Kotra pharmabcine

March 10th, 2017

Corporate Presentation Jin-San Yoo, Dr. rer. Nat. President & CEO of PharmAbcine

Executive Summary-1 1.

PharmAbcine is a leading clinical stage biotech with valuable Platform technologies for development of the next generation therapeutics.

2.

The best fully human antibody based therapeutics for unmet medical needs.

3.

Leading science and most innovative pipelines with strong IP position.

4.

Leadership, Management, Boards, and investors with top global standard.

5.

Plan for KOSDAQ IPO in 2018.

Executive Summary-2 1.

Tanibirumab phase I data was clean and currently, its phase IIa multi center trials in Australia are running smoothly with recurrent GBM patients with 13M PFS with tumor shrinkage at Melbourne site and other tumor shrinkage patient with >7M PFS at Perth site.

2.

This phase IIa is expected to be completed by this August.

3.

We are preparing for phase IIb recurrent GBM global trial including US, Europe, Australia, Japan and South Korea.

4. We also are preparing for multiple clinical trials with Tanibirumab single, and Tanibirumab + immune checkpoint blockade combination in refractory tumors and TNBC. 5. We will accelerate our PMC-001 IND and Phase I in US. 6. We will accelerate our development time of novel immune checkpoint blockade.

Contents

I.

Company Intro

II. People , R&D Asset

III. Marketability IV. Competition

V. Future Plan

Key Milestones 2009.09.

Series A Fund - USD 6 M (Invested by OrbiMed, Novartis Venture Fund, GreenCross, DongYang etc.)

2012.04. ~ 2013.06.

Series B Fund - KRW 10 B (Novartis Venture Fund, Hanwha-Oxford, DongYang, MiraeEsset, KB Investment etc)

2008.09.

Company Establishment

2008

2008.10.

1st GATE Project Best Award (Sponsored by Novartis, KOTRA, Samsung,)

2009

2011

2011.07.

Tanibirumab: Phase I IND approval in Korea

2012

2013

2013.09.

Tanibirumab: Completion of Phase I

2015.01.06 KOSDAQ IPO Tech. Evaluation Passed 2016.02 Tanibirumab: Phase IIa FIH in Australia

2014

2015

2015.03 Series C Fund - KRW 2 B (IMM Investment)

2014.03 ~ 2014.12 Tanibirumab & PMC-001 License-Out (3SBio, Triphase etc.)

2016

2016.04.

Preliminary Listing Application

2015.12.18 KOSDAQ IPO Tech.

Evaluation Passed

Our Key Performances

• Patent Registration : 26 cases

• Fully Human Ab Tech.

(Fully Human Phage Display Library& Innovative Selection System)

Platform Tech.

• Next-generation Bispecific Ab Tech.

(DIG-bodyTM

& PIG-body

TM)

IP Rights

• Patent Application : 14 cases • Trademark Registration: 4 cases

• Co-development with

• Patients-derived CSC Library

Sanofi (‘12, 1 case)

and Disease-bearing Mouse System

• Domestic L/O (‘13, 1 case)

Business Results Human Resources • Specialized Research Group for Ab Dev. • Global-leveled BOD & SAB • Global Human Networks

• Domestic & Oversea L/O

(’14, 4 cases) • Government Grant (‘09~’15, $ 12 M)

Pipelines

• Tanibirumab (Phase IIa) • PMC-001 (Preclinical stage) • PMC-201 & PMC-102 (In vivo completed) • PMC-xxxs (>20 Hit candidates)

PharmAbcine’s People Honored

CEO: Dr. Jin-San Yoo •

PharmAbcine, CEO/President

•

KRIBB, Head of The Therapeutic Antibody Ctr.

