Arcturus Therapeutics Announces Positive Phase 2 Interim Results for mRNA Therapy in OTC Deficiency

SAN DIEGO, CA – June 30, 2025 – Arcturus Therapeutics Holdings Inc. (Nasdaq: ARCT), a commercial mRNA medicines company, today reported positive interim Phase 2 results for ARCT-810, an investigational mRNA therapeutic for Ornithine Transcarbamylase (OTC) deficiency. This data demonstrates strong biological effects, highlighting a potential accelerated path to a pivotal study for this severe rare disease.

About ARCT-810 and OTC Deficiency: ARCT-810 is an intravenously administered mRNA therapeutic designed to deliver functional OTC enzyme to liver cells using Arcturus’ proprietary LUNAR delivery platform. OTC deficiency is the most common urea cycle disorder, where a deficient OTC enzyme leads to toxic ammonia and glutamine buildup, causing severe neurocognitive impairment, crises, and potentially death. Current treatments manage symptoms but don’t address the underlying cause. ARCT-810 has received multiple Orphan Drug designations in the U.S. and Europe.

Key Interim Phase 2 Findings:

• Significant Glutamine Reduction: Combined analysis from two Phase 2 studies showed a significant decrease in glutamine levels, a key biomarker for urea cycle function, consistently observed across patient cohorts.
• Increased Urea Cycle Function (RUF): In the U.S. study, the first three participants showed a statistically significant increase in Relative Ureagenesis Function (RUF) using a new, optimized assay. Two participants achieved clinically meaningful RUF improvements (>50%).
• Stable Ammonia Levels: Patients in both studies maintained ammonia levels within the normal range during treatment and for an extended period afterward.
• Favorable Safety and Tolerability: ARCT-810 was generally safe and well tolerated across all studies (40 participants), with no serious infusion-related reactions observed using an improved 3-hour IV regimen.