Arcturus Therapeutics Holdings Inc.

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If you need assistance at any time, please press star zero, and a member of our team will be happy to help you. ¶¶ © transcript Emily Beynon

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Hello and welcome everyone joining today's Arcturus Therapeutics first quarter 2026 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. To register to ask a question at any time, please press star 1 on your telephone keypad. Please note, this call is being recorded. We are standing by if you should need any assistance. It is now my pleasure to turn the meeting over to Neda Safarzadeh, Vice President, Head of Investor Relations, Public Relations and 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, Dr. Alan Cohen, our chief medical officer, and Dennis Mulroy, our chief financial officer. Dr. Pat Cipicola, 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 statements. 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. The first quarter of 2026 was a period of solid execution for Arcturus as we continue to advance our rare disease pipeline and strengthen our leadership team. I'm very pleased to report that our CF program is now in new uncharted territory. Our 12-week phase two study began enrollment in Q1. We are already well beyond one month of dosing Continuous dosing beyond a month has never been successfully tolerated in the history of inhaled mRNA therapeutics. This is a big deal. And why is that? Because Class 1 CF is a serious disease with serious unmet medical need. And we believe that the nested pulmonary congestion observed in Class 1 CF disease requires consistent chronic dosing that is reasonably well tolerated to be successful. There are specific reasons why Arcturus has been able to achieve tolerable dosing beyond one month. Firstly, our inhaled lunar particle technology includes key delivery lipids that are chemically different from all other technologies competing in this space. Secondly, our messenger RNA manufacturing process to remove undesired impurities is unique, proprietary, and trade secreted. ARCTO32, this is our inhaled mRNA CF therapeutic candidate, continues to showcase these differences in its growing safety and tolerability profile. The CF community is aware of our safety and tolerability profile, which has contributed to the reason why we were able to initiate enrollment of our 12-week open-label Phase II study earlier than originally anticipated. This study is enrolling Class 1 CF participants and monitors lung function measures, including percent predicted FEV1 and lung clearance index, or LCI. We believe there is increasing recognition across the field of both the significant unmet medical need in Class 1 CF and the importance of achieving a well-tolerated repeat dose therapeutic approach to enable durable clinical benefit. Our program is designed with these principles in mind, and we are encouraged by the opportunity to generate meaningful clinical data in a patient population that continues to have no effective treatment options. We look forward to collecting this clinical data, including lung function measures, during and throughout this open-label Phase II study. Arcturus remains committed to advancing our inhaled mRNA therapy for people living with CF class 1 mutations who continue to face significant unmet medical needs. Now moving on to our flagship liver program, ARCT810. This is our mRNA therapeutic candidate to treat ornithine transcarbamylase, or OTC, deficiency. We met with the FDA to discuss the pediatric clinical development strategy for ARC-T810. Following this type C meeting, we're pleased to receive clear regulatory direction on a path toward a pivotal pediatric study. In line with that direction, we are collecting additional exploratory data and look forward to further alignment with the FDA at the end of phase two meeting planned for the second half of 2026. Beyond our clinical rare disease programs, Our partner Meiji in Japan is actively manufacturing CoStave, this is our self-amplifying mRNA COVID vaccine, for the upcoming 2026-2027 season using a two-dose file presentation. All commercial guidance for CoStave in Japan will be provided by Meiji. We also expanded our executive leadership team with the appointments of Dennis Mulroy as Chief Financial Officer, and Dr. Alan Cohen as Chief Medical Officer. I'm pleased that they are both on the call with us today and we will get to hear from them shortly. Both bring extensive and relevant experience that will play important roles as we continue executing across clinical, regulatory and corporate priorities. Many of you will have the opportunity to meet with these gentlemen and I encourage you to do so. Overall, we believe Arcturus is well positioned to advance our pipeline toward meaningful clinical and regulatory milestones for patients and for our shareholders. With that, I'll now turn the time over to our Chief Medical Officer, Dr. Cohen.

