Earnings Call Transcript - ARCT Q2 2025

Operator, Operator

Good day, everyone, and welcome to the Arcturus Therapeutics Second Quarter 2025 Earnings Call. Please note this call is being recorded. It is now my pleasure to turn the conference over to Neda Safarzadeh, Vice President, Head of Investor Relations, Public Relations Marketing. Please go ahead.

Neda Safarzadeh, Vice President, Head of Investor Relations, Public Relations Marketing

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. Pad Chivukula, 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 Factors 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.

Joseph E. Payne, President and CEO

Thank you, Neda. It's good to be with you again, everybody. I will begin with our ARCT-032 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 ARCT-032 over a period of 28 days. There is a serious unmet medical need in the CF community, especially with those that do not qualify or benefit from CFTR modulator therapy. Our present Phase II trial is focused on enrolling subjects that do not benefit from modulators, including Class I or null CF participants. We have completed the enrollment and dosing of all 3 participants in the 5-milligram cohort. After a safety review, we were permitted to proceed with enrolling the second cohort at the 10-milligram dose level. All 6 CF participants in the second cohort are expected to complete dosing in early September. Each participant in the second cohort receives 280 milligrams of ARCT-032 over the span of 28 days. 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 II interim data from these first 9 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 II 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 ARCT-810 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 2 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 ARCT-810 administrations to participants who remained on their standard of care therapy. Mean ammonia levels were stable within the normal range following at least 2 doses of ARCT-810 and remained stable for approximately 28 days after completion of dosing. During the treatment phase and follow-up, 2 out of 3 participants in the Phase II U.S. study showed increases in relative urea genesis function to levels observed in asymptomatic OTC deficient patients as measured by a newly developed and optimized 15N-ureagenesis assay. The remaining participant demonstrated increased 15N-citrulline enrichment. The data taken together suggest improvement of urea cycle function in all 3 participants. This orthogonal supportive data adds further confidence to the glutamine normalization data that we observed. ARCT-810 was generally safe and well tolerated in single-dose Phase I/Ib and multi-dose Phase II studies, comprising 40 participants to-date and including 20 OTC-deficient participants. The company is preparing for meetings with the U.S. 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 in 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, NDA applications were filed by Meiji Seika Pharma to the PMDA for the 2-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 STARR seasonal flu vaccine candidate. Under our collaboration with CSL Seqirus, we conducted a Phase I study in 100 young adults and 35 older adults. All tested dose levels of ARCT-2138 were immunogenic against all 4 influenza strains as measured by a Hemagglutination Inhibition assay in both age groups, demonstrating a modest dose response within that range of the tested doses. ARCT-2138 also induced anti-neuraminidase antibody responses at all tested dose levels against all 4 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 STARR vaccine encoding 8 antigens to induce an immune response in both young and older adults with a dose as low as 2 micrograms and was tolerable up to 20 micrograms. Now moving on to ARCT-2304. This is our next-gen STARR vaccine candidate for pandemic A/H5N1 influenza virus, also known as bird flu. In April, Arcturus received U.S. 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 I trial being conducted here in the U.S. All 3 tested dose levels, 1.5 micrograms, 5 micrograms, and 12 micrograms in the Phase I 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 I 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. Moncef Slaoui as Chairman of the Board, which became effective as of July 1, 2025. And with that, I'll now pass the call to Andy.

