general shareholders meeting 2018 company presentation · - clinical project leader mainly for cvs...

March 29, 2018

Oncolys BioPharma Inc.(TSE mothers: 4588)

Copyright(C) 2018, Oncolys BioPharma Inc. All rights reserved.

General Shareholders Meeting 2018

Company Presentation


Forward looking statements

2

• This presentation material may contain information which is forward-looking and involves risks and uncertainties thatcould cause actual results to differ materially from those reflected in the forward-looking statements. One can identifythese forward-looking statements by use of words such as "strategy," "expects," "plans," "anticipates," "believes," "will,""continues," "estimates," "intends," "projects," "goals," "targets" and other words of similar meaning. These risks anduncertainties include, without limitation, risks associated with the inherent uncertainty of pharmaceutical research,product development, clinical research, seeking regulatory approval and product commercialization, as well as the impactof competitive products, patents, product liability and third-party reimbursement risks associated with the pharmaceuticalindustry, and the other risks and uncertainties.

• Product development involves a high degree of risk. Only a small number of research and development programs resultin the commercialization of a product. Success in preclinical and early clinical trials does not ensure that later stage orlarge scale clinical trials will be successful. Many important factors affect Oncolys BioPharma’s ability to successfullydevelop and commercialize drugs, including the ability to secure necessary funding, to obtain and maintain necessarypatents and licenses, to demonstrate safety and/or efficacy of drug candidates at each stage of the clinical trial process,to overcome technical hurdles that may arise, to meet applicable regulatory standards, to receive required regulatoryapprovals, to be capable of producing drug candidates in commercial quantities at reasonable costs, to competesuccessfully against other products and to market products successfully. There can be no assurance Oncolys BioPharmawill be successful in its efforts to develop and commercialize new products.

• No guarantee is made as to the accuracy, completeness or timeliness of any information, projections or opinionscontained in this presentation material or upon which any such projections or opinions have been based. The informationcontained in this presentation material is compiled for information purpose only and does not constitute an offer orsolicitation to purchase or sell any of the securities in this presentation material.

• This presentation material is a summary translation of the original published in Japanese. In case of any discrepancy, theJapanese original shall prevail.


Table of Contents

1. About Oncolys2. Pipeline & Business Overview3. Message to investors


Company profile

4

Address 4-1-28 Toranomon, Minato-ku, Tokyo, Japan

Foundation March 18, 2004

Ticker &

Market4588（listed on December 6, 2013）

President &

CEOYasuo URATA

Capital 5802 Million (December 31, 2017）

Employees 29（December 31 2017）

Oncolys Bio Pharma

Oncolys BioPharma


Founder profile

1983 Ono Pharmaceutical Co., Ltd.

- Clinical project leader mainly for CVS and CNS

1994 Japan Tobacco Inc. (JT)

2002 Director of R&D Planning, JT

- Innovative HIV drug, Viracept (Agouron), GVAX (Cell Genesys) and Cancer vaccine project (Corixa)

2004 Established Oncolys BioPharma Inc. in Tokyo, Japan

2009 Member of Bio Innovation Research Society

(Ministry of Economy, Trade and Industry of Japan)

2016 Executive Officer, Oncolys USA Inc.

President & CEOYasuo URATA

5


“Powering Future Oncotherapy”

Business concept

6


Our pipeline: oncolytic virotherapy platform

7

Early detection

Prognosis follow-up

Regional treatment

Systemic treatment

O

NHS S

NH

NH

O

O

OO

OH

OBP-702 OBP-405

Oncolytic virotherapy platform


Management goal

Our goal is to bring our innovative biopharmaceutical candidates

from Japan to the world.

8

In-house development & launch

Licensing

Licensing Cancer Diagnostics

① Upfront payment

② Milestone fees

③ Royalties, etc.


OBP-301

“Telomelysin®”

Cancer Diagnosis

1. PTC feasibility study for pancreatic cancer: IRB2. Joint research agreement with Juntendo University3. SAB for NSCLC4. 9 conference presentations, 3 publications