Thank you, Joe, and good afternoon, everyone. From a clinical development perspective, the first quarter reflected meaningful progress across our key programs. Starting with cystic fibrosis, ARCT032 is currently enrolling people with CF with Class 1 mutations in a larger and longer open-label Phase II study over a 12-week period. This study is designed to monitor safety, tolerability, and assess evidence of early clinical benefit, including two pulmonary functional measures, including changes in percent predicted FEV1 and lung clearance index. We've intentionally designed this study to generate a more comprehensive understanding of safety and tolerability, along with early signs of clinical efficacy, which are critical to advancing inhaled messenger RNA therapies in the lung. We are also evaluating two validated quality of life outcome measures, along with changes in high-resolution CT imaging, to support a comprehensive assessment of potential clinical effects. Taken together, these endpoints are intended to provide a robust data package to inform both the therapeutic potential and the feasibility of repeat dosing. Our goal is to establish not only early evidence of activity, but also the feasibility of repeated dosing, which is fundamental to unlocking durable benefit in this patient population. Turning to OTC deficiency, our ARC T810 program continues to broaden its development strategy to address the unmet medical needs of newborns and young children affected by the most severe forms of the disease. Following our recent Type C meeting, the FDA provided clear direction toward a pivotal pediatric development path. We are actively collecting additional exploratory data to help establish the optimal dose and therapeutic effect as we prepare for the end of phase two meeting planned later this year. Across both programs, our focus remains on generating high quality clinical and regulatory data to support thoughtful decision making and efficient advancement through development. We believe this disciplined approach is particularly important in emerging modalities where careful characterization of safety, tolerability, delivery, and clinical effect is essential to long-term success. I'm excited to be part of the Arcturus team, look forward to working closely with our investigators, regulatory partners, and internal team members as we continue moving these important programs forward. With that, I'll now pass the call to Dennis.

Thanks, Alan, and good afternoon, everybody. Our press release issued earlier today includes financial statements for the first quarter ending March 31, 2026, and provides a summary and analysis of our year-over-year performance. Please also reference our most recent Form 10-Q for more details on our financial performance. Cash, cash equivalents, and restricted cash totaled $213.4 million on March 31, 2026, and $232.8 million on December 31, 2025. Year over year quarterly revenue decreased by $27.3 million. The decline was driven by reductions in revenue from our CSL collaboration as Arcturus refocuses on our rare disease clinical programs. Quarterly research and development expenses decreased year over year by $13.4 million which was driven primarily by lower manufacturing costs related to lunar COVID and BARDA, as well as reduced clinical trial costs associated with the lunar COVID program. Additional decreases were attributable to lower payroll and benefit costs associated with lower stock-based compensation expense and a reduction in headcount. Overall reductions were partially offset by higher manufacturing costs related to lunar OTC. General and administrative expenses decreased year over year by $1.8 million due to reduced share-based compensation expense, as well as payroll and benefits associated with reductions in headcount. Through continued execution and strategic refocusing on our existing rare disease clinical programs and therapeutic platform in the first quarter of 2026, Arcturus has maintained a cash runway extending beyond the second quarter of 2028. The company remains in a strong financial position and has cash runway needed to achieve multiple near-term value creating milestones in both therapeutic programs. With that, I'll now pass the call back to Joe.

Thanks, Dennis. Arcturus continues to make steady progress across our rare disease mRNA therapeutic programs while strengthening the foundation of the company. With enrollment now underway in our 12-week open-label Phase II study of ARCT032 and cystic fibrosis, and clear regulatory direction from the FDA on the pediatric development strategy for ARCT810 and OTC deficiency, We remain focused on advancing toward important clinical and regulatory milestones throughout 2026. Supported by a strong balance sheet and an expanded, experienced leadership team, we believe Arcturus is well-positioned to execute on our priorities.

So with that, let's turn the call over to the operator for questions.

Thank you. And if you would like to ask a question, please press star 1 on your keypad. To leave the queue at any time, press star 2. And once again, to ask a question, please press the star and 1 on your telephone keypad. And we will pause a moment to allow everyone a chance to join the queue. And we'll take our first question from Seamus Fernandez with Guggenheim. Please go ahead. Your line is open.

