Benzinga | Dec 7, 2020 07:05AM EST

Arcturus Therapeutics Announces Initiation of Dosing ARCT-810 in Patients with Ornithine Transcarbamylase (OTC) Deficiency

Arcturus Therapeutics Holdings Inc. ((the &ldquo, Company&rdquo, , &ldquo, Arcturus&rdquo, , NASDAQ:ARCT), a leading clinical-stage messenger RNA medicines company focused on the development of infectious disease vaccines and significant opportunities within liver and respiratory rare diseases, today announced that it has initiated dosing in its Phase 1b study of ARCT-810 in patients with Ornithine Transcarbamylase (OTC) deficiency, a serious disease with limited treatment options, at a clinical site in the United States. ARCT-810 is Arcturus' flagship rare disease asset utilizing the Company's novel systemically administered mRNA therapeutic platform.

The ongoing Phase 1b study will evaluate approximately twelve patients with OTC deficiency. ARCT-810 will be administered at doses between 0.2 mg/kg and 0.4 mg/kg, and all dose levels are expected to be within the therapeutic range, based on preclinical study data. The Phase 1b study will assess safety, tolerability and pharmacokinetics, as well as various exploratory biomarkers of drug activity.

Arcturus previously announced that it had completed the ARCT-810 Phase 1, dose escalation study in healthy subjects, at doses up to 0.4 mg/kg. In that study, ARCT-810 was found to be generally safe and well tolerated; no severe adverse events were observed, and no steroid pretreatment was required. The pharmacokinetic profile of ARCT-810 was favorable, and preliminary data shows that no ARCT-810 lipid was detectable in the plasma beyond 48 hours following drug administration.

"We are so encouraged by the progress of the ARCT-810 study in OTC deficiency and the promise this novel mRNA therapeutic approach holds for saving and improving the lives of patients affected with this devastating disorder," said Cynthia Le Mons, Executive Director of National Urea Cycle Disorders Foundation.

"The initiation of dosing in the ARCT-810 Phase 1b clinical trial in patients with OTC deficiency builds upon the favorable prior Phase 1 study results, as well as encouraging preclinical data which showed that ARCT-810 resulted in robust OTC protein expression, improvements in ureagenesis and plasma ammonia, and increased survival," said Steve Hughes, M.D., Chief Development Officer of Arcturus. "We are pleased to have now initiated dosing of ARCT-810 in patients with OTC deficiency. We look forward to obtaining clinical data throughout 2021."

About Ornithine Transcarbamylase (OTC) deficiency

Ornithine Transcarbamylase (OTC) deficiency is a serious urea cycle disorder with a prevalence of approximately 10,000 worldwide. 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 are no FDA approved medicines for OTC deficiency.

About ARCT-810

ARCT-810 utilizes Arcturus' LUNAR(r) lipid-mediated delivery platform to deliver OTC messenger RNA to liver cells. Expression of OTC enzyme in the liver of patients with OTC deficiency has the potential to restore normal urea cycle activity, preventing neurological damage and the need for liver transplantation. The ARCT-810 program is supported by preclinical data in OTC deficiency murine models demonstrating that dosing of LUNAR-OTC results in robust ornithine transcarbamylase protein expression and activity resulting in improvements in ureagenesis and plasma ammonia and in increased survival.