Arcturus Therapeutics Holdings Inc (ARCT) 2021 Q3 法說會逐字稿

Greetings, and welcome to Arcturus Therapeutics Third Quarter 2021 Earnings Call. (Operator Instructions) As a reminder, this conference is being recorded.

It is now my pleasure to introduce your host, Deepankar Roy, Senior Director of Investor Relations. Thank you. You may begin.

Thank you, Doug.

Good afternoon, and welcome to Arcturus Therapeutics Third Quarter 2021 Financial Results and Corporate Update Call. Thank you all for joining us. Today's call will be led 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 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 Forms 10-Q and 10-K filed with the SEC.

In addition, any forward-looking statements represent our views only as of the date such statements are made, November 8, 2021. And Arcturus specifically disclaims any obligation to update such statements to reflect future information, events or circumstances.

With that, I'll now turn the call over to Joe. Joe?

Thank you, Deepankar.

Good afternoon to all. Thank you for joining Arcturus' third quarter quarterly call today. We are looking forward to telling you more about our recent progress highlighted by the advancement of our ARCT-154 COVID vaccine program.

At Arcturus, we are developing differentiated mRNA-based vaccines in novel therapeutics. Since the inception of the company, we've been working to develop a differentiated platform technology. And we've also more recently advanced a number of highly promising pipeline candidates into clinical development. We believe that our approach developing mRNA vaccines and therapeutics has the potential to directly address the underlying molecular basis of many serious diseases. And in doing so, we hope to provide transformative new medicines to patients living with many types of life-threatening conditions.

We've made excellent progress advancing our mRNA-based vaccines, and I'll begin with a discussion of our vaccine programs targeting COVID-19. So let's begin with ARCT-154. This is our vaccine candidate that targets the SARS COV2 variants of concern, including those that are currently widespread across the globe. ARCT-154 utilizes our self-transcribing and replicating RNA, or the STAR technology. This vaccine includes an optimized mRNA sequence along with multiple proprietary modifications to improve its stability and increase its translation. These modifications as well as the key rational optimizations performed may improve the immunogenic profile of the expressed antigen, which, in this case, is the spike protein. I'll take a moment to identify some of the key differentiators for ARCT-154.

Firstly, it was designed to require a low dose level, so only 5 micrograms per dose. Secondly, it's been updated to target the currently widespread variants of concern. Third, it includes rational modifications to the antigen intended to improve immunogenicity, such as inactivating the furin cleavage site. Also it utilizes our proprietary LUNAR delivery technology, our lipid nanoparticle platform. And finally, ARCT-154 utilizes a self-amplifying mechanism that's designed to extend the duration of antigen expression, and this platform has shown robust T cell responses in multiple preclinical models.

While we've previously disclosed ARCT 154 preclinical data demonstrating strong neutralizing immunogenicity in nonhuman primates to SARS-CoV-2 Alpha, Beta, Gamma and Delta variants. The preclinical NHP data demonstrate that ARCT-154 elicits approximately 14- to 26-fold greater neutralizing antibody titers than ARCT-021, our first-generation COVID vaccine candidate. In addition, we have observed robust T cell responses to these various strains following administration of ARCT-154 in nonhuman primates.

But shifting on to human clinical trials. We've been working closely with our collaborators, Vinbiotech to operationalize a Phase I/II/III study designed to efficiently and rapidly apply for an EUA or an emergency use authorization application in Vietnam and also provide for a path to full approval in Vietnam. This study has the potential to lead to an EUA in Vietnam as early as the first quarter of 2022. All phases of this trial are sponsored and funded by Vinbiotech and the randomized observer-blind study with both placebo-controlled and active controlled cohorts that will assess the safety, immunogenicity and efficacy of ARCT-154 against COVID-19.

