BrightPath Biotherapeutics Co.Ltd. · TSE:4594
BrightPath Biotherapeutics Co.Ltd — Investor Presentation (August 2021)
42 slides from BrightPath Biotherapeutics Co.Ltd's investor presentation, August 2021
Slide 1: Corporate Presentation
Corporate Presentation August 2021 Listed on Tokyo Stock Exchange (Mothers) Code: 4594
Slide 2: Disclaimer
Disclaimer The material that follows is a presentation of general background information about BrightPath Biotherapeutics Co., Ltd. (“BrightPath”) as of the date of this presentation. This material prepared solely for information purpose and is not to be construed as a solicitation or an offer to bu
Slide 3: Pipeline of BrightPath
== Pipeline of BrightPath BrightPath_ Biotherapeutics
Slide 4: Development Focus
Development Focus Cancer immunotherapeutics as a main growth driver of pharmaceuticals Cancer Immunotherapeutics ($94.7bn) CAGR 20.2% source : EvaluatePharma, July 2020 3
Slide 5: Approved Cancer Immunotherapeutics
Approved Cancer Immunotherapeutics Increasing numbers of immunotherapeutics have been approved globally, with the revenues of the marketed products forecast to reach $50bn (2024e) Enhancement Immunity Cycle and of activation Approved Immunotherapeutics ( ) : estimated sales for 2024, EvaluatePharm
Slide 6: BrightPath Pipeline
BrightPath Pipeline Focused on cancer immunotherapies Multiple modalities (vaccine, antibody, cell therapy) Clinical Stage 4 Adoptive cell transfer T cell 5 iPS-NKT (Investigator-initiated) BP2301 (HER2 CAR-T) 3 Enhancement 6 of antigen- T cell presentation Cancer antigen BP1401 Cancer cell TLR9
Slide 7: Pipeline
_Pipeline products ges Cancertype _—_ Discovery Pre. al Phase1 Phase2 Cancer vaccines GRN-1201 Tumor associated antigens © NSCLC Melanoma SCT BP1101 Neoantigen Tr BP1209 Neoantigen + Delivery rss) BP1401 TLR9 agonist Cr si—isSSCS@YS Cells iPS-NKT iPS cell-derived iNKT cells | HNSCC D> BP2301 HER2 CA
Slide 8: Near-term Events
Near-term Events FY2020 FY2021 FY2022 Cancer vaccines GRN-1201 Tumor associated antigens P2 Stage 1 Read-out BP1101 Neoantigen FY2021 4Q ESMO 2021 BP1209 Neoantigen+Delivery 1005P ”A new platform of personalized neoantigen cancer vaccines directed by BP1401 TLR9 agonist checkpoint inhibitor antibodi
Slide 9: GRN-1201
GRN-1201 Cancer vaccine comprised of four TAAs induces cytotoxic T cell to eradicate cancer cells Combination with immune checkpoint blockade antibodies increases antitumor effects 4 T cell 5 3 6 T cell Cancer antigen Antigen = Marker of Cancer Vaccine- Vaccine- Cancer cell Cancer cell induced C
Slide 10: GRN-1201 (cont’d)
GRN-1201 (cont’d) Address unmet medical needs in NSCLC First-line therapy PD-L1 expression ≧50％ GRN-1201 added to first-line pembrolizumab therapy to increase responders Anti-PD-1 PD-L1 expression 22% Not effective in 55% ≧50％ or not est. # of pts: 71,000 (US+ EU+ JP, 2025) ＊ 52% PD-L1 expression
Slide 11: GRN-1201 (cont’d)
GRN-1201 (cont’d) Ongoing Phase 2 trial of GRN-1201 in addition to pembrolizumab as first- line NSCLC therapy A Pilot, Open-Label, Multi-Center, Multi-Dose Study of GRN-1201 Added to Study title Pembrolizumab in Subjects with Non-Small Cell Lung Cancer with High PD-L1 Expression US clinical trial
Slide 12: GRN-1201 (cont’d)
GRN-1201 (cont’d) Preliminary analysis in the initial stage of Phase 2 supports the mechanistic hypothesis of GRN-1201, suggesting that the immune response may contribute to better clinical outcome 180 ELISPOT (IFNγ production 症例A cell count) - Case A Spot numbers/10 PBMC count Peptide A 160 Pepti
Slide 13: iPS-NKT
iPS-NKT Novel allogeneic cell therapy using iPS cell-derived invariant NKT cells iNKT cells, unique subset of T cells, are implicated in the regulation of broad immune responses, but their limited frequency had been an obstacle to acquire sufficient numbers of iNKT cells from patients to induce
Slide 14: iPS-NKT (cont’d)
iPS-NKT (cont’d) A first-in-human investigator-initiated trial in patient with head and neck cancers started in June 2020 A Phase I study of iPS-NKT cell intra-arterial infusion therapy in patients with recurrent or Study Title advanced head and neck cancer (First in human study) Recurrent or adva
Slide 15: iPS-NKT (cont’d)
