Q1 2025 Arcturus Therapeutics Holdings Inc Earnings Call
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So far as the day, Vice President head of Investor Relations Public relations and marketing. Please go ahead.
Speaker Change: Thank you operator, good afternoon, and welcome to Armstrong of Therapeutics quarterly financial update on pipeline progress call.
Joe Payne: Today's call will be led by Joe Payne, our president and CEO and Andy <unk>, Our CFO, Dr departure of a fuller our CFO.
Speaker Change: <unk> will join them for the Q&A session.
Speaker Change: Before we begin I would like to remind everyone that the statements made during this call regarding matters that are not just sturdy called Fox are forward looking statements within the safe Harbor provisions of the private Securities Litigation Reform Act of 1995.
Speaker Change: 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 the statements.
Speaker Change: Please see the forward looking statement disclaimer on the company's press release issued earlier today.
Speaker Change: The risk factors section in our most recent Form 10-K.
Speaker Change: Subsequent filings with the SEC.
Speaker Change: In addition, any forward looking statements represent our views only as of the date such statements are made.
Speaker Change: <unk>, specifically disclaims any obligation to update such statements and with that I will now turn the call over to Joe.
Joe Payne: Thank you it's good to be with you again everybody.
Joe Payne: Over the last few months there has been elevated interest in our mrna therapeutics pipeline given that we have meaningful clinical datasets forthcoming. So I will begin today's call with updates pertaining to our mrna therapeutics pipeline.
Joe Payne: I will begin with an update on the E. R. C. T. O 32. This is our messenger RNA therapeutic candidate for cystic fibrosis.
Joe Payne: Arcturus is advancing enrollment in the open label Phase II multiple ascending dose study in adults with CF, who are not eligible for CFT, our modulator therapies or we're not taking CFT our modulators due to.
Joe Payne: Drug intolerance poor response or lack of access to March leaders.
Joe Payne: Each adult participants in the phase II CF study is expected to receive daily inhaled treatments of ERC T O 42 or over a period of 28 days.
Joe Payne: The study began last December and to date. The study continues in multiple subjects without safety or tolerability issues.
Joe Payne: The company expects to complete phase III enrollment by the end of the year.
Joe Payne: And provide phase two interim data for the first two cohorts in mid 2025.
Joe Payne: I'll now move onto our ear C. T 10 program. This is our messenger RNA therapeutic candidate for ornithine transcribe families or OTC deficiency.
Joe Payne: <unk> continues to enroll participants in the open label Phase II OTC deficiency study with five intravenous infusions Husky, our Cta 10 over a period of two months.
Joe Payne: The company previously completed the dosing phase.
Joe Payne: Involving a cohort of eight people in the dosing was at 0.3 Megs per kilogram of a placebo controlled European study enrolling OTC deficient individuals.
Joe Payne: The company expects to provide phase two interim data this quarter or Q2 2025.
Joe Payne: Yeah.
The U S phase II study evaluates several biomarkers, including glutamine and pneumonia.
Joe Payne: Elevated glutamine levels can occur when ammonia scavengers are used particularly in individuals with urea cycle disorders, such as OTC deficiency.
Joe Payne: While ammonia scavengers reduce circulating ammonia glutamine may still be elevated due to its role as a temporary ammonia repository.
Joe Payne: And therefore may be used as a useful biomarker to ascertain proper urea cycle function and OTC deficient individuals.
Joe Payne: We are also utilizing a newly developed and improved 15 and urea Genesis assay.
Joe Payne: This is supported by a newly published paper out of Harper Lee's lab at the University of Zurich.
Joe Payne: This 15 and urea Genesis assay is expected to provide important data for monitoring the effect of <unk>.
Joe Payne: And the company's clinical development program.
Joe Payne: We are encouraged by the comprehensive data we have collected to date with our CF and OTC programs and.
Joe Payne: And given the current market conditions, we have made a strategic decision to focus our resources toward our mrna therapeutics pipeline.
Joe Payne: I'll now shift your attention to our partner to COVID-19 vaccine program.
Joe Payne: We are pleased about the recent EU approval of coast. Dave. This is our self amplifying mrna COVID-19 vaccine.
<unk> received an initial milestone payment from CSL, our global vaccine partner in relation to the EU approval of Kosta.
