Arcturus Therapeutics Holdings Inc. · NASDAQ:ARCT
Arcturus Therapeutics — Corporate Update (March 2021)
42 slides from Arcturus Therapeutics's corporate update, Mar 1, 2021
Slide 1: | -ARCTURUS “THERAPEUTICS |
[*: “Se | -ARCTURUS 4 “THERAPEUTICS |
Slide 2: Forward Looking Statements
ARCTURUS THERAPEUTICS FORWARD LOOKING STATEMENTS mr om RNA MEDICINES 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
Slide 3: Company Highlights
ARCTURUS THERAPEUTICS K Company Highlights ie RNA MEDICINES Arcturus is a Clinical-Stage mRNA Vaccines and Medicines Company Publicly Traded (Nasdaq: ARCT) * Headquarters: San Diego, CA * Number of Employees: 124 * Founded: 2013 Promising Therapeutic Candidates * LUNAR-COV19 (COVID-19 Vaccine) * LUN
Slide 4: Proprietary mRNA Technologies Driving Promising Therapeutic Programs
ARCTURUS THERAPEUTICS Proprietary mRNA Technologies Driving Promising Therapeutic Programs Broad and Strong Intellectual Property Portfolio : mRNA & STARR™ mRNA mRNA Chemistry Program Indication 5 ——— LUNAR-COV19 COVID-19 Vaccine mRNA Design & Modifications mRNA Manufacturing Process LUNAR-FLU Flu V
Slide 5: Arcturus Pipeline
ARCTURUS THERAPEUTICS of MRNA Medicines Arcturus Pipeline BUILDING INNOVATIVE RNA MEDICINES Franchise Product invdittion Route of Cell Prevalence go Anticipated Name Adi ration Target Worldwide es Milestones LUNAR-COV19 Myocytes & Phase 3 Initiation Q2 (ARCT-021) COVID-19 Intramuscular Dendritic Cel
Slide 6: Partnerships Maximize Platform
ARCTURUS THERAPEUTICS Partnerships Maximize Platform Program Partner Indication LUNAR-HBV Gotuenafohmen LUNAR-NASH LUNAR-GSD3 ultragenyX LUNAR-RARE ultrageny LUNAR-RPL Undisclosed Large Pharma Undisclosed LUNAR-AH Animal Health Pharma Hepatitis B Virus (HBV) Nonalcoholic Steatohepatitis (NASH) Glyco
Slide 7: LUNAR Delivery Technology
ARCTURUS THERAPEUTICS UNAR® Delivery Technology Biodegradable, highly optimized for each cell type LUNARAssociates _Lipid Particle in with CellMembrane Endosome F ™-* / A Enters Cel Increased Acidty a5. Viatndocytosis Endosome Ages pH-Mediated RNA Disruption in Cytosol tat ¢ 4 Cm g Biv cokiitel Rapi
Slide 8: STARR mRNA Expression Superior to Conventional mRNA
ARCTURUS THERAPEUTICS kK STARR™ mRNA Expression Superior to Conventional MRNA #8. Self-Transcribing and Replicating mRNA (STARR™) delivered with LUNAR® provides higher | RNA MEDICINES protein expression and potentially longer-lasting duration of protein expression in mouse Protein Expression Over 7
Slide 9: LUNAR-COV19 (ARCT-021)
LUNAR-COV19 (ARCT-021) COVID-19 Vaccine Candidate
Slide 10: Arcturus COVID-19 Vaccine Candidate has Significant Advantages
ARCTURUS THERAPEUTICS \ Arcturus COVID-19 Vaccine Candidate has Significant Advantages BUILDING INNOVATIVE RNA MEDICINES Duke-NUS Partnership DukeNUS Medical School mRNA Vaccine: No Adjuvants, No Viral Vector Used, Readily Updatable as New Variants Arise Self-amplifying (STARR™) mRNA and LUNAR® Non-
Slide 11: Preclinical Data: Robust Immune Response