Hey, guys. Thanks for taking the question. This is Evan laying on for Seamus. Two from me. Want to know, do you see deficiencies? and one on cystic fibrosis. Just first on OTC deficiency, can you share specific FDA feedback on the glutamine and ureogenesis assay specifically? Curious also the discussion between infants and adults, since I don't know if I saw you mentioned a path forward in the adult setting. And second, on cystic fibrosis, just curious anything you can share in terms of patient enrollment in progress there and, you know, what's the potential for a potential interim there? Thanks.

Hey, thanks Evan. I can turn the time over to Alan to address some of the FDA feedback questions pertaining to infants and adults and the biomarker question to him and then I can, we'll go to that point, I can address the CF question.

Right. Thanks, Joe. So we've successfully, as you mentioned, completed the first of two type C meetings with the FDA. And it's clear that we have greater clarity now as to what we need moving forward. And as you mentioned, the utility of the biomarkers, most notably ammonia and glutamine in particular, have been historically highlighted and were identified as areas of greater focus and attention for us moving forward. So greater clarity on which biomarkers to use. Urogenesis is still a biomarker in development, and we're continuing to advance that. But our dependence upon it, I think, will depend on the additional data that we're currently in the process of generating.

And then with respect to your CF questions and the cadence of enrollment, I think the cadence of enrollment is being determined in the upcoming weeks. We just started this study in the first quarter. but we'll be able to give a more accurate enrollment completion timing later this year. We do remind people that we enrolled approximately 13 subjects in 2025 over sequential three cohorts, first, second, and third cohort, and that was limited to the United States. We are expanding enrollment not just in the U.S., but also outside the U.S. or abroad.

Thank you.

Thanks, Evan.

Our next question comes from with Learing Partners. Please go ahead.

Hi. Good afternoon. Thank you for taking the question. Maybe just a quick question regarding the OTC program. So could you tell us what is the type of exploratory data that the FDA is looking for and also whether it would require for you to initiate studies in the pediatric population? Thank you.

Go ahead, Alan. Sure. So, great question and thank you for asking. The first type C meeting that we had, as you alluded to, focused exclusively on what will it take for us to be able to take the adult data that we're still in the process of generating in our current open phase two study into pediatrics. The results of that meeting suggested that we have a clear path forward. We're continuing to collect additional enrollment data for the 0.3 and the 0.5 dosing groups. Our plan is to then have an end of phase two meeting with the FDA. The intent there is to do sort of the usual necessary tasks, which is to reaffirm and continue to show safety and tolerability. And of course, if you're going to go into young children and newborns, the goal would be to also show enough evidence of clinical efficacy to justify going into such a young, vulnerable population. We have greater clarity now as a result of that meeting. We're in the process of completing that data set, and we should have sufficient data later this year to take that total data set, bring it forward to the FDA, and continue our conversations and hopefully get into a pediatric study sometime in the months and years ahead.

Thank you. Thank you. We will move next with Yanan Xu with Wells Fargo.

Please go ahead.

Hi. Thanks for taking our question. This is Kuan Nung for Yanan. So our question is around cystic fibrosis. Since there is no placebo control for the 12-week study, can you talk about the variability of FEV1 and LCI, and how should we prepare to interpret the data without placebo control? Thank you.

Yeah, that's correct. There's no placebo arm in the present study. Maybe Alan can comment on the REACH study and placebo strategy going forward. With respect to variability of FEV, that's well understood. We are collecting two lung function parameters, FEV and LCI, and maybe Alan can comment on the value of doing that.