Andrew H. Sassine, CFO

Thank you, Joe, and good afternoon, everyone. The press release issued earlier today includes financial statements for the second quarter of 2025 and provides a summary and analysis of year-over-year performance. Please also reference our most recent Form 10-Q for more details on the financial performance. As we announced on our last quarterly call in May, our restructuring plan is in the final stages of implementation as we continue to consolidate operations. We have streamlined our internal pipeline to focus on our OTC and Cystic Fibrosis programs, which enabled us to extend our runway into 2028. As I provide a summary of our financial results for the second quarter of 2025, please take note of the significant reduction in year-over-year and sequential operating expenses. Revenue for the 3 and 6 months ended June 30, 2025, was $28 million and $58 million, respectively, representing decreases of $22 million and $30 million compared to the same period in 2024. The declines were primarily driven by lower revenues from the CSL collaboration reflecting lower supply agreement activity and amortization of the upfront payment as CoStave progresses toward global commercialization. Total operating expenses for the 3 months ended June 30, 2025, were $40 million compared with $71 million for the 3 months ended June 30, 2024. Total operating expenses for the 6 months ended June 30, 2025, were $86 million compared to $139 million in the prior year. Research and development expenses were $29.6 million for the 3 months ended June 30, 2025, compared with $58.7 million in the prior year. The significant decrease was primarily driven by lower manufacturing costs for our COVID, Flu, and Cystic Fibrosis program and reduced clinical trial expenses for COVID and OTC. Lower payroll and employee benefits also contributed to the decrease, which were partially offset by higher clinical costs for the CF following the ramp-up of Phase II trials in 2025. Research and development expenses were $64.5 million for the 6 months ended June 30, 2025, compared to $112.2 million in the prior year. The decrease was primarily driven by lower manufacturing and clinical costs for the CoStave program, reflecting the program's transition from the development to commercial phase. Additional decreases resulted from lower payroll and benefit expenses and reduced facilities and equipment costs. These reductions were partially offset by higher clinical expenses for the Cystic Fibrosis programs. General and administrative expenses were $10.3 million and $21.7 million for the 3 and 6 months ended June 30, 2025, respectively, compared with $12.3 million and $27.2 million in the comparable period last year. The decreases in both periods were primarily due to reduced share-based compensation expense as well as reduced headcount and employee benefits. We expect general and administrative expenses to continue to decrease slightly during the next 12 months. For the 3 months ended June 30, 2025, Arcturus reported a net loss of approximately $9.2 million or $0.34 per diluted share compared with a net loss of $17.2 million or $0.64 per diluted share in the 3 months ended June 30, 2024. Cash, cash equivalents, and restricted cash were $253.4 million as of June 30, 2025, and $293.9 million on December 31, 2024. Based on the current pipeline and the reallocation of resources to the Cystic Fibrosis and OTC programs, the cash runway remains extended into 2028. In summary, the company remains in a strong financial position and has the cash runway needed to achieve multiple near-term value-creating milestones for both the therapeutic programs. We look forward to an exciting second half of 2025 with upcoming clinical data readouts from both our therapeutics and vaccine programs. I will now pass the call back to Joe.

Joseph E. Payne, President and CEO

Thanks, Andy. Arcturus had a productive quarter, making excellent progress across our mRNA therapeutics and vaccines pipeline. We look forward to sharing 2 cohorts of Phase II CF data in September. And with that, let's turn the time over to the operator for questions.

Operator, Operator

We'll take our first question from Lili Nsongo with Leerink Partners.

Lili Nsongo, Analyst

Maybe 2 CF-related questions. So as we get closer to the readout, can you maybe give us a refresher as to how you think about the bar for success there? And in terms of the patients that have already been enrolled, could you give us a little more granularity in terms of the ratio of modulator-eligible to non-eligible patients?

Joseph E. Payne, President and CEO

Thank you for the questions. To clarify, the historical precedent for cystic fibrosis treatments has been centered around modulators, which the regulatory bodies have indicated require a 3% threshold to move forward in development. It's important to note that modulators are small molecules that distribute throughout the body, primarily targeting Delta 508 participants. In contrast, our approach with Arcturus involves developing an inhaled messenger RNA therapeutic that is delivered directly to the bronchial epithelial cells. We're also focusing on the most challenging segment of the CF community, namely Class I subjects or those who do not respond to modulators. In response to your question, the FDA has communicated that establishing safety, tolerability, and a positive measurable FEV would permit further advancement. If we can demonstrate that our treatments are safe and effective with a positive FEV, we'll move ahead in the development process. This would represent a significant advancement for modulator non-responders, although there is an established expectation from the modulator field that a 2.5% to 3% threshold will be necessary, which will likely influence our discussions with the regulatory agency. Regarding your second question about the distribution of modulator non-responders in our trial, I can provide some clarity. The vast majority of the nine subjects enrolled so far are Class I subjects. While we do have some participants who are not Class I modulators, a strong majority fall into that Class I category.

