Arcturus Therapeutics Holdings Inc. · NASDAQ:ARCT
Arcturus Therapeutics — Corporate Update (September 2026)
31 slides from Arcturus Therapeutics's corporate update, Sep 23, 2026
Slide 1: Interim OTC Deficiency Phase 2 Results and LUNAR 2.0 Platform
therapeutics PRESENTATION Interim OTC Deficiency Phase 2 Results and LUNAR 2.0™ Next-Generation mRNA Delivery Platform September 23, 2026
Slide 2: Forward Looking Statements
Forward Looking Statements ARCTURUS = This presentation contains forward-looking statements. These statements relate to future events and In some cases, you can identify forward-looking statements by terms such involve known and unknown risks, uncertainties and other factors which may cause our actu
Slide 3: Today's Key Messages
Today's Key Messages ARCTURUS @ ARCT-810 Clinical Evidence + Generally safe and well-tolerated across repeated dosing * ALL subjects maintained normal ammonia levels & exhibited reduction in glutamine despite generally increased protein intake C3) ARCT-2601 Utilizes LUNAR 2.0™ + Preliminary non-GLP
Slide 4: ARCT-810 (LUNAR-OTC) mRNA Therapeutic Candidate for OTC Deficiency
— as OO ——— ARCT-810 (LUNAR-OTC) mRNA Therapeutic Candidate for Ornithine Transcarbamylase (OTC) Deficiency AX AgcTuRus
Slide 5: Ornithine Transcarbamylase (OTC) Deficiency
The most common Fes urea cycle disorder ARCTURUS” Ornithine Transcarbamylase (OTC) Deficiency r LUNAR-OTC Aims to Restore Enzyme Function © 10,000 prevalence in U.S./Europe © The urea cycle converts neurotoxic ammonia to water-soluble urea that can be excreted in urine © Deficiency in OTC causes ele
Slide 6: ARCT-810 Clinical Trials
ARCT-810 Clinical Trials ARCTURUS’ © Phase 1 —Healthy Volunteers + Safe and generally well-tolerated in 24 adults © Phase 1b — Single, Ascending Dose Study in OTC Deficiency Adults + 0.2-0.5 mgikg in 16 adults + Safe and generally well-tolerated © Phase 2- Single Dose, Multiple Administrations, Plac
Slide 7: U.S. Phase 2 Study Overview
U.S. Phase 2 Study Overview Ac ancturus (ON * Open-label, dose-ascending, multiple dose administration study * 0.3 mg/kg and 0.5 mg/kg, 5 IV infusions every 2 weeks with 4-week follow-up ¢ Enrolled adolescents and adults with confirmed OTC deficiency ¢ Participants directed to maintain baseline diet
Slide 8: U.S. Phase 2 Summary of Safety and Tolerability
U.S. Phase 2 Summary of Safety and Tolerability Ac acrunus — « No serious adverse events ¢ Most treatment emergent adverse events eee A 4 4 (TEAEs) in both 0.3 mg/kg and 0.5 mg/kg Uses id us dosing cohorts were mild to moderate in Refeclpants wit releted TEBE," - 4 severity — Most common TEAEs were
Slide 9: U.S. Phase 2 Efficacy Measures
U.S. Phase 2 Efficacy Measures Ac arctuus Participant Baseline Characteristics Expansion of prior Phase 2 s ‘One participant discontinued after a single dose of AR kK Clinically-relevant biomarkers of urea cycle — plasma ammonia and glutamine OTC enzyme activity through urea cycle byproduct enrichme
Slide 10: Changes in Clinically Relevant Biomarkers: Ammonia
Changes in Clinically Relevant Biomarkers: Ammonia —_( arciuaus Objective: Stable first morning fasting plasma ammonia levels with ARCT-810 Results * 2/7 (29%) participants had elevated ammonia at baseline + At0.3 mg/kg and 0.5 mg/kg dose levels, mean ammonia levels were similar or lower than baseli
Slide 11: Changes in Clinically Relevant Biomarkers: Glutamine
