Arcturus Therapeutics Holdings Inc.

Greetings and welcome to the Octurus Therapeutics Third Quarter 2023 Earnings Conference Call. At this time, our participants are in listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Netta Saravade, Vice President, Head of Investor Relations, Public Relations, and Marketing. Thank you. You may proceed.

Thank you, operator. Good afternoon and welcome to Arcturus Therapeutics' third quarter 2023 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. Pat Chivakula, 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 Secretary's 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 statements are made. Arcturus specifically disclaims any obligation to update such a statement. And with that, I will now turn the call over to Joe.

Thank you, Netta. It's good to be with you again, everybody. I'm going to begin my remarks with an update on progress regarding our monovalent COVID-19 vaccine, ARCT154. Following favorable clinical results from the Phase III pivotal studies, the new drug application is currently under review by Japan's Pharmaceuticals and Medical Devices Agency, or the PMDA. The ARCT154 Japan NDA submission is supported by an active controlled Phase III booster vaccine study, which was conducted in Japan, and a placebo-controlled Phase III primary vaccination series efficacy and safety study, which was conducted in Vietnam. The ARCT154 Phase III booster vaccine study achieved its pre-specified primary endpoint, demonstrating the non-inferiority of an immune response against the SARS-CoV-2 ancestral strain as compared to Comirnaty. In addition, the superiority of ARCT154 in neutralizing antibody response against the SARS-CoV-2 Omicron BA4-5 variant was also demonstrated as a key secondary endpoint. Updated preliminary Phase III booster data was recently presented at the 11th International mRNA Health Conference in Berlin. In a heads-up comparison to an FDA-approved monovalent mRNA vaccine, monovalent ARCT154 showed multifold improvement in durability and multifold superior titers of neutralizing antibodies against Omicron BA4 and 5. And this was at the six months post-boost mark. These phase three booster results were consistent with the phase one slash two booster clinical trial durability data that were collected previously and presented at the ninth ESWI influenza conference in Valencia. All of these observed clinical benefits were achieved with the STAR next generation mRNA technology, which is administered at five micrograms. This is an 83 to 92% lower dose level compared to approved mRNA vaccines. This lower dose level highlights the potential safety and tolerability benefits of this next generation mRNA vaccine platform technology. Based on all the clinical data collected to date, we believe that the next generation STAR mRNA platform is an effective and differentiated vaccine technology that may offer a longer lasting immune response relative to the older conventional mRNA platform technologies. Supported by the ARCT154 clinical data, Meiji Seika Pharma, the partner of CSL Securus, submitted a Japan NDA to support ARCT154 as a primary series and booster vaccine for COVID-19. The review of this application remains underway and is on track for approval in December. We filed a marketing authorization application in Europe, and we are seeking approvals for ARCT 154 and other major markets. We continue to mature the value and scope of the Star Next Generation mRNA vaccine platform by collecting meaningful bivalent vaccine clinical data as well. We're pleased to report today that the planned enrollment target of 850 participants has been reached in the ongoing Phase 3 bivalent COVID vaccine trial, comparing immunogenicity to bivalent Comirnaty. The initial top line results of the study are expected in Q1 of 2024, followed by an anticipated PMDA approval in Q3 2024. In summary, we are delighted with the rapid progress we have achieved this year with our Star Next Generation mRNA vaccine platform. We believe ARCT 154 provides clear validation of the broader opportunity for Arcturus' mRNA vaccine and therapeutic programs. Our strategic collaboration with CSL, which is Arcturus' exclusive global licensee, is focused on developing and commercializing next-generation mRNA vaccines and continues to make substantial progress. Our partnered Lunar Flu program which is also now known as ARCT2138 continues to progress with funding and operational support from CSL. Lunar Flu utilizes Arcturus' next-generation mRNA platform and we are intending to initiate a phase one clinical trial which is expected to begin soon. I'll now move on to ARCT810. This is our messenger RNA therapeutic candidate for Ornithine Transcarbamylase or OTC deficiency. This investigational medicine is designed to functionally replace the deficient OTC enzyme in the liver, restoring urea cycle activity and preventing metabolic crises that cause neurological damage. ARCT 810 could reduce the need for ammonia scavengers and ease the rigid dietary protein restrictions that OTC patients face today, thus improving the quality of life for those with the disease. ARCT 810 has received orphan drug designation and rare pediatric disease designation from the FDA. ARC-TA10 is currently being evaluated in two ongoing clinical studies in patients, a Phase 1B study in adults and a multi-dose Phase 2 study in adolescents and adults with OTC deficiencies. A Phase 1B single ascending dose study is being conducted in the United States and has completed dosing of all planned four cohorts in a total of 16 subjects. We expect the final database lock to occur later in this fourth quarter of 2023. The ARCT 810 Phase 2 study is being conducted in the United Kingdom and Europe and plans to enroll up to 24 adolescents and adults with OTC deficiency. The ongoing study evaluates two dose levels and includes up to six biweekly administrations for each participant. We remain committed to the development of ARCT 810 and we are taking various actions to address the continued challenging enrollment rate in Europe by adding study sites and patient services to improve screening participation. Updated guidance of interim phase two data is expected in H1 or the first half of 2024. Moving now to our ARCT 032 program. ARCT032 is an inhaled messenger RNA therapeutic candidate for cystic fibrosis, formulated with Arcturus' lunar delivery technology, which has been optimized for bronchial epithelial cell delivery. We completed enrollment and dosing in a Phase I study in New Zealand of 32 healthy subjects across four ascending single-dose cohorts. We look forward to presenting safety and tolerability study results of this Phase 1 study at an appropriate conference in the first half of 2024. We're pleased to report that we have initiated enrollment and scheduled dosing of the first patient in a Phase 1B clinical study in New Zealand, which is designed to enroll up to eight adults with cystic fibrosis, with each participant receiving two administrations of ARCTO32. We are presently guiding interim data in H1 2024. Arcturus is sincerely grateful for the continued support of the CF Foundation. In September, the organization agreed to increase its financial commitment to $25 million to advance ARCT 032. In October 2023, ARCT 032 received rare pediatric disease designation from the FDA. As such, if ARCTO32 achieves FDA approval for a pediatric indication, our person is eligible to receive a priority review voucher of a subsequent marketing application for a different product. New data was presented at the North American Cystic Fibrosis Conference, or the NACFC, in November. This new proof of activity in vivo data was collected with a CF ferret model, also known as G551D. The ferrets in the study require continuous treatment with the CFTR modulator Kalydeco to prevent disease progression. A single administration of ARCTO32 showed successful transfection of airway epithelial cells and restoration of mucociliary clearance above the level maintained with Kalydeco.

