Arcturus Therapeutics Holdings Inc. Q2 FY2021 Earnings Call

Greetings, and welcome to the Arcturus Therapeutics Second Quarter 2021 Earnings Call. At this time all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce Neda Safarzadeh, Senior Director and Head of Investor Relations, Public Relations and Marketing. Thank you. You may begin.

Thank you, operator, and good afternoon, everyone. We are joined today by Joseph Payne, President and CEO; Andy Sassine, CFO; Dr. Pad Chivukula, CSO and COO; and Dr. Steve Hughes, our Chief Medical Officer. Before we begin, I would like to remind everyone that except for statements of historical facts, the statements made by management and any responses to questions on this conference call constitute forward-looking statements that involve substantial risks and uncertainties for purposes of the Safe Harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements other than the statements of historical facts included in this communication, including those regarding our planned, anticipated or potential development, manufacturing and commercialization activities or events including with respect to funding, initiation, design or completion of clinical trials the likelihood of success of the company's Coronavirus COVID-19 vaccine candidate or other product candidates, the company's manufacturing and other operations, and the company's current and future cash and financial position are forward-looking statements. Actual results and performance could differ materially from those projected in any forward-looking statements as a result of many factors, including, without limitation, an inability to develop end-market product candidates, unexpected clinical results and general market conditions that may prevent such achievements or performance. Such statements are based on management's current expectations and involve risks and uncertainties, including those discussed under the heading Risk Factor in Arcturus' most recent annual report on Form 10-K with the SEC and in other filings that Arcturus makes with the SEC. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise. Now it is my pleasure to pass the call to Joe Payne, President and CEO. Joe, please go ahead.

Thank you, Neda. Good afternoon to all. Thank you for joining the Arcturus quarterly call today. Arcturus is developing a powerful new class of mRNA-based vaccines and therapeutics. Over the last decade, our team has developed a differentiated platform technology, as well as highly promising pipeline candidates. We believe that our approach has the potential to directly address the underlying molecular basis of many serious diseases and could make a transformative difference in the lives of patients confronting many life-threatening conditions. This quarter has been an exceptionally productive period for Arcturus, where we have made substantial progress with our mRNA-based vaccines, our therapeutic programs, as well as the advancement of our underlying core technologies. In addition, we have also been effective at obtaining non-dilutive financial support to drive our pipeline forward in a very capital-efficient manner. I'll begin with a discussion of the progress we've made with our vaccine programs targeting COVID-19, starting with ARCT-021, our lead program. ARCT-021 is a differentiated single-shot COVID-19 mRNA vaccine candidate that clinically exhibits a promising T-cell response profile. This profile is attributed to the STARR™ or self-transcribing and replicating mRNA technology. We believe that our approach may provide meaningful advantages compared to currently available vaccines for COVID-19. We believe this single-shot dosing regimen would be highly favored, even required, in certain regions of the world compared to the two-shot regimens employed with currently authorized mRNA vaccines for emergency use. We have an ongoing fully enrolled ARCT-021 Phase 2 study. We have previously discussed the encouraging preliminary tolerability and immunogenicity data from this study, as well as from our prior completed Phase 1 study. Specifically, immunogenicity data from the study shows greater than 90% seroconversion for IgD antibodies binding to the full-length spike protein at day 28 following a single-shot dose of ARCT-021. The full results from the Phase 2 study remain blinded, and we expect to obtain those data later this year. Based on the available supportive data, we've made excellent progress advancing ARCT-021 to Phase 3 development. We are very pleased to report today that ARCT-021 has been selected by a global entity for inclusion in a Phase 3 vaccine trial against COVID-19, and we expect this study to begin imminently. After the specifics of the Phase 3 study are announced, we will provide more details with respect to this program. We can disclose that this will be a multinational placebo-controlled Phase 3 study designed to enroll tens of thousands of participants, and we'll evaluate a five-microgram dose of ARCT-021 administered as a single-injection regimen. Again, this is a differentiating feature of ARCT-021. Importantly, this large Phase 3 study upon commencement will be sponsored and funded by the global entity. We are understandably very grateful for their support and we look forward to the initiation of the ARCT-021 Phase 3 study as we look to bring this vaccine to communities in need across the world as rapidly as possible. I will also note that outside of Singapore, Vietnam, and Israel, Arcturus retains full global economic and distribution rights to ARCT-021. We've also made progress providing access to our vaccine technology in order to broaden the ability of individuals across the world to access COVID-19 vaccines. Earlier this month, we announced an agreement with Vinbiocare to establish a manufacturing facility in Vietnam for the manufacture of our Arcturus investigational COVID-19 vaccines. Vinbiocare will build out a manufacturing facility in Hanoi and Arcturus will provide access to our proprietary manufacturing technologies. In exchange, Vinbiocare has made a substantial $40 million upfront payment to Arcturus. Vinbiocare will also purchase the mRNA drug substance from Arcturus and pay a royalty on the doses manufactured. This is a strategically important transaction for Arcturus, and we believe this is also financially attractive, providing valuable capital to support the manufacturing efforts and continued development of our pipeline. While we have driven forward our lead vaccine candidate along with our manufacturing capacity, we've also advanced our next-generation self-amplifying mRNA vaccines targeting the highly prevalent SARS-CoV-2 variants that are circulating across our planet. As we all know, cases have been growing at a concerning rate driven in large part by the highly transmissible Delta variant. Here in the U.S., daily cases again topped 100,000 and alarming increases in transmission have been seen in many other countries across the world. Our expectation is that this Delta variant, and additional SAR-CoV-2 variants will remain endemic in the human population for years to come. Fortunately, we at Arcturus can rapidly update our mRNA vaccines as needed to address variants of concern. We identified ARCT-154, a next-generation two-shot mRNA vaccine that has been optimized to elicit high levels of neutralizing antibodies against the variants. Preclinical data has shown that our next-generation vaccines result in substantially increased levels of neutralizing antibodies to the variants of concern. If the observed increases of neutralizing antibodies in primates translate to similar fold increases in humans, then ARCT-154 could be an excellent vaccine to protect against the variants of concern, including the Delta variant. ARCT-154 utilizes STARR™ technology, that's the self-amplifying mRNA molecule. Therefore, it retains a promising T-cell profile in primates as well. In all of our studies, preclinically and clinically, we observe self-amplifying mRNA to generate better T-cell responses than conventional mRNA. The robust T-cell responses are attributed to the self-amplifying mRNA mechanism of antigen expression. I'll now turn the time over to Steve Hughes, our Chief Medical Officer here at Arcturus, to discuss our efforts targeting viral variants in more detail, including our clinical development progress, as well as the progress we've made with our mRNA therapeutic franchise. Steve?