ARCTURUS THERAPEUTICS Preclinical Data: Robust Immune Response Humoral Immunity Cellular Immunity BUILDING INNOVATIV RNA MEDICINES STARR™ induces more robust titers compared to conventional mRNA 7 Days Post Single Dose ' 1 1 1 Single Dose. os Single Dose ‘Single Dose 1 CD8* IFN-y sR 02g § sme Dye —
Slide 12: ARCT-021 Significantly Effective in Challenge Models
ARCTURUS THERAPEUTICS ARCT-021 Significantly Effective in Challenge Models K BUILDING INNOVATIVE RNA MEDICINES Mouse Model (transgenic human ACE2) Primate Model (macaque) 1007 10° + **1 pb oois9 7 Days After SARS-CoV-2 Virus Challenge g saa e * Lung viral titers exceeded 13,100 (median) 2 so 2 404 i
Slide 13: ARCT-021 Clinical Trial and Manufacturing Update
ARCTURUS THERAPEUTICS K ARCT-021 Clinical Trial and Manufacturing Update MA Phase 1/2 Clinical Trial * Completed dosing all subjects (n=106), including older adults * At interim analysis, observed high seroconversion rates for IgG binding antibodies, and Th1 dominant CD4+ immune responses, neutraliz
Slide 14: Lyophilization Process Advantage Over Conventional Frozen Liquid
ARCTURUS THERAPEUTICS Lyophilization Process Advantage Over Conventional Frozen Liquia A BUILDING INNOVATIVE Freeze Thaw 7 Conventional RNA A Vaccine Cold Chain/ Frozen Liquid Requires Ultra-Low Temperature Storage Ready for Use Arcturus RNA Vaccine Cold Chain Bulk Diluent Formulation Added Lyophili
Slide 15: LUNAR-OTC (ARCT-810)
LUNAR-OTC (ARCT-810) Ornithine Transcarbamylase (OTC) Deficiency
Slide 16: OTC Deficiency Market Opportunity
ARCTURUS THERAPEUTICS K OTC Deficiency Market Opportunity HN S) Ornithine Transcarbamylase (OTC) Deficiency: The most common urea cycle disorder * The urea cycle converts neurotoxicammonia to water-soluble urea that can be excreted in urine * Deficiency in OTC causes elevated blood ammonia, which ca
Slide 17: LUNAR-OTC
ARCTURUS THERAPEUTICS LUNAR-OTC Disease Normalization Following Single and Repeat Dosing in OTC Mouse Model 100 > : : : 1 me/kg —— LUNAR-OTC 1 mg/kg, n=10 Surviving Animals (%) 50 > LUNAR-OTC 0.3 mg/kg, n=10 40 — High Protein Diet (Control), n=10 30 20 10 0 7 #14 21 28 35 42 49 56 Time (Days) ft + +
Slide 18: LUNAR-OTC
ARCTURUS THERAPEUTICS LUNAR-OTC Exceeds Therapeutic Target of 10% Enzyme Replacement at all Doses in OTC-Deficient Mouse Model Periportal Expression in the Liver of OTC Protein OTCD impacts ureagenesis (ammonia detoxification) 16 2 90 * The main site of ureagenesis is 3B 80 the periportal region of
Slide 19: ARCT-810 Clinical Update
ARCTURUS THERAPEUTICS ARCT-810 Clinical Update Phase 1 Clinical Trial Completed * Double blind, randomized 2:1 active to placebo, dose-escalation trial in healthy adult volunteers * All Adverse Events (AEs) mild or moderate * Favorable PK profile: No LUNAR® lipids detectable after 48 hours following
Slide 20: LUNAR-CF (ARCT-032)
LUNAR-CF (ARCT-032) Cystic Fibrosis
Slide 21: Cystic Fibrosis Market Opportunity
Cystic Fibrosis Market Opportunity kK ®) cy Cystic Fibrosis: The most common rare disease in the United States BUILDING INNOVATIVE RNA MEDICINES 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 a
Slide 22: Delivery of LUNAR-mRNA to Rodent Airways
ARCTURUS THERAPEUTICS Delivery of LUNAR®-mRNA to Rodent Airways Nebulization: Upper/Lower Airways LUNAR® + Luciferase mRNA
