costs ◼ Material Non-cash Costs include depreciation, amortization, share based payments and impairment. ◼ Material Non-recurring Costs include restructuring costs, M&A related professional fees and other material one-off items. + Material Non-cash Costs (Depreciation, Amortization, Share based payments, Impairment...etc.) + Material Non-recurring Costs (Restructuring costs and Other material one -off items...etc.) Costs under “IFRS” Costs under “Core” OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Estimation of potential market size 43 Multi-billion USD annual peak sales potential for our post-pre-clinical pipeline Category Indication2 Number of Patients Our Candidates Market Size Individual Products Neurological disorders Dementia ~55 million $7.3 billion (2010) $3.9 billion (2009/Aricept) M1 agonist, M1/M4 agonist Schizophrenia ~20 million $20.7 billion (2011) $5.7 billion (2013/Abilify) M4 agonist, M1/M4 agonist, GPR52 agonist Substance use disorders ~10.4 million1 - - - - mGlu5 NAM Narcolepsy ~3 million $2.3 billion (2022) $1.7 billion (2020/Xyrem) OX2 agonist Other - - - - - CGRP antagonist, GPR52 agonist Immunological disorders Cancer ~42 million $178.9 billion (2022) $21.0 billion (2022/Keytruda) A2a antagonist, EP4 antagonist, CXCR4 mAb IBD ~10 million $23.5 billion (2022) $7.5 billion (2022/Humira) CCR6 antagonist, GPR35 agonist, EP4 agonist Atopic Dermatitis ~13.3 million $8.1 billion3 (2022) $7.0 billion (2022/Dupixent) H4 antagonist, PAR2 mAb Other T2DM/Obesity ~420 million $58.3 billion (2022) $8.8 billion (2022/Ozempic) GLP1 agonist Anorexia ~10 million - - - - MC4 antagonist Total ~$299 billion/year ~$56 billion/year Source (Number of patients)：World Health Organization, Evaluate Pharma, The European Federation of Crohn‘s & Ulcerative Colitis Associations (EFCCA), Narcolepsy Network, Inc., GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (October 2016). “Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015”. Lancet. 388 (10053): 1545–1602 1 The number of patients with drug addiction Source (Peak Sales):Sales of each indications are extracted form Evaluate Pharma’s data of sales by disease and sales by individual products (as of 30 June. 2022). 2 Nxera may target one segment in the market for specific diseases. 3 Since there is no applicable indication category, the market size of “Eczema” is stated. Current market size for Atopic Dermatitis may be larger than stated above. OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Partnered pipeline (1/2) 44 Compound Target / Mechanism of Action Modality Indication Partner Disc. PCC Ph1 Ph2 Ph3 App Mkt Partnered Seebri® Breezhaler® LAMA SME COPD Ultibro® Breezhaler® LAMA+LABA SME COPD Enerzair® Breezhaler® LAMA+LABA+ICS SME Asthma ORAVI® Antifungal agent miconazole SME Oropharyngeal candidiasis NBI-1117568 Muscarinic M4 agonist SME Schizophrenia NBI-1117569 Muscarinic M4 preferring agonist SME Neurology diseases NBI-1117570 Muscarinic M1/M4 agonist SME Neurology diseases NBI-1117567 Muscarinic M1 preferring agonist SME Neurology diseases PF-07054894 CCR6 antagonist SME Inflammatory bowel disease PF-07258669 MC4 antagonist SME Malnutrition PF-06954522 GLP-1 agonist SME Type 2 Diabetes (Not disclosed) CGRP antagonist SME Neurology diseases (Not disclosed) Multi target SME/LME Multiple indications (Not disclosed) Multi target SME Neurology (Not disclosed) Multi target SME Diabetes/Metabolic Note: SME = small molecule. LME = large molecule. Seebri®, Ultibro®, Enerzair® and Breezhaler® are registered trademarks of Novartis AG. OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Partnered pipeline (2/2) 45 Compound Target / Mechanism of Action Modality Indication Partner Disc. PCC Ph1 Ph2 Ph3 App Mkt Co-development KY1051 CXCR4 mAb mAb Immuno-oncology (Not disclosed) PAR-2 Peptide Inflammatory diseases (Not disclosed) AI-Augmented Drug Discovery SME Neurology diseases (Not disclosed) Multi target AI-powered SME/LME Immune diseases (Not disclosed) Gut-brain axis drug discovery SME Gastrointestinal disorders Co-owned companies TMP301 mGlu5 NAM SME Substance use disorders ORX750 OX2 agonist (Oral) SME Narcolepsy 1/2, IH ORX142 OX2 agonist (Oral) SME EDS in neurology ORX489 OX2 agonist (Oral) SME Neurology Note: SME = small molecule. LME = large molecule, IH: Idiopathic Hypersomnia, EDS: Excessive Daytime Sleepiness OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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In-house pipeline 46 Compound Target / Mechanism Modality Indication Partner Disc. PCC Ph1 Ph2 Ph3 App Mkt In-house Programs PIVLAZ® ETA antagonist SME Cerebral vasospasm QUVIVIQTM Dual Orexin antagonist SME Insomnia NXE0048149 1 GPR52 agonist SME Neurology diseases NXE0039732 EP4 antagonist SME Immuno-oncology NXE0033744 EP4 agonist SME Inflammatory bowel disease NXE0027477 GPR35 agonist SME Inflammatory bowel disease (Not disclosed) Muscarinic M1 agonist (JP) SME Neurology diseases (Not disclosed) SARS CoV-2 Mpro SME Coronaviruses Multiple programs Not disclosed SME/LME Neurology diseases Multiple programs Not disclosed SME/LME GI and Inflammatory diseases Multiple programs Not disclosed SME/LME Immunology diseases In-house Programs (No longer internally funded. Targeting academic / industrial partnership) NXE’310 SSTR5 agonist Peptide Hypoglycaemic disorders NXE’097 GLP-1 antagonist Peptide Hypoglycaemic disorders NXE’023 Dual GLP-2/GLP-1 agonist Peptide Intestinal failure/NASH (Not disclosed) Apelin agonist Peptide Pulmonary Arterial Hypertension NXE’641 Dual orexin antagonist SME Insomnia and sleep disorders (Not disclosed) PAR-2 mAb mAb Atopic Dermatitis/Pain Note: SME = small molecule. LME = large molecule. 