Arcturus Therapeutics Holdings Inc. · NASDAQ:ARCT
Arcturus Therapeutics — Investor Presentation (December 2020)
45 slides from Arcturus Therapeutics's investor presentation, Dec 8, 2020
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: 113 * 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 mRNA Design & Modifications mRNA Manufacturing Process LUNAR® Delivery Lipid Chemistry Formulation Design LUNAR® Drug Product
Slide 5: Arcturus Pipeline of mRNA Medicines
ARCTURUS THERAPEUTICS Arcturus Pipeline of mRNA Medicines BUILDING INNOVATIVE Product lndication Route of Cell Prevalence Name Administration Target Worldwide 2021 Milestones. Phase 2 Initiation Q1 ncaa cOvID-19 Intramuscular eet Global Phase 3 Initiation Q2 endritic Cells eae VACCINES LUNAR-FLU Inf
Slide 6: Partnerships Maximize Platform
ARCTURUS THERAPEUTICS K Partnerships Maximize Platform ele Program Partner Indication LUNAR-HBV Gohvonagohwen Hepatitis B Virus (HBV) LUNAR-NASH Nonalcoholic Steatohepatitis (NASH) LUNAR-GSD3 ultragenyX Glycogen Storage Disease Type III LUNAR-RARE ultragenyx Undisclosed Rare Disease LUNAR-RPL Undisc
Slide 7: LUNAR Delivery Technology
ARCTURUS THERAPEUTICS LUNAR® Delivery Technology Biodegradable, highly optimized for each cell type LUNAR Associates Lipid Particle in with Cell Membrane Endosome a 7 / ( 4 pH-Mediated RNA Disruption in Cytosol ms alla 4 Ce a Elvecebiotel
Slide 8: STARR mRNA Superior to Conventional mRNA
ARCTURUS THERAPEUTICS kK STARR™ mRNA Superior to Conventional mRNA cant ican Self-Transcribing and Replicating mRNA (STARR) delivered with LUNAR® provides higher protein expression and potentially longer-lasting duration of protein expression in mouse Protein Expression Over 7 days STARR™ eS | 4010
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: Simple, No Adjuvants, No Viruses STARR™ mRNA: Produces 30X More Protein than Conventional mRNA ° LUNAR® Technology: Non-v
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 STARR mRNA Vccna dose (9) f 1 1 1 08" Fe SingleDose Single Dose Single Dose f on
Slide 12: Publication BioRxiv Preprint
ARCTURUS THERAPEUTICS Publication BioRxiv Preprint Promising pre-clinical results involving Arcturus’ self-transcribing and replicating mRNA (STARR™) based vaccine ARCT-021 (LUNAR-COV19) allenge S IgG Avidity f 1 1 1 1 1 1 i cS7BLGS 1007 i 1 1 : . *0 H Z <r) 3 1 zz . Eo ! 23° : a s F $3 gs « 33 2 +
Slide 13: ARCT-021 (LUNAR-COV19) Update
ARCTURUS THERAPEUTICS ARCT-021 (LUNAR-COV19) Update Phase 1/2 Clinical Trial * Completed dosing all subjects (n=106), including older adults * For both single and prime-boost regimens, at the interim analysis, observed high seroconversion rates for IgG binding antibodies, and Th1 dominant CD4+ immun
Slide 14: Lyophilization Process Advantage Over Conventional Frozen Liquid
ARCTURUS THERAPEUTICS Lyophilization Process Advantage Over Conventional Frozen Liquid BUILDING INNOVATIVE RNA MEDICINES £ rreeze Thaw y Conventional RNA Vaccine Cold Chain Arcturus RNA Vaccine Cold Chain Frozen Liquid Requires Ultra-Low Temperature Storage Bulk Formulation Lyophilized Powder Cake D
Slide 15: LUNAR-OTC (ARCT-810)
LUNAR-OTC (ARCT-810) Ornithine Transcarbamylase (OTC) Deficiency
Slide 16: OTC Deficiency Market Opportunity
ARCTURUS THERAPEUTICS kK OTC Deficiency Market Opportunity ae tis 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, whi
Slide 17: LUNAR-OTC: Disease Normalization in OTC Mouse Model
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: Exceeds Therapeutic Target of 10% Enzyme Replacement
ARCTURUS THERAPEUTICS LUNAR-OTC Exceeds Therapeutic Target of 10% Enzyme Replacement at all Doses in OTC-Deficient Mouse Model + OTCD impacts ureagenesis Periportal Expression in the Liver of OTC Protein (ammonia detoxification) 16 2 90 * The main site of ureagenesis is 3B 80 the periportal region o
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
LUNAR-CF Cystic Fibrosis
Slide 21: Cystic Fibrosis Market Opportunity