OBP-801Epigenetic cancer treatment

1. Solid tumor Phase 1 Cohort 3 in progress2. Possibility of 2wks sustained delivery explored 3. Pre-clinical study with Kyoto Prefectural University of Medicine

extending the application into ophthalmologic field

AI-004Novel HBV drug

1. Compound screening at Kagoshima University in progress

Others 1. Completed 1.4 bn JPY financing by third-party allotment

FY2017: achievements and status

9

＜R&D-related＞

1. Melanoma P2　 Started

2. Esophageal cancer P1 Started

3. HCC P1/2 Multiple administration (Cohort 5) in progress

4. Solid tumors, with PD-1 P1/2 Started

5. Esophageal caner (USA) Scientific Advisory Board（SAB) meeting

6. 9 conference presentations, 4 publications

＜Business-related＞

1. Milestone fee from Hengrui

2. Co-Development fund from Medigen


Financial year ending December 2018 full year forecast

230

-1,400

-1,500

-1,200

-900

-600

-300

0

0

100

200

300

400

500

FY2012 FY2013 FY2014 FY2015 FY2016 FY2017 FY2018forcast

Sales OP

10

(単位：百万円)

(JPY: million)

Sales OP CP NP

Forecast FY2018 230 △1,400 △1,400 △1,400

Results FY2017 229 △1,078 △1,087 △1,090

yoy +1 -322 -313 -310

R&D and SG&A

SG&A

(JPY 100 million)

R&D

SG&A

1,6bn

0,7bn

(forecast)


Table of Contents

1. About Oncolys2. Pipeline & Business Overview3. Message to investors


Developmental pipeline

12

Pharmaceuticals

Diagnostics

IndicationProjectPre-clinical

Phase Ⅰ Phase Ⅱ Phase Ⅲ

Melanoma

Solid tumor

HIV

OBP-801

OBP-601

HBVOBP-AI-004

Anti virus

Oncolytic virus

Small molecule

Tumor diagnostics

Category Indication Basic ResearchPipeline/Project Clinical Study Clinical Usefulness

OBP-401/1101

Esophageal cancer

HCC

OBP-702 Solid tumor

On

coly

tic

viru

s

Ophthalmic use

Exploratory

Solid tumor


Oncolytic virus immunotherapy

13

1. Local/regional injection2. May be effective on metastatic cancer cells 3. No hair loss / nausea4. Possibility of cancer treatment without operation


Virotherapy for cancer: a brief history

14

Regression of Burkitt’s Lymphoma in association with Measles Infection

Bluming AZ, and Ziegler JLLancet, 2 (7715):105-106, 1971

1912 DePace et al.

Attenuated rabies virus Uterine cervical cancer

1922 Levaditi & Nicolau

Vaccinia virus, NDV Ascitis tumors (mouse)

1950Pack

Attenuated rabies vaccine Melanoma

1952 Southam et al.

Myxo, paramyxo, arbovirus Various tumors

1957Suskind et al.

Coxsackie B Various tumors

1965 Cassel et al.

NDV Ascitis tumors (mouse)

1974 Asada

Mumps Various tumors

World’s first oncolytic virusapproved by FDA 27 October 2015


Telomelysin：mechanism

15

Normal cellNo cytophathy

Cancer cell

No replication

Ref.) The Lancet Oncology Vol. 3 Jan. 2002

(Telomerase activity+)

(Telomerase activity－）

Control group

Colorectal cancer

（15 days after administration）

Telomelysin

Ref) Curr. Cancer Drug Targets, 7: 191-201, 2007 )

Day 0 Day 14 Day 28Lung cancer

Replication of Telomelysin

Induced cell death and diffusion of Telomelysin

Control group

Telomelysin


Telomelysin project

16

※Jiangsu Hengrui’s project is not included in this table. )

Melanoma

Esophageal

Cancer

HCC

Anti PD-1Investigator initiated

clinical research

JP

US

Taiwan

Korea

RadiationInvestigator initiated

clinical trial

RadiationOBP sponsored clinical

trial

Monotherapy

Sarcoma

JP

JP

Radiation

Radiation

HNSCC

Planning

Phase ⅢTumor type Pre-clinical Phase Ⅰ Phase ⅡCountryTreatment

Monotherapy

Esophageal Cancer


“A cure without operation”


Esophageal cancer overview

18

1 Lung 1,590,000

2 Liver 780,000

3 Stomach 720,000

4 Colorectal 690,000

5 Breast 520,000

6Esophagealcancer

400,000

Number of cancer death worldwide

Ref: WHO 2012 research

340,000

53,000

26,00024,000

13,000

Esophageal cancer incidence worldwide

アジア

欧州

アフリカ

北米

その他

Ref: 2012 IARC data

Total:456,000 cases

<Esophageal cancer treatment without operation>

①Radiotherapy for inoperable patients→Unmet Medical Needs

②Combination with radiochemotherapy before operation→Adjuvant therapy

③Combination with immunotherapy(anti-PD-1 antibodies)

Radiation

(Number of patients)

Asia

Europe

Africa

N. America

Others


Investigator-initiated clinical research with radiation

19

(Ref: Press release from Okayama University etc.)

