Backup Compound Strategies: Commercial and Tactical Considerations

Only about 20% of compounds that advance to clinical trials reach the market. Given this high rate of attrition and ever-increasing costs, companies need fallback plans as an alternative to canceling projects and writing off significant investments. Planning optimal backup compound strategies is often difficult. This Insight Pharma Report:  

• Describes how companies are addressing strategic and tactical issues concerning backup compounds and predicts how they are likely to do so in the future
• Provides perspective on best practices to adopt in addressing relevant backup compound issues and how evolution in de-risking technologies may affect those practices
• Presents case histories that illustrate the use of backup compounds in practice
• Examines strategic issues in backup compound selection and utilization, as well as tactical considerations, and investigates trends in the field
• Covers business-related matters that bear significantly on backup strategies and tactics
• Analyzes the results of an extensive Insight Pharma Reports survey conducted among individuals active in commercial small-molecule drug discovery
• Includes complete transcripts of interviews with industry veterans who are highly knowledgeable about backup compound-related issues

Backup Compound Strategies:

Commercial and Tactical Considerations begins by considering definitions for backup compounds, reviewing key literature references that present expert views on the topic, and presenting case studies that describe how medicinal chemists approach design and selection of backup compounds. Backup strategies currently in effect, and the types of issues companies consider when deciding whether to designate and advance backup compounds once a drug candidate is selected, are examined. These issues include the necessity for backup compounds; whether backup strategies are ad hoc or policy-based; whether to advance backups based on the same or different chemical scaffold as the prototype; how to best deal with addressing backup compound-related questions before a prototype has advanced to the stage where information needed for such decision-making becomes available; and the role of biomarkers and backup compounds in drug repositioning.

Backup Compound Strategies: Commercial and Tactical Considerations then considers tactical aspects affecting backup compound design and selection, focusing first on descriptive tools that are used to assess and compare how close candidate compounds come to meeting requirements for product viability: the target product profile and the clinical utility index. We then focus on the use of biomarkers to help predict how compounds will fare downstream in the pipeline. This includes the effects of biomarkers for predictive toxicology, predictive efficacy, and mechanism of action.

Backup compound strategies are next viewed from the business and commercial perspectives, and the effects of evolutionary changes in drug discovery R&D on backup compound strategies and tactics are considered. Decision and risk analysis tools that are employed, and their utility in dealing with backup compound-related issues, are described before turning to a discussion of backup compounds as viewed from the perspective of the project portfolio as well as with respect to in-licensing deals.

Results, conclusions, and observations from Insight Pharma Reports’ survey of individuals involved with commercial small-molecule R&D on practices, attitudes, and opinions concerning backup compounds are presented. Also examined is the impact of the changing role of medicinal chemistry in pharma, and trends suggesting how backup compound strategies and tactics may evolve in coming years.

About the Author

Ken Rubenstein, PhD, a biochemist and molecular biologist, received his PhD at the University of Wisconsin and postdoctoral training at the University Of Pennsylvania School Of Medicine. He was a key innovator and research manager for Syva Company, the diagnostics branch of Syntex Corporation. During his 13 years with Syva, Dr. Rubenstein became vice president, scientific affairs, and a function that included strategic planning. Since 1983, he has served as a technology and marketing consultant to biomedical companies and an industry analyst, with more than 40 published studies to his credit.

Table Of Contents

Executive Summary

Chapter 1
IntroductionNature and Scope of the Report

Chapter 2
Nature and History of Backup Compound Strategies
2.1. Definitions
2.2. Scientific and Business-Related Literature on Backup Compounds
2.3. Case StudiesPfizer’s Alpha7 Nicotinic Acid Acetylcholine Receptor Agonist Program
Amgen’s TRPV1 Antagonists
SKF Labs and Tagamet

Chapter 3
Strategic Considerations
3.1. Need for Backup Compounds
3.2. Backup Strategy: Ad Hoc or Policy-Based
3.3. Same Versus Different Chemical Scaffold for Backups
3.4. Backup Decisions Based on Scant Information
3.5. Backups and Drug Repositioning

Chapter 4
Tactical Considerations
4.1. The Target Product Profile (TPP)
4.2. The Clinical Utility Index
4.3. Use of Biomarkers to De-Risk Backups
4.4. Predictive Toxicology

Chapter 5
Business Considerations
5.1. Survey ResultsPosition Category
Work Focus
Formal vs. Ad Hoc Backup Strategy
Advancing Backups If Proof of Concept for Target Not Established
Backups for In-Licensing
Level of Advancement for Backup Compounds
Effects of Changes in Medicinal Chemistry Structures on Backup Compounds
Effect of Stakeholders on Backup Strategies
Recent Trend in Extent to Which Backup Compounds Are Advanced
Reasons for Abandoning Projects
Likelihood of Advancing a Backup Through Phase I Clinicals
Utility of In Vitro Predictive Toxicology in Qualifying Backup Compounds
Change in Emphasis on Backups Predicted in the Future
5.2. Evolution of the Pharmaceutical Industry and Effects on Backup Strategies
5.3. Risk and Decision Management Tools As They Affect Backup Strategies
5.4. Portfolio-Oriented Considerations and Backup Strategies
5.5. Backup Strategies When In-Licensing Drug Candidates
5.6. The Pfizer Torcetrapib Story

