As I mentioned earlier, the TB Alliance is a virtual drug development organization and conducts its R&D work through its robust network of partners including pharmaceutical and biotechnology companies, academia, and research organizations. The type of partnerships span the gamut. For example, PA-824, currently in Phase II development, was in-licensed by the TB Alliance from Chiron Corporation (which is now part of Novartis) and is being developed by the Alliance on its own. On the other hand, the TB Alliance is developing moxifloxacin, currently in Phase III development, in collaboration with Bayer. In all agreements with its industry partners, the TB Alliance includes a commitment to affordability, that is, the products will be made available a little over cost. With all its partnerships, the TB Alliance owns rights to the TB indication.
With the support of its funders and partners, the TB Alliance has made important strides in the nine years since its inception. It has built the largest single portfolio of TB compounds in history. These compounds will serve as the building blocks for the creation of a novel, greatly improved anti-TB regimens. Three of the drug candidates are in late-stage clinical trials. Moxifloxacin, currently in Phase III development and the most advanced project in the TB Alliance portfolio is scheduled to enter registration in 2013. Simultaneously the TB Alliance is undertaking strategic initiatives to advance the field of TB drug development as a whole. Some of these initiatives include support for the creation of biomarkers of treatment efficacy that can shorten the duration of TB trials, mapping of global capacity to conduct Phase II and III clinical trials, working with regulatory authorities to define the pathway of approval for new TB drugs and regimens and development and testing of a new paradigm of developing TB treatments that can dramatically reduce development time. A little more about this in the next slide. The TB Alliance also has a discrete Access team whose sole purpose is to determine how to make the drugs, once developed, to the poor populations that most need these drugs. The idea is not to duplicate existing systems but to identify and work with existing systems and stakeholders like the WHO and the Gobal fund and in-country mechanisms to ensure that new drugs are available, affordable and adopted. The TB Alliance portfolio currently has 22 projects spanning from discovery to Phase III clinical development. Of its three clinical projects, Moxifloxacin , the compound the TB Alliance is developing with Bayer AG and other partners, is in Phase III development, the last phase of clinical development before registration. It is one of the most advanced clinical development programs for the treatment of active TB in over forty years. The TB Alliance expects to register a moxifloxacin-based regimen that will shorten the duration of therapy for drug-sensitive TB to four months by 2013. PA-824 , the first novel TB drug candidate developed by a not-for-profit organization to reach clinical trials, is in Phase II development and showing significant promise for improving treatment of both drug-sensitive and drug-resistant TB. In addition, the TB Alliance recently entered into collaboration with Tibotec, Inc. to develop TMC-207 , currently in phase II development, which could become the first drug in over forty years with a new mechanism of action (and, therefore, ability to fight drug-resistant TB).
TB Alliance: Improving Treatments Against TB
Improving Treatments Against TB Partnering for Cures Meeting December 2, 2009
TB Alliance Mission <ul><li>The TB Alliance is a humanitarian agency developing new, better and faster-acting drugs and treatments against tuberculosis (TB). </li></ul><ul><li>Inherent in our mission is the need to ensure that the drugs and regimens are affordable, adopted for use, and made widely available. </li></ul><ul><li>No new TB drug has been developed in over 40 years. The TB Alliance undertakes initiatives to catalyze TB drug development. </li></ul>
The Organization <ul><li>Founded in 2000 </li></ul><ul><li>Not-for-profit Product Development Partnership (PDP) headquartered in New York, with offices in Brussels and Pretoria </li></ul><ul><li>Entrepreneurial, virtual drug development approach </li></ul><ul><li>Largest portfolio of TB drug candidates in history </li></ul>TB Alliance PHARMA BIOTECH ACADEMIA INSTITUTES GOVERNMENTS FOUNDATIONS