Day 1 Day 4 Day 18 Day 32

Radiation therapy

5 times/week (Mon- Fri) x 6 weeks

Toshiyoshi Fujiwara, M.D., Ph.D.Professor & Chairman

Department of Gastroenterological Surgery, Okayama University Graduate

School of Medicine, Dentistry, and Pharmaceutical Sciences

6 CR in 10 cases


Oncolys’ Phase I clinical trial with radiation

20

1. Phase I completion expected within 2018

2. Preparation for Phase II/III for Radiation + Telomelysin

Multicenter trial in Japan

Preliminary consultation with PMDA

Trial expected to start in 2019

Clinical trial is in progress in Okayama University and NCCHE.

Radiation + Telomelysin


Scientific advisory board meeting

21

Discussion on expanded indication of Telomelysin(20 Jan)

Case Stage Combination

１ Stage IV Metastatic ICI

２ cStage II/III Inoperable CRT

３ cStage II/III Operable CRT

Name Specialty Institution

Manish Shah, MD Medical OncologyWeill Cornell Medicine/NewYork-Presbyterian

David Ilson, MD, PhD Medical OncologyMemorial Sloan KetteringCancer Center

Khaldoun Almhanna, MD Medical Oncology Moffitt Cancer Center

Toshiyoshi Fujiwara, MD, PhD Surgical Oncology Okayama University

Lawrence Kleinberg, MD Radiation Oncology Johns Hopkins

Tanguy Seiwert, MD Immunologist U. Chicago

Kenneth Wang, MD Endoscope Specialist Mayo Clinic

Field Willingham, MD Endoscope Specialist Emory University

（ICI: Immune Checkpoint Inhibitor , CRT: Chemoradiotherapy）

＜Stomach and gastroesophageal cancer>


Esophageal cancer treatment perspectives

22

Stage Ⅰ・Ⅱ・ⅢOperation applicable

Stage ⅣMetastasis/operation inapplicable patients

＋

Pre-operative chemotherapy/radiation

＋ Radiation

Stage Ⅰ・ⅡOperation/chemotherapy

inapplicable patients

＋

ICI: pembrolizumab

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 )

Ref.) PMDA 2014 Patient Report (2014), NCC Center for Cancer Control and Information Services, Cancer today IARC website.


Melanoma

“Enhancing tumor immunity”


Melanoma overview

24

100,00075,000

22,000

6,000

28,000

Melanoma incidence worldwide in 2012

欧州

北米

アジア

アフリカ

その他

（Ref：GLOBOCAN2012）

1. Most cases are curable if surgically-treated early.2. Prone to metastasis →Brain, lung, liver3. Median survival of terminal stage patients is

6 months while one-year mortality is 75%.

Total:231,000 cases

Europe

N. America

Asia

Africa

Others


American, Female in 50s, melanoma with metastasis to left femoral area

Before administration After 4 weeks

33mmx16mm25mmx8mm

(↓33.4%)

1.Solid tumor patients who have no other treatment choices participated in this clinical trial.

2.Tumor shrinkage was confirmed in 7 out of 22 patients.

3.Fever (around 38℃) 24-48 hours after administration observed

4. Telomelysin administered via out-patient visit

US Phase I: tumor size reduced in 7/22 patients

25


Phase Ⅱ in progress in the US

26

Unresectable or metastatic melanoma – Max. 50 patients to be enrolled6 months, high dosage group only, multiple locationEfficacy, safety and immunological response

Investigators Clinical trial sites

Dr. Eric Whitman Atlantic Health Systems

Dr. Robert Andtbacka Huntsman Cancer Institute

Dr. Mohammed Milhem University of Iowa

Dr. Sanjiv Agarwala St. Luke's University Health Network Inc.

Dr. Sunil Reddy Stanford University


Hepatocellular Cancer (HCC)

“Challenge to refractory cancer”


HCC overview

28

HBV/HCV

infection

Chronic Hepatitis

Hepatic Cirrhosis

HCC

1.Surgery/resection

2.Embolization/ablation

3.Chemotherapy

590,000

63,000

59,00033,000

33,000

HCC incidence worldwide

アジア

欧州

アフリカ

北米

その他

Total:782,000 cases

Asia

Europe

Africa

N. America

Others

Number of cancer death worldwide

1 Lung 1,590,000

2 Liver 780,000

3 Stomach 720,000

4 Colorectal 690,000

5 Breast 520,000

6 Esophageal 400,000

Ref: WHO 2012 research Ref: 2012 INAC data

Common treatment options


HCC: Phase I/II in Taiwan/Korea (1)

29

1Max dose（Cohort4）administration completed& multiple administration（Cohort5）in progress

2Expected to advance to Phase Ⅱ soon, as monotherapy or in combination with CPI

National Taiwan Univ.

