California-based Trellis Bioscience LLC is advancing a first-in-human trial of inhaled TRL1068, a human monoclonal antibody designed to disrupt bacterial biofilms, marking the first time the molecule has been tested via pulmonary delivery. The trial is notable because it applies an established mechanism — biofilm collapse through displacement of bacterial DNA-binding proteins — to an inhalation route that could, in principle, reach lung infections where systemic antibiotics consistently underperform.
The Phase I study (NCT07644195), conducted with support from the National Institute of Allergy and Infectious Diseases (NIAID), enrolls 14 healthy adults across two sequential part. The drug is delivered at a fixed 60 mg dose via the Aerogen Solo vibrating mesh nebulizer. A sentinel dosing approach — in which one active and one placebo participant are observed for at least 24 hours before the remaining cohort is dosed — reflects standard caution for a novel delivery route. Primary endpoints cover safety and tolerability over 30 days; secondary endpoints characterize systemic pharmacokinetics. Immunogenicity, assessed by anti-drug antibody detection via electrochemiluminescence assay, is also a secondary endpoint. The trial is set to begin enrollment in Q4 2026 at Celerion in Lincoln, Nebraska, with primary completion expected by December 2026.
TRL1068 — assigned the INN calpurbatug, where the -tug suffix designates an unmodified native human antibody — was discovered internally at Trellis using the company's proprietary CellSpot platform, which screens millions of human B-lymphocytes from healthy donors to identify naturally occurring antibodies without genetic engineering. Its target is the DNABII family of bacterial proteins, specifically integration host factor (IHF) and histone-like (HU) protein, which anchor extracellular DNA within the biofilm matrix. By binding a highly conserved epitope on these proteins with subnanomolar affinity, TRL1068 shifts the equilibrium of DNABII binding away from the eDNA scaffold, collapsing the three-dimensional meshwork that gives biofilms their structural integrity and antibiotic tolerance. The antibody does not kill bacteria directly; it acts as an adjunct that exposes embedded organisms to antibiotics and immune effectors that the intact biofilm would otherwise exclude. Preclinical data published in Antimicrobial Agents and Chemotherapy demonstrated potentiation of antibiotic efficacy in animal models, and Trellis has noted that because the bacterial target is only accessible after bacterial cell death — when DNABII proteins are released into the extracellular space — resistance development is expected to be infrequent.