Publications by Biophoenix' Principals

The Outlook for the Biotech Sector in the Post-genomic Era:
Strategies for Drug Discovery, Diagnostics and Personalized Medicine.
Publisher:Reuters/Datamonitor
Year of publication:2002
Type of publication:Management report
Publisher's reference (if any):RBHC0089
Author(s):Sreten Bogdanovic and Beata Langlands
Approximate page count:250
Price when published:$1,200
Remarks:
  1. Page numbers, where given, refer to the draft manuscript (which may differ from the published version).
  2. The copyright in this report is owned by the publisher, to whom any requests for copies should be addressed.
  3. The price shown is for a single copy of the print version. Multiple copies and electronic copies usually have different prices. 
            OUTLOOK FOR THE BIOTECH SECTOR IN THE POST-GENOMIC ERA:
                Strategies for drug discovery, diagnostics, and
                             personalized medicine.
        
        TABLE OF CONTENTS
        
        EXECUTIVE SUMMARY
        
        Chapter 1 Technology overview
        
          1.1 Introduction to the post-genomic era 
          
          1.2 Structural genomics
             1.2.1 Sequencing
             1.2.2 Genotyping
               1.2.2.1 Pharmacogenomics
          
          1.3 Key characteristics of the completed human genome
          
          1.4 Gene expression
          
          1.5 Functional genomics
          
          1.6 From the genome to the proteome
             1.6.1 Transcriptomics 
             1.6.2 Glycomics 
          
          1.7 Proteomics 
             1.7.1 Structural proteomics 
             1.7.2 Functional proteomics 
             1.7.3 Proteins and diseases 
          
          1.8 Cellomics
          
          1.9 Systems biology
          
          1.10 The search for disease markers
          
          1.11 Bioinformatics
        
        Chapter 2  Drug Discovery
          
          2.1 Traditional and genomics-based drug discovery
             2.1.1 Market drivers
             2.1.2 The drug discovery process
               2.1.2.1 Target identification 
               2.1.2.2 Target validation 
               2.1.2.3 Lead generation 
               2.1.2.4 Lead optimization 
             2.1.3 Limitations 
          
          2.2 Functional genomics in drug discovery
          
          2.3 Proteomics in drug discovery 
             2.3.1 Targeting protein expression
             2.3.2 Targeting protein interactions
          
          2.4 SNP scoring in drug discovery
          
          2.5 Increasing the efficiency of drug discovery
             2.5.1 Integrated use of technologies
          
          2.6 Target identification in the post-genomic era
             2.6.1 Targeting gene regulation 
          
          2.7 Target validation in the post-genomic era
             2.7.1 Role of functional genomics 
             2.7.2 Antisense inhibition assays 
          
          2.8 Lead generation in the post-genomic era
          
          2.9 Lead optimization in the post-genomic era
          
          2.10 Rational drug design in the post-genomic era
          
          2.11 Prediction of safety and efficacy of drugs
          
          2.12 Managing bioinformatics information 
             2.12.1 Commercial exploitation of data
             2.12.2 Trends in genomics/proteomics databases
             2.12.3 Bio-simulation technologies
        
        Chapter 3 Development of small molecule drugs and
        biotherapies 
        
          3.1 Traditional drug development 
             3.1.1 Market drivers
             3.1.2 The drug development process
               3.1.2.1 Preclinical stage 
               3.1.2.2 Clinical stage
               3.1.2.3 Limitations 
          
          3.2 Drug development in the post-genomic era 
             3.2.1 Role of pharmacogenomics
               3.2.1.1 Preclinical testing 
               3.2.1.2 Clinical trials 
               3.2.1.3 Existing drugs
               3.2.1.4 Advances in SNP scoring 
             3.2.2 Computer-based management solutions 
             3.2.3 Drug delivery advancements
               3.2.3.1 Delivery of biopharmaceuticals
             3.2.4 Directed molecular evolution
             3.2.5 Drug development outsourcing industry 
          
          3.3 New and emerging biotherapies
             3.3.1 Protein therapy 
             3.3.2 Antisense therapy 
             3.3.3 DNA vaccines and gene therapy 
             3.3.4 Glycotherapy
          
          3.4 Major therapy areas
             3.4.1 Infectious disease
             3.4.2 Cardiovascular disease
             3.4.3 Oncology
        
