Slide 1: Summary of the 52-week interim data analysis of JR-171-101 extension study
Summary of the 52-week interim data analysis of the phase I/II, open label, multicenter, multinational (Japan, Brazil, US) extension study of JR-171-101 for the treatment of MPS I. (ClinicalTrials.gov identifier NCT04453085) October 4, 2023 Copyright © 2023 JCR Pharmaceuticals Co., Ltd. All rights r
Slide 2: 注意事項
注意事項 本日のミーティングは機関投資家・アナリストを対象に実施しております。 本資料中の開発見通し等の将来に関する記述は、当社が現在得ている情報をもとになされた当社の判断に基づくものであり、既知あるいは 未知のリスクや不確実な要素を含んでいます。実際の結果は、様々な要因によりこれら将来に関する記述内容とは大きく異なる可能性があ ることをご承知ください。そのような要因の例としては、経済情勢の悪化、法律・行政制度の変化、新製品上市の遅延、競合会社の価格・ 製品戦略による圧力、当社製品の販売力の低下、生産中断、当社の知的財産権に対する侵害、重大な訴訟における不利な判決等があ りますが、これらに限定
Slide 3: Forward-Looking Statement
FORWARD-LOOKING STATEMENT Today's meeting is for institutional investors and analysts. This presentation contains forward-looking statements that are subject to a number of risks and uncertainties, many of which are outside our control. All forward-looking statements regarding our plans, outlook, st
Slide 4: Mucopolysaccharidosis type I (MPS I) – Disease Introduction
Mucopolysaccharidosis type I (MPS I) – Disease Introduction JR-171 therapeutic hypothesis Main symptoms* Coarse facial Developmental delay, low features DQ, attention deficit, corneal clouding executive functioning hearing loss airway obstruction 30% 65% → respiratory failure heart valve disease → c
Slide 5: Lepunafusp alfa (JR-171) – Molecular Design and postulated MoA
Lepunafusp alfa (JR-171) – Molecular Design and postulated MoA Molecular Design Mechanism of Action JR-141 Uptake into the brain hIDS hIDS Postulated therapeutic benefit 1. Superior efficacy of on CNS disease compared to standard ERT. Anti-hTfR mAb Uptake into somatic organs M6PR Nucleus Endosome 2.
Slide 6: Objectives of the JR-171-101/102 Clinical Trial
Objectives of the JR-171-101/102 Clinical Trial Primary Objectives • To determine the safety and tolerability of JR-171 in patients with MPS I. Secondary Objectives • To evaluate the plasma PK of JR-171 after intravenous administration. • To explore the efficacy of JR-171 on central nervous and soma
Slide 7: Executive Summary of Interim Results
Executive Summary of Interim Results 52 Weeks Interim Results of Ph1/2 Study Safety Efficacy • No serious adverse drug reactions. • Stabilized organ volumes and walking ability in ERT- • All drug related IARs were manageable and reversible: exposed individuals ‒ All IARs were controlled by common me
Slide 8: Clinical Trial Outline of Study JR-171-101 and JR-171-102
Clinical Trial Outline of Study JR-171-101 and JR-171-102 Open label, multicenter, multinational trial to evaluate the safety, PKs and explore the efficacy for the treatment of MPS I Status: Completed w/o safety Primary Endpoints Part 1 concerns - Frequency and severity of adverse events - Anti-drug
Slide 9: Patient Demographics in the JR-171-102 Study
Patient Demographics in the JR-171-102 Study Overall Brazil Japan US Participants 14 10 2 2 Age range 6M-32Y 6M-32Y 4-14Y 16-17Y Male/Female 9/5 7/3 1/1 1/1 Treatment-naïve 1 1 0 0 MPS IS 1 1 0 0 MPS IHS 4 1 2 1 MPS IH 8 8 0 0 MPS I post HSCT 1 0 0 1 S：Scheie syndrome HS：Hurler-Scheie syndrome H：Hur
Slide 10: Assessment of Safety
Assessment of Safety Copyright © 2023 JCR Pharmaceuticals Co., Ltd. All rights reserved. JR-171_7
