a world-class biotechnology company in asiamops.twse.com.tw/nas/str/654020151022m001.pdf · eusol...

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)


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)


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


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


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


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


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


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.


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) ✔ ✔ ✔ ✔ ✔ ✔


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


Facilities

Compliance to international standard

Scale for global market

Speed in execution


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


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


2 x 500L Single-use trains


Harvest by Filtration


Ä KTA-Ready Chromatography


Virus Removal & Formulation


4 X 2,000L Drug Substance

& Drug Product Manufacturing

JHL- Biotech Wuhan - Facilities


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.


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


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


China – B1 Development


3L Applikons – 06APR2015

PA800s/HPLCs – 30MAR2015

China – B1 200L pilot facility


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


Commercial Facility: Modular Design (KuBio)


KuBio assembled


Commercial Facility



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


Thank you!


a world-class biotechnology company in asiamops.twse.com.tw/nas/str/654020151022m001.pdf · eusol...

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