Antibody therapy to clear CF lung infections fares well in early trial
CMTX-101 aims to break through toxic biofilms
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CMTX-101, an antibody-based therapy designed to help clear bacterial lung infections, was tolerated well among people with cystic fibrosis (CF) in an early clinical trial.
Developer Clarametyx Biosciences said trial data also suggest the experimental therapy may help decrease inflammation and reduce counts of infectious bacteria.
“The strong results of this 2a study not only demonstrate safety and tolerability of CMTX-101, but also show clinically meaningful measures of efficacy, including preservation of [lung] function and reduction in key inflammatory biomarker levels,” David V. Richards, CEO of Clarametyx, said in a company press release.
With the positive results from the CF trial in hand, Clarametyx is planning a Phase 2 study to test CMTX-101 in people with bronchiectasis, a disease that, like CF, is often marked by lung inflammation and hard-to-treat bacterial lung infections.
One reason these infections can be difficult to treat is that infectious bacteria will form biofilms, protective layers of proteins and other molecules that act like a fortress, sheltering the bacteria from antibiotics and infection-fighting immune cells. CMTX-101 is designed to disrupt these biofilms, essentially taking a battering ram to the fortress door, allowing antibiotics and immune cells to more effectively fight the infection. Last year, U.S. regulators granted the therapy fast track designation, aiming to expedite its development.
‘Highly encouraging results’
“These highly encouraging results support the potential for CMTX-101 to play a significant role in the treatment of CF and other chronic biofilm-driven respiratory diseases,” said Jerry Nick, MD, primary investigator of the trial and a pulmonologist at National Jewish Health. “This well-conducted, early-stage trial demonstrated meaningful and sustained improvements in inflammatory biomarkers, pulmonary function, and microbiological burden, illustrating its promise to address persistent unmet needs of the CF population, even in the era of highly effective CFTR modulators.”
CF is a genetic disorder marked by abnormally thick, sticky mucus, which builds up in the lungs and other organs. Within the lungs, this abnormal mucus provides a fertile breeding ground for infectious bacteria, and as such, bacterial lung infections are a common problem in people with CF.
The new data come from a Phase 1b/2a trial (NCT06159725) that enrolled 42 people with CF who had chronic infections of Pseudomonas aeruginosa, a type of bacteria that frequently causes problematic lung infections in CF patients. All participants were already receiving standard-of-care therapies, including antibiotics and CFTR modulators. All received a single dose of CMTX-101, or a placebo, delivered by infusion into the bloodstream.
The main goal of the trial was to evaluate the experimental treatment’s safety. Clarametyx said the therapy was “generally well tolerated,” with no neutralizing antibodies against the treatment detected. The company didn’t give specifics on safety outcomes, noting that details will be presented at an upcoming medical conference.
Clarametyx noted that, after four weeks of CMTX-101 treatment at a dose of 5 mg/kg, there was a 77% reduction in levels of the inflammatory marker neutrophil elastase. Richards said that this marker is “strongly linked to pulmonary exacerbations, airway inflammation and disease progression.”
Clarametyx said CMTX-101 treatment also led to reductions in other inflammatory counts, and within four weeks of the one-time treatment, 13 out of 17 participants given the 5 mg/kg dose had a reduction of at least 70% in levels of P. bacteria. Lung function measures remained stable throughout the month-long study.
CF is caused by mutations in the gene that encodes CFTR, a protein that regulates mucus production. CFTR modulators are medicines that can improve the protein’s function in people with certain underlying mutations.