Well, I want to pause now and emphasize that we have had an efficient quarter progressing ARCT-154. It was just last August, August 2021, when we first announced the 100-participant Phase I cohort and had commenced enrollment. Then the 300-participant Phase II and the 600-participant Phase III cohorts initiated enrollment shortly thereafter. Then last month in October, we announced that the Phase IIIb cohort had begun enrolling. The Vietnam Ministry of Health gave approval to advance into this large Phase IIIb trial based upon its assessment of early safety data from the first 1,000 individuals dosed in the Phase I and II and IIIa cohorts.

Well, I'm very pleased with the extraordinary effort of our team. I'm excited to report today that enrollment of the ARCT-154 Phase IIIb study is completed. And a Phase IIIc sub-study is expected to meet target enrollment this week. This will bring us to a total of over 19,000 participants in the combined study. The Phase I/II/IIIa cohorts have now completed 2 doses of ARCT-154 given 28 days apart.

The Phase III trial has been amended. The size of the Phase IIIb is now about 16,000 participants, and it also includes an immunogenicity noninferiority sub-study of approximately 2,000 participants, which we call the Phase IIIc cohort. The total size of Phase IIIb and Phase IIIc is anticipated to be around 18,500 participants. This sub-study will evaluate immunogenicity noninferiority of ARCT-154 against AstraZeneca's COVID vaccine. The Phase IIIb cohort has completed enrollment with over 16,000 participants, and the Phase IIIc sub-study is expected to meet target enrollment this week.

The safety and immunogenicity data from the Phase I, II and IIIa cohorts has the potential to form the basis for filing an EUA or emergency use authorization application in Vietnam in December. The immunogenicity noninferiority data from Phase IIIc, together with the safety and efficacy data from the other phases of the trial, are designed to form the basis of filing for potential full approval in Vietnam in the second half of 2022. Dr. Steve Hughes, our CMO or Chief Medical Officer, he's going to provide more details later in today's call regarding the ARCT-154.

I'll now move on to ARCT-021. ARCT-021 is a differentiated COVID mRNA vaccine candidate, and this was our first vaccine to enter the clinic. And we've previously discussed that a single administration of ARCT -- or we shared this data that a single administration of ARCT-021 resulted in what we expect to be a meaningful humoral and T cell response. We have an ongoing fully enrolled ARCT-021 Phase II study, and we have previously discussed the encouraging preliminary tolerability and immunogenicity data from this study.

Specifically, immunogenicity data from the study shows greater than 90% 0 conversion for IgG antibodies binding to the full-length spike protein at Day 28, following a single shot dose of ARCT-021. As previously reported, ARCT-021 has been selected by a global entity for inclusion in the Phase III vaccine trial against COVID-19 and is sponsored and funded by the entity. At this time, per our agreement, we're unable to discuss further specifics. However, we are understandably very grateful for this group's support, which has been so valuable in the global fight against COVID-19.

I'll now turn the time over to Dr. Steve Hughes.

Thanks, Joe.

I would like to begin with some additional details about the reasons for the changes to the ARCT-154 Phase III study design mentioned by Joe. As many of you know, the COVID vaccine rollout in Vietnam has been very successful, with almost 1/3 of the vaccine-eligible population now fully vaccinated. Consequently, it was no longer deemed ethical to maintain participants on placebo for a prolonged period of time. In consultation with the Vietnam Ministry of Health and our collaborators Vinbiotech the Phase IIIb placebo-controlled period was, therefore, reduced to 2 months.

Additionally, however, the Ministry of Health has now opened a path to approval based on immunogenicity noninferiority comparison with the vaccines that are already authorized in Vietnam. So our protocol amendment has also included a new cohort, Phase III, in order to take advantage of this additional potential path to full approval for ARCT-154. The Phase IIIc sub-study will obtain comparative immunogenicity data for ARCT-154 against AstraZeneca COVID-19 vaccine. This comparator was chosen because there's already immunogenicity data in the Vietnamese population for AstraZeneca COVID-19 vaccine using the same assays as we are using in the Phase III study and also because this vaccine could be made available by the Vietnam Ministry of Health within an expedited time frame. Amending the protocol in this way also adds valuable comparative data to inform potential prescribers of ARCT-154.