Joe Payne: We continue to make progress expanding the global co state franchise.
Joe Payne: Company anticipates, a marketing authorization application or MAA filing in the United Kingdom. In Q2, 2025, followed by a U S. BLA filing in Q3 2025.
Joe Payne: The W. H O is expected to announce the updated COVID-19 strained later this week.
Joe Payne: And we along with our partner CSL secures well update co Steve Accordingly to support <unk> distribution efforts in Japan this upcoming season.
Joe Payne: Yeah.
Joe Payne: Our star self amplifying mrna platform continues to benefit from meaningful publications.
Joe Payne: The company recently published a comprehensive analysis of safety data for Ko, Steve with a 12 month follow up from the pivotal clinical study in Vietnam, which had over 17000 participants who received at least one dose of the study vaccines.
Joe Payne: The study confirmed the favorable Reactogenic city profile.
Joe Payne: [noise] acceptable tolerability of ERC to $1 54 was also observed in older participants and individuals at high risk of severe COVID-19, due to underlying medical conditions.
Joe Payne: Long term data from this large trial suggests that the S. A mrna COVID-19 vaccine is safe and well tolerated and did not include any reports of myocarditis or pericarditis.
Speaker Change: And April Arcturus has Japanese partner Meiji sake of pharma published an analysis characterizing the distribution and clearance of <unk> $1 54 in coated spike protein and non structural proteins in the lymph nodes and injection site muscle in mice.
Joe Payne: Following a single intramuscular where vaccination.
Joe Payne: 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.
Joe Payne: And as expected. The study also confirmed that the replication is limited.
Joe Payne: Now moving to <unk> 20, 304. This is our SA mrna vaccine candidate for pandemic influenza, a which is also known as H five N one where the bird flu virus.
Joe Payne: In April Arcturus received U S. FDA fast track designation for <unk> 23, or four as a reminder, this project has been supported in hole with federal funds from the HHS S. P R and BARDA.
Joe Payne: The company recently completed the recruitment of 212 adults, which included 80 participants over the age of 60 years old.
Joe Payne: In a randomized placebo controlled phase one trial being conducted here in the U S.
Joe Payne: The company expects interim phase one data.
In the second half of 2025.
Andy: And with that I'll now pass the call to Andy.
Andy: Thank you Joe and good afternoon, everyone.
Andy: The press release issued earlier today includes financial statements for the first quarter of 2025.
Andy: And provides a summary and analysis of year over year.
Andy: <unk> financial performance.
Andy: Please also reference our most recent Form 10-Q for more detail on the financial performance.
Andy: I am pleased to announce we were able to extend our cash runway until the first quarter of 2020.
Andy: However, it was not a.
Andy: Decisions.
Andy: 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 C F and O T C program exclusively.
Andy: I am happy to announce that we have received the initial milestone payment from CSL in relation to the U a E. You close date of approval.
Andy: We anticipate an additional milestone payment.
Speaker Change: Update provide an update on our second quarter call.
Andy: I will now provide a summary of our <unk>.
Speaker Change: <unk> results for the first quarter of 2025.
Speaker Change: Three months ended March 31, 2025 revenues were $29 4 million compared to 38 million in the second period of two.
Speaker Change: 2020 in the same period of 2024.
Speaker Change: The decrease primarily reflects lower development milestone revenue recognized under the CSL collaboration agreement.
Kosta: Kosta, you've transitioned from the development stage to commercialization.
Kosta: Research and development expenses were $34 9 million for the three months ended March 31st 2025, compared to $53 $6 million comparable period last year.
Kosta: The decrease in research and development expenses was primarily driven by lower manufacturing costs associated with the coast de Luna flu and BARDA program.
Kosta: Partially offset by increased manufacturing and clinical costs.
Kosta: Lunacy.
Kosta: Lunar OTC program.
Kosta: R&D expenses also declined sequentially.
Kosta: For fourth quarter from fourth quarter, a 24 by almost $9 million.
Kosta: We anticipate additional quarterly declines in the second half of fiscal year thought.
Kosta: 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.
Kosta: The decrease in general and administrative expenses was primarily attributable to reduced <unk>.
Kosta: Share based compensation costs.
Kosta: 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.
Kosta: Covid program to see yourself.
Kosta: For the three months ended March 31, 2025, Arcturus reported a net loss of approximately $14 1 million or.