•

LG Life Science, Head of Therapeutic Antibody Division

•

The SCRIPPS Research Institute, TSRI Senior Associate

•

Howard Hughes Medical Institute at Stanford Univ., HHMI Associate

•

Max-Planck-Institute (MS & Ph.D), MPI Fellow

•

Georg-August Univ. Goettingen (BS)

Global-leveled Management •

Finance and BD : Dr. Sung-Woo Kim

•

Management : Dr. Christopher Kim

PharmAbcine (KAIST/Tech. Analyst) Oxford Bioscience Partners (Texas

Univ./Carnegie Melon Univ., MBA) •

Berkeley MBA) •

R&D : Prof. Dong-Sup Lee Seoul Nat’l Univ. (SNU, MD/Ph.D)

Commendation from MFDS (‘16)

•

Commendation from Ministry of Science, ICT, and Future Planning (‘15)

•

Commendation from Ministry of Health and Welfare (‘14)

•

Commendation from Ministry of Trade, Industry and Energy (‘14)

•

TechConnect National Innovation Award (14’, TechConnect World)

•

Korea Eureka Day Award (14’, KIAT)

•

Pharma Idol (‘12, 7th Annual China Pharmaceutical R&D summit)

•

The 1st GATE project Best Award (’08, Novartis, KOTRA, Samsung etc.)

Innovative R&D Center

Global-leveled SAB • •

Management : Dr. Hongbo Lu OrbiMed (Washington Univ./UC

•

•

Chairman : Prof. Waun Ki Hong MD Anderson Cancer Center, USA Director : Prof. Dong Moon Shin Winship Cancer Institute, USA Director : Prof. Do Hyun Nam Samsung Medical Center, KOREA

•

Head : Dr. Weon Sup Lee PharmAbcine (KAIST)

•

Team 1 Leader : Dr. Jinsang Yoo PharmAbcine (SKKU)

•

Team 2 Leader : Dr. Keun Hee Oh PharmAbcine (SNU)

•

Team 3 Leader : Dr. Sung Ho Ahn PharmAbcine (Tokyo Institute of Technology)

PharmAbcine’s Strategic or financial Investors

And Angel investor!

Our Business Model Leading Global Antibody Therapeutics Management from Global Standard BOD

Profit Structures

(OrbiMed, Novartis, Oxford Biosciences) Internal Discovery and Pipeline Development • Licensing out after PK/Tox study • Profit from Upfront and Milestones (fixed and running royalties)

Innovative Technologies  Fully Human mAb Tech.

 Bispecific Ab Platform Tech.  Cancer Stem Cell (CSC) Library  ADC-based Pipelines

Co-Development with Strategic Partners • Build Competitive Pipelines • Licensing out after Phase I or Phase II • Profit from Upfront and Milestones (fixed and running royalties)

 CAR-T/NK based pipelines  Immune checkpoint blockades

Clinical Sciences from Global Standard SAB (MD Anderson Cancer Center, Winship Cancer Institute, Samsung Medical Center)

Fee based Service • OEM Service for Research Antibody Production • OEM Service for Antibody Biopanning • Profit from Fee for Service

I. PharmAbcine’s antibody library Fully Human Antibodies Highly Successful Screening Hit rate High Diversity (about 10^12) Living Antigen Customized Antibody Selection System Accumulated know-how and experience to handle right panning!

Diverse antibodies with cross species cross reactivity, sub nanoM affinity and Biology against most druggable targets!

II. Fully human IgG pipeline, as best in class

Fully human IgG against:

KDR EGFR EGFRviii cMET ANG2 TIE2 VEGF-C

PD-1 PD-L1 CTLA-4 OX40 TIM3 VISTA PMC-1 PMC-2 PMC-3

Anti-cMET agonistic antibody was out-licensed to ViroMed who’s developing for ischemia, diabetic ulcer, and non oncology indications. http://immuno-oncologynews.com/2014/11/24/3sbio-pharmabcine-sign-agreement-tanibirumab/ http://eng.kddf.org/Tasks/?mode=view&TaskId=104&p=1&DiseaseId=Others

