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

ARCT-810 generally safe and well tolerated, demonstrating encouraging activity across key urea cycle biomarkers in ongoing Phase 2 study

LUNAR 2.0™ produces greater than 30-fold higher protein expression in multiple NHP studies – unlocks new therapeutic opportunities

ARCT-2601, an OTC deficiency therapeutic candidate utilizing LUNAR 2.0™, to be integrated by YE 2026 into ongoing Phase 2 study as advised by the FDA

Arcturus to acquire myNEO, an AI discovery company, to improve mRNA design quality, accelerate innovation, and enhance target identification capability

Presentation at 4:30 p.m. ET today

SAN DIEGO--( BUSINESS WIRE )-- Arcturus Therapeutics Holdings Inc. (the “Company,” “Arcturus,” Nasdaq: ARCT), a messenger RNA medicines company focused on the development of liver and respiratory therapeutics, today announced encouraging interim Phase 2 results from ARCT-810 in ornithine transcarbamylase (OTC) deficiency and introduced LUNAR 2.0™, the Company’s next-generation mRNA delivery platform, and additional liver pipeline programs.

“The ARCT-810 Phase 2 interim results validate Arcturus’ mRNA liver therapeutics platform and the introduction of LUNAR 2.0™ marks the beginning of a new and exciting chapter for Arcturus,” said Joseph Payne, President and CEO of Arcturus. “We are very pleased that ARCT-2601, utilizing LUNAR 2.0™, is positioned to be efficiently integrated into our ongoing OTC deficiency Phase 2 study later this year.”

“The greater than 30-fold improvement demonstrated by the next-generation platform is exciting and has the potential to translate into a more effective and more convenient therapy,” said Dr. Marshall Summar, former founding member and Executive Committee member of the NIH Urea Cycle Disorders Consortium, a recognized expert in rare diseases and OTC deficiency. “I believe ARCT-2601 has the potential to become a new standard of care for OTCD patients, particularly in severe onset, if approved, and I am excited to see the potential impact of Arcturus’ next-generation mRNA delivery platform across other programs.”

“Validating clinical data, a compellingly differentiated LUNAR 2.0™ mRNA delivery platform, and a proprietary AI computational engine, support the continued advancement of Arcturus’ growing mRNA therapeutics pipeline, including ARCT-2601, and the initiation of new programs, such as Phenylketonuria (PKU) and Gout,” said Dr. Pad Chivukula, Chief Scientific Officer of Arcturus.

ARCT-810 Phase 2 Interim Results

Generally safe and well tolerated

Reduced and/or maintained first morning fasting ammonia within the normal range, including during increased protein intake by participants

Reduced glutamine, achieving normal range in some participants

In the Phase 2 study to date, ARCT-810 was generally safe and well tolerated, reduced and/or maintained first morning fasting ammonia within the normal range, including during increases in protein intake by participants; reduced glutamine, with participants at the 0.5 mg/kg dose level achieving mean glutamine values within the normal range during treatment. Weight gain was observed in all participants.

LUNAR 2.0™

LUNAR 2.0™ is the Company’s next-generation mRNA delivery platform that incorporates improved lipids and an enhanced formulation process specific to these lipids. In non-human primates (NHPs), LUNAR 2.0™ demonstrated a 40-fold improvement compared to LUNAR 1.0 in expressing human erythropoietin (hEPO). In a separate NHP study, LUNAR 2.0™ exhibited 38-fold more potency than ATX-95, the key lipid in ARCT-810, in expressing human ornithine transcarbamylase (hOTC). LUNAR 2.0™ unlocks new therapeutic opportunities previously inaccessible, including Phenylketonuria (PKU) and Gout.

ARCT-2601 Utilizes LUNAR 2.0™

ARCT-2601 is Arcturus’ next-generation investigational mRNA therapeutic for OTCD. To date, ARCT-2601 has demonstrated a similar safety profile to ARCT-810 in non-GMP pre-clinical studies. The U.S. Food and Drug Administration provided favorable feedback and regulatory-path clarity for ARCT-2601, following a Type C meeting in June this year. Based on the data and the feedback from the FDA, Arcturus plans to initiate dosing of ARCT-2601 near year-end in participants with OTCD, ages 12 years and older, under an amended Phase 2 protocol that integrates ARCT-2601 into the current ARCT-810 Phase 2 study. Based on data in non-human primates, ARCT-2601 is anticipated to provide benefits of lower and/or less frequent dosing.

Arcturus to Acquire myNEO

Arcturus has entered into a definitive agreement to acquire myNEO, subject to customary closing conditions. The transaction is expected to close in October. Arcturus has been working closely with myNEO since 2024. The acquisition brings a differentiated computational engine, supported by proprietary intellectual property, intended to fortify Arcturus’ AI infrastructure by improving mRNA design quality and enhancing target identification capabilities.

Presentation: Today at 4:30 p.m. ET

Domestic: 1-800-347-6865

International: 1-203-518-9757

Conference ID: Arcturus

Webcast: Link

About Ornithine Transcarbamylase Deficiency