Arcturus Therapeutics Q1 2025 Earnings Call Transcript

Quartr
Provided by Quartr
May 12, 2025

Key Takeaways

  • ARCT032 cystic fibrosis candidate is progressing in a Phase II multiple ascending dose study with no safety issues so far, and the company expects to complete enrollment by year-end and report interim data for the first two cohorts by mid-2025.
  • ARCT810 for OTC deficiency continues enrolling in Phase II, with interim biomarker data (including glutamine and a new 15N ureogenesis assay) expected in Q2 2025.
  • Costave mRNA COVID-19 vaccine received EU approval triggering an initial milestone payment, with a UK MAA filing slated for Q2 2025 and a U.S. BLA submission in Q3 2025.
  • ARCT2304 H5N1 influenza vaccine earned FDA Fast Track designation, has completed Phase I enrollment, and should deliver interim data in the second half of 2025.
  • Financially, Arcturus extended its cash runway through Q1 2028 by focusing R&D spending on its CF and OTC programs, securing the resources to reach multiple near-term milestones.
AI Generated. May Contain Errors.
Earnings Conference Call
Arcturus Therapeutics Q1 2025
00:00 / 00:00

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Operator

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.

Neda Safarzadeh
Neda Safarzadeh
VP, Head of Investor Relations, Public Relations, and Marketing at Arcturus Therapeutics

Thank you, Operator. Good afternoon and welcome to Arcturus Therapeutics' quarterly financial update and pipeline progress call. Today's call will be led by Joe Payne, our President and CEO, and Andy Sassine, our CFO. Dr. Pad Chivukula, our CSO and COO, will join them for the Q&A session. Before we begin, I would like to remind everyone that the statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement.

Neda Safarzadeh
Neda Safarzadeh
VP, Head of Investor Relations, Public Relations, and Marketing at Arcturus Therapeutics

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. I will now turn the call over to Joe.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

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. 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 II 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 II CF study is expected to receive daily inhaled treatments of ARCT-032 over a period of 28 days.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

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 II enrollment by the end of the year and provide phase II interim 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 II 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 mg per kilogram of a placebo-controlled European study enrolling OTC deficient individuals. The company expects to provide phase II interim data this quarter, or Q2 2025. The U.S. phase II study evaluates several biomarkers, including glutamine and ammonia.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

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 15-N ureagenesis assay. This is supported by a newly published paper out of Haberle's Lab at the University of Zurich. This 15-N 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. Given the current market conditions, we have made a strategic decision to focus our resources toward our mRNA therapeutics pipeline.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

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. The 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. The WHO is expected to announce the updated COVID strain later this week, and we, along with our partner CSL Seqirus, 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.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

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 reactogenicity 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 sa-mRNA COVID vaccine is safe and well tolerated and did not include any reports of myocarditis or pericarditis. In April, Arcturus' 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.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

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. 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 U.S. 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 BARDA.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

The 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 I trial being conducted here in the U.S. The company expects interim phase I data in the second half of 2025. With that, I will now pass the call to Andy.

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

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 details 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 programs exclusively. I am happy to announce that we have received the initial milestone payment from CSL in relation to the EU KOSTAIVE approval. We anticipate an additional milestone payment and will provide an update on our second quarter call.

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

I will now provide a summary of our financial results for the first quarter of 2025. Over the three months ended March 31st, 2025, revenues were $29.4 million compared to $38 million 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 31st, 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 BARDA programs, partially offset by increased manufacturing and clinical costs for the LUNAR CF and LUNAR OTC programs.

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

R&D expenses also declined sequentially from fourth quarter 2024 by almost $9 million, and we anticipate additional quarterly declines in the second half of fiscal year 2025. 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 reduced 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. For the three months ended March 31st, 2025, Arcturus Therapeutics reported a net loss of approximately $14.1 million, or $0.52 per diluted share, compared with a net [audio distortion] of [$3 million], or $1 per diluted share in the three months ended March 31st, 2024.

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

Cash and cash equivalents and restricted cash were $273.8 million as of March 31st, 2025, compared to $293.9 million on December 31st, 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 programs. I will now pass the call back to Joe.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

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

Operator

Thank you. As a reminder, if you would 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. Once again, that is Star one to take a question. We'll take our first question from Lili Nsongo with Leerink Partners. Please go ahead.

