The Global Alliance for TB Drug Development

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

Global Alliance for TB Drug Development

Biotechnology Industry Organization International ConventionChicago, ILMay 4, 2010

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 50 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 50 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

TB Alliance PortfolioLead

Identification

Lead Optimizatio

n

Preclinical

Phase I Phase II Phase III

DISCOVERYDISCOVERY CLINICALCLINICAL DEVELOPMENTDEVELOPMENT

Whole-Cell Screening

Phenotypic Screening

GyrB Inhibitors

InhA Inhibitors

Mycobact. Gyrase InhibitorsNitroimidazoles

Riminophenazines

TMC-207Moxifloxacin

TB ALLIANCE TB ALLIANCE PROGRAMSPROGRAMS

LeuRS Inhibitors

RNA Polymerase Inhibitors

Topoisomerase I Inhibitors

Tryptanthrins

Protease InhibitorsEnergy Metabolism Inhibitors

NITD Portfolio

Natural ProductsMenaquinone Syn InhibitorsMalate Synthase Inhibitors

PA-824

Diarylquinoline

Industrial Partners

• Chiron Corporation/Novartis• Bayer Healthcare AG• Tibotec (Subsidiary of Johnson & Johnson)• GlaxoSmithKline• Anacor Pharmaceuticals• Novartis Institute for Tropical Diseases• AstraZeneca

Academic Partners• New York Medical College• Rutgers University• Colorado State University• Institute of Microbiology (China)• Institute of Materia Medica (China)• Korea Research Institute of Chemical Technology (Korea)• University of Auckland (New Zealand)• University of Pennsylvania• Johns Hopkins University• Infectious Disease Research Institute• University of Illinois at Chicago• Texas A&M University

May 3, 2010

TB Alliance and AstraZeneca announced that they have entered

into a research collaboration agreement to accelerate the

discovery, development and clinical use of drugs against tuberculosis, especially drug resistant strains.

The Collaboration

• The TB Alliance and AstraZeneca will:– contribute promising TB drug discovery

projects into a joint portfolio that will be co-developed

– focus on novel compound classes– create a seamless path to clinical-stage

development– share resources

TB Alliance Commitment

• The TB Alliance will contribute its ongoing collaborations with several world-leading researchers at:– University of Pennsylvania– Rutgers University– New York Medical College

AstraZeneca Commitment

• Projects will come from its TB research center in Bangalore, India

• The joint portfolio will be resourced by a core group of scientists based at AstraZeneca’s TB research center in Bangalore, India

Global Alliance for TBDrug Development

www.tballiance.org