Q2 2025 Arcturus Therapeutics Holdings Inc Earnings Call
Speaker #1: We will begin shortly. Please stand by. Your program is about to begin. Good day, everyone, and welcome to the Arcturus Therapeutics second quarter 2025 earnings call.
Speaker #1: At this time, all participants are in listen-only mode. Later, you will have the opportunity to ask questions during the question-and-answer session.
Speaker #1: You may register to ask questions by pressing the star and one on your telephone keypad. You may withdraw your question by pressing star two.
Speaker #1: Please note this call is being recorded, and it will be standing by should you need any assistance. It is now my pleasure to turn the conference over to Neda Safarzadeh, vice president, head of investor relations, public relations marketing.
Speaker #1: Please go ahead.
Speaker #3: 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.
Speaker #3: And Andrew Sassine, our CFO, and Dr. Pat Shivakula, 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 under the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995.
Speaker #3: 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.
Speaker #3: 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 10K and in subsequent filings, with the SEC.
Speaker #3: 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.
Speaker #3: And with that, I will now turn the call over to Joe.
Speaker #4: 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.
Speaker #4: Arcturus is advancing enrollment of adult CF participants in the open-label phase two multiple ascending dose CF study. With daily inhaled treatments of ARCT 032, over a period of 28 days.
Speaker #4: 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 2 trial is focused on enrolling subjects that do not benefit from modulators, including Class 1 or null CF participants.
Speaker #4: We have completed the enrollment and dosing of all three participants in the 5 mg cohort. After a safety review, we were permitted to proceed with enrolling the second cohort at the 10 mg dose level.
Speaker #4: All six CF participants in this 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.
Speaker #4: 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.
Speaker #4: And to the novel chemical features of our optimized lunar delivery technology. The company expects to provide phase two in term data from these first nine enrolled participants next month in September 2025.
Speaker #4: 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 three initiation in 2026.
Speaker #4: 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 two Phase 2 multiple-dose studies conducted in the OTC program.
Speaker #4: In each study and in the combined analysis of both phase two 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.
Speaker #4: Mean ammonia levels were stable within the normal range following at least two doses of ARCT-810 and remained stable for approximately 28 days after completion of dosing.
Speaker #4: During the treatment phase and follow-up, two out of three participants in the phase two US study showed increases in relative ureogenesis function to levels observed in asymptomatic OTC deficient patients.
Speaker #4: As measured by a newly developed and optimized 15N ureogenesis assay. The remaining participant demonstrated increased 15N citrulline enrichment. The data taken together suggests improvement of urea cycle function in all three participants.
Speaker #4: This orthogonal supportive data adds further confidence to the glutamine normalization data that we observed. ARCT 810 was generally safe and well tolerated, and single dose phase one/one B and multi-dose phase two studies comprising 40 participants to date and including 20 OTC deficient participants.
Speaker #4: 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 3 pivotal trial in pediatric studies.
Speaker #4: Phase three 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.
Speaker #4: 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 two-dose lyophilized vaccine presentation and for the upcoming season's COVID variant update.
Speaker #4: With anticipated approvals this fall, the U.S. BLA filing to the FDA remains on track for September, with an approval decision expected in 2026. Moving on to ARCT-2138, this is our next-generation STAR seasonal flu vaccine candidate.
Speaker #4: 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 ARCT 2138 were immunogenic against all four influenza strains as measured by a hemagglutinin inhibition assay, and both age groups, demonstrating a modest dose response within that range of the tested doses.
Speaker #4: ARCT 2138 also induced antineuraminidase 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 comparative vaccines.
Speaker #4: 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 immune response in both young and older adults with a dose as low as two micrograms and was tolerable up to 20 micrograms.
Speaker #4: Now, moving on to ARCT 2304. This is our next-gen STAR vaccine candidate for the pandemic A/H5N1 influenza virus, also known as the bird flu. In April, Arcturus received U.S. FDA Fast Track designation for ARCT 2304.