Sure. Great question, and an important question. As you know, the... Requirements for percent predicted FPV1 and spirometry is active performance characteristics and reproducibility with the person performing the test. The good news about cystic fibrosis patients is that they've been accustomed, unfortunately, to doing spirometry since they're in school. And since most of the adults that we're enrolling are well into their 20s and beyond, they have decades of experience performing spirometry almost daily. We have set in this cohort four study parameters from screening and baseline to allow for a small variation from the two measures, but not an excessive amount so that there is enough consistency between screening and baseline that we feel confident that an individual is producing reproducible, reliable tests throughout the course of the study. That was something we didn't have in place before. I think it's necessary. I believe that it's going to mitigate any concerns that we may have moving forward. Now, in terms of LCI, the challenge with LCI in adults is that there just simply has not been a very large natural history database of people with cystic fibrosis. The good news is that the Cystic Fibrosis Foundation, recognizing the sensitivity of that tool, in particular for measuring changes in small airways, which is likely to be the place where early demonstration of clinical efficacy is most likely to be observed. They are currently completing a large prospective open label study in exactly the same population that we're targeting for our cohort four and subsequent studies. And that data should be shared later this year, going into 2027 by the CF Foundation at the upcoming NACFC meeting. So we're looking forward to seeing that data starting to be presented. And they have assured all sponsors, including us, that we'll have access to that data moving forward. So we'll have a normative data set, which we hope to use as we bring forward the data we'll be generating on our study drug in the months and years ahead as well.

The only thing I would add is that I just want to remind everyone on the call that the FDA has not defined a threshold of success for FEV or LCI. at least for our program. In the modulator space, they have. But for a new modality like inhaled mRNA, for class 1 CF, there's no minimum threshold that we must observe. Anything positive would be viewed seriously. And like what Alan mentioned, the REACH study will be very likely to be very helpful as well. Anyway, thanks for the question.

Thank you for all the comments.

Thank you.

We will move next with Myles Minter with William Blair. Please go ahead.

Hi, this is Jake on for Myles. Thanks for taking our question. One of your competitors recently discontinued its inhaled CFTR mRNA trial. We were just wondering if you've seen any of the manifestations that were described there and led to the discontinuation and whether you've had any discussions with the CF Foundation or regulators regarding patient enrollment of this new cohort now that that trial has been discontinued? Thank you.

Yeah, the short answer is no. There's significant differences between the technology that we use to deliver the RNA molecule versus our competitors, and we touched that on in the script earlier on today's call. But I would like to also highlight that we have utilized no steroids as a co-treatment before, during, or after the dosing period. And that's a point of differentiation. And there's reasons for that that are safety and tolerability related. And also, we've been approved by regulators for unsupervised dosing at home. And that's not been the case for some of the other companies in this field. And that's another point of differentiation. And the reason behind that, again, is all because we're using a different technology. It's a different chemistry. And it also includes a different manufacturing process to purify the mRNA molecule, which could be a contributor to remove the impurities that cause those undesired immunogenicities and immune responses. But anything else to add, Alan?

No, I think Joe covered the majority of it. The only thing I would add is that, you know, it's worth pointing out that at the completion of our Cohort 3 study, which went up from 5 to 10 to 15 milligrams daily for 28 days, that we were given the ability to move forward with a longer study, allowing for either 10 or 15 milligrams daily in cohort four. So our safety monitoring committee saw nothing clinically worrisome and have allowed us to not only go up to 15 milligrams if we choose to daily, but we also have the freedom and ability to take those patients out to 12 weeks, which we are currently embarking on right now, initiating at a 10 milligram dose once daily.

Thank you. We will move next with Mayank Mamthani with B. Reilly Securities.

Please go ahead.

Yes. Good afternoon, Dean. Thanks for taking our questions. And good to hear 032 study is progressing ahead of plan. Did I hear that you've had certain patients move past the one-month exposure window? And just curious if, you know, like the VORTEX study, there are any go-no-go decisions, interest study, or duration of treatment, because both studies were kind of, you know, comparable on timelines and how further along they were. There, you know, mechanisms built in your study that informs continuation based primarily on tolerability reasons, but also obviously efficacy reasons also, and then have a follow-up.

Yeah, it's a good question. With respect to the first, we have initiated the 12-week study in the first quarter. So that means that we are well beyond a month of dosing already in the study. We are continuing to enroll at a pace that's going to be understood in the coming weeks. But yes, we're well beyond that one-month study. With respect to intermediate go-no-go opportunities and decisions that are built into the protocol, I'll have Alan comment on that.

Yeah, I mean, the good news about an open-label clinical trial is that we're going to be able to, in an active way, monitor patient progress and look for safety signals as well as early signs of efficacy. It's our impression that before the end of this calendar year, we should have enrolled and have sufficient enough data in hand that we will be able to speak a little bit more clearly to the future longevity of the program as well as the direction of the program moving forward.

