Funding in Return for Rights Outside the Developed World: Public-Private Partnerships

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Funding in Return for RightsOutside the
Developed WorldPublic-Private Partnerships

• Gerald J. Siuta, Ph.D.
• Consultant, Business Development
• September 27, 2007

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What is a Public-Private Partnership?

• An organization that pursues a social mission by
  employing the best practices of the private
  sector and drawing upon resources from the
  public and private realms

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(No Transcript)
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Types of Public-Private Partnerships

• Basic Knowledge/Research
• SNP Consortium
• Improvement of Access to Health Products
• International Trachoma Initiate
• Global Coordinating/Funding Mechanisms
• Global Fund to Fight AIDS, Tuberculosis and
  Malaria
• Health Services Strengthening
• Global Campaign for Microbicides
• Public Education and Advocacy
• Corporate Council on Africa
• Regulation, Quality and Standards
• Anti-Counterfeit Drug Initiative
• Product Development Partnership (PDP)
• Global Alliance for TB Drug Development

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PDP Operations

• Provide specific disease expertise
• Fill development gaps
• Have purchasing power US1B for TB alone
• Unique deals, not charity projects
• Undertake clinical development
• Build extensive networks for market access in
  developing countries
• Provide credibility with advocates, NGOs and
  activists

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How PDPs Work
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Who are PDPs?
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• Case Study
• TUBERCULOSIS

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Global Tuberculosis Epidemic

• One-third of the worlds population is infected
  with Mycobacterium tuberculosis (M.tb)
• 2 billion people
• 8-9 million develop active disease annually
• 2 million deaths occur each year
• 1 person dies every 15 seconds
• 400,000 cases of MDR-TB each year
• Leading cause of death in HIV-positive people
• 12 Million people are TB/HIV co-infected

TBs economic toll 16 billion a year
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Current TB Drug Therapy

• Active TB
• Standard therapy 4 drugs (isoniazid, rifampin,
  pyrazinamide ethambutol) for 2 months, followed
  by isoniazid and rifampin for 4 months
• Latent TB
• Standard therapy isoniazid for 9 months
• Multi-Drug Resistant TB (MDR-TB)
• Individualized, prolonged therapy, few available
  drugs, poorly tolerated and difficult to
  administer
• TB/HIV Co-Infection
• Treatment as in active TB, but drug interactions
  with antiretroviral agents make simultaneous
  therapy difficult
• Extensively Drug Resistant TB (XDR-TB)
• No treatment available

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The Need for New TB Drugs

• Complex 6-9 months treatment with a 4
  drug combination regimen
• No new anti-TB drug in over 40 years
• TB/HIV co-infections fueling each other
• MDR-TB is on the rise
• Unattractive market for private sector
• No capitalization of public sector research

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History of the TB Alliance

• Cape Town Declaration February 2000
• Hosts Rockefeller Foundation and the Medical
  Research Council of South Africa
• Over 120 organizations (health, science,
  philanthropy and private industry)
• Results
• Support goals of Stop TB Initiative
• Create Scientific Blueprint
• Develop Pharmacoeconomic Analysis

Build a Global Alliance for TB Drug Development
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The TB Alliance

• Independent, international Product Development
  Partnership founded in October 2000
• Non-profit organization
• Headquarters in New York City
• Offices in Brussels and Cape Town
• Entrepreneurial, virtual RD approach
• Out-source RD to public and private partners
• Pro-active fundraising
• Over US 200 million raised
• Support 200 FTE worldwide and 35 FTE in-house

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Our Mission

• Develop an entirely new therapeutic regimen that
  will shorten or simplify the treatment of
  tuberculosis
• Coordinate and act as catalyst for global TB drug
  development activities
• Ensure Affordability, Adoption and Access (AAA
  Strategy)

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AAA Strategy

• Affordability
• Appropriate pricing in developing countries
• Adoption
• Ensure that new drugs are incorporated into
  existing treatment programs
• Access
• Procurement and distribution to those patients
  who need them most

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Our Vision
10 Days
2 Months
6 Months
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Profile of a New TB Drug

• Shorten treatment to less than 2 months
• Novel mechanism of action (MDR/XDR-TB)
• Orally active
• Once daily or intermittent therapy
• Compatible with HIV treatment
• Low cost of goods

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Financial Support

• Bill and Melinda Gates Foundation
• Rockefeller Foundation
• Netherlands Ministry for Development Cooperation
• United States Agency for International
  Development (USAID)
• Governments of Great Britain and Ireland

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Types of Deals

• In-Licensing
• IP Assignment
• Sponsored RD
• Collaborative RD
• Freedom to Operate
• Clinical Trials

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TB Alliance Portfolio
Discovery
Clinical Development
Compounds, Analogs and Derivatives
Nitroimidazole Analogs (U. of Auckland/U. of
Illinois at Chicago)
Moxifloxacin (Ethambutol Substitution) (Bayer)
Quinolones (KRICT/Yonsei University)
Moxifloxacin (Isoniazid Substitution) (Bayer)
Multi-Functional Molecules (Cumbre)
Nitroimidazole PA-824 (Chiron/Novartis)
Mycobacterial Gyrase Inhibitors (GlaxoSmithKline)
InhA Inhibitors (GlaxoSmithKline)
Pleuromutilins (GlaxoSmithKline)
Focused Screening (GlaxoSmithKline)
Riminophenazines (Institute of Materia
Medica/BTTTRI)
Screening and Target Identification (AstraZeneca)
Malate Synthase Inhibitors (GlaxoSmithKline/Rockef
eller U./Texas AM U.)
Active TB Alliance program
TB Alliance in discussion
New Targets (University of Pennsylvania)
Protease Inhibitors (Queen Mary, University of
London)
Proteasome Inhibitors (Cornell University)
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Chiron/Novartis

