Slide 1: FY2025 R&D Meeting
FY2025 R＆D Meeting Keiichi Kuwano Director, Research & Development March 2, 2026 Nippon Shinyaku Co., Ltd.
Slide 2: Our Drug Discovery
Our Drug Discovery • We select the most appropriate modality for intractable and rare diseases from small molecules, nucleic acids, and gene therapies. • Many intractable and rare diseases are hereditary disorders, and these three modalities can target the causative genes. • Differentiation by imple
Slide 3: Focus Areas
Focus Areas 3
Slide 4: Our Focus Areas
Our Focus Areas Jaypirca® Uptravi® Erleada® MonoVer® r/r-MCL PAH 2016 Prostate cancer Iron deficiency r/r-CLL CTEPH 2021 2019 anemia Main Products 2025 Pediatric PAH 2025 2023 (Indications, Year of launch) Vyxeos® Viltepso® High-risk AML DMD 2024 2020 NS-401 CAP-1002 Main pipeline LY3527727 NS-863 N
Slide 5: Intractable and Rare Diseases
Intractable and Rare Diseases 85% of our development pipeline targets intractable or rare diseases. • The average ratio of intractable and rare diseases is 28% among 69 companies with sales over 100 billion yen and more than 10 products under development. • Nippon Shinyaku’s ratio is 85%, ranked at
Slide 6: Why Rare Diseases?
Why Rare Diseases? Success rates in development for rare diseases are relatively high • Probability of success from P1 to approval is about 3x higher than for chronic diseases. • Depending on requirements, regulatory pathways for Accelerated Approval may be available. Source: "Clinical Development S
Slide 7: Our Pipeline and Disease Areas
Our Pipeline and Disease Areas Disease area Development pipeline Hematology NS-401, LY3527727, NS-917 Immunology GA101, NS-229 Neuromuscular ZX008, CAP-1002, NS-089, NS-035, NS-050, NS-051 Pulmonary hypertension (PH) NS-863, NS-421 Congenital RGX-121, RGX-111 Specialty metabolism Ophthalmology ATSN-
Slide 8: Modalities
Modalities 8
Slide 9: Types of Modalities
Types of Modalities We are advancing our research and development activities centered on the following three core modalities. Small Nucleic Gene Molecules Acid Therapies Nippon Shinyaku leverages three modalities capable of acting on genes, with strength in selecting the optimal modality for disease
Slide 10: Small Molecules: Current Status and Strategy
Small Molecules: Current Status and Strategy • Although modalities are diversifying, small-molecule drugs are expected to remain at the Current Status center of drug discovery in the future. • Advances in AI and protein conformational analysis will enable drug discovery even for targets that are dif
Slide 11: Nucleic Acid Drugs: Current Status and Strategy
Nucleic Acid Drugs: Current Status and Strategy Current Patent competition for nucleic acid drugs is intensifying, and securing in-house patents is an Status • important issue. • Limited therapeutic effect due to lack of tissue transferability Potential for patent acquisition: Application of express
Slide 12: Modality Mechanisms
Modality Mechanisms DNA mRNA Protein Gene Gene expression modulation Gene expression supplementation RNA cleavage modulation Gene Nucleic Small Therapies Acid Molecules 12
Slide 13: Open Innovation
Open Innovation 13
Slide 14: Open Innovation in Progress
Open Innovation in Progress • Search for novel disease-causing genes Target Search • Disease mechanism elucidation by AI • Gene expression enhancing nucleic acids targeting loss-of- Modality Technology function diseases • RNA-targeted small molecules for genetic diseases • Acquisition of innovative
Slide 15: Strategic Alliance with Boston Children's Hospital (BCH)
