The Challenge

Antibiotics are designed to eliminate disease-causing bacteria, but most bacterial infections involve biofilms that shield the bacteria from the effects of these medicines. Further, these infections are often caused by multiple types of bacteria, for which pathogen-specific antibiotics may not be effective.

As a result, antibiotics are less ineffective, or approaches involving longer antibiotic regimens, multiple antibiotics or higher antibiotic concentrations are required to resolve the infection.

Recalcitrant bacterial infections that do not respond to these current antibiotic treatment strategies contribute to further spread of infection. They may also lead to a cascade of inflammatory reactions and complications for patients.

In many cases, depending upon the type of infection, a single course of antibiotics does not effectively clear a bacterial infection, leading to the need for multiple courses of therapy, higher doses, and in some cases, extended hospitalization.1

The Opportunity

Biofilm-targeting approaches could dramatically improve outcomes for challenging bacterial infections by improving the immune system’s efficiency in destroying bacteria, and by improving the effectiveness of all antibiotics. Specific areas of focus include:

  • Challenging respiratory infections
  • Chronic diseases like cystic fibrosis, which are associated with susceptibility to infection

The approach could also be applied in a preventive strategy to help avoid the formation or maturation of biofilms, allowing the immune system to more effectively counter emerging bacterial colonies. This may help reduce the incidence and severity of bacterial infections.

Pipeline

With a defined universal target within the biofilm, the platform has the potential to generate a robust and diverse pipeline of therapeutics and vaccines. Initially, we are focusing on chronic and recurrent infections of the respiratory tract.

Pipeline Arrow
  • A 2-Part First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of CMTX-101 (NCT05629741).
  • CMTX-101 is an immune-enabling antibody therapy with broad-spectrum activity currently in a Phase 1 clinical trial for moderate-to-severe bacterial pneumonia.
Pipeline Arrow
  • A Phase 1b/2a Study To Evaluate The Safety Of CMTX-101 In People With Cystic Fibrosis (NCT06159725).
  • Clinical studies initiated to evaluate CMTX-101 as an add-on to front-line antipseudomonal therapy in people with cystic fibrosis with chronic bacterial infections.
Pipeline Arrow
  • CMTX-301 employs Clarametyx’ anti-DNABII technology through a vaccination approach in at-risk populations.
  • The first focus areas are otitis media (OM) and pulmonary disease, in which an anti-biofilm vaccination approach could help enable the body’s normal immune responses to prevent recurrent infection. This could substantially reduce the use of antibiotics in these common bacterial infections.
Pipeline Arrow
  • Discovery efforts are evaluating opportunities to apply this technology to areas of defined unmet need, including:
    • Nontuberculosis mycobacterial lung disease (NTM)
    • Non-CF bronchiectasis
    • COPD
    • Prosthetic joint and implant infection

Publications

Preliminary data support the efficiency and speed of this approach as well as the complementary nature to immune function:

Disruption of nontuberculous mycobacteria biofilms induces a highly vulnerable to antibiotic killing phenotype. Biofilm, 2023.

Monoclonal antibodies that target extracellular DNABII proteins or the type IV pilus of nontypeable Haemophilus influenzae (NTHI) worked additively to disrupt 2-genera biofilms. Biofilm, 2022.

Z-form extracellular DNA is a structural component of the bacterial biofilm matrix. Cell, 2021.

A Humanized Monoclonal Antibody Potentiates Killing by Antibiotics of Diverse Biofilm-Forming Respiratory Tract Pathogens | Antimicrobial Agents and Chemotherapy. ASM Journals, 2022.

Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance (Antibiotics). MDPI journals, 2022.

The extracellular innate-immune effector HMGB1 limits pathogenic bacterial biofilm proliferation. Journal of Clinical Investigation, 2021.

Nontypeable Haemophilus influenzae newly released (NRel) from biofilms by antibody-mediated dispersal versus antibody-mediated disruption are phenotypically distinct. Biofilm, 2020.

Targeting a bacterial DNABII protein with a chimeric peptide immunogen or humanized monoclonal antibody to prevent or treat recalcitrant biofilm-mediated infections. EBioMedicine, 2020.

Immunization with a Biofilm-Disrupting Nontypeable Haemophilus influenzae Vaccine Antigen Did Not Alter the Gut Microbiome in Chinchillas, Unlike Oral Delivery of a Broad-Spectrum Antibiotic Commonly Used for Otitis Media. mSphere, 2020.

Redirecting the immune response towards immunoprotective domains of a DNABII protein resolves experimental otitis media. NPJ Vaccines, Nature, 2019.

Monoclonal antibodies against DNA-binding tips of DNABII proteins disrupt biofilms in vitro and induce bacterial clearance in vivo. EBioMedicine, the Lancet, 2016.

Evaluation of the kinetics and mechanism of action of anti-integration host factor-mediated disruption of bacterial biofilms. Molecular Microbiology, 2014.

Biofilms can be dispersed by focusing the immune system on a common family of bacterial nucleoid-associated proteins. Mucosal Immunology, 2011.

1. Sources: Peyrani P, Arnold FW, Bordon J, et al. Incidence and Mortality of Adults Hospitalized With Community-Acquired Pneumonia According to Clinical Course. Chest. Jan 2020;157(1):34-41. https://doi.org/10.1016/j.chest.2019.09.022; Ramirez JA, Tzanis E, Curran M, et al. Early Clinical Response in Community-acquired Bacterial Pneumonia: From Clinical Endpoint to Clinical Practice. Clin Infect Dis. Aug 1 2019;69(Suppl 1):S33-S39. https://doi.org/10.1093/cid/ciz397