Arcturus Therapeutics (ARCT) Status Update summary

Clinical data highlights

• ARCT-810 demonstrated significant and consistent reductions in plasma glutamine, normalizing levels in both European and U.S. phase II studies, with effects persisting for weeks post-dosing.

• Statistically significant increases in ureogenesis (RUF) were observed, with two patients reaching levels typical of asymptomatic individuals, indicating improved urea cycle function.

• Ammonia levels remained stable and within normal range throughout treatment and follow-up, supporting the positive biomarker findings.

• Safety profile was favorable, with no serious infusion-related reactions and only isolated, asymptomatic transaminase elevations, consistent with disease pathology.

• Subjective improvements in patient well-being were reported, especially among those with more severe disease backgrounds.

Scientific and clinical rationale

• Glutamine is a sensitive and stable biomarker for monitoring metabolic control in OTC deficiency, rising before ammonia and predicting crisis risk.

• The 15N-ureagenesis assay provides a direct, reliable measure of urea cycle function and distinguishes between symptomatic and asymptomatic patients.

• Improvements in both glutamine and ureagenesis reflect restoration of urea cycle activity, supporting the mechanism of ARCT-810 as a functional protein replacement.

• Early intervention with mRNA therapy could delay or prevent the need for liver transplantation, especially in severe pediatric cases.

• mRNA therapy offers advantages over current treatments by addressing the underlying enzyme deficiency rather than just managing symptoms.

Regulatory and development updates

• ARCT-810 has received multiple regulatory designations, including Orphan Drug, Fast Track, and Rare Pediatric Disease, facilitating accelerated development.

• Ongoing phase II studies are completing enrollment at 0.3 and 0.5 mg/kg doses, with plans to discuss a multi-biomarker-driven pivotal trial design with the FDA.

• The protocol is flexible to allow expansion into younger patient populations, pending regulatory discussions.

• No baseline differences dictated dose group assignment; enrollment is ongoing in both dose cohorts.

• Further guidance on next steps and timing for Phase 2 completion and Phase 3 initiation will be provided in upcoming quarterly communications.