Strategic Alliance with Boston Children's Hospital (BCH) The No.1 children's hospital in the U.S. • World-class medical institution with outstanding clinical and research achievements • 3,000 researchers and 3,000 peer-reviewed papers per year Affiliated with Harvard Medical School • A center for cu
Slide 16: Pipeline
Pipeline 16
Slide 17: Pipeline (1/2)
Pipeline (1/2) Code No. Stage Origin Indications Schedule Country ID# (Generic name) Co-development with ― Japan jRCT2080224893 Launch NS-065/NCNP-01 National Center of Neurology Duchenne muscular dystrophy P3 (viltolarsen) ― U.S. NCT04060199 and Psychiatry Preparation for NS-401 In-license blastic
Slide 18: Pipeline (2/2)
Pipeline (2/2) Code No. Stage Origin Indications Schedule Country ID# (Generic name) endometriosis Temporarily suspended Japan jRCT2031210685 NS-580 In-house chronic prostatitis/ （friluglanstat） Temporarily suspended Japan jRCT2031230134 chronic pelvic pain syndrome Co-development with Japan jRCT204
Slide 19: NS-863: PAH and PH-ILD
NS-863 PAH (pulmonary arterial hypertension) PH-ILD (pulmonary hypertension associated with interstitial lung disease) 19
Slide 20: Our Product Line for Pulmonary Hypertension (PH)
Our Product Line for Pulmonary Hypertension (PH) Approved in 2009 Approved in 2015 Approved in 2016 tadalafil macitentan selexipag (Adcirca®) (Opsumit®) (Uptravi®) O O S Br N NH H N N N O O O hydrolysis O N O S N O N N N N H N Br Phosphodiesterase 5 Endothelin receptor PGI 2 receptor NS-304 (prodrug
Slide 21: Vascular Lesions in Pulmonary Hypertension (PH)
Vascular Lesions in Pulmonary Hypertension (PH) Pulmonary hypertension (PH) involves pulmonary artery spasm or organic stenosis. Spasm of the pulmonary arteries Inhibition of Vasodilators vasoconstrictors Endothelin receptor antagonists Supplementation of PDE5 inhibitors vasodilatory factors PGI2 re
Slide 22: Positioning in pulmonary hypertension (PH) treatment
Positioning in pulmonary hypertension (PH) treatment Oral administration selexipag Vascular remodeling Endothelin receptor antagonist NS-863 PDE5 inhibitor (PDGFR inhibitor) sGC stimulator improvement Vasodilation seralutinib (Inhaled PDGFR inhibitor) Currently in P3 PGI analog (Intravenous / Subcut
Slide 23: Unmet Medical Needs in Pulmonary Hypertension (PH)
Unmet Medical Needs in Pulmonary Hypertension (PH) PAH • Overall survival has been improving with existing therapies, but the median is still less than 10 years • Non-oral PGI2 is used in severe cases, significantly reducing quality of life Unmet Medical Needs: Organic stenosis Improved therapeutic
Slide 24: NS-863: Summary
NS-863: Summary PAH (pulmonary arterial hypertension) Indications PH-ILD (pulmonary hypertension associated with interstitial lung disease) Selective inhibition of platelet-derived growth factor Mechanism of action receptor (PDGFR) Form of In-house development development Dosage form Oral • Unlike p
Slide 25: NS-863: Non-clinical study in SuHx-induced PAH Rat Model
NS-863: Non-clinical study in SuHx-induced PAH Rat Model Sugen5416 0 1 2 3 4 5 6 7 8 wk Slc:SD, , 6w Hypoxia Normoxia ・・・・ Efficacy PAH induction Randomization Administration evaluation Right ventricular hypertrophy Occlusive lesions Each point represents the mean ± S.E.M. of 6-8 rats. ## Each point
Slide 26: NS-863: Non-clinical study in SuHx-induced PAH Rat Model
NS-863: Non-clinical study in SuHx-induced PAH Rat Model Sugen5416 0 1 2 3 4 5 6 7 8 wk Slc:SD, , 6w Hypoxia Normoxia ・・・・ Efficacy and Red blood cell PAH induction Randomization Administration evaluation Right ventricular systolic pressure（RVSP） Red blood cell (RBC) number Each point represents the
Slide 27: NS-863: Global P2 Study Design
