Biotech Collaboration in Taiwan
Chung-Hsiun Wu, Ph.D., CEODevelopment Center for Biotechnology
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Outline
1. About DCB
– R&D capabilities
– BD capabilities
– Collaboration cases
2. Future Prospects
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The best partner for biotech industry!
Mission:To facilitate the development of the biotech industry in Taiwan
• 35 years of history, a government founded non-profit organization
• 400 employees (60% R&D)
• 5 spun-off companies
• 2500+ former employees → workforce in pharmaceutical / healthcare
industry• Promoter for governmental policies• Think-tank for biotech policy• R&D: New drug development (biologics, small molecules)• Developing emerging technology • Training professional workforce• Promoting collaborations among industry, academia, and research institutes
About DCB
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USA
CHINA
JAPAN
TAIWANHeart of Asia
• National Biotechnology Research Park• Xizhi Campus• Nankang Software Park
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Three Campuses
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A: Translational Medicine Research Center B: Core Thematic Center C: BioHub Taiwan D: Bioinformatics Center E: Development Center for Biotechnology F: Taiwan Food and Drug Administration G:National Laboratory Animal Center Academia Sinica (0.5km away)
Basic Research
Translational MedBioinformatics
New Drug DevelopmentPreclinical
Study
RegulatoryOffice
Commercialization Incubation
We are here !Eco-Friendly Campus
Innovation/ Incubation/ Integration
National Biotechnology Research Park
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Board of DirectorsChairman
Supervisors
Auditing Office
Occupational Safety & Health
Human Resource
Accounting
Strategic Planning & Project Management
President Office
Translational Medicine
Laboratory
Division of Industrial
Development
Division ofAdministration
Innovation & Entrepreneur Core (IEC)
Legal Affairs & IP Management
Drug Commercialization Center (DCC)
Biotechnology and Pharmaceutical Industries Promotion Office (BPIPO)
Public Affairs
Project Management
Institute of Pharmaceutics
Institute for Drug
Evaluation Platform
Institute ofBiologics
President
Global Research Collaboration
400 Employees (2019)
Ph.D.: 68 Associate: 17
M.S.: 212 Others: 8
B.S.: 52
Alumni Club
Special Tasks
Organization
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RD Focus ---New Drug Development
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Services for Preclinical
Studies
Business
Development
New Drug
Development
From Bench-top to Commercialization
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Lead
Discovery
Validation
Optimization
Preclinical
ADME ToxIND
Clinical Trials
Phase I, II, IIINDA Market
Innovative projects
Clinical Trial
R&D Focus --- New Drug Development
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• Drug Design, Medicinal Chemistry, and Formulation
• DM/PK (ADME), Animal Pharmacology , and Toxicity Testing
• Process Development for GMP Production
Per-Clinical Research IND Clinical Study NDA Market
Regulatory Support
Cell Line Development Process Development & Process Characterization(QbD)
Analytical Development CGMP Manufacturing (Mammalian cell& Microbial)Protein Characterization
Documentation SupportBiosafety Test (TFBS)Toxicology (QPS)
Quality Management
Integrated R&D Core Capability
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BioengineeringProtein
EngineeringProtein
ExpressionProtein
Characterization
Biologics Development-1Infectious Diseases
Institute of Biologics
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Biologics Development-2Immunotherapy
Institute of Biologics
• Protein expression/ purification- Parallel system scale-down development (100-250ml) - Bioreactor process development (5L/50L )- Purification process development- Continuous bioprocess
•Biofunctional assay •Antibody engineering
- Humanization- Affinity maturation- Mono-glycosylated Ab
• Phage display• B cell/plasma cell• High throughput screening system
• Ab types – IgG, BsAb, ADC, scFv, Fab, CAR-T
• Antibody Characterization - Physical, chemical, biological, formulation and stability studies
•CHO/vector engineering - High yield cell line screening
• Microbial cell line development for scFv, Fab, BsAb(secreted)• Medium optimization / Metabolic engineering • Minibioreactor system
PreclinicalDevelopment
LeadAntibody
Candidateantibody
LeadOptimization
Antibody Screening
IND Filing