Speaker #4: 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.
Speaker #4: We've completed recruitment of 212 adults, including 80 participants over the age of 60 years old. This is in a randomized, placebo-controlled phase one trial being conducted here in the U.S.
Speaker #4: All three tested dose levels, 1.5, 5, and 12 micrograms, in the phase one BARDA funded study were well tolerated. With the majority of reported solicited AEs being mild to moderate and short-lived.
Speaker #4: No safety concerns were raised from the available clinical data. The results from this ongoing Phase 1 study are expected later this year. Before passing the call onto our CFO, we're very pleased to announce that Arcturus has appointed Dr. Monsef Slaoui as Chairman of the Board.
Speaker #4: Which became effective as of July 1st, 2025. And with that, I'll now pass the call to Andy.
Speaker #5: 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.
Speaker #5: 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.
Speaker #5: We have streamlined our internal pipeline to focus on our OTC and cystic fibrosis program, 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.
Speaker #5: Revenue for the three and six months ended June 30, 2025, was $28 million and $58 million, respectively. This represents decreases of $22 million and $30 million compared to the same period in 2024.
Speaker #5: The decline was 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.
Speaker #5: Total operating expenses for the three months ended June 30, 2025, were $40 million compared with $71 million for the three months ended June 30, 2024.
Speaker #5: Total operating expenses for the six months ended June 30th, 2025, were 86 million dollars compared to 139 million dollars in prior year. Research and development expenses were 29.6 million for the three months ended June 30th, 2025, compared with 58.7 million in the prior year.
Speaker #5: 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.
Speaker #5: 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 two trials in 2025.
Speaker #5: Research and development expenses were 64.5 million for the six months ended June 30th, 2025, compared to 112.2 million dollars 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.
Speaker #5: 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 program.
Speaker #5: The general and administrative expenses were 10.3 million in 21.7 million dollars for the three and six months ended June 30th, 2025, respectively. Compared with 12.3 million in 27.2 million dollars in the comparable period last year.
Speaker #5: 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.
Speaker #5: For the three months ended June 30th, 2025, Arcturus reported a net loss of approximately 9.2 million dollars or 34 cents per diluted share. Compared with a net loss of 17.2 million or 64 cents per diluted share in the three months ended June 30th, 2024, cash, cash equivalents, and restricted cash were 253.4 million dollars as of June 30th, 2025, and 293.9 million dollars on December 31st, 2024.
Speaker #5: Based on the current pipeline and the reallocation of resources to the cystic fibrosis and OTC programs, the cash run rate 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 therapeutic programs.
Speaker #5: 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.
Speaker #4: Thanks, Andy. Arcturus had a productive quarter making excellent progress across our mRNA therapeutics and vaccines pipeline. We look forward to sharing two cohorts of phase two CF data in September.
Speaker #4: And with that, let's turn the time over to the operator for questions.
Speaker #1: Thank you. And at this time, if you would like to ask a question, please press the star and one on your telephone keypad. You may withdraw your question by pressing star two.
Speaker #1: Once again, to ask a question, please press the star and one or your telephone keypad. We'll take our question from Lily Zongo with Lyrink Partners.
Speaker #1: Please go ahead. Your line is open.
Speaker #6: Hi. Good afternoon. Thank you for taking my question. Maybe two 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?
Speaker #6: And, in terms of the patients that have already been enrolled, could you ive us a little more granularity in terms of the ratio of, modulator eligible to non-eligible patients?
Speaker #6: Thank you.
Speaker #7: Hey, Lily. Thanks for the estions. Yeah, just to refresher for, you know, the historical precedent for cystic fibrosis is all through modulators, with the with respect to regulatory engagement.
Speaker #7: And what they've established is a 3% threshold would be sufficient to advance this into further in development. now, I do remind people that modulators are small molecules.
Speaker #7: They're systemically distributed throughout the entire body. The class of subjects or participants they're typically working with are Delta F508s. In contrast, Arcturus is developing an inhaled messenger RNA therapeutic that's topically delivered to the bronchial epithelial cells.