In addition to the trial of ARCT-154 in Vietnam, we also gained approval from the Singapore Health Sciences Authority and the U.S. FDA to enroll a Phase I/II study with 2 of our next-generation vaccines, ARCT-154 and ARCT-165, together with ARCT-021 administered as both a primary vaccination series and as a booster following initial vaccination with Comirnaty. I'm pleased to report that the Comirnaty booster cohort for this study is now fully enrolled, while the other cohort in the study continues to involve vaccine-naive participants.

I will turn now to ARCT-810, our therapeutic candidate for ornithine transcarbamylase or OTC deficiency. This is a rare and serious disease with no approved treatments that address the root cause of the disease. Our therapeutic candidate aims to restore expression of the normal ornithine transcarbamylase enzyme in the liver of patients with OTC deficiency. This has the potential to restore UA cycle activity, preventing neurological damage and the need for liver transplantation.

We previously completed a Phase I healthy volunteer dose-escalation study with ARCT-810, have demonstrated 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. This dose is within the anticipated therapeutic range that we have estimated based upon our preclinical studies.

We have obtained approval from the U.K. Health Research Authority to initiate a Phase II multiple-dose clinical trial for ARCT-810, and we are currently recruiting sites. The ARCT-810 Phase II study is a randomized, double-blind, placebo-controlled, nested single and multiple ascending dose design that includes both adolescents and adults who have OTC deficiency. The study is designed to involve -- enroll 24 adolescent adults in multiple countries in Europe. And we anticipate that enrollment will commence in Q1 2022. The study is currently under review by multiple other EU regulators, so we anticipate approval to proceed in additional countries very soon. Our other study, the Phase I/II single-dose study of OTC patients in the United States remains ongoing. We have a number of additional centers open now and continue to screen additional participants for enrollment.

Moving briefly now to our cystic fibrosis program. We have continued to progress the necessary preclinical studies to enable ARCT-032, our mRNA therapeutic candidate for cystic fibrosis, to move into clinical studies. And we anticipate the submission of a clinical trial application for ARCT-032 in the first half of 2022.

Our flu vaccine program also continues to make good progress in preclinical studies, and we anticipate advancing our flu vaccine into the clinic in the second half of 2022. Current flu vaccines typically have relatively poor efficacy, and we believe that this can be improved upon with our mRNA technologies. In addition, our mRNA-based vaccines have the advantage of being able to be rapidly adapted to target circulating flu strains.

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 third quarter of fiscal year '21 and provides a summary and analysis of a year-over-year and sequential performance. Please reference our 10-Q for more details on the financial performance.

Today, I will go over our financials and present some operating metrics as we continue to 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 Vietnam. Finally, I will provide some insights regarding our cash position and expected run rate.

As you heard Joe mention, we have had a very productive quarter and have had significant developments in our ARCT-154 program. ARCT-154 is our next-generation vaccine candidate that we have partnered with Vinbiotech, who is sponsoring and funding our study targeting the COVID-19 and variants of concern. Vinbiotech is a part of the Vingroup, one of Vietnam's largest corporations, and this partnering arrangement has resulted in significant savings of well over $200 million in clinical trial and manufacturing expenses.

Our manufacturing strategy and diversification continues to be supported by our partnerships across the globe. The facility build-out in partnership with the Vingroup in Vietnam can potentially produce up to 200 million doses per year remains on track to begin production next year. As mentioned in our last call, we now have manufacturing partnerships in Asia, Europe and the U.S.A. for the drug substance, drug product, lyophilization and fill-finish production. We continue to plan for the potential that one or more of our vaccines could receive emergency use authorization, and we expect to have the capacity to produce hundreds of millions of vaccine doses.

