Arcturus Therapeutics Holdings Inc. · NASDAQ:ARCT
Arcturus Therapeutics — Investor Presentation (November 2021)
44 slides from Arcturus Therapeutics's investor presentation, Nov 16, 2021
Slide 1: Next Generation RNA Medicines
Next Generation RNA Medicines November 2021
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) HQ: San Diego, CA Founded 2013 160+ Employees f "- Therapeutic Candidates LUNAR-COV19 (cowin-19Vvaccine) LUNAR-OTC (omithine Transcarbamylase Deficiency) LUNAR-CF (cystic Fibrosis) Additional Earl
Slide 4: Proprietary mRNA Technologies Driving Therapeutic Programs
Proprietary mRNA Technologies Driving Therapeutic Programs Acacrunus F Broad intellectual property portfolio mRNA Chemistry ~ mRNA & STARR™ mRNA Program Indication LUNAR-COV19 — COVID-19Vaccine mRNA Design & Modifications mRNA Manufacturing Process LUNAR-FLU Flu Vaccine oul LUNAR® Deliver y Se y LUN
Slide 5: Pipeline of mRNA Therapeutic Candidates
Pipeline of mRNA Therapeutic Candidates Multiple mRNA therapeutic and vaccine programs in clinical development Franchise Candidate Indication Prevalence Route of Administration Cell Target ARCTURUS’ Anticipated Milestones Vaccines Hepatic Respiratory LUNAR-COV19 (aRcto21) COVvID-19 Global LUNAR-COV1
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® binds to cell LUNAR® internalized membrane inside endosome mRNA translated into mRNA release protein of interest a ry q Le ( 4 be oohiptel
Slide 8: STARR mRNA Expression Superior to Conventional mRNA
AX aacrurus | STARR™ mRNA Expression Superior to Conventional MRNA Self-Transcribing and Replicating mRNA (STARR™) delivered with LUNAR® provides increased and longer lasting expression in mouse models STARR™ Technology Protein Expression Over 7 days 30-Fold Higher Protein Expression STARR™ mRNA vs.
Slide 9: LUNAR-COV19 (ARCT-021 and ARCT-154)
Slide 10: Arcturus COVID-19 Vaccine Candidates have a Differentiated Profile
Arcturus COVID-19 Vaccine Candidates have a Differentiated Profile an mRNA Vaccine - No Adjuvants, No Viral Seff-Amplifying (STARR™) mRNA and Clinical Data Demonstrate Vector Used, Readily Updatable as LUNAR® Non-viral Delivery Technology Humoral and Cellular Immunogenicity, New Variants Arise and T
Slide 11: Global Manufacturing Footprint
. . ARCTURUS’ Global Manufacturing Footprint. 2 I Germany Recipharm Catalent or stockpiling purposes "1
Slide 12: LUNAR-COV19 (ARCT-021)
Slide 13: Preclinical Data: Robust Immune Response in Mouse Models
Preclinical data: Robust Immune Response in Mouse Models A. aecrurus Humoral immunity i Cellular immunity 7 Days Post Single Dose CD8* IFN-y 1 o STARR™ induces more robust titers compared to conventional MRNA Single Dose Single Dose Single Dose PE] IS come |g) poet ome ] eK tomes i 2 io + Pas e ke I
Slide 14: ARCT-021 in Challenge Models
. Ac arcturus ARCT-021 in Challenge Models ses Mouse model (transgenic human ACE2) H Primate model (macaque) iti 408 Fa P= 0.0189 7 Days After SARS-CoV-2 100% j Virus Challenge = 004 i g g 2 10 + Lung viral titers 2 604 . exceeded 13,100 a 2 (median) in non- # > = 404 vaccinated primates 8 + pas z a
Slide 15: 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 16: LUNAR-COV19 (ARCT-154)
Slide 17: ARCT-154 Preclinical Data and Clinical Trial Update
ARCTURUS’ ARCT-154 Preclinical Data and Clinical Trial Update Phase 1/2/3 Clinical Trial in Vietnam ARCT-154 + Phases 1/2/3 sponsored & funded by Vinbiotech Neutralizing Antibody Titers in Non-Human Primates. — Randomized, observer-blind, placebo-controlled design One Month Post 2nd Dose + Enrollmen
Slide 18: LUNAR-OTC (ARCT-810)
Slide 19: Ornithine Transcarbamylase (OTC) Deficiency
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 damage, coma,
Slide 20: LUNAR-OTC
A mecrurus c LUNAR-OTC 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 (ammonia detoxification) 40 90. 80. 70: 60. 50: 40 30 20 10}... 4 ++ 10% OTC Activity Threshold 0.