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Biologics Capabilities
Her2/CD3Globo H/
CD3
EpCam/CD3
ICOSL-VEGFR2
ICOSL-MSLN
MSLN/ CD3
Pharmacology
PK / PD
Toxicology
CMC
Clinical Phases
Bio Safety
CAR-T
VEGFR2 Globo H
Globo H
TMCC3
MSLN
PDL1
Phage Display
HSV
MDR-01
STAPH Human Library
HSV
H7N9One-Step
Conversion
Human Single B Cell Sorting
Mouse Library
Phage Display
Globo H
TMCC3
CSC-1
VEGFR2
ENO-1
CSF1R
CD73
TMCC3
IL-20
TIM3
PD1
PDL1Humanization
Hybridoma
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Integrated Antibody Platform
© 財團法人生物技術開發中心版權所有 保留一切權利
Cell line development
Bioprocess development &Scale-up process
Purification &Initial formulation
development
Tox materialproduction
Cell line development Bioprocess development
Purification process development Tox material production
5L & 50L
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Cell Line Development & Bioprocess Development
LeadDiscovery
ValidationOptimization
Preclinical, Tox, CMC IND Phase I Phase II
Infectio
nIm
mu
ne
LT-Flu Vaccine 2012 IND
LT-Hib Vaccine 2012 IND
MAb HSV 2014 IND
Therapeutic MAb for MDR Bacteria
MAb H7N9
MAb IL-20
MAb ENO-1
MAb Globo H
ICOS ligand/anti-VEGFR2 bifunctional protein drug
MSLN/CD3 BsAb
Globo H/CD3 BsAb
Her2/CD3 BsAb
CAR-T for Cancer
Mab Tim3
Mab PDL1
MAb CD73
On
colo
gy
Out licensed
LT-Allergy Vaccine 2018 IND
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Pipeline in Biologics
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Medicinal Chemistry
Computer Modeling
Medicinal Chemistry
Institute of Pharmaceutics
In vitro Assays
Mode of Action Analysis
In Vitro Biology
Institute of Pharmaceutics
PreclinicalDevelopment
Hit to Lead
CandidateSelection
LeadOptimization
Target Screening
IND Filing
Small Molecule Synthesis Platform• Ligand-based/structure-based rational drug design• Lead Optimization• Compound library synthesis• Chemical processes optimization• Protein drug modification
In Vitro Anti-Cancer Drug Screening Platform• Kinase activity assay• Human cancer cell cytotoxicity assay• Human normal cell cytotoxicity assay• In Vitro ligand-dependent cell proliferation assay• Tubulin polymerization assay• Colchicine site competitive binding assay
Mode of Action Analysis• Cell-based kinase assay• Cell apoptosis test• Cell cycle analysis
Safety Pharmacology• hERG K+ channel competitive
assay
Caco-2 Permeability assay
Customized Services
Average throughput: Lead to candidate, 1.5 y, 2.5 FTE, ~ 180 compoundscandidate to backup, 1.0 y, 1.5 FTE, ~ 70 compounds
Pharmaceutics Capabilities
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LeadDiscovery
ValidationOptimization
Preclinical, Tox, CMC IND Phase I Phase II Phase III
On
colo
gy
Diabetes
DCB-CA1 2007 TFDA IND
mTOR 2013 US IND; 2014 TFDA IND
Raf 2016 US IND; 2019 TFDA IND
DCB-BO1301 2017 US IND
Hedgehog
ADC
FLT-3
CSF-1R
AXL
PROTACs
PI3K gamma
DCB-WH1 2008 TFDA IND
DCB-BO0101 2015 TFDA IND
Botanical Drug for Periodontic Disease
DCB-AD1 2004 TFDA IND
Inflammation
CNS
IDH1
SYK
Out licensed
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Pipeline in Chemical & Botanical Drugs
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Pharmacology &Drug Disposition
IND Core TeamPreclinical Pharmacology
Development Service of Analysis &
Formulation
Preclinical ADME/PK Services
Institute of Pharmacology & Drug Disposition
Drug Discovery Stage
Early Discovery-Compound Screening
Mid-stage Discovery-Lead Optimization
Late Stage Discovery-Candidate Selection
Oncology• Subcutaneous xenograft models• Orthotopic xenograft models• Syngeneic murine models• Xenograft models in humanized mice• Patient derived xenograft (PDX) models
Metabolism Disorders• Diabetic model• Hyperlipidemia model• Hypertensive model• Hyperuricemia model
Immune-Related Disorders• Rheumatoid arthritis model• Asthma model• Skin diseases• Inflammatory bowel disease (IBD)
Other Models • Wound healing model• Alzheimer's disease model• Pharmacokinetics (PK)• Acute Toxicity Test• Customized service
In-vivo Study (Efficacy Evaluation) Ex-vivo Study(MOA/Biomarker discovery)
DiseaseAnimalModels
Serum biochemistry
Microbiota-related Assay
Serum cytokine analysis
Histopathological analysis
Immune cell polarization
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Preclinical Pharmacology
• Pharmaceutical companies
• Academia
• Biotechnology
• Botanical Drugs
• Health food
• Cosmetic/ Skin care products
Customer / Service Category
• Provides formulation development and analysis for small molecule drugs, protein drugs, herbal medicine, health food and skin care products.
