Slide 1: Financial Results Presentation, Fiscal Year ending December 2017
The Fiscal Year ending December 2017 Financial Results Presentation February 9, 2018 Oncolys BioPharma Inc. (TSE mothers: 4588) Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.
Slide 2: Forward looking statements
Forward looking statements • This presentation material may contain information which is forward-looking and involves risks and uncertainties that could cause actual results to differ materially from those reflected in the forward-looking statements. One can identify these forward-looking statements
Slide 3: Table of Contents
Table of Contents 1. Financial results and future outlook 2. Telomelysin 3. TelomeScan 4. Message to investors Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.
Slide 4: Our pipeline: oncolytic virotherapy platform
Our pipeline: oncolytic virotherapy platform Oncolytic virotherapy platform Systemic treatment Prognosis follow-up Regional treatment O N OH H HN S O S NH Early detection O O O OBP-702 OBP-405 Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved. 4
Slide 5: FY2017 full year earnings results
FY2017 full year earnings results JPY in million Sales OP CP NP FY2017 Full Year 229 △1,078 △1,087 △1,090 FY2016 Full Year 178 △861 △864 △931 YOY +51 △217 △223 △159 Sales 1. License fee for Telomelysin from Hengrui 2. Co-development fund from Medigen 3. Sales of TelomeScan to Deciphera OP 1. Cost re
Slide 6: FY2017: achievements and status
FY2017: achievements and status ＜R&D-related＞ 1. Melanoma P2 Started 2. Esophageal cancer P1 Started OBP-301 3. HCC P1/2 Multiple administration (Cohort 5) in progress “Telomelysin®” 4. Solid tumors, with PD-1 P1/2 Started 5. Esophageal caner (USA) Scientific Advisory Board（SAB) meeting 6. 9 confere
Slide 7: Comparison: budget and actual expenses FY2017
Comparison: budget and actual expenses FY2017 1.6bn ＜Major factors＞ 1.23bn 1. Delay in Telomelysin-related 7 clinical trials 5.7 2. Reduced Telomelysin-related 2 patent costs 0.6 3. Reduced TelomeScan joint research costs 7 6 単位：（億円） Planned budget Results Other SG&A Patent R&D Copyright(C) 2018, On
Slide 8: Financial year ending December 2018 full year forecast
Financial year ending December 2018 full year forecast (JPY: million) Sales OP CP NP R&D and SG&A Forecast FY2018 230 △1,400 △1,400 △1,400 1,6bn Results FY2017 229 △1,078 △1,087 △1,090 yoy +1 -322 -313 -310 500 0 400 -300 0,7bn 300 -600 230 200 -900 SG&A R&D 100 -1,400 -1,200 0 -1,500 (単位：百万円) FY201
Slide 9: Our pipeline
Our pipeline Pharmaceutical Business Pipeline/Project Indication Exploratory Pre-clinical Phase Ⅰ Phase Ⅱ Phase Ⅲ Melanoma Oncolytic Esophageal virus Cancer HCC Solid tumors Small molecule OBP-801 Ophthalmic use OBP-601 HIV Anti virus OBP-AI-004 HBV Diagnostic Business Category Pipeline/Project Indi
Slide 10: Table of Contents
Table of Contents 1. Financial results outline and future outlook 2. Telomelysin 3. TelomeScan 4. Message to investors Copyright(C) 2018 , Oncolys BioPharma Inc. All rights reserved.
Slide 11: Telomelysin: oncolytic virotherapy
Telomelysin：oncolytic virotherapy Normal cell (Telomerase activity－） No replication No cytophathy Induced cell death and diffusion of Cancer cell Replication of Telomelysin Telomelysin (Telomerase activity+) Ref.) The Lancet Oncology Vol. 3 Jan. 2002 Colorectal （15 days after administration） Lung Da
Slide 12: Telomelysin project
Telomelysin project Tumor type Treatment Country Pre-clinical Phase Ⅰ Phase Ⅱ Phase Ⅲ Radiation OBP sponsored clinical trial Esophageal Radiation Investigator initiated JP Cancer clinical trial Anti PD-1 Investigator initiated clinical research Melanoma Monotherapy US Taiwan HCC Monotherapy Korea HN
Slide 13: Esophageal Cancer: Cure without operation
Esophageal Cancer “Cure without operation” Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.