Lili Nsongo
Lili Nsongo
VP, Biotechnology Equity Research at 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 had 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 the potential incoming cash flows that you anticipate within this new guidance? The second question relating to the development of the KOSTAIVE vaccine, how should we think about potential milestones related to U.K. approval and U.S., as well as the timing for those? Thank you.

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

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. 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. A combination of all these factors contributed to the extension of the runway. More importantly, as well, you can probably surmise that the guidance we originally provided remained relatively conservative based on our cash burn historically. 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.

Lili Nsongo
Lili Nsongo
VP, Biotechnology Equity Research at Leerink Partners

It does. Thank you.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

And.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Go ahead. [crosstalk]

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

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

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

We have a milestone associated with the first U.S. revenues from KOSTAIVE, but we're not anticipating that, Lili, till 2028, frankly, assuming approval in 2026 or so with the U.S. 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.

Lili Nsongo
Lili Nsongo
VP, Biotechnology Equity Research at Leerink Partners

Thank you.

Operator

And we'll next go to Yasmeen Rahimi with Piper Sandler. Please go ahead.

Yasmeen Rahimi
Yasmeen Rahimi
Managing Director and Senior Research Analyst in Biotechnology at Piper Sandler

Good afternoon, team. Thank you so much for all the updates. I want to just spend some time, as many investors are very much looking forward to ARCT-032's interim readout here mid-2025. I just want to get a good understanding as we get into this mid-readout now that we have a little bit more granular color in the press release that's noted two doses are going to be provided. I guess, how large could the initial interim cohort be across these two doses? What is sort of the bar for success you want to see? To the extent you can talk about the patient population that you're recruiting for the study, that would be really helpful. Sorry, these are sort of three-pronged questions along the interim readout. Just want to have a good understanding of what we're going to be getting at that interim look.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

No, good questions, Yaz. 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. You asked about how large of a data set to expect. The entire phase II study has been listed at clinicaltrials.gov as 12. Because this is an interim data kind of drawing from two cohorts, you would expect in that 6-9 region of subjects. 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 FEV1 or lung function improvements. The bar that has been established recently is 3%. We believe if we achieve that, that would justify advancing the program.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

Clearly, the higher % that we would get would impact the size and nature and cost of our phase III trial. In terms of the types of patients, I think you might be inferring to maybe class one and non-class one. Approximately half of these subjects would be class one subjects, and the other half would be non-class one. Every single one would be similar in that they're all non-modulator responders. We do not tend to bifurcate the data. We view this group as having similar unmet medical need and presentation. That is it.

Yasmeen Rahimi
Yasmeen Rahimi
Managing Director and Senior Research Analyst in Biotechnology at Piper Sandler

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

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

Thanks, Yaz.

Operator

We'll next go to Seamus Fernandez with Guggenheim Securities. Please go ahead.

Evan Wang
Evan Wang
Equity Research Analyst at 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 competitor program. Can you remind us again the difference of 032 versus some of the other competitor mRNA programs? Just to hone in on that a little bit more, in terms of the dose range you're exploring and what we may see from these first or these three dose cohorts, especially relative to what you studied in healthy volunteers and the initial CF patient studies. In terms of the first two dose cohorts, how should we be thinking about that, I guess, and whether you expect each dose cohort to be efficacious or whether you expect a dose response here? Thank you.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

Yeah, a lot there. All good questions. First of all, our therapeutic is different from our competitors. I think 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. We have showcased these differences in preclinical animal models. Clearly, there is something there with respect to our delivery technology. When you are talking about safety and tolerability, you also have to recognize the level of purity of an mRNA construct. Arcturus has significant intellectual property pertaining to the purification of our mRNA. 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 a safety and tolerability profile.

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

Those would be two key areas of differentiation. We mentioned that there are two cohorts, and each of those is attributed to a different dose level. We have, of course, flexibility built into this phase II study to have a third cohort or third dose level or expand the second level. We have not provided any guidance on the nature of that third dose level, but the data that we intend to share mid-year will be drawing from two different dose levels. 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 will save the details for that disclosure for mid-year.

