Despite the overall health improvements modulator therapies have brought to the cystic fibrosis population, many with CF still rely on antibiotics to treat the persistence of chronic infections. Additionally, with this reliance on antibiotics, antibiotic resistance remains a threat to the CF population by reducing the effectiveness of the limited antibiotics we do have.
Clarametyx, a clinical stage biotechnology company, is developing a novel treatment approach to fight bacterial infections called a biofilm disruptor. A biofilm disruptor makes bacteria more vulnerable to the effects of antibiotics and helps to minimize chronic infections from common CF pathogens.
CF Infections and biofilms
Bacteria have an ability to repel antibiotics, reducing their effectiveness and leading to resistance. This is due to what is called a biofilm – an extracellular defense around the bacterial colonies.
Clarametyx’s therapeutic approach involves using a monoclonal antibody, (the biofilm disruptor) which is specifically designed to rapidly destroy the structure of the bacterial biofilms to break down their defenses. This therapy works by breaking down a specific protein called DNABII that is universally present across bacterial biofilms. So, this technology can treat a range of bacterial infections, including infections in people with CF where multiple types of bacteria are present.
During the course of treatment, when the antibody binds to the specific protein, it causes the protein to be released from the biofilm. This causes the biofilm to collapse and weakens the bacteria’s defenses against both antibiotics as well as enhancing our body’s immune response.
CMTX-101 study details
Currently this study has completed phase 1b, in which participants were dosed with a single IV infusion of CMTX-101, (the monoclonal antibody), to evaluate the drug’s safety in people with CF. Now, the study is enrolling up to 41 adults with CF in Phase 2a for the purpose of determining the optimal dosage of the treatment while evaluating safety, tolerability, the reduction of bacteria from sputum samples, and other endpoint measures assessing a CF patient’s health.
Although CMTX-101 targets a universal protein found in the biofilm of many kinds of bacteria, for the purpose of the study, to understand the degree to which breaking down the biofilm allows antibiotics to work more effectively, all participants will receive a single IV infusion of either the study drug or a placebo followed by 28 days of inhaled antibiotics. To standardize and measure how much of an effect the combination of the biofilm disruptor and the antibiotic have on the bacteria, all participants in the study are required to be colonized with Pseudomonas aeruginosa.
Researchers will monitor adverse events and changes in vital signs by conducting physical exams, blood draws, and sputum collection. They will also track how the body processes CMTX-101 by measuring how much of the drug is present in the blood and sputum.
Goals of this novel therapeutic approach
Recognizing that recurrent infections are a significant challenge for people living with cystic fibrosis and their families, Clarametyx is committed to developing CMTX-101 to help patient’s immune system and the antibiotics we have available to us today to more effectively clear infections. This approach could become a new method in alleviating the burden of chronic infections as well as potentially reducing the issue of antibiotic resistance.
In preliminary nonhuman research, this treatment has shown to rapidly collapse the biofilm, increase the effectiveness of antibiotics and reduce the potential for resistance. It has shown effectiveness across many types of bacterial biofilms, and it has not demonstrated any disruption of the gut microbiome.
If CMTX-101 demonstrates improvement in the effectiveness of antibiotic therapies and our body’s innate immune system, it could help improve the time it takes to treat an infection and eliminate it, and help reduce the need for repeated courses of antibiotics.
David Richards, Chief Executive Officer of Clarametyx states, “The risk of chronic infections, as well as the need for prolonged courses of high-dose antibiotics, place a huge burden on people living with cystic fibrosis and their families. Our goal at Clarametyx is to disrupt bacterial defenses to relieve this burden, improve quality of life and prevent the development of antimicrobial resistance.”
Find out more about this study
If you are interested in learning more about eligibility for this study, visit the Cystic Fibrosis Foundation Clinical Trial Finder and reach out to a research coordinator.
Support from CF researchers
Jerry Nick, MD, Professor in the Division of Pulmonary, Critical Care and Sleep Medicine at the
National Jewish Health Department of Medicine, and the primary investigator of the ongoing study with CMTX-101 says, “We are encouraged by the initial data from the 1b portion of the study, which demonstrated no safety signals with CMTX-101. If clinically confirmed to disrupt bacterial defenses and improve response to antibiotics and natural immunity, CMTX-101 will add a new treatment strategy for people with CF.”
Ella Balasa is 32 years old and has CF. She lives in Tampa Bay, Florida. Ella is a patient advocate and advisor to Clarametyx.
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