A World-Class
Biotechnology
Company in Asia
Biosimilars route to success
Assemble the right team
Secure long term financing
Put in place technology and plant capacity
Select the appropriate products
Develop the right regulatory strategy
Execute the plan and obtain government grants
2CONFIDENTIAL | JHL Biotech | 2015
Company Overview
Founded in 2012 by Racho Jordanov and Rose Lin, two Genentech veterans with
more than 50 years of combined experience, to develop biosimilars and innovative
biologics through bioprocessing and manufacturing innovations.
JHL Biotech is backed by top-tier venture capital firms
A Kleiner Perkins Caufield & Byers (KPCB) China Fund, Sequoia Capital, Biomark
Capital, and China Development Investment Bank (Taiwan)
B PIDC, Milestone Capital, Fubon and Taishin
C Fidelity, Milestone, Tipfront Ltd
Total $ Raised - $135 Million, Cash on hand - $80 Million
JHL Biotech team
– Total headcount ~ 100 (18 Ph.D.’s)
– Management team has previous experience from leading pharma and biotech
companies (Genentech, Roche, Amgen, ImClone, Johnson & Johnson)
Our Mission: Making World-Class Medicines Affordable
CONFIDENTIAL | JHL Biotech | 2015 1
Experienced Leadership
Racho Jordanov
Co-founder
President, CEO
Rose Lin
Co-founder
GM, Taiwan
Genentech
– Led construction of manufacturing plants for Rituxan, Herceptin, Avastin, Xolair in
US and Singapore.
– Responsible for technology transfer of hGH, Activase, Raptiva, Herceptin to DSM,
Ono Pharmaceutical, Cardinal Health, Serono and Novartis.
Serono
– Responsible for construction and FDA approval of Mammalian Cell Culture
facilities in Randolph MA.
– Responsible for construction of Process Development Pilot plant in Switzerland.
Genentech
– Responsible for IND submission of all Genentech clinical products.
– Key roles in Quality, Validation, Manufacturing.
Eusol Biotech, Taiwan
-- Plant Director, responsible for Manufacturing, Quality, Regulatory and Finance
Jinn Lin, PE
GM, China
L&K Engineering Co Ltd (2005-2013)
– President Taiwan, Guam, Chongqing
– Director RSEA
PSENG (1987 - 2005)
MBA (Finance) Rutgers, ME (Mech), BS (Mech)
CONFIDENTIAL | JHL Biotech | 2015 2
Experienced Team
Max Chan
CFO & VP Business Development
TaiGen BioPharmaceuticals-CFO ( 2010-2015)
Himax Technologies NASDAQ: HIMX-CFO (2005-2010)
Nick Kotlarski, PhD
VP Engineering/Validation
Synertec Asia, General Manager (2006-2013)
GroPep Limited, Manufacturing Manager (2002-2006)
David Kapitula
Sr. VP China Operations
Roche/Genentech Singapore, Dir. Quality Control (2009-2013)
Cell Genesys, Sr. Director Quality Control (2006-2008)
Charles Winter
VP Manufacturing and Technology Genentech 17 years Process Development
Gilead Inc. 4 years Director Biotech Development
Peter Pang, PhD
Director, Regulatory Affairs New B Innovation, Dir. Regulatory Affairs (2008-2013)
14 years in FDA, EMA, CFDA, GLP, GMP, GCP guidance in support of
manufacturing, preclinical & clinical projects
Genentech 23 years Process Development - PurificationGreg Blank
Sr. Director, Process Purification
Sohail Qurashi
Dir, QA/QC
Roche, Senior Manager Quality (2004-2015)
Monsanto, Manager QC (2002-2004)
Novo Nordisk, Group Leader (1991-2002)
CONFIDENTIAL | JHL Biotech | 2015 3
Andreas Nechansky PhD
VP Research and Analytical
VELA Labs COO 9 years,
Aphton/Igeneon, 2 years
KC Carswell, PhD
Sr. Director, Process Development