Speaker #7: And we're also engaging the most challenging, group within the CF community, and that's the class one subjects or modulator non-responders. But having said that, the short answer to your question is, comes from the regulatory agency, the FDA, has said that if you establish safety and tolerability, and a positive measurable FEV, then that would be, a significant development to allow us to proceed.
Speaker #7: And so what does that mean? Well, we'll find out. But clearly, if we can establish safe and tolerable medicines with a positive FEV, then we'll be able to proceed further into development.
Speaker #7: This would be a big breakthrough for for the modulator non-responders. but there is a legacy expectation from the modulator space of a, you know, two and a half, three percent threshold that's required.
Speaker #7: So, that will likely play a role in the discussions with the regulatory agency. With respect to your second question, you were asking about what percentage, I believe, or maybe explain further the distribution of modulator non-responders in this trial so far.
Speaker #7: And I can help address that question. And I would say a strong majority of these subjects—these nine subjects to date—are Class 1 subjects.
Speaker #7: We do have representation of modulators that are not Class One, but a solid or strong majority of them are Class One.
Speaker #6: Thank you.
Speaker #7: Thanks, Lily.
Speaker #1: Thank you. Our next question comes from Yasmeen Rahimi with Piper Sensor. Please go ahead. Your line is open.
Speaker #8: Good afternoon, team. Thank you so much for taking our questions. I'm very looking forward to the data in September. Once CF-related and one OTC-related, team, could you talk about the type of safety or efficacy?
Speaker #8: What do you see on a blinded basis, especially around the safety aspect of your product? And then the second one is, could you maybe elaborate as you're going to engage with the agency on pivotal design alignment of what work has been done between allowing the use of biomarkers as a registrational endpoint and could glutamine and be potential use.
Speaker #8: So, I appreciate if you could elaborate on both of these questions, and I'll jump back in the queue.
Speaker #7: All right. Thanks, Yaz. Good to hear from you. In terms of elaborating, on the safety, so for last few decades, the industry has been aggressively developing inhaled RNA therapeutics.
Speaker #7: And, unfortunately, they haven't succeeded. The reason for their collective failure is primarily attributed to toxicology and tolerability issues. Toxicology stems from two areas.
Speaker #7: Either the lipids are too toxic, you know, the delivery system itself, or the impurities in the mRNA drug substance can be a challenge with respect to toxicology and tolerability.
Speaker #7: And this has shown in the clinic through bronchospasms. So undesired inflammatory responses and febrile reactions, which are an undesired immune response or elevated fevers, for example.
Speaker #7: So, inflammatory responses can typically be credited to or blamed for toxic lipids. And then, on the febrile reaction side or undesired immune responses, those can be attributed to impurities in the mRNA construct.
Speaker #7: And what Arcturus has brought forward with this ARCT 032 is strong intellectual property and innovation on the delivery system that addresses this primary concern.
Speaker #7: Of accumulating toxic lipids. And then on the we also have purification IP that we've been building and working on for over a decade now.
Speaker #7: That allows us to effectively purify the drug substance and remove the bad actors, these small double-stranded and single-stranded impurities that can cause these untoward and problematic febrile reactions or undesired immune responses.
Speaker #7: And that's what we're bringing forward. There are improvements in addressing what the field has had challenges with over the last couple of decades. Shifting to OTC, what's been done so far with respect to glutamine socialization and familiarity with the regulatory agency is we've provided, and with respect to our N15 ureogenesis assay as well, they are well-versed and understand our strategy with respect to Phase 2. They are very well aware that we're collecting this data, and they're interested in seeing it.
Speaker #7: We've provided them papers to illustrate the impact of these potential biomarkers and the recent paper as well with respect to ureogenesis. We intend meet with them to share the recent phase two data and throughout the coming months whether that's in a type C meeting or meetings is yet to be determined.
