Arcturus Therapeutics Holdings Inc (ARCT) 2023 Q1 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Arcturus Therapeutics First Quarter 2023 Earnings Conference Call. (Operator Instructions) This call is being recorded on Tuesday, May 9, 2023. I would now like to turn the conference 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 First Quarter 2023 Financial Update and Pipeline progress call. Today's call will be led by Joseph Payne, our President and CEO; and Andy Sassine, our CFO; Dr. Pad Chivukula, our CFO and COO, will join in for the Q&A session as well. 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.

Please see the forward-looking statement disclaimer on the company's press release issued earlier today as well as the Risk Factors section in our most recent Form 10-K and in subsequent filings with the SEC. In addition, any forward-looking statements represent our views only as of the date such as statements are made. Arcturus specifically disclaims any obligation to update such statements to reflect future information, events or circumstances. And with that, I will now turn the call over to Joe.

Thank you, Neda, and good afternoon to all, and good evening to our friends on the East Coast. I will begin my remarks by highlighting our ARCT-154 COVID-19 vaccine Phase III program this is our most advanced clinical program. ARCT-154 has the potential to offer effective and longer lasting protection against COVID-19. I'm very pleased to report that last month, our collaborator, Meiji submitted a new drug application to support potential approval of ARCT-154 as a primary immunization vaccine based on our placebo-controlled Phase III study. Study conducted -- the Phase III study was conducted during a period of multiple variants of concern and met its primary endpoint of preventing COVID-19 and demonstrated a favorable safety profile.

The study was conducted to assess efficacy against COVID-19 in approximately 16,000 individuals, and we're very pleased with the results. The ARCT-154 Phase III comparative study of ARCT-154 as a booster is being conducted by Meiji Seika Pharma, and they have completed enrollment of approximately 828 subjects with interim results expected later this quarter. This noninferiority study is designed to evaluate the safety and immunogenicity of ARCT-154 compared to Comirnaty of Pfizer and BioNTech and administered as a booster dose.

We expect the interim analysis data to be submitted to the PMDA later this quarter. and to seek registration of the ARCT-154 as a primary series and booster later this year, potentially representing our company's first product approval. Such a meaningful milestone could be indicative of the broader platform opportunity for our mRNA medicine technologies to result in novel vaccines and therapeutics over the coming years. If approved, Japanese sales of ARCT-154 could represent a significant commercial opportunity for Arcturus. I will also remind you that the ARCT-154 Phase III Japanese booster study as well as product manufacturing related to this collaboration are being funded by Meiji Seika Pharma and the Japanese government. In April, Meiji Seika Pharma entered into an agreement with CSL Seqirus, whereby Meiji will be responsible for the distribution and sales of ARCT-154 in Japan. We are indeed fortunate to be partnered with competent and experienced commercial partners.

In April 2023, we received an advanced payment of $23.6 million for the manufacturing and supply of ARCT-154 from CSL. The advanced payment is specified -- is for specified manufacturing runs of ARCT-154, which includes the drug substance as well as the reservation fees and related manufacturing requirements. So ARCT is different than conventional mRNA vaccines in meaningful and important ways. The dose is very much lower. The product is lyophilized. It's not a liquid or a frozen liquid. These features bring potential dose-related safety benefits and provide a much better shipping storage and supply chain. ARCT-154 has shown and continues to show broad neutralizing capability against multiple variants of concern. ARCT-154 has the potential to offer not only effective but also longer lasting protection against COVID-19. And on top of this backdrop, we will soon be able to share the Phase III safety and immunogenicity booster data with multiple regulators across the globe. This is indeed an exciting time for our vaccine franchise.

