tb drug development gerald j. siuta, ph.d. business development may 3, 2007
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TB Drug DevelopmentGerald J. Siuta, Ph.D.Business Development
May 3, 2007
Tuberculosis One-third of the world’s population is infected
with Mycobacterium tuberculosis – 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
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)– Prolonged therapy, few available drugs, poorly tolerated
and difficult to administer TB/HIV Co-Infection
– Drug interactions with antiretroviral agents - simultaneous therapy difficult
The Need for New TB Drugs
Complex 6-9 months treatment with a 4 drug combination regimen
No new anti-TB drug in over 30 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 – Feb 2000– Hosts: Rockefeller Foundation & MRC S. 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
International Public-Private Partnership Non-profit organization Based in New York City, Brussels and
Cape Town Entrepreneurial, virtual R&D approach
– Out-source R&D to public or private partners Pro-active fundraising
Public-Private Partnership
An organization that pursues a social mission by employing the best
practices of the private sector and drawing upon resources from the
public and private realms
TB Alliance Mission
To ensure equitable access to a faster tuberculosis cure
that will advance global health and prosperity
Profile of New TB Drug
Shorten the duration of TB treatment or otherwise simplify its completion
Be effective against multi-drug resistant tuberculosis (MDR-TB)
Improve the treatment of latent TB Be compatible with HIV treatment
Goals and Objectives
Develop an entirely new therapeutic regimen that will shorten or simplify the treatment of tuberculosis
Coordinate and catalyze TB drug development activities worldwide
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
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/Agreements
Licensing Sponsored Projects Outsourcing/Contracts Co-Development Co-Investments Partnerships Others
TB Alliance PortfolioDiscovery
Co
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ou
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s, A
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og
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eriv
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es
Nitroimidazole Analogs (University of Auckland, Novartis ITD, NIAID)
Quinolones(KRICT/Yonsei University)
Multi-Functional Molecules(Cumbre)
Bacterial Topoisomerase Inhibitors(GlaxoSmithKline)
InhA Inhibitors(GlaxoSmithKline)
Malate Synthase Inhibitors(GlaxoSmithKline/Texas A&M)
Nitroimidazole PA-824 (Chiron/Novartis)
Preclinical Clinical
Active TB Alliance program
TB Alliance in discussion
Focused Screening – Two Projects(GlaxoSmithKline)
Pleuromutilins(GlaxoSmithKline)
Moxifloxacin (Bayer HealthCare AG)
Proteasome Inhibitors(Cornell University)
New Targets(University of Pennsylvania)
Riminophenazines(Institute of Materia Medica)
Chiron
Novel anti-TB compound (PA-824) Discovered by Pathogenesis, Inc. Exclusive worldwide license Defined scientific milestones Grant-back option Manufacturing rights No royalties in high endemic countries
PA-824
Novel nitroimidazole Potent activity against both active and
slow growing M.tb. Possesses both bactericidal and sterilizing
activity Phase I clinical trials began June 3, 2005
– Preclinical development completed in 3 years
University of Auckland Synthesis of PA-824 analogs Joint program with:
– Novartis Institute of Tropical Diseases (Singapore)
– National Institute of Allergy and Infectious Diseases
Aims to discover new nitroimidazopyrans that may have improved profiles over PA-824
GlaxoSmithKline
Joint drug discovery program at GSK’s Diseases of the Developing World facility in Tres Cantos, Spain
Four individual projects:– Bacterial topoisomerase inhibitors– InhA inhibitors– Pleuromutilins– Focused screening (two projects)
Korea Research Institute of Chemical Technology (KRICT)
Daejeon, South Korea Three year research funding
– Quinolones, pyridones & quinolizines Chemical synthesis at KRICT In vitro and in vivo biological testing at
Yonsei University College of Medicine in Seoul, South Korea
Clinical compound selection in progress
Cumbre Pharmaceuticals
Joint program on the design, synthesis and optimization of two different classes of multi-functional antibiotics
The TB Alliance will have exclusive rights to these compounds for the treatment of tuberculosis and other neglected diseases
Cumbre will retain the rights to pursue the compounds for use in other infectious diseases
Institute of Materia Medica Member of the Chinese Academy of Medical Sciences
that is one of the primary institutions for drug research in China
Joint research partnership for the design, synthesis and evaluation of a class of compounds known as riminophenazines– Originally discovered to be active against TB in the 1950s– Has not been used due to side effect profile
The collaboration will utilize IMM's expertise and integrated capabilities in chemistry, pharmacology and manufacture
The TB Alliance-BayerMoxifloxacin Deal
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
October 18, 2005
TB Alliance and Bayer HealthCare announced a partnership to coordinate a global clinical trial program to study
the potential of moxifloxacin to shorten the standard six-month treatment of TB
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
Phase II program will 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
Nearly 2,500 TB patients are being 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)
Special Recognition
Licensing Executives Society
On September 13, 2006, the Licensing Executives Society Industry/University and Government
Laboratory Transactions Industry Sector presented the TB Alliance and Bayer its Deals of Distinction
Award which recognizes worthy transactions involving licensing and transfer of intellectual property and promote creative and innovative
solutions to business issues
Scrip – World Pharmaceutical News
The TB Alliance-Bayer deal was also one of six finalists for the Scrip 2006 Best Partnership
Alliance Award which recognizes the importance of partnerships involving pharmaceutical and/or
biotech companies, focusing on deals that require strong strategic input from both partners, are
mutually beneficial to both parties, hold promise to address an unmet medical need and demonstrate
strategic potential as well as an innovative business model
Global Alliance for TBDrug Development
www.tballiance.org
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