Arcturus Therapeutics Holdings Inc. · NASDAQ:ARCT
Arcturus Therapeutics — ICIEM 2025
11 slides from Arcturus Therapeutics's conference presentation, September 2025
Slide 1: Restoration of Urea Cycle Function in OTC Deficiency: ARCT-810 mRNA Therapy
RESTORATION OF UREA CYCLE FUNCTION IN OTC DEFICIENCY: ARCT-810 mRNA THERAPY ACROSS TWO CLINICAL STUDIES BENJAMIN GREENER’, RACHAEL BATABYAL?, JUERGEN FROEHLICH', CONSTANCE CROWLEY’, DAVID GELLER’, BROCK PITTENGER’, LAURA RECK CECHINEL?, LAURA ALLAN?, KERRI GALLAGHER, PAD CHIVUKULA', TAMANNA ROSHAN L
Slide 2: Disclosures and Forward Looking Statements
Disclosures and Forward Looking Statements RB, TRL and MS are investigators in Arcturus-sponsored studies and RB, LRC, LA, KG, and TRL have received study funding from Arcturus. The ARCT-810 studies were funded by Arcturus Therapeutics and BG, JH, CC, DG, BP, and PC are employees. This presentation
Slide 3: Background
BACKGROUND • ARCT-810 is an investigational mRNA treatment for ornithine transcarbamylase deficiency (OTCD) formulated with a proprietary lipid nanoparticle (LNP), including an ionizable lipid to target mRNA to the liver. The mRNA is then translated into functional OTC enzyme. • Single doses of ARCT
Slide 4: Methods: ARCT-810-03 Phase 2 Study (EU)
METHODS ARCT-810-03 Phase 2 Study (EU) ARCT-810-03 (EU) is a double-blind, placebo-controlled Phase 2 study to assess safety and PK of repeated doses of ARCT-810 in mild to moderate severity OTCD patients 12 years and older. • 8 patients were randomized 3:1 to receive up to 6 IV infusions administer
Slide 5: Methods: ARCT-810-04 Phase 2 Study (US)
METHODS ARCT-810-04 Phase 2 Study (US) ARCT-810-04 (US) is an ongoing Phase 2a, open-label, multiple ascending repeat dose study to assess safety and pharmacodynamics of ARCT-810 in moderate to severe OTCD patients 12 years and older. • Enrolling at least 9 patients across 3 dose cohorts (0.3 mg/kg,
Slide 6: Methods: Statistical Analysis of Glutamine
METHODS Statistical Analysis of Glutamine Exploratory linear mixed-effects modeling (LMM) and chi-square analysis were performed on individual and pooled studies. • For each patient, we performed a simple linear regression of glutamine (μmol/L) vs Visit Day • Data were cut at 21 days following last
Slide 7: Results: Linear Regression
RESULTS Linear regression • Across both studies, mean glutamine levels declined significantly over time following initiation of mRNA therapy and increases were observed following drug discontinuation in ARCT-810-03. • A negative slope in Figure 1 indicates a downward trend in individual participant
Slide 8: Results: Linear Mixed-Effects Modeling of Glutamine
RESULTS Linear Mixed-Effects Modeling of Glutamine Table 1: LMM Analysis Study n # Observations Fixed Effect Slope One-Tailed p- (µmol/L/day) value (for slope < 0) ARCT-810-03 5 31 -1.82 0.016 ARCT-810-04 3 18 -4.38 0.004 Pooled 8 49 -2.50 0.0055 • LMM analysis (Table 1) across all treated patients
Slide 9: Results: Chi-square test of slope directions
RESULTS Chi-square test of slope directions Table 2: Chi-square test Study Observed Expected Chi-Square One-Tailed (Decreasing, Non- (Decreasing, Non- Statistic p-value Decreasing) Decreasing) ARCT-810-03 (4,1) (2.5, 2.5) 1.8 0.090 ARCT-810-04 (3,0) (1.5, 1.5) 3.0 0.042 Pooled (7,1) (4, 4) 4.5 0.017
Slide 10: Conclusions
Conclusions • Treatment with the mRNA therapy resulted in a mean reduction from baseline in glutamine over the treatment period across two independent Phase 2 studies. • Exploratory (post hoc) analyses indicate that the observed decreasing trend in glutamine is not random. • Based on inspection of a
Slide 11: Acknowledgements
ACKNOWLEDGEMENTS We thank the investigators and study staff who conducted ARCT-810-03 and ARCT-810-04 and the participants who have enrolled in these studies. © 2025 Arcturus Therapeutics, Inc. 11