I'll now move on to update on ARCT-810. This is our mRNA therapeutic candidate for OTC deficiency. This investigational medicine is designed to address the deficient OTC enzyme in the liver and thereby restore urea cycle activity and to prevent metabolic crises that cause neurological damage. ARCT-810 could potentially liberalize the strict dietary protein restrictions that OTC patients face today and improved quality of life for those living with this condition. ARCT-810 utilizes Arcturus' proprietary LUNAR delivery technology. An important attribute of our technology is that the lipids administered are rapidly degraded, which we expect lead to a favorable safety profile. ARCT-810 is being evaluated in 2 ongoing clinical studies in patients, a Phase Ib study in adults and a multi-dose Phase II study in adolescents and adults. Enrollment has begun in the ARCT-810 Phase II study in the U.K. and Europe. The Phase II multiple-dose study is designed to enroll up to 24 adolescents and adults with OTC deficiency and Arcturus plans to share interim Phase II data on a subset of participants later this year in 2023.

Now I'll move on to ARCT-032, our inhaled messenger RNA therapeutic candidate for cystic fibrosis. This program is designed to express fully functional CFTR protein in the lungs of individuals with CF, utilizing our LUNAR delivery technology that has been optimized for inhaled lung delivery. Our approach is agnostic to the underlying mutations associated with the disease. And as a result, ARCT-032 could provide clinical benefit across a wide range of those living with CF, including those that are not well served by currently approved CFTR modulators.

The clinical development of ARCT-032 is supported by encouraging preclinical data, demonstrating successful CFTR protein expression and the airway epithelium of the lung and different animal species and the restoration of the CFTR channel and the CFTR knockout mouse model and shown functional delivery of mRNA in a CF fare model. In addition, in vitro administration of ARCT-032 to bronchial epithelial cells from CF patient donors has also demonstrated robust expression of CFTR protein as well as functional restoration of (inaudible). The ARCT-032 clinical development program continues to advance according to plan.

We're pleased to report today that we have successfully completed the enrollment and administration of a Phase I study with 32 healthy participants, including 8 subjects in each of the 4 doses being tested, and we anticipate reporting study results later this year. The safety and tolerability data support the study expansion and inclusion of patients with CF. Arcturus is working on a protocol amendment to allow the dosing of CF patients and expect to initiate the enrollment in Q3 of this year. With that, I'll now pass the call on to Andy.

Thank you, Joe, and good afternoon, everyone. The press release issued earlier today includes financial statements for the first quarter of 2023 and provides a summary and analysis of year-over-year and sequential financial performance. Please also reference our Form 10-Q for more details on the financial performance. We are happy to see the progress by Meiji on submitting the new drug application to the PMDA in Japan for ARCT-154. We expect the booster data to be submitted shortly by Meiji once it is completed and quality checked in order to seek registration as a booster dose. This NDA submission is the first for an Arcturus vaccine and will be instrumental in the validation of our self-amplifying mRNA vaccine platform. In April 2023, we received an advanced payment of $23.6 million for the manufacturing and supply of ARCT-154 booster vaccines from CSL. The advanced payment is for specified manufacturing runs of ARCT-154, which includes the drug substance utilized as well as the reservation fees and related manufacturing requirements.

We took a number of positive steps to improve our balance sheet this quarter with the elimination of $60 million in long-term debt obligations. By repaying the Singapore loan of $17 million in unused principal and interest, we eliminated $34 million in additional principal and accrued interest on the nonrecourse loan. Additionally, we paid off our $10 million debt obligation to Bridge Bank. As of March 31, 2023, we have no long-term debt, and our balance sheet while current assets increased by $21 million, primarily due to the $90 million in accounts receivable from CSL, which is expected to be collected during the second quarter of 2023. I am happy to report our cash runway remains extended to the beginning of 2026 based on our current pipeline and assuming no sales-based milestones or revenues from any commercial product sales.

I will now provide a quick summary of our financial results for the first quarter of 2023. Our primary sources of revenues were from license fees, consulting and related technology transfer fees, reservation fees and collaborative payments received from research and development arrangements with pharmaceutical and biotechnology partners. Total revenues for the 3 months ended March 31, 2023, was $80.3 million compared with $5.2 million for the 3 months ended March 31, 2022. The increase in revenue is primarily attributable to an increase in revenue of $78.2 million related to the agreement with CSL and associated milestones achieved in the first quarter of 2023.