Slide 14: Investigator-initiated clinical research with radiation (1)
Investigator-initiated clinical research with radiation (1) 6 CR in 10 cases Radiation therapy 5 times/week (Mon- Fri) x 6 weeks Day 1 Day 4 Day 18 Day 32 Toshiyoshi Fujiwara, M.D., Ph.D. Professor & Chairman Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine,
Slide 15: Investigator initiated clinical research with radiation (2)
Investigator initiated clinical research with radiation (2) Cases Dose Case Age Stage Response 001 82 cStage I CR 002 85 cStage I CR 003 92 cStage II PR Cohort 3 completed Level 1 1x1010vp 004 68 cStage Iva SD 005* 79 cStage III PD 006 88 cStage I CR 007 53 cStage II CR Data analysis 001 89 cStage I
Slide 16: Oncolys' Phase I clinical trial with radiation
Oncolys’ Phase I clinical trial with radiation 1. Cohort １ in progress 2. Cohort ２ to be completed within 2018 3. Start preparation for Phase II/III with radiation Multicenter trial Preliminary consultation with PMDA Expected to start in 2019 Copyright(C) 2018, Oncolys BioPharma Inc. All right
Slide 17: Pembrolizumab combination therapy at NCCHE
Pembrolizumab combination therapy at NCCHE Patients with advanced or metastatic tumors Main endpoint: Safety and tolerability Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved. 17
Slide 18: Esophageal Cancer: Scientific Advisory Board Meeting
Esophageal Cancer：Scientific Advisory Board Meeting Discussion on expanded indication of Telomelysin(20 Jan) Name Specialty Institution Weill Cornell Medicine/ Manish Shah, MD Medical Oncology NewYork-Presbyterian Memorial Sloan Kettering David Ilson, MD, PhD Medical Oncology Cancer Center Khaldoun
Slide 19: Tumor virotherapy: clinical trials
Tumor virotherapy: clinical trials # of Indication Sponsors clinical trials Melanoma 16 Amgen, Provectus, Takara Bio, Virttu, Viralytics , Oncolys Solid tumor 11 VBL, Silla Jen, Targovax, Remplimune, VCM Brain tumor（incl. GBM） 10 VBL, DNAtrix, Virttu, VCN HCC（incl. metastatic to liver） 9 Amgen, Sill
Slide 20: Esophageal cancer treatment perspectives
Esophageal cancer treatment perspectives Number of patients: approx. 31,000 in 2014 Estimated incidence: approx. 22,000 between 2015 - 2019 (Incidence worldwide: approx. 456,000 in 2012) (Incidence USA: approx. 17,000 in 2017 ) Stage Ⅳ Metastasis/operation inapplicable patients ＋ Stage Ⅰ・Ⅱ・Ⅲ ICI
Slide 21: Melanoma: Challenge to remote cancer
Melanoma “Challenge to remote cancer” Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.
Slide 22: Abscopal Effect observed in melanoma patients
Abscopal Effect observed in melanoma patients Age: 54 Cytoreductive effect on Sex: Male administration/non-administration sites Race: Caucasian Stage: IV 1. Administration Cohort 1: 1x1010VP site Metastases: 5 1. axillary nodes (left) 2. axillary nodes (right) 3. Subpectoral node (left) 28 days 56 d
Slide 23: Melanoma: 2 patients enrolled
Melanoma：2 patients enrolled Total 4 clinical trial sites are open in the US so far Accelerating patient recruiting to realize an interim analysis Final Visit Week* 0 2 4 6 8 10 12 14 16 18 20 22 24 mandatory mandatory optional optional optional CT CT CT CT CT Trial sites Unresectable or metast
Slide 24: HCC: Challenge to refractory cancer
HCC “Challenge to refractory cancer” Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.
Slide 25: HCC: Phase I/II in Taiwan and Korea
HCC: Phase I/II in Taiwan and Korea Before administration 3 more cases After 4 weeks Moving on to PII after P I → monotherapy or combination with ICI? Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved. 25
Slide 26: Next Generation Telomelysin
Next Generation Telomelysin Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.
Slide 27: Next Generation Telomelysin ①
Next Generation Telomelysin① Next Generation Local therapy Systemic therapy ∟Virotherapy ∟virotherapy ∟T lymphocyte therapy ∟CP Inhibitors Changing tumor microenvironment OBP Telomelysin h4-1BBL hPD-1 A社 E1A-E3 h4-1BBL B社 E1A-E3 hOX-40 + anti-PD-1 Ab Lymphocyte Virus ＋ CPI stimulation ＋ Copyright(C)
Slide 28: Next Generation Telomelysin ②
Next Generation Telomelysin ② NG Telomelysin T cell Immunotherapy T Lymphocyte Co-stimulate molecule Cancer cell PD-L1 CPI PD-1 Cancer cell Oncolytic virus Virus particle Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved. 28
Slide 29: Telomelysin project picture after 2020
Telomelysin project picture after 2020 Tumor type Treatment Country Pre-clinical Phase Ⅰ Phase Ⅱ Phase Ⅲ Radiation Anti PD-1 Investigator initiated clinical trial JP Complete Radiation Esophageal Investigator initiated Complete clinical research Cancer ICI US CRT Monotherapy Taiwan HCC Korea ICI Mon
Slide 30: Table of Contents
Table of Contents 1. Financial results and future outlook 2. Telomelysin 3. TelomeScan 4. Message to investors Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.