Speaker #7: And we haven't communicated the details of that strategy. But rest assured, they are aware of what we're trying to do, and achieving alignment with them is a key objective for this program.
Speaker #7: And we would view it as a value catalyst, actually, or a value add if we can get alignment with the FDA and other regulatory agencies with respect to the Phase 3 trial.
Speaker #7: But I'll pause my comments there. Thank you for the questions.
Speaker #8: Thank you so much.
Speaker #1: Thank you. Our next question comes from Shamus Fernandez with Guggenheim. Please go ahead. Your line is open.
Speaker #9: Great. Thanks for the question. So, you know, I just wanted to confirm that the highest dose data will be sort of fully represented out to 28 days, Joe.
Speaker #9: I just wanted to confirm that, you know, the 10-milligram cohort, and this at least six patients' worth of data, would be available out to 28 days. The second question, yeah, go ahead, Joe.
Speaker #7: No, yes. so the question is, is yes, absolutely, 28 days. all nine subjects, most of of these would also have their day 56 data.
Speaker #7: We do collect FEV after 56 days, and then there's even two months of follow-ups after that. But with respect to the final subject, we'll just have 28-day data.
Speaker #7: the FEV.
Speaker #9: Okay. And, and can you, can you just remind us your, how, how you would define kind clinically meaningful? I ink historically, thought leaders we've talked to have said, you ow, at least 3% on the low end and, but 5% would certainly be clinically meaningful from their perspective.
Speaker #9: I just wanted to get your thoughts around that and if there's a bar for what the FDA might be looking for in terms of what they would define as clinically meaningful as you head to meet the agency in the first half of next year.
Speaker #7: Yeah. I, I, I ink 3% is reasonable. however, I, I, I just want to make sure it's clear that, that, that our our program is not a modulator.
Speaker #7: It's not systemically administered to Delta 508s. It's inhaled mRNA to a more challenging population, where the unmet medical need is more severe, and so that would be part of the conversation with the FDA.
Speaker #7: And also taking into consideration the theoretical likelihood of the FEV elevating further as you extend the study for a longer period of time will be taken into consideration.
Speaker #7: And what I mean by that is, if you saw, you know, 3% after 28 days, then the likelihood of you seeing even more than that in months two or three through extended dosing is theoretically very high.
Speaker #7: So, that would be viewed very positively, even if you, whatever the positive number is. So, just to reiterate what I, you know, said a few times for clarity: the FDA just wants safety, tolerability, and any positive measurable FEV.
Speaker #7: Given that this is a 28-day study, that would indicate a lot of positive feelings and responses, and allow us to advance this further into development as you extend that study even further in Phase 3.
Speaker #9: Okay. Great. I'll jump back in the queue. Thanks so much.
Speaker #7: All right. Take care.
Speaker #10: Yeah. Just to add to Shame, Joe's comments, keep in mind, Shamus, that this, you know, class of population unfortunately has degradation of FEV over, you know, an annual basis.
Speaker #10: And, consequently, their lifespan is, is shortened. And so, an opportunity to, you know, increase it or stabilize it for this class of population would be quite remarkable.
Speaker #10: And certainly offer them, an opportunity to, have an extension of life. So thank ou.
Speaker #1: We will move next with Miles Minter with William Blair. Please go ahead. Your line is open.
Speaker #11: Hi. This is Jake on from Miles. Thanks so much for taking our estion. I wanted to ask a couple more on CF. we're sort of wondering what the interest level was in, in patient enrollment after the vertex and Moderna trial pause, whether you saw any difference in, in appetite for your trial.
Speaker #11: And maybe sort of comment, we'd love your comments on, the reopening of that trial and, and whether you think they're going to be le to, to get over the safety issue, that, that was raised with the DSMB there.
Speaker #11: Thanks.
Speaker #7: Yeah. With respect to first question, we have, several sites open and recruiting subjects. and in the, and in the sites where there was overlap with competitors, if, if those competitors are no longer recruiting, and yes, that would directly, help or impact our recruitment.
