Arcturus Therapeutics has announced the initiation of Phase 2 multiple ascending dose studies for its mRNA therapeutic candidates, ARCT-032 for cystic fibrosis (CF) and ARCT-810 for ornithine transcarbamylase (OTC) deficiency. Dosing commenced in December 2024, marking a significant step forward in the development of novel treatments for these rare diseases. The company anticipates interim data from both programs in the first half of 2025.
ARCT-032 for Cystic Fibrosis
Cystic fibrosis, a life-shortening disease affecting approximately 40,000 people in the U.S. and over 105,000 worldwide, is characterized by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. These mutations lead to a reduction or absence of CFTR protein function in the airways, causing disruption of ion transport and the accumulation of thick mucus. While CFTR modulator medicines are available, approximately 15% of individuals with CF do not benefit from these treatments due to absent CFTR protein or drug intolerance.
ARCT-032 is an inhaled investigational mRNA therapeutic designed to express normal, functional CFTR in the lungs of individuals with CF. The Phase 2 study (NCT06747858) involves daily treatments of ARCT-032 over a 28-day period. ARCT-032 utilizes Arcturus’ LUNAR® lipid-mediated aerosolized platform to deliver CFTR messenger RNA to the lungs, potentially restoring CFTR activity and mitigating the downstream effects that cause progressive lung disease.
Dr. Pad Chivukula, Chief Scientific Officer of Arcturus Therapeutics, stated that ARCT-032 has the potential to address the significant unmet medical need in the CF community for those who do not qualify for or benefit from available treatment options.
ARCT-810 for Ornithine Transcarbamylase Deficiency
Ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder, is caused by mutations in the OTC gene, leading to a non-functional or deficient OTC enzyme. This deficiency results in high blood ammonia levels, which can cause seizures, progressive neurocognitive impairment, coma, and death if untreated. In Europe and the U.S., approximately 10,000 people have OTC deficiency. Current treatments include a low-protein diet and nitrogen scavenging medications, which do not address the underlying cause of the disease. Liver transplant is a curative option but carries significant risks.
ARCT-810 is an intravenously administered investigational mRNA therapeutic designed to express normal, functional OTC enzyme in the liver of individuals with OTC deficiency. The first OTC deficient participant receiving 0.5 mg/kg ARCT-810 initiated dosing in December 2024 in the United States. Each participant is expected to receive five intravenous infusions administered over two months. Arcturus previously completed the dosing phase (N = 8; 0.3 mg/kg) in a placebo-controlled European study and expanded the Phase 2 clinical program into the United States with an open-label multiple-dose study (NCT06488313).
According to Dr. Chivukula, ARCT-810 is the only mRNA therapy currently in clinical development intended to enable liver cells to produce OTC enzyme and therefore address the underlying cause of OTC deficiency.
Arcturus Therapeutics' mRNA Platform
Arcturus Therapeutics, founded in 2013 and based in San Diego, California, is a commercial mRNA medicines and vaccines company with enabling technologies including LUNAR® lipid-mediated delivery and STARR® mRNA Technology. The company's pipeline includes RNA therapeutic candidates for OTC deficiency and CF, along with partnered mRNA vaccine programs for SARS-CoV-2 (COVID-19) and influenza.