Kosta: Or 52 cents per diluted share compared with a net.
Kosta: Okay.
Kosta: Or $1 per diluted share in the three months ended March 31 2024.
Kosta: Cash and cash equivalents and restricted cash of $273 8 million as of March 31, 2025, compared to $293 9 billion.
Kosta: December 31 2024.
Kosta: This $20 million decline in cash was 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 include significant cost reductions.
Kosta: In summary.
Kosta: Company remains in a strong financial position and has a cash runway needed to achieve multiple near term value creating milestones.
Kosta: Therapeutic programs.
Kosta: We look forward to another exciting year with multiple upcoming clinical data from a C S and OTC program.
Joe Payne: I will now pass the call back to Joe.
Joe Payne: Hey, Thanks, Andy Arcturus continues to make excellent progress across our therapeutics pipeline.
Joe Payne: 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.
Joe Payne: Thank you as a reminder, if you'd like to ask a question. Please press star one on your telephone keypad, you may remove yourself from the queue at any time by pressing star two and once again that is star one to take the question.
Speaker Change: Our first question from Billy Sanaga with Leerink partners. Please go ahead.
Billy Sanaga: Hi, good afternoon discipline, and he said well somebody think thank you for taking the question and thank you for the update this quarter.
Speaker Change: I just have two questions. 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.
Speaker Change: Sure.
Speaker Change: Cash flow or.
Speaker Change: Incoming cash flow that's you anticipate within the this new.
Speaker Change: Guidance and then the second question relating to the development of the Clos Ste vaccine, how should we think about potential milestone related to U K approval and U S. That's one of the timing sort of thank you.
Speaker Change: Sure Louise Thank you for that question.
Speaker Change: It was not an easy decision early but as you know.
Speaker Change: In this environment I think it was very prudent for us to focus on our two most critical programs.
Speaker Change: And as a consequence of that you know we had to make some tough decisions with respect with respect to cost reductions.
Including some elimination of early development and R&D programs as well as you know consolidation of our facility.
Speaker Change: Combination of all of these factors.
Speaker Change: Contributing to the extension of the runway, but more importantly, as well you can probably you know.
Speaker Change: Surmised that guidance. We originally provided remained relative considered relatively conservative based on you know our cash burn historically, so hopefully you'll appreciate that we tend to be a hopefully under.
Speaker Change: Promising and over delivering with respect to our cash runway.
Speaker Change: That answers your question.
Speaker Change: It does.
Speaker Change: Please go ahead yeah.
Speaker Change: Yeah. You you also asked a second question with respect to milestones potential milestones associated with the U K.
Speaker Change: Filing or a U S filing and there's no milestones associated with those Andy you wanted to comment further we have a we have a milestone associated with.
Speaker Change: The first U S. You know a <unk> revenues from coast date, but we're not anticipating that literally till 2028, frankly, assuming approval and you know 26 or so with the U S. BLA filing this year, so we're not including that in our forecast.
Speaker Change: Hopefully you will appreciate.
Speaker Change: We'd like to remain conservative with respect to that milestone.
Speaker Change: Thank you.
Speaker Change: And we will next go to Yasmin Rahimi with Piper Sandler. Please go ahead.
Yasmin Rahimi: Good afternoon, and thank you so much for all of that I think one or two in some time.
Speaker Change: So very much looking forward to S. E. T is zero already too and Tom laid out here at 2025.
Speaker Change: Just wanted to get a good understanding as we get into Smith weed out now that we've got a little bit more granular color in the press release. It noted two doses are going to be provided.
Speaker Change: I guess how.
Speaker Change: How large could that initial interim cohort E are caught these two doses.
Speaker Change: What's sort of the bar for.
Speaker Change: For success you want at E and then to the extent you can talk about the patient population that you.
Speaker Change: Great. Thank you were cutting for the study that would be really helpful. Sorry. These are like set up.
Speaker Change: Yeah. Good question.
Speaker Change: Read out just wanted to have a good understanding of what we're gonna be cutting at that interim look.
Speaker Change: No that's it.
Speaker Change: Good questions yes.
Speaker Change: We're also excited about this mid year update for our CF program.
Speaker Change: There is considerable interest in it it's a great commercial opportunity and.