Evan Wang
Evan Wang
Equity Research Analyst at Guggenheim Securities

Got it. Thank you.

Operator

Thank you. Next, we will go to Miles Minter with William Blair. Please go ahead.

Operator

Hi, this is Jake on for 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 net need there in null 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.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Oh, okay. Great questions. First of all, with respect to some sort of regulatory acceleration, whenever you see excellent phase II 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. 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 I'd like to remind everyone listening that if you have a dysfunctional urea cycle, then your body cannot convert that ammonia into urea. What does it do? It converts ammonia into glutamine.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Glutamine is just a great biomarker that can help us understand this disease. In terms of what would we be looking for in glutamine levels, it would be simply to restore normal levels. Very often, it's well known that folks suffering from urea cycle disorders, including OTC deficiency, have elevated glutamine levels. If we could restore those into the normal range, that could be some convincing evidence that our therapeutic.

Operator

Next, we will go to Whitney Ijem with Canaccord. Please go ahead.

Whitney Ijem
Whitney Ijem
Managing Director at Canaccord Genuity

Hey, guys. Thanks for taking the questions. Just sticking with CF, can you talk about the time points that you're measuring FEV1 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 the zero and 28 days, and then if there's subsequent time points and if we should expect all those for both cohorts in the upcoming data.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

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 II trial and the details there, but also our competitors. That's a good reference for people to look at. We are going to be measuring FEV1 or lung function improvement before this 28-day treatment cycle. What do I mean by before? There's a screening process where FEV1 is measured. Then, of course, at day zero prior to first administration. There's a few measurements throughout the cycle. Of course, afterwards, it's approximately seven FEV1 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?

Whitney Ijem
Whitney Ijem
Managing Director at Canaccord Genuity

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

Joe Payne
Joe Payne
President and CEO at Arcturus Therapeutics

Yeah. Yeah.

Whitney Ijem
Whitney Ijem
Managing Director at Canaccord Genuity

Yeah. Okay. Okay.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Maybe not the entire follow-up because these can be a few months in nature, the follow-up. We may not have the entire follow-up for.

Whitney Ijem
Whitney Ijem
Managing Director at Canaccord Genuity

Right.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

We intend to have safety, tolerability, and the lung function values for the complete treatment course. Correct.

Whitney Ijem
Whitney Ijem
Managing Director at Canaccord Genuity

Okay. Perfect. Excellent. Okay. Just to follow up, to clarify on the U.S. KOSTAIVE milestone, is it that there is not a milestone on approval or that you are not including a milestone on approval in your guidance to be conservative?

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

Okay. Yep. 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 first commercial sales until 2028. Hopefully that gives you some perspective as to the cash runway does not include a U.S. milestone related to first commercial sales.

Whitney Ijem
Whitney Ijem
Managing Director at Canaccord Genuity

Okay. Also, not one related to EU—I'm sorry, U.S. approval.

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

Right. There is no milestone with U.S. approval. It's related to commercial sales. Correct.

Whitney Ijem
Whitney Ijem
Managing Director at Canaccord Genuity

Okay. Perfect. Perfect. Thank you very much.

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

Thank you, Whitney.

Operator

Thank you. Next, we'll go to Pete Stavropoulos with Cantor Fitzgerald. Please go ahead.

Samantha Schaeffer
Samantha Schaeffer
Biotech Equity Research Associate at Cantor Fitzgerald

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

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

No, it's a great question. We're hoping to be the first to answer that question with data. 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. There is going to be some portion of the lung that just isn't recoverable. We're also optimistic that there is a portion that is. The lung is very well known to regenerate and heal effectively if you can reverse the dysfunctional biology. 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 may be different from systemic treatments like you see in the modulator business. We're different. We're topically administered.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Accessibility to these cells is going to be a key marker of success. As the lung heals, then more cells would be accessible. At least theoretically, we anticipate a steady improvement over an extended period of time. What is just unknown at this point is how long that time period is and how much material is required. We're anxiously awaiting the data.