Thanks, Joseph. I'll start with a further update on our novel vaccine programs designed to target widely circulating SARS-CoV-2 variants, including the highly contagious Delta variant that is now prominent across many countries. Arcturus has advanced ARCT-154 and ARCT-165 to next-generation STARR™ mRNA vaccine candidates that have been designed to effectively target SARS-CoV-2 variants of concern. ARCT-154 utilizes an optimized STARR™ mRNA sequence where we have incorporated multiple modifications, including for stability and increased translation, as well as changes made to increase the immunogenicity of the spike protein. Preclinical data demonstrate strong neutralizing immunogenicity in non-human primates to SARS-CoV-2 Alpha, Beta, Gamma, and Delta variants and we have provided additional experimental data in the press release issued this morning. Preclinical non-human primate data demonstrate that ARCT-154 elicits meaningfully higher neutralizing antibodies than ARCT-021, including neutralizing antibodies against the Delta variant. Also, as we observed with ARCT-021, we have observed robust T-cell responses with ARCT-154. Based on the strong supportive frequency data, we have taken steps to rapidly advance these novel vaccine programs towards clinical development in multiple studies. Earlier this month, we announced approval for a clinical trial application from the Singapore Health Sciences Authority to enable advancement of ARCT-154 and ARCT-165 into a Phase 1/2 clinical trial. This study will evaluate the vaccines both as a primary vaccination series and as a booster following initial vaccination with Comirnaty. We have been working with our partner Vinbiocare to initiate a pivotal trial with ARCT-154, and CTA approval from the Vietnam Ministry of Health was recently received to advance ARCT-154 into a Phase 1/2/3 clinical study. The trial, which is being sponsored and funded by Vinbiocare, is a randomized observer-blind placebo-controlled design that will assess the safety immunogenicity and efficacy in up to 21,000 participants with the potential for emergency use authorization by the Vietnam Ministry of Health as early as December 2021. I will now turn to ARCT-810, our therapeutic candidate for Ornithine transcarbamylase or OTC deficiency. ARCT-810 utilizes Arcturus LUNAR® lipid-mediated delivery platform to deliver OTC messenger RNA to the liver, the primary target tissue in OTC deficiency. Expression of the normal Ornithine transcarbamylase enzyme in the liver of patients with OTC deficiency has the potential to restore urea cycle activity, preventing neurological damage and the need for liver transplantation. To date, we have completed a Phase One healthy volunteer dose escalation study with ARCT-810. The study demonstrated that administration of ARCT-810 was associated with favorable tolerability and an attractive pharmacokinetic profile up to the top dose of 0.4 milligrams per kilogram, which is within the anticipated therapeutic range based upon data from our preclinical studies. Based upon these encouraging data, we have advanced this program to mid-stage development and last month we obtained approval from the UK Health Research Authority to initiate a Phase Two multiple-dose clinical trial for ARCT-810, and we are currently recruiting sites. The ARCT-810 Phase Two study is a randomized double-blind placebo-controlled nested single and multiple ascending dose design that includes adolescents and adults with OTC deficiency. ARCT-810 Phase Two study interim results from a subset of participants are expected in the second half of 2022. Before I close, I will also mention that our collaborator Ultragenyx recently got orphan drug designation and IND allowance for a Phase 1/2 study to evaluate safety, tolerability, and efficacy of UX053 in patients with GSD-3, and the study is expected to begin in the second half of 2021. UX053 is an investigational mRNA-based therapy encoding full-length glycogen debranching enzyme encapsulated in a lipid nanoparticle, and was developed by the Arcturus R&D team. We're very pleased to see this program advanced into clinical development. Furthermore, we believe that the progress made with UX053 represents another example of the broad application that is possible with our mRNA technology platform. I will now pass the call on to Andy, our CFO.