        Chapter 4  Predictive diagnostics
        
          4.1 Overview of the traditional IVD industry.
          
          4.2 IVDs in the post-genomic era 
          
          4.3 Predictive diagnostics and preventive medicine 
          
          4.4 Predisposition tests 
             4.4.1 Cancer
             4.4.2 Cardiovascular disease
          
          4.5 Early detection of disease 
             4.5.1 Genomics and early detection of disease 
               4.5.1.1 Infectious disease
               4.5.1.2 Cancer
             4.5.2 Proteomics and early detection of disease 
          
          4.6 Detection of pre-symptomatic disease 
          
          4.7 The role of the homebrew market
        
        Chapter 5 Theranostics 
        
          5.1 Drug selection in the post-genomic era 
          
          5.2 Theranostics and personalized medicine 
          
          5.3 Theranostics and established drugs 
          
          5.4 Gene-based theranostics and applications 
             5.4.1 Infectious disease
             5.4.2 Cancer
             5.4.3 Cardiovascular disease
             5.4.4 Other diseases
             5.4.4 Prediction of drug toxicity 
          
          5.5 Proteomics: the next frontier in theranostics
          
          5.6 Impact of bioinformatics 
          
          5.7 Does theranostics improve outcomes?
        
        Chapter 6 Company profiles 
        
          6.1 ACADIA Pharmaceuticals Inc 
             6.1.1 Summary financial data
             6.1.2 Company overview
             6.1.3 Genomic target discovery
             6.1.4 Platform drug discovery technologies
             6.1.5 Applications of platform technologies 
             6.1.6 Drug discovery pipeline 
             6.1.7 Collaborations
          
          6.2 Applera Corp 
             6.2.1 Summary financial data
             6.2.2 Company overview
             6.2.3 Celera Genomics business unit 
               6.2.3.1 Online information business 
               6.2.3.2 Program to discover SNPs in genes 
               6.2.3.3 Drug discovery and development
               6.2.3.4 Collaborations
          
          
          6.3 ArQule Inc 
             6.3.1 Summary financial data
             6.3.2 Company overview
             6.3.3 Integrated drug discovery platform
               6.3.3.1 AMAP Chemistry Operating System 
             6.3.4 Drug discovery products and services
             6.3.5 Internal drug discovery program 
             6.3.6 Collaborations
          
          6.4 Athersys Inc 
             6.4.1 Summary financial data
             6.4.2 Company overview
             6.4.3 Random Activation of Gene Expression
             6.4.4 Applications of RAGE technology 
               6.4.4.1  Functional genomics
               6.4.4.2 Validation of drug targets
               6.4.4.3 Development of protein therapeutics 
               6.4.4.4 Gene discovery
             6.4.5 Collaborations
          
          6.5 Cellomics Inc
             6.5.1 Summary financial data
             6.5.2 Company overview
             6.5.3 Core cellomics competencies 
             6.5.4 Integrated product platform 
               6.5.4.1 Cellular screening products 
               6.5.4.2 Bioinformatics products 
               6.5.4.3 Applications to drug discovery
             6.5.6 Collaborations
          
          6.6 Cytogen Corp 
             6.6.1 Summary financial data
             6.6.2 Company overview
             6.6.3 Core proteomics technology
             6.6.4 Proteomics-based products 
               6.6.4.1 ProChart protein pathway database 
               6.6.4.2 Protein Arrays
          
          6.7 DiagnoSwiss SA 
             6.7.1 Summary financial data
             6.7.2 Company overview
             6.7.3 Technology for rapid protein analysis 
             6.7.4 Microfluidics technology
             6.7.5 Lab-on-a-chip systems 
             6.7.6 Immunoassays on microchip format
          
          6.8 Genaissance Pharmaceuticals Inc 
             6.8.1 Summary financial data 
             6.8.2 Company overview 
             6.8.3 HAP technology platform
             6.8.4 Informatics technology platform
             6.8.5 Applications of HAP technology 
               6.8.5.1 Mednostics program 
               6.8.5.2 HAP2000 partnership program
             6.8.6 HAP drug discovery pipeline
             6.8.7 Collaborations 
          
          6.9 Gene Logic Inc
               6.9.1 Summary financial data 
             6.9.2 Company overview 
             6.9.3 Gene expression technology 
             6.9.4 Gene expression databases
               6.9.4.1 Custom discovery research databases
               6.9.4.2 GeneExpress databases
             6.9.5 Collaborations 
          
          6.10 Keryx Biopharmaceuticals Inc 
             6.10.1 Summary financial data
             6.10.2 Company overview
             6.10.3 KinAce drug discovery technology
             6.10.4 Peptide conversion technology 
             6.10.5 Functional genomics program 
             6.10.6 KinAce drug discovery pipeline
          