Dr. Pei-Jer Chen

National Pusan Univ.

Dr. Jeong Heo

Directly injected to tumor cell

Decide injection location using ultrasonograph


Telomelysin project picture after 2020

30

NG Telomelysin

Lung・Colorectal cancer

Phase Ⅲ

Melanoma

Esophageal

Cancer

HCC

Tumor type Pre-clinical Phase Ⅰ Phase ⅡCountryTreatment

Anti PD-1Investigator initiated

clinical trial JP

Taiwan

Korea

US

RadiationInvestigator initiated

clinical research

Radiation

Monotherapy

Monotherapy

ICI

CRT

US

ICI

ICI併用

HNSCC

Complete

ー US

Radiation

Sarcoma Radiation

JP

JP

（ICI: Immune Checkpoint Inhibitor）

Complete


Next Generation Telomelysin


Cancer cell

32

Next generation Telomelysin

T cell

Cancer cell

T LymphocyteCo-stimulate molecule

PD-1

Virus particle

NG Telomelysin

Immunotherapy

CPI

Oncolytic virus

PD-L1


Telomelysin platform

33

OBP-702

•Local administration

• Indirectly enhance immunity

•Weaker proliferative capacity with stroma cells

•Local/intravenousadministration

•Directly enhance immunity

•Effective in stroma cells

•Diagnostic virus

TelomelysinPlatform

Telomelysin

p53

OBP-702

TelomeScan

GFP

TelomeScanF35

GFP

miR142

p-E1

Next Generation Telomelysin A

p-E1

lymphocyte stimulation molecule

Next Generation Telomelysin B

lymphocyte stimulation molecule

CP suppressor molecule

pCell specific

Fiber

Next GenerationTelomelysin

Telomelysin

TelomeScan

TelomeScanF35

lymphocyte stimulation


Business Development Activities

34


Jiangsu Hengrui Medicine

GMP manufacturing started in China

35

Sales: JPY180 bn（FY2016）

Number of employees: 13,000

Jiangsu Hengrui Medicine（江蘇恒瑞医薬股份有限公司）

CFDA announcement for acceptance of overseas data（8 Oct 2017）

Name Market cap (JPY, bn)

Takeda 4,361

Jiangsu Hengrui 4,129

Astellas 3,285

Chugai 2,966

Otsuka HD 2,838

Daiichi Sankyo 2,483

Shionogi 1,730

Eisai 1,971Ref：Bloomberg and other public data as of 26 March 2018

<Market cap comparison table: major Japanese pharmaceutical companies>

Jiangsu Hengrui


Revised strategic alliance with Medigen

36

Steady cost reduction for R&D

Extended co-developmentHCC

Melanoma Esophageal cancer

HCC CMC/GMP

Stanley Chang, CEO

Taiwan Stock Exchange（3176）HQ：Taipei, Taiwan

Medigen Biotechnology Corp.


“Broaden cancer treatment options”

37


TelomeScan overview

38

Telomerase

activity -

GFP

Telomerase

activity +

Infection

Normal cell

Tumor cell

TelomeScan

1. Express GFP when infected to CTCs2. Detect “live” malignant tumor 3. May be used to decide treatment/medication options after surgery

Fluorescent emission

by GFP


Tumor Metastasis and CTC Phenotype

39Metastasis to other organs

Vascular

CTC

EMT CTC

Primary tumor

Metastasis/Recurrence

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

Hematogenoustranslocation

Vascular invasion


Detecting invisible tumor cells

40

Tumor size

Time

Primary tumor

Metastasis/Recurrence

・Tumor marker・Diagnostic imaging

SurgeryRadiotherapyChemotherapy

Recurrence-free/cureInvisible

tumor

0.5～1cm

CT/MRI/Marker


CTCs detected by TelomeScan

41

Breast

GFP(TelomeScan)

