Treatment of Ornithine Transcarbamylase (OTC) Deficiency

San Diego CA—Arcturus Therapeutics Holdings Inc. (NASDAQ: ARCT), a leading RNA medicines company focused on the development and commercialization of therapeutics towards rare, liver and respiratory diseases with significant unmet medical need, today announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for the Company’s lead product candidate ARCT-810 to treat ornithine transcarbamylase deficiency (OTCD). OTCD is the most common urea cycle disorder. Urea cycle disorders are a group of inherited metabolic disorders that make it difficult for afflicted patients to remove toxic waste products, as proteins are digested. ARCT-810 utilizes Arcturus’ LUNAR® lipid-mediated delivery platform to safely and effectively deliver OTC messenger RNA to liver cells.
The FDA grants Orphan Drug Designation to novel drugs that seek to treat a rare disease or condition and provides 7 years of market exclusivity if approved, plus significant development incentives, including tax credits related to clinical trial expenses, an exemption from the FDA-user fee, and FDA assistance in clinical trial design.
“Orphan Drug Designation is a very important regulatory milestone in our development plan for ARCT-810,” said Joseph Payne, President and Chief Executive Officer of Arcturus Therapeutics. “We are working diligently to address the significant unmet medical need in people afflicted by OTC deficiency and this designation furthers our mission to develop a mRNA therapeutic product utilizing our LUNAR technology.”
“OTC deficiency is a life-threatening genetic disease. Current treatment options involve life-long restriction of protein intake, nitrogen scavenger therapy as well as liver transplant for those patients that are suitable,” said Pad Chivukula, Ph.D., Chief Scientific Officer of Arcturus. “Our therapeutic approach, based on our LUNAR platform, is designed to enable OTC-deficient patients to naturally produce healthy functional OTC enzymes in their own liver cells. By intervening directly in the underlying disease process, ARCT-810 has the potential to be a transformative messenger RNA therapy for these patients.”

About ARCT-810
ARCT-810, Arcturus’ first development candidate, represents a novel approach to treat ornithine transcarbamylase deficiency (OTCD). ARCT-810 is based on Arcturus mRNA design construct and proprietary manufacturing process. ARCT-810 also utilizes Arcturus’ propriety lipid library and employs the Company’s LUNAR® delivery platform to safely and effectively deliver OTC mRNA to hepatocytes. ARCT-810 is an mRNA replacement therapy designed to enable OTC-deficient patients to naturally produce healthy functional OTC enzyme in their own liver cells. Arcturus plans to submit an Investigational New Drug (IND) application to the FDA in the first quarter of 2020. ARCT-810 is advancing toward the clinic on the strength of preclinical proof-of-concept data, demonstrating that LUNAR technology can deliver mRNA to liver cells and results in expression of functional OTC protein in animal models. Replacing the deficient OTC protein restores the urea cycle pathway, resulting in reduced plasma ammonia and urinary orotate concentrations.
About Ornithine Transcarbamylase Deficiency (OTCD)
OTC deficiency is caused by mutations in the OTC gene which leads to a non-functional or deficient OTC enzyme. OTCD is the most common urea cycle disorder. Urea cycle disorders are a group of inherited metabolic disorders that make it difficult for afflicted patients to remove toxic waste products as proteins are digested. OTC deficiency is a life-threatening genetic disease. OTC is a critical enzyme in the urea cycle, which takes place in liver cells, and converts ammonia to urea. This conversion does not occur properly in patients with OTC deficiency and ammonia accumulates in their blood, acting as a neurotoxin and liver toxin. This can cause severe symptoms including vomiting, headaches, coma and death. OTC deficiency is an inherited disease that can cause developmental problems, seizures and death in newborn babies. It is an X-linked disorder, so is more common in males. Patients with less severe symptoms may present later in life, as adults. There is currently no cure for OTC deficiency, apart from liver transplant. However, this treatment comes with significant risk of complications such as organ rejection, and transplant recipients must take immunosuppressant drugs for the rest of their lives. Current standard of care for OTC patients is a low-protein diet and ammonia scavengers to try and prevent patients from accumulating ammonia. These treatments do not address the underlying cause of disease.
About Arcturus Therapeutics Holdings Inc.
Founded in 2013 and based in San Diego, California, Arcturus Therapeutics Holdings Inc. (NASDAQ: ARCT) is an RNA medicines company with enabling technologies – LUNAR® lipid-mediated delivery and Unlocked Nucleomonomer Analog (UNA) chemistry – and mRNA drug substance along with drug product manufacturing. Arcturus’ diverse pipeline of RNA therapeutics includes programs to potentially treat Ornithine Transcarbamylase (OTC) Deficiency, Cystic Fibrosis, Glycogen Storage Disease Type 3, Hepatitis B, and non-alcoholic steatohepatitis (NASH). Arcturus’ versatile RNA therapeutics platforms can be applied toward multiple types of nucleic acid medicines including messenger RNA, small interfering RNA, replicon RNA, antisense RNA, microRNA, DNA, and gene editing therapeutics. Arcturus technologies are covered by its extensive patent portfolio (167 patents and patent applications, issued in the U.S., Europe, Japan, China and other countries). Arcturus’ commitment to the development of novel RNA therapeutics has led to partnerships with Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, Ultragenyx Pharmaceutical, Inc., Takeda Pharmaceutical Company Limited, Synthetic Genomics Inc. and the Cystic Fibrosis Foundation. For more information, visit www.Arcturusrx.com.

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