TB – A Disease of the Past? <ul><li>TB kills 2 million each year even today; that is 5,000 deaths everyday. </li></ul><ul><li>It is the greatest infectious cause of maternal mortality and of death in people with HIV/AIDS </li></ul><ul><li>There are half a million cases of drug-resistant TB; resistance is rising </li></ul><ul><li>TB perpetuates poverty; it is estimated to deplete the incomes of the world’s poorest communities by US$ 12 billion </li></ul><ul><li>TB cannot be conquered without new and better treatments </li></ul><ul><li>Source: WHO </li></ul>
Current TB Therapy and Unmet Needs Unmet Needs <ul><li>Drug-sensitive TB </li></ul><ul><li>4 Drugs, >6 months </li></ul><ul><li>M(X)DR-TB </li></ul><ul><li>>2 years; poorly tolerated; less than 10% penetration </li></ul><ul><li>TB/HIV co-infection </li></ul><ul><li>Drug-drug interactions with HIV/AIDS drugs </li></ul><ul><li>Latent TB Infection </li></ul><ul><li>9-month treatment </li></ul><ul><li>Shorter, simpler therapy </li></ul><ul><li>More effective, safer drugs; shorter, simpler therapy </li></ul><ul><li>Co-administration with ARVs </li></ul><ul><li>Shorter , more easily tolerated therapy </li></ul>Current Therapy
Clinical Development Program <ul><li>Moxifloxacin, Phase III, is one of the most advanced programs against active TB in over 40 years </li></ul><ul><li>PA-824, Phase II, is the first program by a non-profit to reach clinical trials </li></ul><ul><li>TMC 207, Phase II, is the first program with parallel development tracks for drug sensitive and drug resistant TB </li></ul>CLINICAL DEVELOPMENT Phase I Phase II Phase III Moxifloxacin PA-824 TMC 207 Bayer Novartis Tibotec/J&J
Changing Development of TB Treatments <ul><li>Testing regimens containing multiple novel agents </li></ul>ABCD BCDE CDEF DEFG EFGH E A G C H D B F Conventional Development Paradigm ABCD CDEF EFGH EF AB CD GH Alternative Development Paradigm 12 years ABCD EFGH ABCD EFGH 6 years Alternative Development Paradigm 24 years
Annual Expenses <ul><li>Our early successes have created a need for larger funding </li></ul><ul><li>Annual expenses are expected to increase as projects advance through development </li></ul><ul><li>Funding gap over the next five years estimated at $150 million </li></ul>
Organizational Leadership Key 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
Summary <ul><li>Current TB drugs are failing; drug resistance is on the rise </li></ul><ul><li>New drugs and regimens are urgently needed </li></ul><ul><li>The TB Alliance has built the largest portfolio of TB compounds in history </li></ul><ul><li>This progress over the past few years has resulted in a pipeline of products advancing towards the clinic </li></ul><ul><li>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 </li></ul>
Questions “ I refuse to watch another patient 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
Operating Model <ul><li>A flexible, virtual R&D approach: </li></ul><ul><li>In-licensing and independent development </li></ul><ul><li>PA-824 (Chiron/Novartis) </li></ul><ul><li>Collaborative R&D with affordability commitment </li></ul><ul><li>Moxifloxacin (Bayer); GSK mini portfolio (GSK); TB drug portfolio (Novartis); TMC-207 (J&J) </li></ul><ul><li>Contracted R&D with IP rights </li></ul><ul><li>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) </li></ul>
<ul><li>Built the largest single portfolio of TB drug candidates in history </li></ul><ul><ul><li>22 projects spanning discovery to clinical development </li></ul></ul><ul><ul><li>Three projects in late-stage clinical development </li></ul></ul><ul><ul><li>First new drug, reducing treatment time by a third, scheduled for launch in 2013 </li></ul></ul><ul><li>Catalyzing the field of TB drug development </li></ul><ul><ul><li>identification of biomarkers of treatment efficacy </li></ul></ul><ul><ul><li>global mapping of registration-standard clinical trial capacity </li></ul></ul><ul><ul><li>Testing new paradigm for development of TB treatments that can dramatically compress development time </li></ul></ul><ul><ul><li>Working with regulatory authorities worldwide to develop guidelines for TB drug development </li></ul></ul><ul><li>Affordability, Adoption and Availability (AAA) </li></ul><ul><ul><li>Studies on TB-endemic markets to facilitate availability and adoption </li></ul></ul>TB Alliance Accomplishments