Thank you, Steve, and good afternoon everyone. The press release issued earlier today includes financial statements for the second quarter of fiscal year ‘21 and provides a summary and analysis of year-over-year and sequential performance. In our consolidated balance sheet, the second column should be dated as of March 31, 2021, and not March 31, 2020. Please reference our 10-Q for more details on the financial performance. Today, I will elaborate on the major changes impacting our cost and operations as we transition to a later-stage clinical company with multiple programs in our pipeline. I will also provide some details regarding our manufacturing strategy as we prepare for the potential of emergency use authorization in multiple vaccine programs. Finally, I will provide some insights regarding our cash position and expected run rate. We are fortunate that a global entity has selected our ARCT-021 vaccine to be included in a global Phase 3 trial, which they will sponsor and fund with participating countries. We are also very fortunate to partner ARCT-154 for the vaccine program with Vinbiocare, who will sponsor and fund our Stage Phase 3 clinical trials targeting the Delta variant. Vinbiocare Biotechnology is part of the Vin Group, one of Vietnam's largest corporations. Partnering these two vaccines will save us well over $300 million in clinical trial expenses. I will now talk about our global manufacturing footprint. We continue to build out our global manufacturing strategy by adding two key partnerships during the quarter and expanding our capabilities with another strategic partner. We have diversified our manufacturing footprint with strategic partners in Asia, Europe, and the USA. Last week, we announced a key partnership with the Vin Group to produce up to 200 million doses per year in Vietnam starting in 2022. Recently, we signed a joint venture agreement with Axcelead in Japan to form a joint venture called Arcalis to produce mRNA drug substance beginning in 2023. Axcelead is a Japanese company that formed a comprehensive collaborative partnership with Hitachi to develop solutions for next-generation biopharmaceuticals. We also expanded our relationship with Recipharm in Germany to significantly expand drug product capabilities, including fill-finish production of our lyophilized vaccines. We are also fortunate to have continued strong relationships with Aldebaran in the United States and Polymun in Austria. We continue to plan for the potential that one or more of our vaccines could receive emergency use authorization later this year or early next year. Along with our global manufacturing partners, we expect to have the capacity to produce hundreds of millions of doses annually. I want to provide some color on our quarterly expenditures and forecasted cash runway. Our total recurring operating expenses averaged about $55 million in each of the first two quarters of fiscal year ‘21. Approximately $10 million is attributed to G&A and that should increase by $1 million or $2 million for the remainder of 2021. The remaining $45 million in R&D expenses relate to our current pipeline, supporting our OTC cystic fibrosis, LUNAR flu, and COVID vaccine programs, including stockpiling long lead time raw material and vaccines for the EUA. This amount is expected to increase in the second half of 2021 as we ramp our production of ARCT-154 vaccines. Our cash balance at the end of the second quarter was $434 million and we received the remaining $30 million for the upfront payment for Vinbiocare last week. Based on our current pipeline, the company's cash position is expected to be sufficient to support operations for more than two years. I will now pass the call back to Joe.

