Arcturus Therapeutics (ARCT) Status update summary

Key clinical results and program updates

• ARCT-810 demonstrated safety and tolerability in phase II, with no serious adverse events and normalization of ammonia and reduction of glutamine in all participants, even as protein intake increased.

• Biomarker changes support increased urea cycle activity, suggesting restored OTC enzyme expression and improved metabolic control.

• Increased protein tolerance was observed, indicating potential for improved quality of life.

• Regulatory feedback elevated ammonia as a key endpoint, especially in pediatrics, with glutamine reduction also important in adults.

• ARCT-2601, using the LUNAR 2.0 platform, will be integrated into the ongoing phase II study, with FDA agreement to leverage existing data and accelerate development.

LUNAR 2.0 platform and pipeline expansion

• LUNAR 2.0 enables over 30-fold higher protein expression in primates, allowing for lower, less frequent dosing and shorter infusion times.

• Preclinical data show ARCT-2601 provides durable protection in disease models at lower doses, with no new safety signals and faster tissue clearance.

• The platform's potency is expected to enable monthly or less frequent dosing, with the goal of single-syringe, rapid infusions.

• AI-enabled mRNA design, enhanced by the acquisition of myNEO, will accelerate candidate selection and immunological screening for new indications.

• Pipeline expansion targets PKU and gout, leveraging LUNAR 2.0 and computational design to address additional liver-based metabolic diseases.

Regulatory and clinical development strategy

• FDA supports integrating ARCT-2601 into the current phase II study, with a small cohort to assess safety, PK, and biomarkers before proceeding to pivotal trials.

• Endpoints for future studies will focus on durable ammonia and glutamine suppression, metabolic stability, and improved protein tolerance.

• The pivotal pediatric study is planned for the second half of 2027, with the potential for a single study to support approval, following recent regulatory precedents.

• ARCT-2601 is expected to replace ARCT-810, offering improved convenience and efficacy without resetting the clinical development timeline.

• Data from the integrated ARCT-2601 cohort are anticipated in the first half of next year, informing dosing frequency and protocol design.