Approach effectively degrades bacterial protective shields to enable immune or antibiotic intervention
Clarametyx Biosciences Inc., ("Clarametyx") a preclinical stage biotechnology company developing targeted, immune-enabling biologic therapies to counter persistent infections associated with biofilms, today announced the publication of a new study in eBioMedicine. The study demonstrates the potential impact of addressing resistant or recalcitrant infections by targeting the universal stabilizing structure of bacterial biofilms, a protective layer over bacteria that is present in as much as 80 percent of bacterial infections and contributes to persistent infections, inflammation, and resistance to therapeutic interventions.
The novel approach departs from prior anti-biofilm technologies that attack species-specific targets, instead targeting the critical DNA-binding proteins within the scaffold of biofilms, a feature common to all bacterial pathogens. The technology directs antibodies to bind to these structural proteins, which results in rapid disruption of the biofilm, releases the bacteria and in doing so, renders them far more vulnerable to attack by the immune response and or antibiotics.
"The concept of targeting bacterial biofilms has advanced dramatically in recent years. This new mechanism overcomes many of the limitations of prior technologies because it can effectively re-route an ineffective natural immune reaction to the biofilms or can be used together with many different antibiotics to enhance their effect, regardless of the bacterial pathogen," said Lauren Bakaletz, Ph.D., study author, co-inventor of the technology, Director of the Center for Microbial Pathogenesis and Vice President of Basic Sciences for the Abigail Wexner Research Institute (AWRI) at Nationwide Children’s Hospital and co-chair of the Clarametyx scientific advisory board. "With this novel approach, we have an opportunity to shift the paradigm for clinical management of a multitude of diseases characterized by recalcitrant biofilms that evade effective intervention today."
The series of preclinical evaluations described the ability of a rationally-designed monoclonal antibody directed against specific regions of the DNA-binding proteins as well as its antigen-binding fragment (Fab) to disrupt established biofilms and resolve active experimental otitis media caused by non-typeable Haemophilus influenzae (NTHI), a well-characterized biofilm-related disease. The study also showed that vaccination with the same immunogen could induce antibodies that prevented biofilm formation and disease development in a viral-bacterial co-infection model. Further, the study describes the humanization of the rationally-designed antibody and demonstrates the retention of both in vitro and in vivo activity after humanization, indicating potential utility for indication-optimized therapeutic agents to treat biofilm-mediated bacterial disease.
"Importantly, these results support the premise of focusing on one universal target in the biofilm that can dramatically improve intervention across bacterial pathogens, instead of looking at a pathogen-by-pathogen approach," said Steven Goodman, Ph.D., study author, co-inventor of the technology, Director of the Oral GI Microbiology Research Affinity Group in the Center for Microbial Pathogenesis at AWRI and co-chair of the Clarametyx scientific advisory board. "We believe this technology has the potential to resolve infections characterized by communities of heterogenous bacteria where other single-pathogen approaches have failed."
Prior in vitro studies have demonstrated the efficacy of the approach against 22 distinct bacterial species, including Gram-positive and Gram-negative species and the high priority ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.).
"The findings from this exciting research represent a dramatic advancement of this technology from target discovery to development of a humanized therapeutic antibody with clinical potential. These results signal the possibility of a two-pronged approach against bacterial biofilms to either mediate active disease or to prevent disease through an active immunization regimen," said Charles McOsker, Ph.D., co-founder and Chief Scientific Officer of Clarametyx. "Importantly, this study validated that the humanized antibody maintained efficacy in preclinical models, a critical step toward the initiation of clinical studies."
About Clarametyx Biosciences
Clarametyx Biosciences is combating the formidable challenge of persistent and recalcitrant infections through an innovative technology platform targeting the biofilm—a protective layer around bacteria—to enable a more effective immune response or antibiotic intervention. The Columbus, Ohio-based company is building a dynamic pipeline of immune-enabling therapies and vaccines for life-threatening bacterial infections associated with biofilms. Its lead candidate, CMTX-001, is a humanized monoclonal antibody in preclinical development for hospital-acquired pneumonia. For more information, visit us on the web or on LinkedIn.