Operator, Operator

Our next question comes from Yasmeen Rahimi with Piper Sandler.

Yasmeen Rahimi, Analyst

I'm really looking forward to the data coming in September, specifically one related to CF and one related to OTC. Could the team discuss the safety and efficacy data? What do you observe on a blinded basis, especially regarding the safety of your product? Additionally, could you provide more details on your engagement with the agency regarding the pivotal design alignment and the work done to permit the use of biomarkers as a registrational endpoint? Would glutamate potentially be applicable? I would appreciate more information on both of these questions, and I'll join back in the queue.

Joseph E. Payne, President and CEO

All right. Thanks, Yas. Good to hear from you. Regarding safety, the industry has been working on inhaled RNA therapeutics for decades, but these efforts have not been successful. The main reasons for this are issues related to toxicology and tolerability. Toxicology issues often arise from either the lipids used in the delivery system being too toxic or impurities in the mRNA drug substance. Clinically, this shows up as bronchospasms, which are unwanted inflammatory responses, and febrile reactions, or unwanted immune responses like elevated fevers. Inflammatory responses are generally linked to toxic lipids, while febrile reactions can be linked to impurities in the mRNA construct. Arcturus is addressing these challenges with ARCT-032 by offering strong intellectual property and innovations in the delivery system that tackle the problem of accumulating toxic lipids. We have also been developing purification intellectual property for over a decade, which enables us to effectively purify the drug substance and eliminate harmful impurities that can lead to problematic febrile reactions or immune responses. We are focused on improving the issues the field has faced for many years. Switching to OTC, we have made progress in familiarizing the regulatory agency with our approach regarding the N15-ureagenesis assay. They understand our strategy and are looking forward to seeing our data. We have shared papers demonstrating the impact of potential biomarkers, including a recent study on ureagenesis. We plan to meet with them to discuss the recent Phase II data in the upcoming months, although the exact format of those meetings is still being decided. It's important to us to achieve alignment with the FDA and other regulatory agencies regarding the Phase III trial, and we see this alignment as a potential value addition for the program. I'll stop my comments there. Thank you for the questions.

Operator, Operator

Our next question comes from Seamus Fernandez with Guggenheim.

Seamus Christopher Fernandez, Analyst

Great. Thanks for the question. I just wanted to confirm that the highest dose data will be fully represented out to 28 days. I wanted to confirm that the 10-milligram cohort and at least six patients' worth of data would be available out to 28 days. Please go ahead with your next question.

Joseph E. Payne, President and CEO

No, yes. So the first question is, yes, absolutely, 28 days, all 9 subjects. Most of these would also have their day 56 data. We do collect FEV after 56 days. There's even 2 months follow-ups after that. But with respect to the final subject, we'll just have 28-day data. They are in the study.

Seamus Christopher Fernandez, Analyst

Can you remind us how you would define clinically meaningful? Historically, thought leaders we've spoken with have indicated that at least 3% on the low end is significant, but 5% would definitely be considered clinically meaningful from their perspective. I would like to hear your thoughts on this and if there is a standard the FDA might be looking for regarding what they define as clinically meaningful as you prepare to meet with the agency in the first half of next year.

