Arcturus Therapeutics Holdings Inc. · NASDAQ:ARCT
Arcturus Therapeutics — Investor Presentation (January 2020)
25 slides from Arcturus Therapeutics's investor presentation, Jan 10, 2020
Slide 1: Arcturus Therapeutics
[*: “Se | -ARCTURUS 4 “THERAPEUTICS |
Slide 2: Forward Looking Statements
ARCTURUS THERAPEUTICS FORWARD LOOKING STATEMENTS sacl Nine 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 achievemen
Slide 3: Investment Highlights
Investment Highlights Xx RNA MEDICINES: Arcturus is an mRNA Medicines Drug Development Company Focused on Rare Diseases LUNAR® Delivery Platform Validated by Multiple Strategic Partners * More than $1 Billionin potential milestones and royalties Broad and Strong Intellectual Property Portfolio * 182
Slide 4: 2019 Summary
2019 Summary x RNA MEDICINES: Ultragenyx Collaboration Expanded, $30M ultragenys pharmaceutic Cystic Fibrosis Foundation Increased Commitment to $15M cystic risrosis FOUNDATION Fundraising Completed, $23M from Institutional Investors Advanced Pipeline ¢« LUNAR-OTC: ARCT-810 Nominated, Received Orpha
Slide 5: Key Value Drivers: Platform & Pipeline
ARCTURUS THERAPEUTICS K Key Value Drivers > Platform & Pipeline eee enone RNA MEDICINES: Platform: LUNAR® Delivery, mRNA Drug Substance, and STARR (Self-Transcribing And Replicating RNA) Technology ™ fohmronafohuson ultrageny, : an ence oe pharmaceutical he RNA peeple® Strategic Partners: More than
Slide 6: LUNAR Delivery Technology
ARCTURUS THERAPEUTICS LUNAR® Delivery Technology mugs mene LUNAR Associates Lipid Particle in with Cell Membrane Endosome F _™.* / 4 pH-Mediated RNA Disruption in Cytosol ms alla 4 Ce a Elvecebiotel
Slide 7: Arcturus Platform: Enabling Genetic Medicines
ARCTURUS THERAPEUTICS Arcturus Platform: Enabling Genetic Medicines Program Partner Indication Arcturus iiebierels Program Chemistry Delivery Status wnarssos —Ultragenyx eee oR wane satan LUNAR-RARE ultragenyx tundlsclosed Rare mRNA ‘iets Preclinical LUNAR-HEV — Gofunonagofmen Hepatitis B RNA ‘oetev
Slide 8: Arcturus Pipeline of mRNA Medicines
ARCTURUS THERAPEUTICS Arcturus Pipeline of mRNA Medicines x BUILDING INNOVATIVE RNA MEDICINES: Expected Route of Prevalence N: Indicati T t Or lame indication canoes wanmer fen argetOrgan _—Target Cellls ees Ornithine PON ARS Transcarbamylase Q1. 2020 Intravenous (iv.) Liver Hepatocytes > 10,000 (AR
Slide 9: LUNAR Platform Preclinical Proof-of-Concept Demonstrated
ARCTURUS THERAPEUTICS { LUNAR? Platform Preclinical Proof-of-Concept Demonstrated kX BUILDING IINOVATIVE RNA > S oe shared. At | Health (arcT-810) LUNAR-NASH SENSES felon a LUNAR-CF mRNA mRNA Intravitreal mRNA Ultragemy Neoantigens SYNTHETIC GENOMICS LNAR-6sD3 mRNA ultragenyX LUNAR® Platform Preclin
Slide 10: OTC Deficiency Market Opportunity
ARCTURUS THERAPEUTICS kX OTC Deficiency Market Opportunity esse anne © ©) RNA MEDICINES: Ornithine Transcarbamylase (OTC) Deficiency: The most common urea cycle disorder © The urea cycle converts neurotoxic ammonia to water-soluble urea that can be excreted in urine * Deficiency in OTC causes elevat
Slide 11: LUNAR-OTC Disease Normalization in Mouse Model
ARCTURUS THERAPEUTICS LUNAR®-OTC Disease Normalization Following Single and Repeat Dosing in OTC Mouse Model Surviving Animals (%) ent Mice on High Protein Di Weekly LUNAR-OTC Treatment —— LUNAR-OTC 1 mg/kg, n=10 —— LUNAR-OTC 0.3 mg/kg, n=10 — High Protein Diet (Control), n=10 0.3 mg/kg 0 7 #14 21 2
Slide 12: LUNAR-OTC Enzyme Replacement in Mouse Model
ARCTURUS THERAPEUTICS \ LUNAR-OTC seer RNA MEDICINES: 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) 110. CCCs: ii§§ been — = 2 90. * The main site of
Slide 13: ATX Lipids are Effective and Degrade Rapidly
ARCTURUS THERAPEUTICS ATX Lipids are Effective and Degrade Rapidly y, 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 =