Thank you. And then on the REACH data that you're looking to learn, NACFC. We're just curious, you know, on the LCI, what, according to you, sort of good looks like and what correlations that, you know, you're curious about.

Yeah, there's several reasons why we've included Lung Clearance Index into this new protocol for the fourth cohort. The first, of course, is to add an additional measure of lung function that is respected, understood, and can be a potential endpoint for us in the study. With respect to the correlation of LCI to other parameters, maybe you can comment on that.

Yeah, I mean, the interesting thing about LCI is that I mentioned earlier, and one of the questions that we got earlier was talking about the variability of the performance characteristics of spirometry. The nice thing about lung clearance index and why it was used almost exclusively in young children who can't perform spirometry is that it's a passive maneuver. It doesn't require active involvement of the patient itself to perform it. So it's actually very reproducible and highly reliable. So all you really have to do is form a seal around the mouthpiece, and then the equipment does the rest. So right now, the only outstanding information we have is what the CF Foundation is generating right now with the REACH study, which is What's the normal rate of decline of lung clearance index within the population that we're studying? So we have a comparative group. So really right now, it's not only a more sensitive measure, and by the way, it's also, as you may know, been an approvable endpoint for some of the modulators, in particular in Europe and rest of the world. So we know it's reliable. We know it's reproducible. It has really not been used in adults just simply because it wasn't perceived as necessary. But I think increasingly it's being appreciated for the sensitive way with which it measures a more distinct, more peripheral, more acutely portion of the airway that may prove to be much more useful for purposes of a study like this in these patients moving forward.

And LCI also has a correlation between mucus plug reduction and insomuch that that's the encouraging data we saw in our second cohort that we've shared. you know, we'd like to see that correlate with a lung function measure. And lung clearance index has a nice correlation to these reductions of mucus plugs and other studies.

Got it. And lastly, any insight on your plans for combining with a modulator for maybe, you know, non-responder population? Is there anything you could do in the ongoing protocol? Thanks for taking the question.

Did you understand the question?

Yeah, I think I did, and if I didn't, please correct me. I guess the question, as I understood it, was obviously the highest unmet medical need population are those with null mutations and those who are unable to tolerate or are unable to get access to modulators. That's obviously the patient population that we're focused on now. Is our therapeutic potentially beneficial to a broader population of patients who may be on modulators? Yes, the answer is yes. And that would obviously be the next place we'd want to go. But obviously, we're going to need to generate sufficient data to make that justifiable, and we look forward to hopefully getting that data in the years ahead.

Thank you. Thanks, Mahe.

Thank you.

We will move next with Adam Walsh with Roth Capital Partners. Please go ahead.

Hi, good afternoon, and thanks for taking my questions. On the adult Type C meeting timing, when would we expect to hear about that outcome?

Sure. We've shared previously that both of these Type C meetings would be completed in the first half of this year, and we're well on track for that. So the second would be sometime this quarter. It's a near term. It's on the near term horizon here, very soon.

Wonderful. And then how is the team segmenting pediatric versus adolescent versus adult for OTC? And what is the realistic enrolled patient number for the pediatric pivotal given the targeted severity?

Sure. Great questions. I'll take this one. This is Alan. The population that we believe has the highest unmet need are those who tend to be under the age of six, so preschool age up to early school age. By the time, unfortunately, most of these kids with OTC deficiency who manifested in the birth period, by the time they get to school age, they're either unfortunately having a liver transplant or if they're unable to be stable enough for that, they die. So the segmentation for the pediatric population would almost exclusively be focused on that exact population, children in the first weeks and months of life up through probably age six.

Excellent. And then one more, if I may, just on 032 and CF. How's the team approaching interim versus full disclosure given the open label design? I know this was touched upon on the last call, and you may not be advanced enough to comment on it, but will you be anticipating any disclosure on interim given the open label study?

Yeah, the language we've used on this call today, Adam, is that you're right, it's an open label study. It's already started. And we're expressing confidence on today's call that later this year we should have sufficient enrollment and data to inform our next steps. So I think we're going to be in a really good place to understand where we are with this program later this year.