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

Thank you, Joe, and good afternoon, everyone. The press release issued earlier today includes financial statements for the third quarter ended September 2023 and provides a summary and analysis of year-over-year financial results. Please also reference our most recent 10Q for more details on the financial performance. Arcturus recently achieved a $35 million milestone from CSL. The milestone payment will be used to fund development activities for the Lunar COVID-19 Vaccine Program with CSL. We are very pleased with the ARCT 154 new drug application to the PMDA in Japan and we believe that this product could represent a highly differentiated vaccine option for patients. Furthermore, the development and manufacturing plan supporting ARCT 154 was carried out in a financially disciplined and efficient manner that leverages multiple external collaborations. The two ARCT 154 Phase III Japanese booster studies and the product manufacturing related to this collaboration are being funded by Meiji Seika Pharma and the Japanese government. Meiji Seika Pharma has an agreement with CFL Securus, whereby Meiji will be responsible for the regulatory approval, marketing, distribution, and sale of ARCT-154 in Japan, as well as coordinating the manufacturing of COVID vaccine products with Arcalis for the Japanese market. Arcalis, located in a strategic biomedical research and development hub in Japan, is poised to become a key player in the global mRNA drug manufacturing landscape. This CDMO is designed to support the production of mRNA vaccines as well as our mRNA-based therapeutics and has already completed the construction of a state-of-the-art mRNA drug substance manufacturing facility. To date, $165 million has been awarded to Arcalis by the Japanese government. These funds are being used to build mRNA drug substance formulated drug product capability and to construct a DNA template manufacturing facility. We expect this facility to become a leading manufacturer of mRNA-based vaccines and therapeutics with the ability to manufacture a vaccine within 100 days of an emerging viral strain. We expect this entity to provide meaningful financial dividends to our company over the coming years due to our substantial equity position. We are greatly appreciative of the Japanese government for their financial support. I will now summarize our financial results for the third quarter of 2023. Our primary source of revenue was 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. For the three months ended September 30th, 2023, we reported revenues of $45.1 million compared with $13.4 million for the three months ended September 30th, 2022. Revenues increased by 31.7 million during the three months ended September 30th, 2023 as compared to the prior year period. The increase was primarily attributable to revenue recognized from the collaboration agreement with CFL Securus and grant revenue recognized from the agreement with BARDA. Revenue increased by $90.3 million during the nine months ended September 30, 2023, as compared to the nine months ended September 30, 2022. The increase was attributable to an increase in revenues of $133 million, primarily related to the collaboration agreement with CSL Secure. This increase was primarily offset by less revenue in 2023 from other COVID program customers. Total operating expenses for the three months ended September 30th, 2023 was $64.5 million, compared with $50.2 million for the three months ended September 30, 2022. Our research and development expense consists primarily of external manufacturing costs, in vivo research studies, and clinical trial performed by contract research organizations, clinical and regulatory consultants, personnel-related expenses, facility-related expenses, and laboratory supplies related to conducting R&D activities. R&D expenses were $51.1 million for the three months ended September 30, 2023, compared with $37.7 million in a comparable period last year, primarily reflecting increased clinical research and manufacturing costs and personnel-related expenses. General and administrative expenses primarily consist of salaries and related benefits of our executive, administrative, legal, and accounting function, and professional fees for legal and accounting services, as well as other general and administrative expenses. G&A expenses