Samantha Schaeffer
Samantha Schaeffer
Biotech Equity Research Associate at Cantor Fitzgerald

That's very helpful. One short follow-up question. Besides FEV1, are there any other measurements that you could or will look at that might enhance the investigator's conviction in the program, something like quality of life measurements or others?

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

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 FEV1 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 FEV1 to justify advancing this into a phase III trial. We are supporting that dataset with some questionnaires to see if we can support what we observe with respect to lung function improvements.

Lili Nsongo
Lili Nsongo
VP, Biotechnology Equity Research at Leerink Partners

That's great. Thank you guys so much.

Andy Sassine
Andy Sassine
CFO at Arcturus Therapeutics

Thank you, Samantha.

Operator

Next, we'll go to Tom Shrader with BTIG. Please go ahead.

Tom Shrader
Tom Shrader
Equity Research Analyst at 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. Do you have a sense of the minimum safety database for indication of this? Is 100 about right, or are you flying sort of completely blind at this point?

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

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

Tom Shrader
Tom Shrader
Equity Research Analyst at BTIG

In OTC, it seems like there's two deliverables. One, you're helping OTC, but in a 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?

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

No, yeah. There's not going to be a biosampling 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, as one of those biomarkers. But then there's also a functional readout, and the 15-N ureagenesis assay is also of interest there. 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 new exciting way to track disease progression or healing.

Tom Shrader
Tom Shrader
Equity Research Analyst at BTIG

Okay. Great. Thank you.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Thank you, Tom.

Operator

Next, we'll go to Yigal Nochomovitz with Citi. Please go ahead.

Yigal Nochomovitz
Yigal Nochomovitz
Director of Biotech Equity Research at 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 feel would be sufficiently strong to move forward. I'm wondering if you could comment on that with respect to the upcoming data. On OTC, you mentioned some biomarkers. You mentioned the 15-N assay. I'm wondering, are you also going to measure uric acid and uridine? Because those are also urinary biomarkers that would be interesting. 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.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Good. Thanks, Yigal. I'll first start with the thresholds in CF. These numbers that have been communicated over this last quarter especially are based on historical precedents in the modulator space. If you can have a 3%—if you can show a 3% improvement in FEV1 over a treatment course, then in order to re-prove that in a phase III study would require potentially hundreds of people. That is a significant endeavor, nonetheless, one that we would pursue in order to prove that this is real. If the FEV1 value goes up to 5%, then your phase III trial could be as low as 50 people, definitely or at least confidently below under 100 people.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

If you go north of 5%, then in higher FEV1 responses, it would not change the size of the phase III trial because earlier on this call, there was a question about how many people you would need to establish a significant enough safety database, and 100 is approximated at this point. Whether you see higher levels of FEV1, you would still need at least 50%, we estimate, or 50 participants in the phase III trial. Shifting to the OTC program, uric acid is a biomarker we are tracking as well, and that is in the urine. That is associated with the urea cycle and hyperammonemia. There are several amino acids and biomarkers that we are 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 is elevated as well.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

They still have some challenges with hyperammonemia that's outside of their ammonia scavenger medicine and their diet. Glutamine is a more common biomarker that's more well understood in the community. You're absolutely right. There's other biomarkers we're measuring as well.

Yigal Nochomovitz
Yigal Nochomovitz
Director of Biotech Equity Research at Citi

Okay. Thanks. 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, six or 12 people? 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%? Obviously that will impact the way you power things.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

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

Yigal Nochomovitz
Yigal Nochomovitz
Director of Biotech Equity Research at Citi

Got it. All right. Thanks so much.

Operator

Next, we'll go to Yanan Zhu with Wells Fargo. Please go ahead.

Yanan Zhu
Yanan Zhu
Senior Equity Research Analyst at Wells Fargo

Oh, great. Thanks for taking our questions. On cystic fibrosis, I thought previously the guidance was data 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? What might be the venue for the update? 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, is expected to be fairly broad, or could this be even like a 20% response rate still considered a worthwhile product to move forward with? Thanks.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Yeah. Thanks, Yanan. You bring up a great question. With respect to the bar of a response rate, that has not really been established by the field. We're going to have to make a call based upon this data, the FEV1, and the consistency of it. There is not 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. As long as there is some level of consistency within these 12 subjects, and remember, multiple dose levels will be evaluated within this group, then that is likely considered success and we'll be able to receive approval to advance this into a phase III trial. You asked another question, though. It was about the.