That's great. Thank you.

Thank you. We will move next with Whitney Ijem with Canaccord.

Please go ahead.

Hi, thank you for taking our questions. This is Angela Chan on for Whitney. Can you remind us what preclinical data you have of lunar CF to penetrate the mucus and any data around like endosomal escape or production of functional protein? And then can you also remind us what cells are you reaching within the lung?

Sure, sure. So we have Pat here with us. He can comment on the ferret data, etc.

Yeah. Well, first of all, we worked for many years with the CF Foundation to develop our preclinical package. And we've done quite a bit of work on looking at LNP stability in sputum. And then we've also done a lot of work preclinically in mouse, rodents, and ferrets, as well as non-human primates. And what we see is in the CF mouse model, for example, that we can get to various bronchial epithelial cells. We have a pretty broad distribution, and some of this data was recently published with some of our collaborators, and I think that's available, and we can provide that to you.

Did we address your question?

Great. Yeah, if you could send that, that would be great. And then maybe a follow-up is on dosing. Currently, are you doing anything to address kind of the distribution of drug into the lower lobes? Like, is there a way you can try to impact the distribution of drugs?

Right now, our anticipation is we won't have to modify the position of the patient or anything like that to access different lobes or parts of the lung. So, that's not our anticipation, but...

This is Pat again. When we did our initial preclinical evaluation of the nebulizer that we were going to use, we optimized the particle size of the nebulizer so that it does get distributed throughout the lung.

This is Alan. Just to add one more piece to that, I think your question is probably coming from the high-resolution CT data that we shared and generated in our last cohort. which showed a preponderance of effect mostly in the lower segments of the thoracic cage and within the lower segments of the lung. We know that ventilation, perfusion, and ventilation in general differs with aerosols in particular in the lower and upper segments of the lung. One of the things that we're hoping to achieve if we're going now from a four-week dosing strategy to 12-week strategy is a much more thorough application of our therapy throughout the lung And we hope to see that manifest as the study goes beyond the four-week period. So, we think this is more so a byproduct of time and not necessarily dose.

Got it. Thank you so much.

Thank you.

We will move next with Yigal Nokomobitz with Citigroup. Please go ahead.

Hi, this is Juwon Kim on for you all. Thanks for taking our questions. Maybe two quick ones from us. Just to confirm, firstly, do you need to enroll more patients at the 0.3 or 0.5 Migs per K dose for the exploratory data that needs to be generated, or is that just from longer follow-up?

The short answer is we just need to complete the scheduled study as dictated and communicated at the Type C meeting. So there's nothing too extraordinary there. We just need to complete that data set and also analyze it and then present it in a way that they requested. It was just a reanalysis of the data that they wanted to appreciate, and we said that we'd provide that to them at the EOP2 meeting.

Gotcha. And also, CF, I believe that you noted that you're planning on conducting the HRCT scans in the 12-week study. Can you provide additional detail on how frequently the assessment as well as LTI and FEV1 measurements might be conducted? And are you seeking to enroll a certain number of patients at CUS? Thank you very much.

Yeah, with respect to high-res CT scan, it's before and after. We typically do not propose to take several of these high-res CT scans during a study. It's typically before and after. With respect to the other lung function measurements and the cadence of that throughout the 12-week study, maybe, Alan, you can comment on that, what you're comfortable sharing.

Yeah, we haven't really shared that kind of level of granularity, but I think it's appropriate to just consider that every time a patient comes back to a clinic to get evaluated and to get another scheduled amount of drug, that's a perfect time, particularly at a CF center, to repeat testing in a controlled setting. We are not using home monitoring nor home spirometry or lung clearance index equipment in the household or in the home. So we want consistent measures being performed in an appropriate skilled center. so that we can have reliable data. So we're collecting that data at every time point that the patient's coming back. So it's at a regular cadence over the course of 12 weeks.

Got it. Thank you. And are you looking to enroll a certain number of patients like few of us?

Yeah, for 20 subjects, up to 20 subjects is what's presently in the protocol for CF. Or were you asking about OTC?