Slide 11: Summary of Adverse Events
Summary of Adverse Events JR-171-101/102 study (Part 2) 2.0 mg/kg (n=6) 4.0 mg/kg (n=8) Overall (n=14) n (%) events n (%) events n (%) events Adverse events 6 (100) 74 8 (100) 109 14 (100) 183 Serious adverse events 1 (16.7) 1 1 (12.5) 2 2 (14.3) 3 Adverse drug reactions 2 (33.3) 6 4 (50) 13 6 (42.9
Slide 12: Occurrence of IARs
Occurrence of IARs P02-01 Bars: treatment period : IARs P02-02 P02-03 2.0 mg/kg/wk P02-04 P02-05 Discontinuation P02-06 P04-01 P04-02 P04-03 (ERT naïve) P04-04 4.0 mg/kg/wk P04-05 P04-06 P04-07 P04-08 0 20 40 60 80 100 120 Treatment duration (weeks) Consistent with other ERTs, IARs appear to be less
Slide 13: Assessment of somatic Efficacy
Assessment of somatic Efficacy Copyright © 2023 JCR Pharmaceuticals Co., Ltd. All rights reserved. JR-171_10
Slide 14: Relative Changes in Serum/Urine Heparan Sulfate Levels
Relative Changes in Serum/Urine Heparan Sulfate Levels A Serum Heparan Sulfate B Urine Heparan Sulfate Naïve (4.0mg/kg) (n=1) Naïve (4.0mg/kg) (n=1) Mean±SD 40 2.0mg/kg (n=6) 40 2.0mg/kg (n=4) 20 4.0mg/kg (n=7) 4.0mg/kg (n=5) 20 Relative Change (%) Relative Change (%) 0 0 -20 -20 -40 -40 -60 -60 -80
Slide 15: Changes in Organ Volumes
Changes in Organ Volumes A Mean Changes in Liver Volume B Mean Changes in Spleen Volume Mean±SD 60 10 Naïve (4.0 mg/kg) (n=1) Naïve (4.0 mg/kg) (n=1) 9 50 2.0 mg/kg (n=6) 2.0 mg/kg (n=6) Spleen volume (mL/kg BW) Liver volume (mL/kg BW) 8 4.0 mg/kg (n=7) 4.0 mg/kg (n=7) 40 7 6 30 5 4 20 3 10 2 1 0 0
Slide 16: Changes in Six-Minute Walk Test
Changes in Six-Minute Walk Test 700 700 All Mean±SD Individual Six minute-walking distance (m) 600 600 32Y 17Y 500 500 12Y 400 14Y 400 300 300 16Y 200 200 10Y 2.0 mg/kg 100 100 4.0 mg/kg 0 0 BL 13 26 52 BL 13 26 52 week week • An increase in 6MWD was observed in 5 out of 6 evaluable subjects. • Nota
Slide 17: Summary of Assessment of somatic Efficacy
Summary of Assessment of somatic Efficacy • Stabilization or decrease in somatic biomarkers (urinary and serum heparan sulfate and dermatan sulfate (not shown)) and organ volumes indicate that JR-171 at either dose provides appropriate somatic disease control. JCR internal Data Copyright © 2023 JCR
Slide 18: Assessment of Exploratory Efficacy on Central Nervous Signs and Symptoms
Assessment of Exploratory Efficacy on Central Nervous Signs and Symptoms Copyright © 2023 JCR Pharmaceuticals Co., Ltd. All rights reserved. JR-171_15
Slide 19: Changes in Heparan Sulfate Levels in the Cerebrospinal Fluid
Changes in Heparan Sulfate Levels in the Cerebrospinal Fluid A All subjects B Individual subjects 8000 8000 2.0 mg/kg HS concentration in CSF (ng/mL) Mean±SD 4.0 mg/kg 7000 7000 6000 6000 5000 5000 4000 4000 3000 3000 2000 2000 1000 1000 0 0 BL 13 26 52 BL 13 26 52 week week • A significant reductio
Slide 20: Changes in Neurocognitive Function in Severe MPS I Subjects
Changes in Neurocognitive Function in Severe MPS I Subjects Measured using the Bayley Scales of Infant Development (BSID) A Changes in Age-Equivalent Score (in months) B Changes in Development Quotient at 52 Weeks at 52 Weeks compared to Baseline compared to Baseline 20 70 Severe untransplanted(≤ 4
Slide 21: Changes in Neurocognitive Function in Severe MPS I Subjects – Natural History