Total operating expense for the 3 months ended March 31, 2023, was $65.5 million compared with $38.8 million for the 3 months ended December 31, 2022. The sequential increase in the 3 months ended March 31 is primarily attributable to increases in manufacturing costs for various COVID programs related to the CSL collaboration and to a lesser extent, for increases in costs associated with start-up activities on the manufacturing and supply agreement with CSL and an increase in clinical trial expenses related to our cystic fibrosis and OTC programs. For the 3 months ended March 31, 2023, our Perth reported net income of approximately $50.8 million or $1.87 per diluted share compared with a net loss of $51.2 million or $1.94 per diluted share in the 3 months ended March 31, 2022, and net income of $117.3 million or $4.33 per diluted share in the 3 months ended December 31, 2022.

We recorded a onetime gain on debt extinguishment related to the Singapore loan of $34 million during the 3 months ended March 31, 2023. Additionally, we reported net interest income of $2.5 million for the 3 months ended March 31, 2023. Our cash position was $330.1 million as of March 31, 2023, compared to $321.8 million on March 30, 2022. As mentioned earlier, we expect to collect $90 million in the second quarter of 2023 associated with the CSL milestone we achieved in the March quarter. And in April, we received $23.6 million related to the manufacturing and supply of ARCT-154 from CSL. In summary, we believe that the company remains on a strong financial position and has the resources needed to achieve multiple near-term value-creating milestones for the vaccine and therapeutic programs over the next 9 months. I will now pass the call back to Joe.

Thanks, Andy. We have continued to make excellent progress and advanced our proprietary messenger RNA and LUNAR delivery technologies toward later stages of clinical development and potentially having our first product approval later this year. So this is an exciting time at Arcturus. Our strategic collaboration with CSL, which is focused on the development and commercialization of next-generation mRNA vaccines is making strong progress. Our teams are working towards the development and commercialization of next-generation mRNA vaccines, including those targeting COVID and influenza. And I look forward to providing more information about our progress and upcoming milestones in the coming quarters. So with that, we'd like to turn the time over to the operator for questions.

(Operator Instructions) Your first question is from Yasmeen Rahimi from Piper Sandler.

I guess the first one is, I know you noted that the booster data is expected later this quarter. Given that the study finished enrollment in February, and we're already in May, like are we really, really imminent like are we just I guess, still in the month of May or potentially June or will it fall in July? And then maybe comment again, a lot of our clients are asking, what was the rationale for Meiji to file ahead or instead of waiting for the booster data? And so if you could address that and then 2 follow-ups.

Sure. So first, with respect to your first question. Meiji informed us that the interim Phase III safety and immunogenicity booster data are presently undergoing final analysis and quality control procedures. So this means we're close, right, that the audited QC booster data should be submitted to the PMDA later this quarter. And with respect to your next question on the filing strategy, we're just adhering to very clear guidance from the PMDA regulator. So with respect to filing that we want to approve not only the booster, but the platform itself and the primary vaccination regimen. So the NDA was filed as such, according to what they guided.

Okay. And then the third question that I think a lot of our investors are trying to figure out is how to quantify the approval in Japan. So I guess question #1, what is the time frame by which you will be granted approval? And then how soon could you negotiate with the regulatory -- with the Japan authorities in terms of purchasing vaccines. I guess, at what junction will we find out how many doses of AARCT-154 was purchased?

Yes. In terms of framing the size of the Japanese market opportunity, I think it's helpful for people to understand that approximately 57 million mRNA boosters have been distributed and dosed since September 1 of last year. So that's approximately 250 days and an approximately 57 million mRNA booster shots have been distributed in Japan. So you can base your mathematical speculations and calculations on that.

You typically don't comment. Yes, on with respect to orders and discussions with the respective government that will be conducted by our partners, Meiji and CSL. And as soon as we have information available, we would be happy to disclose that information with the market.

The next one is from Pete Stavropoulos from Cantor Fitzgerald.

So I have one question on the vaccine 154. So we expect to hear about the data from Meiji study. Are there any details of the study that you can provide in terms of what the noninferiority margin may be? Is this study evaluating immunogenicity only against the Wuhan strain or only show activity against variance of concern?

The study is definitely evaluating the original Wuhan strain and other variants of concern are being evaluated as part of the study with respect to the statistical parameters, maybe I can throw that to...

