Arcturus Therapeutics Holdings Inc (ARCT) 2025 Q1 法說會逐字稿

Good day. I would like to welcome everyone to Arcturus's Therapeutics first quarter 2025 earnings call. (Operator Instructions) Today's call is being recorded. I would now like to turn the call 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; and Andy Sassine, our CFO. Dr. [Pad Chivukula], our CFO 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 employed by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the risk factor section in our most recent form, 10-K and in subsequent filings with the SEC.

In addition, any forward-looking statements represents our views only as of the date such a 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, Neda. It's good to be with you again, everybody. Over the last few months, there has been elevated interest in our mRNA therapeutics pipeline, given that we have meaningful clinical data sets forthcoming. So I will begin today's call with updates pertaining to our mRNA therapeutics pipeline.

I will begin with an update on ARCT-032. This is our messenger RNA therapeutic candidate for cystic fibrosis. Arcturus is advancing enrollment in the Open label phase 2 multiple ascending dose CF study in adults with CF, who are not eligible for CFTR modulator therapy or are not taking CFTR modulators due to drug intolerance, poor response, or lack of access to modulators.

Each adult participant in the phase 2 CF study is expected to receive daily inhaled treatments of ARCT-032 or over a period of 28 days. The study began last December, and to date the study continues in multiple subjects without safety or tolerability issues.

The company expects to complete phase two enrollment by the end of the year and provide phase two in term data for the first two cohorts in mid-2025. I'll now move on to our ARCT-810 program. This is our messenger RNA therapeutic candidate for ornithine transcarbamylase or OTC deficiency.

Arcturus continues to enroll participants in the Open label phase 2 OTC deficiency study with five intravenous infusions of ARCT-810 over a period of two months. The company previously completed the dosing phase, involving a cohort of eight people, and the dosing was at 0.3 mix per kilogram of a placebo-controlled European study enrolling OTC deficient individuals. The company expects to provide phase 2 interim data this quarter, or Q2 2025.

The US Phase 2 study evaluates several biomarkers, including glutamine and ammonia. Elevated glutamine levels can occur when ammonia scavengers are used, particularly in individuals with urea cycle disorders such as OTC deficiency.

While ammonia scavengers reduce circulating ammonia, glutamine may still be elevated due to its role as a temporary ammonia repository. And therefore may be used as a useful biomarker to ascertain proper urea cycle function in OTC deficient individuals.

We are also utilizing a newly developed and improved 15N ureagenesis assay. This is supported by a newly published paper out of Haverly's lab at the University of Zurich. This 15N ureagenesis assay is expected to provide important data for monitoring the effect of ARCT-810 in the company's clinical development program.

We are encouraged by the comprehensive data we have collected to date with our CF and OTC programs. And given the current market conditions, we have made a strategic decision to focus our resources toward our mRNA therapeutics pipeline.

I now shift your attention to our partnered COVID-19 vaccine program. We are pleased about the recent EU approval of KOSTAIVE. This is our self-amplifying mRNA COVID-19 vaccine. Arcturus received an initial milestone payment from CSL, our global vaccine partner, in relation to the EU approval of KOSTAIVE.

We continue to make progress, expanding the global KOSTAIVE franchise. Company anticipates a marketing authorization application or MAA filing in the United Kingdom in Q2 2025, followed by a US BLA filing in Q3 2025.

The WHO is expected to announce the updated COVID strain later this week. And we, along with our partner CSL Securus will update KOSTAIVE accordingly to support Meiji's distribution efforts in Japan this upcoming season.

Our star self-amplifying mRNA platform continues to benefit from meaningful publications. The company recently published a comprehensive analysis of safety data for KOSTAIVE with a 12-month follow-up from the Pivotal clinical study in Vietnam, which had over 17,000 participants who received at least one dose of the study vaccine.