Thanks, Andy. As we can hear from this call already, this has been a very productive quarter, and Arcturus has made substantial progress advancing our mRNA-based therapeutics and vaccine platforms. We believe that we have developed a powerful technology with the potential for broad applications across multiple diseases with both mRNA vaccines and mRNA therapeutics. To recap our recent progress: number one, we advanced ARCT-021, our lead vaccine program and obtained external support and funding by a global entity for inclusion in a multinational placebo-controlled Phase 3 vaccine trial. Number two, we identified ARCT-154 as a next-generation vaccine designed to elicit potent neutralizing immunogenicity to widely circulating SAR-CoV-2 variants and obtained CTA approvals in multiple countries to support its clinical development, including a Phase 3 study in Vietnam fully funded by Vinbiocare. Third, we have been approved to transition ARCT-810, our lead systemically administered mRNA therapeutic into a multiple-dose Phase 2 clinical study. And finally, we've also made considerable progress strengthening our core capabilities and increased our manufacturing capacity. So we expect to have an exciting second half of the year ahead with a number of anticipated milestones with our vaccine and therapeutic candidates and we look forward to keeping you informed of our progress. At this point, we can now go ahead and open the line for questions. Operator, please proceed.

Thank you. We will now be conducting the question and answer session. Our first question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed with your questions.

Hi, team, thank you so much for all the great updates. I have three questions for you. Maybe the first one is, can you tell us what is the secret sauce behind ARCT-154 that drives almost a 15 to 20-fold higher neutralizing antibody versus ARCT-021 and maybe, versus other self-amplifying mRNA that we have seen? Second question for you is, did you run convalescent human neutralizing antibodies in your sera analyses? And can you provide the ranges in the severity of that? And then I have a follow-up question regarding ARCT-021.

Great questions. Yes. Thanks for joining the call. I'll pass the mic over to Pad to address your question as to why ARCT-154 exhibits high neutralizing antibodies.

Thanks Joe. Obviously, we learned a lot over the last year in terms of improving immunogenicity of these spike protein based constructs. Some of the key optimizations that we've done for ARCT-154 include the modification and stability of the RNA and increasing the translatability of the replicates. So that's a key important change that we've made. And then we've also changed the spike protein to be more immunogenic. Some of the improvements of the spike protein include we added some key amino acid substitutions to make it more immunogenic. Well, we've also expressed the spike protein in its pre-fusion state and then finally, inactivated the site; we found preclinically that all of these modifications lead to enhanced stability and immunogenicity of the constructs.

Regarding the human convalescent sera panel, I might refer to Steve. Clinically, we had a number of approximately 147.

Yes. So the human convalescent sera, we've tested our human clinical samples and we haven't tested the non-human primate samples against those yet, but just as a comparison, the geometric mean titer from the human convalescent sera that we had, as Joe said, was around about 147 with titers at the low end down to 10 and at the high end up to 1000 or more, but with a mean value of around about 140. So in these assays, we would be considerably above that. But we do still need to follow up with the monkey testing in comparable convalescent sera samples.

Thank you, Steven. Then if I may ask a last question. So the Phase 3 for ARCT-021 is funded by a global entity. Has this global entity selected other vaccines from other sponsors for running a Phase 3? And how soon could we be expecting the completion of a large Phase 3 study that is funded by this global entity? And could you provide a little bit more detail in terms of this very big announcement?

No, it's great questions. At this time, we can't comment on any more detail until the details of the Phase 3 are announced. Once they are, we'll be able to speak more freely.

Are you the only sponsor selected for this funding, or are there additional sponsors? I'd like to hear your thoughts on that.