Speaker Change: It's an exciting program, but you asked about how large of a dataset to expect the entire phase two studies has.
Speaker Change: It has been listed in our clinical trials Dot Gov is 12. So because this is an interim data cut of drawing from two cohorts you would expect in that six to nine region of subjects. So head with respect to the bar of success at <unk>.
Speaker Change: Clearly this is 28 daily administration so.
Speaker Change: It's a significant hurdle to have.
Speaker Change: Reasonable safety and Tolerability achieved in.
Speaker Change: In addition to that we'd be looking for Oh F.
Speaker Change: <unk> or lung function improvements and the bar that has been established recently as 3%. We believe is is if we achieve that that that would justify advancing the program.
Speaker Change: Clearly the higher a percentage that we would get would impact the size and nature and cost of our.
Speaker Change: <unk> phase III trials.
Speaker Change: In terms of the types of patients I think he might be inferring to maybe class one and non class one it would've approximately half of these subjects would be class one subjects and the other half would be non class one but every single one would be similar in that they're all non modulator responders.
Speaker Change: And so we don't tend to bifurcate the data we view this group is happy.
Speaker Change: Having similar unmet medical need and presentation. So Scott.
Speaker Change: And that's it.
Speaker Change: Very helpful. Thank you I'll jump back in the queue. Thanks.
Speaker Change: Thanks, Yes.
Seamus Fernandez: Well next go to Seamus Fernandez with Guggenheim Securities. Please go ahead.
Speaker Change: Hey, guys. This is Evan Wang on for Seamus Thanks for the questions.
Speaker Change: Just following up on cystic fibrosis, we've seen some tolerability issues around cause that Arrow program can you remind us again difference of about three two versus some of the other competitor mrna programs and just to hone in on that a little bit more in terms of the dose range youre exploring and what we may see from this these first four these three dose cohorts, especially <unk>.
Speaker Change: All of them to what you studied in healthy volunteers and the initial CF patient studies.
Speaker Change: Then you know in terms of the first two dose cohorts.
Speaker Change: How should we be thinking about that I guess weather and whether you expect each dose cohort to be efficacious or whether you expect a dose response here. Thank you.
Speaker Change: Yeah, a lot there are all good questions first of all our therapeutic is different from our competitors.
Speaker Change: I think the key points of differentiation that would be number one our delivery technology, our lunar 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 showcased these differences in preclinical.
Speaker Change: Animal models.
Speaker Change: So clearly there's there's there's something there too 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.
Speaker Change: The 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 are.
Speaker Change: Two key areas of differentiation, we we mentioned that Theres two cohorts in each of those or is attributed to a different dose level.
Speaker Change: Of course flexibility built into this.
Speaker Change: A phase II study to have a third cohort or third dose level or expand to the second level. We haven't provided any guidance on the nature of that third dose level, but ah.
Speaker Change: The data that we intend to share.
Speaker Change: Year will involve two well be drawing from two different dose levels.
Speaker Change:
Speaker Change: Uh huh.
Speaker Change: None of these levels of.
Speaker Change: Of.
Speaker Change: Dosing is wasted we believe you asked if all of these could be efficacious as somewhat that that may indeed be the case, but who will save the details and the for that disclosure for mid year.
Speaker Change: Got it thank you.
Speaker Change: Thank you and next we'll go to Myles Minter with William Blair. Please go ahead.
Speaker Change: Hi, This is Jake on for Myles. Thanks, So much for taking our question couple for you first on C. S. We're just wondering if you guys have.
Speaker Change: Talked about any sort of accelerated approval pathway for <unk> three to given that that need their adult <unk> patients.
Speaker Change: Then a second question on OTC you guys mentioned measuring glutamine is a biomarker. There just wondering if you have any sort of initial bar for success wherever we should expect a percentage of normal on on glue to me. Thank you.
Speaker Change: Okay, great questions first of all with respect to some sort of regulatory acceleration.
Speaker Change: Uh huh.
Speaker Change: Whenever you see excellent phase II data that would always warranted discussion with regulators to accelerate approval pathway.
Speaker Change: Especially like you mentioned for serious diseases, where there is significant unmet medical need.
Speaker Change: Oh.
Speaker Change: We have not shared any data so we don't know.
