Arcturus Therapeutics Holdings Inc. presented Phase 1 results in healthy volunteers and Phase 1b interim data in people with CF for ARCT-032, an inhaled investigational mRNA therapeutic, at the 47thEuropean Cystic Fibrosis Conference in Glasgow, Scotland. ARCT-032 administration was generally safe and well tolerated with no serious or severe adverse events in healthy volunteers and the first four dosed participants with CF. The Phase 1b trial showed improvements in FEV1 (Forced Expiratory Volume in 1 second) in the four adults with CF after two inhaled administrations.

The absolute change in percent predicted FEV1 averaged +4.0% on Day 8 (5 days after 2nd dose). The relative change in FEV1 averaged +5.8% on Day 8. The observed increases in FEV1 are encouraging and consistent with the previously reported data in the CF ferret model that demonstrated markedly improved mucociliary clearance (MCC) after a single dose of ARCT-032. Of the four participants in Phase 1b to date, one had 2 Class I mutations and the other three had F508del mutations and were being treated with Trikafta®.

No bronchospasm or febrile reactions were observed in the CF participants. Dose-related, mild-to-moderate febrile reactions (elevated temperature associated with headache, muscle aches, back pain, or nausea) occurred in some healthy volunteers. Dose-related transient declines in FEV1 observed in healthy volunteers were mitigated by pretreatment with albuterol, a commonly used bronchodilator.

No serious adverse events or dose limiting toxicities were observed at any dose level. Cystic fibrosis is a life-shortening disease with a worldwide distribution. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in a reduction or absence of CFTR protein and/or function in the airways, causing insufficient chloride transport to maintain airway surface homeostasis.

CF mucus is more difficult to clear, thus clogging the airways and leading to infection, inflammation, respiratory failure, or other life-threatening complications. Currently approved CFTR modulator therapies are designed to increase function of the CFTR channel to help reduce symptoms yet are ineffective in some people with CF because of their underlying mutations. ARCT-032 has received Orphan Medicinal Product Designation from the European Medicines Agency (EMA) and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) to treat Cystic Fibrosis.

ARCT-032 utilizes Arcturus' LUNAR® lipid-mediated aerosolized platform to deliver CFTR messenger RNA to the lungs. Expression of a functional copy of the CFTR mRNA in the lungs of people with CF has the potential to restore CFTR activity and mitigate the downstream effects that cause progressive lung disease. The ARCT-032 program is supported by preclinical data in rodents, ferrets and primates, as well as demonstrating restoration of CFTR expression and function in human bronchial epithelial cells.