III. DIG-Body Platform and its pipeline:

IgG Backbone Primary target

Func. Domain secondary target

KDR EGFR cMET PD-1 PD-L1 PMC-1 PMC-2 PMC-3

TIE2 DLL4 EGFR cMET PD-1 PD-L1 PMC-1 PMC-2 PMC-3 PMC-4

IV. TIG-Body Platform and its pipelines:

IgG Backbone Func. Domain as primary target as secondary target KDR EGFR EGFRviii cMET PD-L1 PMC-1 PMC-2 PMC-3

DLL4 EGFR EGFRviii cMET PD-L1 PMC-1 PMC-2 PMC-3 PMC-4

Func. Domain as tertiary target CD3

V. PIG-Body Platform and its pipeline

IgG Backbone as primary target KDR

Func. Domain as secondary target cMET

VI. 3G-System Platform for the best performing: CHO cell based High Performance System

>3g/L

3G-Cell line Completed: Protein X Protein Y Avastin biosimilar Zaltrap/Eylea biosimilar On going: Humira biosimilar Xolair biosimilar

VII. Next Generation ADC and CAR-T/NK ADC technology with LinXis

CAR-T Technology with

PharmAbcine: anti-EGFRvIII gene sequence Partner: CAR-T technology

CAR-NK technology with KRIBB

PharmAbcine: anti-EGFRvIII mAb LinXis: Lx® Technology Product: LIN004 (Pre-IND) http://www.linxispharmaceuticals.com/technology/pipeline/

PharmAbcine: anti-cMET mAb-ADC Under the codevelopment partnership

PharmAbcine: anti-EGFRvIII gene sequence KRIBB: CAR-NK technology

Summary of Science & Technologies Commercialization Tech.

Platform Tech.

Fully Human Ab Development Technology Bispecific Ab Development

•

Commercialization Technology

Tumor and tumor microenviroment targeting Ab: Tanibirumab, anti-Tie2, anti-Ang2, etc.

Phase IIa 1 case

•

ADC or CAR-T/NK cells: anti-EGFRvIII

L/O 3 cases

•

Immune checkpoint targeting: anti-Ox40, PDL1, Tim3, VISTA, etc.

•

Tumor and tumor microenviroment targeting Ab: PMC-001 (DIG-KT), PMC-201 (DIG-KN), PMC-404 (DIG-AVc), etc.

•

Technology Ab Therapeutics

Ref.

Immune checkpoint blockades:

L/O 2 cases

anti-PDL1 & CD47

•

Fee for service: 1. Ab discovery (Biopanning) 2. Cell line develop (3G Expression System) 3. Ab production (from lab to pilot scale) 4. Ab characterization

> 2 cases/year

Selected Pipeline roadmap summary Discovery (Early Stage)

`

Pre-clinic (Late Stage)

Phase I

Phase II

Phase III

recurrent GBM

2016 ~ 2019 AMD

2016 ~ 2018

Tanibirumab (Anti-VEGFR2)

TNBC

2018 ~ 2020 China IND 2017

PMC-001, (Anti-VEGFR2 & Tie2)

2018~2019

Gastric cancer

2020 ~ 2024

Pancreatic cancer

US IND 2018

2019~2020

2021 ~ 2022 Breast, Colorectal, Liver cancer

2021 ~ 2024

PMC-307, (Anti-VISTA)

IND 2018

2020

> 20 PMC-XXX, Anti-TME

IND 2019

2020

Tanibirumab Summary-1 

A fully human mAb and targets VEGFR2 (KDR) which is major factor on tumor angiogenesis.



The only mAb therapeutics having murine cross-reactivity among VEGFR2 targeting mAbs under clinical development and therefore, is applicable to translational research using various disease bearing mouse model systems and as a result, can increase the possibility of success in clinical study.



Phase I study was successfully completed at Samsung Medical Center in Korea and Phase IIa with recurrent GBM patients is scheduled to initiate in Australia early this year. (http://clinicaltrials.gov/ct2/show/NCT01660360?term=tanibirumab&rank=1)



Received Innovation Award from TechConnect World which holds a technology exhibition annually in USA (‘14) (http://www.techconnectworld.com/World2014/participate/innovation/innovation_awards.html)



Selected as Best Project in National Research Project 2015 (‘15)



License-Out : TaeJoon pharma (Korea) – indication: Eye diseases, territory: Global 3Sbio (China) – indication: All diseases except eye diseases, territory: China, Russia, Brazil,

♦ IP status Registered

Thailand, Taiwan

Korea, Japan, China, Singapore, EP (15 countries), Australia, Canada, USA

Tanibirumab Summary-2  Preclinical result

 Tanibirumab had shown Anti-cancer efficacies in various tumor-bearing mouse models.  A549 Lung Cancer - Efficacy: Tanibirumab = Avastin - Apoptosis: Tanibirumab = Avastin  MCF-7 Breast Cancer - Tanibirumab > Avastin  MCF-7 Breast Cancer Metastasis - Tanibirumab > Avastin  Colo205 Colon Cancer

Efficacy comparison between Tanibirumab and Avastin in U87-MG GBM orthotopic mouse model

 Hep3B Liver Cancer

Phase I result

http://www.ncbi.nlm.nih.gov/pubmed/25942475 http://www.ncbi.nlm.nih.gov/pubmed/26325365



Up to cohorts 8 (24 mg/kg ) has no DLT observed.



Study of PK/PD from Phase I suggested that increase of some biomarkers (VEGF-A, sVEGFR-2, PlGF) were observed.



Displayed no common side effects like hypertension, bleeding, hemorrhage appeared in Cyramza, Avastin, Zaltrap, Sutent, Nexavar and other VEGF antagonists.



Shown several SD patients (~60%) from all terminal staged cancer patients in Phase I.



Revealed reversible capillary hemangioma on the skin to 50% of patients who were treated with Tanibiruamb http://meetinglibrary.asco.org/content/149434-156

PMC-001(DIG-KT) Summary-1  VEGF/VEGFR2 and Ang2/Tie2 pathways are well known as major factors that induce tumor angiogenesis and metastasis.  It is expected to have superior anti-cancer activity to Avastin by simultaneously neutralizing VEGF/VEGFR2 and Ang2/Tie2 pathways.  We have constructed global-leveled bispecific antibody by DIG-bodyTM platform technology and licensed-out in early developmental stage.  We have received Korea Eureka Day Award from the Government (‘14).  License-Out : 3Sbio(China) – All indications for human (China and Korea)

♦ IP Status Registered Pending

Korea, Australia, Singapore, Russia, China, Japan, EP USA, Canada, Brazil, India

PMC-001(DIG-KT) Summary-2 ďƒ˜ Preclinical Results

Recurrent GBM Orthotopic Model

Liver Cancer Xenograft Model

Anti-tumor efficacy test in Hep3B-xenografted mouse

Pancreatic Cancer Orthotopic Model

Anti-tumor efficacy test in Avastin resistant, U87-MGxenografted mouse

Pancreatic Cancer Metastasis Model

Anti-tumor and anti-metastasis efficacy test in CFPAC-1_Luc- xenografted mouse

Tanibirumab and PMC-001 are best candidate to combine with Immune Checkpoint blockade

Angiogenesis inhibitors like Avastin and Cyramza with Immune Checkpoint blockades combinations shows synergy of efficacy and manageable safety.

Since Avastin, Cyramza, Tanibirumab and PMC-001 have tendency to normalize and stabilize disorganized , leaky and fragile tumor vessel temporary in early phase.

During that period of time, immune checkpoint blockade can be delivered to tumor site more efficiently by using the temporary normalized vessel.

In the same way, the activated killer T cell can utilize this normalized vessel to reach tumor mass.

Tanibirumab and PMC-001 are best candidate to combine with Immune Checkpoint blockade

Inhibitors of VEGF-VEGFR2 pathway also help activated killer T cell to infiltrate into cancer cells.

We strongly believe that Tanibirumab and PMC-001 will be the best candidate to combine with Immune Checkpoint blockades to perform the superiority to Avastin or Cyramza due to their limitation.

PATIENTS ARE WAITING! LET’S WORK TOGETHER! THANK YOU!

wincancer@gmail.com