Joseph E. Payne, President and CEO

Yes, I think 3% is reasonable. However, I want to clarify that our program is not a modulator. It's not systemically administered to Delta 508s. It's inhaled mRNA that targets a more challenging population with a more severe unmet medical need. This will be part of our discussion with the FDA. Additionally, we will consider the theoretical possibility of further FEV elevation as the study is extended over a longer period. What I mean by this is if we observe a 3% improvement after 28 days, then the likelihood of seeing even greater improvements in months 2 or 3 with extended dosing is theoretically very high. This would be viewed very positively, regardless of the actual positive number. The FDA is primarily concerned about safety, tolerability, and any measurable positive FEV, especially given the 28-day study. This would indicate a lot of positive responses and feelings, allowing us to advance further into development as we extend the study into Phase III.

Andrew H. Sassine, CFO

Just to add to Joe's comments, keep in mind, Seamus, that this class of population unfortunately has a degradation of FEV on an annual basis. Consequently, their lifespan is shortened. An opportunity to increase it or stabilize it for this class of population would be quite remarkable and certainly offer them an opportunity to have an extension of life.

Operator, Operator

We will move next with Myles Minter with William Blair.

Jacob Roberge, Analyst

This is Jake on for Myles. I wanted to ask a couple more questions regarding CF. I was curious about the level of interest in patient enrollment after the Vertex and Moderna trial was paused, and whether you observed any change in interest for your trial. Additionally, we would appreciate your thoughts on the reopening of that trial and whether you believe the safety issue raised by the DSMB can be resolved.

Joseph E. Payne, President and CEO

Yes. With respect to the first question, we have several sites open and recruiting subjects. In the sites where there was overlap with competitors, if those competitors are no longer recruiting, yes, that would directly help or impact our recruitment rate there. But only a small number of sites do we have overlap with our competitors. We're working closely with the CF Foundation, and they've identified sites that have limited competition for us for recruitment. So from that perspective, no. With respect to your other question, it would be inappropriate for me to speculate on what's happening with our competitors with the Vertex program. I don't want to come across as catalyst, but we frankly don't care that much. When we started this process, there were a half dozen of these companies aggressively pursuing this, and we've just been putting our head down and executing and working hard. Here we are, and I think we'll just keep doing that. We definitely have a different delivery technology than our competitors, a different IP estate around purifying. I think those are areas of innovation and intellectual property that we tend to emphasize as points of differentiation with our competitors. We'll leave it at that.

Operator, Operator

Our next question comes from Whitney Ijem with Canaccord.

Angela Qian, Analyst

This is Angela Qian on for Whitney. We have 2 questions on CF. The first one is, do you intend to proceed to a higher dose cohort? Or do you plan to initiate the regulatory conversations based on these 2 cohorts? And then the second one, can you just remind us what your preclinical data has suggested at the comparable doses and the degree of dose response. So when we think about the potentially 3% FEV1 benefit, is that something that you believe could be achieved with a lower dose?

Joseph E. Payne, President and CEO

Both are good questions. The current Phase II trial design consists of 12 subjects and 3 doses; we have 3 subjects taking 5 milligrams, followed by 6 subjects at 10 milligrams, and an additional 3 subjects at 15 milligrams. This is the plan we initiated and received approval for, and we have been executing according to it. The first two cohorts, the 5-milligram group, has been completed, and the 10-milligram group will finish the dosing phase in early September, at which point we can share some of the interim data. Regarding the dose response, we anticipate that a dose response will be observed with our therapeutic. However, it’s important to note the context of the modulator community and CFTR biochemistry, which hasn't consistently demonstrated this in past modulator studies. In those cases, increasing the dose didn’t necessarily enhance efficacy beyond a certain point. While we do expect to see a dose response with our therapy, if we don’t, that’s acceptable as it might reflect a threshold response akin to what has been seen with modulators. Did I answer your question, Angela?

Operator, Operator

Our next question comes from Pete Stavropoulos with Cantor Fitzgerald.

