September 30, 2005

Lan-Yang Ch’ang, Ph.D.Institute of Biomedical Sciences

Academia Sinicalychang@ibms.sinica.edu.tw

Scientific Impacts to the Biotech Future

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?

Human Genome Project (1990-2003)

3 billion letters of A, C, G or T

2001: Draft Sequence2003: finished Sequence~ 30,000 Genes

US$ 3 billion !

The scientific quest of life

What is life?

Why is life what it is?

How do we know why life is what it is?

Life on Mars?

Life under the Sea?

What makes us different genetically?

Gene Number in Eukaryotes

Human 32,000 2.9 GbMustard Weeds 25,498 115 MbFly 13,601 116 MbWorm 19,099 97 MbYeast 5,800 12 Mb

Species # of Genes Genome Size

Bio-Complexity of Human Life

Exon ~2%Intron 24%Intergenic 74%

Geno-Complexity

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

Pheno-Complexity

• DNA Methylation• Histone Acetylation

TranscriptionActivation or Silencing

• Protein Modifications• Complex Formation Functional Entity

• Protein Interactions Biochemical Cascade

Biological Processes of Life

FertilizationFetal

DevelopmentNeonatal

DevelopmentAdolescence

Maintenance& Aging

Gene Repertoire

Energy & Metabolism Information Processing Communications

Genetic FactorsEnvironmental Factors

Gene mRNA Protein Structure

Genome Transcriptome Proteome

Bioinformatics

SNPs

Disease GeneDisease Gene

Clinical Trials

Lead CompoundLead Compound

New DrugNew Drug

Chemical Library & HTS

Optimization

DNA Chip

Protein Chip

Peptide map

Function

Animal ModelHaplotypes

SNPs: single nucloetide polymorphisms

Gene

mRNA

Protein

Structure

Genome

Transcriptome

Proteome

SNP

New Drug

DNA Chip

Protein Chip

Protein Profiling

GeneDiscovery

mRNA Profiling

TargetDiscovery

DrugDiscovery

ModelingLead Identification

Virtual Screening

Splicing Variants

Isoforms & Modification

Target

DrugLead

Dx

Channels ConsumersHealthcareProviders

Pipelines

Research & Development

Drug Development

The Roadmap of Biotech Development

30,000 Genes

Target

HTS

Drug Lead

Preclinical

Clinical Trial

DRUG

Disease Gene Discovery

Disease Gene Discovery

New Paradigm in Drug Development

Phase IV Phase I Phase II Phase III

Genome

Drug Discovery

Drug Discovery

Drug Development

Drug Development

US$ 1 billion10 years

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

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

Impacts of Biotechnology in the Future

Century 20 Century 21

Quality of Living Quality of Life

Bio-Century 21

DiseaseDiscovery

GeneDiscovery

DrugDiscovery

• Trauma• Infectious• Hereditary• Environmental

• Complex Diseases• Aging-related Diseases

Disease Management Life Management

• New Diagnostics• New Therapeutics• Theranostics

• Individualized Healthcare• Predictive Medicine• Tissue Engineering

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

1970 1980 1990 2000

• Recombinant DNA• Hybridoma• DNA Sequencing•

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

HGP

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

IHMP

Technology Development for Life Sciences

Mabs in the Cancer Pipeline

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

1. ~600 anticancer drugs in development2. >130 are Mab products3. ~13% of the cancer therapeutic market4. Annual growth of 60% since 20025. More FDA approvals

US FDA Approved Mab Drugs (I)

Rituxan (Genentech)• 11/’97 for non-Hodgekin’s 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

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-Hodgekin’s 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

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

US FDA Approved Mab Drugs (III)

Current Market of Mab Drugs2003 (>US$4 billion) • Genentech (61%): Rituxan & Herceptin• Roche (33%): MabThera (Rituxan in EU)• Berlex (2%): Campath• Others: Bexxar (Corixa) & Panorex (Centocor)

2004Erbitux (ImClone)• US market: BMS; $84 M in Q3• EU market by Merck; $30 M in Q3Avastin (Genentech)

Worldwide market: Genentech Roche, Chugai

Biotech Industry: New Revolution

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

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

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

VC Investment in Biotech: Jan.-Feb.,2005

USACanada

UK

US$ 198.6 MUS$ 14.6 M

US$ 4.3 M

10 companies2 companies

1 company

US$ 384.4 M 19 companies

SwitzerlandGermany

US$ 60.5 MUS$ 14.6 M

2 companies2 companies

FranceItaly

US$ 42.9 MUS$ 36 M

1 company1 company

TOTAL

Biotech Deals: Jan.-Feb.,2005

1. Buyout: 6 deals for US$1,453.4 M

2. Merge & Acquisition: 5 deals

3. Licensing: 2 deals

4. Collaboration: 6 deals

6. Co-promotion: 1 deal

Biotech Industry: Where do we go?

1970 1980 1990 2000

• Recombinant DNA• Hybridoma• DNA Sequencing•

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

HGP

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

IHMP

Technology Development for Life Sciences

• Biopharmaceutics• Immunotherapy

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