Kyowa Kirin Co., Ltd. · TSE:4151
Kyowa Kirin — Investor Day (December 2023)
39 slides from Kyowa Kirin's investor day presentation, Dec 11, 2023
Slide 1: Kyowa Kirin R&D Meeting 2023
Kyowa Kirin R&D Meeting 2023 December 11, 2023 Takeyoshi Yamashita, Ph.D. Director of the Board, Senior Managing Executive officer and Chief Medical Officer Yoshifumi Torii, Ph.D. Executive Officer, Vice President, Head of R&D Division
Slide 2: Forward-looking statements disclaimer
This document contains certain forward-looking statements relating to such items as the company’s (including its domestic and overseas subsidiaries) forecasts, targets and plans. These forward- looking statements are based upon information available to the company at the present time and upon reason
Slide 3: Our Vision toward 2030
Provide pharmaceuticals for Vision unmet medical needs We are focused on developing medicines for diseases where there is a clear patient need for new options. We make full use of multiple therapeutic modalities, including Our Vision toward 2030 biotechnology such as antibody technology, and beyond,
Slide 4: Kyowa Kirin's Strengths
Research & Development Concept Technology x Biology x OI The Kyowa Kirin Group is aiming to Technology Disease Biology build a competitive technology platform by enhancing and We will continue to evolve our Continue to provide “Only-one combining its drug discovery antibody technology, while also va
Slide 5: The key drivers of our future growth
The key drivers of our future growth Global Strategic Products rocatinlimab (atopic dermatitis) KHK4951 nAMD Development Pipelines (Ph2 or later) rocatinlimab (asthma) KHK4951 DME Ph2 start schedule under consideration Scheduled to start within 2023 REGULGENTTM Early-Stage Pipelines (Ph1 or earlier)
Slide 6: Today's agenda
Today’s agenda ◼ Development Pipeline using REGULGENTTM - Our bispecific antibody technology ⚫ About REGULGENTTM ⚫ KK2260 ⚫ KK2269 ◼ Toward the Successful Creation and Delivery of Life-changing Value ⚫ KHK4951 (Ph1 study results and Ph2 studies overview) ⚫ Orchard Therapeutics plc (HSC-GT) 5 © Kyowa
Slide 7: Development Pipeline using REGULGENT
Development Pipeline using REGULGENTTM Our bispecific antibody technology ⚫ About REGULGENTTM ⚫ KK2260 ⚫ KK2269 6 © Kyowa Kirin Co., Ltd.
Slide 8: 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
Slide 9: Development Pipeline using REGULGENT
Development Pipeline using REGULGENTTM Our bispecific antibody technology ⚫ About REGULGENTTM ⚫ KK2260 ⚫ KK2269 8 © Kyowa Kirin Co., Ltd.
Slide 10: Relationship between cells and iron
Relationship between cells and iron TfR11 recycling Iron is an important element for cell growth Recycling endosome and survival ◼ DNA synthesis Ribonucleotide reductase - requires iron ions in the active center ◼ Energy generation Iron ion is required for ATP production via TCA cycle2 in mitochondr
Slide 11: Relationship between cancers and iron
Relationship between cancers and iron ◼ Many cancer types have an association with ◼ High expression of TfR1 in many cancer types iron which affects cancer growth and prognosis TfR1 expression of ESCC patient: Chan et al., ONCOLOGY REPORTS, 2014 Survival after surgery of ESCC patients: Wada et al.,
Slide 12: Anticancer effects and systemic side effects of iron depletion
Anticancer effects and systemic side effects of iron depletion Modified from: Yamasaki et al., N Engl J Med, 2011 ◼ Efficacy of Deferoxiamine, an Iron Chelator, in Hepatocellular Before Carcinoma Dosing Anticancer effect observed by iron depletion in cancer cells Two months after dosing ◼ However, s
Slide 13: KK2260: EGFR-TfR1 bispecific antibody
KK2260: EGFR-TfR1 bispecific antibody To avoid systemic side effects = selective iron depletion in cancer cells ⚫ No neutralizing activity when bound to TfR1 only or EGFR only ⚫ Cross-links TfR1 and EGFR to induce TfR1 degradation in lysosomes OFF EGFR binding domain ON EGFR TfR1 TfR1 binding Lysoso
Slide 14: KK2260: Drug Efficacy and Safety in Nonclinical Studies
KK2260: Drug Efficacy and Safety in Nonclinical Studies ◼ Efficacy: ESCC1 PDX2 model (EGFR+/TfR1+) ◼ Safety • 200 mg/kg of KK2260 was administered 2000 to cynomolgus monkeys once a week x 4 times Tumor volume [mm3] Vehicle 1500 → No serious toxicity, including skin toxicity3, was observed. Mild and
Slide 15: Development Pipeline using REGULGENT
Development Pipeline using REGULGENTTM Our bispecific antibody technology ⚫ About REGULGENTTM ⚫ KK2260 ⚫ KK2269 14 © Kyowa Kirin Co., Ltd.
