Arcturus Therapeutics (NASDAQ:ARCT) CEO and President Joe Payne outlined the company’s current focus on messenger RNA (mRNA) therapeutics, emphasizing a leaner operating profile and a near-term set of clinical and regulatory milestones expected over the coming months.
Speaking at a J.P. Morgan-hosted event, Payne described Arcturus as an mRNA medicines company founded in 2013 and based in San Diego. He said the broader biotech downturn has led Arcturus to become “much leaner and more focused,” with approximately 100 employees and a strategy centered on what he characterized as “value-creating assets.”
Commercial and partnered programs
However, he said the remainder of his remarks would focus on Arcturus-owned therapeutic candidates rather than partnered vaccine programs.
Platform approach: LUNAR delivery and manufacturing
Payne emphasized Arcturus’ delivery platform, which he described as a differentiated lipid nanoparticle system called LUNAR. He said the technology is designed to be biodegradable and non-accumulating and can be optimized for specific cell types. Payne added that Arcturus has developed the ability to deliver mRNA to hepatocytes via intravenous administration, to myocytes via intramuscular administration, and to airway cells via inhaled delivery.
He also underscored manufacturing capabilities as a key differentiator, describing the complexity of producing and purifying mRNA drug substance at scale, formulating it with LUNAR lipid nanoparticles, and performing fill/finish and lyophilization.
Cystic fibrosis: advancing an inhaled mRNA therapeutic
Payne positioned the company’s cystic fibrosis (CF) program as its flagship lung asset. The candidate is an inhaled mRNA therapy intended to drive production of CFTR protein in the lung. He said inhaled mRNA has historically faced safety and tolerability challenges, but Arcturus believes it has reached an acceptable safety threshold and is now in Phase 2.
Payne said Arcturus is preparing to initiate a Phase 2, 12-week study (described as a fourth cohort) in up to 20 CF participants, with daily dosing planned to begin in the first half of the year. He said the CF Foundation has committed approximately $25 million to the program. Payne also cited regulatory designations received for the program, including Rare Pediatric Disease and Orphan Drug designation from the FDA and Orphan Medicinal Product designation from the European Commission.
The company’s initial target population is Class I CF patients who are “null” for the CFTR transporter and therefore ineligible for CFTR modulator therapies, Payne said. He characterized this segment as having the highest unmet need because “there’s nothing to modulate.”
On clinical progress, Payne said a Phase 1 study in 32 healthy volunteers across four ascending doses was safe and well tolerated. A Phase 1b multiple-dose study in seven CF participants supported advancement into Phase 2. In the ongoing Phase 2 program, Arcturus has evaluated 5 mg, 10 mg, and 15 mg daily dosing over 28 days, with the first two cohorts completing dosing and the 15 mg cohort nearing completion.
Payne summarized interim imaging results using high-resolution CT scans analyzed with Thyrona’s FDA-cleared AI technology. He said no mucus plug reduction was observed at 5 mg, while “significant mucus plug reductions” were observed at 10 mg. In the second cohort, he said four of six subjects showed reductions, with a 28%–33% decrease in mucus plugs and mucus volume among responders.
During Q&A, Payne said Arcturus has dosed up to 27 mg in humans and currently expects 15 mg to be the likely dose going forward, though he said the company has not finalized whether the longer study will use 10 mg or 15 mg pending remaining data from the third cohort. He added that the company has not seen “anything that’s alarming or concerning” regarding delivery technology or the mRNA at the tested doses.
Payne attributed historical inhaled mRNA tolerability problems to two issues: impurities in mRNA and lipid accumulation/inflammation. He said Arcturus has addressed impurities through purification innovations and said its lipids are “chemically different,” designed to be “relatively benign, safe, and biodegradable.”
Looking ahead, Payne said the longer 12-week study is intended to explore whether extended treatment can drive further improvements, arguing that as mucus clearance and healing occur, more cells may become accessible to inhaled therapy over time.
OTC deficiency: biomarker signals and regulatory path focus
Payne also highlighted ARCT-810 for ornithine transcarbamylase (OTC) deficiency as the company’s flagship liver program. He described OTC deficiency as a urea cycle disorder associated with elevated ammonia, and said current management relies on ammonia scavengers and strict dietary protein limitation.
He said ARCT-810 is designed to replace the missing OTC enzyme in the liver rather than manage ammonia indirectly. Payne described Phase 1 testing in 24 healthy volunteers up to 0.4 mg/kg as generally safe and well tolerated, and a Phase 1b study up to 0.5 mg/kg in 16 subjects with no serious or severe adverse events. He said the program has progressed into two Phase 2 trials, including one in Europe and one ongoing in the U.S.
On designations, Payne said ARCT-810 has received Orphan Drug, Fast Track, and Rare Pediatric Disease designations from the FDA and Orphan Medicinal Product designation from the European Commission.
Payne discussed interim Phase 2 biomarker data, emphasizing reductions in glutamine levels, increases in ureogenesis as measured by an N15 ureogenesis assay, and ammonia remaining stable within normal range. In the European Phase 2 study, he said eight subjects were evaluated, including two on placebo. He said the company was close to enrolling a sixth subject in the U.S. trial and expected to wrap it up relatively soon.
Payne said glutamine levels normalized after a “handful of doses,” with levels rising again about a month after treatment was stopped. On ureogenesis, he said relative ureogenesis function increased by 15% after 28 days (five doses), and two of three participants achieved greater than 50% relative ureogenesis function. He described the findings as evidence of improved urea cycle function.
For next steps, Payne repeatedly pointed to regulatory clarity as the key value driver, saying investors are seeking a clear path from data to approval. He said Arcturus plans Type C meetings with regulators to align on pivotal trial strategies, with separate discussions anticipated for severe pediatric patients (six years and younger) and for adolescent/adult populations.
Cash runway and near-term priorities
In closing remarks and Q&A, Payne said Arcturus has extended its cash runway into 2028 following expense reductions and restructuring. He said the company believes this positions it to pursue 2026 clinical milestones, including initiating the expanded CF cohort and advancing regulatory alignment for ARCT-810.
Payne added that while the company remains “laser-focused,” it is also allocating a small portion of its budget to additional programs, with potential pipeline updates “likely later 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.
