Arcturus Therapeutics (NASDAQ:ARCT) used a presentation at Guggenheim’s 2026 Emerging Outlook Biotech Summit to highlight upcoming milestones for its messenger RNA (mRNA) rare disease pipeline, with CEO Joe Payne emphasizing progress in inhaled mRNA for cystic fibrosis (CF) and an intravenously dosed liver-targeted program for ornithine transcarbamylase (OTC) deficiency.
Positioning as an mRNA medicines company with rare disease focus
Payne described Arcturus as an mRNA medicines company with “a pair of rare disease therapeutic products” in advanced development, both in Phase 2. He said the company views itself as a leader in inhaled mRNA, calling it a “big white space opportunity” and noting that “no one’s been successful with inhaled mRNA.”
CF: ARCT-032 dose escalation and early signals
Payne reviewed Phase 2 data generated across three cohorts dosed daily for 28 days at 5 mg, 10 mg, and 15 mg of inhaled mRNA. He said Arcturus has escalated to 15 mg daily, which he described as a “substantial dose of mRNA to be inhaled,” and framed tolerability as a key hurdle given what he characterized as decades of safety and tolerability challenges for inhaled RNA approaches.
Across the early cohorts, Payne said the company observed a dose-responsive and “significant drop in mucus and mucus plugs,” measured using high-resolution CT scans. He added that investors are now focused on whether mucus plug reduction will translate into measurable lung function benefits, particularly over longer treatment periods.
Planned Phase 2b: larger, longer, with stronger baseline and added endpoints
Arcturus plans to initiate a Phase 2b study (also described as a fourth cohort in the Phase 2 program) in the first half of the year. Payne said the design differs meaningfully from the earlier cohorts, including:
- More patients: 20 subjects, compared with the smaller early cohorts.
- Longer treatment: 12 weeks, compared with 28 days previously.
- More robust baseline: multiple baseline measurements and review of one to two years of historical data per patient.
- Protocol adjustments to reduce variability: if baseline measurements are unstable due to factors such as illness or seasonal effects, patients can withdraw and reinitiate once baseline is steady.
- Multiple lung assessments: lung function endpoints including both FEV and lung clearance index (LCI), along with pre- and post-treatment high-resolution CT scans.
Payne described LCI as a more sensitive assessment that is used in CF drug approvals in children and said Arcturus plans to evaluate it in adults alongside FEV. He also said high-resolution CT imaging is expected to provide supportive evidence, although he noted it was not anticipated to be a primary endpoint.
On dose selection, Payne said 10 mg produced “promising and significant” mucus plug reduction, while 15 mg evaluation is ongoing. He said the company is focused first on confirming safety and tolerability at 15 mg and, if tolerability and mucus plug reduction are supported, it would “likely proceed with 15 mg” in the upcoming cohort.
Payne also discussed how the company is thinking about meaningful clinical change, noting that for FEV, improvement is “typically” around 3% to 4%. He added that LCI is more sensitive and that improvements could potentially be detected even when changes are not captured by FEV. He cited one subject who experienced a 3.5% increase in FEV over 28 days, which he attributed to resolution of larger mucus plugs visible on imaging.
Regarding timing, Payne said the company would provide more detailed guidance after seeing recruitment rates. He described a planned footprint of “well over 10 sites” in the U.S. and additional international sites, and said the patient population is motivated, but he did not provide a specific data timeline. He noted that interim looks are possible.
OTC deficiency: biomarker results and near-term regulatory discussions
Payne characterized ARCT-810, the company’s OTC deficiency program, as a “dark horse” asset and said Arcturus has established safety and tolerability and shown effects in multiple Phase 2 trials on biomarkers including ammonia, urea, and glutamine. He highlighted that the company has shown it can “normalize glutamine after just a handful of doses.”
He argued that the key overhang for the program is uncertainty around the regulatory path, which he said has limited investor ability to value the asset. Payne said Arcturus expects “a pair of Type C meetings” with the FDA in the first half of the year, including one focused on pediatric patients six years old and under, whom he described as having the most significant unmet need.
Payne also focused on glutamine as a potential biomarker of interest, explaining that while current standard of care includes ammonia scavengers and diet control, patients can still feel unwell, which he attributed to glutamine dynamics and effects in the brain. He said glutamine has not historically served as a biomarker in trials, and suggested that value inflection would come if regulators align on its relevance.
On trial execution, Payne said pediatric recruitment could be relatively quick due to family motivation, while adult recruitment has historically been more difficult.
Balance sheet and operating posture
Payne said Arcturus reported “$237 million plus” in cash as of Sept. 30 and expects to provide an updated figure in early March on its quarterly/annual call. He said the company’s runway extends “well into 2028.” Payne also stated that Arcturus has not raised money in approximately five years, and described a leaner operating model, noting headcount has been reduced from about 220 to under 100 people as the company focuses on CF and OTC development progress this year.
About Arcturus Therapeutics (NASDAQ:ARCT)
Arcturus Therapeutics Holdings Inc is a clinical-stage biotechnology company dedicated to developing messenger RNA (mRNA) medicines that address a range of diseases. The company leverages its proprietary STARR® mRNA platform to enable precise control over mRNA expression, supported by its lipid nanoparticle delivery technology, LUNAR®. Arcturus’s approach is designed to address both therapeutic and prophylactic applications, with an emphasis on vaccines and treatments for rare genetic and infectious diseases.
The company’s pipeline includes ARCT-810, an mRNA therapeutic candidate for phenylketonuria (PKU), and ARCT-021 (also known as LUNAR-COV19), a COVID-19 vaccine candidate developed in collaboration with Duke-NUS Medical School in Singapore.