We'd love to speak more in detail on this. And there will be an appropriate time to do so in the near future. But at this time, we can't comment any further.

Okay, thank you. Thanks Joe. Congrats.

Yes. Thank you. Yes. Thanks for joining the call.

Thank you. Our next question comes from the line of an unidentified analyst. Please proceed with your questions.

Hi Joe and team. It's great progress. And thanks for taking my question. So maybe related to the trial in Singapore and that we'll look at 154 and 165 as boosters. So how should we think about the next step for these two assets beyond the Phase 1/2 study? And maybe on a broader level, what is your latest view on the booster approach, particularly in the U.S. and the EU market? And I have one follow up. Thank you.

Speculative questions, but Steve, do you want to address the booster market?

Yes. Thanks, let me take the questions in reverse order. So clearly, there is a booster market; the United States is working towards approval for giving booster injections. And more than one country in Europe has announced that they're going to be giving booster injections, I think Israel as well. So clearly, there is an evolving booster market. And that booster market is focused around emerging variants of concern. So with respect to 154 and 165, obviously, we have that clearly in our line of sight in terms of addressing the market need. And as we mentioned earlier, our platform approach allows us to very quickly pivot to address emerging variants of concerns as well. One thing I would like to add, though, is that what we've seen for in the monkey data is very, very similar responses to all of the variants of concern that we've tested. And so what we're anticipating is that these vaccines will allow us to cover emerging variants as well as the existing variants of concern.

Great, and then maybe on ARCT-810 in OTC deficiency, can you provide some insights on the dose that you have thought about for the Phase 2 study? And what biomarkers should investors focus on to get a sense of the advocacy in the upcoming Phase 2 study? Thank you for taking my question.

Okay, yes, great question. Thanks. So if you recall, in our Phase One study in healthy volunteers, we tested all the way up to 0.4 milligrams per kilogram; fairly confusing between the frequency and the top dose was very well tolerated. So within the multiple dose study, we're testing 0.3 and 0.4 milligrams per kilogram. So we're at the top of our dose range, which sits very, very nicely in the anticipated therapeutic range that comes out of our animal studies.

And our biomarkers that are on the top of our dose range, which sits very, very nicely in the anticipated therapeutic range that comes out of our animal studies.

Yes. On the biomarker side, really the traditional biomarkers for this disease and also looking at the 24-hour ammonia profile. So these are two key biomarkers for us, and then also the UAS cycle as well.

Great, thank you.

Thanks, Brian.

Thank you. Our next question comes from the line of Nick Abbott with Wells Fargo. Please proceed with your questions.

Good afternoon. Thanks for taking the questions. Congratulations on some terrific progress here. So my first question is on ARCT-154. How good is a single dose of ARCT-154? I think Joe said in your prepared remarks a single dose would be mandatory in certain geographies. So is there a plan to include a single dose in the Phase 3?

No, that's a great question. It's something that we're going to be evaluating. But ARCT-021 is our single-shot vaccine asset with a clinically promising T-cell response profile, whereas ARCT-154 is right now intended to be a two-shot vaccine or a one-shot booster optimized for high neutralizing antibodies targeting the variants, especially Delta. So we're viewing this as two separate assets. But having said that, are we going to be looking at blood samples and evaluating biomarkers after a single administration of ARCT-154? Yes. Is ARCT-154 a self-replicating mRNA vaccine? Yes, which implies that it has a promising T-cell profile as well. So we'll be closely monitoring it if that may have feasibility, at some later point.

Thanks. And then on ARCT-021, just looking at the graph you provide, which is very helpful. I mean, it appears to be around about half a lot less in terms of T-cell response on the ARCT-021 part. Is there a reason for that do you think? Or is this just sort of noise between different experiments done at different times?

Yes, it's a fair observation.

Yes, a fair observation.

Pad, do you want to comment on it?

Sure. Thanks Joe. Our T-cell data at least from our perspective, the T-cell data are comparable. As you can see, there's a couple of points that are above the median. But I think from our understanding, T-cells are important, and we're eliciting T-cells for both drugs, both ARCT-154 and ARCT-021.

But nonetheless, it is a fair observation. ARCT-021 does a great job at eliciting T-cell response.

And it brings me to it.

