Clarametyx Biosciences has achieved a significant milestone in its Phase 1b/2a clinical trial of CMTX-101, an investigational immune-enabling antibody therapy designed to treat cystic fibrosis-associated pulmonary infections. The Independent Data Monitoring Committee (DMC) has approved continuation of the trial following positive interim analysis results from the first 21 participants, with no safety concerns identified and encouraging efficacy trends observed.
Interim Analysis Demonstrates Bacterial Burden Reduction
The randomized, double-blind, placebo-controlled trial is evaluating CMTX-101 as an adjunctive therapy to standard of care antibiotics in people with cystic fibrosis. The interim analysis assessed safety and tolerability, pharmacokinetics, immunogenicity, and reduction of pulmonary Pseudomonas aeruginosa burden, along with additional exploratory endpoints.
Participants treated with CMTX-101 demonstrated a reduction in P. aeruginosa burden based on prespecified statistical criteria at both tested dose levels of 5 and 30 mg/kg. Importantly, CMTX-101 was detected in the sputum of all treated participants, confirming drug delivery to the target site of infection.
"Interim findings from this study have identified encouraging trends that support the potential benefit of CMTX-101, with no safety issues," said Jerry Nick, MD, Professor in the Division of Pulmonary, Critical Care and Sleep Medicine at National Jewish Health and primary investigator of the study.
Favorable Safety Profile Maintained
The therapy demonstrated a generally well-tolerated safety profile, consistent with findings from a prior clinical study. Notably, no antidrug antibodies were detected in the treated participants, suggesting minimal immunogenicity concerns at the tested doses.
Trial Expansion and Timeline
The study will continue evaluating both doses of CMTX-101 versus placebo among approximately 20 additional participants across 23 study sites, with significant support from the Cystic Fibrosis Therapeutics Development Network. Full study enrollment is expected to be complete by the end of 2025.
The complete dataset will include exploratory endpoints such as respiratory function, inflammatory biomarkers, and quality of life assessments, providing comprehensive insights into CMTX-101's therapeutic potential.
Novel Biofilm-Targeting Mechanism
CMTX-101 represents an innovative approach to treating chronic respiratory infections by targeting bacterial biofilms—protective layers that shield bacteria from antibiotics and immune responses. The therapy is designed to precisely destroy the universal underlying structure of bacterial biofilms, undermining extracellular bacterial defenses and enabling more effective antibiotic and immune intervention.
"The goal of treatment is to dramatically improve the effectiveness of antibiotic therapies and innate immune system effectors, improving the time to resolution of the infection and reducing the need for repeated courses of antibiotics," according to the company's description of the mechanism.
Broader Therapeutic Applications
Beyond cystic fibrosis-associated infections, CMTX-101 has potential applications in treating other chronic respiratory conditions. The company is exploring opportunities to expand to nontuberculous mycobacterial (NTM) lung disease, non-CF bronchiectasis (NCFB), and chronic obstructive pulmonary disease (COPD).
David V. Richards, Chief Executive Officer of Clarametyx, expressed satisfaction with the interim results: "We are pleased that the findings from the first 21 participants enrolled support progressing the study without modification. The full dataset will help us further understand the full potential of CMTX-101 as a novel therapeutic solution to a variety of chronic respiratory conditions."
The trial is registered at ClinicalTrials.gov under identifier NCT06159725, with 23 participating study sites providing access to the cystic fibrosis patient population.
