Nippon Shinyaku Co., Ltd. · TSE:4516
Nippon Shinyaku — Investor Day (February 2025)
59 slides from Nippon Shinyaku's investor day presentation, Feb 18, 2025
Slide 1: FY2024 R&D Meeting
FY2024 R＆D Meeting February 18 th, 2025 Nippon Shinyaku Co., Ltd.
Slide 2: Agenda
AGENDA Introduction 01 Toru Nakai Representative Director, President R&D activities 02 Kazuchika Takagaki Director, Research & Development 03 Q&A 2
Slide 3: Introduction
Introduction Toru Nakai Representative Director, President 3
Slide 4: Key Theme III: Continuous Pipeline Expansion
Key Theme III : Continuous Pipeline Expansion Licensing in products in the clinical stage and strengthen in-house drug discovery by leveraging open innovation and AI drug discovery system to continuously expand the pipeline. Modified from May 27, 2024 The 7th Five-Year Medium-Term Management Plan (F
Slide 5: Establishing a Foundation for Growth Overcoming the Patent Cliff
Establishing a Foundation for Growth Overcoming the Patent Cliff ❶Speed and success probability ❷R&D speed for new modalities in clinical development • Delay of start of the studies for NS- • The length of time for development of 089/NCNP-02 and NS-050/NCNP-03 next-generation nucleic acid drugs and
Slide 6: Business Strategy for Pharmaceutical Segment
Business Strategy for Pharmaceutical Segment Launching an average of two or more new products per year Business through the three pillars of in-house drug discovery, in-licensing, Strategy and PLCM, prioritizing response to the patent cliff. ■In-house drug Focusing on nucleic acid and small molecule
Slide 7: Establishing a foundation for growth overcoming the patent cliff
Establishing a foundation for growth overcoming the patent cliff We plan to achieve revenues of 300 billion yen in FY2030 by promoting investment in R&D pipeline, in-licensed products, M&A, etc. during the 7th Medium-Term Management Plan period. Modified from May 27, 2024 The 7th Five-Year Medium-Te
Slide 8: FY2024 R&D milestones to date
FY2024 R&D milestones to date 2024 Apr Research alliance with MiNA Therapeutics May Launch of Vyxeos (Japan) Aug Launch of Jaypirca (Japan) Exclusive strategic collaboration for ATSN-101 (U.S. and Japan) Nov Start of co-promotion activities for Yuvanci (Japan) Additional indication (pediatric PAH) f
Slide 9: R&D activities - For continuous pipeline expansion -
R&D activities - For continuous pipeline expansion - Kazuchika Takagaki Director, Research & Development 9
Slide 10: New / outside technology
New / outside technology 10
Slide 11: Small molecule activated RNA: Research collaboration with MiNA
Small molecule activated RNA: Research collaboration with MiNA saRNA is a type of nucleic acid that enhances gene expression Chemically synthesized double-stranded RNA of 21 bases (similar to siRNA) cellular membrane 1. Forming a complex with 6. Increase in gene RNA-binding proteins expression produ
Slide 12: AI Drug Discovery
AI Drug Discovery Workflow aimed at the Discovery Research Laboratories • Design compounds that bind to target molecules (known/unknown structure) using AI • Predict the physical properties, kinetics, and safety of compounds before synthesisPredicts physical properties/kinetics/safety of compounds b
Slide 13: AI Drug Discovery
AI Drug Discovery Information Creation of highly unique drug discovery by building a knowledge network system that integrates public and in-house data • Comprehensive acquisition of drug discovery information from disease names to patents, clinical, genetic mutations, target molecule groups, existin