The study confirmed the favorable reactagegenicity profile. Acceptable tolerability of ARCT-154 was also observed in older participants and individuals at high risk of severe COVID-19 due to underlying medical conditions. Long-term data from this large trial suggests that the FA mRNA COVID vaccine is safe and well tolerated and did not include any reports of myocarditis or pericarditis.

In April, Arcturus's Japanese partner Meiji Seika Pharma published an analysis characterizing the distribution and clearance of ARCT-154 encoded spike protein and non-structural proteins in the lymph nodes and injection site muscle in mice following a single intramuscular vaccination.

The study showed the encoded spike protein reached its highest level approximately three days after vaccination and quickly disappeared from the injection site muscle. The spike protein persisted up to 28 days in lymph nodes after vaccination, and the data suggests that this prolonged spike protein expression may be credited for the observed higher immunogenicity. And as expected, the study also confirmed that the replication is limited.

Now moving to ARCT-2304. This is our SA mRNA vaccine candidate for pandemic influenza A, which is also known as H5N1, or the bird flu virus. In April, Arcturus received US FDA fast track designation for ARCT-2304. As a reminder, this project has been supported in whole with federal funds from the HHS, ASPR, and BARTA.

Company recently completed the recruitment of 212 adults, which included 80 participants over the age of 60 years old. In a randomized placebo controlled phase 1 trial being conducted here in the US. The company expects in phase 1 data in the second half of 2025.

And with that, I will now pass the call to Andy.

Thank you, Joe, and good afternoon, everyone. The press release issued earlier today includes financial statements for the first quarter of 2025 and provides a summary and analysis of year-over-year and sequential financial performance. Please also reference our most recent Form 10-Q for more detail on the financial performance.

I am pleased to announce we were able to extend our cash runway till the first quarter of 2028. However, it was not an easy decision. Due to the current market environment and uncertainty regarding our regulatory process, we have made the decision to focus our research and development expenditures on our CF and OTC program exclusively.

I am happy to announce that we have received the initial milestone payment from CSL in relation to the EU co-stave approval. We anticipate an additional milestone payment and we'll update, provide an update on our second quarter call.

I will now provide a summary of our financial results for the first quarter of 2025. Three months ended March 31, 2025. Revenues were $29.4 million compared to $38 million in the second period of 2020 -- in the same period of 2024.

The decrease primarily reflects lower development milestone revenues recognized under the CSL collaboration agreement as KOSTAIVE transitions from the development stage to commercialization. Research and development expenses were $34.9 million for the three months ended March 31, 2025 compared to $53.6 million in the comparable period last year.

The decrease in research and development expenses was primarily driven by lower manufacturing costs associated with the KOSTAIVE, LUNAR-FLU, and [barter] programs. Partially offset by increased manufacturing and clinical costs for the LUNAR CF and LUNAR OTC programs.

R&D expenses also declined sequentially for fourth quarter -- from fourth quarter '24 by almost $9 million. We anticipate additionally quarterly declines in the second half of fiscal year '25. General and administrative expenses were $11.3 million for the three months ended 2025, compared to $14.9 million in the comparable period last year.

The decrease in general and administrative expenses was primarily attributable to reduce share-based compensation costs. We expect general and administrative expenses to decrease during the next 12 months, driven by lower share-based compensation costs and a reduction in expenses related to the commercial transition of the COVID program to CSL.

The three months ended March 31, 2025. Our (inaudible) supported a net loss of approximately $14.1 million or $0.52 per diluted share. Compared with a net (technical difficulty) million or $1 per diluted share and the three months ended March 31, 2024.

Cash and cash equivalents and restricted cash for $273.8 million as of March 31, 2025 compared to $293.9 million in December 31, 2024. This $20 million decline in cash is reflective of our annualized cash burn this fiscal year. As stated earlier, I am pleased to report that the cash runway now extends into 2028 with the reallocation of resources to the CF and OTC programs, which includes significant cost reductions.

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 the therapeutic programs. We look forward to another exciting year with multiple upcoming clinical data from our CF and OTC program.