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 3 quarters of fiscal year '21. Approximately $11 million is attributed to G&A and is expected to increase nominally in the fourth quarter. The remaining approximately $45 million in R&D expenses relate to our current pipeline supporting our COVID vaccine candidate, OTC, cystic fibrosis and LUNAR-FLU and other programs, including stockpiling long lead time raw materials, and vaccine for potential EUA. This amount is expected to increase in the next 2 quarters as we continue to build prelaunch inventory of ARCT-154 vaccine.

Our cash balance at the end of the third quarter was $414 million. Based on our current pipeline, the company's cash position is expected to be sufficient to support operations for 2 years.

I will now pass the call back to Joe.

Thanks, Andy.

So as we have heard, here at Arcturus, we've continued to make substantial progress advancing our mRNA-based vaccine and therapeutic platforms. Thank you all for your time today and for your interest in Arcturus. We look forward to keeping you informed of our progress, no doubt.

At this point, we can now go ahead and open the line for questions. Operator, please proceed.

(Operator Instructions) Our first question comes from the line of Yasmeen Rahimi with Piper Sandler.

And congratulations on really a remarkable accomplishment of enrolling the 16,000 patients into the Phase III. So maybe the first question for you would be to provide us some color on -- do you think that enough events have occurred by December when you file for emergency authorization? What is the bar for -- to be granted emergency authorization in Vietnam? So if you could provide some color around that. And then I have a follow-up question for you, Joe.

Sure. Thanks, Yas, for joining the call. I'll pass that question on to Steve.

So thank you for the question. Actually, the emergency use authorization doesn't require COVID events for approval in Vietnam. So we're anticipating that the EUA is going to be based upon immunogenicity data provided from the first 1,000 participants, together with safety data from those 1,000 participants and also from the 16,000 participants in the Phase IIIb part of the study. The events will form part of the filing for a full approval subsequently. And for that full approval, we actually have 2 shots on goal, the event rate and also the immunogenicity noninferiority compared with the AstraZeneca COVID-19 vaccine.

And then maybe a question that we get quite frequently from clients are, when we should be expecting the immunogenicity data. If you could provide some commentary on sort of the state -- cadence of the milestones between now and emergency authorization, so I think that would be really helpful.

Sure. Yes. With respect to data timing, I think it's understood that we -- this program is partnered with Vinbiotech, and it's also -- we're working closely with the Vietnam Ministry of Health, so they will obviously have first access to the data. And because Vinbiotech is sponsoring and funding the trial, we'll be working with them with respect to the disclosure process of the data.

So it's challenging, as you can understand, to give guidance or specific guidance as to the timing of that data. But no doubt there will be data included in the emergency use approval application process. And we wouldn't be going through this if we didn't deem it or consider favorable data.

Our next question comes from the line of Nick Abbott with Wells Fargo.

Congratulations to you and your partners in Vietnam for some pretty heavy lifting here. First question is, so did I hear you say that 1/3 of the population has been vaccinated in Vietnam?

Yes. So the statistics that were in the public domain as of November 4 were around 26 million people in Vietnam have been vaccinated. And obviously, the eligible ones are the adults and the adolescents. So the younger children at this point are unvaccinated. So it's going to be around 1/3 or more, thereabouts.

That's -- I see. So that 26 million represents 1/3 or more?

Yes. So the population of Vietnam is about 100 million, but the 26 million -- obviously, that 100 million isn't all adults. It's a wide range of ages. And so we're estimating that it's currently around about 1/3 or thereabouts that are fully vaccinated as of November 4.

And so given the rate of vaccination, what proportion do you expect to be vaccinated at the time your vaccine is approved? And then how many doses do you expect to have stockpiled at launch?

Maybe I can deal with the first part of that, and then I'll pass over to Joe or Pad for the second part. So Vietnam is aggressively rolling out its vaccine campaign, but the ability to continue through and vaccinate all of the eligible population is going to be dependent upon those vaccines arriving. I don't believe that they have all of the vaccine sitting in a warehouse somewhere to vaccinate their entire population, so they're dependent upon vaccines coming in that have been promised by other entities and other companies. And so far, those promises are sufficient to vaccinate a large majority of their population.