1: Exclusive license-out option OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Glossary 47 Basic Terminology/Technology GPCR G Protein-Coupled Receptor There are about 800 types of GPCRs in the human body. While 400 of them are known to be potential drug targets, about 300 of them are not yet drugged NxStaRTM Stabilized Receptor Nxera’ proprietary technology to stabilize a GPCR by engineering a small number of single point mutations outside of the ligand-binding site. It enables to identify the structure of GPCRs to be used for SBDD drug discovery as well as antibody drug discovery as antigens SBDD Structure-Based Drug Design A method to design drugs on a computer base based on the analysis of the three-dimensional structure of the drug target (e.g., protein receptor) TPD Targeted Protein Degradation Drugs that promote the degradation of target proteins (e.g., receptors) in cells and aim for therapeutic effects by reducing disease-causing proteins PAM Positive Allosteric Modulator A regulator that binds to unusual active sites (allosteric sites) on the receptor to increase the affinity and effect of the agonist NAM Negative Allosteric Modulator A regulator that binds to an unusual active site on the receptor (allosteric site) and reduces the affinity and effectiveness of the agonist Ag Agonist A therapeutic drug that binds to a receptor and activates an intracellular signaling system similar to biological substances Ant Antagonist A therapeutic drug that suppresses biological reactions by binding to receptors and preventing them from binding to biological substances PK Pharmacokinetics Research and testing on the relationship between drug dosage and blood concentration. Mainly describes the rate process of ADME PD Pharmacodynamics Research and testing on the relationship between drug concentration and pharmacological effects ADME Absorption, Distribution, Metabolism and Excretion A series of process in the absorption of drugs into the body, distribution within the body, metabolism in the liver and other organs, and excretion in the kidneys and other organs POM Proof of Mechanism Proof of mechanism of action, mainly through biomarkers. It can suggest the possibility of efficacy in fewer cases than POC POC Proof of Concept Proof of a therapeutic concept, primarily through clinical efficacy and safety Ach Acetylcholine A neurotransmitter released from the peripheral parasympathetic and motor nerves to transmit nerve stimuli IND Investigational New Drug Information packages for development candidates to be submitted to the U.S. Food and Drug Administration (FDA) at the time of initiation of clinical trials Ph1 Phase1 A study in humans. The main purpose is to confirm the safety of the drug candidate mainly by healthy volunteers. Ph2 Phase2 A study in humans. The main purpose is to confirm the efficacy of the drug candidates on a small scale (however, the number of patients varies greatly depending on the disease) Ph3 Phase3 A study in humans. The main purpose is to determine the efficacy of the drug candidates on a large scale (however, the number of patients varies greatly depending on the disease) NDA New Drug Application An application to the U.S. Food and Drug Administration (FDA) for approval to market a new drug Disease/Drug LAMA Long Acting Muscarinic Antagonist An inhalant that dilates bronchial tubes and improves respiratory function by inhibiting the action of acetylcholine receptors (M3), which increase parasympathetic nerves. LABA Long Acting Beta2-Agonist An inhalant that improves respiratory function by stimulating sympathetic beta2 receptors to dilate the bronchi. ICS Inhaled Corticosteroid An inhalant that suppresses airway inflammation to prevent coughing attacks and other symptoms caused by asthma, also promotes the action of beta 2 stimulants and improve airway hyperresponsiveness. mCRPC Metastatic Castration–Resistant Prostate Cancer Cancer that has spread (metastasized) beyond your prostate gland and for which hormone therapy is no longer effective in stopping or slowing the disease. COPD Chronic Obstructive Pulmonary Disease A group of diseases that causes damage to the bronchi and lung due to smoking or inhalation of toxic substances, resulting in breathing problems. AD Alzheimer’s Disease Alzheimer's disease is a progressive neurologic disorder that causes the brain to shrink (atrophy) and brain cells to die, the most common cause of dementia . DLB Dementia with Lewy Bodies Protein deposits, called Lewy bodies, develop in nerve cells in the brain regions involved in thinking, memory and movement (motor control), the second most common type of dementia. OVERVIEW STRATEGIC ROADMAP PIPELINE PLATFORM FINANCIALS APPENDIXJP/APAC
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Midtown East, 9-7-2 Akasaka Minato-ku Tokyo 107-0052 Japan F17, 410 Teheran- Ro GangHam-Gu Seoul 06192 South Korea Steinmetz Building Granta Park, Cambridge CB21 6DG United Kingdom Spaces Grosspeter Tower, Grosspeteranlage 29, 4052 Basel Switzerland 48 Locations
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BREAKTHROUGHS IN PROGRESS ● BREAKTHROUGHS IN PROGRESS ● BREAKTHROUGHS IN PROGRESS Thank you