I will now pass the call back to Joe.

Hey, thanks, Andy. Arcturus continues to make excellent progress across our therapeutics pipeline, and we look forward to multiple key clinical data sets across our mRNA therapeutics and our partnered vaccine programs this year.

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

(Operator Instructions)

Lili Nsongo, Leerink Partners.

Hi, good afternoon. This is Lili Nsongo from Leerink. Thank you for taking the question and thank you for the update this quarter. I just have two questions. So the first one, could you provide maybe a little more color in terms of the changes that have taken place in order to be able to extend the cash runway as well as, the potential, in cash flow, well, incoming cash flows that you anticipate within the -- this new guidance. And then the second question, relating to the development of the KOSTAIVE vaccine, how should we think about potential milestones related to UK approval and US as well as the timing for those. Thank you.

Sure, Lili. Thank you for that question. It was not an easy decision, Lili, but as you know in this environment, I think it was very prudent for us to focus on our two most critical programs, and as a consequence of that, we had to make some tough decisions with respect to cost reductions including some elimination of early development in R&D programs as well as, consolidation of our facility.

So a combination of all these factors, contributed to the extension of the runway, but more importantly as well, you can probably summarise that guidance we originally provided remain relative conservative relatively conservative based on our cash burn historically. So hopefully you'll appreciate that we tend to be hopefully under promising and over delivering with respect to our cash runway. I hope that answers your question.

It does. Thank you.

Yeah, with -- yeah, you also asked a second question with respect to milestones -- potential milestones associated with the UK filing or US filing, and there's no milestones associated with those. Andy wanted to comment further.

We have a milestone associated with the first US, a revenues from KOSTAIVE, but we're not anticipating that Lili till 2028, frankly. Assuming approval in '26 or so with the US BLA filing this year. So we're not including that in our forecast, hopefully, you'll appreciate, that we'd like to remain conservative with respect to that milestone.

Thank you.

Yasmeen Rahimi, Piper Sandler.

Good afternoon, team. Thank you so much for all the updates. Wanted to spend some time as many investors are very much looking forward to ARCT-032 interim readout here mid 2025. I just want to get a good understanding as we get into this mid read out, now that we have a little bit more granular color and the press releases noted two doses are going to be provided.

I guess, how large could the initial interim cohort be across these two doses? What sort of the bar that for success you want to see? And then to the extent you can talk about the patient population that you that you're recruiting for the study, that would be really helpful. Sorry, these are like sort of [three] questions along the interim readout just want to have a good understanding of what we're going to be getting at that interim look?

No, good questions. Yes, we're also excited about this mid-year update for our CF program. There's considerable interest in it. It's a great commercial opportunity and it's an exciting program, but you asked about how large of a data set to expect. The entire Phase 2 study is has been listed at clinicaltrials.gov as 12. So because this is an interim data kind of drawing from two cohorts, you would expect in that 6 region to 9 region of subjects.

So with respect to the bar of success, clearly this is 28 daily administrations. So it's a significant hurdle to have reasonable safety and tolerability achieved. In addition to that, we'd be looking for FEV or lung function improvements. And the bar that has been established recently is 3%. We believe is if we achieve that that would justify advancing the program. Clearly the higher percentage that we would get would impact the size and nature and cost of our Phase 3 trial.

In terms of the types of patients, I think you might be inferring to maybe Class 1 and non-Class 1. It would approximately half of these subjects would be Class 1 subjects and the other half would be non-Class 1. But every single one would be similar in that they're all non-modulator responders and so we don't tend to bifurcate the data. We view this group as having similar unmet medical need and presentation, so. That's it.

Very helpful. Thank you, Joe. I'll jump back to the queue.

Thanks, Yas.

Seamus Fernandez, Guggenheim Securities.

Hey guys, this is Evan Wang on for Seamus. Thanks for the questions. Just following up on cystic fibrosis. We've seen some tolerability issues from a competitive program. Can you remind us again the difference of 32 versus some of the other competitor mRA programs?