Slide 14: In-licensing
In-licensing 14
Slide 15: Deramiocel (CAP-1002) for the treatment of DMD-cardiomyopathy
Deramiocel (CAP-1002) for the treatment of DMD-cardiomyopathy by cell (exosome) therapy 15
Slide 16: Positioning in the DMD treatment options
Positioning in the DMD treatment options Our Nucleic acid drug Viltep NS- NS- product （Exon skipping） so 089 050 and pipeline Cell (exosome) therapy CAP-1002 Exon skipping 51 45 53 44 50 55 % in DMD population 13% 8% 8% 6% 4% 2% 59% amenable to Viltepso motor function Main patients Main patients ame
Slide 17: Duchenne Muscular Dystrophy (DMD)
Duchenne Muscular Dystrophy (DMD) What is DMD? Due to a genetic mutation that causes dystrophin to be lost, the structure that connects the cytoskeleton actin and basement membrane to reinforce the muscle cell membrane is not formed, and muscle cells become fragile. The broken muscle cells are regen
Slide 18: Duchenne Disease Trajectory
Duchenne Disease Trajectory Source: Materials provided by Capricor Therapeutics 18
Slide 19: Deramiocel (CAP-1002): Cell therapy for DMD-cardiomyopathy
Deramiocel (CAP-1002): Cell therapy for the expected indication of DMD-cardiomyopathy • Cell therapy derived from transplant-qualified human hearts (allogeneic sources). • Exosomes (extracellular vesicles) secreted from CAP-1002 are expected to reduce oxidative stress, inflammation, and fibrosis, an
Slide 20: Production of deramiocel (CAP-1002)
Production of deramiocel (CAP-1002) Deramiocel Manufacturing Facility San Diego, California EDC：explant-derived cell MCB：master cell bank CDC：cardiosphere-derived cell Source: Materials provided by Capricor Therapeutics 20
Slide 21: Deramiocel (CAP-1002): Clinical Trials
Deramiocel (CAP-1002): Clinical Trials P2 study (HOPE-2) P2 Open-label extension study (HOPE-2 OLE) Testing period March 2018 - March 2020 July 2020 - ongoing Total 20 cases Number of 8 active drug (7 cases of non-ambulatory) 13 cases (all non-ambulatory) cases 12 placebo (11 cases of non-ambulatory
Slide 22: Deramiocel (CAP-1002): HOPE-2 OLE study data
Deramiocel (CAP-1002): HOPE-2 OLE study 36 months data Cardiac Endpoint Skeletal Muscle Endpoint Median change in left ventricular ejection fraction (LVEF) Change in PUL 2.0 score 1 Baseline LVEF >45% While LVEF worsened by 5.0% over 2 years in the natural history data of At 3 years post-treatment,
Slide 23: Deramiocel (CAP-1002): Development timeline and partnership
Deramiocel (CAP-1002): Development timeline and partnership NS Pharma, a U.S. subsidiary of Nippon Shinyaku, is currently preparing for the product launch. BLA submission completed in December 2024 Expected PDUFA 2025 2H (FDA approval date) full FDA approval with data of HOPE-2 and HOPE-2 OLE Expect
Slide 24: Gene therapy
Gene therapy 24
Slide 25: Gene therapy: In-Licensed products
Gene therapy：In-Licensed products Code name ATSN-101 RGX-121 RGX-111 Origin Athena Therapeutics, Inc. Regenex Bio Inc. Mucopolysaccharidosis GUCY2D-associated Leber type II Mucopolysaccharidosis Indication congenital amaurosis (MPS II; Hunter type I (MPS I) (LCA1) syndrome) AAV serotype AAV5 AAV9 AA
Slide 26: ATSN-101 for the treatment of GUCY2D-associated LCA1
ATSN-101 for the treatment of GUCY2D-associated Leber congenital amaurosis (LCA1) 26
Slide 27: ATSN-101: Summary of expected indications
