Arcturus Therapeutics Holdings Inc.

Good day, everyone, and welcome to the Arcturus Therapeutics Second Quarter 2025 Earnings Call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question and answer session. You may register to ask questions by pressing the star and 1 on your telephone keypad. You may withdraw your question by pressing star 2. Please note, this call is being recorded. and that will be standing by should you need any assistance. It is now my pleasure to turn the conference over to Netta Safarzadeh, Vice President, Head of Investor Relations, Public Relations Marketing. Please go ahead.

Thank you, Operator. Good afternoon and welcome to Arcturus Therapeutics Quarterly Financial Update and Pipeline Progress Call. Today's call will be led by Joe Payne, our President and CEO. and Andy Sassine, our CFO. Dr. Pat Chivakula, our CSO and COO, will join them for the Q&A session. Before we begin, I would like to remind everyone that the statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by this statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the risk factor section in our most recent Form 10-K and in subsequent filings with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made. Arcturus specifically disclaims any obligation to update such statements. And with that, I will now turn the call over to Joe.

Thank you, Netta. It's good to be with you again, everybody. I will begin with our ARCT032 program. This is our messenger RNA therapeutic candidate for cystic fibrosis. Arcturus is advancing enrollment of adult CF participants in the Open Label Phase II Multiple Ascending Dose CF study with daily inhaled treatments of ARCT032 over a period of 28 days. There is serious unmet medical need in the CF community, especially with those that do not qualify. or benefit from CFTR modulator therapy. Our present phase two trial is focused on enrolling subjects that do not benefit from modulators, including class one or null CF participants. We have completed the enrollment and dosing of all three participants in the five milligram cohort. After a safety review, we were permitted to proceed with enrolling the second cohort at the 10 milligram dose level. All six CF participants in the second cohort are expected to complete dosing in early September. Each participant in the second cohort receives 280 milligrams of ARCTO32 over the span of 28 days. And dosing at this level for 28 consecutive days is differentiating. And it's attributed to our modification design and proprietary purification of our mRNA drug substance and to the novel chemical features of our optimized lunar delivery technology. The company expects to provide phase two and term data from these first nine enrolled participants next month in September 2025, and we expect to complete enrollment for this study as planned by year end. Arcturus anticipates meetings with the FDA and regulatory agencies in the first half of 2026 to discuss the phase two data and plans for pivotal trials, including the enrollment of adolescent and pediatric participants, followed by Phase III initiation in 2026. I'll now move on to our ARC T810 program. This is our messenger RNA therapeutic candidate for ornithine transcarbamylase, or OTC, deficiency. In June, the company, along with key opinion leaders, announced positive interim data from two Phase II multiple dose studies conducted in the OTC program. In each study and in the combined analysis of both Phase II studies, decreases in glutamine levels to within normal range were observed following multiple ARCT810 administrations to participants who remained on their standard of care therapy. Mean ammonia levels were stable within the normal range following at least two doses of ARCT810 and remained stable for approximately 28 days after completion of dosing. During the treatment phase and follow-up, two out of three participants in the Phase II U.S. study showed increases in relative ureogenesis function to levels observed in asymptomatic OTC-deficient patients, as measured by a newly developed and optimized 15N ureogenesis assay. The remaining participant demonstrated increased 15N citrulline enrichment. The data taken together suggest improvement of a urea cycle function in all three participants. This orthogonal support of data adds further confidence to the glutamine normalization data that we observed. ARCT810 was generally safe and well tolerated in single dose phase 1 slash 1B and multi-dose phase 2 studies comprising 40 participants to date and including 20 OTC deficient participants. The company is preparing for meetings with the US FDA and other regulatory agencies to discuss the clinical significance of the observed biomarker changes in relation to the design of the Phase III pivotal trial and pediatric studies. Phase III biomarker and trial design alignment with the FDA and other regulatory agencies is expected in the first half of 2026. I will now provide regulatory updates to our partnered COVID-19 vaccine, also known as CoStave. A marketing authorization application to the United Kingdom's MHRA was filed by CSL, our partner, with an approval expected next month. Moving to Japan, MDA applications were filed by Meiji Seika Pharma to the PMDA for the two-dose lyophilized vaccine presentation and for the upcoming season's COVID variant update, with anticipated approvals this fall. U.S. BLA filing. to the FDA remains on track for September with an approval decision expected in 2026. And moving on to ARCT 2138, this is our next generation star seasonal flu vaccine candidate. Under our collaboration with CSL Securus, we conducted a phase one study in 100 young adults and 35 older adults. All tested dose levels of ARCT2138 were immunogenic against all four influenza strains as measured by a hemagglutinin inhibition assay in both age groups, demonstrating a modest dose response within that range of the tested doses. ARCT2138 also induced anti-neuraminidase antibody responses at all tested dose levels against all four influenza strains. The frequencies of unsolicited adverse events and medically attended adverse events were similar to comparator vaccines. No major safety concerns were raised from the study results. Overall, the study showed the potential of our next generation star vaccine encoding eight antigens to induce an immune response in both young and older adults with a dose as low as two micrograms and was tolerable up to 20 micrograms. Now moving on to ARCT 2304. This is our next gen star vaccine candidate for pandemic A slash H5N1 influenza virus, also known as the bird flu. In April, Arcturus received US FDA fast track designation for ARCT 2304. This is the program contracted with and funded by BARDA. This contract was highlighted by the HHS in their recent press release as a program that was not impacted by their new budget and vaccine policy. We've completed recruitment of 212 adults, including 80 participants over the age of 60 years old in a randomized placebo-controlled phase one trial being conducted here in the US. All three tested dose levels, 1.5, 5, and 12 micrograms, in the Phase 1 BARDA-funded study were well tolerated, with the majority of reported solicited AEs being mild to moderate and short-lived. No safety concerns were raised from the available clinical data. The results from this ongoing Phase 1 study are expected later this year. And before passing the call on to our CFO, we're very pleased to announce that Arcturus has appointed Dr. Monsef Slaoui as chairman of the board. which became effective as of July 1st, 2025. And with that, I'll now pass the call to Andy.