Arcturus Highlights ARCT-810 Phase II Data, Unveils Next-Gen OTC Therapy Platform

Arcturus Therapeutics presented preliminary Phase II data for ARCT-810, its mRNA therapeutic candidate for ornithine transcarbamylase, or OTC, deficiency, while outlining plans to introduce a next-generation delivery platform into the program.

OTC deficiency is a urea-cycle disorder in which deficient OTC enzyme activity can lead to toxic ammonia accumulation.

Chief Medical Officer Alan Cohen said the condition affects roughly 10,000 people across the United States and Europe.

Current management includes protein restriction, fluid intake and ammonia-scavenger medicines, while liver transplantation remains the only cure for severe patients.

ARCT-810’s Phase II study showed encouraging preliminary results: all eight participants maintained normal ammonia levels, glutamine fell by roughly 15% to 25%, and no serious adverse events or hyperammonemia events were reported.

Most adverse events were mild to moderate, though two grade-three cases of asymptomatic transaminitis occurred.

Arcturus introduced LUNAR 2.0, which produced approximately 38- to 40-fold higher protein expression than earlier formulations in non-human primate studies.

The platform is being incorporated into ARCT-2601, which could enable lower doses, shorter infusions and potentially pediatric-focused development.

The company plans to add ARCT-2601 to the ongoing study by year-end, pending required data, and is targeting a Phase II/III pediatric trial in the second half of 2027.

Arcturus also highlighted preclinical mRNA programs for phenylketonuria and gout and announced plans to acquire computational immunology company myNEO.

The company’s open-label U.S. Phase II study enrolled eight adolescents and adults with confirmed OTC deficiency, with four participants each receiving 0.3 mg/kg or 0.5 mg/kg of ARCT-810.

Participants received five intravenous infusions administered every two weeks over 10 weeks, followed by a four-week observation period.

Cohen said ARCT-810 was generally safe and well tolerated across repeated dosing.

The study reported no serious adverse events, no adverse events of special interest and no hyperammonemia events.

All participants experienced at least one treatment-emergent adverse event, though most were mild to moderate.

The most common events were headache, transaminitis and infusion-related reactions, each reported in two of eight participants.

Two grade-three events, both asymptomatic transaminitis, resolved without intervention after study treatment stopped, according to Cohen.

One patient discontinued after an intravenous infiltration and injection-site reaction that the company characterized as a procedural event rather than a systemic drug effect.

Across both dose cohorts, mean first-morning fasting ammonia levels were generally similar to or lower than baseline, according to the presentation.

Arcturus said all participants achieved and maintained normal plasma ammonia levels after dosing.

Glutamine, another biomarker used to assess nitrogen burden and urea-cycle activity, declined in all participants.

Mean glutamine levels fell by roughly 15% to 25% from pre-treatment levels, the company said, before returning toward baseline during the one-month period after treatment discontinuation.

The company also reported that participants generally consumed more protein during treatment than at baseline, despite instructions to maintain stable protein intake.

Cohen said this observation, together with stable or lower ammonia and lower glutamine levels, supported the view that ARCT-810 increased urea-cycle activity and prote...