ATSN-101：Summary of expected indications What is LCA?1,2 LCA (Leber congenital amaurosis) is a family of diseases caused by mutations in ~20 different genes. The estimated number of patients is around 10,000 (Japan)3 and just under 50,000 (USA) 4. All forms of LCA are inherited in autosomal recessiv
Slide 28: Features of ATSN-101
Features of ATSN-101 Modality Gene therapy Development stage P1/2 Dosage and 1×1011 vg per eye administered as a single subretinal injection administration Dosage form Vial RMAT designation, orphan designation, rare pediatric disease Designations designation by the U.S. FDA Mechanism of action The G
Slide 29: ATSN-101: U.S. P1/2
ATSN-101: U.S. P1/2 Testing period September 2019 - May 2027 Number of 15 cases Trial design Multicenter open-label single eye dose escalation study Trial sites 2 sites in the U.S. • 18 years and older (cohorts 1-4), 6-17 years (cohort 5) • Genetically diagnosed with Leber's congenital cataract • Al
Slide 30: ATSN-101: Efficacy evaluation (BCVA)
ATSN-101: Efficacy evaluation of U.S. P1/2 clinical trial Efficacy: BCVA (best-corrected visual acuity) improvement Improvement trend was observed. Source: Figure 5, The Lancet Volume 404, Issue 10456, 7-13 September 2024, Pages 962-970 Safety and efficacy of ATSN-101 in patients with Leber congenit
Slide 31: ATSN-101: Efficacy evaluation (FST)
ATSN-101: Efficacy evaluation of U.S. P1/2 clinical trial Efficacy: FST (full-field stimulus threshold) improvement In the high-dose group (1.0×1011 vg/eye), the response to light was significantly improved compared to that of the untreated group. The effect continued at the one-year point. Source:
Slide 32: ATSN-101: Safety evaluation of U.S. P1/2 clinical trial
ATSN-101: Safety evaluation of U.S. P1/2 clinical trial Safety: Treatment-Emergent Adverse Event (TEAE) cohort Total 1 2 3/4 5 Number of cases 15 3 3 6 3 Any TEAE 15 (100%) 3 (100%) 3 (100%) 6 (100%) 3 (100%) Any serious TEAE 2 (13%) 0 1 (33%) 0 1 (33%) 1 15 (100%) 3 (100%) 3 (100%) 6 (100%) 3 (100%
Slide 33: RGX-121/111 for Mucopolysaccharidosis Type II and I
RGX-121/111 for the treatment of Mucopolysaccharidosis Type II and Mucopolysaccharidosis Type I, respectively 33
Slide 34: RGX-121/111: Summary of expected indications
RGX-121/111：Summary of expected indications What is Mucopolysaccharidosis? Mucopolysaccharidoses (MPS) are a group of rare inherited metabolic diseases, classified within a larger group of disorders called lysosomal disorders, and involve the deficiency of enzymes that breakdown of mucopolysaccharid
Slide 35: Features of RGX-121
Features of RGX-121 Modality gene therapy Development stage rolling BLA (submission expected to be completed in 1Q of CY2025) Dosage and administration 2.9 x 1011 copies/g brain administered into CNS Dosage form frozen liquids in vials RGX-121 is an investigational gene therapy that is designed to u
Slide 36: RGX-121: P1/2/3 clinical study
RGX-121: P1/2/3 clinical study Number of cases Part1: 15 cases, Part2: 10 cases Eligible age 4 Months to 5 Years Trial design Open-label, single-arm, open-label study Trial sites 4 sites in the U.S., 1 site in Brazil Single, intracisternal (IC) administration. If the approach is difficult due to bon
Slide 37: RGX-121: Part 1 Study Design
RGX-121: P1/2/3 clinical study Part 1: Study Design The primary endpoint was safety at 24 weeks. Evaluation period of 104 weeks, followed by transition to long-term follow-up. Both patients receiving ERT (13 cases) and patients not receiving ERT (2 cases) were entered, and in the case of patients re