Sorry. This is the key thing: if you look at the ARCT-021 graph, the data is spread more widely. So there are a couple on each of the things; there are a couple of animals that scored much higher than the remaining animals. And that pushes the average up, whereas for ARCT-154, the data is tighter. So I think it's just variability. And if we tested more animals, those two sets of graphs would have come much closer together. I think a key observation I take away from the graphs is the consistency of the responses for both ARCT-021 and ARCT-154. We are not seeing that it is staggeringly better against one and not so good against the others. We're seeing a nice, consistent response across all of the variants.

Yes. Like you see variability with neutralizing antibodies, but not with T-cells, and this could be a very important feature of our vaccine franchise.

And you interpret that as you're targeting conserved epitopes or epitopes?

Exactly.

And then you just, maybe one more for me, just going back to what you said earlier, Joe, will it be a trial of ARCT-154 as a booster to ARCT-021? And then my last one is what is the rationale and strategy for ARCT-165? Thank you.

So yes, we do have plans to boost ARCT-021 with ARCT-154 and also ARCT-165 for that matter. So we'll make a subsequent disclosure on that once we have approval for that trial to move forward. ARCT-165, I think we're trying to develop a broad vaccine portfolio so that we can have coverage against multiple variants in multiple different countries. We were very fortunate in being able to take two of our assets forward into Phase 3 clinical trials. For ARCT-165, we're going to really assess how well it performs within the study in Singapore and whether there are any unique advantages in certain situations of ARCT-165 over ARCT-154 or ARCT-021 before we decide how to move that one forward. We'll be doing neutralizing antibody testing and binding antibody testing and T-cell testing against multiple different variants of concern to profile those vaccines in more detail.

Great. Thanks for the answer.

Thanks, Nick.

Thank you. Our next question comes from the line of Seamus Fernandez with Guggenheim. Please proceed with your questions.

Oh, great. Thanks. And congrats on all the progress guys. A couple of things just for clarification, just hoping to get maybe a better sense of how you're proceeding in Singapore specifically with the ARCT-154 and ARCT-165 program. Specifically, I'm just wondering if you would happen to incorporate a parallel head-to-head immunogenicity study versus Pfizer's vaccine, in part because you're also doing your testing on top of Comirnaty. So just wanted to get a better sense of if we're going to see head-to-head data as we saw today versus your historical vaccine, if we might get something similar in the Singapore study from an immunogenicity perspective as a boost program. And then separately, once full approval of Comirnaty has been executed, is it possible to run a head-to-head of ARCT-154 against the same exact model so that investors who might be skeptical of the magnitude of change here obviously, it looks quite substantial to me. But for those who might be skeptical, that might be one way to approach the comparison. Just wondering if you would consider doing something like that.

Yes. We're already considering it. We've already received approval to proceed with evaluating ARCT-154 as a booster to not only other Arcturus vaccine assets but also to Comirnaty. So we're already looking into that and evaluating that. And considering that data can be compared head to head and understand the value of this particular vaccine.

Well, I think that, as you noted, at this point, we can't get the Pfizer vaccine to do the comparison. It's not commercially available. So within the study in Singapore, it's actually not possible right now to do a direct head-to-head comparison. And I think what we'll have is the human data with real antibody levels in humans using well-validated assays that we can then compare with the existing Pfizer data. So I'm not sure there will actually be a need. One other important question really is how do the antibody levels, how are they maintained over time? So for the Pfizer vaccinated individuals, we'll know when they were vaccinated. So we'll know from their baseline sample, how far that they are from the original vaccination, and as we collect the data from our study over time, we'll be able to compare our antibody levels over time at a similar time point. So for example, if somebody was six months out from their Pfizer vaccine, and they've got an antibody level of X, we can have a look when they're six months out with our vaccine to see what the antibody levels are at that time as well. So we can do some indirect comparisons in that way. And I just think that the data emerging from the study will kind of overtake the need to do a direct head-to-head comparison.

Go ahead.

No, no, please. No, go ahead. Joe.

Okay, no, I was just going to add on to your question about the primate data and how investors should be convinced of how important this data is: the entire vaccine community has been collecting data this past year, and we've now gained considerable confidence and there's convincing evidence that immune responses against SARS-CoV-2 are similar to those reported in humans and authentically represent COVID-19 observed in the human population. So these primate models serve to be an excellent model and can be relied upon.