Yanan Zhu
Yanan Zhu
Senior Equity Research Analyst at Wells Fargo

The timing and venue.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Oh, the timing and venue. Yeah. Because this dataset 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 dataset. That is the reason for focusing on a mid-year interim data update. In terms of a venue, we have not decided on that. That is something that we will communicate relatively soon here.

Yanan Zhu
Yanan Zhu
Senior Equity Research Analyst at Wells Fargo

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 U.S., I was wondering, with the new leadership at CBER, have you had any interactions with FDA very recently? What is the expectation for this filing? Thanks.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

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. 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. 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. That is almost a credo at Arcturus. We want to provide that. We're believing we're providing data to support that notion. I think the science will stand on its own legs throughout this process.

Yanan Zhu
Yanan Zhu
Senior Equity Research Analyst at Wells Fargo

Great. Thanks for taking the questions.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Yeah. Thank you, Yanan.

Operator

We'll go next to Yale Jen with Laidlaw & Company. Please go ahead.

Yale Jen
Senior Managing Director and Senior Biotech Analyst at Laidlaw & Company

Good afternoon, and thanks for taking the questions. Just two from us. The first one is for the ureagenesis assay you mentioned during the call. Could you elaborate a little bit more in terms of any specific readout that can be very relevant to the data release? Maybe the second question really here is that on a big picture perspective, given that you are 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? Thanks.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Yeah. The early stuff does not consume a lot of resources. 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. We've already done a considerable effort there already to date. 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.

Yale Jen
Senior Managing Director and Senior Biotech Analyst at Laidlaw & Company

Okay. In terms of the ureagenesis assay, any specific readout that we should pay attention to?

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

Yeah. I encourage people to go to the 15-N ureagenesis paper that I've highlighted a couple of times on this call out of the University of Zurich. It's new. It comes out of the Journal of Metabolic Health and Disease. The title of it is Characterization and Treatment: Monitoring of Ureagenesis Disorders Using Stable Isotopes. We just believe it's a significant upgrade on the ureagenesis assays of decades ago. It's a considerably better process. We'll be collecting data within the context of what's been utilized in this paper.

Yale Jen
Senior Managing Director and Senior Biotech Analyst at Laidlaw & Company

Okay. Great. Thank you very much.

Joe Payne
Joe Payne
CEO at Arcturus Therapeutics

We will provide more details on this at the right time. We have just planted that seed, if that makes sense.

Yale Jen
Senior Managing Director and Senior Biotech Analyst at Laidlaw & Company

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

Operator

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
Joe Payne
CEO at Arcturus Therapeutics

Hey, thanks everyone for participating on the call. I know there are some conferences up, and we can meet face-to-face. If there are any remaining questions, do not hesitate to reach out to our team, and we will get back to you. Thanks, everybody.

Operator

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

Executives
    • Joe Payne
      Joe Payne
      President and CEO
    • Andy Sassine
      Andy Sassine
      CFO
    • Joe Payne
      Joe Payne
      CEO
    • Neda Safarzadeh
      Neda Safarzadeh
      VP, Head of Investor Relations, Public Relations, and Marketing
Analysts
    • Samantha Schaeffer
      Biotech Equity Research Associate at Cantor Fitzgerald
    • Analyst at William Blair
    • Evan Wang
      Equity Research Analyst at Guggenheim Securities
    • Yanan Zhu
      Senior Equity Research Analyst at Wells Fargo
    • Tom Shrader
      Equity Research Analyst at BTIG
    • Yigal Nochomovitz
      Director of Biotech Equity Research at Citi
    • Yasmeen Rahimi
      Managing Director and Senior Research Analyst in Biotechnology at Piper Sandler
    • Yale Jen
      Senior Managing Director and Senior Biotech Analyst at Laidlaw & Company
    • Lili Nsongo
      VP, Biotechnology Equity Research at Leerink Partners
    • Whitney Ijem
      Managing Director at Canaccord Genuity
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