An infectious attitude
LONDON—As antibiotic-resistant superbugs continue to pose a larger problem each year, two heavy hitters are stepping up to the plate to tackle the issue. AstraZeneca PLC and the Broad Institute of MIT and Harvard have signed a two-year collaboration for the identification of new chemical compounds to target bacterial and viral infections.
Per the terms of the agreement, screening and hit-to-lead chemistry will be done in the Broad’s Chemical Biology Platform. For its part, AstraZeneca will optimize, develop and commercialize potential compounds from high-quality leads.
“We believe new and collaborative approaches between the private and public sectors will help speed the discovery and development of new treatments, particularly for antibiotic-resistant infections,” said Dr. Manos Perros, vice president and head of the AstraZeneca Infection Innovative Medicines Unit, in a press release. “We are very pleased to work hand-in-hand with the Broad Institute to combine our unique resources and strong histories in innovation, discovery and development to speed advancements in treatments for infections. Through this collaboration we have already identified several new potential projects to pursue.”
Jacques Dumas, vice president of Infection Strategy, Innovative Medicines at AstraZeneca, says the collaboration “provides an excellent match of capabilities and expertise.” The Broad, he says, brings its unique compound library and “the infrastructure to rapidly screen and identify actives.” AstraZeneca, Dumas notes, will “provide assays for the collaboration, therapeutic area expertise and a proven drug discovery platform including animal models and PKPD.”
“There is a tremendous amount of medical need in the areas AstraZeneca Infection works on. For antibacterials, older drug classes have gradually lost activity because of the emergence of bacterial resistance,” says Dumas. “The number of ‘superbugs’ increases at such an alarming pace that there is an urgent need to discover new classes of antibiotics to control them now and in the future. In addition, only a few drugs are approved to treat and prevent respiratory viral infections, such as influenza, RSV or human rhinovirus. While these infections are benign in many cases, they lead to a number 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 maintained a commitment to working in this very, very difficult area of discovering new anti-infective agents. They have all of the required expertise in place, the bacterial genomics expertise, the biochemistry, all that of course will be tremendously helpful in target identification for new lead compounds,” says Foley. “I think their commitment to anti-infective research, coupled with their expertise in the space and the Broad’s investment in new chemistry, was really what attracted the two institutes to each other.”
The Broad’s chemical library consists of 100,000 customized Diversity-Oriented Synthesis compounds, with molecular shapes not found anywhere else. Foley explains that the compounds are more complex, “more like the natural product drugs that were initially so successful in this field.” The Broad believes “stereochemistry and molecular complexity are two key components, and that’s where our compound collection is very different,” he adds.
He notes that the struggle to develop new classes of antibacterial agents against antibiotic-resistant bacteria will be “an ongoing battle for humanity.”
“I think the biggest mistake we made as a society was thinking that we won the war against bacteria, and we stopped working in this space 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 to escape 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 available to us,” says Foley.
The World Health Organization’s “Global Burden of Disease” report lists infectious and parasitic diseases as the world’s second-largest leading cause of death and disability. “Superbugs” that have evolved resistance to antibiotics are on the rise, but only two new classes of antibiotics have made it to the market in the past 30 years.
“We certainly feel that this new collaboration holds the potential to create new opportunities in the field of infection, both inside and outside of AstraZeneca. Our mission is to change the way serious infections are managed and treated in the future,” says Dumas. “We won’t accomplish this long-term goal with a single deal. Therefore, we are working on a series of external collaborations to build a sustainable pipeline.”