Yes. Sure. This is Pad. Thanks for the question. Again, maybe we'll be doing all the synthesis clinical analysis. But they're going to be looking for a nifty threshold of just 0.67 and then an objective response rate of negative 10%. But a lot of that analysis can be done by them, and they're going to be sharing a lot of the data going forward.

Okay. And can you provide any color with regards to the CSL milestones? Do you expect more in the balance of this year? And if so, what would be those -- would drive those milestones?

Unfortunately, we don't give specific guidance with respect to the development milestones. But as soon as we have achieved and earned them, we will report them to the market as we progress throughout the year.

Right. One last question for 032. You fully enrolled the Phase I, it's completed in terms of healthy volunteers. I know the focus is safety and tolerability. But will you be looking at any biomarkers in healthy volunteers and also in cystic fibrosis patient populations? How will you evaluate the pharmacodynamic response?

Sure. So with respect to the healthy volunteers, we don't expect any biomarker data to be meaningful. All of the healthy volunteers already have healthy levels of CFTR in their lungs, for example. But we are closely tracking safety and tolerability and feasibility of dosing. This is the first patient population or subjects or volunteers that have inhaled LUNAR delivery technology. So we're very happy to report today that we've evaluated 4 different dose levels, which is basically an extension of time and chair. You can imagine each of these cohorts of 8 are people sitting in the chair, inhaling the technology for a period of time, the actual ARCT-032 drug product. And we're happy to report today that we've completed the trial, and we've provided some guidance that we intend to amend the protocol to add patients and enroll CF patients in Q3. And in patients is where we can find some potential biomarker or a more meaningful biological proof-of-concept data.

Is there any color you can give on what that -- what you potentially could look at?

Yes, there will be an appropriate time for us to do that. I think that will be at the next quarterly call once we detail the timing of CF patient enrollment and more specifically.

The next one is from Seamus Fernandez from Guggenheim Securities.

This is Boran Wang on for Seamus. 2 questions. First on Care bid. Can you talk about how the monovalent primary and booster approval in Japan helps set up the platform and streamline development for a bivalent future variance? And I guess, in terms of how you guys are thinking about continued development? And then I have a follow-up on that.

It is correct that mRNA platforms benefit from clock speed and rapid updatability with respect to future updates. And Arcturus is no doubt a next-generation mRNA platform. So we benefit from clock speed and rapid updatability benefits, which is becoming more overstated now, now that we realize that this is a perpetual and seasonal COVID vaccine market. I also want to highlight that with our manufacturing presence in Japan, (inaudible), that's a local presence of the manufacturing capability, too. So it's not just -- ARCT-154 is not only a great asset itself, but it sets the stage for future updates quickly and that can be manufactured efficiently right in locally in Japan.

Great. And then on CF, what from the healthy volunteer study really enabled expansion to CF patients? Was there a specific market you're looking at? And what does the amended protocol look like? Will it expand from New Zealand? And I guess when do you plan to update investors on potential patient data? Will that later 2023 update include both or just healthy volunteers?

So this last set of questions. I just want to restate your question that you're focusing on the CF program, correct, Seamus?

Correct.

Okay. Yes. So we definitely intend to modify. We definitely intend to modify the protocol to include CF patients. So I think the appropriate time to give a more specific update will likely be on the next call with respect to more specific timing of that in terms of the biomarker or any sort of strategic thinking as to when we can get some sort of proof of concept for ARCT-032 in patients. This is too early to provide guidance.

The next one is from Yigal Nochomovitz from Citi.

This is Carly on for Yigal. First, we had a follow-up related to one of the prior questions. I guess what's your expectation as far as how Meiji's data could potentially be leveraged outside of Japan? I guess, given the updated FDA guidelines related to use of bivalent RNA vaccines, should we assume CSL will be focused on bivalent rather than 154 for major markets? Just any thoughts you have on that dynamic would be helpful.