Slide 38: RGX-121: Part 1 Results
RGX-121: P1/2/3 clinical study Part 1: Results Neurodevelopmental Assessments Demonstrate Continued Skill Acquisition or Stability in the Majority of CAMPSIITE® Dose-Finding Participants ≧-2SD In the Neurodevelopmental Assessments of the Bayley Scales of Infant Development (BSID-III), patients with
Slide 39: RGX-121: Part 2 Study Design
RGX-121: P1/2/3 clinical study Part 2: Study Design • The primary efficacy endpoint of Part 2 is the proportion of patients at 16 weeks compared to baseline achieving a reduction in CSF HS D2S6 levels to at or below the upper limit detected in attenuated MPS patients(100 ng/ml)1. An immunosuppressiv
Slide 40: RGX-121: Part 2 Results
RGX-121: Clinical P1/2/3 study Part 2: Results S = Patients with severe condition A = Patients with attenuated condition N = Normal people Natural history data 16 weeks after treatment administration, the level of HS D2S6 in the CSF decreased by 86%, and primary endpoint was met: i.e. 8 of 10 cases,
Slide 41: Pipeline overview
Pipeline overview 41
Slide 42: NS-065/NCNP-01 (viltolarsen)
NS-065/NCNP-01 (viltolarsen) - Treatment for Duchenne muscular dystrophy - ・Japan : Launch Development Phase ・U.S. : Launch ・Global : P3 open-label extension study in progress Co-development : Origin National Center of Neurology and Psychiatry Development Nippon Shinyaku Mechanism of action Exon 53
Slide 43: NS-304 (selexipag)
NS-304 (selexipag) - Treatment for pulmonary hypertension, arteriosclerosis obliterans - Japan : P2b（ASO） Japan : Uptravi® tablets 0.2 mg and 0.4 mg for the additional Development Phase indication of pediatric pulmonary arterial hypertension (PAH) Uptravi® tablets for pediatric 0.05 mg approved and
Slide 44: CAP-1002 (deramiocel)
CAP-1002 (deramiocel) - Treatment for Duchenne muscular dystrophy - U.S. : P3 (Duchenne muscular dystrophy) Development Phase U.S. : BLA Filing (Duchenne muscular dystrophy cardiomyopathy) [Jan. 2022] Partnership for commercialization in U.S. Origin [Feb. 2023] Partnership for commercialization in J
Slide 45: RGX-121 (clemidsogene lanparvovec)
RGX-121（clemidsogene lanparvovec） - Treatment for Mucopolysaccharidosis Type Ⅱ - Development Phase U.S. : Rolling submission [Jan. 2025] Partnership for commercialization in U.S., Japan and other Origin Asian countries : REGENXBIO Inc. Development REGENXBIO Inc. Mechanism of action Iduronate-2-sulfa
Slide 46: ZX008 (fenfluramine hydrochloride)
ZX008 (fenfluramine hydrochloride) - Treatment for rare intractable epilepsy - Japan : Launch (Dravet syndrome) Development Phase Japan : Launch（Lennox-Gastaut syndrome) Japan：P3 (CDKL5 deficiency disorder) [Mar. 2019] Distribution partnership in Japan : UCB S.A. (former Origin Zogenix, Inc.) Develo
Slide 47: GA101 (obinutuzumab)
GA101 (obinutuzumab) - Treatment for lupus nephritis, pediatric nephrotic syndrome, extra renal lupus - Japan：P3（LN） Development Phase Global : P3（PNS） Japan：P3（ERL） [Nov. 2012] Origin Licensed-in from : Chugai Pharmaceutical Co., Ltd. Development Co-development : Chugai Pharmaceutical Co., Ltd. Mec
Slide 48: LY3527727 (pirtobrutinib)
LY3527727(pirtobrutinib) - Treatment for Mantle cell lymphoma, Chronic lymphocytic leukemia - ・Launch (for patients with relapsed or refractory mantle cell lymphoma who Development Phase are resistant or intolerant to other BTK inhibitors) ・ P3 (MCL and CLL) Origin [Mar. 2024] Alliance agreement in