Speaker #7: We're at there. but only a, a, a small number of sites. Do we have overlap with our competitors? We're working closely with the CF Foundation and, and they've identified sites that have limited competition for us for recruitment.
Speaker #7: So from that perspective, no. With respect to, of, your other question, it would be, I don't know, inappropriate for me to speculate on, on, you know, what's appening at, with our competitors like with the vertex program.
Speaker #7: I don't want to come across as callous, but we frankly don't care that much. When we started this process, there was a half dozen of these companies aggressively pursuing this.
Speaker #7: And we've just been putting our head down, executing, and working hard. And here we are. I think we'll just keep doing that.
Speaker #7: But, we definitely have a different, delivery technology than our competitors. A different IP estate around purifying and I think those are, areas of innovation and intellectual property that we tend to emphasize as points of differentiation.
Speaker #7: With our competitors, and, and we'll leave it at that.
Speaker #11: Thank you.
Speaker #7: Thank you.
Speaker #1: Thank you. Our next question comes from Whitney Ejim with Canaccord. Please go ahead. Your line is open.
Speaker #12: Okay, guys. This is Angela Chan on for Whitney. we've had two 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 two cohorts?
Speaker #12: And then the second one, can you just remind us what our preclinical data has suggested at the comparable doses and the degree of dose response?
Speaker #12: So when we think about, you know, the potentially 3% FEV1 benefit, is that something that you believe could be achieved with the lower dose?
Speaker #7: Both good questions. First of all, the present phase two trial design is a 12-subject trial with three doses: we have three subjects at 5 milligrams, followed by six subjects at 10 milligrams.
Speaker #7: And then an additional three subjects at 15 milligram dosing. That's the the present plan. We do have flexibility built into that plan because we this is what was initiated and approved upon.
Speaker #7: But we've been executing according to that plan. And, and the first two cohorts, we've already discussed our, the 5 milligrams completed and the 10 milligram.
Speaker #7: It's also going to be, completed at least the dosing phase in early September. And we'll be able to communicate some of those interim data with respect to the, the, the dose response with respect to the dose response we, you would expect that, a dose response with a therapeutic like ours; however, we do want to reference the modulator community and the CFTR biochemistry that, that has not necessarily been observed in the modulator space.
Speaker #7: That was more of a threshold situation where you, you increase the dose until it worked, but then you doubled or tripled the doses and it didn't improve the, the, the efficacy further.
Speaker #7: So if, while we do expect a dose response, with respect to our, our therapeutic, if we don't see it, that's also okay because it may just be a threshold type response, like you see with the modulators.
Speaker #7: and then did I address your estion? Angela?
Speaker #12: Yes. Yes. Thank ou.
Speaker #7: Thank you.
Speaker #1: Thank you. Our next question comes from Pete Stavropoulos with Cantor Fitzgerald. Please go ahead. Your line is open.
Speaker #13: Hi. This is Sarah Medeiros on for Pete. congrats on the progress and thanks for taking our questions. now back to CF. I assume you'll be showing both absolute and relative changes for FEV.
Speaker #13: 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.
Speaker #13: And then just a follow-up. Besides FEV, are there any other measurements that you could or will look at to enhance the investigator's conviction in the program, including things like quality of life?
Speaker #7: Okay. I'll, I'll out there. Good question. in terms of the FEV data, and other lung programs and inhaled therapeutic programs look at area above the baseline as, as we measure FEV throughout the patient experience in trial.
Speaker #7: We'll be looking at kind of area under the curve, and that'll be the best way to add the most weight and confidence in the data.
Speaker #7: In terms of the baseline characteristics, I know that we’ve included a broad range for formality purposes of 40 to 100 percent baseline.
Speaker #7: But it's more like in that 60 to 80 percent range. for, the strong majority of these nine subjects. So I'd say that would be more typical.
