Arcturus Therapeutics Holdings Inc. · NASDAQ:ARCT
Arcturus Therapeutics — Investor Presentation (February 2022)
48 slides from Arcturus Therapeutics's investor presentation, Feb 17, 2022
Slide 1: Next Generation RNA Medicines
Next Generation RNA Medicines February 2022
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements. These statements relate to future events and involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future p
Slide 3: Arcturus Therapeutics
Arcturus Therapeutics Clinical-Stage mRNA Vaccines and Medicines Company Publicly Traded (Nasdaq: ARCT) Therapeutic Candidates HQ: San Diego, CA LUNAR-COV19 COVID-19 Vaccine Founded 2013 (Primary and Booster) 160+ Employees LUNAR-OTC Omithine Transcarbamylase Deficiency LUNAR-CF Cystic Fibrosis Addi
Slide 4: Proprietary mRNA Technologies Driving Therapeutic Programs
A mecrurus c Proprietary mRNA Technologies Driving Therapeutic Programs Broad intellectual property portfolio mRNA Chemistry ~ mRNA & STARR™ mRNA Program Indication LUNAR-COV19 COVID-19 Primary and Booster Vaccine mRNA Design & Modifications mRNA Manufacturing Process LUNAR-FLU Flu Vaccine oul LUNAR
Slide 5: Pipeline of mRNA Therapeutic Candidates
ARCTURUS’ Pipeline of mRNA Therapeutic Candidates Multiple mRNA therapeutic and vaccine programs in clinical development Route of Anticipated Franchise Candidate Indication Prevalence Aarinetaton Milestones EUA Filing Commenced LUNAR-COV19 COvID-19 Global Intramuscular —_MYocytes & Phase Dec 2021 by
Slide 6: Licensed Platforms
A mecrurus c Licensed Platforms Program Partner Indication Stage LUNAR-GSDIII ultragenyx Glycogen Storage Disease Type III Phase 1/2 * LUNAR-RARE ultra genyx Undisclosed Rare Disease Preclinical LUNAR-HBV Gohmenafohon Hepatitis B Virus (HBV) Preclinical LUNAR-NASH Nonalcoholic Steatohepatitis (NASH)
Slide 7: LUNAR Delivery Technology
LUNAR® Delivery Technology LUNAR® interacts with LUNAR® internalized cell membrane inside endosome mRNA translated into mRNA release protein of interest
Slide 8: STARR mRNA Expression Superior to Conventional mRNA
AC arcrunus c Self-Transcribing and Replicating mRNA (STARR™) delivered with LUNAR® provides increased and longer lasting expression in mouse models STARR™ mRNA Expression Superior to Conventional MRNA STARR™ Technology Protein Expression Over 7 days 30-Fold Higher Protein Expression STARR™ mRNA vs.
Slide 9: LUNAR-COV19
Slide 10: Arcturus COVID-19 Vaccine Candidates have a Differentiated Profile
Arcturus COVID-19 Vaccine Candidates have a Differentiated Profile Ac arcturus an mRNA Vaccine - No Adjuvants, Self-Amplifying (STARR™) mRNA. Clinical Data Demonstrate No Viral Vector Used, Readily and LUNAR® Non-viral Delivery Humoral and Cellular Updatable as New Variants Arise Technology Immunoge
Slide 11: Global Manufacturing Footprint
. . ARCTURUS’ Global Manufacturing Footprint. 2 I Germany Recipharm Catalent or stockpiling purposes "1
Slide 12: LUNAR-COV19 ARCT-154, ARCT-165
Slide 13: Preclinical Data: ARCT-154 Neutralizing Antibody Titers in Non-Human Primates
A mecrurus c Preclinical Data: ARCT-154 — Neutralizing Antibody Titers in Non-Human Primates a ae t ; iB = N S104 3 z : 1024 is _ | Limit of s = Detection 8 & 2 10 LL oO £ s < Non-Human primate (NHP) data one month after second dose (7.5 mcg/dose); NHP serum was analyzed using a non-replicating vesi
Slide 14: Clinical Trial Update: ARCT-154 and ARCT-165
Clinical Trial Update: ARCT-154 and ARCT-165 ARCT-154 - Phase 1/2/3 Clinical Trial in Vietnam + Phases 1/2/3 sponsored & funded by Vinbiotech + Randomized, observer-blind, placebo-controlled design + Enrollment completed with over 19,000 participants ARCTURUS’ 100, 300, 600 3:1 ARCT-154 : Placebo Sa
Slide 15: Phase 1/2 Booster Clinical Trial Data — Neutralizing Antibodies
Phase 1/2 Booster Clinical Trial Data — Neutralizing Antibodies ARCTURUS’ Against D614G in Validated Pseudovirus Microneutralization Assay ARCT-154 ARCT-165 oo 28x as 24x 3 i oa i 10°4 10° 1024 § 104 Pseudovirus Neutralization (AU/m|) Pseudovirus Neutralization (AU/ml) 10" ™—T 10" T—1—T Days Data fr
Slide 16: Booster Data — Broad Neutralization Against Variants of Concern (ARCT-154)
Phase 1/2 Booster Clinical Trial Data — Broad Neutralization Activity Against Variants of Concern upon Boosting with ARCT-154 (5 mcg) in Exploratory Surrogate Virus Neutralization Assay 24 Beta Delta 10° 10° Pe z _~ vioay | ad tt z 2 ] [ 3 & f wy is 2 "i § Lf wy 1A 2 S ,A3 3 oe § r 8 H |i b 2 + cs .