were $13.4 million for the three months ended September 30th, 2023, compared with $12.5 million in the comparable period last year. The increase resulted primarily from personnel expenses due to increased headcount and salary, increased travel and consulting expenses, as well as an increased rent expense associated with the new headquarters facility. With the three months ended September 30th, 2023, our tourists reported a net loss of approximately $16.2 million, or 61 cents per diluted share, compared with a net loss of $35.3 million, or $1.33 per diluted share, in the three months ended September 30, 2022. Cash equivalents and restricted cash worth $369.1 million as of September 30, 2023, and $394 million on December 31, 2022. we have achieved approximately $365 million in upfront payments and milestones from CSL Secures as of September 30, 2023. We expect to continue to receive future milestone payments from CSL that will support the ongoing development of the COVID and flu program and three additional vaccine programs by CSL. Finally, I'm happy to report the expected cash runway now extends through the end of 2026 based on the current pipeline and programs. In summary, we believe the company remains in a strong financial position and has the resources to achieve multiple near-term value-creating milestones for the vaccine and therapeutic programs. Furthermore, with the anticipated 154 product approval in December in Japan, we look forward to beginning to report potential commercial shares. in the next few years.

Thanks Andy. We've continued to make excellent progress and advance our proprietary messenger RNA and lunar delivery platform technologies toward later stages in clinical development and we're excited about the progress toward our first potential product approval in December with ARCT 154. The achievement would definitely mark a a critical milestone for the platform and for Arcturus. And so with that, we'd like to turn the time over to the operator for questions.

Thank you. At this time, we will conduct a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, It may be necessary to pick up your handset before pressing the star key. Once again, that's star one at this time. One moment while we pull for our first question. First question comes from Yasmin Rahimi with Piper Sandler. Please proceed.

Good afternoon, team. Thank you so much for all the updates. The first question is directed to the upcoming Japan approval. Many clients are asking us if we should be expecting Any update in terms of the commitment of Japan's order for vaccines for 2024 at the time of the approval? That's question one. Question two, would love to hear your thoughts on, you know, given that the bivalent vaccine enrollment is complete, when we should be expecting data and in terms of the next steps with the program. And then third is congrats on the CF program and patient dosing. Are you planning to get to eight patients or is there an opportunity to maybe report data on, you know, a small cohort in 2024? And I'll jump back into the queue. And thank you for letting me ask my question.

Hey, Yaz, thanks. With respect to government orders that may be associated with the approval of ARCT 154, Meiji is primarily responsible for collecting or soliciting those orders, whether that's from the government or from the private sector in Japan. We're unfortunately, we do not have insight into that, so I'm unable to address that. But clearly an order cannot happen until the platform or a particular asset is approved. So I won't be able to speak to any details on that. With respect to the patients being recruited to support the Phase 1B trial for cystic fibrosis, we indicated that the first patient is getting dosed here shortly, but we're more than willing to share interim data if required. The guidance we've provided is in the first half of next year with respect to the safety and tolerability data of the Phase 1B trial for cystic fibrosis. Now, you asked a question about when data for another program, and this is for the bivalent. And so, yeah, the bivalent booster data, we've guided that. The bivalent, I'm just looking at my notes to confirm. Yes, enrollment is completing very soon, in fact, later this month. But we are going to be providing data next year. So top line data is expected in Q1 and an anticipated approval or PMDA approval in Q3 of 24.

