September 30, 2005

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Scientific Impacts to the Biotech Future
September 30, 2005
Lan-Yang Chang, Ph.D. Institute of Biomedical
Sciences Academia Sinica lychang_at_ibms.sinica.edu.t
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Scientific Impacts to Human life

• Physics Nuclear Engineering Energy
• Chemistry Chemical Engineering Synthetics
• Mathematics Computer Engineering Information
• Biology Genetic Engineering Therapeutics
• -Genome Engineering Synthetic
  Genomes

Biotech Future? What How?
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Human Genome Project (1990-2003)
3 billion letters of A, C, G or T
2001 Draft Sequence 2003 finished Sequence
30,000 Genes
US 3 billion !
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The scientific quest of life
What is life?
Why is life what it is?
How do we know why life is what it is?
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Life on Mars?
Life under the Sea?
What makes us different genetically?
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Gene Number in Eukaryotes
Species of Genes Genome Size
Human 32,000 2.9 Gb Mustard Weeds 25,498
115 Mb Fly 13,601 116 Mb Worm 19,099
97 Mb Yeast 5,800 12 Mb
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Bio-Complexity of Human Life
Geno-Complexity
Exon 2 Intron 24 Intergenic 74

• 3,000 Mb Genome
• 40,000 Human Genes
• 50 Repetitive Elements

Pheno-Complexity

• DNA Methylation
• Histone Acetylation

Transcription Activation or Silencing

• Protein Modifications
• Complex Formation

Functional Entity

• Protein Interactions

Biochemical Cascade
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Biological Processes of Life
Gene Repertoire
Energy Metabolism
Information Processing
Communications
Fertilization
Fetal Development
Neonatal Development
Adolescence
Maintenance Aging
Environmental Factors
Genetic Factors
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Gene
mRNA
Protein
Structure
Function
Genome
Transcriptome
Proteome
DNA Chip
Peptide map
Animal Model
SNPs
Protein Chip
Haplotypes
Bioinformatics
SNPs single nucloetide polymorphisms
Disease Gene
Chemical Library HTS
Lead Compound
Optimization
New Drug
Clinical Trials
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Target Discovery
Drug Discovery
Gene Discovery
New Drug
Gene
Genome
SNP
Splicing Variants
Target
DNA Chip
mRNA
Transcriptome
mRNA Profiling
Isoforms Modification
Protein Profiling
Dx
Protein
Proteome
Protein Chip
Drug Lead
Virtual Screening
Structure
Modeling
Lead Identification
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The Roadmap of Biotech Development
Research Development
Drug Development
Pipelines
Consumers
Healthcare Providers
Channels
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New Paradigm in Drug Development
Disease Gene Discovery
Genome
30,000 Genes
Drug Discovery
Target
HTS
Drug Development
Drug Lead
Preclinical
US 1 billion 10 years
Clinical Trial
Phase IV
Phase I
Phase II
Phase III
DRUG
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Impacts of Biotechnology in the Future
Century 21
Century 20
Quality of Living
Quality of Life

• Disease Management
• Medical team
• Clinical Diagnosis
• Operation/Replacement
• Physical/Chemical Treatment
• Biotherapeutics

• Life Management
• Individual Genetic Profiles
• Individualized Medicine
• Preventive Medicine

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Bio-Century 21
Disease Discovery
Gene Discovery
Drug Discovery

• Trauma
• Infectious
• Hereditary
• Environmental

• Complex Diseases
• Aging-related Diseases

Disease Management
Life Management

• Individualized Healthcare
• Predictive Medicine
• Tissue Engineering

• New Diagnostics
• New Therapeutics
• Theranostics

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Key Issues for the Biotech Future

• Changes in Population Dynamics
• Effects of New Healthcare Policies
• New Initiatives in Pipeline Development
• Transformation in Industrial Leadership
• Challenges in Business Intelligence
• Emergence of New Competitions

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Technology Development for Life Sciences
HGP
IHMP
1970
1980
1990
2000

