The Challenge

Antibiotics are designed to eliminate disease-causing bacteria, but biofilms shield the bacteria from the effects of antibiotics, so this requires higher concentrations of antibiotics to resolve the infection or renders the antibiotic ineffective. Despite use of potent regimens that often employ multiple antibiotics, biofilm-related infections are difficult to resolve. These recalcitrant infections can contribute to further spread of infection and may also contribute to a cascade of inflammatory reactions.

Understanding Biofilms

Biofilm-related infections are challenging and often resistant to normal immune system responses and standard antibiotic regimens.

Biofilms include an extracellular matrix that acts as a shield to protect bacteria from attacks by the immune system or antibiotics. This protective element contributes to persistent, harmful inflammatory responses, as well as extended duration and severity of disease.

Within the matrix lies a lattice-like structure of extracellular DNA (eDNA) and “linchpin” binding proteins, which are universally present across biofilms protecting a wide range of bacteria.

1000

Biofilm-encased bacteria can be up to 1,000 times more resistant to antibiotics than those unprotected by biofilms.

Conventional antibiotics are designed to eliminate the disease-causing bacteria but cannot penetrate the biofilm’s protective scaffold. So, despite use of potent regimens that often employ multiple antibiotics, biofilm-related infections are difficult to resolve. These recalcitrant infections contribute to a cascade of chronic inflammatory reactions, leaving only mechanical or surgical approaches as successful interventions.

80%

Bacterial biofilms are responsible for approximately 80 percent of human bacterial infections, and include infections such as bacterial pneumonia, COPD-related respiratory infections, chronic sinusitis and otitis media, and chronic wound-related infections. These infections carry significant morbidity and mortality, and contribute substantial costs to the U.S. healthcare system.

Our Immune-Enabling Technology

Our non-antibiotic antibody therapy platform is designed to collapse biofilms by binding to and separating key “linchpin” binding proteins, which are universally present across biofilms protecting a wide range of bacteria. By removing these connecting proteins, the biofilm rapidly collapses to enable more effective immune response and antibiotic intervention.

This antibody-driven approach represents a fully novel strategy to combat biofilms. Supported by a growing body of evidence, these attributes may overcome the limitations of prior attempts to target the biofilm based on its critical modes of action:

  • Immune-enabling: Enables a more efficient immune reaction to eliminate disease-causing bacteria
  • Antibiotic-sensitizing: Enhances the effectiveness of bacterial elimination
  • Inflammation-suppressing: Decreases biofilm-associated inflammation and reduced inflammatory reaction without impairing immune response

In addition to therapeutic applications, the same technology may serve as a powerful vaccination tactic, enabling the body’s immune response to effectively counter new bacterial threats by preventing development of the biofilm barrier.

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.

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  • CMTX-101 is an immune-enabling antibody therapy with broad-spectrum activity that is in development for a first indication in moderate-to-severe pneumonia caused by Gram-positive or Gram-negative bacteria.
  • Moderate-to-severe pneumonia is a challenging disease with high fatality rates that causes more than 250,000 hospitalizations annually in the U.S. It contributes significant costs to the U.S. healthcare system through increased length of hospital stay, greater use of antibiotic interventions, need for ventilation, and higher ICU resource utilization.

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  • CMTX-301 employs Clarametyx’ anti-DNABII technology through a vaccination approach in at-risk populations. This approach prevents the development of bacterial biofilm, enabling the body’s normal immune responses to more effectively destroy bacterial pathogens.
  • The first targeted indication is otitis media (OM).
  • Preventing formation of biofilm and eliminating bacteria at potential infection sites will reduce the incidence of OM, and thus reduce antibiotic usage.

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  • Beyond the current focus on respiratory tract infections — including chronic indications such as cystic fibrosis, recurrent acute otitis media, and sinusitis — the company envisions potential opportunities in areas such as chronic wounds, orthopedic implant/joint infections, and endocarditis (dialysis-related), among others.

Publications

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