Kyowa Kirin Co., Ltd. · TSE:4151

Kyowa Kirin — Technical Presentation (September 2024)

39 slides from Kyowa Kirin's technical presentation, Sep 26, 2024

  1. Slide 1: Kyowa Kirin R&D Meeting 2024

    Kyowa Kirin R&D Meeting 2024 September 26th, 2024 Director of the Board, Senior Managing Executive officer and Chief Medical Officer Takeyoshi Yamashita, Ph.D.

  2. Slide 2: Our Vision toward 2030

    Our Vision toward 2030 Provide pharmaceuticals for unmet medical needs We are focused on developing medicines for diseases where there is a Our Vision toward 2030 clear patient need for new options. We make full use of multiple therapeutic modalities, including biotechnology Kyowa Kirin will realize

  3. Slide 3: Story for Vision 2030

    Story for Vision 2030 Strategies for creating and delivering life-changing value Disease Science Value Global deployment of delivery on products developed by Focus disease areas: bone & mineral, intractable taking full advantage of our own hematological diseases/hemato oncology, and rare diseases th

  4. Slide 4: Research and Development Strategy Image Based on Story for Vision 2030

    Research and Development Strategy Image Based on Story for Vision 2030 Assets in focus disease Disease Science: Focus disease areas ADC areas KK2845 ◼ Bone & Mineral HSC-GT ◼ Intractable hematological diseases/hemato oncology Lenmeldy/Libmeldy KK8123 ◼ Rare diseases HSC-GT Explore UMN, causes and me

  5. Slide 5: Today's Agenda

    Today’s Agenda ◆ Rocatinlimab — ROCKET-Horizon Results and T-cell rebalance ◆ KK2845 ― Kyowa Kirin’s First ADC Pipeline ◆ REGULGENTTM ― Proprietary Bispecific Antibody Technology and Its Characteristics ◆ HSC-GT Products ― Latest Conference Presentation Data 5 © Kyowa Kirin Co., Ltd.

  6. Slide 6: Rocatinlimab

    Rocatinlimab 6 © Kyowa Kirin Co., Ltd.

  7. Slide 7: Rocatinlimab - ongoing Clinical Trials

    Rocatinlimab - ongoing Clinical Trials HORIZON: placebo-controlled monotherapy rocatinlimab (N = 726) IGNITE: placebo-controlled monotherapy evaluating two rocatinlimab doses (N = 769) Adult SHUTTLE: placebo-controlled trial evaluating two rocatinlimab doses with topical therapy (N = 746) Moderate t

  8. Slide 8: ROCKET HORIZON Study design

    ROCKET HORIZON Study design Monotherapy Treatment (24 Weeks) 20210146 N = 543 Rocatinlimab Dose 1 Q4W Long-term Randomization + loading dose at W2 Maintenance Trial Screening N = 726 (3:1) N = 183 Placebo Q4W + loading dose at W2 Safety Follow-Up Week 0 Week 2 Week 24 (Baseline) (Loading Dose) (Prim

  9. Slide 9: ROCKET HORIZON: Summary of Results

    ROCKET HORIZON: Summary of Results ◼ Co-primary endpoints were achieved ⚫ vIGA-ADTM 0/11 with a ≥ 2-point reduction from baseline: Ex-US rocatinlimab 19.3% vs. Placebo 6.6% (12.8% difference, p<0.001) ⚫ EASI-752： Ex-US For US rocatinlimab 32.8% vs. Placebo 13.7% (19.1% difference, p<0.001) ⚫ rIGA 0/

  10. Slide 10: Critical Role of OX40 Signaling in T-Cell Driven Inflammation and AD Pathogenesis

    Critical Role of OX40 Signaling in Orchestrating T-Cell Driven Inflammation and AD Pathogenesis Langerhans cells are activated From 2023 AAD annual Meeting 2023 upon encounter with antigens 17-21 March 2023 that penetrate skin and express OX40L1-3 • Inflammation • Epidermal dysfunction Following TCR

  11. Slide 11: OX40 Signaling induces T-cell imbalance

    OX40 Signaling induces T-cell imbalance From 2023 AAD annual Meeting 2023 17-21 March 2023 (Modified) TH2 cell : Cytokines OX40L MHC OX40 Resting T cell (OX40- T cell) receptor expression TCR Naïve T cell Effector Memory T cell - Amplification of pathogenic T cell number and activity > through OX40

  12. Slide 12: Rocatinlimab Rebalances T-cells by Targeting OX40 Receptor

    Rocatinlimab Rebalances T-cells by Targeting OX40 Receptor • T-cell imbalance is a root cause of inflammatory disease • Atopic dermatitis is driven in part by the proliferation of pathogenic T-cells • Rocatinlimab has the potential to inhibit and reduce pathogenic T-cells across heterogeneous patien

  13. Slide 13: ROCKET program – Future Plans

    ROCKET program – Future Plans The results of the HORIZON trial introduced today are the first of eight pivotal study readouts in the ROCKET program We will continue this program to further our understanding of the profile of rocatinlimab 13 © Kyowa Kirin Co., Ltd.