And just to honen in on that a little bit more, in terms of the dose range you're exploring and what we may see from this, these first or these three dose cohorts, especially relative to what you studied in healthy volunteers and the initial CF patient studies.

And then, in terms of the first two dose 3 cohorts, how should we be thinking about that I guess whether and whether you expect each dose cohort to be efficacious or whether you expect a dose response here. Thank you.

Yeah, a lot there. All good questions. First of all, our therapeutic is different from our competitors. I think that the key points of differentiation would be number one, our delivery technology. Our LUNAR lipid nanoparticle delivery technology is exclusive to us. We discovered this and are applying it to the CF program, and it's chemically different from what everyone else is utilizing and we've showcased these differences in preclinical animal models.

So clearly there's something there to -- with respect to our delivery technology. When you're talking about safety and tolerability, you also have to recognize that the level of purity of an mRNA construct, and Arcturus has significant intellectual property pertaining to the purification of our mRNA and how this could potentially impact safety and tolerability is on.

Removing impurities effectively if we do that, then that would logically enhance or expand the therapeutic index and improve the safety and tolerability profile, and those would be two key areas of differentiation. We mentioned that there's two cohorts and each of those is attributed to a different dose level.

We have, of course, flexibility built into this. A phase 2 study to have a third cohort or third dose level or expand the second level. We haven't provided any guidance on the nature of that third dose level, but, the data that we intend to share, mid-year will involve to -- we'll be drawing from two different dose levels.

And none of these levels of dosing is wasted we believe. You asked if all of these could be efficacious and somewhat that may indeed be the case, but we'll save the details and then for that disclosure and for mid-year.

Got it thank you.

Myles Minter, William Blair.

Hi, this is Jake on from Miles. Thanks so much for taking our question. Couple for you. First on CF. We're just wondering if you guys have talked about any sort of accelerated approval pathway for ARCT-032 given that need there and all mutant patients.

And then a second question on OTC. You guys mentioned. Measuring glutamine as a biomarker there. Just wondering if you have any sort of initial bar for success where we should expect a percentage of normal on glutamine. Thank you.

Okay, great questions. First of all, with respect to some sort of regulatory acceleration, whenever you see excellent phase 2 data that would always warrant a discussion with regulators to accelerate the approval pathway, especially like you mentioned for serious diseases where there's significant unmet medical need.

We have not shared any data, so we don't know -- it would be too early for me to guide whether this is good or great or excellent data, but to simply address your question, if it's considered excellent data then yes we would be looking to accelerate the clinical path for sure.

With respect to glutamine, I think it, I'd like to remind everyone listening that if you have a dysfunctional urea cycle, then your body cannot convert that ammonia into urea. So what does it do? It converts ammonia into glutamine. So glutamine is a -- is just a great biomarker that can help us understand this disease. In terms of what are -- would we be looking for in glutamine levels, it would be simply to restore normal levels.

So very often. You would -- it's well known that, folks suffering from urea cycle disorders, including OTC deficiency, have elevated glutamine levels. And if we could restore those into the normal range, that could be some convincing evidence that are therapeutic.

Whitney Ijem, Canaccord.

Hey, guys, thanks for taking the questions. Just sticking with CF. Can you talk about the time points that you're measuring FEV in the study and what the duration of follow up. I guess we should expect from both cohorts? I'm I guess curious if there's interim time points you're looking at between 0 days and 28 days and then there's subsequent time points and if we should expect all those for both cohorts in the upcoming data.

Yeah, the details pertaining to this trial design are available on clinicaltrials.gov and also the CF Foundation tracker that tracks not only our phase 2 trial and the details there but also our competitors, and that's a good reference for people to look at.

We're going to be measuring FEV or lung function improvement. This 28 day treatment cycle. So what do I mean by before? Well, there's a screening process where FEV is measured, and then of course, at day 0, prior to first administration, and then there's a few, measurements throughout the cycle and then of course afterwards it's approximately 7 FEV measurements taken.

