1

Improving Treatments Against TB

Partnering for Cures MeetingDecember 2, 2009

2

TB Alliance Mission

• The TB Alliance is a humanitarian agency developing new, better and faster-acting drugs and treatments against tuberculosis (TB).

• Inherent in our mission is the need to ensure that the drugs and regimens are affordable, adopted for use, and made widely available.

• No new TB drug has been developed in over 40 years. The TB Alliance undertakes initiatives to catalyze TB drug development.

3

TB Alliance Vision

10 days

FDCs

2 – 4 months6 – 30 months

The Organization

4

TB Alliance

PHARMABIOTECH

ACADEMIA INSTITUTES

GOVERNMENTS

FOUNDATIONS

•Founded in 2000

•Not-for-profit Product Development Partnership (PDP) headquartered in New York, with offices in Brussels and Pretoria

•Entrepreneurial, virtual drug development approach

•Largest portfolio of TB drug candidates in history

TB – A Disease of the Past?• TB kills 2 million each year even today; that is 5,000 deaths everyday.

• It is the greatest infectious cause of maternal mortality and of death in people

with HIV/AIDS

• There are half a million cases of drug-resistant TB; resistance is rising

• TB perpetuates poverty; it is estimated to deplete the incomes of the world’s

poorest communities by US$ 12 billion

TB cannot be conquered without new and better treatments

Source: WHO

5

Current TB Therapy and Unmet Needs

6

Unmet Needs• Drug-sensitive TB

4 Drugs, >6 months

• M(X)DR-TB>2 years; poorly tolerated; less than 10% penetration

• TB/HIV co-infection Drug-drug interactions with

HIV/AIDS drugs

• Latent TB Infection9-month treatment

Shorter, simpler therapy

More effective, safer drugs; shorter, simpler therapy

Co-administration with ARVs

Shorter , more easily tolerated therapy

Current Therapy

TB Alliance Portfolio

7

Anacor Pharmaceuticals

Lead Identification

Tibotec/J&J

Lead Optimization

Preclinical

GlaxoSmithKline

GlaxoSmithKline

Phase I Phase II Phase III

University of Auckland

NovartisBayer

Institute of Materia Medica

DISCOVERY CLINICAL DEVELOPMENT

University of Illinois

University of Pennsylvania School of Medicine

Infectious Disease Research InstituteNew York Medical College

Korea Research Inst of Chem Tech and Yonsei Univ

Rutgers, State University of New Jersey

GlaxoSmithKlineGSK Whole-Cell Screening

Bi-Functional Molecules

LeuRS Inhibitors

InhA Inhibitors

Mycobacterial Gyrase Inhibitors

Nitroimidazoles

Riminophenazines

PA-824

Moxifloxacin

TB ALLIANCE PROGRAMS

Phenotypic Screening

Protease Inhibitors

Topoisomerase I Inhibitors

Tryptanthrines

RNA Polymerase Inhibitors

Energy Metabolism Inhibitors

NITD Portfolio Novartis Institute for Tropical Diseases

Institute of Microbiology, Chinese Academy of Sciences Natural Products

Colorado State UniversityMenaquinone Synthesis Inhibitors

GlaxoSmithKlineMalate Synthase Inhibitors

TMC 207 Tibotec/J&J

Next Generation Diarylquinoline University of Auckland, Colorado State University

Clinical Development Program

• Moxifloxacin, Phase III, is one of the most advanced programs against active TB in over 40 years

• PA-824, Phase II, is the first program by a non-profit to reach clinical trials • TMC 207, Phase II, is the first program with parallel development tracks for drug

sensitive and drug resistant TB

8

CLINICAL DEVELOPMENT

Phase I Phase II Phase III

Moxifloxacin

PA-824

TMC 207

Bayer

Novartis

Tibotec/J&J

Changing Development of TB Treatments

Testing regimens containing multiple novel agents

9

ABCD BCDE CDEF DEFG EFGH

E A G C H DBFConventional Development Paradigm

ABCD CDEF EFGH

EF AB CDGHAlternative Development Paradigm

12 years

ABCD EFGH

ABCD EFGH

6 years

Alternative Development Paradigm

24 years

Optimizing Resources

10

% Partner Contributions

Annual Expenses

11

• Our early successes have created a need for larger funding

• Annual expenses are expected to increase as projects advance through development

• Funding gap over the next five years estimated at $150 million

Organizational LeadershipKey Staff Scientific Advisory Committee

Dr. Melvin Spigelman, President and CEO Dr. Stewart Cole , Ecole Polytechnique Federale de Lausanne

Dr. Marshall Burke, Sr. VP, External Affairs Dr. Frank L. Hurley, RRD International, LLC

Elizabeth Gardiner, VP, Market Access Dr. Stefan Kaufmann, Max Planck Institute for Infection-Biology

Dr. Ann Ginsberg, Chief Medical Officer Dr. Richard Losick, Harvard University

Stephen Jasko, Chief Financial Officer Dr. G. Lynn Marks, GlaxoSmithKline

Dr. Zhenkun Ma, Chief Scientific Officer Prof. Lester E. Mitscher, University of Kansas

Colleen Pero, Chief Administrative Officer Dr. Valerie Mizrahi, University of the Witwatersrand (S. Africa)

Dr. Paranji R. Narayanan, Formerly of TB Research Centre (India)

Dr. Philippe Prokocimer, Trius Therapeutics

Dr. Eric Rubin, Harvard School of Public Health

Dr. Christine Sizemore National Institute of Allergy and Infectious Diseases

Dr. Eve E. Slater, Columbia University College of Physicians and Surgeons

12

Summary

• Current TB drugs are failing; drug resistance is on the rise• New drugs and regimens are urgently needed• The TB Alliance has built the largest portfolio of TB compounds in

history• This progress over the past few years has resulted in a pipeline of

products advancing towards the clinic

We are at an inflection point but only with donor support can we convert the early strides into new drugs and

regimens in the field

13

Questions

14

“I refuse to watch anotherpatient die because the treatment is simply too long and complicated…

Imagine what a two-month therapy would do for the Philippines, where 75 people die every day from tuberculosis.”

--Dr. Charles Yu, PhilCAT

Extra Slides

15

TB Alliance Funders

16

Operating Model A flexible, virtual R&D approach:• In-licensing and independent development

PA-824 (Chiron/Novartis)

• Collaborative R&D with affordability commitment

Moxifloxacin (Bayer); GSK mini portfolio (GSK); TB drug portfolio (Novartis); TMC-207 (J&J)

• Contracted R&D with IP rights

Quinolone (KRICT); Nitroimidazole (ACSRC); Riminophenazine (IMM); Phenotypic screening (UIC); Energy metabolism (UPenn); Protease (IDRI); Tryptanthrine (KRICT); RNAP (Rutgers); LeuRS (Anacor); Menaquinone (CSU); Topo I (NYMC); Natural products (IMCAS)

17

• Built the largest single portfolio of TB drug candidates in history– 22 projects spanning discovery to clinical development– Three projects in late-stage clinical development– First new drug, reducing treatment time by a third, scheduled for launch in 2013

• Catalyzing the field of TB drug development– identification of biomarkers of treatment efficacy – global mapping of registration-standard clinical trial capacity – Testing new paradigm for development of TB treatments that can dramatically

compress development time– Working with regulatory authorities worldwide to develop guidelines for TB drug

development• Affordability, Adoption and Availability (AAA)

– Studies on TB-endemic markets to facilitate availability and adoption

18

TB Alliance Accomplishments