Slide 23: LUNAR, an aerosolized delivery platform for lung
ARCTURUS THERAPEUTICS LUNAR®, an aerosolized delivery platform for lung Aerosolized LUNAR® Aerosolized LUNAR® -mRNA (EGFP) LUNAR®-mRNA (hCFTR) is biologically Particles are Breathable maintains activity active in vivo (NPD, Mouse) Pre-Nebulization al ZA 1 2 3 4 5 Breathable Range (microns) Post-Nebu
Slide 24: Delivery of LUNAR-mRNA into Epithelial Airways in Ferret
Delivery of LUNAR®-mRNA into Epithelial Airways in Ferret KX EGFP conversion in tracheal epithelial airways observed in the ROSA26TG Ferret model ¢ Ferrets are an excellent species for modeling certain human lung diseases* * Novel LUNAR® formulations of CRE mRNA were tested in a transgenic ROSA26T7G
Slide 25: Moving Forward
Moving Forward
Slide 26: Anticipated Near-Term Milestones and Cash Position
ARCTURUS THERAPEUTICS Anticipated Near-Term Milestones and Cash Position ARCT-021 (LUNAR-COV19) Phase 3 Initiation Q2 2021 Emergency Use Authorization (EUA) H2 2021 ARCT-810 (LUNAR-OTC) Phase 2 Multiple Dose Study Clinical TrialApplication Q22021 ARCT-032 (LUNAR-CF) Clinical Trial Application (CTA)
Slide 27: Management Team
ARCTURUS THERAPEUTICS Management Team HEOLSE. Joseph E.Payne,MSc Pad Chivukula, Ph.D. Andrew Sassine, MBA _Steve Hughes, M.D. Lance Kurata, J.D. President & CEO CSO & COO cFO Chief Medical Officer Chief Legal Officer © MERCK Nitto (Fidelity &./ONIS M . Board of Directors £ £000 £6 PeterFarrell, Ph.D
Slide 28: Scientific Advisory Board
ARCTURUS THERAPEUTICS Scientific Advisory Board HPISHADDSE BUILDING INNOVATIVE RNA MEDICINES Jeff Colyer, Ooi Eng Eong, FrederickG. Hayden, Peter A. Patriarca, RobertT. Schooley, Jonathan Smith, Michael Hodges, Drew Weissman, Mo. BMBS, FRCPath, Ph.D. M.D.,FACP MOD. MO. Pho. M.D.,BSc. MD. Pho. CEO of
Slide 29: Slide 29
Slide 30: Appendix
Appendix
Slide 31: LUNAR-COV19 Preclinical Seroconversion Data
ARCTURUS THERAPEUTICS LUNAR-COV19 Preclinical Seroconversion Data Seroconversion Rate (% of Animals) — STARR™ mRNA vs. Conventional mRNA single LUNAR® Delivery : pase (i) STARR™ mRNA (%) Conventional mRNA (%) Day 10 Day 19 Day 10 Day 19 0.2 40 60 20 20 2 80 100 20 ie} 10 100 100 40 80 100% of mouse
Slide 32: Preclinical Data: Anti-Spike Protein Levels Continue to Increase Up to 50 Days
ARCTURUS THERAPEUTICS kX Preclinical Data: Anti-Spike Protein Levels Continue to Increase Up to 50 Days 7 7 RNA MEDICINES Single Administration of LUNAR-COV19 0.2 ng Dose 2.0 ng Dose 10.0 ng Dose 000 00. £ -- STARR, © STARR £ “© STARR Ba a mRNA mRNA Bs oe mRNA 4 = 6000 8 = 6000. N BE] eas ue va Ny 3
Slide 33: Preclinical Data: Neutralizing Antibodies Continue to Increase for 60 Days
ARCTURUS THERAPUETICS Preclinical Data: Neutralizing Antibodies Continue to Increase for 60 Days Single Administration (small dose, 2ug) of LUNAR-COV19 PRNT50 1001 Virus neutralization assay: Serum dilutions are incubated with SARS-CoV-2 virus, then added to cells. The cells die forming plaques, whi
Slide 34: Preclinical Data: Arcturus Vaccine elicits a Balanced Cell Mediated Immune Response