Goals
• Oral (Liquid, Tablet, Capsule; Immediate release/ controlled release/ Sustained release /Long-acting /Enteric)
• Parenteral (Liquid, Lyophilized, Implant)
• Topical (Cream, Ointment, Gel)
• Mucoadhesive/Oral cavity (Gel, Ointment, Patch, Spray)
• Inhalation/Nasal spray (MDI, nebulizer)
Formulation Development/Product Design
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Services in Analytics & Formulation
In vitro ADME
Caco-2 Permeability and PAMPA Protein binding Microsomal stability Metabolite identification CYP P450 reaction-phenotyping
In vivo DMPK
Bioavailability In vivo metabolite identification In vivo drug-drug interaction evaluation Toxicokinetics (TK) Allometric PK scaling PK/PD modeling and simulations
Biologics Analysis mAb characterization Drug-to-antibody ratio distribution for ADCs PK assays for antibody-drug conjugate
Do not copy or distribute without permission from DCB
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Services in Preclinical ADME/PK
Initiation Project charter,Requirements
gathering
Plan Schedule,Estimate costTest facility
Confirm TimelineTracking Progress
Control qualityproblem-solving
Study ProtocolAgreement/Approval
Study Conduct
Final Report
Archive
Planning
Project close
Execution& control
Archive
Drug Development
PK
PD
CMC
Tox.
Early clinical development
plan
Assist to IND filing
Study plan
Draft report
Sponsor Request
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Project Management
IND Core Team
Anti-ENO-1 Therapeutic Antibody
H2L LO CS PCTarget discovery
NHRI DCB Biotech Company in Taiwan
FY100
• Pharmacology Analysis• Indication Analysis (Multiple Sclerosis)
• Efficacy Examination• Candidate Selection (High Yield Cell Line
MCB Development)
• Non-GLP PK/TOX in Rodent• Patent Application and Deployment
• Process Development• Stability Test• Consultation for Technology
Development• Chemistry, Manufacturing, and
Controls (CMC)• IND Application
(Aimed for Year 2019)
• Target Generation
This project was initiated by NHRI for exploratory development. DCB carried on and added value to this biologics, and licensed out to a biotech company in Taiwan. DCB further provides the services and developmental consultation to the licensee. It is the indicative case for successful commercialization of a basic science research in Taiwan.
FY104
Multiple sclerosis results from neuron injury caused by the immune system attack.
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Zhaohe Cao (Crassocephalum crepidioides)-based anti-cancer botanical drug (DCB-BO1301) is a first and successful case that Academia Sinica transferred their findings to DCB for further research, and then co-exclusively licensed the technology to a domestic company.
102 106
LO CS PCTarget discovery I
Academic Unit Academia Sinica
Value added-• Scale-up and establish a Chemical
Manufacturing Control (CMC)• Validate anti-tumor activities• Complete toxicology analyses to
prove safety in animals• IND Application & Submission• US FDA Approval(Middle-stream research and development)
• Take over to translate potential herbal medicines from the bench top to human clinical trials
• Mode of action• Discover anti-inflammatory • Discover anti-melanoma
bioefficacy
Non-profit Governmental Organization Development Center for Biotechnology (DCB)
Local Pharmaceutical Company
(Upstream discovery research)(Downstream
Commercialize Product)
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Crassocephalum crepidioides ExtractsBotanical Drug for Cancer Therapy
Misoprostol Long-Acting,1994Misoprostol Fast-Acting,1997
mTOR injection, 2011
Calcitonin Nasal Spray Solution. 1996, 2005
台灣寶Bio-Bac生物農藥(百泰 1995;日本市場 2004)
ACE intermediate, 1998 (駿瀚)
Fluconazole manufacturing process(Matrix Lab.2002; US market)
DCB-BO0101 Botanical Drug,2014
DCB-CA1癌症治療輔助藥物, 2013
Calcitonin for injection, 1993Granisetron Prolonged-action injection, 2008
DCB-WH1 Botanical Drug, 2007
Anti-HSV mAb, 2012
LT adjuvant platform, 2013
Zhaohe Cao (Crassocephalum crepidioides)-based anti-cancer botanical drug 2017
Anti-VEGF mAb,2013Raf inhibitor, 2015 Anti-ENO-1 mAb, 2015
DCB-AD1 Botanical Drug
CSF1RAnti-Cancer inhibitor
Raf Anti-cancer inhibitor
HC Botanical drug
Nek2/Hec1 Anti-Cancer inhibitor
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Partners and Licensees
2013.4CGMP Biopharmaceutical
Pilot Plant Facility acquired by EirGenix, Inc.
