Slide 1: Arcturus Therapeutics / Alcobra Merger: Enabling a New Era of RNA Medicines
Arcturus Therapeutics / Alcobra Merger Enabling a New Era of RNA Medicines September 28, 2017
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 diffe ren t from any futu
Slide 3: Transaction Terms
Transaction Terms 3 ALL STOCK TRANSACTION Each holder of Arcturus outstanding capital stock immediately prior to the merger will receive ordinary shares of Alcobra in the merger. NAME AND OWNERSHIP Alcobra shareholders are expected to own 40% of the combined company and Arcturus shareholders are exp
Slide 4: Arcturus Therapeutics Summary
RNA Medicines company focused on significant opportunities in rare, liver and respiratory diseases Strong Intellectual Property Created • UNA Oligomer Chemistry • LUNAR™ Delivery Technology • >110 Patents and Patent Applications, Issued in US, EU, JP, CN and Other Countries Diverse Pipeline Establis
Slide 5: Management Team
Management Team 5 Joseph Payne President & CEO • Co - founded Arcturus in 2013 • 20 years of successful drug discovery experience at Merck Research Labs, DuPont Pharmaceuticals, Bristol - Myers Squibb, Kalypsys , and Nitto • MSc in Synthetic Chemistry from the University of Calgary Pad Chivukula, Ph
Slide 6: Arcturus Pipeline of RNA Medicines
Arcturus Pipeline of RNA Medicines Name RNA Indication Partner LUNAR - OTC mRNA Ornithine Transcarbamylase (OTC) Deficiency LUNAR - RLD mRNA Rare Liver Disease LUNAR - HBV RNA Hepatitis B In Discussion LUNAR - TKD Undisclosed NASH LUNAR - RARE1 mRNA Rare Liver Disease LUNAR - RARE2 mRNA Rare Liver D
Slide 7: Ornithine Transcarbamylase (OTC) Deficiency: the most common urea cycle disorder
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 • Incidence estimated at 1 in 56,000 1 • Up to 180 new patients each year in US & Europe 2 Unmet Medical Need • Present
Slide 8: LUNAR-OTC Proof of Concept in OTC Disease Mouse Model
N o r m a l M i c e D i s e a s e M i c e L U N A R - O T C T r e a t e d M i c e 0 1 2 3 Plasma Ammonia Level after Protein Challenge A m m o n i a L e v e l s R e l a t i v e t o B a s e l i n e p=0.0003 unpaired t-test LUNAR - OTC Proof of Concept in OTC Disease Mouse Model Disease Normalization
Slide 9: Million People Worldwide are Infected with Chronic Hepatitis B Virus
350 Million People Worldwide are Infected with Chronic Hepatitis B Virus • HBV causes a chronic infection that leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma • 880,000 people die each year from complications of HBV 1 • >1 million chronically infected people in the US, largely untre
Slide 10: LUNAR-HBV Preclinical POC: Significant Reduction of HBsAg in Mice
LUNAR - HBV 10 Preclinical POC: Significant Reduction of HBsAg in Mice LUNAR - HBV demonstrates robust reduction of Hepatitis B in mice: • AAV - HBV mouse model: HBsAg 3 log; HBV DNA 3 log; HBeAg 2 log LUNAR - HBV appears to provide comprehensive HBV coverage: • Targets all known HBV transcripts • I
Slide 11: Arcturus Platforms: UNA Oligomer Chemistry and LUNAR Delivery Technology
Arcturus Platforms UNA Oligomer Chemistry and LUNAR™ Delivery Technology 11 O Base OH O P O - O O UNA U nlocked N ucleomonomer A gent UNA Oligomer Chemistry and LUNAR™ Nanoparticle Delivery Enables Multiple Classes of RNA Therapeutics & Chemistry Delivery mRNA siRNA LUNAR™ Nanoparticle
Slide 12: UNA Oligomer Chemistry
UNA Oligomer Chemistry 12 Feature Potential Benefit Proprietary Chemistry All RNA Medicines Potency Clinical Efficacy Longevity of action Less frequent dosing Reduces Off - Target Effects Safety and Tolerability Reduces Immunogenicity Safety Arcturus UNA Oligomers = The Next Generation of RNA Chemis
Slide 13: LUNAR Nanoparticle Delivery
LUNAR™ Nanoparticle Delivery 13 Feature Potential Benefit Proprietary Delivery All RNA Medicines Potency Preclinical Efficacy Biodegradable No Accumulation of Lipids Manufacturing Efficiency Reduced Cost of Goods Arcturus LUNAR™ Nanoparticles = Next Generation of RNA Delivery
Slide 14: RNA Approaches to Medicine
RNA APPROACHES TO MEDICINE geRNA Gene Editing mRNA Up - Regulation siRNA Gene Silencing microRNA Multiple Genes 14 Arcturus Platforms Controlling Gene Expression
Slide 15: LUNAR delivery to multiple cell types versus GalNAc
LUNAR™ can be used for delivery to hepatocytes, stellate cells, myocytes and lung cells LUNAR™ can be used to deliver messenger RNA and mixtures of RNA 15 RNA Companies Utilizing GalNAc Delivery Technology What does GalNAc do? Delivers a single small RNA molecule to hepatocytes via GalNac receptor W
Slide 16: Competitive Advantages
Competitive Advantages 16 Novel UNA chemistry and LUNAR™ delivery technologies provide composition of matter IP LUNAR™ is not limited to a specific type, modality, or size of nucleic acid Specific production of desired proteins in multiple cell types including liver hepatocytes, liver stellate cells
Slide 17: Arcturus Platforms: Key Advancements in RNA Medicines
Arcturus Platforms 17 Key Advancements in RNA Medicines Functional Delivery to Multiple Cell Types mRNA Half - Life Extension in vivo in vivo Delivery in Primates Safely Deliver RNA in Multiple Species UNA and LUNAR™ Platforms Overcome Challenges in mRNA Therapeutic Development Source internal Arctu
Slide 18: LUNAR Unlocks Potential for mRNA
Potentially Improved Safety: Transient not Permanent Significant Opportunity: Infectious Disease, Oncology, Metabolic, Cardiovascular Disease, Gene Editing CHAPERONES RECEPTORS CRISPR TALEN ENZYMES LUNAR™ Unlocks Potential for mRNA 18 GPCRs TRANSPORTERS TRANS - MEMBRANE PROTEINS ENGINEERED NUCLEASES
Slide 19: Summary
RNA Medicines Company, Founded in 2013, 52 FTEs, San Diego, CA Focused on significant opportunities in rare , liver and respiratory diseases Strong Intellectual Property Created • UNA Oligomer Chemistry • LUNAR™ Delivery Technology • >110 Patents and Patent Applications, Issued in US, EU, JP, CN and
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