ARCTURUS THERAPUETICS Preclinical Data: Arcturus Vaccine elicits a Balanced Cell Mediated Immune Response %of CDS T cells h BUILDING INI RNA MEDIC CD8* IFN-y Th1/Th2 ratio RNA Dose | % IFN-y+ CD8* T Cells 4+ Th1/Th2 (ue) . 0 4.0 4.6 Ly + 0.2 4.5 53 f. = . 2.0 6.0 5.0 10.0 8.0 6.0 Ong O2n9 2p9 1049 O
Slide 35: Arcturus Safety Profile
ARCTURUS THERAPEUTICS Arcturus Safety Profile k External Validation * Multiple strategic partnerships over many years confirms the positive potential safety profile of Arcturus LUNAR® and mRNA Arcturus is committed to developing safe mRNA products * 15 studies over several years with strategic partn
Slide 36: ATX Lipids are Effective and Biodegradable
ARCTURUS THERAPEUTICS ATX Lipids are Effective and Biodegradable K BUILDING INNOVATIVE RNA MEDICINES Protein Expression (in vivo) Esterase Catalyzed Degradation (in vitro) Z 300: 120% z mm PBS 2 mE ATX 10 100% & 200 mm ATX 2.0 B 80% o & 3 E 60% —O—%ATXLO E 100 & “i Oe %ATX2.0 © —e% mcs 2 20% 3 = o{_
Slide 37: ATX 2.0 Lipid is Biodegradable and Clears in vivo
ARCTURUS THERAPEUTICS K ATX 2.0 Lipid is Biodegradable and Clears in vivo ounuono naovarwe foi “= 0.5 mg/kg 250000 “© 0.5 mgikg = 1mgk _ -& 1 mgfkg 00000 wa/kg = 30000. 3 £ > 2 E 150000. © 20000: Ps a S 100000. x z & 10000. = S000. ot = + oF = 3 ay 7 3 * sf we we FUP OM Oe Time (hours) Time (hours)
Slide 38: Key Existing Country Relationships
ARCTURUS THERAPEUTICS K Key Existing Country Relationships voy setae Singapore DukeNUS Research Partnership with Duke-NUS Medical School Medical School Financial Support from the Economic Development Board of Singapore EDB « $10 M Grant for Research and Preclinical Work singap@re + $6.7 M Grant for
Slide 39: Drug Substance: mRNA Design
ARCTURUS THERAPEUTICS Drug Substance: mRNA Design Arcturus’ proprietary mRNA optimization platform Improve mRNA sequence . Protein Expression Chemistry Duration Process Functional Activity S'cap | 5’ UTR Coding Region 3° UTR Poly(A) tail Proprietary mRNA Opti x BUILDING INNOVATIVE RNA MEDICINES Sust
Slide 40: Drug Substance (mRNA) Manufacturing
Drug Substance (mRNA) Manufacturing K BUILDING INNOVATIVE RNA MEDICINES |A Template IVT and Capping re Buffer Exchange & Purification Process Caneanietiion Features Benefits Optimized IVT Method Reduced Cost; Higher Purity Improved Capping Reaction Reduced Cost of Goods Proprietary Purification Proc
Slide 41: Drug Substance (mRNA) Manufacturing
ARCTURUS THERAPEUTICS Drug Substance (mRNA) Manufacturing INNOVATIVE RNA Yield RNA Purity 6 4100 5 90 3: E w cP > a a Bs 5 7 2 a 1 60 0 50 125 125 125 125 125 125 scale [g] scale [gl Hi Non-GMP Lots Produced at Arcturus GMP Lots Produced at CMO as part of recent GMP campaign ee 12.5 g lots produced
Slide 42: LUNAR Versatility
ARCTURUS THERAPEUTICS LUNAR® Versatility K Compatible with RNA of Various size BUILDING INNOVATIVE RNA MEDICINES % Encapsulated RNA Particle Size 15 2 100 im Yr E % E 2” 2 Rg 2 ° ca S00 5 ui a R25 28 0 0 20 1800 © 1@00:«=«-2000»««5000-»««900 © 10000 © 12000 20 1800 © 1800» 2000» 5000» 9800» 10000» 1
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