Changes in Clinically Relevant Biomarkers: Glutamine (ws Objective: Reduction in plasma glutamine levels following ARCT-810 Results + 7/T (100%) participants had elevated glutamine at baseline + At0.3 mg/kg and 0.5 mg/kg dose levels, mean glutamine levels were lower than baseline — Follow-up Period
Slide 12: Ammonia & Glutamine ARCT-810 Dose Comparison
Ammonia & Glutamine ARCT-810 Dose Comparison Acarcturus Ammonia Glutamine gS 120 ‘Treatment Period — Follow-up Period — 1300: Treatment Period — Follow-up Period — = P -@ 0.3 mgikg ‘ooo © 0.3 mgikg E 108 D OSmgkg — F 4499, DO 0.5 mgikg P_ 80. z 25 1000 32 2 Eg oo 2 900 ad = soo. wo i g 3 10. 3 = 20:
Slide 13: Biomarker Reductions Observed Despite Increased Protein Intake
ARCTURUS Biomarker Reductions Observed Despite Increased Protein Intake x Objective: Stable protein intake (within 25% of baseline) Results + At0.3 mg/kg and 0.5 mg/kg dose levels, mean protein intake generally increased above baseline + 5/7 (71%) participants had 21 timepoint that exceeded 25% base
Slide 14: U.S. Phase 2 Study Summary
U.S. Phase 2 Study Summary Ac arcturus (eee ¢ Multiple doses of ARCT-810 at both dose levels was generally safe and well- tolerated — Similar safety profiles between 0.3 mg/kg and 0.5 mg/kg ¢ Evidence suggesting ARCT-810 increases urea cycle function — As detected by clinically-relevant biomarkers o
Slide 15: Key Opinion Leader, Dr. Marshall Summar
Key Opinion Leader, Dr. Marshall Summar K © 2026 Arcturus Therapeutics, Inc. Marshall Summar, M.D., Former founding member and Executive Committee member of the NIH UCD Consortium, a recognized expert in rare diseases and OTC deficiency, will participate in the presentation. Previously Chief of the
Slide 16: KOL Perspective: ARCT-810 Phase 2 Data
KOL Perspective: ARCT-810 Phase 2 Data Ac acrunus (CN + The glutamine result is what persuades a metabolic physician: elevated in every participant despite mostly normal ammonias, down in every participant on drug, and back toward baseline once dosing stopped. That is drug effect, not variability. *
Slide 17: Advances in LUNAR Delivery Platform: LUNAR 2.0
therapeutics ADVANCES IN LUNAR DELIVERY PLATFORM LUNAR 2.0™
Slide 18: How IV mRNA-LNP Medicines Work
How IV mRNA-LNP Medicines Work Acareturus ApoE carries the particle to the hepatocyte — but escaping the endosome is where the pathway is lost RATE-LIMITING STEP ( — — Four-lipid particle ApoE corona forms Hepatocyte uptake Endosomal escape An ionizable lipid, DSPC, cholesterol After IV dosing the P
Slide 19: Next Generation LNP: 40-Fold Higher Expression
Next Generation LNP: 40-Fold Higher Expression Acareturus — = 60 rire Relative Fold Enhancement in Human EPO Protein Expression — <5 50 ry oa Fold Enhancement 2 pod Over LUNAR 1.0 8 oe 40-| 0.3 maikg 5s ALC-315 2.2 &5 30 ° = 20 ATX-126 (Lipid in KOSTAIVE®) 14 as a 3 10 ATX-2 (LUNAR 1.0) 1.0 gd cmp a
Slide 20: ARCT-2601 Highly Effective in OTC-Deficient Model
ARCT-2601 Highly Effective in OTC-Deficient Model ae aaa aes ARCTURUS Survival in OTC-deficient mice on a high-protein diet srayentier — 100 100- 30 g : 80 _ o.3me/ke __ HUNAR; OTC: mg/kg, 11-20 z is — LUNAR 2.0-hOTC 0.1mg/kg = <= 50 = LUNAR-OTC 0.3 mg/kg, n=10 ® 40. _ Fw > High Protein Diet (Contro
Slide 21: ARCT-2601: 38-Fold Higher hOTC Expression in NHP
ARCT-2601: 38-Fold Higher hOTC Expression in NHP A jeciysus compared to ATX-95 (Lipid in ARC T-810) Herageetias — 60: fb Relative Fold Enhancement in Human OTC Protein Expression 50: ~38X 5 e wo Lipid Fold Enhancement 3 240 .3 maikg P Over ATX-95 ES 30 ALC-315 5.3 3 of 5 2 20 SM-102 2.5 = mn ATX-95
