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 RNA medicines for diseases with significant unmet medical needs and accelerated clinical paths.

Our external development partners include Janssen Pharmaceuticals, Inc., Ultragenyx Pharmaceutical Inc., Takeda Pharmaceutical Company Limited, CureVac AG and Synthetic Genomics, Inc.

LUNAR-OTC

In a wholly owned program, Arcturus is developing a messenger RNA (mRNA) medicine to treat ornithine transcarbamylase deficiency, a life-threatening genetic disease that affects over 10,000 people worldwide.

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 is working to develop mRNA 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-OTC is currently in Phase 2 ongoing clinical studies.

LUNAR-CF

Arcturus is collaborating with the Cystic Fibrosis Foundation 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-COV19

Arcturus is in collaboration with Duke-National University of Singapore (Duke-NUS) Medical School is developing an mRNA vaccine to prevent COVID19 coronavirus infection.

COVID-19
SARS-CoV-2 is a novel coronavirus. Coronaviruses, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) cause respiratory tract infection in humans. Most patients have mild symptoms and good prognosis. However, for COVID-19, patients have developed severe pneumonia, pulmonary edema, acute respiratory distress syndrome (ARDS) or multiple organ failure. The World Health Organization has declared the outbreak to be a pandemic, a “public health emergency of international concern.”

The LUNAR-COVID19 Solution
Arcturus is combining its self-replicating mRNA STARR™ Technology with their LUNAR® RNA medicine delivery technology to developing a prophylactic vaccine against COVID-19. The combination of these two technologies results in (1) an mRNA vaccine that can be produced more rapidly than conventional adjuvanted protein based vaccine; (2) a significant reduction in the mRNA dose required to elicit a protective immune response; and (3) an increase in the duration of antigen expression potentially yielding protection from COVID-19 with a single dose. LUNAR-COVID19 is currently undergoing phase 3 clinical trials.

LUNAR-FLU

Influenza Virus
Influenza, the disease commonly called “flu” is caused by RNA viruses belonging to the Orthomyxoviridae family. Flu season, the period where the virus is most contagious, typically starts in October and ends in May in the US. During the 2019-2020 flu season, the CDC estimates 39 to 56 million American flu illnesses, approximately 0.5 million hospitalizations, and 24 to 62 thousand deaths. High risk groups include for example children, the elderly, pregnant women, health care workers, and people with diabetes or pulmonary complications such as asthma and COPD. Vaccines against influenza are targeting hemagglutinin (HA), which is a glycoprotein in the viral envelope and is responsible for the virus’ ability to infect cells. Like most other RNA viruses, the influenza virus has a high mutation rate. This results in so-called genetic drift which results in the regular occurrence of new strains. The genetic drift requires vaccine manufacturers to predict the influenza strains that will be prevalent for an upcoming influenza season, manufacture and distribute the vaccines in time to be protective. Manufacturing methods for influenza vaccines have improved to decrease the time of manufacture but still are slow to respond if an unpredicted mutation occurs, especially if the mutation results in a more contagious strain. Development of vaccine technology that can quickly respond to viral genetic variations would allow for a later manufacturing start and may therefore be engineered based on more recent epidemiological data than vaccines for which production needs to start earlier each year.

The LUNAR-FLU Solution
Arcturus is combining its self-replicating mRNA STARR™ Technology with their LUNAR® RNA medicine delivery technology to developing a prophylactic vaccine against influenza. The combination of these two technologies results in (1) an mRNA vaccine that can be produced more rapidly than conventional inactivated flu vaccines; (2) a significant reduction in the mRNA dose compared to standard mRNA vaccine technologies; (3) more rapid production cycle to meet market demands and potentially allow for better seasonal flu strain prediction; (4) the ability to include antigens to increase the coverage against multiple influenza strains as a result of genetic drift.