Chapter 6
Trends and Observations
6.1. Changing Role of Medicinal Chemistry in Pharma
6.2. Conclusions from Industry Survey

Chapter 7
Interview Transcripts
7.1. Bruce Littman, MD, President, Translational Medicine Associates
7.2. Malcolm MacCoss, PhD, Founder and Member, Bohicket Pharma Consulting
7.3. John A. Lowe III, PhD, Consultant, JL3 Pharma
7.4. William Greenlee, PhD, Principal, MedChem Discovery Consulting
7.5. Michael Liebman, PhD, Co-founder, IPQ Analytics and Managing Director, Strategic Medicine, Inc.
7.6. Perry B. Molinoff, MD, Professor of Pharmacology, University of Pennsylvania School of Medicine

References

Company Index

List Of Fifures

Figure 2.1. Pfizer’s Prototype Compound PHA-543613
Figure 2.2. Amgen’s Lead Compound AMG 517
Figure 4.1. Target Product Profile (TPP) in the Context of a Broader Strategic Evaluation Framework

List Of Exhibits

Exhibit 5.1. Nature of Organization (Commercial, Small-Molecule Emphasis)
Exhibit 5.2. Nature of Position (Commercial, Small-Molecule Emphasis)
Exhibit 5.3. Nature of Position (Big Pharma/Biotech)
Exhibit 5.4. Nature of Position (Small to Midsize Pharma/Biotech)
Exhibit 5.5. Nature of Position (Pre-Commercial Pharma/Biotech)
Exhibit 5.6. Work Focus (Commercial, Small-Molecule Emphasis)
Exhibit 5.7. Work Focus (Big Pharma/Biotech)
Exhibit 5.8. Work Focus (Small to Midsize Pharma/Biotech)
Exhibit 5.9. Work Focus (Pre-Commercial Pharma/Biotech)
Exhibit 5.10. Backup Strategy in Organization Most Often (Commercial, Small-Molecule Emphasis)
Exhibit 5.11. Backup Strategy in Organization Most Often (Big Pharma/Biotech)
Exhibit 5.12. Backup Strategy in Organization Most Often (Small to Midsize Pharma/Biotech)
Exhibit 5.13. Backup Strategy in Organization Most Often (Pre-Commercial Pharma/Biotech)
Exhibit 5.14. Percent of Projects for Which Proof of Concept for the Target Is Established Prior To Start of Medicinal Chemistry (Commercial, Small-Molecule Emphasis)
Exhibit 5.15. Percent of Projects for Which Proof of Concept for the Target Is Established Prior To Start of Medicinal Chemistry (Big Pharma/Biotech)
Exhibit 5.16. Percent of Projects for Which Proof of Concept for the Target Is Established Prior to Start of Medicinal Chemistry (Small to Midsize Pharma/Biotech)
Exhibit 5.17. Percent of Projects for Which Proof of Concept for the Target Is Established Prior To Start of Medicinal Chemistry (Pre-Commercial Pharma/Biotech)
Exhibit 5.18. Likelihood of Advancing Backups If Proof of Concept for Target Is Not Established (Commercial, Small-Molecule Emphasis)
Exhibit 5.19. Likelihood of Advancing Backups If Proof of Concept for Target Is Not Established (Big Pharma/Biotech)
Exhibit 5.20. Likelihood of Advancing Backups If Proof of Concept for Target Is Not Established (Small to Midsize Pharma/Biotech)
Exhibit 5.21. Likelihood of Advancing Backups If Proof of Concept for Target Is Not Established (Pre-Commercial Pharma/Biotech)
Exhibit 5.22. For High-Priority Projects with Unproven Targets, Designated Backup Compounds Tend To Be From the Same or a Different Chemical Series (Commercial, Small-Molecule Emphasis)
Exhibit 5.23. For High-Priority Projects with Unproven Targets, Designated Backup Compounds Tend To Be From the Same or a Different Chemical Series (Big Pharma/Biotech)
Exhibit 5.24. For High-Priority Projects with Unproven Targets, Designated Backup Compounds Tend To Be From the Same or a Different Chemical Series (Small to Midsize Pharma/Biotech)
Exhibit 5.25. For High-Priority Projects with Unproven Targets, Designated Backup Compounds Tend To Be From the Same or a Different Chemical Series (Pre-Commercial Pharma/Biotech)
Exhibit 5.26. Desirability of Including Backup Compounds When In-Licensing Drug Candidates (Commercial, Small-Molecule Emphasis)
Exhibit 5.27. Desirability of Including Backup Compounds When In-Licensing Drug Candidates (Big Pharma/Biotech)
