Arcturus Therapeutics' Cystic Fibrosis mRNA Therapy Shows Mixed Results in Phase II Trial

Arcturus Therapeutics' experimental inhaled mRNA therapy for cystic fibrosis (CF) has yielded mixed results in a Phase II clinical trial, leading to a significant drop in the company's stock price. The therapy, ARCT-032, failed to demonstrate meaningful lung function improvements but showed potential in reducing mucus volume in some patients.

Trial Results and Stock Impact

In the ongoing open-label, multiple ascending dose Phase II trial, six adults with Class I CF received 10 mg doses of ARCT-032 daily for 28 days. The primary endpoint of the study was to assess the incidence and severity of adverse events. However, investors were particularly focused on the secondary endpoint of forced expiratory volume in one second (FEV1), a measure of lung function.

The initial analysis comparing FEV1 values from the first day to Day 28 showed no meaningful improvement, falling short of the previously set 3% benchmark for FEV1 increase. This disappointing outcome led to a dramatic decline in Arcturus' stock price, with shares plummeting by 50-55% following the announcement.

Despite the negative market reaction, Arcturus highlighted some potentially promising efficacy signals. Using AI-enhanced high-resolution computed tomography screening, the company observed reductions in mucus volume and the number of mucus plugs in four out of six evaluated patients. This outcome was described as "encouraging" and "a meaningful trend indicative" of the asset's therapeutic benefit by Arcturus.

Safety Profile and Future Plans

ARCT-032 demonstrated a generally safe and well-tolerated profile during the trial. Treatment-related adverse events identified in a previous single-dose Phase I trial were observed in some participants for the first few doses but ceased with continued dosing.

Arcturus is currently conducting a third stage of the trial, enrolling six more patients to receive a higher dose of 15 mg. The company is also preparing for a 12-week safety and preliminary efficacy trial set to begin in the first half of 2026, which will enroll up to 20 patients.

Dr. Juergen Froehlich, Arcturus' Chief Medical Officer, expressed encouragement about the early signals of mucus plug reduction, particularly given that Class I CF patients do not produce the cystic fibrosis transmembrane conductance regulator (CFTR) and therefore don't respond to available CFTR therapies.