Speaker Change: It would be too early for me to guide whether this is good or grade are excellent data, but to simply address your question. If it's considered excellent data then yes, we would be looking.
Speaker Change: Looking to accelerate the clinical path for sure.
Speaker Change: With respect to glutamine, I, I think I I'd like to remind everyone listening that if you have a dysfunctional urea cycle.
Speaker Change:
Speaker Change: 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 to create a biomarker that that can help us understand this disease in terms of what or would we be.
Speaker Change: Looking for including me levels would be it would be simply to restore normal.
Speaker Change: <unk> levels so.
Speaker Change: Very often you would it's well known that our folks suffering from urea cycle disorders, including OTC deficiency have elevated glutamine levels.
Speaker Change: And if we could restore those into the normal range that could be a some convincing evidence that debt that our therapeutics.
Speaker Change: And next we'll go to Whitney I, Jim with Canaccord. Please go ahead.
Whitney: Hey, guys. Thanks for taking the question just sticking with CF.
Whitney: Can you talk about the time points that you're measuring SUV in the study and what the duration of follow up I guess, we should expect from both cohorts.
Speaker Change: Im curious if theres interim time points Youre looking at between zero and 28 days and then stares subsequent time points and if we should expect all of those for both cohorts in the upcoming data.
Speaker Change: Yeah that they the details pertaining to this trial design are available on clinical trials Dot Gov and also the CF Foundation tracker.
Speaker Change: That tracks not only our.
Speaker Change: Phase II trial, and the details there, but also our competitors and that's a good reference for people to look at.
Speaker Change: We are going to be measuring F D V or lung function improvement.
Speaker Change: This 28 day treatment cycle, so what do I mean by before while Theres a screening process, where <unk> is measured and then of course. It you know a day zero, but you know prior to first administration and then there's a few measurements throughout the cycle and then of course afterward.
Speaker Change: It's approximately seven F E V measurements taken.
Speaker Change: We haven't shared the specific details of that just for competitive purposes, but but there's plenty of data points and in this study to gifts.
Speaker Change: A decent level of conviction to advance this program further into development.
Speaker Change: Did I address your question.
Speaker Change: Whitney.
Speaker Change: I think so for the first just to clarify though for it. So we should expect the full 28 days and then maybe some additional follow up from both cohorts or is it that well it shake out yeah. Okay. Okay, maybe not the entire follow up because these can be a few months and nature of the follow up. So we may not have the entire follow up for it.
Speaker Change: We intend to have safety tolerability and the the lung function values.
Speaker Change: For the complete treatment course correct.
Speaker Change: Okay perfect excellent. Okay, and then just a follow up to clarify on the U S coast safe 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.
Speaker Change: Okay, Yes.
Speaker Change: There is a milestone associated with first commercial sales in the U S and that milestone is not included in our guidance because we're not anticipating for commercial sale until 2028.
Speaker Change: And so hopefully that gives you some perspective.
Speaker Change: Two.
Speaker Change: The cash runway does not include a U S milestone related to first commercial sale.
Speaker Change: Okay, and also not one related to <unk>.
Speaker Change: I'm, sorry U S approval.
Speaker Change: Right. There is no milestone with U S approval, it's related okay.
Speaker Change: Wholesale correct, Okay perfect perfect. Thank you very much.
Speaker Change: Thank you Whitney.
Speaker Change: Thank you and next we'll go to Pete Stavropoulos with Cantor Fitzgerald. Please go ahead.
Samantha: Hi, This is Samantha on the line for Pete Thanks for taking our question. So on the CF program given that the impaired.
Speaker Change: Peer function impede mucociliary clearance and you go to do.
Speaker Change: Do you see potential for Oh, 32, 10, normalize or remodel the lungs and if it can can you speculate on the length of time of peak I'm curious to hear your thoughts.
Speaker Change: No. It's a great question, where we were hoping to be the first answer that question with data, but are just some basic comments is that these patients that are participating in our trial do not have 100% lung function and some of that dysfunction is attributed to irreversible damage. So there's going to be.
Speaker Change: Some portion of the lung that just isn't recoverable.
Speaker Change: But we're also optimistic that there is a portion that is and so the lung is is very well known to regenerate and heal effectively if you can reverse the dysfunctional biology, so we hope to see that our in our upcoming trial results in terms of the time because this is a topically.
