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Tackling the TB epidemic

LONDON—As tuberculosis drug sensitivity and resistance reaches epidemic proportions in many still-developing parts of the world, three organizations have teamed up to tackle this crisis: global pharma AstraZeneca PLC, Indian biopharmaceutical firm Cellworks Inc. and England's Wellcome Trust.

With approximately $925,000 in funding from the Wellcome Trust, AstraZeneca and Cellworks will collaborate on the design of novel combination therapies to treat multi-drug resistant tuberculosis (MDR-TB).

"AstraZeneca is pleased to join this effort to speed the delivery of improved treatment combinations for TB patients worldwide. Our continued investment in infectious disease research has positioned us to collaborate with organizations like Cellworks that share our passion for medical innovation. AstraZeneca would like to acknowledge and thank the Wellcome Trust for funding this important work. We believe that new medicines and new combination therapies to treat TB will be delivered through a concerted effort from multiple partners rather than one company's lab," said Dr. Manos Perros, head of AstraZeneca's Infection Innovative Medicines unit, in a statement announcing the collaboration.

Tuberculosis, a contagious bacterial infection that involves the lungs but may spread to other organs, affects approximately one-third of the world's population, according to the World Health Organization. Incidence of the condition is higher in certain geographic areas; as a point of comparison, about 80 percent of the population in many Asian and African countries test positive, while only 5 to 10 percent of the United States population tests positive. People who reside in developing nations tend to contract tuberculosis because of compromised immunity, largely due to high rates of HIV infection and the corresponding development of AIDS.

MDR-TB has become a serious public health concern in many of these countries, as its treatment is longer and requires more expensive drugs. People with MDR-TB are usually treated with at least four effective antibiotics over a typical course of 18 to 24 months.

AstraZeneca and Cellworks intend to tackle this difficult issue by employing Cellworks' proprietary predictive platform—to date used with success in oncology and autoimmune disorders—to model MDR-TB and "rationally identify synergistic combinations that might have the highest efficacy and lowest possible toxic burden compared to all currently available combinations," says Anand Anandkumar, managing director of Cellworks Group India.

The two companies previously used this platform to develop a virtual predictive model for the bacterium E.coli. AstraZeneca's India group used the platform to validate the vulnerability of target genes.

"Thus, we have already had a successful collaboration model where Cellworks does the in silico work, and AZ India does the experimental validation," says Anandkumar. "AZ India is the only one within the big pharma companies that have a dedicated program in the anti-tubercular drug discovery space in India. They have a state-of-the-art biosafety lab that allows them to do all the experiments required for preclinical drug discovery in the TB space."

Cellworks will create predictive dynamic maps of MDR-TB and use its proprietary simulation and analysis techniques to emulate drug resistance, search tens of thousands of combination quartets from an existing pool of anti-infective drugs and identify top-performing drug combinations that work against MDR-TB. AZ India will do the in-vitro testing, followed by validation using in-vivo models.

"Upon successfully completing this project, Cellworks and AZ will seek additional funding from various channels including the Wellcome Trust to allow taking the MDR combination to human trials," says Anandkumar. Patients across the world will benefit from a formal methodology that allows for the selection of effective drug combinations, he adds.

"Trying to identify and analyze these combinations using today's wet-lab based approaches would requires tens of years and many tens of millions of dollars, if not more, in expenses. So in effect, this collaboration will identify the best combination therapies for the most varied conditions in a very short amount of time," he notes.

Founded in 2005, Cellworks approaches drug development by combining functional proteomics data with sophisticated engineering technologies and methodologies. The company recently released the fifth generation of its platform, which has garnered several awards, grants and more than 20 applications and filed patents. Cellworks' drug pipeline is currently focused on oncology and rheumatoid arthritis. The company is headquartered in Saratoga, Calif., with its R&D center in Bangalore, India.