Sarah Kristen Medeiros, Analyst

This is Sarah Medeiros on for Pete. Congrats on the progress. Now back to CF. I assume you'll be showing both absolute and relative changes for FEV. So how should we think about presentation and interpretation of the endpoint when taking into consideration the patient's baseline, for example, like a high versus a low FEV baseline? And then just a follow-up, besides FEV, are there any other measurements that you could or will look at to enhance the investigators' conviction in the program, including quality of life?

Joseph E. Payne, President and CEO

Thank you for the question. Regarding the FEV data and our inhaled therapeutic programs, we will analyze the area above the baseline as we monitor FEV throughout the trial. We'll focus on the area under the curve, as it's the most reliable method to assess the data. While our baseline characteristics indicate a wide range of 40% to 100%, the majority of the 9 subjects fall in the 60% to 80% range, which is more typical. For additional measurable responses, participants will complete a questionnaire with about 20 questions related to respiratory health from the CF quality of life module. This questionnaire is well-established in the modulator field, and we are applying it similarly. To further clarify, consider an analogy of someone who quits smoking: they may feel immediate improvements in the first week or month, but lung function usually enhances over a longer period, extending into months two and three. We anticipate that with an inhaled therapeutic like Arcturus, initial lung function improvements and better overall feeling could continue to develop over those months as well.

Operator, Operator

Our next question comes from Tom Shrader with BTIG.

Thomas Eugene Shrader, Analyst

I think I'll ask some vaccine questions. Your U.S. BLA for COVID, is that going to be for approval of an updated vaccine? Or would that be for the historical vaccine? And so you would need for next year to update? And then on the seasonal flu vaccine, that's obviously getting very interesting. Your thoughts on the interplay of the antigens, do you feel like you have to be as good on hemagglutinin protective antibodies if you have neuraminidase? Is that understood that neuraminidase could cover for some hemagglutinin?

Joseph E. Payne, President and CEO

Good questions. Thanks, Tom. Regarding the U.S. BLA, the initial strategy is to approve the platform with the original multi-dose vial presentation. Like in other countries and regulatory agencies we've interacted with, an updated variant vaccine is expected on an annual basis. This approval is primarily to establish the platform in the U.S. Concerning your seasonal flu question about the interplay of antigens, we will share the results of the Phase I clinical study. It involves an 8-valent vaccine that includes 4 HA and 4 NA antigens. We will assess the platform's ability to generate a balanced immune response against multiple antigens without interference. Changes to the WHO and U.S. CDC recommendations regarding vaccine composition, indicating that certain antigens may no longer be necessary, will necessitate further development of the candidate. I hope this addresses your question.

Thomas Eugene Shrader, Analyst

I guess really my question is, are your hemagglutinin levels as high as the high-dose protein vaccine? Can you say that yet? And do you know when that will be presented?

Joseph E. Payne, President and CEO

Yes, that will be later this year. What we have disclosed today is that we observed a good dose response of immunogenicity against all four versions of the flu. However, details will be provided later this year.

Operator, Operator

Our next question comes from Yigal Nochomovitz with Citigroup.

Yigal Dov Nochomovitz, Analyst

On CF, could you just comment on the timing of the end of Phase II meeting with the FDA? Am I correct that it's been delayed a bit relative to your initial projections? And if so, is that related to the comments you made regarding seeing continuous improvements in months 2 and 3 and potentially wanting to see additional boost on FEV1 beyond the first month that would present a stronger data package to present to the FDA?

Joseph E. Payne, President and CEO

Yes. We've indicated or guided that we'll be completing the Phase II trial enrollment process this year with respect to the third cohort. Shortly after then, we'll have engagement with the FDA. It's an end of Phase II meeting that would be great. But it's at that time that we would discuss with them what's required for a Phase III study. I can only speculate, but we're not expecting to need any other additional trials to allow us to shift or transition to a pivotal trial, especially with adult subjects. The expectation at this point is that the end of Phase II meeting will be in the first half of next year, and we'll be able to initiate Phase III as soon as possible in 2026 without the need or requirement to do any additional trials.