Speaker Change: Administered agent.
Speaker Change: The time course to two.
Speaker Change: To restoration it.
Speaker Change: It may be different from systemic treatments like you see in the modulator business.
Speaker Change: We're different we're topically administered so accessibility to these cells is going to be.
Speaker Change: A key marker of success and as the lung heels, then more cells would be accessible so at least theoretically we anticipate.
Speaker Change: A steady improvement over an extended period of time, but what is just unknown at this point just how long is that time period and how much material is required but we were anxiously awaiting the data.
Speaker Change: That's very helpful and one short follow up question. Besides E. V are there any other measurement that you could or will look at that might enhance the investigators convection in the program something like quality of life measurements or others.
Speaker Change: Yeah. There's a survey that we're provided there's a validated CF questionnaire that over the last couple of decades in the modulator field.
Speaker Change: Have improved these questionnaires significantly and that will complement our <unk> data in terms of other mechanisms like mucociliary clearance or others with the FDA came back with some simple guidance there that all they need to see is F. E V to justify advancing this into a phase III trial, but we are supporting that.
Speaker Change: <unk> data set with with some questionnaires.
Speaker Change: To see if we can support.
Speaker Change: Supports what we observe in with respect to lung function improvements.
Speaker Change: That's great. Thank you guys so much.
Samantha: Thank you Samantha.
Speaker Change: Next we'll go to Tom Shrader with BTG. Please go ahead.
Speaker Change: Hi, good afternoon. Thanks for taking the question you've commented that the next CF trial is going to depend a lot on the the size of the efficacy signal, but do you have a sense of the minimum safety database for indication that this is 100 about right or are you flying.
Speaker Change: We are completely blind at this point.
Speaker Change: We're definitely not completely blind I think hundreds is it is it is reasonable.
Speaker Change: Unfortunately, it it depends on.
Speaker Change: How successful the phase II results are if if the more successful they are the more leverage we have to decrease this number and get this into two real subjects commercially as fast as possible, but 100 is reasonable so that would that would imply that we had 39 subjects in phase one and phase one b, we add another dozen that would get us.
Speaker Change: Silver 50 after phase two that we'd probably need a minimum of 50 people to strengthen the database to achieve that hundred but we have not just to be clear we haven't received that.
Speaker Change: But that that's a reasonable.
Speaker Change: Estimate.
Speaker Change: And then in O T C. It seems like there's two deliverables, one you're helping O T C. But in a grander plan that you're getting stuff into the liver is that the same read out 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.
Speaker Change: Both questions are that there's yeah, there's not going to be a bio sampling or or some sort of tissue removal as part of this process. The FDA doesn't require that for these you know significant rare diseases, but we do have a biomarker strategy.
Speaker Change: We've alluded to glutamine for example is one of those Biomarkers, but then there's also a functional readout and in the 15 and urea Genesis assay.
Speaker Change: It is a.
Speaker Change: Also of interest there are that.
Speaker Change: Great paper, just came out last week out at the University of Zurich that I've I encourage people listening to referred to but that's another a new exciting way to track disease progression or are healing.
Speaker Change: Okay, great. Thank you.
Speaker Change: Thank you Tom.
Speaker Change: Next we'll go to <unk> with Citi. Please go ahead.
Speaker Change: Yeah, Hi, Thanks, I had one question on CFS and one on O T C C.
Speaker Change: Yes, I think in the past you've talked about some thresholds for F. E V. One improvement that you would feel would be citizens is generally strong to move forward.
Speaker Change: I'm wondering if you could comment on that with respect to the upcoming data.
Speaker Change: And then on OTC you mentioned some Biomarkers you mentioned the <unk> assay I'm wondering are you also and then measure erotic acid and uridine because those are also urinary biomarkers there would be interesting.
Speaker Change: [noise] glutamine, but I think alanine is another one that could be interesting as a as a biomarker and and liver ammonia, which you can't measure.
Speaker Change: <unk>.
Speaker Change: Good. Thanks, Yigal ill first start with the thresholds in CF are these numbers that have been communicated over this last quarter, especially or are based on historical precedence, but in the modulator space, but if you. If you can have a 3% and if you can show a 3% improvement in F E V over a treatment.
Speaker Change: Of course, and then in order to re prove that in our phase III study would require a potentially hundreds of people.
