An infectious attitude

LONDON—As antibiotic-resistant superbugs continue to pose alarger problem each year, two heavy hitters are stepping up to the plate totackle the issue. AstraZeneca PLC and the Broad Institute of MIT and Harvardhave signed a two-year collaboration for the identification of new chemicalcompounds to target bacterial and viral infections.

Per the terms of the agreement, screening and hit-to-leadchemistry will be done in the Broad's Chemical Biology Platform. For its part,AstraZeneca will optimize, develop and commercialize potential compounds fromhigh-quality leads.

"We believe new and collaborative approaches between theprivate and public sectors will help speed the discovery and development of newtreatments, particularly for antibiotic-resistant infections," said Dr. ManosPerros, vice president and head of the AstraZeneca Infection InnovativeMedicines Unit, in a press release. "We are very pleased to work hand-in-handwith the Broad Institute to combine our unique resources and strong historiesin innovation, discovery and development to speed advancements in treatmentsfor infections. Through this collaboration we have already identified severalnew potential projects to pursue."

Jacques Dumas, vice president of Infection Strategy,Innovative Medicines at AstraZeneca, says the collaboration "provides anexcellent match of capabilities and expertise." The Broad, he says, brings itsunique compound library and "the infrastructure to rapidly screen and identifyactives." AstraZeneca, Dumas notes, will "provide assays for the collaboration,therapeutic area expertise and a proven drug discovery platform includinganimal models and PKPD."

"There is a tremendous amount of medical need in the areasAstraZeneca Infection works on. For antibacterials, older drug classes havegradually lost activity because of the emergence of bacterial resistance," saysDumas. "The number of 'superbugs' increases at such an alarming pace that thereis an urgent need to discover new classes of antibiotics to control them nowand in the future. In addition, only a few drugs are approved to treat andprevent respiratory viral infections, such as influenza, RSV or humanrhinovirus. While these infections are benign in many cases, they lead to anumber of hospitalizations and deaths in 'at-risk' populations."

Dr. Michael Foley, director of the Broad's Chemical Biology Platform,says the collaboration was the result of mutual interest.

"AstraZeneca is one of the few companies that has maintaineda commitment to working in this very, very difficult area of discovering newanti-infective agents. They have all of the required expertise in place, thebacterial genomics expertise, the biochemistry, all that of course will betremendously helpful in target identification for new lead compounds," saysFoley. "I think their commitment to anti-infective research, coupled with theirexpertise in the space and the Broad's investment in new chemistry, was reallywhat attracted the two institutes to each other."

The Broad's chemical library consists of 100,000 customizedDiversity-Oriented Synthesis compounds, with molecular shapes not foundanywhere else. Foley explains that the compounds are more complex, "more likethe natural product drugs that were initially so successful in this field." TheBroad believes "stereochemistry and molecular complexity are two keycomponents, and that's where our compound collection is very different," headds.

He notes that the struggle to develop new classes ofantibacterial agents against antibiotic-resistant bacteria will be "an ongoingbattle for humanity."

"I think the biggest mistake we made as a society wasthinking that we won the war against bacteria, and we stopped working in thisspace as aggressively as we did in the 40s, 50s and 60s. We declared victory,but the bacteria never stop evolving, they never stop looking for ways toescape the drugs that we have. So we stopped aggressively working in this area,and now the bacteria are becoming resistant to the drugs that we have availableto us," says Foley.

The World Health Organization's "Global Burden of Disease"report lists infectious and parasitic diseases as the world's second-largestleading cause of death and disability. "Superbugs" that have evolved resistanceto antibiotics are on the rise, but only two new classes of antibiotics havemade it to the market in the past 30 years.

"We certainly feel that this new collaboration holds thepotential to create new opportunities in the field of infection, both insideand outside of AstraZeneca. Our mission is to change the way serious infectionsare managed and treated in the future," says Dumas. "We won't accomplish thislong-term goal with a single deal. Therefore, we are working on a series ofexternal collaborations to build a sustainable pipeline."