Thank you so much. I'll jump back in the queue. Thanks, yes.

The next question comes from Miles Minter with William Blair. Please proceed.

Hey, thanks for the questions. Just relevant to what Meiji's been saying previously, which was potential approval of the monovalent vaccine in October, and you've been more conservative saying fourth quarter, I think that's panned out nicely. But is there anything else going on there from like a regulatory conversations point of view? I know you've shown us the six month durability data now. Did the PMDA request that because you have it? I'm just wondering why there's an optical delay from October to December. And maybe that's just the fault of MAGI and not of your own, but any clarity there would be great. And I've got a follow-up.

No, just the day 29 data was a prerequisite for the primary endpoint. The six-month data was not. However, this data is aware to the regulatory agency and taken into consideration as they proceed. you know, look at regulatory approval going forward. And we've guided again that approval is in December.

Okay. And then maybe just, sorry, was there a comment there? No.

Sorry, maybe just one on the cystic fibrosis program. Do you have to dose those CF patients in a stepwise fashion? So a single patient would receive two administrations, be monitored for safety before clearance to dose the next patient? Or can you get these patients in eight of them at a time and dose them all together? Thank you.

Yeah, we anticipate, this is Pat, and we anticipate dosing all the cohort all together. That's correct.

Okay. Thanks, Pat. Thanks for the question. The next question comes from Simush Hernandez with Google Home. Please proceed.

Thanks for the question. So, just a couple of quick ones here. In terms of the progression of potential milestones going forward, just hoping that if you guys could help us understand, you know, the sort of key steps forward from a milestone perspective, whether it be from the COVID program you know, the flu program or potentially other programs. And perhaps, you know, just in percentage terms, maybe not without absolute numbers, you know, where some of the key, you know, sort of catalyst milestones would really lay out or as a percentage of the terms of CSL, you know, what's possible in 2024. Obviously, we know what the runway is now through 2026 with the existing cash But it seems like that could be drawn out quite significantly in 2024 as more of these programs advance and as we see more of the COVID, you know, 154 applications move through into other jurisdictions more broadly. So just trying to get a better sense of the breakdown of those, you know, potential milestones. And then the second question just, and then I'll jump back in the queue. On OTC, is there a consideration just given how excruciating, frankly, the recruitment has been of this patient population? Is there just a view that the demand among patients is just really not there or that they're just too hard to find and this indicate might be smaller than what we thought previously? It just sort of begs the question, is it worth it to keep pursuing this indication, given the very challenging nature of recruiting the trial? Thanks.

Sure. Thanks, Seamus, for the questions. First, I'll walk through some of the near-term milestones, as you've asked. So with our internal programs, Starting with our OTC deficiency program, we've indicated that the database is being locked relevant to the Phase 1 and Phase 1B data for the OTC program. That database lock is going to occur later this quarter. With respect to Phase 2 interim data, we're guiding the first half of 2024. Now shifting to the CF program, we're

Hey, Joe, let me answer that question. I think he was referring to the financial milestones, and I think what the – is that correct, Seamus? You were referring to the financial, trying to understand, you know, the various programs and obviously with the cash runway going to – okay, that's what I thought. Correct.

From the back, deal with CSL.

Yeah, no, no, that's what I thought the question was pertaining to. So we typically don't guide, you know, specifically on, you know, the individual milestones because they're frankly, you know, very lumpy, right? And we don't know when they're going to start and initiate a certain, you know, program and when would the catalyst for that program be achieved, right? So in terms of not disappointing people, I'd rather say, you know, announce those milestones when we achieve them and can more freely be able to articulate how we, you know, we're able to accomplish that feat. And what's going to be critical here as we go forward is the guidance that we give you with the amount of cash that we have to give you a perspective of kind of what we're burning, you know, outside of the CFL and the BARDA relationships as well as the contributions from the Cystic Fibrosis Foundation. So if you take basically the number of years and divide it by our cash, you're going to come close to about $120 million in burn. And our goal will be to bring that down even more. So consequently, it's the guidance that's going to be critical to understanding the timing of when these milestones come in. And they're pretty significant, obviously. you know, over a billion dollars in development milestones spread out over three to five programs. So, you know, they're pretty meaningful. They're going to have significant impact on our operations. And, you know, as we achieve them, we will, you know, certainly be able to explain how we earned them and why we did. And hopefully that'll provide you enough comfort that, you know, we, are well funded into at least for the next three years without any revenue milestones in our forecast. No commercial milestones or revenues are included in our forecast. That would be certainly considered supplemental and we will update the market assuming we do have revenues in 2024.