Slide 49: NS-580
NS-580 - Treatment for endometriosis, Chronic prostatitis/Chronic pelvic pain syndrome - Japan : P2b (endometriosis) Temporarily suspended Development Phase Japan : P2a (CP/CPPS) Temporarily suspended Origin Nippon Shinyaku Development Nippon Shinyaku Mechanism of action Inhibition of membrane-assoc
Slide 50: NS-089/NCNP-02 (brogidirsen)
NS-089/NCNP-02（brogidirsen） - Treatment for Duchenne muscular dystrophy - Development Phase Global：P2 Co-development : Origin National Center of Neurology and Psychiatry Development Nippon Shinyaku Mechanism of action Exon 44 Skipping Indication Duchenne muscular dystrophy Dosage form Injection ・Imp
Slide 51: NS-229
NS-229 - Treatment for Eosinophilic granulomatosis with polyangiitis - Development Phase Global：P2 Origin Nippon Shinyaku Development Nippon Shinyaku Mechanism of action JAK1 inhibitor Indication eosinophilic granulomatosis with polyangiitis (EGPA) Dosage form Oral agent ・Potent and highly selective
Slide 52: NS-401 (tagraxofusp)
NS-401 (tagraxofusp) - Treatment for blastic plasmacytoid dendritic cell neoplasm - Development Phase Japan : P1/2 [Mar. 2021] Origin Licensed-in from: The Menarini Group Development Nippon Shinyaku Induction apoptosis of cells by inhibiting protein synthesis by Mechanism of action specifically targ
Slide 53: NS-050/NCNP-03
NS-050/NCNP-03 - Treatment for Duchenne muscular dystrophy - Development Phase Global：P1/2 Co-development : Origin National Center of Neurology and Psychiatry Development Nippon Shinyaku Mechanism of action Exon 50 Skipping Indication Duchenne muscular dystrophy Dosage form Injection ・Improvement in
Slide 54: ATSN-101
ATSN-101 - Treatment for GUCY2D-associated Leber congenital amaurosis - Development Phase US : P1/2 [Nov. 2024] Partnership for commercialization in U.S. Origin Development and sales license agreement in Japan : Atsena Therapeutics, Inc. Development Atsena Therapeutics, Inc. Mechanism of action GUCY
Slide 55: RGX-111
RGX-111 - Treatment for Mucopolysaccharidosis Type Ⅰ - Development Phase Global : P1/2 [Jan. 2025] Partnership for commercialization in U.S., Japan and other Origin Asian countries : REGENXBIO Inc. Development REGENXBIO Inc. Mechanism of action Alpha-L-iduronidase Gene therapy Indication Mucopolysac
Slide 56: NS-917 (radgocitabine)
NS-917 (radgocitabine) - Treatment for relapsed or refractory acute myeloid leukemia - Development Phase Japan : P1 [Mar. 2017] Origin Licensed-in from : Delta-Fly Pharma, Inc. Development Nippon Shinyaku Mechanism of action DNA strand-break by incorporating itself into DNA Indication relapsed or re
Slide 57: NS-025
NS-025 - Treatment for urological diseases - Development Phase Japan : P1 Origin Nippon Shinyaku Development Nippon Shinyaku Mechanism of action － Indication Urological diseases (to be determined) Dosage form Oral agent Feature － 57
Slide 58: NS-863
NS-863 - Treatment for cardiovascular diseases - Development Phase Japan : P1 Origin Nippon Shinyaku Development Nippon Shinyaku Mechanism of action － Indication Cardiovascular diseases (to be determined) Dosage form Oral agent Feature － 58
Slide 59: Safe Harbor Statement
Safe Harbor Statement • Materials and information provided during this presentation may contain so-called “forward-looking statements.” These statements are based on current expectations, forecasts and assumptions that are subject to risks and uncertainties which could cause actual outcomes and resu