PDPs and Alternative IP Management/Tech Transfer

Strategies for ImprovedGlobal Health

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

Biotechnology Industry Organization Annual MeetingAtlanta, GA

May 20, 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

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 35 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

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

and 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• New York Medical College

Lead Identification

Lead Optimizatio

nPreclinical Phase I Phase II Phase III

Malate Synthase Inhibitors

Riminophenazines

GSK Focused Screening

InhA Inhibitors

Mycobacterial Gyrase Inhibitors

Nitroimidazoles

Quinolone TBK-613

Multifunctional Molecules

PA-824

Moxifloxacin

TB Alliance Portfolio

TB ALLIANCE TB ALLIANCE PROGRAMSPROGRAMS

DISCOVERYDISCOVERY CLINICALCLINICAL DEVELOPMENTDEVELOPMENT

Phenotypic Screening

March, 2009

Protease Inhibitors

Energy Metabolism Inhibitors

NITD Portfolio

RNA Polymerase Inhibitors

Topoisomerase I Inhibitors

Tryptanthrines

April 2009

Chiron/Novartis

• PA-824 – 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

PA-824

• Worldwide exclusive license in 2002 for the treatment of tuberculosis

• Defined scientific milestones

• Grant-back option

• Manufacturing rights

• No royalties in endemic countries

• Presently in Phase II clinical trials

Bayer HealthCare

• Moxifloxacin - fluoroquinolone antibiotic

• Orally active

• Once-a-day dosage

• Marketed in 141 countries for the treatment of several acute respiratory and uncomplicated skin and soft tissue infections

Moxifloxacin for TB

• Novel mechanism of action: kills M.tb. by inhibition of DNA gyrase

• In vivo mouse studies showed that 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 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

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)

GlaxoSmithKline

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

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

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

Global Alliance for TBDrug Development

www.tballiance.org