Public/Private Partnerships in Global Health Initiatives

Gerald J. Siuta, Ph.D., CLPConsultant, Business Development

New York University Global Health AllianceNew York City, NY

March 27, 2009

Global Tuberculosis Epidemic• One-third of the world’s 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

TB’s economic toll: $16 billion a year

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

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

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 forTB Drug Development

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 R&D approach– Out-source R&D to public and private partners

• Pro-active fundraising– Over US $200 million raised

• Support ~ 200 FTE worldwide and 38 FTE in-house

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)

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

Our VisionFDCs

10 Days

2 Months

6 Months

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

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

Types of Deals

• In-Licensing

• IP Assignment

• Sponsored R&D

• Collaborative R&D

• Freedom to Operate

• Clinical Trials

Industrial Partners

• Bayer HealthCare

• Chiron/Novartis

• GlaxoSmithKline

• Novartis Institute for Tropical Diseases

• sanofi-aventis

Academic Partners• Infectious Disease Research Institute• Institute of Materia Medica (China)• Johns Hopkins University• Korea Research Institute of Chemical

Technology/Yonsei University (South Korea)• Rutgers, The State University of New Jersey• Texas A&M University• University of Auckland (New Zealand)• University of Illinois at Chicago• University of Pennsylvania

Lead Identification

Lead Optimizati

onPreclinical Phase I Phase II Phase III

Malate Synthase Inhibitors

Riminophenazines

Focused Screening

InhA Inhibitors

Mycobacterial Gyrase Inhibitors

Pleuromutilins

Nitroimidazoles

Quinolone TBK-613

Multifunctional Molecules

PA-824

Moxifloxacin

TB Alliance PortfolioTB ALLIANCE TB ALLIANCE PROGRAMSPROGRAMS

DISCOVERYDISCOVERY CLINICALCLINICAL DEVELOPMENTDEVELOPMENT

Phenotypic Screening

Protease Inhibitors

Energy Metabolism Inhibitors

NITD Portfolio

RNA Polymerase Inhibitors

Bayer HealthCare

• Moxifloxacin

• Fluoroquinolone antibiotic

• Orally active

• Once-a-day dosage

• Approved in 104 countries for the treatment of bacterial respiratory and skin infections

Bayer HealthCare

• Moxifloxacin

• Fluoroquinolone antibiotic

• Orally active

• Once-a-day dosage

• Approved in 104 countries for the treatment of bacterial respiratory and skin infections

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

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

Moxifloxacin Clinical Trials

• Evaluate whether substitution of moxifloxacin for one of the standard TB drugs (isoniazid or ethambutol) eliminates TB infection faster than current therapy

• Trials to be run in Brazil, Canada, South Africa, Spain, Tanzania, Uganda, the United States and Zambia

• More than 3,000 TB patients to be enrolled

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

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)

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

Chiron/Novartis

• Worldwide exclusive license for the treatment of tuberculosis

• Defined scientific milestones

• Grant-back option

• Manufacturing rights

• No royalties in developing world

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

• One lead compound has been selected for further preclinical evaluation

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

GlaxoSmithKline

• Joint drug discovery program at GSK’s Diseases of the Developing World facility in Tres Cantos, Spain

• Five individual projects:– Mycobacterial gyrase inhibitors– InhA inhibitors– Malate synthase inhibitors – Pleuromutilins– Focused screening

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

Global Alliance for TBDrug Development

www.tballiance.org