Slide 16: About CD40 agonistic antibody
About CD40 agonistic antibody Modified from: Immunity, Volume 39, Issue 1, Cancer Immunity Cycle 2013, 1–10 ◼ Expectations 3. Antigen presentation 4. T-cell migration in lymph nodes and To cure cancer by inducing de novo priming of anti-tumor T and infiltration cells anti-tumor immunity in patients
Slide 17: KK2269: CD40-EpCAM bispecific antibody
KK2269: CD40-EpCAM* bispecific antibody Examples of EpCAM-high expressing tumors KK2269 Cancer cells Dendritic cells CD40 EpCAM Tumor-specific T cell Underline: elicitation and activation Cytotoxic T lymphocyte Cancer types to be evaluated in Ph1 ◼ Targets CD40 and EpCAM simultaneously, exerting CD4
Slide 18: KK2269: Dendritic cell activation
KK2269: CD40-EpCAM* bispecific antibody Examples of EpCAM-high expressing tumors KK2269 Cancer cells Dendritic cells CD40 EpCAM Tumor-specific T cell Underline: elicitation and activation Cytotoxic T lymphocyte Cancer types to be evaluated in Ph1 EpCAM(+) cancer cell Function as a CD40 Human moDC* a
Slide 19: KK2269: Efficacy and safety confirmed in non-clinical studies
KK2269: Efficacy and safety confirmed in non-clinical studies Survival rate 100 Control Control ◼ Efficacy (%) (%) KK2269 • KK2269 showed remarkable synergy with certain KK2269 DTX 80 chemotherapy Docetaxel survival KK2269+DTX KK2269 + Docetaxel • Characteristic delayed tumor regression free surviva
Slide 20: Full value of KK2269 in chemo combination
Full value of KK2269 in chemo combination 1. Chemo Evaluation of activation of dendritic 2. Tumor disruption（ICD*） cells in tumor IL-12 • Release of tumor antigens and cross presentation immunostimulants Th1/CTL activation 3. Accumulation of dendritic Vital co-stimulatory cells in tumors DC factors
Slide 21: Toward the Successful Creation and Delivery of Life-changing Value
Toward the Successful Creation and Delivery of Life-changing Value ⚫ KHK4951（Ph1 study results and Ph2 studies overview） ⚫ HSC-GT (Orchard Therapeutics plc) 20 © Kyowa Kirin Co., Ltd.
Slide 22: KHK4951: tivozanib eyedrop
KHK4951: tivozanib eyedrop ◼ Active ingredient - tivozanib: A small molecule VEGFR inhibitor discovered by Kyowa Kirin with high selectivity and potent activity ◼ Completed Ph1 study in patients with exudative neovascular age-related macular degeneration (nAMD) • Abnormal angiogenesis results in mac
Slide 23: Nano-crystallized formulation for delivery to posterior ocular tissues
Nano-crystallized formulation for delivery of active ingredients to the posterior ocular tissues Drug concentration in the posterior ocular tissue after topical instillation of tivozanib eye-drop to rats Anterior ocular tissue Posterior ocular tissue Concentration in posterior ocular tissue (ng/g) 5
Slide 24: Ph1 study
The 77 th annual congress of Japan clinical ophthalmology Ph1 study Tivozanib Primary objective Healthy volunteers in cohorts 1 and 2 eye drops Safety and tolerability (TEAEs) Inclusion criteria Cohort 1 R • Age ≥ 20 to < 50 years Single dose Follow-up period Other objectives 1:1 • Visual acuity ≥ 2
Slide 25: Ph1 study: Dosage regimen
The 77 th annual congress of Japan clinical ophthalmology Ph1 study: Dosage regimen Single dose Multiple doses (tid) for 21 days Cohort 1, HVs Cohort 2, HVs Cohort 3, nAMD patients Step 1: 0.5 w/v%, 1 drop Step 1: 0.5 w/v%, 1 drop Step 1: 0.5 w/v%, 1 drop Japanese, with NLO Japanese, with NLO Japane
Slide 26: Ph1 study: Safety
The 77 th annual congress of Japan clinical ophthalmology Ph1 study: Safety Tivozanib (tid), HVs Tivozanib (tid), nAMD patients Placebo Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 1 Step 2 Step 3 (tid), Jpn Jpn Jpn Jpn White Jpn Jpn Jpn Jpn nAMD Any TEAE or ocular AE in the study eye HVs HVs with
Slide 27: Ph1 study: Serum Drug Concentration
