Transcript Document

TB Drug Development
Gerald 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 for
TB 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
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Licensing
Sponsored Projects
Outsourcing/Contracts
Co-Development
Co-Investments
Partnerships
Others
TB Alliance Portfolio
Compounds, Analogs and Derivatives
Discovery
Preclinical
Clinical
Nitroimidazole Analogs
(University of Auckland, Novartis ITD, NIAID)
Moxifloxacin
(Bayer HealthCare AG)
Quinolones
(KRICT/Yonsei University)
Nitroimidazole PA-824
(Chiron/Novartis)
Multi-Functional Molecules
(Cumbre)
Bacterial Topoisomerase Inhibitors
(GlaxoSmithKline)
InhA Inhibitors
(GlaxoSmithKline)
Pleuromutilins
(GlaxoSmithKline)
Focused Screening – Two Projects
(GlaxoSmithKline)
Riminophenazines
(Institute of Materia Medica)
Active TB Alliance program
Malate Synthase Inhibitors
(GlaxoSmithKline/Texas A&M)
Proteasome Inhibitors
(Cornell University)
New Targets
(University of Pennsylvania)
TB Alliance in discussion
Chiron
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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 multifunctional 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-Bayer
Moxifloxacin Deal
Moxifloxacin
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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 TB
Drug Development
www.tballiance.org