Earnings Call Transcript - ARCT Q3 2021

Operator, Operator

Greetings, and welcome to Arcturus Therapeutics Third 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. If anyone should require operator assistance during the conference, 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.

Deepankar Roy, Senior Director of Investor Relations

Thank you, Doug. And 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 and they involve known and unknown risks, uncertainties, and assumptions that may cause actual results. Performance and achievements 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 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 will now turn the call over to Joe. Joe?

Joseph Payne, President and CEO

Hey, thank you, Deepankar. Good afternoon to all. Thank you for joining our 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 and novel therapeutics. Since the inception of the Company, we've been working to develop a differentiated platform technology, and we have 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. Let's begin with ARCT-154. This is our vaccine candidate that targets the SAR-CoV-2 variants of concern, including those that are currently widespread across the globe. ARCT-154 utilizes our self-transcribing and replicating RNA, or 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 fewer. 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 pre-clinical data demonstrating strong neutralizing immunogenicity in non-human primates to SAR-CoV-2, Alpha, Beta, Gamma, and Delta variants, the preclinical data demonstrates 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 variant strains following administration of ARCT-154 in non-human primates. But shifting onto human clinical trials, we've been working closely with our collaborators, VinBiotech, to operationalize a Phase 1/2/3 study designed to efficiently and rapidly apply for an EUA or 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. This randomized observer-blind study with both placebo controls and active controlled cohorts 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 2021 when we first announced the 100-participant Phase 1 cohort and had commenced enrollment. Then the 300-participant Phase 2 and the 600-participant Phase 3 cohorts initiated enrollment shortly thereafter. Then last month in October, we announced that the Phase 3B cohort had begun enrolling. The Vietnam Ministry of Health gave approval to advance into this large Phase 3B trial based just upon its assessment of early safety data from the first 1000 individuals dosed in the Phase 1 and 2 and 3A cohorts. While I'm very pleased with the extraordinary effort of our team, I'm excited to report today that enrollment of the ARCT-154 Phase 3B study is completed. A Phase 3C 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 1/2/3A cohorts have now completed 2 doses of ARCT-154 given 28 days apart. The Phase 3 trial has been amended. The size of the Phase 3B is now about 16,000 participants, and it also includes an immunogenicity non-inferiority sub-study of approximately 2,000 participants, which we call the Phase 3C cohort. The total size of Phase 3B and Phase 3C is anticipated to be around 18,500 participants. This sub-study will evaluate immunogenicity non-inferiority of ARCT-154 against AstraZeneca's COVID vaccine. The Phase 3B cohort has completed enrollment with over 16,000 participants. And the Phase 3C sub-study is expected to meet the target enrollment this week. The safety and immunogenicity data from the Phase 1, 2, and 3A cohorts has the potential to form the basis for filing an EUA or Emergency Use Authorization application in Vietnam in December. The immunogenicity non-inferiority data from Phase 3C, 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, is going to provide more details later in today's call regarding ARCT-154. I'll now move onto ARCT-021. ARCT-021 is a differentiated COVID mRNA vaccine candidate, and this was our first vaccine to enter the clinic. We have shared 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 2 study. We have previously discussed the encouraging preliminary tolerability and immunogenicity data from this study. Specifically, immunogenicity data from the study shows greater than 90% seroconversion 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 3 vaccine trial against COVID-19, which 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 will now turn the time over to Dr. Steve Hughes.

