Bacteria have evolved ways to evade the use of antimicrobials, leading to the rise of multidrug-resistant bacteria. This is particularly true in the case of Gram-Negative bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae, E.coli and Pseudomonas aeruginosa.
Given the high unmet medical need and the dwindling number of effective antibiotics, Bioharmony Therapeutics is developing a pipeline of lysins for infections caused by multidrug-resistant Gram-Negative bacteria.
Gram-negative bacterial infections
Are a major global health threat due to a paucity of effective therapeutic options. To combat antimicrobial resistance, lysins and engineered lysin-derived peptides have shown promising results as antibacterials. Lysins are bacteriophage-derived enzymes that degrade cell wall peptidoglycan leading to rapid bacterial death.
MDR A. baumannii can cause skin, urinary tract, intra-abdominal, respiratory tract and bloodstream infections. Of growing concern is the increase in carbapenem resistant A. baumannii. In 2010, 44.7% and 49.0% A. baumannii isolates were found to be resistant to commonly used carbapenems, imipenem and meropenem, respectively. Infections caused by carbapenem resistant A. baumannii are associated with limited, suboptimal and often delayed effective treatment, leading to increased mortality, prolonged hospital stay, and greater clinical costs. Bioharmony’s lysin program is highly differentiated from the other antibiotics currently approved or under development. Phage-encoded lytic antimicrobial peptide P307SQ-8C, a 39 amino acid phage-encoded engineered lytic antimicrobial peptide, is being developed as a nebulized drug BH01 for the treatment of A. baumannii infections, including MDR and CRAB infections in patients with hospital acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) patients. BH01 is highly differentiated from small molecule antibiotics. Not only do the usual characteristics of a lysin differ from antibiotics, Bioharmony’s approach of treating infections directly at the site of infection in the lung is novel. HABP and VABP patients are treated with systemic antibiotics that are not only ineffective in treating infections in the lung due to PK limitations, but have systemic toxicity issues. Locally delivered lysins via inhalation into the lungs can change the treatment paradigm for VABP patients, especially patients infected with MDR A. baumannii. Ventilated patients developing secondary bacterial pneumonia due to viral pandemics becoming common. Fast acting, narrow-spectrum nebulized BH01 treatment against A. baumannii delivered via ventilators would be an effective therapy for VABP patients.
BH02 and BH03 are composed of the same 39aa peptide as BH01, and are formulated either as a spray (BH02 for burns) or as a bladder wash (BH03 for UTI) for the treatment of infections caused by MDR and CRAB.
Infections caused by P. aeruginosa are common in hospitalized patients, often severe and life-threatening, especially in immunocompromised hosts. P. aeruginosa is the second most common organism isolated in nosocomial pneumonia (17% of cases), the third most common organism isolated in both urinary tract infection (UTI) and surgical site infection (11% of cases). P. aeruginosa is the the most common bacteria found in people with cyctic fibrosis with more than 50% of all CF patients harboring P. aeruginosa. Once infected, it is difficult to eradicate P. aeruginosa from the airways, leading to chronic long term infections, made additionally difficult by the presence of multidrug resistance. Fast acting, narrow-spectrum aerosolized lysins as treatments against P. aeruginosa delivered via nebulizers would be an effective therapy for CF patients.