September 30, 2005 Lan-Yang Ch’ang, Ph.D. Institute of Biomedical Sciences Academia Sinica 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 ( ) 3 billion letters of A, C, G or T 2001: Draft Sequence 2003: 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 Human32, Gb Mustard Weeds25, Mb Fly13, Mb Worm19, Mb Yeast 5, Mb Species # of Genes Genome Size

Bio-Complexity of Human Life Exon ~2% Intron24% Intergenic74% Geno-Complexity 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 InteractionsBiochemical Cascade

Biological Processes of Life Fertilization Fetal Development Neonatal Development Adolescence Maintenance & Aging Gene Repertoire Energy & MetabolismInformation ProcessingCommunications Genetic Factors Environmental Factors

GenemRNAProteinStructure GenomeTranscriptomeProteome Bioinformatics SNPs Disease Gene Clinical Trials Lead Compound New Drug Chemical Library & HTS Optimization DNA Chip Protein Chip Peptide map Function Animal Model Haplotypes SNPs: single nucloetide polymorphisms

Gene mRNA Protein Structure Genome Transcriptome Proteome SNP New Drug DNA Chip Protein Chip Protein Profiling Gene Discovery mRNA Profiling Target Discovery Drug Discovery Modeling Lead Identification Virtual Screening Splicing Variants Isoforms & Modification Target Drug Lead Dx

Channels Consumers Healthcare Providers Pipelines Research & Development Drug Development The Roadmap of Biotech Development

30,000 Genes Target HTS Drug Lead Preclinical Clinical Trial DRUG Disease Gene Discovery New Paradigm in Drug Development Phase IV Phase I Phase II Phase III Genome Drug Discovery Drug Development US$ 1 billion 10 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 Disease Discovery Gene Discovery Drug Discovery Trauma Infectious Hereditary Environmental Complex Diseases Aging-related Diseases Disease ManagementLife 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

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 development 2.>130 are Mab products 3.~13% of the cancer therapeutic market 4.Annual growth of 60% since 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 Drugs 2003 (>US$4 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

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 USA Canada UK US$ M US$ 14.6 M US$ 4.3 M 10 companies 2 companies 1 company US$ M 19 companies Switzerland Germany US$ 60.5 M US$ 14.6 M 2 companies France Italy US$ 42.9 M US$ 36 M 1 company TOTAL

Biotech Deals: Jan.-Feb., 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?

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