Steve Hughes, Chief Medical Officer

Thanks, Joe. I would like to begin with some additional details about the reasons for the changes to the ARCT-154 Phase 3 study design mentioned by Joe. As many of you know, the COVID vaccine rollout in Vietnam has been very successful, with almost the entire vaccine-eligible population not fully vaccinated. Consequently, it was no longer deemed ethical to maintain participants on placebo for a prolonged period. In consultation with the Vietnam Ministry of Health and our collaborators at VinBiotech, the Phase 3B placebo-controlled period was therefore reduced to two months. Additionally, however, the Ministry of Health has now opened a path to approval based on immunogenicity non-inferiority comparison with vaccines that are already authorized in Vietnam. Thus, our protocol amendment has also included a new cohort, Phase 3C, in order to take advantage of this additional potential path to full approval for ARCT-154. The Phase 3C sub-study will obtain comparative immunogenicity data for ARCT-154 against the AstraZeneca COVID-19 vaccine. This comparison is chosen because there's already immunogenicity data in the Vietnamese population for the AstraZeneca COVID-19 vaccine using the same assays as we are using in the Phase 3 study. And also because this vaccine could be made available by the Vietnam Ministry of Health with an expedited timeframe. 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 1-2 study with two 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. I'm pleased to report that the 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 (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 the expression of the normal Ornithine Transcarbamylase enzyme in patients with OTC deficiency. This has the potential to restore activity, preventing neurological damage and the need for liver transplantation. We previously completed a Phase 1 healthy volunteer dose escalation study with ARCT-810, which demonstrated that administration of ARCT-810 was associated with a favorable and attractive pharmacokinetic profile up to the top dose of 0.4 milligrams per kilogram. This dose is within the anticipated therapeutic range that we've estimated based upon our preclinical studies. We have obtained approval from the UK Health Research Authority to initiate a Phase II multiple dose clinical trial for ARCT-810, and we're currently recruiting sites. The ARCT-810 Phase 2 study is a randomized, double-blind, placebo-controlled, nested single and multiple ascending dose design that includes both adolescents and adults with OTC deficiency. The study is designed to enroll 24 adolescents and adults in multiple countries in Europe, and we anticipate that enrollment will commence in Q1 2022. The study is currently under review by multiple EU regulators, so we anticipate approval to proceed at additional countries very soon. Our other study, the Phase 1-2 single-dose study of OTC patients in the U.S., remains ongoing. We have a number of additional centers open 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 candidate for cystic fibrosis, to move into clinical studies. We anticipate submitting 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.

Andy Sassine, CFO

Thank you, Steve. And good afternoon, everyone. The press release issued earlier today includes our financial statements for the third quarter of fiscal year '21 and provides a summary and analysis of 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 mentioned, we have had a very productive quarter and have had significant development in our ARCT-154 program. ARCT-154 is our next-generation vaccine candidate that we have partnered with VinBiotech, which is sponsoring and funding our studies, targeting COVID-19 and variants of concern. VinBiotech is a part of the Vin group, 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 continue to be supported by our partnerships across the globe. The facility built in partnership with the Vin group in Vietnam can potentially produce up to 200 million doses per year and remains on track to begin production next year. As mentioned in our last call, we now have manufacturing partnerships in Asia, Europe, and the USA for the drug substance, drug product, 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 three 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 candidates, OTC, Cystic Fibrosis, lunar flu, and other programs, including stockpiling, long lead time raw material, and vaccines for potential EUA. This amount is expected to increase in the next two quarters as we continue to build pre-launch inventory of the 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 two years. I will now pass the call back to Joe.

Joseph Payne, President and CEO

Hey, thanks, Andy. 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 our company. 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.

Operator, Operator

Thank you. Ladies and gentlemen, at this time, we will be conducting a question-and-answer session. Our first question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed with your question.

Yasmeen Rahimi, Analyst

Thank you, team. Congratulations on the impressive achievement of enrolling 16,000 patients into Phase 3. My first question is whether you believe enough events will have occurred by December when you file for Emergency Authorization. Can you provide insight on the criteria needed for Emergency Authorization in Vietnam? I also have a follow-up question for you, Joe.

Joseph Payne, President and CEO

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

Steve Hughes, Chief Medical Officer

Hi, Yasmeen. 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 3B part of the study. The events will form part of the filing for full approval subsequently. And for that full approval, we actually have to show some goal. The event rate and also the immunogenicity non-inferiority compared with the AstraZeneca COVID-19 vaccine.

Yasmeen Rahimi, Analyst

Thank you, team. And then maybe a question that we got quite frequently from clients is when we should be expecting the immunogenicity data. If you could provide some commentary on the expected cadence of the milestones between now and emergency authorization, I think that would be really helpful. And thank you for taking my questions.

Joseph Payne, President and CEO

Sure. Yes. With respect to data timing, I think it's understood that this program is partnered with VinBiotech. And we're also 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 regarding the timing of that data. But without a 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 to be favorable data.

Yasmeen Rahimi, Analyst

Thanks, Joe. I'll jump in and come back in the queue to let my colleagues ask questions.