Genentech, Principal Engineering/Sr. Group Leader, MSAT 6 years
Xoma, Sr. Fermentation Development Scientist 2 years
Experienced Team (cont’d)
John Chan, PhD
Group Leader, Formulation
PhD University of Sydney
B.Pharm
Peter Wang
Associate Driector, Purification Mfg
& Business Development
Gloria Cheng
Group Leader, Purification PD
Toby Hong, PhD
Group Leader, Bioanalytical Dev
Tim Lin
Group Leader, Cell Culture PD
Jennifer Kuan, PhD
Associate Director, Cell Culture Mfg
Wan-Ting Hsieh, PhD
Group Leader, QC/AD
Amber Chen, MBA
Ass. Director, Finance & Accounting
15 Years Experience
Amgen (2011 – 2013)
Genentech (2004 – 2009)
Clemson University, SC, USA
University of Chicago Medical Center,
8 Years Experience
Thermo Fisher, Mycenax, Academia Sinica
8 Years Experience
PharmaEssentia, Academia Sinica
University of Pennsylvania (Biophysical Chemistry)
National Taiwan University (M.S., Chemistry)
15 Years Experience
BenQ, Chimei Innolux, Yuanta
CONFIDENTIAL | JHL Biotech | 2015 4
18 Years Biotech Industrial Experience,
UBI Asia Biotech Pharmaceutical, Univ. Idaho Chemistry, NTHU
Jill Liu, US CPA, CIA, MBA, LLM
Financial Controller
15 Years Experience
PWC, BNP Paribas, IT startups
JHL Biotech Inc. Organization
7CONFIDENTIAL | JHL Biotech | 2015
Business Strategy Based on Capabilities
Developing
proprietary
biosimilar
pipeline
Contract
Manufacturing
partnerships
Collaboration &
Licensing of
innovative
biologics
Deep biologics
development &
manufacturing
expertise
Revenue Model
Near-Term
(1-3 yrs)
Med-Term
(3-5 yrs)
Long-Term
(5-10 yrs)
Commercial sales (major markets)
Commercial sales (emerging markets)
Upfront & milestone (partnerships)
Biosimilars Commercial sales (emerging markets)
Upfront & milestone (partnerships)
Manufacturing (initial infrastructure)
Development costs (focus on CMC; start clinical studies)
Revenue
Expenses
Contract manufacturing
Manufacturing (expand infrastructure)
Development costs (emerging market being more significant)
NME Partnerships (licensing, clinical)
Development costs (global market)
Business Strategy
Process Development & Manufacturing of Mammalian Cell-based Biologics
Specialty
Biosimilars
High-
Value
Biosimilars
Innovative
Biologics
Scientific Risk
Target Mkt
Market Value
Time to Revenue
Low
Regional
Low
Short
Low
Global
Medium
Medium
High
Global
High
Long
Infliximab
Trastuzumab
Adalimumab
Bevacizumab
Cetuximab
Omalizumab
Rituximab for regional markets
rhDNase (Pulmozyme)
Anti-NKp46 mAb for T1D (BioLineRx)
Other NME’s
Balanced
portfolio
approach to
build a world-
class biotech
company
Core
Competency
JHL Product Pipeline
Project Type Indication Dev. Stage NME / Biosimilar
Product portfolio
JHL1101 mAb Rheumatoid Arthritis Pre-Clinical Biosimilar
JHL1922 Enzyme Cystic Fibrosis Pre-Clinical Biosimilar
JHL1149 mAb Oncology Pre-Clinical Biosimilar
JHL1188 mAb Oncology Pre-Clinical Biosimilar
JHL1228 mAb Auto-immune Pre-Clinical Biosimilar
JHL1148 mAb Macular Degeneration Pre-Clinical NME
JHL1155 mAb Oncology Pre-Clinical NME
JHL1311 mAb Type 1 Diabetes Pre-Clinical NME
JHL1922 Enzyme Acute Coronary Syndrome Pre-Clinical NME
11
Biosimilar Market Potential
First generation products are
mostly recombinant proteins
– ESA
– G-CSF
– Human Growth Hormone
In the next 10 years, ~$100B of
biologics are expected to lose
patent protection
Second generation will include
higher-value monoclonal
antibodies.
