Arcturus Therapeutics announces interim results from ARCT-032 trial

Arcturus Therapeutics (ARCT) announced interim results from its ongoing Phase 2 clinical trial of ARCT-032, an investigational inhaled mRNA therapy for people with cystic fibrosis. In the second cohort of the study, six Class I CF adults received inhaled 10 mg doses of ARCT-032 daily over 28 days. The treatment was generally safe and well tolerated. Treatment related AEs that were identified in the single-dose Phase 1 study were also observed in some participants for the first few doses but ceased with continued dosing. One SAE occurred in a participant well after the end of the dosing period. The Data Monitoring Committee found no convincing evidence that the SAE is related to ARCT-032 and approved the study to proceed. The expanded third cohort is ongoing and aims to enroll up to six subjects to determine if there is a dose escalation response at 15 mg and if ARCT-032 continues to be generally safe and well tolerated. The company intends to initiate a 12-week safety and preliminary efficacy study in up to 20 CF participants in the first half of 2026. Initial analysis comparing FEV values from Day 1 to Day 28 did not demonstrate meaningful improvement. However, a post hoc exploratory analysis comparing the average of two pre-treatment FEV measurements for the baseline with the Day 42 post-treatment value, assuming an extended activity of functional CFTR protein triggered by daily ARCT-032 administration, suggests improvements in lung function, in four of six Class I CF participants with an average absolute increase of 3.8% and a relative increase of 5.1% in percent predicted FEV. While the magnitude of these changes falls within the range of natural variability of FEV1 measurements, such exploratory analyses can provide valuable directional signals, though they warrant cautionary interpretation. High resolution computed tomography scans, analyzed using FDA 501(k)-cleared AI technology from Thirona, revealed reductions in mucus burden in four of six Class I CF participants. Decrease in mucus plugs and mucus volume in four of six Class I CF participants is a meaningful trend indicative of ARCT-032 therapeutic activity. A larger, longer-duration study is planned to substantiate the clinical relevance of these findings. The HRCT mucus reduction and supporting lung function data from the second cohort, combined with additional data collected from the ongoing third cohort will guide dose selection, treatment duration, and endpoint strategy for future studies, including the conduct of a 12-week safety and preliminary efficacy clinical trial that is planned to begin in the first half of 2026.