But as I said, the rollout of the vaccine campaign is dependent upon those vaccines arriving in a timely fashion. I believe that the Vietnamese government has said it's targeting having everybody vaccinated by the end of the first quarter next year. So it remains to be seen whether they actually achieve that. And we would be anticipating an emergency use authorization in the early part of next year, so ahead of that.

And then with respect to your manufacturing guidance, maybe, Andy, you can speak to where we are with respect to stockpiling of ARCT-154?

Yes. We don't give specific guidance with respect to the quantity of the vaccine that we're producing, but we are obviously in discussions with, not only the Vietnam Ministry of Health, but also other countries that are also looking to stockpile the vaccine for -- the 154 for the variants of concern.

Okay. And then maybe as a kind of follow-up to that, as in the past, if an approval in Vietnam would be accepted in the countries or even by WHO, can you update us on where you are in discussion? And how would -- this facility that's in Vietnam, would that be supporting other countries, assuming -- in Asia, for example, what are the mechanics there of who sells that product in those other countries?

It's a great question. Clearly, we're establishing strong relationships with Vietnam and Singapore and the Southeast Asian part of the world, and how we expand from there is a key business strategic question. We brought on Nirdosh recently. He's leads our -- he's our Chief Regulatory Officer, a lot of experience at Merck internationally with vaccine expansion. And so he's helping guide in that effort.

But clearly, there's an opportunity in Southeast Asia, and it is unusual times still in that part of the area with respect to the pandemic. So it's hard to draw on precedents for this, but clearly, there will be some level of appreciation for the Vietnamese Ministry of Health with respect to ARCT-154 in Southeast Asia, and we'll go from there.

And maybe just a last one for me on this, and that is, are you -- I mean, obviously, you've got the booster study going, but that's a small study. I think clinicaltrial.gov had said 72 patients for the trial, which is prime boost and as a booster dose. So are you and Vinbiocare planning to more formally study a booster -- 154 as a booster in Vietnam?

Well, we already have an active booster trial ongoing in Singapore and the United States. This is something that is clearly significant opportunity. This heterologous boosting, the mix and matching is now being readily accepted globally from multiple ministries of health. So it presents an opportunity to help transition those that have never received a messenger RNA vaccine, different types of vaccines and transition them over to the messenger RNA side. So that does reflect a significant opportunity. So we are speaking about this regularly and looking at opportunities to collect more data with respect to using our vaccines as boosters, no doubt.

Our next question comes from the line of Brian Cheng with Cantor Fitzgerald.

So it seems that the Vietnamese government is pretty receptive in mixing different vaccines. From our research, it seems that they have allowed mixing of Pfizer with AstraZeneca vaccines, they allow Pfizer and Moderna vaccines. And as you pointed out that 1/3 of the population is now fully vaccinated and there is still quite a bit of shortage in the region. So how receptive do you think the government will give you the green light to be mixed with other vaccines? And I have one more follow-up.

Yes, I think that acceptance is assumed at this point based upon the FDA approving mixing and matching, but we haven't had specific discussions on that with them at this point. But you can appreciate that the Vingroup or Vinbiotech is building a facility -- a substantial state-of-the-art facility next year, and the large portion of those manufactured vaccines will be intended as boosters, no doubt.

Okay. And then on the Vingroup front, it seems that they've also facilitated the remdesivir distribution in Vietnam earlier this year. Can you give us some color on how Vingroup is gearing up for the launch? And since they already seem to have some distribution in place for remdesivir, do you anticipate them to have to ramp up significantly for your COVID vaccine launch?

Well, you're right. They're strengthening their position in the COVID space. Our relationship -- I just want to remind the folks on the call that our relationship with Vingroup and Vinbiotech is exclusively limited to the area of Vietnam. So that's going to be where they have the most expertise and the ability to facilitate a very successful launch. They're extremely well known and warmly endorsed by the President. And per our conversation with them when I met him personally, he warmly introduced and endorsed in the group and the CEO of Vinbiotech. So we're we have good partners with respect to Vietnam, no doubt. We have no concerns about a commercial launch in Vietnam.