Yes. it's correct. The different regulatory agencies have been providing guidance on mRNA vaccines. And you're correct that in the United States, they've now mandated by valency for conventional mRNA but they have not mandated bivalence for other platforms and other types of technologies. And we have not yet shared our Phase III booster data with the regulatory agencies here in the U.S. So whether the FDA will consider our technology more like conventional mRNA or significantly different to be treated differently is yet to be established, but we are prepared in either situation. We're aggressively advancing our monovalent technology in Japan and our bivalent technology, we've provided updates with respect to milestones. That activity is ongoing in Europe and U.S. So we're prepared in either situation, depending on what a particular regulatory agency requests or expects. Did I address your question, Carly?

Yes, that's very helpful. And a follow-up related to that. I guess I know you and CSL have talked about the bivalent COVID program as well as a seasonal flu program. We were just curious if developing a combo COVID flu vaccine was covered under that agreement you have with CSL or if that might be part of your planning?

Yes. I can't speak to the details of a combined product in the CSL collaboration. We did disclose that the license is for COVID and flu, so it implies that there's potential there. But a combined product is definitely fascinating and interesting, but we haven't provided any guidance with respect to timing of a combined product.

Okay. Got it. And then just last question from us. As far as the $23.6 million advanced payment from CSL that you disclosed, can you just elaborate on what triggered that? I guess, was that specifically related to manufacturing runs to supply the Japan market? Any just clarity you could give there would be great.

Sure. As you can imagine, you have to prepare for manufacturing of 154, which required to manufacture drug substance, which is utilized in the production of the vaccine as well as reservation fees and related manufacturing requirements. So if you want to get certain orders in by a certain time, you need to prepare for or that potential opportunity, if that makes sense.

The next one is from Yanan Zhu from Wells Fargo Securities.

So on 154, are primary vaccine data required by the Japan regulators for approving the booster indication? And is the decision to submit the primary vaccine data by Meiji informed by the booster data that they might be seeing?

You do not -- it's not prerequisite to get the booster approved to have the primary approved, but it is very helpful, as you can appreciate, to get the platform and the primary approved for subsequent updates or future bivalent or more mature monovalent technologies as they come forward. So that is why the PMDA and Meiji and CSL and trust and our teams, we wanted to make sure that the primary vaccine was also included in this NDA because it allows for approval of the platform and accelerated time lines for subsequent updates as needed.

Right. And then the question on whether this decision actually was in part encouraged by what maybe saw with the Booster data. because obviously, it's a consuming time consuming process to submit like the large -- very large data set for the primary vaccine data, right?

Yes. We can allow you to speculate according to your own wisdom. We can only comment that the study has been ongoing since December that we've -- that Meiji has been collecting data after -- since February, but we can't comment as to whether they made decisions based on that data or not.

And we get this question from clients, whether -- about whether the monovalent 154 could compete effectively with the available bivalent vaccine in the Japan market. Could you shed some color on that?

Sure. I mentioned on this call that there's already been, I guess, 57 million mRNA boosters distributed and dosed in Japan just since September 1. So there's definitely a significant mRNA vaccine booster market in Japan. As for whether this self-amplifying mRNA next-generation technology can compete, that's one of the purposes of this Phase III heads-up comparison. And we'll let the Japanese government and Meiji take care of -- answer that question through orders in the future.

This is Pad. And I'll just add a couple of other comments to this. We and others have shown that the South or amplifying technology can potentially lead to higher neutralization titers as well as longer duration. So I think we will be tracking that in our Phase III booster trial. And I think if those data are positive, and I think we do believe that the monovalent could compete with some of the data that we're seeing with bivalent.

Yes, the lower dose, the lyophilized nature of the product and broad neutralizing capability and extended durability.

So maybe a couple of questions on the CF program. I was wondering, could you remind us whether the healthy volunteer study is a single dose or multiple dosing? And how do you think about whether the highest dose in healthy volunteers is sufficient to cover your potentially therapeutic dose in patients? And lastly, if this is a multi-dose in health of volunteers, would you have any like drug accumulation data in the lung in addition to blood?