Slide 17: Booster Data — Broad Neutralization Against Variants of Concern (ARCT-165)
A mecrurus c Booster Clinical Trial Data — Broad Neutralization Activity Against Variants of Concern upon Boosting with ARCT-165 (5 mcg) in Exploratory Surrogate Virus Neutralization Assay 10°5 woe +22 — 222+ - ae 10°5 woo 10-4 14 4014 Surrogate Neutralization (AU/mL) Surrogate Neutralization (AU/mL
Slide 18: Booster Data — Neutralizing Antibodies Against Omicron
Phase 1/2 Booster Clinical Trial Data — Neutralizing Antibodies ARCTURUS Against Omicron in Exploratory Microneutralization Assay ARCT-154 ARCT-165 s | pas S ics wo wo a a = 4 = 4 5 5 0 aa £ £ 3 104 2 10° Zz 4 Zz o | ry 2 2 s s 3 8 2 2 3 10 B 10 n q o a 3 a co} Loa to! 401 1 2 4 + @ 1 2 Days Days Da
Slide 19: LUNAR-COV19 ARCT-021
Slide 20: STARR Preclinical Data Using Ancestral/Wuhan Strain
STARR™ Preclinical Data Using Ancestral/Wuhan Strain ARCTURUS — Robust Immune Response in Mouse Models Humoral immunity i Cellular immunity STARR™ induces more robust titers compared to conventional MRNA 7 Days Post Single Dose CD8* IFN-y a Single Dose poe ‘Single Dose. a ‘Single Dose % ~ LE] ISS o2
Slide 21: ARCT-021 Activity Against Ancestral/Wuhan Strain in Challenge Models
AC arcrunus c ARCT-021 Activity Against Ancestral/Wuhan Strain in Challenge Models Mouse model (transgenic human ACE2) 1004 100% = © & Eo a = ao 8 + pas 5 LUNaRcovis 2meg 2 . LUNAR-COV19 10 meg o 0 2 4 6 8 1 12 14 Days post infection ARCT-021 significantly effective in a virus challenge study in the
Slide 22: ARCT-021 Clinical Trials
ARCT-021 Clinical Trials Phase 1/2 Clinical Trial + Completed dosing all subjects (n=106), including older adults + High seroconversion rates for IgG binding antibodies, and Th1 dominant CD4+ immune responses, neutralizing antibodies (PRNT50) Geometric Mean Titer (GMT) levels in the range of titers
Slide 23: LUNAR-OTC ARCT-810
Slide 24: OTC Deficiency: ARCT-810 Market Opportunity
ARCTURUS’ Ornithine Transcarbamylase (OTC) Deficiency: ARCT-810 Market Opportunity (6) The most common urea cycle disorder The urea cycle converts neurotoxic ammonia to water-soluble urea that can be excretedin urine Deficiency in OTC causes elevated blood ammonia, which can lead to neurological dam
Slide 25: LUNAR-OTC Periportal Expression in the Liver of OTC Protein
ARCTURUS LUNAR-OTC batts Exceeds target of 10% enzyme replacement at low, medium, and high doses in OTC-deficient mouse model Periportal Expression in the Liver of OTC Protein + OTCD impacts ureagenesis 440 (ammonia detoxification) 400 90. 80. 70: 60. 50: 40 30: 20: 10+-- + The main site of ureagene
Slide 26: ARCT-810 Clinical Update
ARCT-810 Clinical Update Acarcrurus Phase 1 Clinical Trial in Health Volunteers Completed + Single doses of ARCT-810 (OTC mRNA) up to 0.4 mg/kg found to be generally safe and well tolerated + All doses tested were in the expected therapeutic range Phase 1b Clinical Trial in OTC-Deficiency Adults Ong
Slide 27: LUNAR-CF ARCT-032
Slide 28: Cystic Fibrosis: ARCT-032 Market Opportunity
Cystic Fibrosis: ARCT-032 Market Opportunity Cystic Fibrosis 85,000-100,000 worldwide prevalence Caused by genetic mutations in the CFTR gene, resulting in aberrant flux of ions in and out of cells, causing thick mucus buildup in lung airways Chronic airway obstruction leads to infection and inflamm
Slide 29: Aerosolized LUNAR Delivery Platform for Lung
