Arsanis optimizes our monoclonal antibodies (mAbs) by addressing the unique features and pathogenic processes of each targeted bacteria. To do so, we use multiple discovery approaches, combining our expertise in molecular bacterial pathogenesis, our knowledge of preclinical and clinical development of anti-infective agents, and partnerships that provide access to leading scientific and discovery platforms.
We prioritize target selection for each of our programs based upon numerous factors, including unmet medical need, multi-drug resistant pathogens, diseases with significant morbidity and mortality, and the ability to address these needs via a mAb therapeutic approach.
While other mAbs in development focus on single targets, Arsanis sets out to address the unique underlying biology of the selected pathogen for each of our programs. To address certain bacterial pathogens successfully, our mAbs must target all of the relevant biological targets that contribute to disease, ensuring a comprehensive approach to interrupting bacterial pathogenesis. For example, ASN100 targets six individual cytotoxins produced by Staphylococcus aureus that are critical to pneumonia pathogenesis.
Since the introduction of penicillin in the 1940s, antibiotics have significantly reduced the morbidity and mortality associated with bacterial infection. Due to widespread and indiscriminate use of antibiotics, bacteria have and will continue to develop resistance to antibiotics. Particularly troubling bacteria accumulate resistance to multiple antibiotics and are termed multi-drug resistant (MDR). MDR bacteria are spreading at an alarming rate, with resistance being reported rapidly following the introduction of each new antibiotic class. In extreme cases, bacteria accumulate resistance to nearly all available antibiotics (termed extensively-drug resistant or XDR), and some Gram-negative bacteria have been identified that are resistant to all available antibiotics, classified as pan-drug resistant (PDR).
Although hospitals have implemented antibiotic stewardship efforts to reduce the emergence and spread of MDR bacteria by avoiding unnecessary antibiotic use and selecting optimal antimicrobial regimens, these practices often cause hospitals to: (a) hold the most effective antibiotics in reserve and (b) discourage the prophylactic administration of antibiotics to high-risk patients. In addition, there are growing numbers of immunocompromised patients for whom traditional antibiotics are less effective, irrespective of bacterial resistance.
The Cost of Serious Infections
Infections caused by resistant pathogens are difficult to treat, requiring the use of last-line antibiotics and sometimes older antibiotics that have serious toxicities. According to the US Centers for Disease Control and Prevention (CDC), more than 2 million people annually become infected with antibiotic-resistant bacteria, and more than 23,000 patients die as a direct result of these infections, primarily in healthcare settings such as hospitals and nursing homes. In addition, many more patients will die from other conditions complicated by antibiotic-resistant infections. Global healthcare costs associated with antibiotic-resistant infections are growing and are currently estimated at $5 billion annually.
The Shortcomings of Existing Approaches
Traditional antibiotic and vaccine approaches are becoming increasingly insufficient in addressing the problem of acute bacterial infections in healthcare settings for multiple reasons.
Monoclonal antibody (mAb) technology is among the most successful and versatile therapeutic platforms ever developed by the pharmaceutical industry. Since the first mAb approval in 1986, dozens are used today as primary treatments across a wide range of diseases, primarily for cancer and immune disorders. In the infectious diseases space, palivizumab, a mAb targeting respiratory syncytial virus (RSV), has been used for almost 20 years to prevent serious disease in neonates.
While mAbs have been successfully applied in many therapeutic areas, they have yet to be fully leveraged for acute bacterial infections, where they hold the potential to address critical unmet medical needs and to change the course of antibiotic resistance. Antibodies have proven effective for the prevention of serious bacterial infections dating back to the efforts of Emil von Behring (Recipient of the 1901 Nobel Prize in Physiology or Medicine) with diphtheria antitoxin. More recently, several mAbs have been approved for treatment and/or prevention of anthrax (raxibacumab, obiltoxaximab) and recurrent Clostridium difficile infection (bezlotoxumab).
Advances in our knowledge of bacterial pathogenesis have now opened new possibilities of expanding the use of mAbs to acute bacterial infections.
Our current programs address specific pathogens and pathogenic processes selectively, rather than broadly eliminating bacteria, potentially allowing Arsanis to address critical infections while minimizing collateral damage from antibiotic overuse, resistance, and microbiome disruption.
The ability to selectively and safely target causative pathogens represents a novel approach to the prevention of infections in high-risk patients, providing clinical and health economic benefits to patients and ushering in a new era in infection management.
We believe that targeted prevention fills an important middle ground between traditional prophylactic efforts (through vaccines) and post-infection treatment (through antibiotics). Our vision is to identify high-risk patients colonized with a specific pathogen, and then work to maintain their immune response by interrupting bacterial processes that disrupt it.
Targeted prevention could profoundly impact patient outcomes and healthcare spending. This approach would provide healthcare providers with new options to proactively reduce infections in acute care settings and lessen the downstream need for multiple antibiotic courses that contribute to resistance, toxicity, and subsequent infections. Targeted prevention of infection could also reduce mechanical ventilation days, shorten hospital stays, reduce healthcare costs, and decrease the risk of re-hospitalization.