– First wave: Remicade, Rituxan,
Herceptin, Humira, Enbrel
– Next wave: Other mAb’sSource: Decision Resources 2011 for US/EU5.
ROW added based on assumed 30% of WW total
JHL In-House Lead Candidates under Development
Project Reference Product Global Branded
Sales (2013)
Regional Focus
JHL1101 Rituxan® $8 Billion China, SE Asia
JHL1922 Pulmozyme® $640 Million EU, US
JHL1149 Avastin® $11 Billion Global
JHL1149 Lucentis® $5 Billion Global
JHL1188 Herceptin® $7 Billion Global
JHL1228 Humira® $7 Billion Global
13
JHL recognizes that while innovative biologics can hit the “jackpot,” the
biosimilar market is a large piece of the pie and has higher CAGR growth
Biosimilar Regulatory Landscape
Russia
China
India
Brazil
US
Canada
Europe
Australia
Japan
Mexico
South
Africa
Saudi
Arabia
Iran
Cuba
Venezuela
Colombia
Ecuador
Peru
Chile
Argentina
Jordan
Taiwan
S. Korea
SingaporeMalaysia
Pathway final
Pathway in development
Plans to develop pathway
No specific pathway
Snapshot as of 2013
Europe Guidance issued (2005)
USBPCIA enacted* (2010);
draft guidance issued (2012)
Canada Guidance issued (2010)
MexicoDraft guidance issued (2009);
operating rules signed (2011)
Australia Adopted EU legislation (2008)
Japan Guidance issued (2009)
WHO Guidance issued (2009)
Brazil Guidance issued (2010)
India Guidance issued (2012)
ChinaGuidance issued (2015)
Russia No specific pathway
ROW
Some countries have or are
adopting guidance following the
EMA and/or WHO (eg, Malaysia,
Taiwan, Korea); many others
have not yet adopted regulatory
standards to approve biologics
* BPCIA, Biologics Price Competition and Innovation Act
Complexity of biosimilars requires technical know how
15CONFIDENTIAL | JHL Biotech | 2015
Source: Citi Research, Company data.
Biosimilar Development is Complex
The end-product is only the “tip of the iceberg”
The full picture includes: process development, characterization, manufacturing,
pre-clinical, clinical, etc.
Source: Adapted from Kozlowski S, Swann P. Advanced Drug
Delivery Reviews 2006; 58: 707–722.
The in vitro characterization stage leads to four assessment possibilities for
proposed biosimilar products (FDA guidelines):
1. Not similar. Further development through the abbreviated biosimilar pathway is “not
recommended.”
2. Similar. Additional analytical data or other studies are necessary.
3. Highly similar. The sponsor may “conduct targeted and selective animal and/or
clinical studies to resolve residual uncertainty and support a demonstration of
biosimilarity.”
4. Highly similar with fingerprint-like similarity. The sponsor may “use a more
targeted and selective approach to conducting animal and/or clinical studies to
resolve residual uncertainty and support a demonstration of biosimilarity”
(emphasis added).
Aiming for a “Highly Similar” assessment
17CONFIDENTIAL | JHL Biotech | 2015
d
JHL utilises its excellence in early stage product development to develop a “highly
similar” biosimilar product that minimises the requirements of resource-intensive pre-
clinical and clinical studies.
Process Science and
Analytical
Development
CONFIDENTIAL | JHL Biotech | 2015 9
Discovery / Research
Nonclinical Phase I Phase II Phase III Commercial
Antibody Generation and
Cell Line Development
Upstream Process Development
Downstream Process Development
Analytical Development
Formulation Development
cGMP Manufacturing
Regulatory Support
Ongoing Technical Development / Support
Process Development @JHL Biotech
Analytical Capabilities is Key to Success
Structural Characterization– Amino acid sequence
– Amino acid composition
– Terminal amino acid sequence
– Peptide map
– Sulfhydryl group(s) and
disulfide bridges
– Carbohydrate structure
Physicochemical Properties– Molecular weight or size
– Isoform pattern
– Electrophoretic pattern
– Liquid Chromatographic
pattern
– Spectroscopic profiles
Functional Assays
Analytical Development
Thorough physiochemical characterization of the cell line and product are critical to the success of process development and the product.