Slide 14: ATX 2.0 Lipid Rapidly Clears in vivo
ARCTURUS THERAPEUTICS K ATX 2.0 Lipid Rapidly Clears in vivo supe meane 40000 “= 0.5 mgkkg 250000 © 0.5 mgikg = 1 mgikg Per “& 1 mg/kg = 30000 3 £ > 2 £ 150000. © 20000: g a S 100000. x z & 10000 =< 50000 ot * -- ot - 3 x + 3 ° . ie ec * ££ fg yw Time (hours) Time (hours) technology) lly degraded fn
Slide 15: Arcturus Safety Profile
Arcturus Safety Profile x External Validation * Multiple strategic partnerships over many years confirms the positive safety profile of Arcturus LUNAR® and mRNA Arcturusis committed to developing safe mRNA products * 15 studies over several years with strategic partners Top Safety Concern for RNA Me
Slide 16: Cystic Fibrosis Market Opportunity
ARCTURUS THERAPEUTICS Cystic Fibrosis Market Opportunity K BUILDING INNOVATIVE RNA MEDICINES: w) Cystic Fibrosis: The most common rare disease in the United States * Caused by genetic mutations inthe CFTR gene, resulting in aberrant flux of ions in and out of cells, causing thick mucus buildupin lun
Slide 17: LUNAR Delivery of mRNA to Lung (Mouse)
ARCTURUS THERAPEUTICS LUNAR® Delivery of mRNA to Lung (Mouse) Nebulization LUNAR® + Luciferase mRNA BUILDING INNOVATIVE RNA MEDICINES: LUNAR® Delivery of mRNAinto Bronchial Epithelial Cells (BECs) 16
Slide 18: Aerosolized LUNAR
Aerosolized LUNAR® KX BUILDING INNOVATIVE RNA MEDICINES: Aerosolized LUNAR® Aerosolized LUNAR® -mRNA (GFP) Aerosolized LUNAR®-CF Particles are Breathable maintains activity is functional in vive (mouse) Formulation Lots Aerosolized LUNAR’ Aerosolized LUNAR’ al zo 4 2 3 4 5 Breathable Range (microns)
Slide 19: Drug Substance: mRNA Design
ARCTURUS THERAPEUTICS Drug Substance: mRNA Design kK BUILDING INNOVATIVE RNA MEDICINES: Arcturus’ proprietary mRNA optimization platform Sustained hEPO activity in NHPs upon repeat dosing Weekly Dosing in Non-Human Primates (NHPs) Optimize Improve 10. I PBS control mRNA sequence Protein Expression z
Slide 20: Drug Substance (mRNA) Manufacturing
Drug Substance (mRNA) Manufacturing xX BUILDING INNOVATIVE A Template IVT and Capp ig Purification Pracess Buffer Exchange & Production Reaction Concentration RNA MEDICINES: Features Benefits Optimized IVT Method Reduced Cost; Higher Purity Improved Capping Reaction Reduced Cast of Goods Proprietary
Slide 21: Drug Substance (mRNA) Manufacturing
ARCTURUS THERAPEUTICS Drug Substance (mRNA) Manufacturing x Yield [g/L] RNA Yield 100 9 Xoo > z 5 7 a 60 50 05 2 8 10 128 128 128 Scale [g] Hi Non-GMP Lots Produced at Arcturus BUILDING INNOVATIVE RNA MEDICINES RNA Purity 08 2 8 10 128 128 128 Scale [g] GMP Lots Produced at CMO as part of recent GMP
Slide 22: Drug Product (LUNAR + mRNA) Manufacturing
Particle size (nm) ARCTURUS THERAPEUTICS Drug Product (LUNAR® + mRNA) Manufacturing xk BUILDING INNOVATIVE RNA MEDICINES: Particle Size %Encapsulated MRNA 100.0 100.0 80.0 80.0 ¢ 3 é 60.0 = 60.0 40.0 % 400 a 20.0 ” 20.0 0.0 0.0 on 03 1.0 3.0 10.0 01 03 10 3.0 10.0 Batch Size (mRNA in grams) Batch Si
Slide 23: Board of Directors
ARCTURUS THERAPEUTICS BUILDING INNOVATIVE Board of Directors ae £ A000 £OE PeterFarrell, Ph.D. KarahParschauer,JD Edward W.Holmes, M.D. JamesBarlow,MA Magda Marquet, Ph.D. Joseph, Payne, MSc Andrew Sassine, MBA Emil D. Kakkis, M.D., Ph.D. . me ResMed ultragenya Sceecuwems <3Allergan OALTHEA € MERCK
Slide 24: Management Team
ARCTURUS THERAPEUTICS Management Team £S&S@x Joseph E. Payne, MSc Pad Chivukula, Ph.D. Andrew Sassine, MBA. Steve Hughes, M.D. President & CEO C80 & COO CFO Chief Development Officer merck Nitto Fidelity &»!ONIS x BUILDING INNOVATIVE RNA MEDICINES: 2B
Slide 25: Slide 25
Arcturus Therapeutics Holdings — Investor Presentation (January 2020) on 6ix