Speaker #7: and then you asked about additional, h, in addition to FEV responses, we are, asking these, participants to, include a questionnaire. and, and address answers there.
Speaker #7: There's about 20 questions, for example, on the respiratory module of the CF questionnaire. This is a well-understood, quality of life questionnaire that, that has been used in the modulator space.
Speaker #7: And we're using the same thing there. So, as you think of it, just to elaborate on this a little more, you know, as I think it's helpful to think of someone who stops smoking, right?
Speaker #7: The first week and first month, they feel better. But their lung function improves. Throughout, you know, not just in the initial weeks and a month, but in, in two and three months.
Speaker #7: So there's continuous healing and continued lung function improvements. And, and, and so that's, you ow, likely what we would expect with an inhaled therapeutic like Arcturus, is in the first month.
Speaker #7: That if it's working, that people would see some elevated lung function, feel a lot better. But that could continue on into months two and three.
Speaker #7: Okay?
Speaker #12: Thank you.
Speaker #1: Thank you. Our next question comes from Tom Schrader with PTIG. Please go head. Your line is open.
Speaker #14: Good afternoon. Thank ou for taking my questions. I think I'll have some vaccine questions. your USBLA for COVID, is that going to be for approval of an updated vaccine or would that be for the historical vaccine?
Speaker #14: 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?
Speaker #14: 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?
Speaker #14: thank ou.
Speaker #7: Good questions, thanks, Tom. First of all, with respect to the USBLA, the initial strategy here is to approve the platform and the original multi-dose file presentation.
Speaker #7: it would be fully expected like in other areas in other countries and regulatory agencies that we've been interacting with that an updated, a variant vaccine would be expected, on an annual basis.
Speaker #7: and so yeah, this one that's getting approved is just basically to set the foundation for the platform and get that approved in, in the US.
Speaker #7: with respect to the, answering your question on, it was a seasonal flu question. With, the interplay of antigens, let's see what can I do there.
Speaker #7: You know, we, we are sharing, the outcome of the phase one clinical study. It's an eight-valent, right? There's eight, there's eight antigens including four HA and four NA antigens.
Speaker #7: In this seasonal influenza vaccine, and we're going to evaluate the ability of this platform to induce a balanced immune response against multiple antigens without interference.
Speaker #7: But the changes of the WHO and the US CDC recommendations on vaccine composition, where these sorts of antigens are no longer required. So it will require further development of the candidate.
Speaker #7: But that's probably, I don't know if I'm specifically addressing your question, but that's.
Speaker #14: I guess my really my question is, are your, are your hemagglutinin levels as high as the high-dose protein vaccine? Can you say that yet?
Speaker #14: And do you know then when that would be presented?
Speaker #7: Yes. that's later this year. We'll, we'll be able to, what we've disclosed today is that we saw a nice, dose response of, immunogenicity against all four.
Speaker #7: conversions of the flu, right? So, but, but with respect to details, that will be forthcoming later this year.
Speaker #14: Okay. Thank ou.
Speaker #7: Yeah. Thank you, Tom.
Speaker #1: Thank ou. Our next question comes, comes from Eagle Nokomovitz with CD Group. Please go ahead. Your line is open.
Speaker #9: Yeah. Hi, Joan Annie. Thank you for taking the question. On CF, could you just comment on the timing of the end-of-phase two meeting with the FDA?
Speaker #9: Am I corrected? It's, been delayed a bit relative to your initial projections and if so, is that related to the comments you made regarding being continuous improvements in months two and three and potentially wanting to see additional boost on FEV1 beyond, beyond the first month that would present a stronger data package to present to the FDA?
Speaker #9: Thank you.
Speaker #7: Yeah. We've indicated or guided that we'll be completing the phase two trial enrollment process this year. with respect to the third cohort. But, you know, shortly after then, we'll have an engagement with the FDA if it's an end of phase two meeting that would be great.