ARCTURUS THERAPEUTICS Cystic Fibrosis Market Opportunity ®) cy Cystic Fibrosis: The most common rare disease in the United States 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 obstructi
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: LUNAR-CV
LUNAR-CV Targeted Messenger RNA Therapeutic Cardiovascular Disease; LDL-Cholesterol Reduction
Slide 26: HoFH Market Opportunity
ARCTURUS THERAPEUTICS kK HoFH Market Opportunity pated wisi © Homozygous Familial Hypercholesterolemia (HoFH): * Severely elevated LDL Cholesterol (LDL-C) levels increases risk for cardiovascular disease * In ~90% of HoFH patients, the LDL receptor (LDL-R) is deficient or absent that leads to low or
Slide 27: LUNAR-CV, Targeted mRNA Therapeutic
ARCTURUS THERAPEUTICS LUNAR-CV, Targeted mRNA Therapeutic Targets Hepatocytes in LDL Receptor Knock-out Mouse Model Result: LDL-Cholesterol is bound and cleared from the plasma 400: 200 } Normal Levels Serum LDL-Cholesterol (mg/dL) in vivo Proof-of-Concept: 0 Hepatocytes Expressing LDL Receptors in
Slide 28: Moving Forward
Moving Forward
Slide 29: Anticipated Near-Term Milestones and Cash Position
ARCTURUS THERAPEUTICS Anticipated Near-Term Milestones and Cash Position LUNAR-COV19 (ARCT-021) Phase 2 Initiation Qi 2021 Phase 3 Initiation Q2 2021 Emergency Use Authorization (EUA) H2 2021 LUNAR-OTC (ARCT-810) Phase 2 Multiple Dose Study Initiation Mid-2021 LUNAR-CF Development Candidate (DC) Sel
Slide 30: 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 Development Officer Chief Legal Officer © MERCK Nitto (Fidelity &./ONIS M . Board of Directors £ £000 £6 PeterFarrell,
Slide 31: 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 32: Slide 32
Slide 33: Appendix
Appendix
Slide 34: 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 35: Preclinical Data: Anti-Spike Protein Levels Continue to Increase Up to 50 Days
ARCTURUS THERAPEUTICS x Preclinical Data: Anti-Spike Protein Levels Continue to Increase Up to 50 Days RNA MEDICINES Single Administration of LUNAR-COV19 0.2 ng Dose 2.0 ng Dose g 7 4. staRR g 1) -w STARR Be coo] * mRNA B soo) MRNA 82 “PBS. gE 8 ¥ aaoo 5 B 000. 23 I ge GS 2000 A tJ §S2m: ; ra 5 z g
Slide 36: Preclinical Data: Neutralizing Antibodies Continue to Increase for 60 Days
ARCTURUS THERAPUETICS kX y/ Preclinical Data: Neutralizing Antibodies Continue to Increase for 60 Days Single Administration (small dose, 2ug) of LUNAR-COV19 UILDING INNOVATIVE RNA MEDICINES PRNT50 100 SARS-CoV-2 Neutralization (PRNT50 titer) Virus neutralization assay: Serum dilutions are incubated
Slide 37: Preclinical Data: Balanced Cell Mediated Immune Response
ARCTURUS THERAPUETICS Preclinical Data: Arcturus Vaccine elicits a Balanced Cell Mediated Immune Response %of CDS T cells CD8* IFN-y Th1/Th2 ratio (ug) i 0 = z= 0.2 2.0 10.0 Ong O29 2ng9 10p9 On9 O29 2pg9 10,9 Dose (3015) Results Summary RNA dose dependent increase in IFN-y positive CD8* T-cells RNA
Slide 38: 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 39: 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 40: 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 41: Key Existing Country Relationships
ARCTURUS THERAPEUTICS Key Existing Country Relationships 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 Phase 1/2 Cl
Slide 42: 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 43: Drug Substance (mRNA) Manufacturing
Drug Substance (mRNA) Manufacturing K BUILDING INNOVATIVE |A Template IVT and Capping re Buffer Exchange & Reaction Henahiteelteln Peers Concentration RNA MEDICINES Features Benefits Optimized IVT Method Reduced Cost; Higher Purity Improved Capping Reaction Reduced Cost of Goods Proprietary Purifica
Slide 44: 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 45: Drug Product (LUNAR + mRNA) Manufacturing
Particle size (nm) ARCTURUS THERAPEUTICS Drug Product (LUNAR® + mRNA) Manufacturing Particle Size %Encapsulated MRNA 100.0 100.0 %Encapsulated mRNA kK BUILDING INNOVATIVE RNA MEDICINES 20.0 20.0 60.0 60.0 40.0 40.0 20.0 200 00 00 ot 03 1.0 30 10.0 oa 03 10 3.0 10.0 Batch Size (mRNA in grams) Batch S
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