Aerosolized LUNAR® Delivery Platform for Lung Expressionis preserved after Aerosolized LUNAR® particles are in the respirable size range aerosolization of LUNAR®-mRNA Formulation Lots Pre-Nebulization 1 2 3 4 5 Breathable Range (microns) Accuns fi i ARCT-032is biologically active in vivo (mouse) LUN
Slide 30: LUNAR-mRNA Delivery to Airway Epithelium
LUNAR®-mRNA Delivery to Airways Epi Transduction demonstrated by brown and green staining helium eed 4 * f poe Br 4 2) Triereann adinsiene nrodents species
Slide 31: Functional Restoration of Chloride Current with ARCT-032
Functional Restoration of Chloride Current with ARCT-032 Ac errs E CFTR-deficient (G551D) Ferret Bronchial Epithelial Cells CFTR-mediated CI Currents — LUNAR®-RhCFTR 5 meg _ LUNAR®-RhCFTR 50 meg —| LUNAR®-RhCFTR 25 meg — LUNAR®-RhCFTR 100 meg — LUNAR®-dTomato 100meg = — VX-770 CRTL “<~ LUNAR®-RhCFTR
Slide 32: Restoration of CFTR Expression and Function in Human Bronchial Epithelial Cells
Restoration of CFTR Expression and Function in Human bronchial Acarcturus epithelial cells with F508del mutation Increased C/B band ratio in F508del’/* High levels of mature CFTR protein were HBE cells transduced with ARCT-032 generated in F508del”’* HBE cells transduced with ARCT-032 ARCT-032 resto
Slide 33: Moving Forward
Moving Forward
Slide 34: Anticipated Near-Term Milestones
AC ascrunus c Anticipated Near-Term Milestones ARCT-154(COVID vaccine candidate targeting VOCs) EUA Filing in Vietnam Completion of Submission Q1 2022 ARCT-154(COVID vaccine candidate targeting VOCs) Clarity on Regulatory Path for Booster Indication Q1 2022 ARCT-021 (COVID vaccine candidate) Phase 3
Slide 35: Team Arcturus
Team Arcturus Management Team &e*e@eeeark Joseph E. Payne, MSc Pad Chivukula, Ph.D. Andrew Sassine, MBA Lance Kurata, J.D. Dushyant Varshney, Ph.D. Kelly Lindert, M.D Steve Hughes, M.D President & CEO CSO & COO CFO Chief Legal Officer cTo CDO, Vaccines _ Strategic Clinical Advisor merck Nitto Fideli
Slide 36: Team Arcturus: Scientific Advisory Board
ARCTURUS” Team Arcturus Scientific Advisory Board ©3392 2D § Jeff Colyer, Ooi Eng Eong, Frederick. Hayden, Peter A. Patriarca, M.D. Robert T. Schooley, Jonathan Smith Michael Hodges, Drew Weissman, Mo. MBS, FRCPath, Ph.D. M.D., FACP MD. PhD. MD., BSc. MD, PRO. Principal of mmuno- CEO ofVirtusConsutt
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Slide 38: Appendix
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Slide 39: LUNAR-COV19 Seroconversion Data against Ancestral/Wuhan Strain
LUNAR-COV19 Seroconversion Data against Ancestral/Wuhan Strain (Preclinical) Seroconversion rate (% of Animals) - STARR™ mRNAvs. conventional mRNA LUNAR® Delivery Single STARR™ mRNA (%) Conventional mRNA (%) Dose (mcg) Day 10 Day 19 Day 10 Day 19 02 40 60 20 20 a 80 100 20 0 10 100 100 40 80 100% of
Slide 40: Preclinical Data: Anti-Spike Protein Levels Continue to Increase up to 50 Days
A mecrurus c Preclinical Data: Anti-Spike Protein Levels Continue to Increase up to 50 Days Single administration of LUNAR-COV19 ancestral/Wuhan strain spike protein mRNA in conventional mRNA or STARR™ format (in mice) 0.2 mcg Dose 2.0 mcg Dose 10 mcg Dose 8000 8000 8000 § -* STARR § -@ STARR £ -e S
Slide 41: Preclinical Data: Neutralizing Antibodies Continue to Increase for 60 Days
A mecrurus c Preclinical Data: Neutralizing Antibodies Continue to Increase for 60 Days Single administration (small dose, 2 mcg) of LUNAR-COV19 ancestral/Wuhan strain spike protein (mouse) PRNTSO Virus neutralization assay: Serum dilutions are incubated with SARS- CoV-2 virus, then added to cells.