Lung

Immunostaining

Prostate

CD45 Bright-fieldComposite

Ovary

Phenotyping

Cytokeratin

Cytokeratin

Cytokeratin

Vimentin

Mesenchymal CTC

Epithelial CTC

Tumor type


Application to precision medicine

42

（# of C

TC

）

Chemoradiation therapy（CRT）

Follow-up

Recurrence5weeks

Treatment complete

Treatment continued

Gene analysisSelection of treatment

CTC CTCCTCCTC CTCCTC CTCCTCCTCCTCCTC

＜NSCLC＞ Project led by University of Pennsylvania


HPV Detected in Cancer Cell

43

HPV

HPV is NOT detected in Blood Stream, but in ONLY CTC

Cervical Cancer 1, 2

~100%

Head & Neck Cancer 2

12~70%

Vaginal Cancer 1

60~90%

HPV is the cause of Cancer

1; Braaten KP et al. Rev Obstet Gynecol. (2008)2; IARC. IARC monographs on the evaluation of carcinogenic risks to humans. Human papillomaviruses. Vol 90. Lyon, France:IARC (2007)


HPV Typing in CTCs

44

CTC

po

siti

ve r

ate

(%)

0

20

40

60

80

100

39.0%(16/41)

0

20

40

60

80

100

Primary Recurrence

32.4%(11/34)

71.4%(5/7)

Total

< Sensitivity >(≥1 cell/7.5ml of peripheral blood tested positive)

Cervical CancerC

TC p

osi

tive

rat

e(%

)

< HPV Typing in CTCs >

Takakura et al., Cancer science (2017)

# StageHPV type

CTC Primary

2 IIA 16 16

4 recurrence undetected 33

5 IB1 16 16

6 IB1 16 16

10 recurrence 16 16

16 IB1 16 16

Detected in 5/6 pts


Joint research towards the practical use

45

1. Practical use in clinical settings across Japan for detection of early and recurrent tumors

2. Automation of tumor detection system

Joint research with Division of Respiratory Medicine, Juntendo University since Nov. 2017 Juntendo promotes it as a cross-sectional research project joined by medical doctors

in wide range of oncology-related fields.

Juntendo University

Oncolys Biopharma

<TelomeScan long-term targets>


Next step

46

N. America, 2015

Korea, 2014Licensed

Licensing/collaboration activities

Japanese corporates and academia

Non-Japanese corporates


Table of Contents

1. About Oncolys2. Pipeline & Business Overview

3. Message to investors


Our US base accelerates BD/RD activities in the US

48

New Jersey

http://www.google.co.jp/url?sa=i&source=images&cd=&cad=rja&docid=R0g-4UYZkgqsuM&tbnid=pjTc_i_zulXubM:&ved=0CAgQjRwwADiEAg&url=http://www.flash-map-shop.com/northamerica-c-6.html&ei=qrHDUZiLF4mBiQey7oDoAg&psig=AFQjCNHFai4jx05DXn9QkcYPJogdEBqkCQ&ust=1371865898430028

http://www.google.co.jp/url?sa=i&source=images&cd=&cad=rja&docid=R0g-4UYZkgqsuM&tbnid=pjTc_i_zulXubM:&ved=0CAgQjRwwADiEAg&url=http://www.flash-map-shop.com/northamerica-c-6.html&ei=qrHDUZiLF4mBiQey7oDoAg&psig=AFQjCNHFai4jx05DXn9QkcYPJogdEBqkCQ&ust=1371865898430028


Oncolys’ financial grounds in mid-long term

49

Co-development fund from Medigen

Milestone fees & virus sales based on current license agreements Jiangsu Hengrui, Wonik Cube, Deciphera, etc.

Steady income

New license agreements

More license agreements New pipeline Next generation

Telomelysin

OBP-XXXX

Further Growth & Business Expansion

OBP-YYYYStronger financial grounds


Recent oncolytic virus deals in the world

50

Pipeline Licensee Licenser Type Deal size

T-VEC

（Imlygic®）BioVex Amgen

Licensing(Acquisition）

JPY 110bn

CAVATAK® (CVA21) Viralytics MerckLicensing(Acquisition)

JPY 42.3bn

NG-348 PsiOxus Therapeutics Bristol-Myers SquibbLicensing/Co-development

JPY 103bn（Upfront JPY 6.5bn）

VSV-GP ViraTherapeutics Boehringer IngelheimCo-development/Conditionalacquisition

JPY 27.3bn（Upfront JPY 2.6bn）

WO-12 Western Oncolytics PfizerLicensing/Co-development

Not disclosed

ONCR-001 Oncorus Celgene Capital alliance Not disclosed

（Ref：company websites and public information as of Jan 2018）

（1USD=JPY110、1EUR=JPY130、1AUD=JPY85）


“Powering Future Oncotherapy”

Again, our business concept

51


Thank you!

52

general shareholders meeting 2018 company presentation · - clinical project leader mainly for cvs...

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