Arcturus Reports Interim Phase 2 OTC Data for ARCT-810, Advances LUNAR 2.0

Arcturus Therapeutics reported interim Phase 2 findings for ARCT-810 in ornithine transcarbamylase (OTC) deficiency, showing that the investigational mRNA therapy was generally safe and well tolerated, with encouraging activity across key urea-cycle biomarkers. The company is also advancing ARCT-2601, a next-generation OTC deficiency candidate using its LUNAR 2.0 mRNA delivery platform, toward integration into the ongoing Phase 2 study by year-end 2026.

ARCT-810 Shows Activity Across Key Urea-Cycle Biomarkers

In the ongoing Phase 2 study, intravenous ARCT-810 was generally safe and well tolerated. Treatment reduced or maintained first-morning fasting ammonia within the normal range, including during periods when participants increased protein intake. Glutamine levels also declined, with participants receiving 0.5 mg/kg achieving mean glutamine values within the normal range during treatment. Weight gain was observed in all participants.

First-morning fasting ammonia is an important biomarker in OTC deficiency because hyperammonemia contributes to the neurological morbidity associated with the disease. Arcturus cites prior analyses showing that fasting ammonia is the least variable ammonia measurement and correlates with 24-hour ammonia exposure, which is associated with the risk of hyperammonemic crises. Glutamine provides another measure of urea-cycle function and can increase as the body buffers excess nitrogen before ammonia levels rise.

mRNA Therapy Targets the Underlying Enzyme Deficiency

OTC deficiency is the most common urea-cycle disorder and results from mutations in the X-linked OTC gene. Reduced or absent OTC enzyme activity impairs the conversion of toxic ammonia to urea in the liver, leading to hyperammonemia and potentially severe neurological complications, including seizures, progressive neurocognitive impairment, coma and death. Severe disease often presents early in life, while milder cases may be diagnosed during adolescence or adulthood.

ARCT-810 is an intravenously administered investigational mRNA therapy that delivers OTC mRNA to hepatocytes to produce functional OTC enzyme. The approach addresses the underlying enzyme deficiency, unlike current management with protein restriction, essential amino acid supplementation and nitrogen-scavenging medicines, which primarily control ammonia levels. Liver transplantation remains the only established curative option but carries substantial surgical and long-term immunosuppression-related risks.

LUNAR 2.0 Shows Higher Protein Expression in Preclinical Studies

Arcturus also introduced LUNAR 2.0, a next-generation mRNA delivery platform incorporating improved lipids and an enhanced formulation process specific to those lipids.

In non-human primate studies, LUNAR 2.0 produced a 40-fold improvement over LUNAR 1.0 in expressing human erythropoietin. In a separate study, the platform demonstrated 38-fold greater potency than ATX-95, the key lipid used in ARCT-810, for expression of human OTC.

These findings remain preclinical. Their significance will depend on whether the higher protein expression observed in NHP studies translates into clinically meaningful improvements in exposure, dosing frequency, efficacy or tolerability.

ARCT-2601 to Enter the Phase 2 Program

Arcturus is applying LUNAR 2.0 to ARCT-2601, its next-generation investigational mRNA therapy for OTC deficiency. In non-GMP preclinical studies, ARCT-2601 demonstrated a safety profile similar to ARCT-810. NHP data also suggest the potential for lower or less frequent dosing.

Following a Type C meeting with the FDA in June 2026, Arcturus received favorable regulatory feedback and clarity on the development path for ARCT-2601. The company plans to begin dosing patients aged 12 years and older near year-end 2026 under an amended Phase 2 protocol that will integrate ARCT-2601 into the ongoing ARCT-810 study.

Arcturus to Acquire AI Discovery Company myNEO

Arcturus has entered into a definitive agreement to acquire myNEO, an AI discovery company, with the transaction expected to close in October 2026, subject to customary closing conditions. The companies have worked together since 2024.

The acquisition will add myNEO’s proprietary computational engine and intellectual property to Arcturus’ technology capabilities, with a focus on improving mRNA design quality and strengthening target identification. The company plans to use these capabilities alongside its expanding mRNA platform and pipeline.

Arcturus also identified phenylketonuria (PKU) and gout as potential therapeutic areas for LUNAR 2.0.

The interim ARCT-810 findings provide clinical data supporting continued development of Arcturus’ OTC deficiency program, while LUNAR 2.0 has demonstrated substantially higher protein expression in preclinical studies. The next key test will be whether ARCT-2601 can reproduce these delivery advantages clinically after entering the amended Phase 2 program.

Reference

Arcturus Therapeutics Announces Interim OTC Deficiency Phase 2 Results and Introduces LUNAR 2.0™ Next-Generation mRNA Delivery Platform, Arcturus Therapeutics , 23 September 2026

Study for Adolescents and Adults with Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810, ClinicalTrials.gov ID NCT05526066