Our next question comes from the line of Seamus Fernandez with Guggenheim.

So I have a few here. First off, can you just help us better understand the head-to-head -- basically providing an additional pathway to approval? I'm just trying to get a better understanding of what the feasibility is of the efficacy study at this point and if patients who received placebo in your study will be crossed over or can get vaccine. We've seen this be a bit of a problem -- quite a significant problem for some other clinical programs kind of -- trying to operate placebo-controlled studies. So that's my first question.

I just want to clarify if the efficacy study itself, rather than the immunogenicity study, can actually achieve an event-based completion.

Well, we definitely have 2 shots on goal, but that's the intent. Steve, maybe you can comment on...

So yes. So thanks for the question, Seamus. Both parts of the study are in play at the moment still. And you may have noticed that the event rate in Vietnam was going down. Now that they've eased restrictions in Vietnam, it's climbing back up again. So I think the door is still open to get enough events. And you remember that both the Pfizer and the Moderna study got very large numbers of events within a very short period of time this time last year. So it still remains possible for us to get enough events to the event-based comparison.

But what's happened more recently -- and I think it's possibly been driven by the announcement from the consortium of Canada, Singapore, the United Kingdom, Australia, et cetera, about an immunogenicity noninferiority route to registration. So they published their guidance document about how to achieve registration for immunogenicity noninferiority comparison with an already licensed vaccine. And I think Vietnam are kind of following suit with that, and they've recently issued some guidance around what the pathway to registration based upon that kind of comparison would be. So we've taken advantage of that, and we've taken advantage of the Ministry of Health's enthusiasm for the study and cooperation in the study to rapidly open up the immuno noninferiority study compared with the AstraZeneca COVID-19 vaccine. And that vaccine was basically the one that was ready to go and could be provided most quickly by the Vietnam Ministry of Health.

So that -- so now we have 2 routes to full registration. Even in the eventuality that the event rate doesn't get to target before we have to cross the placebos over to active vaccine, we still have the noninferiority route to a full registration in Vietnam. And neither of those endpoints affects the emergency use authorization, which is going to be based entirely on the Phase I, II and IIIa cohorts' immunogenicity data.

And I'll just add one comment -- and I'll add a comment that we're working with Vietnam with respect to conducting our efficacy trial in areas that are perhaps last -- or one of the last groups to receive approved vaccines. And Vietnam has a really tight understanding of their citizens in terms of who's received vaccine and who hasn't. And so this information has been leveraged by Vinbiotech as well to help us achieve that -- the adjudicated numbers in the placebo group.

And then with regard to the head-to-head immunogenicity data, can you just help us understand, one, is the Delta -- one is Delta, one is Wuhan, what exactly is the data? And can you just help us understand what the noninferiority margins are and why you didn't choose to pursue superiority? Maybe you've seen superiority for some other studies?

So we can't comment too much on the details of the noninferiority margin at this point in time. They are consistent with noninferiority margins that have been used in other studies that have resulted in emergency use authorization with FDA. So the margins are very similar there. And as you would expect, the evaluations are going to be based upon both neutralizing antibodies and binding antibodies and also demonstrated ability to neutralize variants of concern.

Okay. So basically, a broad immunogenicity assay comparison? I just want to clarify that.

Yes. So the guidance that's been issued by the Vietnamese Ministry of Health is very similar to what's already in the public. So the Vietnamese Ministry's guidance, as far as I can tell, isn't currently in the public domain. It was a personal communication from the Ministry of Health to our partners in Vinbiotech and us. This is why I can't comment too much on it because it's not been disclosed by the Ministry of Health yet.

But broadly speaking, it's very similar to the guidance that's already been issued by the consortium of regulators, including the U.K., Singapore, Health Canada and Australian regulator about the pathway to immuno noninferiority studies for registration.