Yigal Dov Nochomovitz, Analyst

Am I correct that this is the first time you have specified the doses of the 5 and the 10? Is there a specific reason for sharing the data only in September?

Joseph E. Payne, President and CEO

No. People, it allows us to speak more freely as we enter the September bank conference season and engage with investors, so that they can now understand that this is a generous dose. For example, previous attempts at inhaled mRNA therapeutics maxed out at 80 milligrams per month, and we're now showing data at 280 milligrams. That's a big difference. If we elevate further to the 15-milligram dose cohort, that's 420 milligrams over 4 weeks. We can now point to and speak to actual data that is more meaningful. That's why.

Yigal Dov Nochomovitz, Analyst

Okay. That's helpful. And then on OTC, do you have any updates on the higher 0.7 mg per kg? Earlier in the summer, we were discussing that possibility.

Joseph E. Payne, President and CEO

It's a good question. We don't have a definitive answer. There are reasons to proceed at 0.7 mg per kg, and there are reasons to truncate the timeline and get this into Phase III more quickly. But right now, I think it's a conservative, reasonable expectation that we'll elevate the dose and get some experience at 0.7 mg per kilogram just to give more therapeutic index comfort to the regulatory agency. We haven't officially guided that yet, but I think that's a conservative expectation.

Operator, Operator

Our next question comes from Yanan Zhu with Wells Fargo.

Yanan Zhu, Analyst

Maybe still on the CF program, given there is no placebo arm, could you talk about what we could look into the data to get comfort in terms of discerning treatment effect versus placebo effects? Of course, if there's a dose response, that will make things easier, but I'm not sure the sample size and also potential as you have highlighted earlier, whether there might be one. Given that background, can you elucidate on potential ways to analyze the data?

Joseph E. Payne, President and CEO

Well, the opportunity to implement a placebo strategy will be in Phase III, and that's still to be negotiated the details of that with the FDA. However, there will be plenty of opportunities to implement a placebo arm or a placebo strategy into Phase III if requested. It is somewhat self-controlling. These folks have been measuring their FEV for quite a while. We'll leverage their past experience as some sort of self-control. But with respect to the placebo arm, that's yet to be determined and will likely be included in a Phase III trial. Remind people too, that our Phase I trial did have 32 subjects in it already. We have a pretty good experience with respect to safety. But the shift of the attention from a regulatory perspective will now go to duration. We only have 28 days of experience, right? That's the other purpose that the Phase III trial will fulfill, and will focus on an extended duration, whether it's 2, 3, 4, 5, or 6 months will be determined at a later time.

Yanan Zhu, Analyst

Great. Can I ask a quick follow-up? You mentioned that some patients are followed out to 56 days. Will there be FEV1 measurement in the off-treatment period?

Joseph E. Payne, President and CEO

There's an FEV measurement at day 56, but according to my recollection, there are no further FEVs after day 56.

Yanan Zhu, Analyst

I guess the question is, would we see any FEV1 data after the treatment period has ended, perhaps as a way to discern treatment effect?

Joseph E. Payne, President and CEO

Yes. Well, that's the reason why we're measuring day 56 because the treatment phase ends day 28. It will be interesting to share what happens to the FEV response 28 days after dosing has been suspended. We will be able to share some insight there.

Yanan Zhu, Analyst

Great. Great. Sorry, if I may ask the last question in terms of kinetics or onset of effect based on your understanding of the translation of the mRNA and the protein getting into place to start working, what's the sense of the onset of action and that kinetics?

Joseph E. Payne, President and CEO

Yes. The onset of action is relatively quick, right? In order to get the first cells that are available to be transfected and introduce new CFTR into those cells. Upon subsequent administrations, we also see that even more cells will be impacted. So the threshold of how many cells will need to be transfected and delivered an mRNA that's encodes and expresses CFTR, how many of those cells will need to be impacted before we see a physiological response or FEV improvement is the question we're addressing. Biologically, it's a different question. How long will it take for the phlegm to clear after someone stops smoking, right? It's a good analogy. It might be weeks or months depending on the person and variable depending on how long they could have smoked, for example.