We haven't shared the specific details of that, just for competitive purposes, but, there's plenty of data points in the study to give, a decent level of conviction to advance this program further into development. Did I address your question, Whitney?

I think so for the, just to clarify though for so we should expect the full 28 days and then maybe some additional follow up from both cohorts or is it that -- well should it yeah, okay.

Maybe not the entire follow up because these can be a few months in nature the follow up so we may not have the entire follow up for. We intend to have safety tolerability and the lung function values for the complete treatment course correct.

Okay, perfect, excellent. Okay, and then just to follow up to clarify on the US KOSTAIVE's milestone, is it that you -- there is not a milestone on approval or that you are not including a milestone on approval in your guidance to be conservative?

Okay, yeah, we -- there is a milestone associated with first commercial sales in the US, and that milestone is not included in our guidance because we're not anticipating commercial sales until 2028. And so hopefully that gives you some perspective as to the cash runway does not include a US milestone related to first commercial sale.

Okay, and also not one related to EU -- I'm sorry, US approval.

Right. There is no milestone with US approval. It's related to sales. Correct.

Okay, perfect, thank you very much.

Thank you, Whitney.

Pete Stavropoulos, Cantor Fitzgerald.

Hi, this is Samantha on the line for Pete. Thanks for taking our questions. So on the CF program, given that the impaired CSTR function [impedes mucociliary] clearance and mucos plugging, do you see potential for 032 to normalize or remodel the lungs? And if it can you speculate on the length of time this may take? I'm curious to hear your thoughts.

No, it's a great question. We're hoping to be the first to answer that question with data, but, just some basic comments is that these patients that are participating in our trial do not have a 100% lung function, and some of that dysfunction is attributed to irreversible damage.

So there's going to be some portion of the lung that just isn't recoverable. But we're also optimistic that there is a portion that is. And so the lung is very well known to regenerate and heal effectively if you can reverse the dysfunctional biology. So we hope to see that in our upcoming trial results.

In terms of the time, because this is a topically administered agent, the time course to restoration. It may be different from systemic treatments like you see in the modulator business. We're different, we're topically administered.

So accessibility to these cells is going to be a key marker of success. And as the lung heals, then more cells would be accessible. So at least theoretically we anticipate a steady improvement over an extended period of time, but what is just unknown at this point is how long is that time period and how much material is required. But we were anxiously awaiting the data.

That's very helpful. And one short follow-up question besides FEV, are there any other measurements that you could or will look at that might enhance the investigators conviction in the program, something like quality of life measurements or others?

Yeah, there's a survey that we're provided. There's a validated CF questionnaire over the last couple of decades in the modulator field. They have improved these questionnaires significantly, and that will complement our FEV data. In terms of other mechanisms like mucociliary clearance or others, the FDA came back with some simple guidance there that all they need to see is FEV to justify advancing this into a phase 3 trial, but we are supporting that data set with some questionnaires to see if we can support what we observe in with respect to lung function improvements.

That's great. Thank you, guys, so much.

Thank you, Samantha.

Tom Shrader, BTIG.

Good afternoon. Thanks for taking the question. You've commented that the next CF trial is going to depend a lot on the size of the efficacy signal, but do you have a sense of the minimum safety database for an indication of this is 100 about right, or are you flying sort of completely blind at this point?

We're definitely not completely blind. I think 100 is reasonable. Unfortunately, it depends on how successful the phase 2 results are. If the more successful they are, the more leverage we have to decrease this number and get this into -- to real subjects commercially as fast as possible, but 100 is reasonable, so that would imply that we had 39 subjects in Phase 1 and Phase 1b. We had another dozen that would get us over 50 after Phase 2, that we'd probably need a minimum of 50 people to strengthen the database to achieve that 100, but we have not -- just to be clear, we haven't received that. But that that's a reasonable estimate.