Speaker Change: And so that's a significant.
Speaker Change: Endeavour Nonetheless, one that we would pursue a in order to prove that this is a real but if the F&B value goes up to 5%.
Speaker Change: Then your phase III trials could be as low as 50 people definitely are at least confidently below under 100 people.
Speaker Change: So there and if you go north of 5% then are in higher higher FPV responses. It wouldn't change the size of of the phase III trial because earlier on this call. There was a question about how much how many people would you need to establish it as a significant enough safety data.
Speaker Change: <unk> hundred.
Speaker Change: 100 is approximated at this point, but but so whether you see higher levels of MTV you'd still need them at least 50%. We estimate are 50 50 participants in the phase III trial.
Speaker Change: Shifting to the OTC program.
Speaker Change: Ironic as it is is a biomarker we are tracking as well and that's in the urine and that is associated with.
Speaker Change: You know the urea cycle in Hyperammonemia.
Speaker Change: And then also there is a several amino acids and biomarkers that were exploring a glutamine is just a more.
Speaker Change: Ah well understood and and and frequently used by clinicians and doctors to track people on ammonia scavengers are to look at glutamine to see if that's elevated as well then they still have some challenges with hyperammonemia that's outside of their ammonia scavenger.
Speaker Change: Medicine and in their diets. So so glutamine is a more common bio marker, that's well more well understood in the community, but you're absolutely right. There's other biomarkers, we're measuring as well.
Speaker Change: 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.
Speaker Change: Relatively small sample size six or 12 people. So what does that mean in terms of how much dispersion you're willing to accept and be comfortable that now whether it's the 3% of the 5% because obviously that will impact the way you power things.
Speaker Change: Yeah, Yeah, Yeah of course, we'd like to see elevated consistency.
Speaker Change: And in small data set such as this.
Speaker Change: The opportunity to share that data and discuss it but.
Speaker Change: At this time, it's just it's just too early to comment further on that but yes. We are to address your the core of your question are more consistent.
Speaker Change: Dataset would put would be preferred.
Speaker Change: Alright, thanks, so much.
Speaker Change: Next we'll go to yen and Sue with Wells Fargo. Please go ahead.
Speaker Change: Oh, great. Thanks for taking our questions.
Speaker Change: Uh-huh cystic fibrosis I thought.
Speaker Change: Previously the guidance was data second corner.
Speaker Change: That guidance is mid year.
Speaker Change: Okay to assume that the more likely the data will be in the third quarter.
Speaker Change: What might be the venue for the update.
Speaker Change: And efficacy.
Speaker Change: I was wondering.
Speaker Change: In terms of Ah.
Speaker Change: You talk about the bar for S E V. One.
Speaker Change: Wondering what is the bar for proportion of patients meeting with that 3% minimum thresholds.
Speaker Change: Proof that we did you know.
Speaker Change: Would it be.
Speaker Change: Like if the response rate if we can call them that are in.
Speaker Change: Right.
Speaker Change: I expect it to be Saturday broad or could you just be a even that like a 20% response rate are still considered a worthwhile caught up to go forward with.
Speaker Change: Yeah. Thanks Shannon.
Speaker Change: You bring up a great question with respect to the bar of a response rate that that hasn't really been established by the field. We're gonna have to make a call are based upon the this data the F E V and the consistency of it there isn't a you know some sort of feedback we've received from the FDA for example on this question.
Speaker Change: We have received feedback from the FDA that the 12 subjects may very likely be sufficient to advance. This so as long as there is some the.
Speaker Change: Level of consistency within these 12 subjects and remember multiple dose levels will be evaluated and within this group than that Oh.
Speaker Change: Likely considered a success and we'll be able to risk.
To receive approval to advance this into a phase III trial.
Speaker Change: Then you asked another question, though it was about.
Speaker Change: The timing of ammonia.
Speaker Change: Oh, the timing and venue yeah well.
Speaker Change: This data set is evolving data.
Speaker Change: Data from two cohorts now we wanted to allow that extra few weeks just to schedule and get our additional additional numbers to strengthen the dataset. So it's just a.
Speaker Change: That that's the reason for you know focusing on maybe a mid year.
Speaker Change: Data interim data update in terms of the venue, we haven't decided on that.
Speaker Change: But.