          6.11 Lexicon Genetics Inc 
             6.11.1 Summary financial data
             6.11.2 Company overview
             6.11.3 The Genome 5000 program 
             6.11.4 Gene knockout technology
             6.11.5 OminBank library and database 
             6.11.6 LexVision gene function database
             6.11.7 Drug discovery programs 
             6.11.8 Functional Genomics programs
             6.11.9 Collaborations
          
          6.12 Lynx Therapeutics Inc
             6.12.1 Summary financial data
             6.12.2 Company overview
             6.12.3 Megaclone technology and applications 
             6.12.4 Proteomics technology and applications
             6.12.5 Internal product development
             6.12.6 Collaborations
          
          6.13 Myriad Genetics Inc
             6.13.1 Summary financial data
             6.13.2 Company overview
             6.13.3 An integrated proteomics platform 
             6.13.4 Genomic technologies
             6.13.5 Predictive medicine produsts
             6.13.6 Drug discovery pipeline 
             6.13.7 Collaborations
          
          6.14 Neurogen Corporation 
             6.14.1 Summary financial data
             6.14.2 Company overview
             6.14.3 Accelerated Intelligent Drug Discovery
             6.14.4 Drug discovery pipeline 
             6.14.5 Collaborations
          
          6.15 Orchid BioSciences Inc 
             6.15.1 Summary financial data
             6.15.2 Company overview
             6.15.3 SNP-IT SNP scoring technology 
             6.15.4 Combined Technologies 
             6.15.5 SNP scoring products and services 
             6.15.6 Collaborations
          
          6.16 Rigel Pharmaceuticals Inc
             6.16.1 Summary financial data
             6.16.2 Company overview
             6.16.3 Combinatorial biology platform
             6.16.4 Proteomics program
             6.16.5 Drug discovery portfolio
             6.16.6 Collaborations
          
          6.17 Rosetta Inpharmatics Inc 
             6.17.1 Summary financial data
             6.17.2 Company overview
             6.17.3 Informational genomics platform 
               6.17.3.1 Rosetta Resolver System 
               6.17.3.2 FlexJet DNA microarray technology 
               6.17.3.3 Coherent data sets
             6.17.4 Collaborations
          
          6.18 SEQUENOM Inc 
             6.18.1 Summary financial data
             6.18.2 Company overview
             6.18.3 MassARRAY genotyping technology 
             6.18.4 SNP assay portfolio 
             6.18.5 Disease gene discovery programs 
             6.18.6 Extensive DNA sample repository 
             6.18.7 Drug and diagnostics program
             6.18.8 Collaborations
          
          6.19 Synaptic Pharmaceutical Corp 
             6.19.1 Summary financial data
             6.19.2 Company overview
             6.19.3 SNAP drug discovery platform
             6.19.4 Drug discovery programs 
             6.19.5 Collaborations
          
          6.20 Vertex Pharmaceuticals Inc 
             6.20.1 Summary financial data
             6.20.2 Company overview
             6.20.3 Chemogenomics platform
             6.20.4 Drug discovery technologies 
             6.20.5 Drug discovery pipeline 
             6.20.6 Collaborations
        
        Chapter 7 Conclusions - trends and opportunities
        
        7.1 Post-genomic biotechnology is changing medicine 
        7.2 Young companies are driving the changes 
        7.3 Towards personalized and predictive medicine
        7.4 Drug discovery is in transition 
        7.5 Tackling the critical issue of productivity 
        7.6 Role of alliances in drug discovery 
        7.7 Post-genomic outsourcing industry 
        7.8 Business models in bioinformatics 
        7.9 IP issues in the post-genomic era 
        
        Appendix 1  Terms and Abbreviations
EXECUTIVE SUMMARY

This report provides a comprehensive overview of the exciting and fast-evolving advances transforming the Biotech sector in the post-genomic era. Drug discovery and development are examined in detail, as is the development of in vitro diagnostics (IVDs) enabling the practice of preventive and personalized medicine. Both industry-wide and proprietary approaches are discussed. The report also discusses trends in the post-genomic markets for drugs and IVDs and changes that have occurred as a result of technological advances and regulatory implementations.

Drug discovery has traditionally been an expensive, time-consuming and risky process. Small molecule drugs on the market interact with a total of only about 500 protein targets, predominantly targets located outside the cell. Genomics has created an explosive growth in the number of potential drug targets while proteomics has shifted the focus to designing drugs targeting proteins located within cells and disrupting protein pathways. Drug discovery companies are increasingly targeting gene regulating proteins, or gene switches, such as transcription factors, kinases and ligases. Sequence data is also being used to produce drugs with improved specificity directed at traditional targets.