And then in OTC it seems like there's two deliverables. One, you're helping OTC, but in the grander plan that you're getting stuff into the liver is that the same readout or what I'm really asking is do you have any way to monitor uptake into the liver that isn't correction of OTC or is it really the same readout for both questions?

No, -- yeah, there's not going to be a bio sampling or some sort of tissue removal as part of this process. The FDA doesn't require that for these significant rare diseases. But we do have a biomarker strategy. We've alluded to glutamine, for example, is one of those biomarkers. But then there's also a functional readout, and the 15N urea genesis assay is also of interest there that a great paper just came out last week out of the University of Zurich that I encourage people listening to refer to, but that's another a new exciting way to track disease progression or healing.

Okay, great. Thank you.

Thank you, Tom.

Yigal Nochomovitz, Citi.

Yeah, hi, thanks. I had one question on CF and one on OTC. On CF, I think in the past you've talked about some thresholds for FEV1 improvement that you would deal would be, sufficient sufficiently strong to move forward. I'm wondering if you could comment on that with respect to the upcoming data.

And then on OTC, you mentioned some biomarkers, you mentioned the N15 assay. I'm wondering, are you also going to measure erotic acid and uridine, because those are also urinary biomarkers that would be interesting. And you mentioned glutamine, but I think alanine is another one that could be interesting as a biomarker in lieu of ammonia, which you can't measure. Thanks.

Good. Thanks, Yigal. I'll first start with the thresholds and CF. These numbers that have been communicated over this last quarter, especially are based on historical precedents, but in the modulator space. But if you can have a 3% and if you can show a 3% improvement in FEV over a treatment course, then in order to reprove that in a Phase 3 study would require potentially hundreds of people.

And so that's a significant endeavor. Nonetheless one that we would pursue in order to prove that this is real. But if the FEV value goes up to 5%, then your Phase 3 trials could be as low as 50 people. Definitely, or at least confidently below under 100 people.

So there -- and if you go north of 5%, then in higher FEV responses, it wouldn't change the size of the Phase 3 trial because earlier on this call there was a question about how much -- how many people would you need to establish a significant enough safety database and 100 is approximated at this point. But so whether -- you see higher levels of FEV you'd still need. At least 50%, we estimate or 50 participants in the Phase 3 trial.

Shifting to the OTC program, erotic acid is a biomarker we are tracking as well, and that's in the urine and that is associated with the urea cycle and hyperamminemia. And then also there is several amino acids and biomarkers that we're exploring.

Glutamine is just more well understood and frequently used by clinicians and doctors to track people on ammonia scavengers to look at glutamine to see if that's elevated as well, then they still have some challenges with hyperamminemia that's outside of their ammonia scavenger medicine and their diet. So glutamine is a more common biomarker that's well more well understood in the community, but you're absolutely right, there's other biomarkers we're measuring as well.

Okay, thanks. And then just going back to the 3% versus 5%, what are you assuming there in terms of the dispersion of the data given it's obviously a relatively small sample size, 6 people or 12 people, so what does that mean in terms of how much dispersion you're willing to accept and be comfortable with, whether it's the 3% or the 5% because obviously that will impact the way you power things.

Yeah, of course we'd like to see elevated consistency in in small data sets such as this. We'll have the opportunity to share that data and discuss it, but at this time, it's just too early to comment further on that. But yes, to address your, the core of your question, a more consistent data set would be preferred.

Got it. Alright. Thanks so much.

Yanan Zhu, Wells Fargo.

Great. Thanks for taking our questions. So on cystic fibrosis, I thought, previously, the guidance was the date of second quarter. Given that the guidance is mid-year, is it okay to assume that more likely the data will be in the third quarter and what might be the venue for the update.