iPS-NKT (cont’d) Enhanced functionality of iNKT Cells iPS cell-derived NKT cells promote secretion of anti-tumor IFN-γ and reduce immunosuppressive IL-4 NKT line: iNKT cells before reprogramming into iPSC iPS-NKT: iNKT cells re-diffrentiated from iNKT cell- derived iPSC DC: co-culture with dendr
Slide 16: iPS-NKT (cont’d)
iPS-NKT (cont’d) In vivo Anti-tumor Activity iPS-NKT cells suppress the proliferation of cancer cells Tumor size (Fluorescence Intensity: Total Flux [photons/second]) Source: Yamada et al., Stem Cells. 2016 15
Slide 17: iPS-NKT (cont’d)
iPS-NKT (cont’d) Established iPS master cell bank as renewable starting cell source and robust cGMP process from iPSC to NKT cells to mass produce homogeneous NKT cells Pre-diagnosis Post-diagnosis Autologous cell therapy Patient Apheresis Production Administration of single dose Diagnosis Allogen
Slide 18: iPS-NKT (cont’d)
iPS-NKT (cont’d) Benchmarking CAR-transfected iPSC-derived effector-cell products for expansion strategy (IND filing year) Hematology CAR Solid tumor CAR Un- Company CD19 BCMA CD38 EGFR GPC3 MICA modified Fate Tx 2018 2020 2021 2022 iPSNK Century Tx 2021 2022 Cytovia Tx 2021 2022 2022 2022 iPSNKT
Slide 19: BP2301
BP2301 Autologous HER2 CAR-T cell therapy for solid tumors HER2 is a clinically validated target and HER2 CAR-T has third party’s precedent successful clinical outcome in sarcoma* BP2301 demonstrates a stem cell memory-rich phenotype, which is expected to improve the anti-tumor efficacy Flow
Slide 20: BP2301 (cont’d)
BP2301 (cont’d) piggyBac transposon-based CAR gene transfer enables CAR-T cells to maintain stem cell memory-like phenotype with self-renewing, long-term persisting ability and durable antitumor effects T cell differentiation and phenotypes Persistence of memory-rich CAR-T cells Cell death Sel
Slide 21: BP2301 (cont’d)
BP2301 (cont’d) BP2301 cells exhibits dominant of stem cell memory phenotype without early T cell exhaustion TEFF TSCM PD-1 72.5 % 0.3 % CD45RA PD-1 TEM TCM CCR7 CD3 SCM: Stem Cell Memory CM: Central Memory EM: Effector Memory EFF: Effector Source: Shinshu University, BrightPath 20
Slide 22: BP2301 (cont’d)
BP2301 (cont’d) Memory-rich BP2301 exhibits long-term functional persistence and exhaustion resistance BP2301 exhibits robust serial killing Tumor: Osteosarcoma cells(U2-OS) E:T =1:1 Tumor alone Round 1 +HER2 CAR-T cells Tumor alone Round 2 +HER2 CAR-T cells Tumor alone Round 3 +HER2 CAR-T cells
Slide 23: BP2301 (cont’d)
BP2301 (cont’d) BP2301 mediates robust antitumor function in vivo Vehicle CD19.CAR HER2.CAR Vehicle Tumor size (Fluorescence Intensity: Total Flux Day 6 Day14 [photons/second]) Day21 CD19.CAR Day28 Day35 HER2.CAR Day42 Source: Shinshu University, BrightPath Number of days from cancer cell transpla
Slide 24: BP2301 (cont’d)
BP2301 (cont’d) BP2301 demonstrates long-term functional persistence in vivo BP2301 sustains antitumor function in re-challenge tumor mouse model 1 x 107 Re-challenge tumor Primary tumor Vehicle CD19.CAR HER2.CAR Rechallenge Day0 Rechallenge Day7 Rechallenge Day14 Source: Shinshu University, Bri
Slide 25: BP1101
BP1101 A fully-personalized neoantigen vaccine, induces immunity against antigens derived from cancer-specific genetic mutations (neoantigens), which are completely unique to every patient T cell migration Blood vessel T cell T cells infiltrate cancer tissue Lymph node T cells recognize cancer ant
Slide 26: BP1209
BP1209 Antibody-vaccine conjugate with improved vaccine delivery to dendritic cells and immune induction Anti-dendritic cell marker antibody Neoantigen peptide vaccine (BP1101) ESMO 2021 1005P ”A new platform of personalized neoantigen cancer vaccines directed by checkpoint inhibitor antibodies to
Slide 27: BP1209 (cont’d)
BP1209 (cont’d) Improves anti-tumor immunity by increasing cDC1’s uptake of peptide vaccine and migration to lymph node Dendritic cells’ uptake of vaccine Immune induction in a mouse model and transition to lymph nodes （B6 +MC38 neoantigen） 1.2 cDC1 cDC2 1500 Amount of vaccine transferred to the l
Slide 28: BP1209 (cont’d)
BP1209 (cont’d) Tumor-bearing mouse study demonstrated increased anti-tumor immunity Vaccine (OVA) Day0 3 10 33 E.G7 (EL4/OVA) OVA expressed lymph Tumor cell transplant 2800 2400 2000 saline Tumor size (mm3) 1600 adjuvant only 1200 Administration 800 Administration vaccine ← BP1101 type 400 vaccin
Slide 29: BP1401
BP1401 Lipid nanoparticle of Type-A TLR9 agonist Suppress tumor growth by changing tumor immune-microenvironment LNP enables intravenous administration expecting safely brought systemic effects, which is differentiated from intratumoral injection-based predecessors in a clinical stage Promote
Slide 30: BP1401 (cont’d)
BP1401(cont’d) BP1401 promotes T-cells’ infiltration to and eradication of tumors Intratumoral administration of BP1401 Predecessors under clinical development are all intratumorally administrated 8 6 40 4000 ** ** N o n -tre a te d ** R e la tiv e E x p r e s s io n R e la tiv e E x p r e s s io
Slide 31: BP1200
BP1200 A novel antibody targeting CD73 Adenosine generation in tumors causes T cell exhaustion and dysfunction CD73 is highly expressed in various tumors and produce adenosine, leading to poor prognosis Dendritic T cell cell CD8+ Production of adenosine in the tumor T cell environment CD4+ T c
Slide 32: BP1200 (cont’d)
BP1200 (cont’d) BP1200 blocks the function of adenosine-generating enzyme (CD73) Superior to benchmarks in clinical stages BP1200 promotes T cell division and cytokine secretion, which leads to enhance anti-tumor immunity • がん免疫を亢進し、抗腫瘍効果を発揮することが期待される Induction of secretion of Inhibition of ad
Slide 33: BP1210
BP1210 Targeting TIM-3 as a novel immune checkpoint following PD-1/L1 BP1210 blocks TIM-3 and inhibits exhaustion of T cell to enhance anti-tumor immunity BrightPath’s target immune checkpoints T cell exhaustion is associated with increased TIM-3 expression T cell T cell Dendritic cell Naive
Slide 34: BP1210 (cont’d)
BP1210 (cont’d) BP1210 promotes T cell proliferation and cytokine secretion Superior to benchmarks in clinical stages SEB stimulation of PBMC (in combination with PD-1 antibody) T cell count IL-2 production IFN-γ production (day6) (day 6) (day 2) 2.0×10 5 6000 15000 (pg/ml) IFN-γ (pg/ml) cell co
Slide 35: BP1210 (cont’d)
BP1210 (cont’d) BP1210 strongly inhibits the binding of ligand PtdSer to TIM-3 • Superior to benchmarks in clinical stages BP1210 promotes T cell proliferation and cytokine secretion • Superior to benchmarks in clinical stages Binding inhibition of PtdSer SEB stimulation of PBMC (in combination
Slide 36: BP1211
BP1211 Anti-PVR antibody to inhibit binding TIGIT to PVR (CD155) and prevent T cell exhaustion BrightPath targeting immunocheckpoints Inhibition of TIGIT binding BP1211 BP1210 (PVR) antibody concentration (log, μg/mL) Red: Clinically validated, regulatory-approved target Bold: BrightPath target
Slide 37: BP1206
BP1206 Anti-HLA-DR antibody targeting HLA-DR on blood cancer cells Antitumor effects in vitro dependent on HLA-DR expression 100 60,000 Cancer cell killing 80 HLA-DR expression (MFI) Viable Cancer Cells (%) 40,000 60 40 20,000 20 0 0 MUTZ-5 (ALL) L428 (HL) GRANTA-519 (DLBCL) JJN-3 (MM) Rmos (BL) O
Slide 38: BP1206 (cont’d)
BP1206: (cont’d) BP1206 exhibits robust antitumor effects in vivo NOG mouse Day -12 0 42 Hodgkin’s lymphoma cell L428 s.c. engraftment (n=10) 10 mg/kg i.p. Q4D x 4 times 1200 1400 PBS Isptype (10mg/kg) 3 complete BP1206 (1mg/kg) 1000 eliminations 1200 BP1206 (5mg/kg) BP1206 (10mg/kg) BP1206 10mg/k
Slide 39: Company Overview
=: Company Overview BrightPath_ Biotherapeutics
Slide 40: Company Profile
Company Profile Company BrightPath Biotherapeutics Co., Ltd. (Tokyo Stock Exchange Mothers: 4594) name Headquarters: 2-2-4 Kojimachi, Chiyoda-ku, Tokyo Location Kawasaki Research Laboratories: 3-25-22 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa Cell Technology Laboratories: 3-25-22 Tonomachi, Kawasak
Slide 41: Business Locations
Business Locations Headquarters: Kojimachi Central Building 7F, 2-2-4 Kojimachi, Chiyoda-ku, Tokyo, Japan Kawasaki Research Laboratories Cell Technology Laboratories Life Innovation Center, 3-25-22 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, Japan Haneda Airport Tonomachi International Strategic Zon
Slide 42: We pioneer immunotherapy, to enable a world where cancer patients can defeat cancer
We pioneer immunotherapy, to enable a world where cancer patients can defeat cancer on their own.
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