• PA-824 A novel nitroimidazole
• Discovered by Pathogenesis, Inc.
• Distinct mechanism of action
• Potent activity against both active and slow
  growing M.tb
• Possesses both bactericidal and sterilizing
  activity

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Chiron/Novartis

• Worldwide exclusive license for the treatment of
  tuberculosis
• Defined scientific milestones
• Grant-back option
• Manufacturing rights
• No royalties in developing world

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Development of PA-824

• Phase I clinical trials began June 3, 2005
• Preclinical development completed in 3 years
• Drug was well tolerated with no definitive
  dose-limiting adverse events
• Phase II extended Early Bactericidal Activity
  (EBA) study has begun in Cape Town, South Africa

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University of Auckland

• Synthesis of PA-824 analogs
• Identified many new pharmacophores, several of
  which have demonstrated potent activity against
  TB
• Optimization has led to nitroimidazole analogs
  that have in vitro activity greater than PA-824

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GlaxoSmithKline

• Joint drug discovery program at GSKs Diseases of
  the Developing World facility in Tres Cantos,
  Spain
• Four individual projects
• Mycobacterial gyrase inhibitors
• InhA inhibitors
• Pleuromutilins
• Focused screening

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GlaxoSmithKline

• Project oversight by Joint Steering Committee
• TB Alliance helps to support 25 full-time
  scientists at GSK working exclusively on the
  TB drug program
• GSK absorbs all remaining overhead costs
• GSK contributes a matching number of staff
• Any resulting medicines will be made affordable
  and accessible to those most in need

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Korea Research Institute of Chemical Technology
(KRICT)

• Located in Daejeon, South Korea
• Synthesized more than 600 quinolones, pyridones
  quinolizines
• In vitro and in vivo biological testing at the
  Yonsei University College of Medicine in Seoul,
  South Korea
• Four lead compounds have been selected for
  further preclinical evaluation

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Cumbre Pharmaceuticals

• Joint program on the design, synthesis and
  optimization of multi-functional antibiotics
• The TB Alliance has exclusive rights to these
  compounds for the treatment of tuberculosis and
  other neglected diseases
• Cumbre retains rights to pursue the compounds for
  use in other infectious disease areas

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Institute of Materia Medica

• Joint research partnership for the design,
  synthesis and evaluation of a class of compounds
  known as riminophenazines
• Class was discovered in the 1950s
• The collaboration will utilize IMM's expertise
  and integrated capabilities in chemistry,
  pharmacology and manufacture

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• The TB Alliance-Bayer
• Moxifloxacin Deal

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Moxifloxacin

• Fluoroquinolone antibiotic
• Orally active
• Once-a-day dosage
• Approved in 104 countries for the treatment of
  bacterial respiratory and skin infections

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Moxifloxacin for TB

• Novel mechanism of action kills M.tb by
  inhibition of DNA gyrase
• In vivo studies showed moxifloxacin reduced
  treatment time by two months when substituted for
  isoniazid
• Safe to use with antiretroviral agents since it
  is not metabolized by the cytochrome P-450
  enzyme system

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October 18, 2005

• TB Alliance and Bayer HealthCare announced a
  partnership to coordinate a global clinical trial
  program to study the potential of moxifloxacin to
  shorten the standard six-month treatment of TB

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The Partnership

• Clinically assess the efficacy and safety of
  moxifloxacin as a front-line agent for the
  treatment of TB
• If clinical trials are successful, register
  moxifloxacin for a TB indication
• Committed to making the product affordable and
  accessible to patients in the developing world

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Moxifloxacin Clinical Trials

• Evaluate whether substitution of moxifloxacin for
  one of the standard TB drugs (isoniazid or
  ethambutol) eliminates TB infection faster than
  current standard therapy
• Trials to be run in Brazil, Canada, South Africa,
  Spain, Tanzania, Uganda, the United States and
  Zambia
• More than 3,000 TB patients will be enrolled

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Bayer Commitments

• Donate moxifloxacin for each clinical trial site
• Cover costs of regulatory filings
• Provide moxifloxacin at an affordable price for
  patients with TB in the developing world

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TB Alliance Commitments

• Coordinate and help cover the costs of the
  clinical trials
• Ensure coordination of information and results
  towards the goal of registration
• Leverage substantial support from
• U.S. Centers for Disease Control and Prevention
  (CDC)
• Orphan Products Development Center of the U.S.
  Food Drug Administration
• European and Developing Countries Clinical Trials
  Partnership (EDCTP)

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• Special Recognition

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Licensing Executives Society

• On September 13, 2006, the Licensing Executives
  Society Industry/University and Government
  Laboratory Transactions Industry Sector presented
  the TB Alliance and Bayer its Deals of
  Distinction Award which recognizes worthy
  transactions involving licensing and transfer of
  intellectual property and promote creative and
  innovative solutions to business issues

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Scrip World Pharmaceutical News

• The TB Alliance-Bayer deal was also one of six
  finalists for the Scrip 2006 Best Partnership
  Alliance Award which recognizes the importance of
  partnerships involving pharmaceutical and/or
  biotech companies, focusing on deals that require
  strong strategic input from both partners, are
  mutually beneficial to both parties, hold promise
  to address an unmet medical need and demonstrate
  strategic potential as well as an innovative
  business model

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• Global Alliance for TB
• Drug Development
• www.tballiance.org