• Recombinant DNA
• Hybridoma
• DNA Sequencing

• Blotting
• RFLP/STRP
• Transgenic/KO
• PCR

• Genome Sequencing
• Genotyping SNP
• Combinatorial Chemistry
• High-throughput Screening
• DNA Microarray
• Protein Chip
• Bioinformatics
• RNAi

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Mabs in the Cancer Pipeline

1. 600 anticancer drugs in development
2. gt130 are Mab products
3. 13 of the cancer therapeutic market
4. Annual growth of 60 since 2002
5. More FDA approvals

• 2001 1.3 B
• 2003 3.0 B
• 2004 4.3 B
• 2008 12.8 B

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US FDA Approved Mab Drugs (I)

• Rituxan (Genentech)
• 11/97 for non-Hodgekins lymphoma
• US market Genentech and Biogen Idec
• EU approval 06/98
• EU market by Roche as MabThera
• Herceptin (Genentech)
• 09/98 for metastatic breast cancer HER2
• EU approval 08/00
• EU market by Roche

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US FDA Approved Mab Drugs (II)

• Campath (Ilex Oncology)
• 05/01 for chronic lymphocytic leukemia
• US market Berlex Lab
• EU approval 07/01
• EU market by Schering as Mabcampath
• Bexxar (Corixa)
• 06/03 for non-Hodgekins lymphoma
• US market GSK
• EU market by Amersham Health
• Panorex (Centocor)
• 1st Mab drug approved in 1995
• For advanced colorectal cancer
• Only available in Germany by GSK

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US FDA Approved Mab Drugs (III)

• Erbitux (ImClone)
• 02/04 for metastatic colorectal cancer
• US market Bristol-Myers-Squibb 84 M in Q3/04
• Switzerland approval 12/03
• EU market by Merck 30 M in Q3/04
• Avastin (Genentech)
• 02/04 for metastatic colorectal cancer
• Worldwide market Roche, Chugai

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Current Market of Mab Drugs

• 2003 (gtUS4 billion)
• Genentech (61) Rituxan Herceptin
• Roche (33) MabThera (Rituxan in EU)
• Berlex (2) Campath
• Others Bexxar (Corixa) Panorex (Centocor)

• 2004
• Erbitux (ImClone)
• US market BMS 84 M in Q3
• EU market by Merck 30 M in Q3
• Avastin (Genentech)
• Worldwide market Genentech Roche, Chugai

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Biotech Industry New Revolution
Every biotech company wants to be a
pharmaceutical company, while the existing
pharmas are heavily invested in biotech R/D.

• AgriBiotech Plant and Animal Genomics
• Nutriceuticals Nutrigenomics
• Cosmeceuticals Nutrigenomics
• BioPharmaceuticals Pharmacogenomics

• Platform Technology -- Tools
• Discovery - Gene to Drug
• Bioinformatics Knowledge Discovery
• CMO/CRO Manufacturing Clinical Trials

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VC Investment in Biotech Jan.-Feb.,2005
USA
US 198.6 M
10 companies
Canada
US 14.6 M
2 companies
Switzerland
US 60.5 M
2 companies
Germany
US 14.6 M
2 companies
France
US 42.9 M
1 company
Italy
US 36 M
1 company
UK
US 4.3 M
1 company
TOTAL
US 384.4 M
19 companies
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Biotech Deals Jan.-Feb.,2005
1. Buyout 6 deals for US1,453.4 M
2. Merge Acquisition 5 deals
3. Licensing 2 deals
4. Collaboration 6 deals
6. Co-promotion 1 deal
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Biotech Industry Where do we go?
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Technology Development for Life Sciences
HGP
IHMP
1970
1980
1990
2000

• Recombinant DNA
• Hybridoma
• DNA Sequencing

• Blotting
• RFLP/STRP
• Transgenic/KO
• PCR

• Genome Sequencing
• Genotyping SNP
• Combinatorial Chemistry
• High-throughput Screening
• DNA Microarray
• Protein Chip
• Bioinformatics
• RNAi

• Biopharmaceutics
• Immunotherapy

• Molecular Dx

• Genomics
• Proteomics
• Bioinformatics
• RNAi
• CRO/CMO