And on efficacy, I was wondering, in terms of -- you talk about the bar for FEV1. I was wondering what is the bar for proportion of patients meeting that 3% minimum threshold of improvement. Would it be, like, if the response rate if we can call them that. It is like expected to be fairly broad or could it just be even like a 20% response rate, still considered a worthwhile product to move forward with? Thanks.

Yeah, thanks, Yanan. You bring up a great question with respect to the bar of a response rate that hasn't really been established by the field. We're going to have to make a call based upon this data, the FEV, and the consistency of it. There isn't a some sort of feedback we've received from the FDA, for example, on this question.

We have received feedback from the FDA that 12 subjects may very likely be sufficient to advance this. So as long as there's some level of consistency within these 12 subjects and remember multiple dose levels will be evaluated within this group, then that is likely considered a success and we'll be able to receive approval to advance this into a Phase 3 trial. Then you asked another question though. It was about --

The timing and venue.

The timing and venue. Well, because this data set is involving data from two cohorts now, we wanted to allow that extra few weeks just to schedule and get additional numbers to strengthen the data set. So it's just the -- that's the reason for, focusing on mid a mid-year data -- interim data update. In terms of a venue, we haven't decided on that, but that is something that we'll communicate relatively soon here.

Okay. If I may also wondering since you are moving ahead with filing the BLA, so you're still on track for filing the BLA for KOSTAIVE in the US. I was wondering with the new leadership at CBR, have you had any interactions with the FDA, very recently and what is the expectation for this filing? Thanks.

Our interactions with the FDA, I'll first comment on that, have been normal. The feedback we've received has been within the expected timeline or even earlier in the example of the fast track designation on the vaccine side.

So we haven't seen any changes to regulatory environments for at least our mRNA-based vaccines and therapeutics. We do recognize that there's a passionate new administration. That -- but all of them and all of the employees we've talked to at each of these agencies are passionate about gaining access to safer and better medicines and vaccines, and that is almost a credo that to us. We want to provide that and we're believing we're providing data to support that notion. So I think the science will stand on its own lakes throughout this process.

Great. Thanks for taking the questions.

Yeah. Thank you, Yanan.

Yale Jen, Laidlaw & Company.

Good afternoon, and thanks for taking the question. Just two from us. The first one is for the eurogenesis, assets. you mentioned during the call. Could you elaborate a little bit more in terms of any specific readout that can -- very relevant to the data release and maybe the second question really here is that the on the big picture perspective that given that you're focusing much more on your in-house programs and so far you have two very active ones. Would you consider a little bit more, maybe even in the early stage, so maybe enrich the pipeline, maybe sometime come out later this year or next year to enrich that? And thanks.

The early stuff does not consume a lot of resources. So clearly we want to be in a position of being able to announce new programs when it's appropriate upon establishing any sort of proof of concept for each of these therapeutic programs and we've already done a considerable effort there already to date. So we're in a position to move if needed. Our focus on our budget and extending the runway hasn't impacted our subsequent programs. That work's already been done.

Okay, In terms of the eurogenesis asset, any specific regard that we should pay attention to?

Yes. I encourage people to go to the 15N urea genesis paper that I've highlighted a couple of times on this call, out of the University of Zurich. It's new. It's called the -- it comes out of the Journal of Metabolic Health and Disease, and the title of it is Characterization and Treatment Monitoring of Urea Genesis Disorders Using Stable Isotopes. But, we just believe it's a significant upgrade on the urea genesis assays of decades ago. It's a considerably better process and we'll be collecting data within the context of what's been utilized in this paper. And we'll provide more details on this at the right time. We just planted that seed.

Okay. Well, great. Thanks a lot and congrats on all the progress.

And this concludes our question answer session. I would now like to turn the call back over to Joe Payne for final and closing remarks.

Hey, thanks everyone for participating on the call. I know there's some conferences up and we can meet face to face, but if there's any remaining questions, don't hesitate to reach out to our team and we'll get back to you. Thanks everybody.

Thank you, and this does conclude today's conference. We thank you for your participation. You may disconnect at any time.