Arcturus Therapeutics Plans 12-Week Phase 2 Cystic Fibrosis Trial After Positive Safety Data

Arcturus Therapeutics has completed three 28-day dosing cohorts in its Phase 2 cystic fibrosis study, successfully administering daily inhaled doses of 5 mg, 10 mg, and 15 mg of ARCT-032, an inhaled therapy that delivers CFTR mRNA to the lungs. The therapy has been consistently well-tolerated across these dose levels, and the 28-day cohorts produced early signals of biological proof of concept, including observed decreases in mucus plugging as assessed by high-resolution CT scans.

The company is preparing to initiate a longer 12-week study designed to better evaluate lung function outcomes. The Chief Executive Officer told investors at the Leerink Partners Global Healthcare Conference that the company hopes the observed changes in mucus plugging translate into measurable lung function improvements in the upcoming study.

The 12-week study will apply lessons from the earlier cohorts, particularly around variability in lung function measures such as forced expiratory volume (FEV). Arcturus plans to strengthen baseline assessments by using multiple baseline measurements rather than relying on a single point, and by requiring baseline stability before enrollment. Patients who show instability—such as those entering or recovering from an infection—may be temporarily withdrawn and allowed to re-screen later.

Arcturus is narrowing baseline lung function eligibility criteria to target a "sweet spot" of patients who are neither too high-functioning nor too advanced in disease, to improve the likelihood of detecting a treatment effect over 12 weeks. The company is not developing a systemic modulator for delta F508 but an inhaled approach for a population described as often having more than 20 years of advanced disease.

The 12-week study will evaluate multiple measures: FEV, lung clearance index (LCI), two quality-of-life measures, and high-resolution CT scans before and after the treatment period. LCI was described as a more sensitive, less subjective, and more passive measure than FEV because it is based on tracking gas washout while the patient breathes normally. In concept, LCI may detect smaller changes such as reductions in smaller mucus plugs, while larger changes might be more readily captured by FEV.

Arcturus has room to increase dose further, referencing prior experience dosing as high as 27 mg in healthy volunteers. However, the company's current focus is more on treatment duration than dose escalation, with the company observing activity at 10 mg and intending to evaluate longer exposure.

To support enrollment of Class 1 CF patients, the company is expanding trial sites into Europe and the Middle East, where the prevalence of Class 1 patients can be significantly higher than in the U.S. U.S. prevalence is approximately 10%, while some international sites can have 20% to 50% Class 1 representation.

Arcturus says it is too early to pursue accelerated approval and may need a Phase 3 depending on Phase 2b results. The company reports a cash runway into the second quarter of 2028.

Arcturus Therapeutics is a messenger RNA medicines company focused on the development of liver and respiratory rare disease therapeutics. The company's pipeline includes RNA therapeutic candidates to potentially treat cystic fibrosis and ornithine transcarbamylase (OTC) deficiency along with its partnered mRNA vaccine programs for SARS-CoV-2 (COVID-19) and influenza. Arcturus developed KOSTAIVE, the first self-amplifying messenger RNA (sa-mRNA) COVID vaccine in the world to be approved.