Great, and then just in terms of the timing of OUS or just the utility of the Vinbiocare clinical trial that's going to be run in Vietnam. Can you just talk about how you can utilize that data to gain approvals in other markets and how far-reaching you think those data could actually end up being?

Yes, thanks. That's a great question as well. So the study has been designed to meet international standards. So it's been designed so that the way the study is laid out and the collection of the endpoints and the way that we're analyzing the data, that it would be acceptable in Europe, the United States, and other geographies as well. In terms of whether conducting the study in an entirely different foreign population will meet the FDA standards, we plan to have those discussions in the very near future. So conceptually, we're planning to use the data to fall wherever we can to get board acceptance and make the vaccine broadly available in different geographies.

I guess as just my final question, in terms of gaining early use authorization, whether it be utilizing some of your antibody titer data, or I guess one question is will you be looking at or be able to do a sub-study of antibody titers based on some of the updates that have been provided by the WHO versus different variants as a way to pursue broader authorizations in developed markets like Europe or potentially even the U.S.?

Yes. We've got a substantial immunogenicity subset within the study where we're collecting CRM over time, different time points, so we will be able to do those evaluations against emerging variants of concern. So if an antibody becomes available in Europe, or the United States or somewhere else, then we should be well positioned to take advantage of that.

Great, thanks for the updates. And I'll jump back into queue. Thanks.

Great, thank you.

Thank you. Our next question comes from the line of an unidentified analyst with Goldman Sachs. Please proceed with your questions.

Hey, this is Rob on for Madhu. Just two questions. How much of a gap do you think there is developmentally between ARCT-021 and ARCT-154, and if ARCT-154 works well, would you only pursue commercialization of ARCT-154? Would you go after both? And then what kind of data should we expect from ARCT-810 OTC readout later this late in 2022? Would it be reasonable to expect scavenger therapy discontinuation and dietary change?

The latter question I'll have Steve comment on it. With respect to our intent pertaining to our two assets, we want to fully develop and market them. That's the intent. ARCT-021 is a single-shot vaccine with a clinically promising T-cell response profile, and that's needed, especially in certain regions. The single-shot nature, for example, while ARCT-154 has been optimized for high neutralizing antibodies, targeting Delta and the other variants, which is also needed over as a booster or as a two-shot vaccine. So I think both of these have a market clearly and we're addressing those in our Phase 3 studies. With respect to the latter question, I don't, Steve, do you want to comment?

No, great question. So ideally, over longer-term therapy, yes, scavenger therapy will be reduced and withdrawn. This particular study won't go out long enough to allow us to do that because you need to maintain the level of stability of the ammonia, 24-hour ammonia curve and UA Genesis assay before we start taking people off their meds. As this study moves out, that we almost certainly the data is positive at that interim analysis, we'll be looking at an open-label extension study to roll the participants over into and that's where we would be doing things like reducing their scavenger therapies or trying to push out the dose interval to longer intervals between each dose.

Okay, thanks.

Thank you.

Thank you. Our next question comes from the line of an unidentified analyst with Wainwright. Please proceed with your questions.

Hello, everyone, this is Thomas. Congratulations on all the recent progress. First question about the Vinbiocare collaboration in Vietnam. So the goal is potential EUA by the Ministry of Health in December 2021. Can you go over some key colors and timeframe between now to December?

Steve, can you address some sort of interim data between now and the anticipated emergency approval in December for the Vietnam study?

So the emergency use authorization will be based on the interim analysis. And that will be the first interim analysis of the data. So as it's a pivotal study, we can't go taking multiple data cuts like we can in earlier phase clinical trials. So we anticipate having the first interim analysis of the study in the November timeframe to enable emergency use authorization in the December timeframe.

Okay, thanks for clarification. And perhaps a question about the collaboration. You mentioned a $40 million upfront payment, but also in the press release, it says the remaining $30 million was received subsequent to quarter end. So was $10 million received in the first quarter or second quarter? And if so, how is that characterized?

Yes. This is Andy Sassine. The $10 million was received prior to the end of the quarter as a deposit and consequently was reflected as a current liability, accrued liability on our balance sheet. Obviously, we executed the transaction and signed the deal subsequent to the quarter, and that the remaining $30 million so that accrued liability will disappear from our balance sheet. Hopefully that helps clarify the accounting treatment of that $10 million deposit.