Operator, Operator

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

Nick Abbott, Analyst

Hello. Thanks for taking my question, and congratulations to you and your partners in Vietnam. Some pretty heavy lifting here. First question is, did I hear you say that the whole of the population had been vaccinated in Vietnam?

Steve Hughes, Chief Medical Officer

Yes. The statistics that were in the public domain as of November the 4th were around 26 million people in Vietnam had been vaccinated. Obviously, the eligible ones are the adults and the adolescents. So the younger children are not vaccinated. So it's going to be around a further more there about.

Nick Abbott, Analyst

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

Steve Hughes, Chief Medical Officer

Yes. The population of Vietnam is approximately 100 million, but the 26 million refers to those who are vaccinated, and it’s important to note that this population includes individuals of various ages. As of November 4th, we estimate that around one-third or so are fully vaccinated.

Nick Abbott, Analyst

Given the rates of vaccination, for the proportion you expect to be vaccinated at a time of your vaccine's approval, how many doses do you expect to have stockpiled at launch?

Steve Hughes, Chief Medical Officer

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 to vaccinate all of the eligible population is going to be dependent upon those vaccines arriving. I don't believe that they have the vaccine sitting in a warehouse somewhere to vaccinate their entire population, so that is 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 that population. That 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?

Andy Sassine, CFO

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 Vietnamese Ministry of Health, but also other countries that are also looking to stockpile the vaccine for the ARCT-154, for their variants of concern.

Nick Abbott, Analyst

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

Joseph Payne, President and CEO

It's a great question. We are building strong relationships in Vietnam and Singapore, as well as in Southeast Asia. How we expand from there is a vital strategic business consideration. Recently, we've welcomed Nirdosh, our Chief Regulatory Officer, who has extensive international experience with vaccine expansion at Merck. He is assisting us in this effort. There is definitely an opportunity in Southeast Asia, and it remains a unique time in the region regarding the pandemic. It's challenging to reference past experiences, but it is evident that the Vietnamese Ministry of Health will recognize the value of ARCT-154 in Southeast Asia. We will move forward from there.

Nick Abbott, Analyst

Thanks, gentlemen. I have one last question regarding your plans for a booster study. I see that you have a small study underway with 72 patients for the prime boost and booster dose. Are you and VinBiotech intending to conduct a more comprehensive study on the booster in Vietnam?

Joseph Payne, President and CEO

Well, we already have an active booster trial ongoing in Singapore and the U.S. This is something that is clearly a significant opportunity. This header longest boosting, 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. We are speaking about this regularly and looking at opportunities to collect more data with respect to using our vaccines as boosters.

Operator, Operator

Our next question comes from the line of Brian Chang with Cantor Fitzgerald. Please proceed with your question.

Brian Chang, Analyst

Hi, guys. Thanks for taking my question. So it seems that the Vietnamese government, they're 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, a third 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 be in giving you the green light to mix with other vaccines? I have one more follow-up. Thanks.

Joseph Payne, President and CEO

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

Brian Chang, Analyst

Okay. And then on the Vin group front, it seems that they also facilitated the Remdesivir distribution in Vietnam earlier this year. Can you give us some color on how Vin group is gearing up for the launch? 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? Thanks.

Joseph Payne, President and CEO

Well, you're right, they are strengthening their position in the COVID space. I just want to remind folks on the call that our relationship with Vin group and VinBiotech is exclusively limited to the area of Vietnam. 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 for our conversation with them when I met him personally. I received a warm introduction and endorsement into the group and the CEO of VinBiotech. So we have good partners with respect to Vietnam, no doubt, and I have no concerns about a commercial launch in Vietnam.

Operator, Operator

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

Seamus Fernandez, Analyst

Thanks for the question, guys. I have a few here. First off, can you just help us better understand the head-to-head comparison basically providing an additional pathway to approval? I am just trying to get a better understanding of what the feasibility is of the efficacy study at this point.