Changes in Neurocognitive Function in Severe MPS I Subjects - Comparison with Natural History of Severe non-Transplanted MPS I - Changes in Cognitive Domain of Development Quotient measured by BSID at 52 Weeks compared to Baseline 25 20 Absolute Change in DQ 15 10 5 1.8 0 -5 -0.4 -10 -15 -20 Subject
Slide 22: Changes in Neurocognitive Function in Attenuated MPS I Subjects
Changes in Neurocognitive Function in Attenuated MPS I Subjects Measured using various forms of the Wechsler Test (depending on age) Mean change full scale and in individual domains of Wechsler IQ Test from Baseline to Week 52 Absolute change in Score 30 20 FSIQ Full scale IQ GAI General ability ind
Slide 23: Narrative Reports – Entries in the Clinical Database
Narrative Reports – Entries in the Clinical Database Language Motor Vigor/Expression Other 0 0 1 Positive 7 7 5 7 7 7 7 no entries 8 Negative Number of Positive comments 10 24 9 23 Negative comments 0 1 0 0 Examples • Livelier conversations • Improved gait, balance, • More active • Better sleep • Co
Slide 24: Narrative Report US-01-01
Narrative Report US-01-01 Background: • 16-years old female post HSCT with baseline DQ of 21.5 (severe); cognitive development age ~ 42 months • Conducted BSID-III at baseline but was unable to perform Wechsler test “School teacher notes more energy; • DQ 21.5 joined class with soccer. Typed full le
Slide 25: Summary of Exploratory Efficacy on CNS Signs and Symptoms
Summary of Exploratory Efficacy on CNS Signs and Symptoms • A significant reduction of heparan sulfate substrate in the cerebrospinal fluid was observed in all subjects. • Despite a low number of subjects enrolled, signals of neurological benefit were observed in subjects with severe and with attenu
Slide 26: Overall Conclusions from 52-Week Data of the JR-171-101 Study
Overall Conclusions from 52-Week Data of the JR-171-101 Study • The overall safety/tolerability profile of JR-171 (lepunafusp alfa) indicates that it is suited for the long-term treatment of individuals with MPS I. • Given the small sample size and limited follow-up, interim analysis indicate that J
Slide 27: Copyright © 2023 JCR Pharmaceuticals Co., Ltd. All rights reserved.
Copyright © 2023 JCR Pharmaceuticals Co., Ltd. All rights reserved.
Slide 28: Appendix
Appendix Copyright © 2023 JCR Pharmaceuticals Co., Ltd. All rights reserved.
Slide 29: MPS (Mucopolysaccharidosis)
MPS (Mucopolysaccharidosis） ribosomes mitochondria rough-surfaced MPS is a group of LSD in which mucopolysaccharides endoplasmic reticulum centrosome such as dermatan sulfate (DS) and heparan sulfate (HS) accumulate. cell nucleus smooth-surfaced endoplasmic reticulum Accumulation of mucopolysacchari
Slide 30: Unmet Need and Value Proposition of JR-171
Unmet Need and Value Proposition of JR-171 Attenuated MPS I Scheie Disease Stable DQ, organomegaly, cardiac, (5%) presentation pulmonary, orthopedic burden Deficiencies in attention, short term Unmet medical memory, attention, executive need (neurol.) Hurler- functioning Scheie (25%) MPS I untranspl
Slide 31: MPS I – Disease Introduction
MPS I – Disease Introduction MPS I is the only LSD in which hematopoietic stem cell transplantation is an established SoC for the severe form of the disease. Hurler- Hurler Scheie Hurler Scheie (>60%) (5%) (>65%) (25%) Attenuated MPS I Severe MPS I Disease Stable DQ, organomegaly, cardiac, Severe co