Analytical knowledge base is developed in parallel with the manufacturing process such that critical quality attributes and process parameters are an integral part of the process evaluation.
Will ensure analytical methods are well designed and appropriately qualified/validated as required though the product life-cycle.
CONFIDENTIAL | JHL Biotech | 2015 16
JHL Analytical Support Capabilities
In-House methods for > 98% of all analytical support Analytical Capabilities Char. PD Form. IP EM COA Stab. TT Safety PV RM
CDC Assay ✔ ✔ ✔ ✔
Cell Based Potency ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
cIEF ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
cSDS Non-Reduced ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
cSDS Reduced ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
ELISA Assays ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
HILIC HPLC ✔ ✔ ✔ ✔ ✔ ✔ ✔
HPAEC PAD ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Identity ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
IEC HPLC ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
SEC HPLC ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
N-Glycan Analysis ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔Mannose Phosphorylation
Glycan Analysis ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Microheterogeniety ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
ProA Titer ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Process Residuals ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Sialic Acid ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
UV Titer ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Residual DNA ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
pH ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Conductivity ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Osmolality ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Endotoxin ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Mycoplasma ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Cell Bank Qualification (QPCR) ✔ ✔ ✔ ✔ ✔ ✔
CONFIDENTIAL | JHL Biotech | 2015 17
Manufacturing Capabilities
0.22mFiltration
Master Cell Bank (MCB)
Working CellBank (WCB)
Shake flask
Incubator
Chromatography
I to III
Ä KTAready
MilliporeSkid
Virus Filtration (VF)
Seed Train
50L
Bioreactor
XDR-50
Production
500L
Bioreactor
XDR-500
Harvest
Depth
Filtration
Skid
Ultrafiltration/Diafiltration
SciLog UF/DF Skid
Bulk FreezeBag in
BioShell
Storage
Cell Line Seed Lab Cell Culture Purification Formulation
Media Preparation Buffer Preparation
CONFIDENTIAL | JHL Biotech | 2015 10
Facilities
Compliance to international standard
Scale for global market
Speed in execution
CONFIDENTIAL | JHL Biotech | 2015 24
Centre of Excellence: Location
Hsinchu – Transport
– Equidistant to Taipei from the
airport
– Positioned on National Highway
– Positioned on High-Speed Rail
• 40 minutes from downtown Taipei
Hsinchu – Statistics
– Oldest city in Northern Taiwan
– Population 500,000
– High-tech hub of Taiwan
25CONFIDENTIAL | JHL Biotech | 2015
JHL Biotech Taiwan – Facility Overview
GMP production– Based on GE FlexFactory® Single-use
– Bioreactor hall with 2 x 500L Bioreactor trains
– Capacity for additional 2 x 1000L Bioreactors
– Purification suites (primary and final polishing room)
– Media and buffer prep areas
– Autoclave/wash areas
Warehouse, Sampling/Dispensing to Grade C
QC laboratories area
Process development laboratory
Utilities area (HVAC, Clean & Black utilities)– Designed for 80 batches/year (4 bioreactors)
Amenities
26CONFIDENTIAL | JHL Biotech | 2015
2 x 500L Single-use trains
27CONFIDENTIAL | JHL Biotech | 2015
Harvest by Filtration
28CONFIDENTIAL | JHL Biotech | 2015
Ä KTA-Ready Chromatography
29CONFIDENTIAL | JHL Biotech | 2015
Virus Removal & Formulation
30CONFIDENTIAL | JHL Biotech | 2015
4 X 2,000L Drug Substance
& Drug Product Manufacturing
JHL- Biotech Wuhan - Facilities
31CONFIDENTIAL | JHL Biotech | 2015
First 2,000L Facility, JHL-1
Wuhan – Access– International airport (4th in China)
– High-speed rail to Beijing, Guanxiao, Shanghai
– Yangtze river
Wuhan - Talent– Most populous city in inland
China (10,000,000)
– 3rd in China for scientific and educational strength
Wuhan - Biolake– 32km2 of >500km2 development
zone for biotech. companies.
