Transformational Medical Technologies Initiative TMTI

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Transformational Medical Technologies Initiative
(TMTI)
Ms. Heather Wargo TMTI Therapeutics Portfolio
Manager Heather.Wargo_at_dtra.mil
To protect the Warfighter and the Nation from
biothreats
Aerobiology in Biodefense III Conference
July 13-16, 2009
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Overview

• What TMTI is, and isnt
• Current Portfolio
• Threat Agents and Aerosol Animal Models of
  Interest
• Opportunities
• Contact Information

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Opportunities

• Portfolio Balance
• Portfolio Gaps
• Animal Efficacy Evaluation

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Organization Chart
Undersecretary of Defense for Acquisition,
Technology and Logistics (USD (ATL)) Defense
Acquisition Executive (DAE)
Army Acquisition Executive (AAE)
Assistant to the Secretary of Defense for Nuclear
and Chemical and Biological Defense ATSD(NCB)
Deputy Assistant to the Secretary of Defense for
Chem and Biol Defense and Chem Demilitarization
Programs DATSD(CBDCDP)
Defense Threat Reduction Agency (DTRA)
TMTI Executive Office (EO)
Joint Program Executive Office (JPEO)
Joint Science and Technology Office (JSTO)
TMTI Program Office
Technologies Portfolio
Therapeutics Portfolio
Pathogen ID Characterization, Drug Discovery,
Drug Evaluation
Hemorrhagic Fever Virus (HFV), Intracellular
Bacterial Pathogens (ICB)
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TMTI is
Designed to spur innovative research to develop

• Technologies to characterize unknown pathogens
  and rapidly develop medical countermeasures to
  newly identified threats

• Broad spectrum countermeasures (one drug, many
  bugs)

• TMTI is an initiative that will translate into a
  program to produce medical countermeasures that
  are
• FDA approved
• Broad spectrum
• Produced using a rapid response capability
  adaptable to new threats

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TMTI is not

• An operational capability in and of itself
• Limited to only ST, or only Advanced Development
• Designed to accelerate or change the FDA approval
  process

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TMTI Technologies Portfolio
Countermeasure discovery platforms
Countermeasure evaluation capabilities
Pathogen characterization capabilities
In vivo assessment, product scale-up and FDA
approval
In silico and in vitro discovery technologies
In silico and in vitro assessment for decision
support
Candidate countermeasures
Recommendations for next steps
Authorized countermeasures
RAPID RESPONSE
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TMTI Technologies Portfolio (cont)

• In vivo evaluation
• Product scale-up process
• Protein expression system

• ID and characterization
• Genetic sequencing and characterization
• Genetic sequences of biological threats and near
  neighbors
• Bioinformatics integration of databases
• Pathway and target ID
• Computational Platform pathway analysis
  host/pathogen interaction
• Host genes essential for innate immune response,
  bacterial intracellular survival, viral
  replication, intracellular killing, sepsis,
  apoptosis
• Bacterial protein/protein interactions, DNA
  replication, intracellular survival

• Discovery platform candidates
• Computational platforms
• Rational drug design
• Pharmacology/toxicity
• Recombinant yeasts for generation of novel
  compounds
• High throughput assays

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TMTI Therapeutics Portfolio
Broad Spectrum HFV / ICBP
Up-regulate Host Response
Counter Pathogen Infection
Immune Enhancement .
Reduce Severity of Disease
Down-regulate Host Response
Pathogen / Host Targets
RAPID RETURN TO DUTY
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TMTI Therapeutics Portfolio (cont)

• Definition Broad Spectrum
• Typically, demonstrated activity against two or
  more viral families or bacterial genera
• Ideally, active against
• gram positive and gram negative ICBP
• HFV and ICBP
• Dual use. Active against biothreat agents of
  interest and non-biothreat agents, i.e., hospital
  acquired infections

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TMTI Therapeutics Portfolio (cont)
1 2 3 4
5 6 7 8
TRL
SM, tRNA hydrolase
Sep 10 / F.t
Cethromycin, protein synthesis
Dec 09 / Y.p
Jul 10 / B.a, F.t, Y.p, or B. spp
SM I3C analogs, mech unknown
ICBP
Oct 11 / Y.p, B.p, or F.t
SM, gyrase, topoisomerase
SM, reduce resistance
Oct 10 / B.a, F.t, or Y.p
SM, membrane biosynthesis
Jun 11 / Y.p, B.p, or F.t
SM, innate immune enhancement
Oct 09 / B.p
Jul 10 / Ebola or Marburg
Off-patent/patent, various targets
ICBP HFV
SM, immunomodulator
Dec 09 / Ebola, F.t, B.a, or Y.p
Antisense, conserved viral genes
Nov 08 / Ebola/Marburg May 10 / Junin
HFV
MAb, TSG101
Aug 09 / Ebola
Pathogen
SM, VP40/TSG101
Sep 10 / Ebola
SM, mech unknown
Host
Dec 09 / Ebola
Apr 12 / Ebola or Junin
Bavituximab, phosphatidyl serine
1-3 5 - 17
10 - 25 18 - 35
45-70 90
PROBABILITY OF SUCCESS TO LICENSURE
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TMTI Target Product Profile Guidelines

• Sets development strategies resulting in end
  products intended for use with warfighters in the
  field
• Communicates expected product characteristics to
  the warfighter and TMTI performers
• Specific for
• HFV Therapeutic
• HFV Prophylaxis
• ICBP Therapeutic
• ICBP Prophylaxis
• Effective against an aerosolized threat

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Aerosol Animal Efficacy Models

• Aerosol delivery is the anticipated route of
  threat agent exposure in a biothreat event
• Countermeasure evaluation under the FDA Animal
  Rule should mimic the conditions of the
  anticipated human exposure route
• Countermeasure evaluation should use standardized
  aerosol exposure procedures and methods for
  delivery

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Threat Agents of Interest and Aerosol Animal
Efficacy Models
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Threat Agents of Interest and Aerosol Animal
Efficacy Models (cont)
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TMTI Portfolio Integration
Technologies Portfolio RAPID RESPONSE
Countermeasure discovery platform
Countermeasure evaluation capability
Pathogen characterization capability
Counter Pathogen Infection
Immune Enhancement .
Reduce Severity of Disease
.
IND / NDA / BLA
Candidate
Therapeutics Portfolio RAPID RETURN TO DUTY
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Opportunities

• Countermeasure Discovery Platforms
• High throughput screening technologies for drug
  candidates
• Drug design capabilities that push the state of
  the art
• Technologies to enhance the drug evaluation
  process (e.g. computer modeling and simulation)
• Host Directed Therapies
• Targeting host factors essential to pathogen
  life cycle
• Enhancement of innate immunity
• Attenuate common final pathways of pathogenesis
• Focused systems biology
• Drug formulation and delivery
• In vivo evaluation

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Upcoming Business Opportunities
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How to Contact Us

• The TMTI website provides general information
  about the TMTI program, its mission, and goals
  www.tmti-cbdefense.org
• Official government solicitations can be found at
  www.fedbizops.gov
• E-mail us directly tmtiwebsite_at_dtra.mil
• Call us 703-767-2347

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Back Up
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TMTI RDTE BudgetBreakdown by Fiscal Year
Millions
Fiscal Year
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TMTI Internal Organizational Chart
Dr. R. Kincaid
Technical Director
x 4
Open
Program Analyst
x 3
x 4
x 4
Open
Financial Analyst
Mr. R. Huffman
Project Manager
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Target Product Profiles - Therapeutic
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Target Product Profiles - Prophylaxis