Yes, it does. Thank you. And perhaps one last question from us regarding ARCT-165. When should we expect preclinical data from perhaps non-human primates study? And can you go over some similarities and major differences between ARCT-165 and ARCT-154?

Yes. Well, if you noticed, we've entered into collaborations or relationships with respect to ARCT-021 and ARCT-154. If we do the same thing with ARCT-165, because of its specific regional profile, that would be an appropriate time to disclose more detail around the preclinical data. So whether when we get human data for it, or when we do some sort of deal around it, if we do, that would be an appropriate time to disclose more detail on ARCT-165.

Okay, sounds good. Looking forward to that and thank you for taking the questions. Looking forward to the unveiling of the Phase 3 study.

Okay, thank you.

Thank you. Our next question comes from the line of an unidentified analyst. Please proceed with your questions.

Good afternoon and thanks for taking the questions. First of all, regarding ARCT-154, besides Vietnam, do you guys own the global rights for the rest of the world, including the United States?

Yes, correct. Yes. We have the global rights to ARCT-154.

Okay, the second question is that the press release reveals that the comparison of neutralizing antibodies of two various variants, you have used a 7.5 microgram in ARCT-021 and you anticipate using 5 micrograms instead for the trials? Was there a reason to use this dose? Was that because there's a fair comparison, or are there other reasons behind it?

No, it's due to the timing of the study. And when we actually set off on the study was earlier on when we were anticipating moving into Phase 3 with a 7.5 microgram dose. As the data rolled out from our Phase 2 study, it showed very clearly that the 5 microgram dose performed as well as the 7.5 microgram dose and was a little bit better tolerated. And so we changed our Phase 3 dose from 7.5 to 5. So it's just a timing legacy issue. But based upon what we know about what we've seen from recent publications about the translation from the studies into humans, and the fact that the five microgram dose performed, at least as well as probably a little bit better than the 7.5 microgram, we would anticipate that if this had been a 5 microgram dose primate study that it would have looked very similar.

Okay, maybe the last question here was about ARCT-165. I understand that you may not really want to review all the information at this point until later. But just in the conceptual wise, was there any sort of general differences between ARCT-154 and ARCT-165 you could sort of describe?

Yes. This is Pad. Sure, we can tell you that the ARCT-165 molecule has a bias towards the beta variant, and we will be talking more about that in future time.

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

Thank you. Appreciate it.

Thank you. Our next question comes from the line of Kumar Raja with Brookline Capital Markets. Please proceed with your questions.

Thanks for taking my questions. So with regard to ARCT-154, how much manufacturing capacity do you have? And when is this 200 million capacity for Vinbiocare guy expected to come on board? And is it mostly for use by Vinbiocare?

Yes. At this point, what we've disclosed is that the Vinbiocare facility will be able to produce up to 200 million doses annually. And we've been guiding that it'll happen in probably the second half of 2022, so that's about all the information we can give you at this point with respect to that capacity. With respect to the other parts of our manufacturing relationships and collaborations, we really haven't given any specific detail except to be able to tell you that we have the capability of producing hundreds of millions of doses annually with those relationships. As you can see, we've expanded it quite substantially in preparation for this opportunity with obviously being very capital-efficient and working very closely with our partners. So two very important attributes that we wanted to execute on. Hopefully, that helps.

And with regard to this manufacturing, that can be shifted from ARCT-021 to ARCT-154 or based on whatever the data you're seeing, how seamlessly can that be done?

Yes, that's correct. One of the advantages of this platform technology is you can modify the payload without very little modifications to the manufacturing process. So it's very streamlined.

Finally, with regard to the preclinical pipeline, what's happening in terms of cystic fibrosis and flu vaccine? Thank you.

Go ahead Steve.

So, the Cystic Fibrosis program, we're anticipating that we'll get an IND submission for a clinical trial application in the early part of next year.

Okay, great. Thanks.

Thank you.

Thank you. That is all the time we have today for questions. I would now like to turn the call back over to Joseph Payne for any closing comments.

Yes. Thanks, everyone. Looks like our time's up, and we're going to be closing the call now. Feel free to reach out to our team. As always, if you have any follow-up questions, we'll be as efficient as we can in our responses. Bye for now, and look forward to seeing you again soon.

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