PowerPoint Guidelines and Tips for the International R

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Zhengming (Jimmy) Chen, Ph.D. Vice President,
Chemistry and PRD zchen_at_dovpharm.com
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From Medicinal Chemistry to API Manufacturing, A
Small Biopharma's Outsourcing Road Map

• Case Study 1 The Company
• Case Study 2 Medicinal Chemistry Lead
  Optimization Projects
• Case Study 3 Process Development
  Manufacturing Projects
• Case Study 4 Drug Product Clinical
  Packaging
• Summary Lessons Learned

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Case Study 1

• The Company
• History
• Pipeline
• Process

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DOV Pharmaceutical, Inc.

• Founded by Bernard Beer and Arnold S. Lippa in
  1995
• Went in public in August, 2002
• Focused on the discovery, acquisition and
  development of novel drug candidates for CNS
  disorders.
• Operates principally in the United States but
  also conducts preclinical and clinical studies
  outside the U.S.

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DOV Product Pipeline
Indiplon
Insomnia Neurocrine
Bicifadine
Pain XTL
Depression
DOV 21,947
Alcohol/Substance Abuse
DOV 102,677
Uptake
Depression, Obesity, Pain
Inhibitors
Three Optimized
Leads
Anxiety
GABAA
Modulators
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DOV Chemistry PRD Projects
Med. Chem.
Chemistry Plan Synthesis Informatics
Process Development
IP Protection
IP assessment Patent preparation FTO issues
Robust Economical Processes
Chemistry PRD
API
Clinical Packaging
cGMP Compliance Raw materials Batch Records
Labels Batch Records cGMP
Drug Product
Formulation Batch Records cGMP
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Case Study 2

• Medicinal Chemistry - Lead Optimization Projects
  
• Logistics
• Decision points
• Worked with companies in US, Europe, EU Asia
• Balance of price, problem solving capability
  and timeline

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Small Pharma MedChem Process
Currently generating lt100 new compounds/month

• A Knowledge based drug discovery platform

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Outsourcing Considerations

• In our RFPs we clearly define the following
• What are our needs?
• Target compounds, amounts, purity timelines
• What would be our contribution in terms of
  resource technology?
• Info about starting materials, synthetic
  procedures, reference papers, reference
  compounds, etc.
• Define Internally
• What is the available budget?
• How do we/could we maintain, control or reduce
  costs?
• Competitive bidding process

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Drug discovery is any thing but cheap
Quotes Evaluations The Magic Triangle

• What does DOV really want?
• Value
• Speed
• Quality
• IP Security
• Innovation
• What do CROs have to offer in the quote?
• Good understanding of chemistry
• Competitive price
• Reasonable timeline
• Track of past performance
• flexibility
• Confidence

Value
Quality
Speed
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Results and Evaluations

• Weekly Updates, with some degree of details
• Conference calls if necessary
• Meet goals or objectives set in RFP
• Final Report in JOC format and it should include
  synthetic schemes, procedures including yields,
  analytical etc
• How do we evaluate success/quality?
• Numbers are important!
• Number-driven metrics will distort the objectives
  away from quality, which is more challenging to
  define and measure

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Challenges

• Proposed compounds could not be made, how much
  time would you like to try?
• A fixed price project took a year to complete
• A FTE project runs out of the proposed timeline
• Failure in clinical trials
• Very tight budget situation.

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Case Study 3

• Process Development and API Manufacturing
  Projects
• Project stages
• Decision points
• Matching Projects with Expertise
• Cost Saving vs Quality vs cGMP Compliance
• Location Site Audit

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Process Development Project

• Route Scouting Stage
• Select a US CRO who has proven ability to quickly
  work through a variety different synthetic routes
• One industrial viable route was developed
• Kg Scale up
• Select a European company who has expertise in
  screening hydrogenation reactions a key
  reaction step
• Further Scale up and potential manufacturing
• Access to semi-retired industry legends for CMC
  projects
• Collaborate with CMOs globally

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Matching Projects with Expertise
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Case Study 4

• Drug Product and Clinical Packaging
• Quote Evaluation Decision Points
• Project Execution and Timeline
• Cost Saving Measures
• plan changes quote updates
• storage items

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Summary Success Factor
Contractor Competency
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Optimizing Outsourcing Model

• Global strategic resources
• East vs West, Outsource and offshore
• Internet based enabling technology
• The world is flat and works 24 hrs
• Virtual R D productivity metrics
• Value metrics
• IP and knowledge management
• Risk management
• Electronic data capture and data submission to
  regulatory authorities

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Opportunities in Life Sciences

• Fund strategies for lower-cost drug discovery and
  development in small companies
• Outsource and offshore RD (China, India, Russia)
  with eyes wide open
• Create capital efficient virtual drug discovery
  and development companies with experienced
  management teams
• Create startups with late stage assets ( PoC in
  multiple animal species or human)
• Start with validated targets and utilize rapid
  in-vivo screening
• Success becomes a matter of finding innovation
  and managing the complex path to market

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Q A