Messenger RNA drug developer Arcturus Therapeutics is ready to kick off its first-ever human trials this year, beginning clinical evaluation of its lead drug candidate and testing a vaccine designed to target the novel coronavirus.
The San Diego biotech on Monday announced it had received the FDA’s OK to enter into the clinic with ARCT-810, an investigational treatment for ornithine transcarbamylase (OTC) deficiency, a rare inherited disease that causes dangerous levels of ammonia to accumulate in the body.
The change marks a pivotal time for Arcturus (NASDAQ: [[ticker:ARCT]]), which only two years ago was embroiled in a messy internal legal battle that threatened its existence. Founder and CEO Joseph Payne, who was temporarily fired during the kerfuffle before being reinstated, is now overseeing the company’s transformation into a clinical-stage enterprise testing its coronavirus vaccine candidate and more.
Arcturus’s lead program is tackling OTC deficiency, an X-linked disorder caused by a mutation to a liver enzyme that plays a key role in breaking down ammonia. Without the enzyme, ammonia rises to an abnormal level and damages the nervous system. Infants with a mutated OTC enzyme can experiences seizures or coma; people affected later in life may experience neurological effects, such as episodes of delirium and erratic behavior, as well as headaches and vomiting. For some, the spikes of ammonia that characterize the disease can be life-threatening. Nearly all patients with OTC deficiency are males; estimates of its prevalence range from 1 in 14,000 to 1 in 77,000 people.
No FDA approved drugs exist for the disorder, which is treated through a diet low in protein and drugs that remove ammonia from the body, but don’t change the course of the disease. The Arcturus treatment, to be delivered intravenously, will be evaluated in a Phase 1b trial in the US with up to 12 patients as well as a study in up to 30 healthy volunteers in New Zealand.
Although the COVID-19 outbreak has stymied many clinical trial plans, the company is optimistic it will soon be able to enroll its first subjects in New Zealand—even though it is currently under a Level 4 alert, which requires all but those providing essential services to stay at home—because restrictions are expected to soon ease because of the number of new COVID-19 infection cases has flattened.
In the US, however, because of the pressure on the healthcare system caused by the outbreak and the prioritization of research into the viral disease at many academic research centers, in addition to social distancing measures, enrollment in the Phase 1b trial won’t start until the second half of this year at the soonest, said Steve Hughes, the company’s chief development officer, speaking on a conference call Monday.
Hughes joined Arcturus in January from San Diego-based Organovo (NASDAQ: [[ticker:ONVO]]), which cut nearly its entire staff in the months after it halted work on its “bioprinted” therapeutic tissue program last year.
The lead Arcturus drug aims to use mRNA, the molecules that carry protein-making instructions, to restore expression of the OTC enzyme in the liver. If that restores the ammonia detoxification process, it could prevent the damage caused by the waste product’s buildup. The drug is delivered using the company’s LUNAR delivery system, which uses lipids to deliver an RNA payload.
The COVID-19 vaccine Arcturus has developed also uses its mRNA and LUNAR delivery technologies—and that gives its candidate an edge over the other mRNA vaccines in development, Payne said on the call. That’s because the technologies allow for lower doses of the drug itself, and obviate the need for some of the materials found in other vaccine candidates, such as a viral vectors, for delivery, and adjuvants, or ingredients included to improve the anticipated immune response, he said.
“That’s a unique advantage because it simplifies the therapeutic vaccine, and the simpler it is, the easier it is to evaluate the safety profile of the therapeutic,” Payne said.
The company has said it plans to dose up to 76 healthy volunteers in Singapore, where it recently struck a deal with a government agency to co-develop a vaccine, starting this summer. If its development is successful, Singapore will own the rights to the vaccine in that country; Arcturus could market it elsewhere.
Image: iStock/RossHelen