Okay. No, that's helpful. And in terms of immunogenicity data, is Arcturus aware of any of the immunogenicity data? Do you have any of that data in hand from the initial 1,000 patients? Or is that going to become first available to you and the team closer to the end of December, and then what follows after that is EUA? And then once we know EUA will receive -- and we'll have a fuller understanding of the immune response at that point. Is that how sort of the disclosure is likely to work?

Yes. We don't have that data yet. And we've implied or indicated on this call that it will be included in the emergency use approval application likely. So that's where we are. And we've given the time line for that.

Anything to add, Steve?

Nothing can happen until the participants that are in that 1,000 patient cohort -- or participant cohort are through at least day 57 on the study, so that they have sufficient safety follow-up and they also have the immunogenicity data from 28 days after their second dose. So there's a latency between those blood samples being drawn and then processed in the lab and us cleaning and locking the database after that day 57 time point.

So that kind of pushes us into the December time frame, which is what we've -- guidance that we've previously given about timing for the EUA application.

Our next question comes from the line of Yigal Nochomovitz with Citigroup.

This is Ashiq Mubarack on for Yigal. I had 2. I guess, just building on some of the earlier questions. If maybe you miss on the Phase IIIc noninferiority, could you still potentially file an EUA based on events maybe earlier than the time line you laid out for full approval?

And then my second question would be how are you thinking about pediatric vaccination given the rates you mentioned in adults and adolescents in Vietnam?

Well, if there's an additional wave or unexpected wave of infections that accelerate the adjudicated infections in the placebo group then yes. But it's difficult to impossible to predict those types of things, so we stay away from guiding based on that. But yes. Technically, yes, it's possible.

And then with relation to the children, we're obviously focusing hard on how we move from the current study into other at-risk groups. And also, that would include boosting and -- the heterologous type of boosting as well. And so we're having discussions with our partners about what the appropriate timing for a pediatric study would be and how we would go down the age groups.

As you know, they currently -- available vaccines for the pediatric populations didn't go straight into young kids. They went into adolescents and then they stepped it down from adolescents to the 5 to 12 range and then from the 2 to 5 range. So that's well-trodden path for this kind of work, and that's a path that we're obviously looking at very carefully.

The other thing, just to note for the pediatric studies, is that they haven't been based on event rate. So in the pediatric populations, they've been largely based upon an immuno-bridging between the adult and the pediatric population. And I would anticipate that, that would be the route to pediatric approval for us as well.

Our next question comes from the line of Yale Jen with Laidlaw & Company.

Congrats on the rapid progressions.

My first question is that given the approval you've been done seems very likely? And should investors start to think about the potential sort of revenue or in what form or shape of revenue at risk might be received from that success effort?

Well, revenue guidance is always a challenge. I'm going to throw that one to our CFO, Andy. Anything on revenue guidance on the vaccine?

Unfortunately, do not provide guidance with respect to revenue. We did share some trends with respect to expenses and -- earlier in the call. And we did kind of share the cash runway to give you kind of a perspective of how many quarters of operating cash do we have, so I hope that is helpful. But it is difficult to forecast revenue with a biotech company I hope you can appreciate that.

And it's important to stress that we do have the manufacturing footprint in place to support decent numbers of vaccines.

Okay. Great. That's helpful. And maybe one more question here, which is related to the booster that you have Singapore and then you have the U.S. study. What should we think about the next step in terms of the trials? And would that be facilitating a potential approval maybe in U.S. or in Singapore possibly in next year?

Yes. So the current booster studies that we have -- or to give just an idea of how the vaccines that are furthest forward, 021, 154 and 165 behave in the booster setting at -- all at the same dose and then also comparatively in the primary vaccination series. So it gives us a very good data set to start making some assumptions and to allow us to design subsequent clinical trials that would be registration focused.