  14. Slide 14: KK2845

    KK2845 14 © Kyowa Kirin Co., Ltd.

  15. Slide 15: Overview of AML and ADC Development Status

    Overview of Acute Myeloid Leukemia (AML) and ADC Development Status AML - Disease Overview • Hematological malignancy characterized by the abnormal proliferation of immature blood cells (blasts) in the bone marrow, suppressing the production of normal blood cells. • Challenges in Current Treatments:

  16. Slide 16: KK2845 – Development History of ADC for r/r AML

    KK2845 – Development History of ADC for r/r AML Galectin-9 (TIM-3 Ligand) Leukemic stem cells (LSC) TIM-3 • Conducted screening for novel therapeutic TIM-3(+) target molecules in collaboration with Kyushu University and identified TIM-3. • TIM-3 is expressed on AML LSCs and blast cells but not on no

  17. Slide 17: KK2845 - Overview

    KK2845 - Overview Green : KK2845-Alexa488 Red : Lysosome Internalization into cells Blue : Nuclear On ice 37℃-2h SG3199 Anti-TIM-3 antibody Note: The arrows indicate where KK2845 merges with lysosomes • Target Molecule : TIM-3 - Aiming to avoid myelosuppression • Payload : SG3199 - the PBD molecule

  18. Slide 18: Evaluation of anti-cellular activity against primary AML cells and normal bone marrow cells

    Evaluation of anti-cellular activity against primary AML cells and normal bone marrow cells KK2845 or CD33-ADC 120 High efficacy against primary AML cells 100 Cell count [%]* KK2845 80 Normal CD34+ Bone marrow CD34+ bone marrow cells derived from cells derived from 60 AML patients healthy donors CD3

  19. Slide 19: In vivo Anti-tumor Activity Evaluation

    In vivo Anti-tumor Activity Evaluation AML Cell Line CMK11-5 (TIM-3 positive) Mouse Model AML Cell Line Kasumi-3 (TIM-3 positive) Mouse Model 500 Non-treatment Tumor volume (mm3) *: p<0.05 450 Non-treatment 400 Venetoclax 350 +Azacitidine Control-ADC 300 250 200 0.25 150 KK2845 100 KK2845 50 Days 0.

  20. Slide 20: ADC Research and Development Strategy

    ADC Research and Development Strategy Creation of new drugs in Intractable hematological diseases/hemato oncology through Kyowa Kirin’s antibody technologies combined with ADC technologies Target Antigen Biology Translational Research # Current status & Plan KK2845 2024 Q3 P1 Initiation Antibody Non

  21. Slide 21: REGULGENT

    REGULGENTTM 21 © Kyowa Kirin Co., Ltd.

  22. Slide 22: Significance of Bispecific Antibody Technology Development

    Significance of Bispecific Antibody Technology Development Limitations of conventional monoclonal antibodies have been noted ⚫ Depletion of target antigens ⚫ Exposure of limitations in efficacy and resistance ⚫ Difficulty in acting on multiple factors ⚫ Limitations in target selectivity and avoidanc

  23. Slide 23: Challenges of Bispecific Antibodies: Physical properties and productivity

    Challenges of Bispecific Antibodies: Physical properties and productivity Desired Undesired Mispairing Physical properties and productivity deteriorate due to L-chain mispairing Since L-chain is common (one type), H-chain—L-chain mispairing does not occur 23 © Kyowa Kirin Co., Ltd. REGULGENTTM

  24. Slide 24: About REGULGENT

    About REGULGENTTM General characteristics • Able to perform actions that IgG cannot by acting on two types of antigens* of bispecific antibodies • Composed of a combination of non-common L-chain antibodies or by utilizing antibody-like molecules * e.g., cross-linking of two types of cells or molecul

  25. Slide 25: Productivity of REGULGENT

    Productivity of REGULGENTTM T : TRAIL-R2 Transient expression using ExpiCHO-STM cells P : PSMA Stable expression using CHO cells (day 8 post-transfection) Titer（mg/L) P IgG T/P REGULGENT 1800 T/P REGULGENT(N-term) (N-term) P/T REGULGENT (C-term) 1600 1400 T/P REGULGENT (C-term) Titer (mg/L) 1200 P/T