Joseph Payne, President and CEO

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

Steve Hughes, Chief Medical Officer

Yes. Thanks for the question, Seamus. The first parts of the study are still in play at the moment. You may have noticed that the event rate in Vietnam was going down. Now that they've eased restrictions in Vietnam, it is climbing back up again. So I think the door is still open to get enough events. And you remember that both Pfizer's 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 for the event-based comparison. But what happened more recently, and I think it may have been driven by the announcement from the consortium of Canada, Singapore, the United Kingdom, and Australia about an immunogenicity non-inferiority route to registration, is that they published their guidance document about how to achieve registration based on immunogenicity non-inferiority comparison with an already licensed vaccine. I think Vietnam is following suit with that, and they've recently issued some guidance around what pathway to registration based upon that kind of comparison would be. So we've taken advantage of that enthusiasm from the Ministry of Health for this study and cooperation on the study to rapidly open up the immune non-inferiority 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. Now we have two routes to full registration. Even in the eventuality that the event rate doesn't get to the target before we have to cross the placebos over to active vaccine, we still have the non-inferiority for the full registration in Vietnam. And neither of those endpoints affects the emergency use authorization, which is going to be based entirely on the Phase 1, 2, and 3A cohorts' immunogenicity data. I'll add a comment that we're working with Vietnam with respect to conducting our efficacy trial in areas that are perhaps one of the last groups to receive approved vaccines. The Vietnamese have a really tight understanding of their citizens in terms of who's received vaccine and who hasn't. This information has also been leveraged by VinBiotech as well to help us achieve that.

Seamus Fernandez, Analyst

Great.

Joseph Payne, President and CEO

There's adjudicated numbers in the placebo group.

Seamus Fernandez, Analyst

Regarding the head-to-head immunogenicity data, could you clarify the specifics of Delta 1 in Wuhan, including the data available? Additionally, could you explain the non-inferiority margins and the reason for not pursuing superiority, especially since you may have seen superiority in other studies?

Steve Hughes, Chief Medical Officer

So we can't comment too much on the details of the non-inferiority margins at this point in time. They are consistent with non-inferiority margins that have been used in other studies that have resulted in emergency use authorization with the 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 have demonstrated the ability to neutralize variants of concern.

Seamus Fernandez, Analyst

Basically, broad immunogenicity assay comparisons. I just want to clarify that.

Steve Hughes, Chief Medical Officer

Yes. So the guidance that's been issued by the Vietnamese Ministry of Health is very similar to what's already in the public domain. That was a personal communication from the Ministry of Health to our partners VinBiotech and us, which is why I can't comment too much on it because it has 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, Canada, and the Australian regulator about the pathway to immunogenicity non-inferiority studies for registration.

Seamus Fernandez, Analyst

Okay. Now, that's helpful. And in terms of immunogenicity data, are you aware of any of the immunogenicity data? Do you have any of that data in hand from the initial 1000 patients or is that going to become first available to you and the team closer to the end of December? And what follows after that is EUA. And then once we know EUA, we'll receive and we'll have a fuller understanding of the immune response at that point, and that's how the disclosure is likely to work.

Joseph Payne, President and CEO

Yeah, 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. That's where we are, and we've given the timeline for that. Anything to add, Steve?

Steve Hughes, Chief Medical Officer

Nothing can happen, and so the participants in that 1000 patient cohort or participant cohort for at least day 57 on the study startup that's 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 date 57 time point. So that kind of pushes us into the December timeframe, which is what we've gotten. So we've previously given about timing for the EUA application.

Seamus Fernandez, Analyst

Okay, perfect. Super helpful. Thanks. I'll jump in the queue.

Operator, Operator

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

Ashik Mubarak, Analyst

Hi, Jin. This is Ashik Mubarak, thanks for taking my questions. I had two, I guess just building on some of the earlier questions. if maybe you miss on the Phase 3C non-inferiority, there's still potentially file in the EUA based on events maybe earlier than the timeline 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? Thanks.

Joseph Payne, President and CEO

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, it’s possible.

Steve Hughes, Chief Medical Officer

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 top-up boosting as well. We're having discussions with our partners about what the appropriate timing for pediatric study would be and how we would go down the age groups. As you know, the currently available vaccines for the pediatric populations didn't go straight into young kids; they spent it to the adolescents, and then they stepped it down from adolescence to the 5 to 12 range and then from the 2 to 5 range. So that's the well-trodden path for this kind of work, and that's a part 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 pediatric populations, and I would anticipate that would be the route to pediatric approval for us as well.

