Strategic Plan

1

Strategic Plan Working Group on TB Drug
Development Maria C. Freire, Ph.D. Chair,
Working Group on TB Drug Development Presentation
to the Global Plan II Steering Committee May
2, 2005 Addis Ababa
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Working Group on TB Drug Development

• A forum to facilitate and foster global
  collaborations for the development of new anti-TB
  drugs.
• A network of over 80 individuals committed to the
  development of a faster cure that will become the
  cornerstone of tomorrows TB control initiatives.

3
Core Committee for Global Plan II

• Dr. Michael Cynamon, Syracuse VA Medical Center
• Dr. Brent Copp, University of Auckland
• Dr. Barry Furr, AstraZeneca Pharmaceuticals
• Dr. Amina Jindani, St. Georges Hospital Medical
  School
• Dr. Tom Kanyok, World Health Organization (TDR)
• Dr. Barbara Laughon, NIAID (NIH)
• Dr. Christine Sizemore, NIAID (NIH)
• Dr. Peter Small, Bill and Melinda Gates
  Foundation
• Dr. Andrew Vernon, Centers for Disease Control
  and Prevention
• Dr. Abubakar Yaro, Africa Health Research
  Organization

4
GPII Development WG Process

• Core Committee teleconferences
• Circulation of drafts
• Email consultations
• Subcommittee formation
• Distribution to wider Working Group

5
Our Goal New TB Regimens

• Shorten and/or simplify treatment of active,
• drug-susceptible TB
• Improve treatment of MDR-TB
• Improve treatment of TB/HIV
• Improve treatment of LTBI

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• Global Plan to Stop TB II

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Shortened Therapy for TBMedium Term Goal
6 months to 1-2 months
130 doses
10 doses
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Shortened Therapy for TBLong-term Vision
7 12 day course of therapy
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Working Group Pipeline, April 2005
Discovery - 17
Preclinical - 4
Clinical Testing - 5
Diarylquinoline R207910 Johnson Johnson
Diamine SQ-109 Sequella Inc.
Cell Wall Inhibitors NIAID, Colorado State
University
Nitroimidazole Analogs Novartis Institute for
Tropical Diseases, NIAID, TB Alliance
Dihydrolipoamide Acyltransferase
Inhibitors NIAID, Cornell University
Nitroimidazole PA-824 Chiron Corporation, TB
Alliance
Gatifloxacin OFLOTUB TDR, Tuberculosis Research
Centre, NIAID, TBRU
Novel Antibiotic Class GlaxoSmithKline, TB
Alliance
Dipiperidines Sequella Inc.
Synthase Inhibitor FAS20013 FASgen Inc.
Moxifloxacin Bayer Pharmaceuticals, CDC TBTC,
Johns Hopkins University, NIAID, TBRU
Picolinamide Imidazoles NIAID, TAACF)
InhA Inhibitors GlaxoSmithKline, TB Alliance
Translocase I Inhibitors Sequella Inc., Sankyo
Proprietary Compound Otsuka
Pleuromutilins GlaxoSmithKline, TB Alliance
Isocitrate Lyase Inhibitors (ICL)
GlaxoSmithKline, TB Alliance
Pyrroles (TB Alliance, Private Sector Partner)
Pyrrole LL-3858 Lupin Limited
Macrolides TB Alliance, University of Illinois at
Chicago
Quinolones KRICT/ Yonsei University, NIAID,
TAACF, TB Alliance
Methyltransferase inhibitors Anacor
Pharmaceuticals
Proprietary Compounds AstraZeneca
Natural Products Exploration NIAID, TAACF,
California State University, University of
Auckland
Thiolactomycin Analogs NIAID, NIH
Nitrofuranylamides NIAID, University of Tennessee
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Concentration of Drugs in Clinic Expected
Approval Dates
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
III
Moxifloxacin
II
NDA
III
Gatifloxacin
II
NDA
Diarylquinoline R207910
I/II
III
NDA
Otsuka Compound
I
II
II/III
NDA
Pyrrole LL3858
I
II
II/III
NDA
Synthase Inhibitor FAS 20013
I
II
II/III
NDA
Nitroimidazole PA-824
I
II
II/III
NDA
Diamine SQ-109
I
II
II/III
NDA
Translocase I Inhibitors
I
II
II/III
NDA
Implications for New Combinations Tested
Simultaneously
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Coordinated, Streamlined Development
Develop effective animal models, surrogate
markers, EBA studies, etc.
Phase II
Phase I
Preclinical
Lead to Preclinical
Candidate
Hit to Lead
Early Discovery
Phase III
Test New Combinations Simultaneously
Identify Possible Combinations
Combination Trials
Combination Trials
Combination Trials
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Strategic Objectives and Targets

• Build a sustainable portfolio of new drug
  candidates
• Accelerate basic discovery biology
• Expand platform technologies to accelerate drug
  development
• Plan and execute clinical trials
• Encourage clear and efficient regulatory guidance
  and processes

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Objectives and Targets 2006 - 2015

• A. Discovery Biology and Chemistry
• B. Drug Development RD
• C. Clinical Trial Planning and Execution
• D. Regulatory Approval and Registration

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Working Group Deliverables

• Clinical Trials start 2005, combination trials in
  2007-8
• Introduction of shorter (2-3 month) regimen by
  2010
• - Moxifloxacin
• - Gatifloxacin
• Sustainable pipeline and regular delivery of new
  drugs available for use in combination by 2015
• Breakthrough regimen (1-2 month) in trials by
  2015 based on rational combinations

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Next Steps

• Circulation to all members of WG
• Costing Analysis
• Impact Analysis
• Coordination with other Tools WG
• Coordination with implementation WG