2016.10Spun off TFBS Bioscience, Inc.
for GLP Biosafety Testing
2011.1GLP Toxicology Lab (acquired by QPS
Taiwan)
2000.6Professional Testing for
Drug Residues and Food Safety
(acquired by TAB )
2018.12Spun off
Botanical Group
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DCB Spin-off Companies
Business Development
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Drug Commercialization
Center
Biotechnology and Pharmaceutical
Industries Promotion Office
Industry & Technology Intelligence Service
Nangang Biotech Incubation Center
Industrial DevelopmentDivision
InternationalLinkage
Licensing &Collaboration
Commercial-ization
IntelligenceHub
Start upIncubation
BPIPO
Business Development Group
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BPIPOTaiwan
Biotech
Industry
One-stop Window
bridging the world to
Taiwan
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Biotechnology and Pharmaceutical Industries Promotion Office (BPIPO)
Start up Creation
• Innovation Assessment
• Business Plan made perfect
• Business Modeling
• Talents Scouting
Early Stage
• Fund Raising
• Coaching and Mentoring
• Training
• Hosting
• Commercialization
• Business Partnering
• Legal , IP
Expansion
• Innovation Diagnostics
• International Networking
• Technology Commercialization
• Clustering
• Business Development
Incubation
Accelerator
Post Incubation
• First Biotech accelerator in Taiwan
• MassChallenge Taiwan chapter
• CEO Clubs, Shared Facilities, Co-working Space.
Nankang Biotech Incubation Center (NBIC)
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Supported by
Qualified Industrial
Analysis and Consulting
Team
Policy
Regulation
Industrial
Dynamics
Market Forecast
Technology Trends
Operational Strategy
Policy planning
EnterpriseManagement
Research Innovation
From Information, Intelligence to
Policy and Decision
Industry & Technology Intelligence Service (ITIS)The Biotech Thinktank
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>30 ExpertsTargets: Academia to Start-ups
High-Potential Project SelectionTechnology Commercialization
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Drug Commercialization Center (DCC)
International Collaborations— Technology Transfer
Business Case& Strategic Planning
Marketing& Partnering
Licensing Negotiation& Due Diligence
Post-licensing Planning & Management
May 2013/ May 2014Assisting in US provisional application & PCT application
May 2013/May 2014Domestic Showcase& Business Partnering
Apr.-Aug. 2014Assisting in exploring the inventor team’s expectation, setting licensing goals and discussing the feasible solutions for financial concerns
Oct. 2013Inviting the lead inventor to bethe speaker in the first annualsymposium of the TaiwanAntibody Association, where hemet the champion of the licensee
Aug.-Dec.2014Assisting KMU in D.D. including preparingIP-related English documentation andnotarizing documents; coordinating withthe external supporting resources toresolve problems or clarify legal concerns.The deal was closed in Dec. 2014, and thedeal value was the highest among thelicense deals of Taiwan academic
Jan.-Oct. 2015Assisting KMU in awardingresearch collaboration with thelicensee, providing suggestions forco-author regarding publicationand consultation for post-licenseIP management, coordinating thesite visit to the licensee’s company
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BD Services Case Report
Future Prospect in Therapies
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Future Prospect in Therapies
Precision Medicine
Nanoparticles
Artificial IntelligenceBig Data
Cell Therapy& Gene Therapy
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Collaboration Welcomed
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Thank You
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陽明大學生技醫藥產業課程
生技產業深耕學院
數位生醫產業分析師
第9屆藥物藥理研討會
生物製程開發暨生物反應器操作
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動物操作應用課程,認識藥物開發臨床前動物藥理(45人)
Industry Oriented Talent Program