32CONFIDENTIAL | JHL Biotech | 2015
JHL- Wuhan site Plan View
5,800 m2
• Administration• Quality Control
• Process
Development3,300 m2
• High-bay warehouse• Sampling (Grade D)
• 150 pallet < -20°C
2,550 m2
• JHL-1 KUBio™
1,100 m2 + Roof
• Central utilities
Future• JHL-2
Future• Fill-finish
• 5,200 m2
CONFIDENTIAL | JHL Biotech | 2015 33
2.5 Hectares
Process Development - China-for-China
Preclinical production at 200L-scale
– 1 x 50 & 1 x 200L GE FlexFactory® Single-use bioreactors
– Millipore POD harvest
– AKTAReady and AKTAPilot Chromatography
– Millipore VF and UF/DF
QC laboratories
Utilities
1/10th of Commercial-scale
Trials start in June, 2015
CONFIDENTIAL | JHL Biotech | 2015 34
China – B1 Development
35CONFIDENTIAL | JHL Biotech | 2015
3L Applikons – 06APR2015
PA800s/HPLCs – 30MAR2015
China – B1 200L pilot facility
36CONFIDENTIAL | JHL Biotech | 2015
XDR50 - 30 Mar, 2015
XDR200 - 30 Mar, 2015
JHL- Biotech Wuhan 4X2000L
LARGEST IN THE WORLD
Manufacture APIs by cell culture for Phase III and sale
– APIs for international markets
‘Big Brother’ of Taiwan Pilot facility
– Identical hybrid GE FlexFactory basis
– 4 x 2,000L single-use cell culture reactors
– Single purification train
Process Development capability
– Receive developed processes (e.g. from Gaithersburg)
– Develop in China for China
Greenfield construction
– Phase 1: API
– Phase 2: Double capacity and add finished product capability
37CONFIDENTIAL | JHL Biotech | 2015
Commercial Facility: Modular Design (KuBio)
38CONFIDENTIAL | JHL Biotech | 2015
KuBio assembled
39CONFIDENTIAL | JHL Biotech | 2015
Commercial Facility
CONFIDENTIAL | JHL Biotech | 2015 40
41CONFIDENTIAL | JHL Biotech | 2015
Facilities Summary
* Capable of small-scale commercial production
MFG (Taiwan) Process Dev (China) Commercial (China)
Purpose Development + Phase II* Pre Clinical Development + Sale
Qualified Q1, 2015 Ready Q2, 2015 Q1, 2016
Capacity
Design Batches/year 40 (80) 12-15 80
MAb capacity/year 30 (60) kg 3-4kg 240 kg
Design Standards
21 CFR
Eudralex
PIC/S Annex 13
WHO
Pharmacopeia USP, EP, CP, TP USP, EP, CP USP, EP, CP, TP
Manufacturing Platform
GE FlexFactory® GE/Millipore
Cell Culture 2 (+2) x 500L 1 x 200L 4 x 2,000L
Downstream 3 day at 1.5 kg 2 weeks at 600g 3 day at 6kg
Biosimilars route to success
Assemble the right team
– More than 250 years combined experience – Genentech, Amgen
Secure long term financing
– $135 Million from KPCB, Sequoia Capital, CDIB, Milestone, Fidelity
Put in place technology and plant capacity
– Two manufacturing plants; Single use technology; 500KG/year capacity for mAbs
Select the appropriate products
– Top 10 market share, difficult to make, orphan drug
Develop the right regulatory strategy
– Clinical trials in EU with products made in China for China and global markets
Execute the plan and obtain government grants
– $10Million CMO revenue in 18 months; First IND/CTA 2015
42CONFIDENTIAL | JHL Biotech | 2015
Thank you!
71CONFIDENTIAL | JHL Biotech | 2015