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.
- 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.
- 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.
- Supported by the Cystic Fibrosis Foundation.
- 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.
- 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:
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