Chunghwa Chemical Synthesis & Biotech Co., Ltd.

Introductionof

Chunghwa Chemical Synthesis& Biotech Co., Ltd.

Profile Founded in 1964 First registered and one of the largest bulk pharmaceutical

chemical manufacturers in Taiwan First Taiwan FDA approved plant (1984)

Turning Points in 1997 Formed the New Management Team in 1997 Invested US$ 20 million to construct

• 4 cGMP Plants for Synthetic Products• 2 cGMP Plants for Biotechnology Products

Established US Sales Office-Pharmaports in 2000 Products Developing both synthetic & biotech products Participate new drug development and contract

manufacturing Global Market Oriented with Emphasis on U.S.A., Europe, Japan

Initial public offering on December 20, 2010

2

Brief History of CCSB

3

Sales from 2004 to 2016

USD Thousands

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

45,000

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Export

Domestic

4

Sales from 1998 to 2016

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

USD Thousands

Synthetic Products Biotech Products Contract Manufacturing

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Americas53.03%

Americas53.03%

Domestic8.22%

Domestic8.22%

Europe7.9%

Europe7.9%

Asia30.79%

Asia30.79%

Sales Area in 2016

ROW0.06%ROW0.06%

6

Management Team

President – Dr. Chih-Ping Yang– Ph.D., Organic Chemistry, Univ. Texas at Austin, USA– General Manager, Chugai Pharma Taiwan 2005-2015– Founder, President & CEO, CytoPharm, Inc., Taiwan 2003-2004– President & CEO, GeneTrol Biotherapeutics, Inc., Oakland, California, USA

2002-2004

VP of Administration Management - Mr. Denry Huang– Deputy Plant Manager

– Marketing & Sales Manager

– General Manager, Shaoguan City Fermentec Co., China

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VP of Sales Management - Mr. Chuan Wen Chen– Marketing Director, Chugai Pharma Taiwan 2009 - 2016

– Business Development & Pharmaceutical Consultant, A-strong Co., Ltd. 2008 - 2009

– General Manager/Pharmaceuticals, Abbott Pharmaceutical Division, Taiwan 2001 - 2008

– Marketing Director, Serono Taiwan 1997 – 2001

Plant Manager – Mr. K. H. Tseng– B.E. in Chemical Engineering

– Pharmaceutical Manufacturing since 1976

Management Team

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Management Team (cont.)

Biotech R&D Lab Director – Dr. Alex Mai– Ph.D. Chemistry, National Taiwan University

– API R&D since 1994

Synthesis R&D Lab Director – Dr. Kevin Lee– Ph.D. Chemistry, National Tsing Hua University

– API R&D since 1994

Analytical R&D Lab Deputy Director – Dr. Ping-Shu Chen– Ph.D. Chemistry, National Sun Yat-sen University

– API R&D since 1997

9

Management Team (cont.)

Regulatory & QA Manager – Dr. W. P. Wang– Ph.D. Ch.E., University of Massachusetts

– Experienced in API R&D, Production and QA/QC since 1995

Chief Operation Officer, Pharmaports – Mr. Joseph Chen– Master, National Yang-Ming University, Taipei, Taiwan – Manager, Global business 2006 – 2016– Sales Specialist, Merck Display Tech. Ltd., Taiwan 2005 – 2006– Account Manager and Marketing Specialist, Everlight Chemical Indl.

Corp., Taipei 2002 - 2005

10

Management Team (cont.)

Production Technology Lab Deputy Director – Dr. Yen-Shih Tung– Ph.D. Chemistry, National Tsing Hua University

– API R&D since 2007-2015

– Production Technology since 2016

Projects Management Office Deputy Manger – Dr. Ting-Huei Lee– Ph.D. Chemistry, University of Sussex, UK

– API R& D since 2005

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CCSB Organization Chart

PresidentDr. Chih-Ping Yang

The BoardChairman

Mr. Derek WangThe Auditor

Mr. Jacky Hong

Engineering Div.Mr. G. F. Tsai

Production Div.

President Office

R&D Div.Dr. Alex Mai

(Acting)

Business Div.Mr. Chuan Wen Chen

Administration Div.Mr. Denry Huang

PharmaportsMr. Joseph

Chen

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Research and Development

13

R & D Manpower

Synthesis Biotech Analytical Total %

Ph.D. 6 5 2 13 25.49%

Master 10 8 8 26 50.98%

Bachelor 4 2 3 9 17.64%

Others 1 2 0 3 5.88%

Total 21 17 13 51

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Biotech Capabilities

Strain ImprovementObtain high producer strain through screening and mutation

Fermentation Process Development & Commercialization

Pravastatin Sodium; Rapamycin (Sirolimus); Mycophenolate Mofetil; Tacrolimus(FK506);Caspofungin; Temsirolimus; Everolimus; Biolimus; Zotarolimus

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Contract Research & Development

Antiarrhythmia Drug– Collaborated with National Science Council & National Taiwan

University in Taiwan Blood Substitute, Antioxidant Drugs

– Collaborated with SynZyme in U.S. funded by DOD & NIH Antiradiation Drugs

– Collaborated with SynZyme in U.S. Macrolide

– Collaborated with a U.S. Biotech company COX II Inhibitor

– Collaborated with a German company

16

Official cGMP InspectionsYear Authorities Nation Product2002 FDA US Methocarbamol