  26. Slide 26: Physical Properties and Stability of REGULGENT

    Physical Properties and Stability of REGULGENT HMWS High-molecular-weight species Stored for one month at 4, 25, and 40°C, and the increase in HMWS (aggregates) and LMWS Low-molecular-weight species LMWS (degradation products) was evaluated by size exclusion chromatography HMWS increase LMWS increas

  27. Slide 27: REGULGENT Technology Pipelines

    REGULGENT Technology Pipelines EGFR binding site CD40 binding site • Disease under development Advanced or metastatic solid tumors • Development status EpCAM Phase 1 binding site TfR1 binding site We will continue to create new pipelines that leverage the KK2260 KK2269 characteristics of this N-term

  28. Slide 28: HSC-GT

    HSC-GT ⚫ HSC-GT MoA ⚫ Lenmeldy/Libmeldy ⚫ OTL-203 (Registrational study) ⚫ OTL-201 (PoC study) 28 © Kyowa Kirin Co., Ltd.

  29. Slide 29: HSC-GT: Enabling localized delivery of therapeutic proteins and enzymes to the CNS

    HSC-GT: Enabling localized delivery of therapeutic proteins and enzymes to the CNS to treat multi-system neurometabolic diseases 5. 1. Gene-correct HSPC cell infusion collection 2. CD34+ HSPC selection 4. Busulfan conditioning 3. Transduction, cryopreservation, and QC testing 29 © Kyowa Kirin Co., L

  30. Slide 30: Metachromatic Leukodystrophy (MLD): A devastating genetic disease

    Lenmeldy / Libmeldy Metachromatic Leukodystrophy (MLD): A devastating genetic disease 30 © Kyowa Kirin Co., Ltd.

  31. Slide 31: Results in Pre-Symptomatic Late Infantile (PSLI) patients

    Lenmeldy / Libmeldy Results in Pre-Symptomatic Late Infantile (PSLI) patients ARSA Activity in CSF Brain MRI Total Score Cognitive Performance Age Equivalent Motor and survival outcomes With extended follow-up (median 6.66 yrs, max 12.19 yrs) Lenmeldy/Libmeldy treatment: - Preserves cognitive functi

  32. Slide 32: OTL-203 – MPS-IH (Hurler Syndrome) disease background

    OTL-203 OTL-203 – MPS-IH (Hurler Syndrome) disease background MPS-IH - Disease snapshot • Multisystemic neurometabolic condition affecting cognition, growth and skeletal function • Diagnosed during first 2 years of life; life-expectancy up to 10 yrs. • Current standard of care: Allogeneic HSCT and/o

  33. Slide 33: PoC study results: Biochemical and early skeletal outcomes

    OTL-203 PoC study results: Biochemical and early skeletal outcomes Biochemical outcome after GT Standing & sitting kyphosis after GT Auxological parameters after GT [Short stature defined as height -2 SDS] 33 © Kyowa Kirin Co., Ltd. 2024 ASGCT Annual Meeting

  34. Slide 34: OTL-201 – MPS-IIIA (Sanfilippo syndrome type A)

    OTL-201 OTL-201 – MPS-IIIA (Sanfilippo syndrome type A) Disease snapshot • Sanfilippo syndrome type A; pathogenic variants in SGSH gene • Accumulation of substrate heparan sulfate leading to severe CNS degeneration w/ some somatic manifestations • Severe phenotype development slows from 3 years of a

  35. Slide 35: Summary of early biochemical and clinical outcomes

    OTL-201 Summary of early biochemical and clinical outcomes SGSH activity Heparan sulphate Early follow up in trial patients - Gain of skills after investigational medicinal product delivery in 4 out of 5 patients - Developmental gains not seen in untreated MPS-IIIA, e.g., acquisition of speech (alth

  36. Slide 36: Summary

    Summary 36 © Kyowa Kirin Co., Ltd.

  37. Slide 37: Research and Development Strategy Image Based on Story for Vision 2030

    Research and Development Strategy Image Based on Story for Vision 2030 Assets in focus disease Disease Science: Focus disease areas ADC areas KK2845 ◼ Bone & Mineral HSC-GT ◼ Intractable hematological diseases/hemato oncology Lenmeldy/Libmeldy KK8123 ◼ Rare diseases HSC-GT Explore UMN, causes and me

  38. Slide 38: Story for Vision 2030

    Story for Vision 2030 Strategies for creating and delivering life-changing value Disease Science Value Global deployment of delivery on products developed by Focus disease areas: bone & mineral, intractable taking full advantage of our own hematological diseases/hemato oncology, and rare diseases th

  39. Slide 39: Kyowa Kirin

    CsyOWa KIRIN

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