The 77 th annual congress of Japan clinical ophthalmology Ph1 study: Serum Drug Concentration * * Healthy volunteers • Mean serum concentrations of tivozanib increased in a dose-dependent manner. • No significant differences in serum pharmacokinetics were observed between HVs and nAMD patients. 26 ©
Slide 28: KHK4951 Ph1 study summary
The 77 th annual congress of Japan clinical ophthalmology KHK4951 Ph1 study summary • There were no serious AEs or AEs leading to discontinuation. Safety • There were no remarkable differences in its safety profiles between Japanese and White, and between HVs and nAMD patients. • Mean serum tivozani
Slide 29: Diabetic Macular Edema (DME)
Diabetic Macular Edema (DME) *Target indication for Ph2 study ◼ As a complication of diabetic retinopathy, high vitreous retina blood sugar causes damage to capillaries in the macula macula, resulting in edema of the macula and impairment of vision cornea ◼ VEGF contributes the development of the di
Slide 30: KHK4951 Ph2 study overview
第77回日本臨床眼科学会 Ph2試験 KHK4951 Ph2 study overview Locations • （For both studies）JP, US, AU, KR Study Completion (estimated) • （For both studies) 2026Q1 Enrollment (estimated) • nAMD 180, DME 150 • Reduction of 15 or more letters in BCVA (Best corrected visual acuity) as measured Primary Endpoint by ETDR
Slide 31: Toward the Successful Creation and Delivery of Life-changing Value
Toward the Successful Creation and Delivery of Life-changing Value ⚫ KHK4951（Ph1 study results and Ph2 studies overview） ⚫ HSC-GT (Orchard Therapeutics plc) 30 © Kyowa Kirin Co., Ltd.
Slide 32: Hematopoietic Stem Cell Gene Therapy (HSC-GT)
Hematopoietic Stem Cell Gene Therapy (HSC-GT) Therapeutic HSC gene Brain Monocyte / High area of focus Macrophage GI Granulocyte Other Areas for potential Organ future T cells Integration Systems expansion B cells NK cells Megakaryocyte Self-renewal Erythrocyte HSC-GT allows delivery of gene-modifie
Slide 33: Gene Therapy Manufacturing
Gene Therapy Manufacturing GMP Cell Product Manufacturing Platform Orchard Therapeutics Supply Chain Lentiviral Vector Drug Product Manufacturing (Cell Processing) Local Treatment of Patient Manufacturing Transport Collect cells from cells to START Isolate HSPCs blood or manufacturing bone marrow fa
Slide 34: Delivering Proteins to Brain
Delivering Proteins to Brain Potential to Treat Multi-System Neurometabolic Diseases via Cross-Correction Blood vessels Gene modified HSCs Migration across blood-brain barrier Distribution throughout brain Blood-brain barrier Supraphysiological Gene modified microglia cell expresses enzyme Defective
Slide 35: Libmeldy (OTL-200, atidarsagene autotemcel)
Libmeldy® (OTL-200, atidarsagene autotemcel) Expected timing of ◼ MLD (Metachromatic Leukodystrophy) Status Next Catalyst Catalyst ⚫ Fatal genetic CNS disorder Launched in Europe PDUFA: March 18, FDA approval ⚫ Rapid and irreversible loss of motor and cognitive function Filed in US 2024 ⚫ In its mos
Slide 36: Development Pipelines: OTL-203, OTL-201
Development Pipelines: OTL-203, OTL-201 OTL-203 OTL-201 ◼ Indication: MPS-IIIA 4 ◼ Indication: MPS-IH1 ⚫ Accumulation of substrate heparan sulfate leading to severe CNS ⚫ Multisystemic neurometabolic condition affecting cognition, degeneration w/ somatic manifestations growth and skeletal function ⚫
Slide 37: Expected Synergy
Expected Synergy Further Development as a Japan-Based Global Specialty Pharmaceutical Company ◼ To be a Japan-based Global Specialty Pharmaceutical Company providing life-changing value to high unmet medical needs in concert with our existing business through Crysvita and Poteligeo Reinforcement of
Slide 38: 2024 and beyond!
Innovative New Drug Creation by Kyowa Kirin Drug Discovery Technology KK2269 KK2260 KHK4951 (tivozanib eyedrop) 2024 and REGULGENTTM rocatinlimab (Bispecific antibody technology) beyond! (AMG 451/KHK4083) Approach to eyedrop formulation utilizing nanocrystallization HSC-GT (Orchard Therapeutics plc)
Slide 39: Gs yOwa KIRIN
Gs yOwa KIRIN