Ashik Mubarak, Analyst

Okay then. Thank you very much.

Operator, Operator

Our next question comes from the line of Yale Jen, with Laidlaw & Company, please proceed with your question.

Yale Jen, Analyst

Good afternoon. And again, congrats on the rapid progressions. My first question is that, given the approval and being done since, there are likely and should investors start to think about the potential on the revenue or in what form to share revenue a your risk might be received from the phone data success effort?

Joseph Payne, President and CEO

Revenue guidance is always a challenge. I want to throw that one to our CFO, Andy. Anything on revenue guidance in vaccine?

Andy Sassine, CFO

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

Joseph Payne, President and CEO

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

Yale Jen, Analyst

Okay, great. That's helpful. And maybe one more question here related to the booster that you have in 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 the U.S. or in Singapore possibly next year? Many thanks.

Steve Hughes, Chief Medical Officer

So the current booster studies that we have are to give us an idea of how the three vaccines that are there, ARCT-021, 154, and 165, behave in the booster setting, all at the same dose. Also comparatively in the priming vaccination series. 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. 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. We actually also have another study ongoing, our Phase II study of ARCT-021 being conducted in the U.S. and Singapore, which has been ongoing since the beginning of the year. In this study, we are actually boosting the participants at the six-month time point with either 021, 154, or 165. So we have two studies where we're looking at getting booster data.

Yale Jen, Analyst

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

Steve Hughes, Chief Medical Officer

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 timeframe 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. So at this point, I can't give guidance about when we would have data for those cohorts.

Operator, Operator

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

Kumar Raja, Analyst

Thanks for taking my questions. And with regard to the ARCT-021 trial, that could 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 data versus 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? Thanks.

Joseph Payne, President and CEO

Yeah, with respect to the ARCT-021 study, we've disclosed everything we can up to this point. Per our agreement, we're unable to discuss further specifics. It's a great question, and it's a fair question, but we're just unable to comment further. The second part of your question was with respect to the HBV program? Yeah, we have a great relationship with Chang Jay, and we continue to progress that program with them. It's an ongoing program, and we announced that we received a milestone successfully with them. We view that as additional positive validation of our platform, especially with intravenously dosed and systemically administered messenger RNA.

Kumar Raja, Analyst

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

Joseph Payne, President and CEO

The CF program has shown some promising data at the recent national CF conference, and we can share that information separately via email. The data includes well-established and ferret models of cystic fibrosis, and the program is continuing to develop. We are also advancing our preclinical data package while preparing for the necessary pre-IND and toxicology studies for that program.

Kumar Raja, Analyst

And maybe finally, what is the latest with regard to the flu program? Thanks.

Joseph Payne, President and CEO

The latest with respect to the flu program? Yes, that is still on track for next year. We indicated that IND or CTA would be filed in the second half of next year.

Kumar Raja, Analyst

Great, thanks.

Operator, Operator

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

Yasmeen Rahimi, Analyst

Thank you so much for taking my follow-up question. Joe and Steve, you commented on Seamus' question on whether you have seen any immunogenicity data from the first 1000 patients, as those data have not been shared yet. But can you comment on whether the Vietnam Health Ministry has seen some preliminary data, or have they made their decisions just on the safety basis to really expedite from Phase 1 to Phase 2 into a 16,000 Phase 3 study? Thank you for taking my follow-up question.

Joseph Payne, President and CEO

I can reiterate the timeline and then turn it over to Steve, but in mid-August we initiated the Phase 1, which means the second shot was mid-September and a month after that is mid-October when the blood draws were 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 can comment.

Steve Hughes, Chief Medical Officer

Yes. As far as we know, the Ministry of Health hasn't seen any immunogenicity data. The timing of assessing those samples wouldn't really have allowed them to see immunogenicity data prior to moving the study from one phase to the next. The immunogenicity data readout from those 1,000 participants isn't going to be back. 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 assessment 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.

Yasmeen Rahimi, Analyst

Thank you so much for the clarity.

Operator, Operator

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

Joseph Payne, President and CEO

Great. Thank you, Doug. This concludes our third quarter update. Thank you for joining us this afternoon to talk about our progress. Please reach out to us with your questions, if you were unable to be accommodated 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.

Operator, Operator

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.