Slide 21: ARCT-810 Clinical Update
A mecrurus c ARCT-810 Clinical Update Phase 1 Clinical Trial in Health Volunteers Completed Phase 1b Clinical Trial in OTC-Deficiency Adults Ongoing Phase 2 Clinical Trial in OTC-Deficient Adolescents and Adults Approved to Proceed Randomized, double-blind, placebo-controlled, nested single and mult
Slide 22: LUNAR-CF (ARCT-032)
Slide 23: Cystic Fibrosis
Cystic Fibrosis ARCT-032 Market Opportunity Cystic Fibrosis 85,000-100,000 worldwide prevalence Caused by genetic mutations in the CFTRgene, 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 inflammat
Slide 24: Delivery of LUNAR-mRNA into Rodent and Non-Rodent Airways
Accuns fi Delivery of LUNAR®-mRNA into Rodent and Non-Rodent Airways Nebulization: upper/lower airways LUNAR targets mice epithelial cells in rodents and nonrodents TdTomato / Fox! / LUNAR® + Luciferase mRNA TdTomato / EGFP / A Ciliated cells (FoxJ1 in rodent/top, Acetylated alpha-tubulin in nonrode
Slide 25: Aerosolized LUNAR Delivery Platform for Lung
, . Ac arcturus r Aerosolized LUNAR® Delivery Platform for Lung o“ Aerosolized LUNAR® Aerosolized LUNAR®mRNA (eGFP) LUNAR® mRNA (hCFTR) is biologically particles are breathable H maintains activity H active in vivo (NPD, mouse) Pre-Nebulization LUNAR® buffer control © LUNAR®-RCETR mRNA Formulation L
Slide 26: LUNAR-mRNA Delivery to Airways Epithelium
LUNAR®-mRNA Delivery to Airways Epithelium FB SAY : ry Ba. euis 4 bs. ; ye wee. rodent and nonrodents)
Slide 27: Delivery of LUNAR-mRNA to Airway Epithelium in a Ferret Model
Accuns fi Delivery of LUNAR®-mRNA to Airway Epithelium in a Ferret Model + Ferrets are a reliable species for modeling certain human lung diseases* + Novel LUNAR® formulations of Cre mRNA were tested in a transgenic ROSA26TG ferret model « Activation of eGFP expression indicates that LUNAR® targets
Slide 28: Functional Restoration of Chloride Current with LUNAR-hCFTR
Functional Restoration of Chloride Current with LUNAR®-hCFTR Acascrurus F CFTR-deficient (G551D) Ferret Bronchial Epithelial Cells CFTR-mediated CI Currents Ise (wAlem?) — LUNAR®-RhCFTR 5 meg —| LUNAR®-RhCFTR 25 meg — LUNAR?-dTomato 100 meg _ LUNAR®-RhCFTR 50 meg — LUNAR®-RhCFTR 100 meg — VX-770 CRT
Slide 29: Moving Forward
Moving Forward
Slide 30: Anticipated Near-Term Milestones
A agcrurus c Anticipated Near-Term Milestones ARCT-021 (COVID vaccine candidate) Phase 3 Initiation Under Discussion with Global Entity ARCT-154(COVID vaccine candidate targeting VOCs) EUA Filing in Vietnam December 2021 ARCT-810(LUNAR-OTC) Interim Phase 2 Data H2 2022 ARCT-032(LUNAR-CF) Clinical Tr
Slide 31: Team Arcturus
Team Arcturus Management Team £®eeecee? @ Joseph E.Payne, MSc Pad Chivukula, Ph.D. Andrew Sassine, MBA Steve Hughes, M.D. Lance Kurata, J.D. Dushyant Varshney, Ph.D. _Nirdosh Jagota, Ph.D. President & CEO CSO & COO CFO Chief Medical Oficer Chief Legal Officer cTo Chief Regulatory Officer merck Nitto
Slide 32: 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
Slide 33: Temeree
Temeree Acdhaic aletes Adcletele ceed CReQe ofcgaiciey asa tee
Slide 34: Appendix
oe! ek AY . ¥ I A Appendix
Slide 35: LUNAR-COV19 Seroconversion Data (Preclinical)
LUNAR-COV19 Seroconversion Data (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 mice seroconverted by day 19 a
Slide 36: 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 (mouse) 0.2 mcg Dose 2.0 mcg Dose 10 mcg Dose Ps s 8 2 ~@ STARR —& mRNA ~® STARR —& MRNA ~@ STARR -& mRNA g 3 8 & 8 3 8 Anti-Spike Glycoprotein (Adjusted MFI) yO eS s 8 An
Slide 37: 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 (mouse) PRNTSO Virus neutralization assay: Serum dilutions are incubated with SARS- CoV-2 virus, then added to cells. The cells die forming plaques, which
Slide 38: Arcturus Vaccine Elicits a Balanced Cell-Mediated Immune Response in Mouse Model
Preclinical Data: Arcturus Vaccine Elicits a Balanced Cell-Mediated Immune Response in Mouse Model _ CD8" IFN-y ‘Th1/Th2 ratio RNA Dose (meg) % IFN-y+ CD8* T Cells ee 12. aeons 15. EN 2 0 4.0 46 a ea e te e a 0.2 48 8s a = 2 4 $ 3 2.0 6.0 5.0 10.0 8.0 6.0 0 02 20 10.0 0 02 20 10.0 meg meg RNA dose d
Slide 39: 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 40: 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 _ = 1 mg/kg _ } = 1 mg/kg = 30000: | 4 7 2 £ 1500004) = 20000-)\ 8 i a \ fs 100000 & om \ s smoot a —— . ot ————_— ; ‘ ° s v > * ot ev F CO ww Time (hours) Time (hours) Igy) is degraded
Slide 41: Key Existing Country Relationships
A mecrurus c Key Existing Country Relationships Singapore Vietnam DukeNUS Research Partnership with @ Collaboration with Vingroup to Medical School ~— [)uke-NUS Medical School Vinsroup Establish Manufacturing Facility $40 million upfront payment and potential royalties based on vaccines produced EDB
Slide 42: 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 43: 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 44: 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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