Oh, no, I just meant amongst those 20 patients, is there a specific number that you're looking to get, XUS versus US?

Oh, go ahead.

Comment on that. Yeah, no, another great question. We added XUS sites in large part because there are jurisdictions in the world that happen to have higher preponderances of people with null mutations. And we're trying to take advantage of the fact that there are high unmet medical needs in parts of the world where the level of care, the nature of care, and the clinical course of the disease is commensurate and consistent with what we observe here in the U.S., Canada, and other parts of the world. So we haven't set a high or low bar in terms of the number of patients to be enrolled in the United States and outside of the United States. It's in our anticipation that it's going to be, you know, perhaps an equal mix, but it really shouldn't matter at this point.

Great. Thank you very much.

Appreciate the call. Thank you.

Thank you. We will move next with Thomas Schrader with BTIG. Please go ahead.

Hi. Good afternoon. This is Ginny on for Tom Schrader. Thank you for taking our questions, and thank you for all the updates. I had a couple questions on the OTC program. For OTC, you're now pursuing late-onset adult and severe pediatric populations, which is a meaningful broadening, but could you help us understand how you're thinking about resource and capital allocation between these two tracks? Is there a scenario where the adult program generates registrational data first and helps de-risk the pediatric program, or do you view these as truly independent developmental paths that need to run in parallel? And as you think about your end of phase two meeting in the second half of the year, could you walk us through your best case versus base case outcome and what that looks like from that interaction? Thank you.

Okay. A lot there, but I think Alan got it. With respect to pediatric and adult regulatory paths, we can comment on that. And then expectations for the EOP2 meeting, go ahead. Okay. Just the path for, you know, what percentage of the budget is allocated or energies and resources to the pediatric path versus the adult path? Or is there more prioritization to the pediatrics?

Well, yeah, so, okay, understood. So rather than getting into granularity on the budgetary likelihood of expenditure, right now, Our pediatric program is predicated on the successful completion, sufficient end-of-phase II data, and a general agreement that we've generated sufficient safety, tolerability, and clinical efficacy data to be able to then go into children. Our expectation and hope is that the pediatric opportunity and unmet medical need is the greatest, and the one that we feel we need to be spending our greatest attention to once we're given the opportunity to do so. Our adult program is almost completed, so right now we're just finishing up enrollment on a small number of patients to complete the grid that Joe was just referring to a moment ago. It's five doses, and then once we complete five doses and have time to analyze the totality of that data and prepare it for our end of phase two meeting, our hope is that we're given the green light to move forward with a pediatric program, and that would be in large part our focus moving forward.

Great. Thank you. Thank you.

And once again, that is star and one on your telephone keypad if you would like to join the queue. We will move next with Yale Jen with Laid Law and Company. Please go ahead.

Good afternoon and thanks for taking the questions. In terms of the pediatric OTC programs, you mentioned most of those patients need transplantation. as the ultimate treatment. I just wonder whether you're thinking that the drug currently you're developing was mainly for a stopgap for those patients before they can ultimately get transplantation, or this is potentially a disease-modifying, the patient can be treated for a long time without the need for transplantation.

Well, first a comment is that the OTC deficiency is definitely a pediatric-centric disease. That's usually when it's diagnosed. And there is a significant unmet need to prevent the undesired liver transplantation that occurs in these young children. So engaging them prior to the severity getting to that point is the timing we're talking about. But is there any other comments?

Yeah, no, I think your question is actually a really good one. Our hope and expectation would be that we're not only forestalling the need for a liver transplant, but we should hopefully be able to keep these children from requiring lung, not lung, liver transplants lifelong if we intervene and do so in as pronounced a way as we hope and expect to do as early as possible in the course of their disease.

Okay, great. This is very helpful, and congrats on all the progress.

Great. Thank you. Great question. Thank you.

Thank you. And at this time, there are no further questions in queue. I will now turn the call back to Joe Payne for closing comments.

Just thanks, everyone, for participating on the call. We appreciate everyone's time. Please don't hesitate to reach out to our team for any remaining questions. We will always get back to you as soon as we can. Thanks again.

Thank you. This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect.