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Moderna Inc  (NASDAQ: MRNA) Moderna Vaccine Against COVID-19 Phase 1 Interim Results Publication Call Transcript

MRNA Conference Call - Final Transcript

Moderna Inc  (NASDAQ: MRNA) Moderna Vaccine Against COVID-19 Phase 1 Interim Results Publication Call dated July 15, 2020

Corporate Participants:

Lavina Talukdar — Head of Investor Relations

Stephane Bancel — Chief Executive Officer

Tal Zaks — Chief Medical Officer

Analysts:

Matthew Harrison — Morgan Stanley — Analyst

Edward Tenthoff — Piper Sandler — Analyst

Salveen Richter — Goldman Sachs — Analyst

Cory W. Kasimov — J.P. Morgan — Analyst

Gena Wang — Barclays — Analyst

Michael Yee — Jefferies — Analyst

Geoff Meacham — Bank of America — Analyst

Hartaj Singh — Oppenheimer — Analyst

George Farmer — BMO Capital Markets — Analyst

Alan Carr — Needham — Analyst

Mani Foroohar — SVB Leerink — Analyst

Jonathan Miller — Evercore ISI — Analyst

Presentation:

Operator

Good morning, and welcome to Moderna’s Conference Call. [Operator Instructions]

At this time, I would like to turn the call over to Lavina Talukdar, Head Investor Relations at Moderna. Please proceed.

Lavina Talukdar — Head of Investor Relations

Thank you, Shannon. Good morning, everyone, and welcome to Moderna’s conference call to discuss the publication of our Phase 1 interim analysis for mRNA-1273, our vaccine against the novel coronavirus. You can access the press release issued this morning as well as the slides that we’ll be reviewing by going to the Investors section of our website. On today’s call are Stephane Bancel, our Chief Executive Officer; Tal Zaks, our Chief Medical Officer; and Stephen Hoge, our President. Also on the line for the Q&A section is David Meline, our Chief Financial Officer.

Before we begin, please note that this conference call will include forward-looking statements made pursuant to the Safe Harbor provision of the Private Securities Litigation Reform Act of 1995. Please see Slide 2 of the accompanying presentation and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements. We undertake no obligation to update or revise the information provided on this call as a result of new information or future results or developments.

With that, I will now turn the call over to Stephane.

Stephane Bancel — Chief Executive Officer

Thank you, Lavina, and good morning or good afternoon, everyone. Thank you for joining the call. I hope everyone is in good health. We are very happy to announce that the New England Journal of Medicine published yesterday the Phase 1 interim analysis of our vaccine against COVID-19 mRNA-1273. We are very excited and encouraged by the interim data as it confirm our strategy to develop mRNA-1273 as quickly and as safely as possible.

Let me briefly summarize the key takeaways from the press release before turning it over to Tal to walk you through the detailed data. The interim analysis of our Phase 1 study evaluated a two dose for prime and the boost, 28 days apart of mRNA-1273 across three dose levels in 45 healthy volunteers aged 18 years to 55 years old. The dose level were 25, 100 and 250 microgram. After vaccination with mRNA-1273, 100% of evaluated participants had neutralizing antibody titers.

In the live SARS-CoV-2 PRNT80 assay, the day 43 geometric mean titer levels at a Phase 3 selected dose 100 microgram were 4.1-fold above those seen in reference convalescent sera n=3. In pseudovirus neutralization assay, ID50, the Day 57 geometric mean titers at the 100 microgram dose were 2.1-fold higher than dose seen in convalescent sera, n=38. We also published T Cell responses and our vaccine elicited Th1-biased CD4 T Cell responses. mRNA-1273 was generally safe and well tolerated. These results reaffirm and expand upon positive interim data announced on May 18. The data supports selection of 100 microgram dose for Phase 3 expected to start July 27.

Let me now turn it over to Tal to take you through the data in more detail. Tal?

Tal Zaks — Chief Medical Officer

Thank you, Stephane, and good morning everyone. Let me start with a quick reminder of the data generated to date with our vaccine, as it give us confidence that these data is consistent and seen across our vaccine platform to date. As many of you know, mRNA-1273 is our 10 vaccine in the clinic and its development was enabled by the learnings we’ve amassed with the other vaccines that we’ve taken to the clinic today in over 1,900 healthy volunteers.

We reported eight positive Phase 1 data sets against nine different viruses. For those keeping count, the discrepancy is because we were able to immunize against two separate respiratory viruses hMPV and PIV3 with a single vaccine containing two separate antigens. In these trials we’ve seen a safety and reactogenicity profile that is consistent with those of marketed adjuvanted vaccines. And we’ve been able to elicit an immune response in the form of neutralizing antibodies time and again. mRNA-1273 is our second vaccine to fully enroll a Phase 2 trial with CMV having fully enrolled in late February.

Slide 5 lists out the eight Phase 1 trials on the level of immunogenicity achieved with each. While the biology for each virus varies, you can see a strong and consistent neutralizing antibody response that our platform is able to elicit. So as a reminder, mRNA-1273 encodes for the full spike S protein in its pre-fusion stabilized form that when administered produces the transmembrane trimeric spike S protein. While the full length intact protein is recognized by B cell receptors and ultimately elicit antibodies that recognize the three dimensional protein, the fact that our mRNA vaccine translates the viral antigen from within the cell is what enables the full length protein to get processed into peptides that are ultimately recognized by T cells, and thus we are eliciting a full immune response comprised of B cell and T cell responses.

Slide 7 now shows the actual three dimensional structure of SARS-CoV-2 using electron microscopy. Now here you can see both the S1 and S2 regions that make up this full spike protein, which mRNA-1273 some encodes codes for. Now in red, you can see just that Receptor Binding Domain with which the virus binds to the S2 receptor, but in green, you can also see the N-Terminal Domain, which is adjacent to that RBD or the Receptor Binding Domain. It’s notable that neutralizing antibodies have also been described to bind not just the RBD, but also the N-Terminal Domain. So by encoding for the full spike protein, mRNA-1273 has the potential to elicit neutralizing antibodies to both the RBD and the NTD domain as well as potential other domains on the full length protein.

So let’s turn to the Phase 1 trial design. Let me just remind you of that, which as you know, is being run by NIAID, part of the National Institutes of Health. This study initially enrolled a total of 45 participants between the ages of 18 to 55 into three dose cohorts, 15 participants each in the 25, 100 and 250 microgram dose levels, and these are the data that I’ll be reviewing. Now the study has since been expanded to include seven additional age cohorts. Enrollment is complete for these cohorts and these data are expected to be published separately.

The vaccination schedule is a prime boost regimen given a month apart totaling two vaccinations per participant. So we started day one, and then the second vaccination is given at day 29. You will note that three participants in this case, two in the 25 microgram group and one in the 250 microgram group didn’t receive, for various reasons, their second or the boost vaccination and there were an additional three missed time points. We are reflecting the total ends in the data tables that provided the blood draws for the analysis of each time point.

Now the primary endpoints for the trial are safety, reactogenicity and tolerability and the key secondary endpoint is immunogenicity, as measured in day 57. Although we did measure the immunogenicity or the titer levels more frequently, so you will see data for days 15, 29 after the first dose and then days 36, 43 and 57 after the boost.

So let me begin with an overview of the safety data. At a high level, mRNA-1273 was generally safe and well tolerated with no serious adverse events reported through day 57. Adverse events were generally transient and mild-to-moderate in severity. And on Slide 9, you can see the frequency and severity of the local adverse events, which when present, were mostly mild or moderate. All participants at the 100 microgram dose level reported mild-to-moderate injection site pain. If we look at the solicited systemic adverse events listed on Slide 10, these were also generally transient and mild-to-moderate in severity.

Now let’s just step back. These are really the anticipated flu-like symptoms that you expect from the administration of any vaccine. In fact, their occurrence and severity is scored according to a specific FDA guidance developed for this purpose. The systemic adverse events graded as severe in our case occurred in the 250 microgram dose cohorts, with three participants experiencing one or more events. It is notable that systemic adverse events were more common after the second vaccinations, suggesting that they correlate with systemic and specific immune activation. They occurred in seven of 13 participants in the 25 micrograms and then all participants in the 100 microgram and 250 microgram groups. The most common, we reported systemic adverse events looking specifically at the 100 microgram dose were fatigue, chills, headache and myalgia. Of note, clinical laboratory values and unsolicited adverse events didn’t show any patterns of concern. So overall, based on these Phase 1 data, mRNA-1273 appears to be generally safe and well tolerated and this safety data would support the choice of 100 microgram as the recommended Phase 3 dose.

So let me now turn to Immunogenicity. I will take you through three data sets. One on binding antibodies and two, describing neutralizing antibodies from two different assays. Each of the data sets are compared to convalescent sera from patients with COVID-19. Binding and pseudovirus data were compared to convalescent sera from 38 individuals with confirmed disease, 15% of which — or whom were classified as having severe COVID-19 illness requiring hospitalization, including ICU care and/or ventilation. 22% had moderate symptoms and 63% had mild symptoms. Their sera was collected between 23 and 60 days after the onset of symptoms and they were taken from individuals of the ages 22 to 84 years old. For the live SARS-COV-2 virus assay, due to the time-sensitive nature of this assay, the convalescent group was comprised of data from only three individuals. Importantly, all three assays are orthogonally supports robust immunogenicity activity, and there is a pretty good correlation between them.

So with that backdrop, starting with binding antibody titers. On Slide 11, you will see a table with the geometric mean titers of binding antibodies at various time points for each of the three dose levels. The geometric mean binding antibody titer value for the convalescent sera group of 38 individuals is listed at the top of the table, and is approximately 142,000. Now looking at the tables, you will see that mRNA-1273 induces dose dependent increases and binding titers across the three dose levels, and between prime and boost vaccination readily seen at the increase between day 29 and day 36 within the dose cohorts. Of note, all participants’ sera converted after one vaccination already at day 15. After two vaccinations at day 57, the geometric mean titers exceeded those seen in convalescent plasma across all dose levels and in fact the 95% confidence intervals are non-overlapping at the 100 microgram and 250 microgram dose levels.

Slide 12, shows you the graphical box plot representation of the distribution of these titers and its useful as it helps to visualize the media and the binding antibody titers and the maximum and minimum values below and above the median range for each dose level relative to infection as seen in the convalescent sera group. After two vaccinations at time points of day 36, day 43 and day 57, the median antibody titers for all doses were well above the median for convalescent sera. What is notable, is the relevantly — is the tight distribution of titers in vaccinated individuals. This vaccine produces a robust and consistent immunogenicity. Additionally note the red dots in the convalescent sera box plot, these red dots represent those three additional individuals with confirmed COVID disease that were used as comparators for the live SARS-COV-2 neutralization assay which we’ll talk about in the next slide.

So here you see the table showing the neutralizing antibody titers from what’s called the plaque-reduction neutralization Test80 or PRNT80. Now the way this is done, is that you measure the ability of the blood to limit the viruses ability to infect cells, and the curves are plotted using successive dilutions starting with relatively undiluted blood that would provide 100% neutralization compared to background and ending up with dilutions that can be distinguished from background level. The PRNT80 thus corresponds to the dilution titer at which the blood from a vaccinated individual can reduce the infectivity of the live SARS-COV-2 by 80%, and people interchangeably use PRNT80s or PRNT50s that point estimate at 50%. The PRNT80 in this case was a more accurate and stringent representation of the neutralizing activity.

In the table you will see the mean values for the PRNTSA at day 1 and day 43 for the 25 microgram and 100 microgram dose cohorts compared to the convalescent sera group, again consisting of three individuals with confirmed COVID-19 disease. The geometric mean titers of neutralizing antibodies for both doses are above the for the convalescent sera group. As a reminder, the convalescent sera group is representative of that larger convalescent sera of the eight additional subjects.

Now Slide 14 shows the graphical representation of the PRNT80 responses. At the 25 microgram and 100 microgram doses, mRNA-1273 was able to induce neutralizing titers against live virus in all participants. The median value is represented by the horizontal lines across the box plots were at or above convalescent sera levels from those three individuals. Finally on immunogenicity, we look at neutralizing antibodies in a pseudovirus neutralization assay. This assay is designed as a single infection cycle high throughput assay that correlates well to what we can learn from a live virus assay. And the titers were scored at the 50% mark, i.e., the titer at which the blood still diluted can reduce infectivity by 50%. Comparing the geometric mean pseudovirus neutralization assay results to the mean values from convalescent sera, here with 38 individuals, we can see a 2.1-fold increase in titer levels at the 100 microgram dose at day 57, above the mean convalescent sera.

Slide 16, now shows the box plots for each doses compared to the box plots for the convalescent sera group. In this presentation of the data, it is easier to visualize that again after the second vaccination at time points 63, 43 and day 57, neutralizing antibodies were detected in all vaccinated individuals. At the 100 and 250 microgram dose cohorts the responses were fairly consistent between individuals and we don’t see a significant further difference between 100 and 250 microgram, both dose levels elicit neutralizing antibodies comparable to values that are in the upper half of the distribution of convalescent sera. Overall, the immunogenicity data I’ve described from all three assays taken together support the choice of the 100 microgram dose level as the optimal Phase 3 dose.

So let me turn to T-cells. As Stephane mentioned earlier in this study, T-cell responses against the S1 and S2 regions on the spike protein were also assessed for the 25 and 100 microgram dose cohorts. On Slide 17 CD4+ T-cell responses against the S1 region for the 100 microgram doses show, and you can clearly see the expression of Th1 type cytokines including TNF-alpha, nterleukin2 and interferon gamma were predominantly expressed at day 43. That indicates that what we see is a response that is of Th1, we do not see the expression of the Th2 cytokines.

Similarly on Slide 18, you can see CD4+ T-cell responses against now peptides from the S2 region, and again you can see the same observation. These are Th1 cytokines at day 43 with minimal to no Th2 type cytokines demonstrated.

So to conclude on the findings from the data from this interim analysis of mRNA-1273, our vaccine against COVID-19, we found the vaccine to be generally well tolerated with no serious adverse events reported. mRNA-1273 induced binding antibody titers in both the time and dose-dependent manner above those seen in convalescent sera. We had observed high neutralizing antibody responses that were dose-dependent, and after two doses of the 100 microgram dose, mRNA-1273 elicited robust neutralizing titers with a geometric mean above those seen in convalescent sera as measured now by two different assays. Vaccination with mRNA-1273 further has been demonstrated to elicit a Th1-biased T-cell response. Overall, these safety and immunogenicity data supported advancement in the later stage clinical trials at the 100 microgram dose level. And I’m super proud of all the Moderna and grateful to the NIAID teams that have worked so well and fast and collaboratively on this program. And I’m extremely thankful for the participants in this Phase 1 study.

So let me now change gears to quickly talk about the clinical development plan for mRNA-1273, where are we and what’s ahead. Given the urgency of the global pandemic, we along with our collaborators at the NIH and with the close support of FDA have been moving the plan along in a parallel fashion with making sure that we expand the safety database for this vaccine carefully. As such, we started the Phase 2 trial after Phase 1 safety data were available, and we expect to start the Phase 3 trial on July 27.

As it relates to the Phase 2, last week we announced that both age cohorts in this trial are fully enrolled. 300 participants in the 18 year to 55 year old age group and 300 participants in the above 55 age group have been enrolled. And this trial is basically designed to confirm the safety reactogenicity and immunogenicity as seen in the Phase 1 with further exploration of the 50 microgram dose level, while we carefully expand the safety database ahead of Phase 3.

So let’s talk about the Phase 3 and our late stage development. There has been a lot of understandable interest in this trial. And I’d like to take this opportunity today to transparently provide you with some relevant details around the trial design and the endpoint definitions to help everybody understand what we’re hoping to achieve and how we’re going about it. The Phase 3 protocol has been reviewed by FDA and is aligned to their recent guidance on clinical trial design for COVID-19 vaccine studies. We plan to randomize 30,000 participants, one-to-one between vaccine arm and placebo with the primary endpoint of prevention of symptomatic disease.

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The primary efficacy analysis will be event-driven based on the [Technical Issue] target efficacy against COVID-19 for powering assumptions here. The point estimate of 60% and 95% confidence interval meant to exclude a lower bound greater than 30%. Data will be reviewed on an ongoing basis by an independent safety monitoring committee led by the NIH. And this trial is expected to have two interim analysis at approximately 53 and 106 events prior to the final event-driven analysis at approximately 151 events.

We define the prevention of symptomatic disease as the following. Participants must have experience at least two of a systemic symptom whether it’s fever, chills, myalgia, headaches or throat or new taste or smell disorder or at least one respiratory sign of symptom which include cough, shortness of breath, difficulty breathing or clinical or radiographical evidence of pneumonia. And of course, in order to be classified as a case, the participant must have at least one demonstration by RT-PCR of positive viral infection.

Now that being the primary endpoint, the key secondary endpoints would include, on one hand, prevention of infection even asymptomatic of SARS-CoV-2 and on the other hand, prevention of more severe disease, in this case as measured by such things as hospitalization. In terms of the plans for filing, I can tell you that we’ve received Fast Track designation and the team is actively preparing indeed for a rolling submission for the BLA so that we’re ready once we have the first interim data that support safety and efficacy.

Let me spend a few minutes just on the trial recruitment. We are working closely with the Operation Warp Speed colleagues and the NIH, including NIAID’s COVID-19 Prevention Trial Network that has recently been launched to conduct the Phase 3 COVE study with the hope to achieve our shared goal that the participants in this trial are indeed representative of the communities at highest risk for COVID-19 and representative of our diverse society.

You can see some of the specific measures we’re taking on the right hand side of the slide. We’ve approached this challenge really at two levels. First, picking vaccination — vaccinating centers and experts in areas of current and anticipated exposure to infection. Think of this as figuring out what the right zipcode to go after or to go to. And second, working with the local investigators and communities in those zipcodes so that we can enable those who are at highest risk for both infection and disease have the opportunity to enroll. As announced, we expect to begin vaccinating volunteers on this trial by the end of this month.

With that, let me turn it back to Stephane.

Stephane Bancel — Chief Executive Officer

Thank you, Tal. With a clinical development plan in place, the team at Moderna has mobilized quickly in order to manufacture as many doses of mRNA-1273 as we can do with high quality of course. We believe that Moderna has a good plan to manufacture 500 million doses annually at 100 microgram as a base case. The new projects that our manufacturing team are executing as we speak are designed to take our capacity up to 1 billion doses annually.

We have designed our supply chain to ensure we can supply the U.S. market from a U.S. supply chain and we can supply outside the U.S. markets from outside the U.S. supply chain. For the U.S., formulated mRNA is being made at our Moderna Technology Center in Massachusetts and Lonza site in New Hampshire. Catalent will do a fill-finish for the U.S. market from Indiana. For outside the U.S., formulated mRNA will be made at Lonza site in Switzerland. ROVI, our latest partner, will do a fill-finish for the outside the U.S. market from Spain.

As many of you are aware, we raised $1.3 billion in equity capital in May, primarily to fund mRNA-1273 stockpiling at risk prior to Phase 3 data or approval. The Moderna board decided to do so to ensure that if mRNA-1273 is approved, we will have hundreds of millions of doses available to help protect as many people as we can at launch. That equity capital from our investors have started to be deployed in Q2 to put all the pieces in place to make hundreds of millions of vials, buying raw material, buying capital equipment to be installed and validated at Moderna Technology Center in Massachusetts as well as Lonza in New Hampshire and Lonza Switzerland, and of course hiring and training personnel.

We have already started to make material at risk in preparation for commercial mRNA-1273 doses. We are moving as quickly and as safely as possible with mRNA-1273 program in order to generate as much data as possible to enable a risk benefit assessment of our vaccine for potential BLA filing. The key upcoming next steps are non-human primate challenge model publication. As we’ve shared before, a non-human primate model has been run and we expect this data to be published in the near future. The start of a Phase 3 trial, with site initiation starting as soon as next week. The Phase 1 interim data for age 55 to 70 and the group of 71 plus the Phase 2 interim data, the Phase 3 interim analysis, the BLA filing upon evidence for Phase 3 safety and efficacy.

It is difficult to believe that it is only six months since the sequence of SARS-CoV-2 virus was made available online. We published encouraging interim Phase 1 data in the New England Journal of Medicine, showing up the vaccination with mRNA-1273 100% of evaluated participants are neutralizing antibody titers. We are no days away from starting to recruit healthy subject for 30,000 participant placebo-controlled randomized Phase 3 study.

Everyone at Moderna understand the responsibility we have to deliver on the promise of mRNA science and to create a new generation of transformative medicines, and we strive to meet this goal every day. Our efforts in the mRNA-1273 program fully exemplify that Moderna teams strive for on a daily basis. I am very grateful to the team for all their efforts and commitment to our mission. I am thankful for our team dedication. It has been a six month intense, seven days a week effort by hundreds of our colleagues at Moderna.

I would like to especially recognize and thank the participants in our clinical trials and the clinical trial site investigators and nurses for the help and dedication. I would also like to thank our collaborators at the NIH and NIAID in taking this journey with us. I will also like to thank the many suppliers and partners helping us to scale at this unprecedented pace in the 12-month timeframe

With that, we’re happy to now take your questions. Operator?

Questions and Answers:

Operator

[Operator Instructions] Our first question comes from Matthew Harrison with Morgan Stanley. Your line is open.

Matthew Harrison — Morgan Stanley — Analyst

Good morning and thanks for taking the question, and thanks for the significant detail on the data and the Phase 3 design. Two questions from me. I guess, first, can you comment broadly on durability of the neutralizing titer response. It appears that the average neutralizing titer declined a bit from day 43 to 57 and I’m wondering, specifically, if you could comment on patients that you’ve followed outside of the study period that you’ve published here and if you’re seeing stability in that neutralizing titer level? And then second, I was also hoping you could comment on CD8 responses and how important you see those or not in the data. I think that’s a question that I’ve gotten a lot from people around the lack of CD8 response. Thanks very much.

Tal Zaks — Chief Medical Officer

Thanks, Matthew. This is, Tal. Let me take the — we don’t have any more data on durability. I haven’t seen beyond what’s there. In fact, these data are fresh and they emerge, so that you can see a lot of time point here almost weekly after the boost. I think it’s very early days to talk about durability as we will see the data, of course, we will share them. There have been recent descriptions, I think coming both out of cohorts from the UK as well as China, whereby the neutralizing antibodies may wane over time. I think, my take away is that it’s entirely plausible but it also seems that those who start with asymptomatic infection or start with lower levels of antibodies, they seem to lose them more quickly, which probably speaks to the quality and type of the immune response to begin with.

I think with that in mind for me it’s reassuring to see that we achieved neutralizing antibodies that are consistently above what you see from people who have actually been sick and who we expect are going to be protected. Now the antibody levels are naturally going to wane over time. The higher you start the longer the durability will see of protective levels of the blood that’s just math and kinetics. But I think the other element here which you alluded to is the T-cell response, because that is really, I think for this virus, I think of it as a — the master coordinator for the response, if you will. My understanding of the data that is emerging is that neutralizing antibodies are really carrying the brunt of the weight of an immune response against this virus and in any case, I think of them as sort of the ultimate thing that we can measure that tells us that the right immune response has occurred.

And I think that’s based on a number of strands of science both the ability to vaccinate effectively, it gets just the spike protein a whole bunch of preclinical species and show you can prevent viral replication and that correlates very nicely with neutralizing antibody levels as well as the utility of — potential utility earlier disease of transfer of convalescent plasma and we can come back to that I’m sure. So as I look at the T-cell responses here, the CD4 is clearly evident and quite robust. It’s enough to tell you that you’ve got the right kind of T-cell for one phenotype. And indeed, I think people have recently described, there was a paper from Alessandro Sette’s group a couple of weeks ago showing that, you actually have and people who’ve been sick everybody gets CD4 response against the Spike protein and those responses correlate very nicely with antibody with neutralizing antibodies.

So our vaccine, also in that regard elicit to what has been described as the relevant immune phenotype for people who have been infected. The CD8s are an interesting question. The — they’re an effector arm against Intracellular viruses as we know them, and against other intracellular changes, and so I think it’s not clear to me what the effect of CD8 cells are in viral clearance. Now that being said, we do see some low but significant elevation. if you look carefully at the data out to day 43 as the T-cell immunology. I’ll tell you that day 43 as far from the ideal time at which to look for T-cells, relative to the infection, I think it’s early data. It’s hard to say. And for me it’s harder to pin what the relevance of the CD8 response is against this virus to begin with.

Matthew Harrison — Morgan Stanley — Analyst

Great. Tal, thanks very much for the response.

Tal Zaks — Chief Medical Officer

Pleasure.

Operator

Thank you. Our next question comes from Ted Tenthoff with Piper Sandler. Your line is open.

Edward Tenthoff — Piper Sandler — Analyst

Thank you very much and congratulations to everyone on this data. It’s just incredible how quickly you guys are moving forward and all the pieces are coming together. I had a question with respect to the manufacturing side. Can you give us a little bit more of a sense in terms of how many vaccines or doses would be prepared by the time of potential approval around year end? And what are some of the steps that go into expanding that capacity with Lonza? Thank you very much.

Stephane Bancel — Chief Executive Officer

Hey, Ted. Good morning, it’s Stephane. Thanks for the question. So on the manufacturing front, as you know, we have not guided precisely in terms of what would be available by the end of the year. We are working very diligently. And the team are doing really a remarkable job, just to make as much product as we can. As I’ve stated on the call today, we have already started to make commercial product at risk, and we’ll continue to do so every day, every week, every month. The way to think I think about the ramp, which I think is behind your question is, as we’ve said in the past, the ramp will increase, so, the capacity will increase every mouth on a forward-looking basis from now on to next month to the month after. So you can’t — most model a ramp that will give us an annual run rate. What we said today in the call and as we’ve said before, when we were assuming 50 microgram for the dose a few months back as you recall. As the dose that we are doing the Phase 3 were 100 microgram. We have a very solid plan to deliver 500 million doses, and we feel very comfortable with this number again on an annual basis.

If I must assume kind of almost a linear ramp, and the team as many actions and plans in place to get this up to 1 billion. So it’s not in the budget, which is why we characterize it as we did on the call, in our remarks, but I wouldn’t bet against the team. As you know, Juan and the team all come from experience in large manufacturing organization. For those of you who are not aware, Juan used to run manufacturing for Novartis worldwide, including the vaccine business when Novartis had the vaccine business. And so there’s still a lot of work to do, which is why we want to be cautious. But you also think about it in that way. So we will not communicate the year end exact number, because there is so many things that could move around that we want to be cautious, but we reassure that the team is pushing hard. Again, we have a big focus on quality, because these products will be injected in people, so quality is very important, but the team is working very hard to make as many doses as we can to help protect as many people as we can assuming the product gets approved.

Edward Tenthoff — Piper Sandler — Analyst

All right. Excellent. Thank you very much for all of your hard work.

Stephane Bancel — Chief Executive Officer

Thank you, Ted.

Operator

Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.

Salveen Richter — Goldman Sachs — Analyst

Good morning and congratulations on the data and two questions from me. So one, can you comment on the meaningful nationally insights you’ve gained regarding your neutralizing antibody data, just given the lack of consistency with assays across the trial. And then secondly, given the need to enroll a diverse population in the Phase 3 and the moving infection rate, how long do you think it will take for you to get to these interim events?

Tal Zaks — Chief Medical Officer

Hi, Salveen, it’s Tal. Thank you for your two questions. Obviously, both are top of mind. So let me start with the neutralizing antibodies. I think you point to a problem that we’re all facing, that hopefully in the near future we will see some standardization of these assays. I know it’s a top priority for my colleagues at the OWS and the NIH, and I think in that regard, I’m really grateful for our ability to collaborate with them from the get-go here. So I anticipate some of these assays are forming the bases for what will end up being harmonized.

That being said, people have described neutralization, live virus microneutralization, pseudovirus neutralization. So there is a variety of assays out there. I think the way I think about it is the live viral one should give you roughly in the ballpark of the similar range of responses. And I think for me the telling bit is to look at the FDA guidance for how do you characterize donor plasma if you want to use plasma from somebody who have convalescent plasma as treatment. And there the FDA basically says that you should look at titers of at least 160, in some cases may be as low as 80, but 160 is what’s in their guidance based on a live virus assay. And this is typically thought to refer to the ID50s or the PRNT50s. And what you see for us I think on the live viral assay is that we get to a geometric mean at the 600 range, 640 or so, and that is at the PRNT80. Now mathematically the PRNT50 should be even higher. So I think both based on what we see with the internal reference set of convalescent plasma in our study and what we understand is sort of the ballpark numbers that are being used out there for similar live viral assays, I think this puts us in a really good place with our vaccine.

The second question is how long will it take to understand safety and efficacy and see an interim? As you rightly point out, that’s a function of infection rates and the infection rates in the people whom we vaccinate. And I think the truth here is I don’t really know. And I think different people are going to have different opinions. So rather than give you my own crystal ball here, what I — what we chose to do is be very explicit transparent about the underlying assumptions powering our study. So you’ve got the full details for our statistical design. You have an understanding of how many events we’re going to be looking at, at the first interim, second interim and final analysis.

The — calling it a success will follow fairly conservative Brian Flemming type crossing rules that will all be done by a independent data safety monitoring committee looking routinely at the data as they emerge. Now when these events happen, I think is a function of what will end up being the infection rates at the sites we go. As you point out these very widely, we’re doing our best with our collaborators and the sites where we’re setting this up to make sure that we’re in areas that are seeing infection rates that are significant and that we are enabling the participation of those individuals who are at highest risk of getting infected. I hope with those parameters in place that in the coming months, we will be able to demonstrate the safety and efficacy based on interim analysis of this trial.

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Salveen Richter — Goldman Sachs — Analyst

Thank you.

Operator

Thank you. Our next question comes from Cory Kasimov with J.P. Morgan. Your line is open.

Cory W. Kasimov — J.P. Morgan — Analyst

Great. Good morning, guys. Thanks for taking the questions, and great to see the continued progress here. So two questions for me as well. First one is just given everything you know today, what do you see as the biggest risk at this point to the Phase 3 trial? And then my second question is putting the cart before the horse a little bit. But curious if you would contract with the government prior to Phase 3 data and/or approval to supply doses of the vaccine? We saw AstraZeneca already engaged in these types of deals, so I’m wondering how you’re thinking about that going forward?

Tal Zaks — Chief Medical Officer

Thank you, Cory. Let me take the first question and I’ll defer to Stephane on the second. I think the biggest risk to the Phase 3 is that which Salveen alluded to in the prior question, which is the attack rate in the population that will get vaccinated. If we — with the current attack rate we are seeing in the U.S., we should be able to vaccinate people, some of whom ultimately by chance and disposition are going to be at risk and will end up being exposed to the virus. And to the degree that we’re able to see those events, the trial will read out sooner and with a robust data set. To the degree that we are unable to capture those individuals and we end up vaccinating people who do not get exposed, I think, it will be very hard to make a determination. We’ll have a great safety database, but it will make it challenging to demonstrate efficacy. So I see that as the greatest risk right now.

And with that, let me turn it over to Stephane to answer the question about contracting.

Stephane Bancel — Chief Executive Officer

Thank you, Tal. Good morning, Cory. So yes, as you know, we have very close partnership with the U.S. government from OWS, Operation Warp Speed, of course. NIAID, BARDA [Phonetic] the FDA and with all of those agencies we have some time daily, sometimes several times a day discussions. As you can appreciate, it will not be appropriate for me to comment on this. Our goal is of use. We are making product at risk. And we want to be helpful starting of course with the U.S. government and U.S. citizens.

Cory W. Kasimov — J.P. Morgan — Analyst

Okay. Thank you. Best of luck with Phase 3.

Stephane Bancel — Chief Executive Officer

Thank you.

Operator

Our next question comes from Gena Wang with Barclays. Your line is open.

Gena Wang — Barclays — Analyst

Thank you for taking my questions. Also wanted to add my congrats on the data. So I have two questions, and first one is regarding the convalescent data. Just wondering, did you see any correlation regarding severity versus the GMT number? And for the live viral, the PRNT80 test, three patients, the one had close to 500 [Phonetic], was that patient more severe versus the other two patients that were roughly around 100? And then my second question is if you can make some comments on the comparison between your pseudo viral neutralizing antibody test versus [Indecipherable]?

Tal Zaks — Chief Medical Officer

Thank you, Gena. I appreciate the sentiment and questions. I think on the convalescent data, we are — or more accurately, I think our colleagues at the NIH are looking at this. I don’t have any explicit data to share as to the one-to-one correlation of where each of those dots falls relative to disease severity. But I think the field at large is informative on this point. And so I would expect that what you’re seeing is a range that roughly would correlate.

I think the important part here for me is to understand the totality of the data because the relevant point is sort of the geometric mean, if you will, of where that convalescent reference ends up. So I think it is a representative cross section in terms of the illness or the burden of disease that we have a convalescent from. And therefore, I’m comfortable that the geometric mean represents a relevant reference for judging how good our neutralizing antibodies are, how good was the vaccine at eliciting high titers.

Comparing it to data from others, as I said before, I think it’s still tricky. I think if you’re looking for a number to latch on to, I think the best comparator to be done is probably looking at live virus versus live virus. I think they used a live virus that’s been engineered to give a more high throughput reporter, which allowed them to demonstrate it. I think our live viral assay is sort of the gold standard here. It’s the virus as exists in nature, it hasn’t been tampered with. And what we’re measuring is the plaques that it actually induces in cell monolayers.

And so I think if I were to pick a number to compare, it’s probably the absolute number and the relative performance relative to convalescent plasma of a live viral assay versus another live viral assay. I think there is a correlation between the pseudovirus neutralization, that’s a single cycle replication assay. So there is a correlation. And if you pull up the supplemental figures from the New England Journal, you can roughly kind of draw that line and see the correlation between the two assays. But I think numerically, those numbers are probably a tad lower just because of the assay characteristics. I hope that answered your question?

Gena Wang — Barclays — Analyst

Thank you. That’s very helpful.

Operator

Thank you. Our next question comes from Michael Yee with Jefferies. Your line is open.

Michael Yee — Jefferies — Analyst

Hey, good morning. Thanks for all the detail, and congrats on the progress. Two questions. One was in thinking about the Phase 3 data that’s in development or Phase 3 study that you’re on. I mean is there any sense that infection rates could actually be very high and the interim data could actually come very quick? And is there any thinking about what would be needed in terms of amount of follow up or amount of safety or amount of people would have actually been dosed in the sense that it was the opposite scenario where the infections actually come very fast. How would you think about that scenario? And then my second question was a little more detailed on the Phase 3. I appreciate that the primary endpoint is actually symptomatic infection. Could you just maybe make a comment about why the endpoint is not actually SARS-CoV-2 infection, and whether that’s important too, because you could still be infectious if you are infected with SARS-CoV-2? Thank you.

Tal Zaks — Chief Medical Officer

Thank you. Great questions. So I think the first one, if we do see a signal very soon, then, as you rightly point out to the duration of follow-up of safety is going to be commensurately short. I think the answer there is going to lie not with us, but actually with the FDA. And we’ve had a pretty close dialog with them, and I’m super grateful for how they stepped up to support not just us, but every and many sponsors of vaccine trials both with individual support and then with a consistent guidance across the industry. They’ve already sort of — we’ve had initial discussions on that in terms of expectations, but I think as you rightly point out to, once we crossed that rubicon it will be up to a dialog with them to understand how we can translate that first signal into a safe deployment for the population given that we’re already manufacturing supplies and hope to have a significant amount of supplies on hand by that time.

Now, that brings me to your second point, which is I think, no matter how long the duration of safety follow-up is here, I think it’s incumbent on us to make sure that deployment from the earliest start occurs in a manner that allows us to continue to understand the safety profile of this vaccine. This will be the first mRNA vaccine ever approved, and if we’re successful. And so, continuing to collect that safety data will require continued close collaboration with those branches of the government that ultimately we expect to be responsible for deploying this vaccine early to those who need it the most. And so that as well will require ongoing work and we’re starting to have those conversations.

Your second question was about the endpoint of symptomatic infection and why not include asymptomatic infection. So for me, there are two reasons why we — and we had considered it, and we’ve had a very robust dialog with our colleagues at the NIH and as well as with the team at FDA on what is the right endpoint and how one defines it. And this has not been easy. I think if you put it all on balance, I think what’s important for us is to demonstrate first and foremost, the ability to prevent disease. Now there is no doubt that there could be and there will be a secondary benefit if one can demonstrate prevention of infection, but I think there are two reasons why prevention of symptomatic disease rose to be the so primary endpoint.

I think the first is as it relates to the population to whom you want to vaccinate and bring this benefit, it is a much more readily understood by the public know what this does is prevent me from getting sick. That’s why I’m getting the vaccine and I think that’s a very powerful endpoint for people to be able to understand what we’re trying to achieve. But I think there is a second element that’s just as important, if you look at the history of vaccines against respiratory viruses, it is interesting that what they do the best is actually protect from disease and in fact the worst the disease, the more effective they are. If you will, even if they don’t prevent full infection, they are — they can blunt the infection by pre-wiring your immune response to rise more quickly to the challenge should you get infected. And in that regard, I think, just scientifically more likely that you can demonstrate a higher level of efficacy against the prevention of disease.

Now, you should still or we hope we would see some prevention of infection as well, but given there is going to be a higher likelihood and therefore a higher point estimate of prevention of symptomatic disease, and that is what people readily understand to care about, I think it made sense for us to include this as the primary and let the other endpoints be the secondary such that the analysis in our ability to quickly understand the data is solely driven off the prevention of symptomatic disease.

Michael Yee — Jefferies — Analyst

Makes sense to me. Thank you.

Operator

Thank you. Our next question comes from Geoff Meacham with Bank of America. Your line is open.

Geoff Meacham — Bank of America — Analyst

Good morning, guys. Thanks for the question and all the detail on data. Just had a few on the Phase 3 design. So when you look at the data so far, it’s clear that the boost those confers better protection from infection. So will the Phase 3 measure the endpoints from the first or the second dose? And can you speak to your assumptions on age knowing that it has a big impact on hospitalization risk? And then real quick, just want to get your thoughts emergency use authorization, the potential for that prior to getting Phase 3 results? Thanks guys.

Tal Zaks — Chief Medical Officer

Thank you, Geoff. Let me take these in succession. So the Phase 3, the primary endpoint is being measured. We are starting to count cases two weeks after the boost because I think that’s when you will achieve the maximum ability to protect. Now that being said, we will of course be counting cases and following everybody very closely from day 1 as soon as they step into the trial, and so we will be able to look secondarily at the ability of the vaccine to prevent cases from earlier on and that’s from the get-go. But the primary endpoint here case definition is that which occurs two weeks after the boost.

In terms of the age, I think you’re right. We believe that older people are the more vulnerable. We are making sure as part of the trial design, that there is a significant portion of the trial that is going to be people who are either older or have comorbid conditions such that we can ensure that we’re not just bringing an effective vaccine to those who are more likely to get infected. We’re also making sure that we understand the safety and efficacy in those who are more likely to get sick, should they get infected. And so the trial will definitely be geared to look at that.

Emergency use authorization, look, I think that question should probably be directed to our colleagues at FDA. Ultimately they’ve given guidance so far in public that expect the bar for an emergency use authorization to be the first clear demonstration of safety and efficacy. I can’t speak to their behalf. It will be a conversation with them as our data matures and emerges as to what is the right points to trigger that. I think we have the advantage I believe of working very closely with several branches of the US government including our colleagues at BARDA, the CDC and the NIH. So obviously as manufacturing gears up, we being the sort of first trial out there and the leading company to be collaborating with the OWS, we expect to be at the tip of the spear here in terms of the eventual deployment once we’re able to show that this vaccine is safe and effective.

Geoff Meacham — Bank of America — Analyst

Okay. Thanks very much. Very helpful.

Operator

Thank you. Our next question comes from Hartaj Singh with Oppenheimer & Company. Your line is open.

Hartaj Singh — Oppenheimer — Analyst

Great. Thank you for the questions. And again really great robust data set there. Just a couple of questions past the Phase 3. Vaccine distribution is — has a higher degree of complexity than most of therapeutics. So just how to think about that in terms of, it is going to be administered in the doctor’s office, could you get a broader distribution moving pharmacy also called refrigeration. And then lastly, the various US and ex-US organizations you have to work with for example, the ACIP in the US or WHA to get further certification. Any initial thoughts on that. Thanks for the questions.