Slide 31: TelomeScan overview
TelomeScan overview TelomeScan is a gene-modified adenovirus which replicates and express GFP when infected to telomerase activity-positive tumor cells. hTERTp IRES CMVp E1A E1B GFP ⊿E1 ⊿E3 Normal cell Adenovirus Type-5 Genome Telomerase activity - TeｌomeScan (OBP-401) TelomeScan Infection Fluoresce
Slide 32: Tumor Metastasis and CTC Phenotype
Tumor Metastasis and CTC Phenotype 1. Detection rate using tumor diagnostic markers currently available is around 30-40%. 2. PET and MRI only detect tumor cells bigger than 1㎝ 3. CTCs seep from tumor cells undetectable by PET and MRI Primary tumor Hematogenous translocation EMT CTC Metastasis/ Vascu
Slide 33: Joint research towards the practical use
Joint research towards the practical use Joint research with Division of Respiratory Medicine, Juntendo University started in Nov. 2017 and promoted as a cross-sectional research project joined by medical doctors in wide range of oncology-related fields. Juntendo Oncolys University Biopharma Long
Slide 34: Future development
Future development 1. Differentiation from ctDNA/cfDNA 2. Precision Medicine 3. New CTC application → HPV detection Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved. 34
Slide 35: Comparison of Liquid Biopsy
Comparison of Liquid Biopsy Circulating tumor DNA CTC cfDNA ctDNA Phenotyping Protein + - - Genotyping RNA + - - DNA +/- + + Early Detection +/- + +/- Clinical Benefit Longitudinal Monitoring + + + Treatment Response + + + Figure was modified from Wyatt AW and Gleave ME, EMBO Mol Med (2015) Copyrigh
Slide 36: Our Target Cancers
Our Target Cancers Challenge to Impossible for cf/ctDNA Phenotyping Lung Ca. Urothelial Ca. RCC Melanoma “PD-L1” Genotyping Cervical Ca. SCCHN Vaginal Ca. Anal Ca. “HPV/KRAS/BRAF/T790M” RNA Prostate Ca. Breast cancer “AR-V7” Non-CTC Pancreatic Ca. Gastric Ca. “PTC” PTC : Peritoneal Tumor Cell Copyri
Slide 37: Application to precision medicine
Application to precision medicine ＜NSCLC＞ Project led by University of Pennsylvania CTC CTC CTC CTC CTC CTC CTC CTC CTC CTC CTC Chemoradiation therapy（CRT） Recurrence 5weeks Treatment continued Gene analysis Selection of treatment （ Follow-up # of CTC Treatment complete ） Copyright(C) 2018, Oncolys
Slide 38: HPV Detected in Cancer Cell
HPV Detected in Cancer Cell HPV is the cause of Cancer Cervical Cancer 1, 2 ~100% Vaginal HPV Cancer 1 60~90% Head & Neck Cancer 2 12~70% HPV is NOT detected in Blood Stream, but in ONLY CTC 1; Braaten KP et al. Rev Obstet Gynecol. (2008) 2; IARC. IARC monographs on the evaluation of carcinogenic ri
Slide 39: HPV Typing in CTCs
HPV Typing in CTCs Cervical Cancer < Sensitivity > < HPV Typing in CTCs > (≥1 cell/7.5ml of peripheral blood tested positive) 100 HPV type # Stage CTC positive rate (%) CTC Primary 80 2 IIA 16 16 60 39.0% 4 recurrence undetected 33 (16/41) 40 5 IB1 16 16 6 IB1 16 16 20 10 recurrence 16 16 0 Total 16
Slide 40: Table of Contents
Table of Contents 1. Financial results and future outlook 2. Telomelysin 3. TelomeScan 4. Message to investors Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.
Slide 41: Further Growth & Business Expansion
Oncolys’ financial grounds in mid-long term Further Growth & Business Expansion More license agreements New pipeline Next generation Telomelysin Stronger financial OBP-XXXX OBP-YYYY grounds New license agreements Milestone fees & virus sales based on current license agreements Jiangsu Hengrui, W
Slide 42: Thank you!
Thank you! 42 Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.