2005 FDA US Pravastatin

2007 KFDA Korea Methocarbamol

2008 TFDA Taiwan Trandolapril

2009 Koln Germany Pravastatin

2009 TFDA Taiwan GMP Systems

2011 FDA US Dexb; MMF; Tacrolimus

2012 Koln Germany Pravastatin

2013 TFDA Taiwan OLO; RAPA

2013 PMDA Japan Tacrolimus

2013 KFDA Korea Tacrolimus

2014 FDA US Full Products

2015 Koln Germany Pravastatin Sodium; Tacrolimus

2015 TFDA Taiwan Full Products

2015 Cofepris Mexico Caspofungin

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Active US DMF List

DMF 26271Ethyl lcosapentate

DMF 26819Everolimus Pre-Mix

DMF 27216Everolimus

DMF 27585Caspofungin Acetate

DMF 30103Omega-3-Varboxylic Acids

DMF 31189Rapamycin (Sirolimus)

DMF 31276Carfilzomib

DMF 13080Methocarbamol

DMF 14234Guaifenesin

DMF 14235Pravastatin Sodium

DMF 17399Rapamycin

DMF 17573Trandolapril

DMF 18494Mycophenolate Mofetil

DMF 18985Tacrolimus

DMF 22430Olopatadine HCl

DMF 23213Tacrolimus SD20

DMF 23434Metaxalone

DMF 23435Mycophenolate Sodium

DMF 24372Mycophenolate Mofetil HCl

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Equipment for Synthesis

Glass-lined Reactors: Total Volume 24,000 L

Stainless Steel Reactors: Total Volume 140,000 L

Hot-Air Tray DryersVacuum Tray DryersDouble-cone Dryers

Hammer MillFitz MillJet Mill

Hastelloy CentrifugesStainless Steel Centrifuges

Dryers

Reactors

SynthesisCentrifuges

Mills

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Equipment for Biotech

1,250 L – 30,000 L FermentorsTotal 137,000 L Fermentation Volume

Filter Press Disk CentrifugeColumnsUltra-filtrationPreparative HPLCLyophilizer

Lyophilization

Biotech

Fermentation

Purification

20

Equipment for Analytical

Analytical

GC/MS

LC/MS

UPLC

X-ray Powder

Diffraction

GC

HPLC

216 inch MPLC system

2 inch and 3 inch HPLC column

Instrumentation

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Waters preparative HPLC system 2 inch DAC column

Instrumentation (cont.)

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Instrumentation (cont.)

Powder X-Ray Diffraction

HPLC

GC

LC Mass

UPLC

24

Instrumentation (cont.)

GC/MS

25

Instrumentation (cont.)

GE AKTA Purifier UPC 100

BioTek Synergy H1 Hybrid Reader

KvickLab Cross

Flow System

26

Instrumentation (cont.)

Pyros Kinetix Flex Automatic Endotoxin Detection System

GEA Niro High Pressure Homogenizer

27

Instrumentation (cont.)

Mbraun Glove box

Type: UNILAB-BBio Rad ChemiDoc XRS+ Imaging System

28

Location & Buildings

CCSB

Taoyuan Int’l Airport

Located in Shu-Lin,New Taipei City

20 km South West of Taipei

34,000 m2

273 Employees

As of December 2017 Taipei Songshan Airport

29

CCSB Campus Layout

30

Chunghwa Chemical Synthesis & Biotech

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cGMP Commercial Plants

cGMP Plants

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Synthetic Pilot Plant

75 L Stainless Steel Reactor

50 L Glass Lined Reactor

50 L Cone Dryer & 25” Centrifuge

33Freeze Dryers

Synthetic Pilot Plant (cont.)

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Synthetic Commercial Plants

3,000 L Glass Lined Reactors

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Synthetic Commercial Plants (cont.)

Stainless Steel Reactors

Cone Dryer in Controlled Room

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Biotech Pilot Plant

5 L Fermentor

600 L Fermentor

22 L Fermentor

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Biotech Commercial Plant

ABEC 75L, 250L & 1250 L Bioreactors

ABEC 250LBioreactors

38

Biotech Commercial Plant (cont.)

Autoclave

Incubator & Shock Box

Biosafety Cabinet

39

Biotech Commercial Plant (cont.)

20,000 L & 30,000 L Fermentors

40

Biotech Commercial Plant (cont.)

5,000 L Glass-lined and Stainless SteelReactors for Purification Process

41

Biotech Commercial Plant (cont.)

Recovery & Purification Equipment Ultra Filtration

42

Whole Drug Life Cycle Support

Pre-clinical Phase I/II Phase III/Launch

Drug Life Time

grams kilograms tons/multi-tons

43

Summary of CCSB

Over 50 years of API manufacturing experience FDA and Health Authorities approved cGMP facilities for

synthesis & biotech APIs Fully cGMP trained and experienced personnel Strong R&D support Proven records for cost effective and on-time delivery of

contract manufacturing from lab to commercial scales Good communication skills & prompt response