NIAID BioDefense Research: Challenges, Opportunities,

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NIAID BioDefense ResearchChallenges,
Opportunities, Sustainability

• Michael G Kurilla, MD-PhD
• Director, Office of BioDefense Research Affairs
• Division of Microbiology Infectious Diseases
• Associate Director, BioDefense Product
  Development
• National Institute of Allergy and Infectious
  Diseases
• November 17, 2005

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Comprehensive BioDefense Research Agenda
DHHS
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NIH BioDefense Research Funding FY00 FY05
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Current Countermeasures
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Anti-infectivePD - A Widening Gap
Demand Pull Respond to the needs of the
marketplace. Need to be flexible, contractual,
committable, not to be subject to political
change.
Supply Push Research provides new opportunities
that lead to innovation.
due to market forcesbeyond biodefense
Provider of acquisition
NIH
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NEEDS PROCESS CMs
Biodefense Anti-infectives (includes
resistance) Diseases of the Developing World
Therapeutics Vaccines Diagnostics

• NIAID
• Infrastructure
• Discovery
• Preclinical
• Clinical

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Reality Check

• Myth
• Scientific breakthroughs lead to new products
• Reality
• Scientific breakthroughs lead to new concepts
  that may yield a new product after decades of
  trial and error (mostly error) and at least 3
  orders of magnitude more funding

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Reality Check

• Myth
• Phase III clinical trials are responsible for
  most of the costs of clinical development for new
  medical products
• Reality
• Total clinical trial costs (including costs of
  goods) typically amount to only 20 25 of the
  total clinical development costs

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Reality Check

• Myth
• The Animal Rule will drastically reduce
  development time and costs for biodefense
  products compared to traditional pharmaceutical
  development
• Reality
• Animal Rule models are disease models (rather
  than infection models), accepted by the FDA, and
  performed under GLP conditions with cGMP product
  including detailed PK/PD or correlates of
  protection analysis combined with human PK or
  immunogenecity data

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Product Development Activities
Basic Applied Advanced Acquisition
Unmet Medical Need
Clinical Indication

• Advanced Product Testing
• Product optimization / formulation
• Pilot lot product
• Animal rule correlates
• IND enabling studies
• Phase I II clinical trials
• Animal efficacy models for EUA
• Large scale reagent production

• Basic Product, what product?
• Microbiology
• Immunology
• Pathogenesis

• Applied Product Search
• Target ID
• Target validation
• Assay development
• In vitro screening
• Medicinal chemistry for SAR
• Animal model development
• In vivo infectious models

• Acquisition Product Demonstration
• Process development
• Scaled up manufacturing
• Phase III clinical trials
• Animal rule efficacy studies
• Other BLA/NDA enabling activities

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Product Development Pathway
Basic Applied Advanced Acquisition
Unmet Medical Need
Clinical Indication
NIH
Academia
PPPs
Biotech
Traditional Large Pharma
BioShield
DOD/SIP
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Developing Capacity

• Intellectual
• Facilities
• Reagents
• Services
• Clinical Testing

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Reagents Services
Biodefense and Emerging InfectionsResources (BEI
Resources) Repository Program (www.beiresources.o
rg)
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Clinical Testing
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Second-Generation Anthrax VaccineRecombinant
Protective Antigen (rPA)

• First generation AVA (Biothrax)
• Filtered B. anthracis culture supernatant
• Highly reactogenic and has a questionable safety
  profile
• Mechanism of protection antibodies against the
  Protective Antigen (PA)
• Second generation rPA
• Highly purified, single recombinant protein
  formulated with Aluminum
• Goal efficacy and safety
• Multiple Contracts Awarded for Development,
  Production and Testing of Anthrax rPA Vaccine
• Development program budget approx. 250 M
• Extensive animal model development program for
  anthrax countermeasures evaluation
• Designed to fulfill FDA/CBER 21 CFR 601.91
  Animal Rule criteria
• Phase 1 and Phase 2 clinical trials
  completed/underway/planned

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Additional Development Projects

• Anthrax
• Monoclonal antibody therapy
• Botulinum
• Vaccine candidates (mono E pentavalent)
• Monoclonal antibody therapy
• Plague
• F1V vaccine candidate
• Tularemia
• Live vaccine strain (LVS) in Phase I testing
• Next generation vaccine candidate
• Smallpox
• Small molecule therapeutics
• Viral Hemorrhagic Fevers
• Novel Ebola vaccine candidate

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Mechanisms of Engineered Threats

• Anti-microbial resistance
• Potential to defeat existing therapies
• Naturally occurring
• Near term intentional activity
• Enhanced virulence
• Potential to enhance infectiousness and reduce
  therapeutic window
• Mid term potential activity
• Chimerism / Immunomodulators
• Potential to defeat existing preventive
  strategies and diagnostics
• Long term potential activity

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Additional Areas of Broad Interest

• Vaccines
• non-needle delivery
• long term stabilization
• more rapid induction
• Therapeutics
• host based directed interventions
• innate immune augmentation
• Diagnostics
• multiplexed adaptive platforms
• host based systems

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