It is widely believed that most potential targets will not prove useful and therefore early target validation has become a key priority. Several approaches to target validation are currently being explored. Improvements are also continually being made to the lead optimization process. Other developments are also discussed in this report which hold the key to unlocking the value of genomics and increasing the efficiency of drug discovery. These include integrated use of technologies, in particular chemical genomics, single nucleotide polymorphism (SNP) scoring, rational drug design, and early detection of drug toxicity. Advances in bioinformatics tools is seen by many industry analysts as key to future of drug discovery and developments.

Following the drug discovery process, optimized lead compounds must undergo preclinical and clinical development and regulatory approval. This lengthy and expensive process can take up to ten years with up to a 90 percent failure rate. One problem with traditional drug development is that strategies have traditionally targeted the average person. In the post-genomic era, SNP genotyping is increasingly being used to determine genotypes associated with drug responsiveness and drug side effects. SNP scoring is expected to reduce the time and costs of drug development by targeting clinical studies, particularly Phase III, to the most appropriate population. Applications of SNP scoring to other stages of drug development are also discussed.

Although big pharma continues to favour small molecule drugs, many biotechnology companies are developing biotherapeutics (proteins and nucleic acid-based drugs) and this may be the most direct way of using new genetic information. The path from a new gene to a new drug is likely to be much faster for a protein drug than a small molecule drug and especially fast for an antisense drug. However, a number of challenges remain to be overcome, such as effective delivery of biotherapeutics and improvement of naturally occuring genes for commercial purposes. Recent progress in the relevant areas is discussed.

Emerging biotherapies are reviewed in this report. These include antisense therapies and gene therapies. Antisense companies are poised to fill their pipelines from the wealth of new sequence data and may become some of the post-genomics era's biggest beneficiaries. Despite slow progress in the gene therapy field following a setback in 1999, promising results are being reported from clinical trials in this area.

A new frontier of the post-genomic era is preventive medicine. This will be enabled by predictive diagnostics, which detect either individuals' predisposition to disease or early and pre-symptomatic disease. Genetic tests for susceptibility to hereditary cancer and cardiovascular disease, as well as other conditions are becoming commercially available. Early detection of some infectious agents can already be achieved by means of nucleic acid testing using amplification technologies. A number of companies are developing tests which aim to detect genomic abnormalities associated with early-stage cancer. Post-genomic technologies are also enabling researchers to discover molecular signatures produced by cells in the early stages of disease that may provide the best means of diagnosing serious diseases at the earliest possible pre-symptomatic stages.

Another post-genomic trend is the development of theranostic tests which predict drug response in individual patients. In 1998, the FDA approved Genentech's therapeutic antibody Herceptin and DAKO's HercepTest for the detection of HER2 protein, the target of Herceptin. This companion diagnostic/therapeutic approach marked the arrival of a new era of personalized molecular medicine. Currently, most theranostic tests are based on detection of genetic polymorphisms. However, the genes in the human genome may give rise to as many as 5 million proteins, and new protein biomarker discoveries are expected to lead to new protein-based theranostic tests.

Theranostic tests are already finding applications in many therapeutic areas. In viral infections, genotyping tests are used to examine viral nucleic acid from infected individuals to detect emerging drug resistance and thereby guide therapy decisions. In cancer, genotyping tests enable physicians to select the most effective chemotherapeutic agents. In cardiovascular disease, genotyping tests are becoming available which predict an individual's response to certain classes of marketed drugs. Theranostic tests are also becoming available for the prediction of susceptibility to adverse drug reactions.

Twenty innovative, predominantly young companies developing technologies and products for the post-genomic era are profiled in this report. Included are drug discovery companies with expertise in sequence-based drug discovery (Acadia Pharmaceuticals, Keryx Biopharmaceuticals, Vertex Pharmaceuticals), functional genomics (Synaptic Pharmaceutical, Lexicon Genetics), rational drug design (Neurogen Corporation), proteomics (Cytogen Corp, Myriad Genetics, Rigel Pharmaceuticals, Athersys), and various integrated or novel technologies (ArQule, Celera Genomics, Lynx Therapeutics, Cellomics); bioinformatics companies (Gene Logic, Rosetta Inpharmatics (a division of Merck & Co); and companies focused on nucleic acid- or protein-based assay development (DiagnoSwiss, Genaissance Pharmaceuticals, Orchid BioSciences, Sequenom, Myriad Genetics).


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