Tackling the TB epidemic

AstraZeneca, Cellworks and Wellcome Trust team up to fight drug-resistant tuberculosis

Amy Swinderman
LONDON—As tuberculosis drug sensitivity and resistancereaches epidemic proportions in many still-developing parts of the world, threeorganizations have teamed up to tackle this crisis: global pharma AstraZenecaPLC, Indian biopharmaceutical firm Cellworks Inc. and England's Wellcome Trust.
With approximately $925,000 in funding from the WellcomeTrust, AstraZeneca and Cellworks will collaborate on the design of novelcombination therapies to treat multi-drug resistant tuberculosis (MDR-TB).
"AstraZeneca is pleased to join this effort to speed thedelivery of improved treatment combinations for TB patients worldwide. Our continuedinvestment in infectious disease research has positioned us to collaborate withorganizations like Cellworks that share our passion for medical innovation.AstraZeneca would like to acknowledge and thank the Wellcome Trust for fundingthis important work. We believe that new medicines and new combinationtherapies to treat TB will be delivered through a concerted effort frommultiple partners rather than one company's lab," said Dr. Manos Perros, headof AstraZeneca's Infection Innovative Medicines unit, in a statement announcingthe collaboration.
Tuberculosis, acontagious bacterial infection that involves the lungs but may spread to otherorgans, affects approximately one-third of the world's population, according tothe World Health Organization. Incidence of the condition is higher in certaingeographic areas; as a point of comparison, about 80 percent of the populationin many Asian and African countries test positive, while only 5 to 10 percentof the United States population tests positive. People who reside in developingnations tend to contract tuberculosis because of compromised immunity, largelydue to high rates of HIV infection and the corresponding development of AIDS. 
MDR-TBhas become a serious public health concern in many of these countries, as itstreatment is longer and requires more expensive drugs. People with MDR-TB areusually treated with at least four effective antibiotics over a typical courseof 18 to 24 months.
AstraZeneca and Cellworks intend to tackle this difficultissue by employing Cellworks' proprietary predictive platform—to date used withsuccess in oncology and autoimmune disorders—to model MDR-TB and "rationallyidentify synergistic combinations that might have the highest efficacy andlowest 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 avirtual predictive model for the bacterium E.coli.AstraZeneca's India group used the platform to validate the vulnerability oftarget genes.
"Thus, we have already had a successful collaboration modelwhere Cellworks does the in-silicowork, and AZ India does the experimental validation," says Anandkumar. "AZIndia is the only one within the big pharma companies that have a dedicatedprogram in the anti-tubercular drug discovery space in India. They have astate-of-the-art biosafety lab that allows them to do all the experimentsrequired for preclinical drug discovery in the TB space."
Cellworks will create predictive dynamic maps of MDR-TB anduse its proprietary simulation and analysis techniques to emulate drugresistance, search tens of thousands of combination quartets from an existingpool of anti-infective drugs and identify top-performing drug combinations thatwork against MDR-TB. AZ India will do the in-vitrotesting, followed by validation using in-vivomodels.
"Upon successfully completing this project, Cellworks and AZwill seek additional funding from various channels including the Wellcome Trustto allow taking the MDR combination to human trials," says Anandkumar.
Patients across the world will benefit from a formalmethodology that allows for the selection of effective drug combinations, headds.
"Trying to identify and analyze these combinations usingtoday's wet-lab based approaches would requires tens of years and many tens ofmillions of dollars, if not more, in expenses. So in effect, this collaborationwill identify the best combination therapies for the most varied conditions ina very short amount of time," he notes.
Founded in 2005, Cellworks approaches drug development bycombining functional proteomics data with sophisticated engineeringtechnologies and methodologies. The company recently released the fifthgeneration of its platform, which has garnered several awards, grants and morethan 20 applications and filed patents. Cellworks' drug pipeline is currentlyfocused on oncology and rheumatoid arthritis. The company is headquartered inSaratoga, Calif., with its R&D center in Bangalore, India.

AstraZeneca completessale of Aptium Oncology assets
LONDON—AstraZeneca PLC also recently announced that it hascompleted the sale of the assets of its subsidiary, Aptium Oncology, whichprovided outpatient oncology management and consulting services in the UnitedStates.
Aptium managed outpatient cancer centers in affiliation withfive hospitals in California, Florida, New Jersey and New York. The subsidiarygenerated revenues of $224 million in 2011. Aptium was a non-core business, andAstraZeneca transferred ownership of these cancer centers to each of thehospitals.
AstraZeneca said the sale will not impact its previouslystated guidance for 2012.

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