Speaker Change: That is something that we'll communicate you know relatively soon here.
Speaker Change: Okay. If I may I'm also wondering since you are moving ahead with holiday on the BLA, So you're still on track for.
Speaker Change: How long it'll be all haynesville cost save U S. A was wearing a with a new leadership at Ciba have you had any interactions with FDA.
Speaker Change: Very recently.
Speaker Change: And what is the expectation for this howdy.
Speaker Change: Our interactions with the F D. A I'll first comment on that had been normal.
Speaker Change: The feedback we've received has been within the expected timeline or even earlier in the examples of fast track designation on the vaccine side.
Speaker Change: So we haven't seen any changes to regulatory environments for at least our mrna based vaccines and.
Speaker Change: In therapeutics.
Speaker Change: We do recognize that there's.
Speaker Change: Our passionate new administration.
Speaker Change: But all of them and all of the employees, we've talked to at each of the these agencies are are passionate about gaining access to safer and better medicines and vaccines and that is almost a credo at arcturus, we want to provide that and we're believing where we're providing data to support that notion.
Speaker Change: So I think I'm the science will win.
Speaker Change: We will stand on its own lakes throughout this process.
Speaker Change: Great. Thanks for taking the questions.
Speaker Change: Yeah. Thank you you know.
Speaker Change: We will go next to Yale Jen with Laidlaw <unk> Company. Please go ahead.
Speaker Change: Good afternoon, and thanks for taking the question.
Speaker Change: Just to want to phone us the first one is although you're regenesis.
Speaker Change:
Speaker Change:
Speaker Change: You mentioned during the call could you elaborate a little bit more in terms of India.
Speaker Change: Read all that good.
Speaker Change: They're relevant to the data released in the movies.
Speaker Change: The second question really here is that.
Speaker Change: On a big picture perspective that given that you're focusing much more on your in house program and so far you have to react.
Speaker Change: Iraq was.
Speaker Change: Would you close it looked at more maybe you mean, the early stage sold maybe enrich the pipe lie.
Speaker Change: Come out later this year or early next year or two.
Speaker Change: You can reach that and.
Speaker Change: Yeah, we did.
Speaker Change: They they early early stuff does not.
Speaker Change: Consume a lot of resources. So you know clearly we wanted to be in a position of.
Speaker Change: Being able to announce new programs when its appropriate upon establishing any sort of proof of concept for each of these therapeutic programs.
Speaker Change: And we've already done a considerable effort there already to date. So we're in a position to move if needed.
Speaker Change: R R.
Speaker Change: Our focus on our budget and extending the runway hasnt impacted our subsequent programs that works already been done.
Speaker Change: Okay in terms of your agenda assay any specific read out that we should pay attention to.
Speaker Change: Yeah, I encourage people to go to the 15 and urea Genesis paper that I have.
Speaker Change: Highlighted a couple of times on this call out of the University of Zurich, It's new.
Speaker Change: It's called the it comes out of the journal of metabolic health and disease.
Speaker Change: And the title of it is characterization and treatment monitoring of urea Genesis disorders using stable isotopes.
Speaker Change: But.
Speaker Change: We just believe it's a significant upgrade on an a on the urea Genesis assays of decades ago.
Speaker Change: Incidentally better processing.
Speaker Change: And we'll be collecting.
Speaker Change: Collecting data.
Speaker Change: Within the context of what's been utilized in this paper.
Okay very helpful.
And we will provide more details on this at the right time, where we just planted that seed.
Speaker Change: Okay.
Speaker Change: Well, great. Thanks, a lot and congrats on all the other provinces.
Speaker Change: And this concludes our question and answer session I would now like to turn the call back over to Joe Payne for final and closing remarks.
Joe Payne: Hey, thanks, everyone for participating on the call I know theres, some conferences up and we can meet face to face, but if theres any remaining questions don't hesitate to reach out to our team and we'll get back to you. Thanks everybody.
Joe Payne: Thank you and this does conclude today's conference. We thank you for your participation you may disconnect at any time.
Joe Payne: [music].
Joe Payne: Hum.
Joe Payne: [music].
Joe Payne:
Joe Payne: Yeah.
Joe Payne: Mhm.
Yeah.
Joe Payne: Hum.
Joe Payne: Uh huh.
Joe Payne: [music].