Exhibit 5.28. Desirability of Including Backup Compounds When In-Licensing Drug Candidates (Small to Midsize Pharma/Biotech)
Exhibit 5.29. Desirability of Including Backup Compounds When In-Licensing Drug Candidates (Pre-Commercial Pharma/Biotech)
Exhibit 5.30. Likely Level of Advancement for Backup Compounds (Commercial, Small-Molecule Emphasis)
Exhibit 5.31. Likely Level of Advancement for Backup Compounds (Big Pharma/Biotech)
Exhibit 5.32. Likely Level of Advancement for Backup Compounds (Small to Midsize Pharma/Biotech)
Exhibit 5.33. Likely Level of Advancement for Backup Compounds (Pre-Commercial Pharma/Biotech)
Exhibit 5.34. Effect of Recent Changes in Medicinal Chemistry in Pharma on Backup Strategies (Commercial, Small-Molecule Emphasis)
Exhibit 5.35. Effect of Recent Changes in Medicinal Chemistry in Pharma on Backup Strategies (Big Pharma/Biotech)
Exhibit 5.36. Effect of Recent Changes in Medicinal Chemistry in Pharma on Backup Strategies (Small to Midsize Pharma/Biotech)
Exhibit 5.37. Effect of Recent Changes in Medicinal Chemistry in Pharma on Backup Strategies (Pre-Commercial Pharma/Biotech)
Exhibit 5.38. Level of Influence of Stakeholders on Backup Strategies (Commercial, Small-Molecule Emphasis)
Exhibit 5.39. Level of Influence of Stakeholders on Backup Strategies (Big Pharma/Biotech)
Exhibit 5.40. Level of Influence of Stakeholders on Backup Strategies (Small to Midsize Pharma/Biotech)
Exhibit 5.41. Level of Influence of Stakeholders on Backup Strategies (Pre-Commercial Pharma/Biotech)
Exhibit 5.42. Change in Recent Years in Degree to Which Backup Compounds Are Advanced (Commercial, Small-Molecule Emphasis)
Exhibit 5.43. Change in Recent Years in Degree to Which Backup Compounds Are Advanced (Big Pharma/Biotech)
Exhibit 5.44. Change in Recent Years in Degree to Which Backup Compounds Are Advanced (Small to Midsize Pharma/Biotech)
Exhibit 5.45. Change in Recent Years in Degree to Which Backup Compounds Are Advanced (Pre-Commercial Pharma/Biotech)
Exhibit 5.46. Reasons for Abandoning Projects (Commercial, Small-Molecule Emphasis)
Exhibit 5.47. Reasons for Abandoning Projects (Big Pharma/Biotech)
Exhibit 5.48. Reasons for Abandoning Projects (Small to Midsize Pharma/Biotech)
Exhibit 5.49. Reasons for Abandoning Projects (Pre-Commercial Pharma/Biotech)
Exhibit 5.50. Likelihood of Work on Backup Compounds to Continue Through Phase I Clinical Studies as Candidate Vulnerabilities Come to Light (Commercial, Small-Molecule Emphasis)
Exhibit 5.51. Likelihood of Work on Backup Compounds to Continue Through Phase I Clinical Studies as Candidate Vulnerabilities Come to Light (Big Pharma/Biotech)
Exhibit 5.52. Likelihood of Work on Backup Compounds to Continue Through Phase I Clinical Studies as Candidate Vulnerabilities Come to Light (Small to Midsize Pharma/Biotech)
Exhibit 5.53. Likelihood of Work on Backup Compounds to Continue Through Phase I Clinical Studies as Candidate Vulnerabilities Come to Light (Pre-Commercial Pharma/Biotech)
Exhibit 5.54. In Vitro Predictive Toxicology Level of Success in Qualifying Backup Compounds (Commercial, Small-Molecule Emphasis)
Exhibit 5.55. In Vitro Predictive Toxicology Level of Success in Qualifying Backup Compounds (Big Pharma/Biotech)
Exhibit 5.56. In Vitro Predictive Toxicology Level of Success in Qualifying Backup Compounds (Small to Midsize Pharma/Biotech)
Exhibit 5.57. In Vitro Predictive Toxicology Level of Success in Qualifying Backup Compounds (Pre-Commercial Pharma/Biotech)
Exhibit 5.58. Change in Emphasis on Backup Compounds Expected During Next Five Years (Commercial, Small-Molecule Emphasis)
Exhibit 5.59. Change in Emphasis on Backup Compounds Expected During Next Five Years (Big Pharma/Biotech)
Exhibit 5.60. Change in Emphasis on Backup Compounds Expected During Next Five Years (Small to Midsize Pharma/Biotech)
Exhibit 5.61. Change in Emphasis on Backup Compounds Expected During Next Five Years (Pre-Commercial Pharma/Biotech)