And James, I can give you a little bit more color on the OTC program. As you know, rare disease programs are typically slower to recruit compared to some of the work that we've done with the vaccines. And it's a well-known phenomenon. And specifically, our OTC trial has been conducted in research centers, which can be slower, of course. So we've taken quite a bit of action to potentially speed that up. There are two key things that we've done in the near term that's going to help in recruitment and try to speed this up is we've enhanced the patient experience. And we've added a concierge service so that we can pay for all of the patient's needs. And then we've also implemented a patient stipend to recognize for a lot of their efforts to be part of these trials. Both of these things and also opening up more sites is going to help in recruitment in the near term.

Great. I guess just as a follow-up question to that, though, is there any concern around the size of the market opportunity for ARCT for O through 2, but just trying to get a better sense of You know, usually there's also demand for, you know, rare conditions where there can be benefits. Obviously, there are other treatment options out there. I'm just wondering if there's an assessment that would make sense as it relates to this program, just because with the CF program advancing as it is, it would seem like resources might be better spent to bring forward other rare disease opportunities. It's just been many, many years. pursuing this. So just, just trying to get a sense of how you guys are thinking.

That's a great question, you know, and I think, you know, Seamus, if we did not see the success that Horizon Pharma was having with the Revicti, I think we would have had a different perspective. But the fact that they're able to generate, you know, over $250 million in revenues annually on only 500 patients is a very encouraging, you know, opportunity for us. And assuming that, you know, Revicti only sequesters ammonia, if our mRNA therapeutics succeed, you know, we can prevent these people from generating ammonia, hopefully, right? And so that, or at least keeping the ammonia at a baseline level and hopefully having a normal, you know, protein diet. So obviously, you know, the opportunity to, you know, have, you know, a small, you know, in selective market share is very lucrative financially for a small company like ours. And certainly, you know, we're discouraged by the, you know, slow uptake and, you know, the patience and recruitment. But, you know, I believe the steps that we've taken here in the near term should, you know, encourage us to accelerate that process here in the first half of next year.

Yeah, we remain committed to the program, and not just as a valuable asset, but it also represents the flagship asset for the platform for intravenously dosed or systemically administered mRNA, and there's value taken into consideration for that.

Appreciate it. Thank you, guys. Thanks, Seamus.

The next question comes from Yakov Yoshamovic with Citi. Please proceed.

Hi, this is Carly on for you all. Thanks for taking our questions. We had a couple on the head to head by valence study. First, just wanted to clarify, was that study requested by regulators in additional geographies outside of Japan? And then second, more generally, I guess, just wondering how you're thinking about the market opportunity in Japan for by valent versus 154, and how that affects Meiji's commercial launch strategy in Japan. Thank you.

Yeah, thank you for the question. All the regulatory agencies have united in their message for monovalent COVID vaccines. The reason that we're proceeding as a collaboration between Meiji, CSL, and Arcturus here, the reason we're we're collecting bivalent data is that we don't have to do it in the future. So if there's ever a reason why the regulatory agency changes their view or opinion and bivalency becomes more important, then we will not need to do a trial at that time. We're just taking care of that now. It does strengthen the platform, though, to have monovalent phase three comparison data and then you know, add to that the bivalent comparative data with bivalent Comirnaty. But that's the reason we're proceeding with collecting the bivalent data, just to strengthen the platform and to prevent us from going back and doing a trial if it's ever requested in the future.

Okay, got it. That makes sense. And then just as one quick follow-up, I think in the past – You and Meiji have maybe talked about an XBB specific vaccine candidate. Just curious if there was an update on the status or the strategy for that program.