Tal Zaks — Chief Medical Officer

Well, let me take it from a clinical perspective. And then I’ll defer to Stephane to talk about how he’s thinking about distribution in the US and ex-US. I think we expect here the initial deployment to really be one that is handled very closely with the appropriate branches of the government. I would defer to them in terms of the settings in which we will ultimately be able to distribute it to the last mile and make sure that the people who need it the most have access to it. I think that dialog is only beginning now in terms of getting prepared for that eventual distribution I’ll let Stephane sort of speak to how we think about the supply chain in its totality and from a global footprint.

Stephane Bancel — Chief Executive Officer

Yes. Thank you, Tal. Good morning. Yes. So, I think Tal started to frame the question correctly, which is in this first phase post-launch or in the case, there will be during BLA review an emergency use of parole [Phonetic] in different geographies that of course will be the decision of local authorities. We see partnering with the government has been very important to make sure that people who need the vaccine the most get it first, because obviously as we understand the disease more and more, we cannot appreciate that not only person with comorbidity factor should be earlier in line versus a young person who has no comorbidity factor and so on. And we do not think this is a decision that company should make, it’s really the — the public health system should make those decisions. So we could see in the case of the U.S. potentially working hand in hand with the CDC where we will ship from our filling facilities finished product to the front depot centers across the country for the U.S., where then they will do allocations to hospitals or pharmacies and/or schools over location that they will decide to do the deployment.

As you have read, I’m sure, through Operation Warp Speed, the Department of Defense is very involved. It could be I think for supply chain reasons. So this is kind of what we anticipate for, I would say the first few months where we know across the industry that there is going to be a very tight supply of the vaccine. And I think as we move over the following quarters into more of a normal setup, I think the more traditional channels will come into play. But what we think is very important and this is really again public health decisions to understand who get the vaccine first. This is not for private company to make those decisions who will not have a right data to be able to make those important decisions.

That’s how we think about it. And I think outside the U.S., is a similar manner, working with governments that are interested to get access to mRNA-1273 so that they can locally decide who gets the vaccine first. Our plan given we’re going to be in a supply constrained world is basically as soon as a lot is approved to basically ship it to whoever orders the lot. So we’re going to be kind of hand to mouth to make sure that we don’t lose any day.

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Hartaj Singh — Oppenheimer — Analyst

Great. Stephane, we’ve got a lot of time to figure this out. But again, thank you for all the questions.

Stephane Bancel — Chief Executive Officer

Thank you.

Operator

Thank you. Our next question comes from George Farmer with BMO Capital Markets. Your line is open.

George Farmer — BMO Capital Markets — Analyst

Thanks again for your time this morning. Congratulations from me as well. Tal, I was wondering if we could drill down into some of the data in the paper. I noticed that at day 29 you see a pretty robust antibody response to the following spike protein as well as the RBD, but based on the data from the pseudovirus neutralization assay, it looks like you’re not seeing much activity. What’s going on there? Are there two different classes of antibodies that are arising here? And what — do you see the boost being extremely important here is really generating neutralizing antibodies over just general binding antibodies?

Tal Zaks — Chief Medical Officer

Hey, George. That’s a really interesting question. I think the truth is, I don’t know. I think what’s generally been observed in the field, and I think it’s true of our data set as well is that the correlation. There is a strong correlation between binding antibodies and neutralizing antibodies, but you have to pass a certain threshold of antibodies. In other words, the binding assays is more sensitive. And in fact, if you look at the backup, I think it’s Plot 5 of the New England Journal, when you see the correlation is sort of dots between the binding antibody levels and the pseudovirus neutralization assay, you will see that at low binding antibody titers, you’re not seeing much as the titers go up, and that’s sort of seems to be irrespective of whether you got a prime or boost. And probably the most telling element there is if you look at the 250 microgram, you give a strong enough initial response you start to actually get into neutralizing antibody territories and you’ve got very high binders. So I think that tells you it’s probably not just an effect of a boost, it’s actually — there is a correlation by the numbers with one assay being more sensitive.

Now that said, I do think that scientifically it makes sense. And from everything we know in immunology that a boost weeks later will indeed get you a higher quality response and a higher quality response, and a higher quality response against SARS-CoV-2 means you got more ability to generate neutralizing antibodies. It’s a bit of a nuance answer because the truth is, I don’t know, but I think there may be an element of it. I think the primary driver though is that you simply have a more sensitive assay when you look at total binding activity.

George Farmer — BMO Capital Markets — Analyst

Okay, great. And then regarding the Phase 2 trial, If I do the math correctly, you probably have your first 350 patients enrolled, volunteers enrolled probably have received their booster already. Can you comment on safety so far? What sort of data are we going to see when the results are ultimately presented? Is it going to be the same type of data that we’re seeing in Phase 1? And then maybe could you just comment generally if anyone that has received the vac that has been enrolled in your trials has been down with COVID-19?

Tal Zaks — Chief Medical Officer

Yeah. So on the Phase 2, your math is right. We’re looking at these data as we speak. I haven’t seen anything surprising, but I can’t really comment yet. We’re still evaluating that. It’s obviously important data for us to look at. We expect to publish them in due course. You’ll see similar data like the ones that have emerged from the Phase 1 in terms of the endpoint. I think you’ll — we expect to have a much more robust understanding of the reactogenicity and safety profile of the vaccine based on larger numbers.

The interesting thing about the immunogenicity is that it will kind of fill out the curve because it will give us another data point at 50 micrograms. But it’s really interesting to me to see how tight the individuals’ cluster within any dose range. I mean if you look at the spread versus infection, it’s pretty clear that this vaccine is giving us not just the response in everybody, but a fairly consistent one at that. And so we’ll be able to describe that. But I don’t think beyond filling out the curve on the immunogenicity plot at 50 microgram, I think really the main takeaway is going to be a deeper and better understanding of the totality of the safety and reactogenicity profile as it emerges. Did I answer all your questions?

George Farmer — BMO Capital Markets — Analyst

Yeah. I was just wondering if anyone has come down with COVID-19?

Tal Zaks — Chief Medical Officer

Yeah, yeah. I think we may have seen one or two cases. I don’t — I think they were — It’s more cases of finding people who had been positive when the antibody titers came in. So I don’t think yet I’ve seen an active case on the trial, on any trial. I think we’ve seen evidence of prior infection because we didn’t make it an eligibility criteria, we just post-fact them, looked at antibody levels on day one at people who entered. So I think there may be one or two individuals so far in that bucket, but I don’t think that’s really informative for what you’re interested in than have MI, which is the ultimate ability of this vaccine to prevent disease.

George Farmer — BMO Capital Markets — Analyst

Okay. Thanks very much.

Tal Zaks — Chief Medical Officer

Thank you.

Operator

Our next question [Technical Issue] from Alan Carr with Needham & Company. Your line is open.