Speaker #7: But, but it's at that time that we would discuss with them what's required for a phase three study. I, I, I can only speculate, but we're expecting to need any other additional trials to allow us to shift or transition to a pivotal trial.
Speaker #7: Especially with adult subjects. So that's the expectation at this point: the end of Phase 2 meeting will be in the first half of next year.
Speaker #7: And we'll be able to initiate Phase 3 as soon as possible in 2026, without the need or requirement to do any additional trials.
Speaker #9: And then just, am I correct? This is the first time that you've actually specified the doses of five and the ten. And is there a specific, driver behind that, relative to sharing the data only in September?
Speaker #7: No. people, it just allows us to speak more freely as we enter the, you know, the September bank conference season. and engage with investors so that they can now understand that this is a generous dose.
Speaker #7: Like, for ample, you know, previous attempts at inhaled mRNA therapeutics, maxed out at 80 milligrams per month. And we're, we're now showing data 280 milligrams.
Speaker #7: So that's a big difference. And if we elevate further to the 15 milligram dose cohort, that's 420 milligrams over four weeks. So we can now speak to and point to actual data that is more meaningful.
Speaker #7: That's why.
Speaker #9: Okay. That's helpful. And then on OTC, any later thoughts, latest thoughts on the, higher 0.7 mix per hit? I know earlier in the summer we, we were debating that possibility.
Speaker #9: I'm wondering if you have any updates there. Thanks.
Speaker #7: No, it's a good question. we don't have a definitive answer. there's reasons to proceed at 0.7 mix per hit and there's reasons to, to truncate the timeline and get this into phase three more quickly.
Speaker #7: But, right now, I think it's a conservative, reasonable next 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.
Speaker #7: But we haven't officially guided that. However, I think that's a conservative expectation.
Speaker #9: Okay. Thanks, Joe.
Speaker #7: Thanks. You go.
Speaker #1: Thank you. Our next question comes from Yanan Zu with Wells Fargo. Please go ahead. Your line is open.
Speaker #14: Oh, great. Thanks for taking our questions. maybe, still on the CF program, given there's no placebo arm, could ou, talk about, what could we, you know, look into the data?
Speaker #14: 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 sure the sample size and also the potential, as you have highlighted earlier, may matter as well.
Speaker #14: But, you know, just given that background, can you, you know, elucidate on potential ways to analyze the data?
Speaker #7: Both. the opportunity to implement a placebo strategy will be in phase three. And that's still to be negotiated. The details of that with the FDA.
Speaker #7: But there will be plenty of opportunity to implement a placebo arm or a placebo strategy into phase three if requested. It is kind of self-controlling.
Speaker #7: you know, these folks have been measuring their FEV for quite a while. And if, we'll be leveraging their past experience, as, as some sort of self-control.
Speaker #7: But, with respect to the placebo arm, that's yet to be determined and will likely be included in a phase three trial. I remind people too that, you know, our phase one trial did have, 32 subjects in it already.
Speaker #7: So we, we have a pretty good experience already with our phase one and then phase one being another seven subjects. And then you add on these, 9 to 12 subjects that were going to be looking at in, phase two by the end of this year will be over 50.
Speaker #7: Subjects of experience with respect to safety. but the, the shift of the attention from a regulatory perspective will now go to, duration. So we only have the 28 days of experience, right?
Speaker #7: that's the other purpose that the phase three trial will fulfill is an extended duration, whether it's two, three, four, five, or six months will be determined in at a later time.
Speaker #14: Oh, great. Can I, ask a quick follow-up? you mentioned some patient, followed out to 50 six days. will there be, FEV1, measurement in the off-treatment period?
Speaker #7: There's an FEV measurement at day 56, but not, and then there's two months of follow-up. But there's, I, I my understanding is on clinicaltrials.org, but my, my recollection of that is is that there's no further FEVs after day 56.
Speaker #14: I guess, the question is, would we see any, FEV1 data after the treatment period has, ended? perhaps as a way to, you ow, discern treatment effect.
