We’re all aware of the downsides of antibiotics. With the emergence of multi-drug resistant bacteria, and the realization that broad spectrum antibiotics can cause collateral damage on our personal, microbial ecosystems there is a worsening inadequacy of the broad spectrum antibiotics concept—which has ruled the practice of medicine for the last even decades—and has created an increasing and quite significant unmet medical need for alternative solutions to both treat and prevent infection.
This week, I will be part of two panel presentations at the BIO International Convention, one of the largest global events for the biotechnology industry. Here, I will discuss this state of medicine, our confrontation with pan-resistant microbes and the future of infectious disease treatment and prevention strategies, including important investigations into the use of antibodies as antibacterial drugs.
Antibacterial monoclonal antibodies (mAbs) have, to date, uniformly failed in the clinic, generally from lack of efficacy. But, we believe that recent developments in a number of areas that include infectious disease pathogenesis research, translational medicine, mAb engineering and manufacturing, and rapid diagnostics are converging to make for a far brighter future in the medium term for antibacterial mAb discovery and development. In fact, these may well serve to shift the paradigms with regard to choice of molecular targets, antibody formats, mode-of-action, pre-clinical validation and the selection of the most relevant patient populations—increasing the likelihood of clinical success.
Our own investigations at MedImmune have focused on the development of an anti-toxin mAb and a novel bispecific mAb. We’re studying these molecules within the context of two bacterial infections: Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). Not only are these bacteria the two most common infection agents among hospitalized patients, they are the most problematic in terms of morbidity and mortality, and the costliest for our healthcare system.
What we believe is that these molecules—the one a dual-target mAb combination and the other that targets the key toxin responsible for cellular/tissue damage and immune dysfunction mediation in S. aureus—may offer protective immunities on their own and have the potential to be combined with traditional antibiotic therapy.
In fact, we’re approaching Phase I and Phase II studies for two of our projects, and plan to be in the clinic for a third project next year. We’ve also had much interest in the European Union (EU) to perform trials for two of these projects, with significant funding for the S. aureus anti-alpha toxin mAb assured, and funding for the P. aeruginosa bispecific mAb committed from the EU’s Innovative Medicines Initiative (see below).
The very good news is that there has been and continues to be more academic funding to study such novel approaches toward drug discovery, and there are increased resources through the National Institutes of Health (NIH) to help perform these investigations. The Innovative Medicines Initiative also has a major program—New Drugs for Bad Bugs, ND4BB—that is helping to fund studies in the clinic, something that we are actively involved in. And, there is the U.S. Food and Drug Administration’s (FDA) Antibacterial Drug Development Task Force, part of the federally legislated GAIN Title of the FDA Safety and Innovation Act (FDASIA).
What this all means is that we at MedImmune are pushing the scientific envelope in the discovery and development of novel drugs for serious infections. These will not only spare suffering and save lives, but also result in a great economic benefit for beleaguered healthcare systems around the world.