Operator, Operator

Our last question comes from Evan Wang with Guggenheim Securities.

Boran Wang, Analyst

Just 2 quick follow-ups from us at Guggenheim. First, with OTC, just wondering when we may see full data there, whether that includes the higher dose cohort or not? And then with influenza, I believe the trial includes a comparator arm or arms based on age. Any comments in terms of, I guess, hemagglutinin response relative to comparator?

Joseph E. Payne, President and CEO

Good questions. Regarding the comparator data, the specifics will be available later this year or whenever CSL feels ready to release it. They will provide guidance on the detailed data. Today, we only shared a high-level summary. It is challenging for us to provide guidance on when the detailed data regarding immunogenicity in relation to comparators will be available. I cannot comment on that. As for your first question about OTC, could you please repeat it? I missed it.

Boran Wang, Analyst

I'm just curious when we may have fuller data with the OTC program.

Joseph E. Payne, President and CEO

Yes, fuller data. It depends if we proceed to the 0.7 mg per kg cohort or truncate the Phase II data as is because we've already shown that it works at 0.3 and 0.5. We may not proceed with 0.7. If we do proceed with 0.7, then that will add a few months to the timeline. Once that decision is made, we'll be able to give more specific guidance as to the completion of the Phase II portion of that. What we did guide in today's press release is that we are in parallel socializing the glutamine biomarker strategy and the N15-ureagenesis. There will likely be a Type C meeting or 2. In the first half of next year, we'll be in a good position to have alignment with the FDA, and that's what we're focusing on now. In the background and in parallel, whether we do 0.7 milligram per kilogram or not depends on some advice and our Board approval.

Operator, Operator

We actually show one more question. We will move next with Yale Jen with Laidlaw & Company.

I-Eh Jen, Analyst

My first question is regarding the CF. You mentioned that you have 15 milligrams for the next dose. When you designed the study, was 15 milligrams chosen mainly to test the highest dose for safety and efficacy, or were there other factors involved? I have a follow-up.

Joseph E. Payne, President and CEO

Yes. The 5, 10, 15-milligram dosing strategy was implemented and agreed upon by the FDA when we designed the Phase II trial. It was based on our experience in the 39 subjects in the CF program. We explored 4 dose levels all the way up to 27 milligrams in Phase I. We looked at intermediate dose levels in the Phase Ib program. The data we're collecting in the Phase II study right now is 5, 10, and 15 milligrams. These were already decided and agreed upon a while ago.

I-Eh Jen, Analyst

Okay, great. One follow-up here is that both for 032 or for 810, before you conduct meetings with FDA, should we anticipate one more data release of either one of those? Or what might be the decision?

Joseph E. Payne, President and CEO

Yes. It makes sense for us to share additional data for both of these programs as we complete the Phase II trials, respectively. We did an interim data release with OTC and a presentation with KOLs at the end of June. I think it makes sense to share the data set when the Phase II is completed and also provide clarity on the Phase III trial design once we have that clarity from our conversations with the regulatory agency. Same thing with the CF program.

I-Eh Jen, Analyst

So should we anticipate those toward the end of this year or maybe to 2026?

Joseph E. Payne, President and CEO

Yes. We expect to complete the Phase II study as planned for CF this year in 2025. Regarding OTC, it depends on whether we include the 0.7 milligram per kilogram cohort, which involves a small number of people, and that decision has not been communicated externally yet.

Operator, Operator

And we show no further questions at this time. I will now turn the call over to Joe for closing remarks.

Joseph E. Payne, President and CEO

get back to you as soon as we can. Good afternoon or good evening, everybody.

Operator, Operator

Thank you. And this does conclude today's program. Thank you for your participation. You may disconnect at any time.