Speaker #7: Yeah. Well, that's the reason why we're measuring day 56, because the treatment phase ends day 28. It'll be interesting to share, what happens to the FEV response 28 days after dosing has been suspended.
Speaker #7: So we will be able to share some insight there.
Speaker #14: Great. Great. sorry if I may ask the last question, last question. in terms of, kinetics or onset of, effect, based on your understanding, of, the, translation of the mRNA and, you know, the protein and, you know, getting into the play, into place, to start working, what's the sense of, the onset, of action and that, kinetics?
Speaker #14: Thank you.
Speaker #7: Yeah. 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.
Speaker #7: But upon subsequent administrations, we also see that even more cells will be impacted. And so the threshold of how many cells will need to be transfected and delivered with mRNA that encodes and expresses CFTR, and 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.
With respect to how uh immunity to see relative to comparator. So I won't be able to comment on that uh with respect to your first question, you asked a when question about OTC, could you restate that because I missed it.
Um, I'm just curious when we may have uh, Fuller data with OTC program.
Oh, okay.
Fuller data. Well, it depends uh, if we proceeded
the 0.7 make per kick cohort or trunk 8 to phase 2 Data, to Asus because we've already shown that it works at 3 and 0.5
We may not, uh, proceed with 7, but if we do,
7, then that
Months to the timeline. So it's, uh, once that decision is made, we'll be able to give more specific guidance as to the completion of the phase 2.
What we did guide in. Today's press release is that, uh, we are in parallel socializing the the group
Green biomarker strategy and the N15 year reagen. And, um, the
there's very likely going to be a type c meeting or 2 uh and then in the first half of next year, we'll be in
uh, a good position to have alignment with the
and that's what we're
focusing on now.
but in the background and then parallel, whether we do 7 milligram,
Or not.
Depends on, you know, some, uh, advice and and of course our board approval Etc.
Great. Thank you.
Yeah, thanks Evan.
Thank you.
We actually show one more question.
We will move next with Yale. Jen with late law and Company. Please go ahead. Your line is open.
Good afternoon and thanks for taking the questions. My first question is also is I know the CF. Now now you reveal that you have a 15 MGS uh that to for the next dose. Uh just curious when you designed the study was 15 basically just to push the highest those you could test the safety and efficacy or any other cons considerations and I have a follow-up.
Agreed upon by the FDA when we designed the Phase 2 trial, it was based on our experience in the 39 subjects in the CF program. So, we explored four dose levels...
7 milligrams.
In in the in Phase 1.
And then we looked at intermediate dose levels.
Of phase 1B program.
and what this uh and and and then the experience were
the the data were collecting in the phase, uh, you know, 2 study right now is
5 105 milligrams. And and these uh, we're already decided
To agreed upon.
Uh, a while.
Okay great. Uh 1 follow up here is that the both for uh 032 or 4810 before you conduct the meetings with FDA. Should we anticipate 1 more data release or of either 1 of those or uh what might be the sort of decision?
Respectively. So we did an interim data release with OTC and a presentation with KO Wells at the end of June. I think it makes sense to...
Uh, share the data set when it's the when when Phase 2 is completed and also, uh, provide Clarity on the phase 3 trial design. Once we have that Clarity from our conversations with the regulatory agency,
And then, uh, same thing with...
So, should we anticipate also toward the end of this year, or maybe 2026?
Uh, for the OTC program.
Yeah. For either 1 of those uh, additional data update. Yeah, well
To study as presently planned for CF this year, in 2025, with respect to OTC. It depends whether we include the 0.7, milligram kilogram cohort a small
Number of people.
uh,
Whether we do that or not, and that hasn't been, uh, communicated externally yet. So it's today is not the day to do that.
Okay, great. Thanks a lot.
Thank you.
And we show no further questions at this time.
Nicole over to Joe for.
For closing remarks.
Hey, thanks everyone for participating on the call.
If there are any remaining questions.
Thank you. And these laws conclude today's program.
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