Yes. This is Pad, and I'll just one of your questions. So again, the Phase I study was a single ascending dose, right, so a single dose, and we also plan to -- when we do the Phase Ib part of this, which is in patients, we intend to use, again, single-dose study. We -- Joe also mentioned that we did a dose escalation for different dose levels. And the dose levels that we chose that went into that Phase I healthy volunteer to study, we're in the therapeutic range of what we saw was effective in preclinical models. So some of the -- so the numbers we see in the healthy volunteers and if that's replicated in patients, we should -- that should be in the right range.

Got it. And will there -- understanding that this is a single dose administration, would we still be able to get some sense of drug degradation in the lung?

Of course, we won't be -- we're not -- I mean, obviously, what you're asking is that if we're going to be doing biopsies in the lung to look at either distribution or the activity. Obviously, that's going to be quite cumbersome, right? But we will be looking at PK, right? Looking at PK, like if you look at some of the data that was presented by the other mRNA companies that have worked on lung diseases, you can get a sense for what we would be looking at.

I'm sorry, just to clarify, I was referring to LNP accumulation in the lung.

Yes, I understand what you're asking. But I mean, the way to look for it is doing a biopsy, for example, right? In the lung, I'm not sure we will be doing that.

The next question is from I-Eh Jen from Laidlaw & Company.

My first question also get to 154. Given that the Meiji and the DSL, I believe, has a deal signed earlier this year, my question is, does CFL also have rights outside of -- outside of Japan for the monovalent vaccine. And would that be something that our payers also could benefit from that economically? And I have a follow-up.

Yes, correct. CSL has obtained in our collaboration, all rights to the COVID bivalent program outside of the United States. So -- I'm sorry, including the United States. So the global license and consequently because of the Meiji opportunity that we had going on concurrently, but the CSL opportunity, we were able to close both transactions simultaneously, and we were fortunate that the collaboration worked out very well for both -- all 3 parties, frankly. And so we're excited to be working with the #1 player in Japan, Meiji with respect to vaccines and flu. And obviously, CSL, the #2 in the world with respect to flu. So we have 2 very prominent players, certainly, in the various markets that we can rely on for commercialization. And as you know, the economics are very attractive in both the COVID monovalent and bivalent opportunity for us is a 60-40 profit split with both CSL and Arcturus.

Okay. Great. And a question on 032 is that you have done the healthy volunteer study for the safety. Do you anticipate either the next trial or in the future to do a longer safety study to ensure that patients will be able to inhale the drug with our -- in the long term without any negative impact?

Well, if you're referring to multiple dose, I'm sure that I can confirm on another time strategy. Yes, yes. So we definitely want to implement that at some point in our clinical strategy. And we'll provide more details on that likely on our next conference call. But the dosing, just so everyone on the call is clear, it's not like we're increasing the dose level where it's time and share. These 4 dose levels are -- as an individual, a volunteer sitting in a chair for a period of time, inhaling our drug. So it's -- as we -- when we say increasing the dose, we're just saying increasing the time and share while they're inhaling the drug, okay?

Okay. And then maybe last one, that remember the last call, you mentioned a little bit on the pipeline side and the HBV side. I'm just curious any updates on that? I know you maybe already presented, but just maybe more color.

Did you ask your question?

Yes, I did. Just in terms of the Hepatitis B virus data so far? Preclinical data.

Yes, the hepatitis B product, yes. So obviously, we presented recently our -- some of our capabilities in the gene editing space because Arcturus is a platform company that's been developing liver targeted nanoparticle that encapsulates mRNA for therapeutics. But we believe that this technology is quite broad and applicable to multiple therapeutic areas and therapeutic modalities. And gene editing is just one of those modalities that we feel very encouraged that this technology can be applied in that arena.

And more specifically, the data for hepatitis B, for example, that was presented in Paris recently, this is well received because it's another example of how our LUNAR technology has the ability to deliver large and very large mRNAs to hepatocytes. And so it opens up the field of opportunity a little bit broader than before.

There are no further questions at this time. I will now hand the call back to Joe.

Thanks for participating on the call, everyone. If there's any remaining questions, of course, reach out to our team, and we'll get back to you right away. Thanks to everyone. Good night.

Thank you. Ladies and gentlemen, the conference has now ended. Thank you all for joining. You may all disconnect.