Arcturus Therapeutics (NASDAQ:ARCT) Chief Executive Officer Joe Payne told investors at the Leerink Partners Global Healthcare Conference that the company has advanced its inhaled messenger RNA cystic fibrosis (CF) program through three Phase 2 cohorts and is preparing to initiate a longer 12-week study designed to better evaluate lung function outcomes.
CF program: 28-day cohorts completed, 12-week study planned
Payne said Arcturus has now completed three 28-day dosing cohorts in its Phase 2 CF study, successfully administering daily inhaled doses of 5 mg, 10 mg, and most recently 15 mg. He emphasized that the therapy has been “consistently well-tolerated” across these dose levels, which he characterized as “generous,” noting that safety and tolerability have historically been major challenges in the field.
Study design changes: baseline stability and patient selection
Discussing the design of the 12-week Phase 2 study, Payne said the company is applying lessons from the earlier cohorts, particularly around variability in lung function measures such as forced expiratory volume (FEV). He said Arcturus plans to “strengthen” baseline assessments by using multiple baseline measurements rather than relying on a single point, and by requiring baseline stability before enrollment. Patients who show instability—such as those entering or recovering from an infection—may be temporarily withdrawn and allowed to re-screen later, he said.
Payne also said Arcturus is narrowing baseline lung function eligibility criteria compared with the earlier approach of enrolling subjects across a wide baseline range (he referenced “40 to 100”). The company, he said, is targeting a “sweet spot” of patients who are neither too high-functioning nor too advanced in disease, to improve the likelihood of detecting a treatment effect over 12 weeks.
Payne noted that Arcturus has a new chief medical officer, Dr. Alan Cohen, who was present at the conference.
Endpoints: FEV, LCI, quality of life, and imaging
Payne said the 12-week study will evaluate multiple measures:
- FEV
- Lung clearance index (LCI)
- Two quality-of-life measures
- High-resolution CT scans before and after the treatment period
He framed the data collection as an effort to better understand how an inhaled mRNA therapy may perform in Class 1 CF patients, emphasizing that Arcturus is not developing a systemic modulator for delta F508 but an inhaled approach for a population he described as often having more than 20 years of advanced disease. He said it may take time to show improvements, likening the process to “peeling away an onion.”
On LCI, Payne described it as a more sensitive, less subjective, and more passive measure than FEV because it is based on tracking gas washout while the patient breathes normally. He said that, in concept, LCI may detect smaller changes such as reductions in smaller mucus plugs, while larger changes might be more readily captured by FEV. He said the correlation between the measures remains unknown and is part of what the company intends to learn.
Dosing and trial footprint
Payne said Arcturus has room to increase dose further, referencing prior experience dosing as high as 27 mg in healthy volunteers. However, he said the company’s current focus is more on treatment duration than dose escalation, arguing that the disease may require extended treatment to see meaningful changes. He said the company observed activity at 10 mg and intends to evaluate longer exposure.
To support enrollment of Class 1 CF patients, Payne said the company is expanding trial sites into Europe and the Middle East, where he said the prevalence of Class 1 patients can be significantly higher than in the U.S. He stated that U.S. prevalence is “approximately 10%,” while some international sites can have 20% to 50% Class 1 representation. He said the company believes the standard of care at those sites is comparable to the U.S. and that Arcturus will provide training as needed, including for LCI.
Regulatory outlook, OTC program, and CSL collaboration updates
On the CF regulatory path, Payne said it is too early to determine whether the 12-week study could support an accelerated approval strategy, and that the company needs the data first. He said a conservative expectation is that Arcturus would conduct a Phase 3 study, with size and duration dependent on safety database needs and the magnitude of efficacy observed. He referenced an external CF Foundation natural history study collecting FEV and LCI in “hundreds” of Class 1 subjects, which he said Arcturus may be able to leverage if Phase 2b results are successful.
Payne said Arcturus plans to initiate the 12-week CF study in the first half of the year and is “very close” to doing so, noting the company already has approval to proceed. He said the study will be open-label, but the company has not provided guidance on timing for sharing results, suggesting there may be an opportunity to share data after 10 subjects complete treatment.
On the company’s ornithine transcarbamylase (OTC) deficiency program, Payne said Arcturus has completed Phase 1/1b work and conducted multiple Phase 2 studies in the U.S. and Europe, with the U.S. effort nearing completion. He said the key objective now is establishing a clear regulatory path in children, which he described as the “most significant commercial opportunity” and highest unmet need. Payne said Arcturus is conducting a pair of Type C meetings with the FDA and expects clarity within the next three months on a path forward, including pediatrics. He also highlighted use of a “15N ureagenesis assay,” which he said has not previously been employed with the FDA, and said ammonia control is expected to remain central in severe pediatric disease.
Payne also addressed the company’s partnered respiratory vaccine franchise with CSL, noting that KOSTAIVE has been approved in multiple regions and commercialized in Japan, with U.K. approval occurring in January. He said arbitration related to a European milestone remains ongoing, and that Arcturus is also in broader discussions with CSL about the overall collaboration after FDA communication ahead of a planned U.S. BLA filing created challenges for vaccine companies. He did not provide specifics on the discussions, but said they could prove positive for Arcturus.
Asked about cash runway, Payne said Arcturus’ runway guidance extends into the second quarter of 2028 and does not include any potential milestone revenue under arbitration, business development, or other ongoing legal matters.
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.
