CMTX-101 Shows Safety and Bacterial Reductions in Cystic Fibrosis Trial

Clarametyx Biosciences reported positive topline results from a phase 1b/2a study of its immune-enabling antibody CMTX-101 in people with cystic fibrosis, showing the therapy was safe and well-tolerated while producing clinically meaningful reductions in inflammatory biomarkers and pulmonary Pseudomonas aeruginosa burden.1

“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 lead investigator Jerry Nick, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at National Jewish Health, in a “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.”1

CMTX-101 is an investigational immune-enabling antibody therapy designed to treat chronic respiratory disease by selectively and rapidly dismantling the shared structural components of bacterial biofilms.1 By weakening extracellular bacterial defenses, the approach enhances immune and antibiotic activity to reduce exacerbations, resolve inflammation, and improve patient outcomes across multiple indications, including nontuberculous mycobacterial lung disease, non-cystic fibrosis bronchiectasis, and chronic obstructive pulmonary disease. The US Food & Drug Administration (FDA) has previously granted Clarametyx a fast-track designation for CMTX-101 to treat cystic fibrosis following a positive interim analysis, announced on August 4, 2025.2

Nick and colleagues conducted a randomized, double-blind, placebo-controlled phase 1/b/2a clinical study to assess the safety and tolerability of a single intravenous dose of CMTX-101 in 42 patients aged ≥ 18 years with cystic fibrosis infected with Pseudomonas aeruginosa. Along with assessing the safety, investigators sought to characterize the pharmacokinetic profile of a single dose and assess whether treatment induced the development of anti-drug and neutralizing antibodies.3

Patients all received standard of care, including stable regimens of cystic fibrosis transmembrane conductance regulator (CFTR) modulators or inhaled antibiotics for ≥ 3 months. CFTR modulators included Alyftrek (vanzacaftor/tezacaftor/deutivacaftor), Trikafta (elexacaftor/tezacaftor/ivacaftor), Symdeko (tezacaftor/ivacaftor), Orkambi (lumacaftor/ivacaftor), or Kalydeco (ivacaftor).4 Inhaled antibiotics include aztreonam inhalation solution (Cayston), Tobramycin inhalation solution (TOBI, Bethkis, Kitabis Pak, or generic), Tobramycin inhalation powder (TOBI Podhaler), and an inhaled form of amikacin.5

The trial met its primary endpoint, demonstrating the safety and tolerability of CMTX-101. Patients on 5 mg/kg of CMTX had a clinically meaningful 77% reduction of neutrophil elastase at day 28 compared to standard of care. Patients receiving CMTX-101 also had meaningful reductions in additional inflammatory biomarkers, including IL-1 beta, IL-8, and calprotectin.1

CMTX-101 also preserved pulmonary function, measured by forced expiratory volume (FEV1) from baseline compared to standard of care. Additionally, CMTX-101 reduced Pseudomonas aeruginosa burden, with 13 out of 17 participants achieving > 70% reduction in colony-forming unit (CFU) count on day 28.

The analysis showed CMTX-101 was generally well-tolerated, with no detection of neutralizing antibodies.

“These encouraging findings support exploring future development of CMTX-101 in bronchiectasis,” said David V. Richards, chief executive officer of Clarametyx. “We are deeply grateful to the patients and their families, as well as the investigators and clinical site teams, whose participation and tireless efforts were essential to the successful completion of this study.”

The company plans to engage with global regulatory authorities in the first half of 2026 to advance a phase 2 study of CMTX-101 in bronchiectasis, a condition with only 1 approved therapy and disease physiology similar to cystic fibrosis.

References

1. Clarametyx Biosciences Announces Positive Topline Data From Phase 2a Study Evaluating CMTX-101 in Cystic Fibrosis. BusinessWire. Published on January 9, 2026. Accessed on January 13, 2026. https://www.businesswire.com/news/home/20260109419506/en/Clarametyx-Biosciences-Announces-Positive-Topline-Data-From-Phase-2a-Study-Evaluating-CMTX-101-in-Cystic-Fibrosis

2. Clarametyx Biosciences Announces FDA Grant of Fast Track and Qualified Infectious Disease Product Designations for CMTX-101. Published on August 4, 2025. Accessed on January 13, 2026. https://www.businesswire.com/news/home/20250804750253/en/Clarametyx-Biosciences-Announces-FDA-Grant-of-Fast-Track-and-Qualified-Infectious-Disease-Product-Designations-for-CMTX-101

3. A Study To Evaluate The Safety Of CMTX-101 In People With Cystic Fibrosis. ClinicalTrials.gov. Published on November 21, 2025. Accessed on January 13, 2026. https://www.clinicaltrials.gov/study/NCT06159725

4. CFTR Modulator Therapies. Cystic Fibrosis Foundation. Accessed on January 13, 2026. https://www.cff.org/managing-cf/cftr-modulator-therapies

5. Antibiotics. Cystic Fibrosis Foundation. Accessed on January 13, 2026. https://www.cff.org/managing-cf/antibiotics