So I don't think that the 76 participants that we have in the U.S. and Singapore clinical trial in itself will be sufficient to enable registration, but it will definitely be sufficient to form the basis for starting additional clinical trial work in that space. And we actually also have another study that's ongoing. Our Phase II study of ARCT-021 that's being conducted in the United States and Singapore and that's been ongoing since the beginning of the year. That study, we're actually boosting the participants at the 6-month time point with either 021, 154 or 165. So we've got 2 studies where we're looking at getting booster information.

Maybe just please one more question. When you mentioned the 76 patients study, is there a plan for -- provide some readout for that study?

So the cohort of participants in the study that's receiving the vaccines as a booster is fully recruited. And so we would anticipate having the immunogenicity data through day 29 for that cohort in the Q1 time frame next year.

The other half of the study is the priming vaccination series again, with the same vaccines. But recruitment in those cohorts is still ongoing, and so at this point, I can't give guidance about when we would have data for those cohorts.

Our next question comes from the line of Kumar Raja with Brookline Capital Markets.

And with regard to the ARCT-021 trial that will be conducted by the global entity, what can you share with regard to that? When do you think we can get more clarity on that? And why was 021 selected there versus the other ones?

And also with regard to the HBV program, can you share what this milestone was and what are the next steps in this collaboration?

Yes. With respect to the ARCT-021 study, we we've disclosed everything we can up into this point. But just per our agreement, we're unable to discuss further specifics. It's a great question. It's a fair question, but we're just unable to comment further.

And the second part of your question was with respect to the HBV program. Yes, we have a great relationship with J&J. We continue to progress that program with them. It's an ongoing program. And we announced that we received a milestone successfully with them, and we view that as a positive -- additional positive validation of our platform, especially with intravenously dosed and systemically administered messenger RNA.

Okay. And maybe with regard to the cystic program, what's happening there? And when can we get updates?

The CF program, we have been -- there's been some additional data presented at the -- there was a national CF conference. And we can provide that to you maybe separately in an e-mail, but it showed some promising data and well-established models and ferret models of cystic fibrosis. So it continues to mature. The preclinical data package matures, while in parallel, we're preparing to go through all the pre-IND-enabling studies -- or the IND-enabling studies and toxicology studies for that program.

And maybe finally, what is the latest with regard to the FLU program?

The latest with respect to the FLU program, did you say? Yes, that's still on -- yes, that's on track for next year. We indicated that the IND or CTA would be filed in the second half of next year.

Our next question comes from the line of Yasmeen Rahimi with Piper Sandler.

Follow-up question. Joe, Steve, you commented on to Seamus' question on whether you have seen any immunogenicity data from the first 1,000 patients that those data have not been shared yet but can you comment on whether the Vietnam Health Ministry have seen some preliminary data? Or have they made their decisions just on the safety basis to really expedite into -- from a Phase I to Phase II into a 16,000 Phase III study?

Yes. I can reiterate the time line and then turn the time over to Steve. But in mid-August, we initiated the Phase I, which means the second shot was mid-September, and a month after that is mid-October, where the blood draw is taken. So the blood to which you're referring to was drawn in mid-October.

With respect to timing of the data and to what extent they understand the immunogenicity data, maybe Steve, you can comment.

Yes. So as far as we know, the Ministry of Health hasn't seen any immunogenicity data. And the timing of the processing of those samples wouldn't really have allowed them to see immunogenicity data prior to moving the study from one phase to the next. So the immunogenicity data readout from those 1,000 participants isn't going to be back -- so the relevant time point, which is day 57, that isn't going to be back from the lab until the end of November or early December. So all of their assessments so far in terms of moving the study rapidly from one phase to the next, has just been focused on whether it's safe to dose progressively larger numbers of individuals.

That is all the time we have for questions. I'd like to hand the call back to management for closing remarks.

Great. Thank you, Doug.

This concludes our third quarter update, and thank you for joining us this afternoon to talk about our progress. Please reach out to us, right, with your questions, if we're unable to accommodate you today.

We look forward to updating you further throughout the balance of the year, and hope you all have a great evening. Bye for now.

Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation. You may disconnect your lines at this time, and have a wonderful day.