Sure, sure. The XBB vaccine update is a monovalent update. Some of our partners have started to communicate about this version of the vaccine. It's called ARCT 2303, and again, it's a monovalent updated asset. And so all the monovalent ARCT 154 data that we're collecting is very meaningful and relevant to that asset. With respect to updates on activities around that asset, we haven't disclosed those publicly, but there will be an opportunity for us to provide an update on our next call.

Okay, that's very helpful. Thank you.

The next question comes from Yanen Zhu with Wells Fargo. Please proceed.

Hello, this is Quan for Yana. Thanks for taking our questions. So two questions on COVID. So the first one is on the data you recently presented at mRNA healthcare conference. Can you Tell us how the data would translate to differentiation and potentially commercial success. And the second question is, after the potential approval in December, can you share with CSL, sorry, would CSL launch based on this, like, monovalent regional vaccine, or would they wait for the, for example, XBB update? Thank you.

Sure. So with respect to the leading commercial or marketing advantages of this platform, as we've touched on them already in this call, but I think clearly the buyers here will be very interested in our durability data. They want a more durable vaccine technology. The increased antibodies, of course, has not only an improved immune response, but an implied efficacy benefit. that would be interesting. And then as we go deeper into the endemic COVID market and as that gets established, there's going to be an increased emphasis on safety. So I think the fact that this technology is a much lower dose is going to be emphasized because of the potential safety benefits associated with dose-related toxicology. So durability, increased antibodies, and a much lower dose with potential safety benefits is going to be the initial strategy. Now, with respect to the, you had another question. Could you repeat that for us?

Sure. So after the potential approval in December, would CSL launch based on this original vaccine, or will they potentially wait for the XBB update? and launch that vaccine in-state?

Thank you. Well, with respect to what we want to do strategically is position ourselves with the right approvals and the manufacturing slots and timelines to address what the market desires or wants. So if we have an approval or approvals in place, then we can proceed to provide an updated monovalent vaccine. If the monovalent 154 gets approved, then we'll be in a stronger position to provide an updated monovalent vaccine if that's what the, if that's where the orders come.

And hey, this is Pat. And just one other thing to add is, you know, we, Joe mentioned on his call earlier, that we filed for EMA approval with our partner, CSL. Once we get the approval, I think CSL will be looking at what the commercial launch looks like, right? So I think they're in charge of that. But as Joe mentioned, we're currently focused on getting the approvals in the various jurisdictions now.

Thanks for all the comments. Thank you.

The next question comes from Pete Staropoulos with Cancer Fitzgerald. Please proceed.

Hi, Joe, Andy, and team. Nice to hear all the updates for the quarter. First question I have for 154, you know, what are your expectations of when you may hear back from the EMA? Sort of rough timelines.

Oh, with respect to hearing back from the EMA? This is going to be a considerable process. We haven't provided any tight guidance. on when approval is expected. I can refer to our partner CSL has guided that in 2024. We anticipate approval with EMA. All right.

And then in terms of Arcalis, you know, I'm just curious, you know, if you could just discuss a little bit if you can leverage that venture for manufacturing other pipeline candidates and perhaps, you know, distribution of drug outside of Japan. And if not already, you know, when do you expect the facility to be operational? And what will be the manufacturing capacity?

Yeah, I can answer that question for you, Pete. We've kind of guided that the drug substance, you know, facility has been completed. And we've kind of given a timeline for drug product and fill finish is probably going to be next year in that timeframe. So in the meantime, we're going to be supplying Japan and any other country through our current, you know, CDMO, you know, group that we've been working with, which includes cattle at El Debron, Ressie Farm, you know, in Europe. So until that plant is up and running and able to, you know, support not only Japan but any other mRNA, you know, product that, that we may be working on, or therapeutics, we certainly would be delighted to have that diversification of manufacturing opportunities in the Far East like that. So it's going to be a very strategic asset for MAGIE, for us, and for CSL, and certainly want to be able to utilize it to the best of the opportunity to address whatever the demand may be you know, on a global basis. Hopefully that will help, you know, answer your question.

It does. Thank you very much. And just one last question for 032 for cystic fibrosis. You know, for the phase 1B, you know, patients I know are going to receive two doses. You know, will you be looking at any pharmacodynamic markers or clinical outcomes? Again, it's only two doses to sort of gauge 032 activity.