Slide 42: Preclinical Data: Dose-Dependent Cell-Mediated Immune Response
Kae Preclinical Data: Arcturus Vaccine Elicits a Dose-Dependent Cell-Mediated Immune Response against Ancestral/Wuhan strain in Mouse Model Th1/Th2 ratio 9 2 CD4+ Th1/Th2 ‘5 RNA Dose (meg) % IFN-y+ CD8* T Cells (IFN-y/IL4) 2 0 4.0 46 3 re 5] @ te = é 4 0.2 45 5.3 8 z 2 iv 3 2.0 6.0 5.0 10.0 8.0 6.0
Slide 43: ATX Lipids Facilitate Delivery and are Biodegradable
A mecrurus c ATX Lipids Facilitate Delivery and are Biodegradable Protein Expression (in vivo) Esterase Catalyzed Degradation (in vitro) 120% FF 300: z Pas fet i ATX 1.0 » & 200 mm ATX 2.0 =o 3 E 60% —O-%ATX1.0 5 & é Fi 100 2 40% —@— % ATX 2.0 £ —e% MC3 2 ” 20% a 0 T T 0% PBS = ATX1.0 ATX20 ° 5 10 1
Slide 44: ATX 2.0 Lipid is Biodegradable and Exhibits a Favorable PK/PD Profile
Ke ATX 2.0 Lipid is Biodegradable and Exhibits a Favorable PK/PD Profile Plasma Liver ee 0.5 mg/kg zeny 0.5 mg/kg = ied = 2000004 Tinks | 4 7 2 £ 1500004) = 20000-)\ 3 i\ 8 \ fs 100000 E 10000 \ < woe] —— of . ot ————_— ; ‘ . s ” . * oc FP & £ CS YS Time (hours) Time (hours)
Slide 45: Key Existing Country Relationships
Key Existing Country Relationships Singapore DukeNUS Research Partnership with Medical School = [yke-NUS Medical School EDB Financial Support from the singap@re Economic Development Board of Singapore $10M Grant for Research and Preclinical Work $6.7M Grant for Phase 1/2 Clinical Trial Executed Manu
Slide 46: Drug Substance: mRNA Design
. Ac arcturus Drug Substance: mRNA Design “we Arcturus’ proprietary mRNA optimization platform i Sustained hEPO activity in NHPs upon repeat dosing Optimize Improve Weekly Dosing in Non-Human Primates (NHPs) mRNA sequence Protein Expression PBS control Chemistry Duration LUNAR-EPO mRNA 0.1 mg/kg Pro
Slide 47: Drug Substance (mRNA) Manufacturing
Drug Substance (mRNA) Manufacturing DNA Template IVT and Capping saat Purification Process Optimized IVT Method Reduced Cost; Higher Purity Improved Capping Reaction Reduced Cost of Goods Proprietary Purification Process Higher Purity in a Shorter Time Efficient Entire Process Less Than One Week Sca
Slide 48: Drug Substance (mRNA) Manufacturing
. Ac arcturus Drug Substance (mRNA) Manufacturing oes RNA Yield RNA Purity 6 100 7 90 = = = = 80 33 2 2 5 70 So a 1 60 0 50 05 2 8 10 125 125 125 05 2 8 10 125 125 125 Scale [g] Scale [a] HH Non-GMP Lots Produced at Arcturus GMP Lots Produced at CMO as part of recent GMP campaign Several successful
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