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市場調查報告書
含鉛化合物之最佳化趨勢
Lead Optimization Strategies: Future developments, threats and opportunities for big pharma, specialty pharma and biotech
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本報告已在2011年07月19日停止出版。
Abstract
Lead Optimization Strategies: Future developments, threats and opportunities for big pharma, specialty pharma and biotech
The pharmaceutical industry has undergone considerable consolidation during
the last 20 years as companies attempt to maintain double-digit sales growth
and shareholder value. Strategic mergers and acquisitions have resulted in
companies revitalizing their drug pipelines to replace blockbuster drugs that
face patent expiration. In many cases, whilst mergers cause a period of less
productive transition, significant cost-savings can be reaped and overheads
reduced. However, more and more companies are resorting to streamlining their
internal programs, both pre-clinical and clinical, to improve productivity and
the cost-effectiveness of bringing drugs to the market as well as in-licensing
late-stage products and outsourcing screening programs which may be less
economical to entertain in-house.
Table of Contents
Executive Summary
- The importance of lead optimization
- Traditional big pharma strategies
- Alternative strategies used by specialty pharma and biotech
- Future developments in lead optimization
- Commercial threats and opportunities
Chapter 1 The importance of lead optimization
- Summary
- Introduction
- Current issues facing the pharmaceutical industry
- Introduction to lead optimization
- Hit generation
- Lead identification
- Lead optimization
- Lead optimization in the R&D process
- Time and costs associated with lead optimization
- Commercial and clinical importance of lead optimization
- Lead optimization strategies
- Traditional big pharma strategies
- Alternative strategies used by specialty pharma and biotech
- Differences in strategy
Chapter 2 Traditional big pharma strategies
- Summary
- Introduction
- A typical screening cascade
- Key strategic components in lead optimization
- Team organization for lead optimization
- Medicinal chemistry functionality
- Sources of hits and leads
- Proprietary collections
- Commercial non-exclusive libraries
- Natural products
- Academic groups
- Advantages and disadvantages of hit sources
- Improving the quality of compound collections
- Case study 1: AstraZeneca
- Case study 2: GSK
- Setting the criteria for hits, leads and candidate drugs
- Key technologies involved in lead optimization
- HTS technologies
- NMR
- Utility of modeling in lead optimization
- In silico modeling
- In vitro modeling
- Computational chemistry
- Virtual screening
- Library design
- HT protein crystallography
- Application of molecular biology in lead optimization
- ADMET screening
- The role of DMPK in lead optimization
- Metabolism and covalent binding
- Toxicity
- Assays for assessing toxicity
- HT chemistry
- Preparative LC-MS chromatography
- Supercritical Fluid Chromatography (SFC)
- Outsourcing lead optimization
- Weaknesses of the traditional lead optimization model
- Sequential data gathering
- Single compound synthesis
- Animal models
- Conclusions
Chapter 3 Alternative strategies used by specialty pharma & biotech
- Summary
- Introduction
- Alternative lead optimization strategies
- Mimicking big pharma cascades
- Short/partial screening cascades
- Computational approaches
- Case study: Locus Pharmaceuticals
- Alternative approaches to screening
- HT crystallography
- Nanotechnology
- Scanning probe microscopy
- Nanoparticle formulation
- Outsourcing lead optimization
- Lessons from specialty pharma/biotech strategies
- Conclusions
Chapter 4 Future developments in lead optimization
- Summary
- Introduction
- Key improvement opportunities
- Reductions in time
- Producing fewer compounds of higher quality more efficiently
- Bridging the chemistry and target space gap
- Miniaturization of chemistry
- More efficient screening cascades
- Systems biology
- Zebrafish model
- Reducing high attrition rates during lead optimization
- The 'omic revolution: transforming drug discovery
- Technology developments
- Lead optimization, 2010-2015
- Conclusions
Chapter 5 Commercial threats and opportunities
- Summary
- Introduction
- Commercial threats
- Industry consolidation
- Increased drug safety requirements
- Avoidance of untested innovative new technologies
- Drive towards lower risk "me too" drugs
- Commercial opportunities
- The genomic revolution
- Changes to orphan drug legislation
- Changes in regulatory guidelines: Biomarkers helping to improve the
chance
- of new drug approvals
- Combinatorial biomarkers aiding efficiency within the D&D process
- In- and out-Licensing opportunities to create new revenues streams for
all
- players within the industry
- Conclusions
Chapter 6 Appendix
- Abbreviations
- References
- Index
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