NS-863: Global P2 Study Design 24 weeks Efficacy and safety evaluation NS-863 High-dose group Randomization Screening NS-863 Low-dose group Placebo group NS863A-P2-01 NS863B-P2-01 Target patients PAH patients PH-ILD patients Number of participants 135 177 Pulmonary vascular resistance Pulmonary vasc
Slide 28: NS-035: Fukuyama Congenital Muscular Dystrophy (FCMD)
NS-035 Fukuyama Congenital Muscular Dystrophy (FCMD) 28
Slide 29: NS-035: Fukuyama Congenital Muscular Dystrophy (FCMD)
NS-035: Fukuyama Congenital Muscular Dystrophy (FCMD) Muscle cells in FCMD patients are Characteristics smaller than normal and have gaps between them. • Congenital muscular dystrophy Normal FCMD (1,000-2,000 patients in Japan) • Hereditary disease whose patients are predominantly Japanese • Muscle
Slide 30: Pathogenesis: Abnormalities of fukutin
Pathogenesis: Abnormalities of fukutin Basement membrane alpha- Laminin dystroglycan Glycosylation Membrane Fukutin NS-065 Cytoplasm NS-089 Abnormalities Abnormal Failure to α-DG with no Vulnerable in the fukutin fukutin fix muscle glycosylation Muscle cells gene protein cells 30
Slide 31: NS-035: Therapeutic Mechanism
NS-035: Therapeutic Mechanism By inhibiting exon trapping occurring in fukutin mRNA precursors, we aim to restore normal fukutin expression and improve muscle function through the recovery of α-dystroglycan (α-DG) glycan chains. fukutin Pre-mRNA fukutin mRNA splicing translation Normal Normal fukuti
Slide 32: NS-035: P2 Study (Japan)
NS-035: P2 Study (Japan) Study design Multi-center, parallel-group/single-group Target patients Typical FCMD patients between 5 and 9 years of age Number of participants 12 or more cases Intravenous infusion Double-blind period • NS-035 group: NS-035 (40 mg/kg) and D-mannitol (500 mg/kg) once a week
Slide 33: Product Life Cycle Management (PLCM) Initiatives: NS-304
Product Life Cycle Management (PLCM) Initiatives NS-304 (selexipag) for the treatment of arteriosclerosis obliterans 33
Slide 34: NS-304: Arteriosclerosis obliterans (ASO)
NS-304: Arteriosclerosis obliterans (ASO) ASO is a disease in which blood vessels in the legs become narrowed or occluded due to atherosclerosis. Treatment (Guideline on the Management of Peripheral Arterial Disease1) 1. Exercise: Improvement of QOL and symptoms of intermittent claudication 2. Drug
Slide 35: NS-304: Overview
NS-304: Overview Generic name selexipag Proprietary name Uptravi Structural formula Mechanism of action Prostacyclin (PGI2 ) receptor agonist Origin In-house Dosage form Film-coated tablet Uptravi® Tablets 1) Pulmonary arterial hypertension (PAH) Indications 2) Chronic thromboembolic pulmonary hyper
Slide 36: NS-304 for ASO
NS-304 for ASO Department/Clinical Cardiovascular Surgery, Cardiology, Internal Medicine, Orthopedics, Specialty Diabetes/Metabolism/Endocrinology Origin In-house Dosage form Tablet Improvement of intermittent claudication associated with arteriosclerosis Indication obliterans (ASO) Oral administrat
Slide 37: NS-304: P3 Study for ASO (Japan)
NS-304: P3 Study for ASO (Japan) P3 study has started after favorable results of P2 study Study design Randomized, double-blind, placebo control, parallel assignment Patients with intermittent claudication associated with Target patients arteriosclerosis obliterans (ASO) Number of participants 194 c
Slide 38: Closing Summary
Closing Summary Nippon Shinyaku advances highly distinctive research through unique combinations of diseases, mechanisms of action, and modalities, creating a series of distinctive and competitive seeds. Focus Diseases Mechanisms of Action Our Approaches to Drug Discovery Modalities 38
Slide 39: 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