Arcturus Therapeutics

Pipeline

Arcturus Therapeutics, Inc. is an RNA medicines company with enabling technologies — UNA Oligomer™ chemistry and LUNAR™ nanoparticle delivery. Arcturus’ versatile RNA therapeutics platform can be applied toward all types of RNA medicines including small interfering RNA, messenger RNA, antisense RNA, microRNA and gene editing therapeutics. The company owns LUNAR™ nanoparticle delivery and unlocked nucleomonomer agent (UNA) technology including UNA Oligomers™, which are covered by its patent portfolio (77 patents and patent applications, issued in the U.S. and other countries). Arcturus’ proprietary UNA technology can be used to target any gene in the human genome, as well as viral genes, and other species for therapeutic purposes. The Company’s commitment to the development of novel RNA therapeutics has led to collaborations and license agreements with Janssen Pharmaceuticals, Inc. (A Johnson and Johnson Company) and Ultragenyx Pharmaceutical, Inc.

PreclinicalPlatformDiscoveryClinical
name

LUNAR-OTC

indication
Ornithine Transcarbamylase Deficiency
api
mRNA

CO-DEVELOPMENT PROGRAM

CureVac

name

LUNAR-CF

indication
Cystic Fibrosis
api
mRNA

GRANT FUNDED PROGRAM

CFFT

name

LUNAR-GSD3

indication
Glycogen Storage Disease Type III
api
mRNA

COLLABORATION PROGRAM

Ultragenyx

name

LUNAR-RARE

indication
Rare Disease
api
mRNA

COLLABORATION PROGRAM

Ultragenyx

name

LUNAR-HBV

indication
Hepatitis B
api
Nucleic Acid

COLLABORATION PROGRAM

Janssen

name

LUNAR-NASH

indication
NASH
api
Nucleic Acid

COLLABORATION PROGRAM

Takeda

name

LUNAR-Replicon

indication
Vaccines and Therapeutics
api
RNA Replicon

LUNAR® LICENSE-REPLICON RNA

CureVac

name

ARB-1467

indication
Hepatitis B
api
UNA Oligomers

UNA OLIGOMER LICENSE

Arbutus

Overview

We have partnered with a number of industry leaders and have a robust and diverse preclinical drug development pipeline. In collaboration with our development partners, we are leveraging the LUNAR and UNA platforms to develop nucleic acid medicines for diseases with significant unmet medical needs and accelerated clinical paths.

Our external development partners include Janssen Pharmaceuticals, Inc., Ultragenyx Pharmaceutical Inc., Millennium Pharmaceuticals, Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited, Cystic Fibrosis Foundation Therapeutics, Inc., Synthetic Genomics, Inc. and CureVac AG.



LUNAR-OTC

In a co-development program with CureVac AG, Arcturus is developing a messenger RNA (mRNA) medicine to treat ornithine transcarbamylase deficiency, a life-threatening genetic disease that affects approximately 1 in 60,000 people.

Ornithine transcarbamylase deficiency
Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. A lack of the OTC enzyme in liver cells results in high blood ammonia levels and can cause seizures, coma, and death in untreated patients. There is currently no cure for OTC deficiency.

Our LUNAR-OTC solution
Arcturus and CureVac are working to develop RNA medicines that enable OTC patients to make healthy functional OTC enzyme in their liver cells. Preclinical studies have shown that our proprietary LUNAR delivery platform safely and effectively delivers OTC mRNA to liver cells in a mouse model of OTC deficiency, resulting in restoration of disease markers to normal levels.

LUNAR-CF

Arcturus is collaborating with Cystic Fibrosis Foundation Therapeutics, Inc. to develop a messenger RNA (mRNA) medicine to treat cystic fibrosis.

Cystic fibrosis
Cystic fibrosis is a common life-threatening genetic disease in the United States. The disease is caused by over 2,000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. There are over 70,000 patients world-wide.

There are no FDA-approved drugs that can treat all 2,000 CFTR mutations. The FDA has approved three CFTR modulator therapies, Kalydeco®, Orkambi® and Symdeko® (Vertex Pharmaceuticals Inc.), to treat fewer than 40 cystic fibrosis-causing mutations. These drugs do not treat the underlying genetic cause of cystic fibrosis.

Our LUNAR-CF solution
We are developing an mRNA therapeutic using our LUNAR delivery platform to deliver normal CFTR mRNA into airway epithelial cells. This allows airway cells to produce functional CFTR protein using their normal cellular machinery. This approach will be the first to treat the underlying defect that causes cystic fibrosis-dysfunctional or absent CFTR protein-in all patients, regardless of mutation type.

We have completed preclinical proof of concept studies, demonstrating that LUNAR is able to deliver mRNA efficiently into lung epithelial cells in animals and is compatible with nebulization. In cell-based assays, we have also demonstrated that our lead CFTR mRNA has improved functional activity and longer duration of protein expression compared to a reference CFTR mRNA.

LUNAR-HBV

Arcturus has partnered with Janssen Pharmaceuticals, Inc., a Johnson & Johnson company, to develop nucleic acid medicines for the treatment of hepatitis B virus infection and other diseases.

Hepatitis B
Hepatitis B is caused by the Hepatitis B Virus (HBV) and affects more than 350 million people worldwide. It is a major cause of liver disease including cirrhosis and liver cancer. There is no cure for chronic HBV infection. In most cases of chronic hepatitis B, antiviral medication suppresses the virus, but does not clear it completely. Therefore, these medications must be taken for life. Unfortunately, many of these medications have common side effects, including fever, headaches, hair loss, and mental problems. As soon as a patient comes off the medication the virus can return.

Our LUNAR-HBV solution
Arcturus and Janssen are developing a nucleic acid medicine to fight HBV without the same side effect issues that plague existing therapies.

LUNAR-NASH

Arcturus, in partnership with Takeda Pharmaceutical Company Ltd., is developing RNA medicines for the treatment of nonalcoholic steatohepatitis (NASH) and other gastrointestinal disorders, utilizing our wholly-owned therapeutic delivery platform, LUNAR.

Nonalcoholic steatohepatitis (NASH)
Nonalcoholic steatohepatitis (NASH) is the most serious form of nonalcoholic fatty liver disease (NAFLD) and affects 3.5-5% of Americans. NASH is predicted to become the leading cause of end-stage liver disease, liver transplant, and hepatocellular carcinoma in the next two decades. There are no FDA-approved drugs to treat NASH. Doctors currently recommend weight loss and increased exercise to control fat deposition, fibrosis and inflammation in the liver.

Our LUNAR-NASH solution
Takeda and Arcturus are collaborating to develop RNA-based therapeutic candidates to treat NASH. Current program activities include lead candidate identification and duration of action studies in various models of disease.

LUNAR-GSD3

Arcturus has partnered with Ultragenyx to develop messenger RNA (mRNA) therapeutic candidates for certain rare disease targets. The first disclosed indication is Glycogen Storage Disease type III.

Glycogen Storage Disease type III
Glycogen Storage Disease type III (GSDIII) is a genetic disease affecting 1 in 100,000 Americans. GSDIII is caused by mutations in the AGL gene that allow glycogen to accumulate in cells. This can cause low blood sugar levels, muscle weakness and liver damage. There are no specific treatments for GSDIII.

Our LUNAR-RARE1 solution
Arcturus and Ultragenyx are developing mRNA medicines to replace the defective AGL gene product and allow cells to breakdown glycogen using normal pathways.