Yes, the primary objective of the phase 1B study is just to understand safety and tolerability in actual CF patients with two administrations and to understand further what type of administration regimen will be ideal for a nice proof of concept study. That's to follow, assuming success, of course. But that's the, now are we looking at other, potential markers of success, yes, but our expectation at this point and the purpose of the study is just to show safety and tolerability in CF patients. We'd be very excited to see if multiple administrations are well tolerated because of the recent data that we shared in CF ferrets that are very, you know, indicative or important data that we bolt onto the human experience that increases the likelihood of success for this program.

All right, actually throw in one last question, if you don't mind. So this is an inhaled product. You know, is there any potential to actually develop some type of inhaled vaccine, you know, to respiratory viruses, you know, either alone or with partner CSL?

Well, it's a great segue to the opportunity, the overall platform opportunity for our technologies. If we're showing proof of concept in large vaccine trials, And in therapeutics, it does present the opportunity to potentially combine these. We haven't provided any guidance on this, but it does give people some sense of excitement of the platform in general that there's a lot of opportunity in the future.

All right. Thank you for taking my questions. Thanks. The next question comes from Ed Arce with HC BrainWrite. Please proceed.

Hi, everyone. This is Thomas Yip asking a couple of questions for Ed. Thank you for taking our questions. Perhaps first question for A10 and OTC. You mentioned that phase two data from the study in Europe are expected in the first half of 2024. Can you discuss what about the phase 1B single ascending dose study in the U.S. with 16 patients? When should we expect to see data from that study?

Correct. The database lock is later this year. Once we've gone through that process, we'll then strategically think of the right time to communicate the data because we need to understand the timing of the interim phase two data. So we may present these at the same time. We may present them separately, but we haven't made that strategic decision yet. But we have informed the market now that the database is getting locked this year for phase one and phase 1B.

Understood. And then perhaps switching gears, O32 and CF, we see that both Phase 1 studies are ongoing. When should we expect data from these studies then?

For the CF study? Yeah, the Phase 1B study. Yeah, we've got some interim Phase 1B data in the first half of next year. With respect to the Phase 1 study, we've now informed the market that we intend to provide a presentation at an appropriate conference in the first half of next year as well.

Understood. Just one last question from us. This one is probably for Andy. The 35 million milestone received from CSL, can you discuss what was the trigger events for the milestone?

Yeah, the milestone was related to our COVID and, you know, the bivalent program.

So hopefully that will help, you know, answer that question. And we've, you know, been able to articulate the progress we're having with the bivalent study in Japan. And we're very encouraged by the speed and, you know, success of that trial moving quite rapidly. Thank you.

Understood. Thank you again for taking our questions. Thank you. The next question comes from Yael Jin with Lay Law & Company. Please proceed.

Good evening, and thanks for taking the question. I'm just going to switch gears to the flu vaccine that will be started soon. My question is that given CSL is a major player in this space, Recently, some of the other messenger RNA flu vaccine has probably had some issues, maybe on the safety or efficacy. So what both you guys and CSL think that how would your messenger RNA vaccine could potentially overcome some of those hurdles and potentially have a better product? Yeah, Greg, first,

Yeah, conventional messenger RNA flu vaccines have, you know, potential challenges relating to, that are dose-related challenges and also durability challenges. And that's where self-amplifying mRNA, this next-generation technology, can prove to be different and in good ways that we could, because the dose is much lower, there may be some additional flexibilities there with respect to multivalency and including different antigens. And also what we've shown in the recent data in our infectious disease vaccine trials is that this next generation self-amplifying mRNA technology is more durable. And that is especially important in the flu shot space or the flu vaccine space. So those would be areas of differentiation.

Okay, great. That's very helpful. And maybe one more question here, which is for the bivalent COVID vaccine. Once they potentially approved in Japan, what is the commercial strategy outside of Japan was being contemplated? And was that something also in the United States as well?

Well, right now, all the regulatory interested in monovalent vaccines and not necessarily by the exchange. So if that does, we're in a position to provide whatever the customer wants, whether that's an updated bivalent technology or monovalent.

Okay, great. Thanks a lot. Appreciate it.

Yeah, thank you.

Thank you. At this time, I would like to turn the call back over to Mr. Payne for closing remarks.

Yeah, thanks, everyone, for participating on the call. If there's any remaining questions, don't hesitate to reach out to the team, and we'll get back to you as soon as we can. Thanks to everyone, and good night.

Thank you. This does conclude today's teleconference. You may disconnect your lines at this time. Thank you for your participation and have a great day.