Slide 22: ARCT-2601 (LUNAR-OTC 2.0) Preliminary Safety Data
ARCT-2601 (LUNAR-OTC 2.0) Preliminary Safety Data. secrurus Three non-GLP preclinical studies, head-to-head against ARCT-810: no new findings wy RODENT SAFETY STUDY - NON-GLP No new findings versus ARCT-810 Ld e * 6 a NHP TOLERABILITY STUDY - NON-GLP eS <_ * No new findings versus ARCT-810 bad bad ®
Slide 23: ARCT-2601: FDA Feedback and Regulatory Plan
ARCT-2601: FDA Feedback and Regulatory Plan Acarcturus FDA Type C Meeting on ARCT-2601 Development: Conducted June 2026 + FDA agreed to leverage platform CMC, non-clinical and clinical data to accelerate the development + FDA agreed to include ARCT-2601 as an arm in the current ongoing ARCT-810 Phas
Slide 24: LUNAR 2.0 Opens Door to Reduced Infusion Time
LUNAR 2.0™ — Opens Door to Reduced Infusion Time ( arciurus Better LNP potency x higher concentration — collapses dose volume — collapses clinic time “wv The Challenge: mRNA-LNP therapeutics targeting the liver must be infused IV PROPOSED — NEAR TERM FUTURE — SYRINGE PUMP <5 Min infusion time { =—_—
Slide 25: Engineering mRNA Therapeutics with AI
Engineering mRNA Therapeutics with Al k ARCTURUS Arcturus’ differentiated computational engine improves design quality, accelerates development, and de-risks pipeline There genther — @ wuat we acquire @ wnat arcturus GAINS © WHerE IT SHOWS UP FIRST Published algorithms, a live platform, Better candi
Slide 26: Expansion of Liver Disease Franchise: PKU
ARCTURUS” Expansion of Liver Disease Franchise: PKU k LUNAR-PKU: Arcturus’s strategy to treat phenylketonuria (PKU) @ DISEASE BACKGROUND ® THERAPEUTIC APPROACH e DELIVERY PLATFORM PKU is a rare inborn error IV-administered MRNA LUNAR 2.0™ LNP delivers of metabolism restores PAH activity mRNA to the
Slide 27: Why PKU Now? Two-Stage Platform Optimization Story
Why PKU Now? Two-Stage Platform Optimization Story Ac ancturus From 24 hours — 6-7 days durability through mRNA + LNP engineering — PAH mRNA-LNPs Optimized PAH Expression 1 mg/kg i.v. in PKU Mice in NHP Liver 4 " 24 ro. r -m- Published PAH Sequence Zio ae -@ ARCT mRNA Gen 1 © pes = . -@ ARCT mRNA Ge
Slide 28: Gout is a Disease Caused by a Missing Enzyme
Gout is a Disease Caused by a Missing Enzyme Acareturus Humans lost the gene to make uricase ~15 million years ago Mammals: uricase ON Humans: gene switched OFF = Arcturus: mRNA turns it back ON Uric acid is dissolved and Uric acid builds up > crystals The liver makes uricase, restores excreted in j
Slide 29: Key Takeaways
SUNN vee) Key Takeaways Acarcrurus @ potency @ arct-2601 (OTC Deficiency) > 30X Improvement Phase 2: YE 2026 higher liver protein expression than LUNAR 1.0 in NHP Highly potent in NHPs, no new preclinical safety signals: FDA-aligned to integrate ARCT-2601 into present ARCT-810 Phase 2 study @ Future
Slide 30: KOL Perspective: The LUNAR 2.0 Platform and ARCT-2601
KOL Perspective: The LUNAR 2.0™ Platform and ARCT-2601 KX ARCTURUS (N + Agreater than 30-fold potency gain is a change in kind, not degree: it moves the objective from supporting the urea cycle to correcting it, and it buys headroom on both dose and interval. * Once-monthly dosing is the variable th
Slide 31: Q&A
Q&A AX © 2026 Arcturus Therapeutics, Inc. 31
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