Alan Carr — Needham — Analyst

Hi. Thanks for taking my question. Just a quick one around manufacturing. You had spoken earlier about having plans to manufacture outside and inside the U.S., can you give any more details around that, around the timing? Is one going to happen later than the other? And relative amount that you expect to be producing in the U.S. versus ex-U.S.? Thanks.

Stephane Bancel — Chief Executive Officer

Yes. So good morning. This is Stephane. So if you go back to the slide where we have a manufacturing program, Slide 24, what you see is the U.S. supply is coming both from a Moderna Technology standpoint, as I said, and the Lonza site in New Hampshire. As you know, we have been making mRNA in Massachusetts plant since July 2018. And when we announced the Lonza deal, we were very specific to see that the first tech transfer was to New Hampshire. And so because of obviously the two nodes of manufacturing capacity of formulated mRNA in the U.S., you will expect the U.S. to be ready first. The Lonza Switzerland facility, the teams are working to make this happen. But because the Moderna Technology Center has been making mRNA for two years now, we have supply for the U.S. market first.

We have not described in detail the split, but we have said that our intent was to be able to make enough product in the U.S. to be able to vaccinate everybody in the U.S. So it kind of gives you a sense as we kind of say that we are able to make 500 million doses with the current plan that we’re working hard in a very specific project to take this effort to billion dose per year. We will at least be able to cover the U.S. population, out of the U.S. if there was enough manpower for U.S. Of course, if we have vaccine made in the U.S. that we are not selling in the U.S. for whatever reason, we’ll of course direct these to countries outside the U.S. who need them.

Alan Carr — Needham — Analyst

Thanks. So that 500 million that you’re referring to on annual basis, is that coming just from the Moderna plus Lonza New Hampshire? Is that including some capacity from Lonza Switzerland too?

Stephane Bancel — Chief Executive Officer

It’s including everything. The numbers we have given, we have not given any split. The numbers were given the base case of 500 million that we know how to do and the up to 1 billion that we are working towards making happen. This is a global number, but I’m just saying to give you a sense, the U.S. capacity will be available first. And we have designed the capacity so that we can supply the U.S. population, out of the U.S. supply chain, if this is required.

Alan Carr — Needham — Analyst

Okay. Thanks for taking my questions, and congratulations on your progress.

Stephane Bancel — Chief Executive Officer

Thank you so much.

Operator

Our next question comes from Mani Foroohar with SVB Leerink. Your line is open.

Mani Foroohar — SVB Leerink — Analyst

Hey, thanks very much for taking my question. Congrats on the data. A couple more nuanced ones. You guys mentioned diving into the data and getting a more nuanced perspective on different patient populations and their response in terms of neutralizing titers. Can you comment on any variability in neutralizing titers that you’ve seen amongst various strains of SARS-CoV-2, perhaps the strain is now becoming more globally dominant in some areas, the RBD d614g strain, Regeneron comment on as well? In terms of — separately in terms of the Phase 3, one of the interesting data that we saw in your Phase 1 published data is that a few of the patients had missed their second dose because of suspected COVID-19. As you’re going to be enrolling the Phase 3, presumably in geographies with high infectivity rates and a very active pandemic environment, how do you think about statistically or in terms of your statistical analysis or in terms of clinical trial operations managing around some number of patients potentially substantially could miss that second dose? And how do you think of that secondary impact on your statistical powering, on any possible triggers for the IDMC to look to expand enrollment if you have an unexpectedly high number of patients who missed that second dose?

Tal Zaks — Chief Medical Officer

Thank you. This is Tal. Let me take them. The first question on strain differences, so as far as we can tell, and I think that’s the emerging science to date and it’s consistent with some of our emerging data as well, these strains are not immunological variance, i.e, they don’t allow somebody who has been sick to know get sick again because they’re going to affected by different strain. And indeed, when you do the in vitro work neutralizing — binding and neutralizing antibodies that recognize the wild-type initial strain team to recognize just as well the various mutations that have been described since then.

These mutations you speak exclusively about the 614 one, it’s outside the receptor binding domain, it’s not predicted to. It’s a single point mutation that’s not predicted to make a big difference. And when you’ve got the full length spike protein, you’re actually you’re generating antibodies against a pretty large diverse set of epitopes that even if one of them got changed, I think we would expect the impact on the vaccine to be de minimis. And so far, I think the preclinical data that people have been describing is consistent with that. We will of course look at that and we — I think we’re in the process of testing some of the Phase 1s here just to ascertain that’s also true in clinic. But scientifically and mechanistically I don’t think it’s a big concern today.

In terms of missed second dose, I think you make a very valid point. We’re having those active discussions with our investigators. I would make sort of three points here. Number one is there is a very careful and explicit monitoring of anybody with symptoms from the moment they step their foot in the trial. And so that includes also rapid diagnosis to swab everybody and make sure that we understand if somebody is getting sick. So we should be able to identify these people, and if you will, the sort of the care package around ensuring a consistent approach to their care should they be sick I think is helpful in that regard.

Number two is still on the safety side of it. There is, as you say, there is a data safety monitoring committee. There are routine and frequent safety calls internally that then escalate to that. That body is able with the separate unblinded statistician to look at the data as it emerges and help us understand both the performance of the trial from the operational elements as well as any safety concerns early on so that we can continue to stay blinded.

Finally as it relates to powering in statistical design, this has been taken into account. So we already account for a certain percentage of dropouts, people not getting to the second dose or people becoming ill before they reach two weeks post the boost to be eligible for that primary endpoint. So the statistical power already accounts for that. That being said, with the support of our collaborators at the NIH both at the level of the data safety monitoring committee and sort of a harmonized oversight group, if we see that that exceeds what we had allotted to in terms of the powering then obviously we’ll have a conversation on whether we need to change the sample size in order to react.

We’re not going to be doing that alone. We’re not going to be doing that based on blinded data. But we put in place the operational mechanisms to ensure that we are able to react in the timely fashion to that.

Operator

Thank you. Our next question comes from Jonathan Miller with Evercore ISI. Your line is open.

Jonathan Miller — Evercore ISI — Analyst

Hey guys. Thanks [Technical Issue] for Jon, if you don’t mind, Jon. My question was two-fold, if I may? First, the PRNT80 titer you guys published in the paper 654. The pseudovirus assay suggest PRNT80 is about two times PRNT50. So is that an accurate analysis? Would it be inaccurate to assume that your PRNT50 on the live virus would have been 1,200 plus, again your PRNT80 654? Second was, for the live virus, your PRNT80 has three patients and there’s values on neutralizing antibody response. But on pseudovirus, two out of those three patients had no neutralizing antibody response. Why is that on the pseudovirus assay? And finally, if you could speak to the significance of lack of CD8 response? Thank you.

Tal Zaks — Chief Medical Officer

Yeah. So I’m just joining [Phonetic], so I don’t forget. Let me start with the end because that’s the easiest. I don’t think there is a lack of CD8 response. I think the CD8 response, there is a response there. It appears low. It was measured at a certain time point that may be suboptimal and I’ve already sort of alluded to what I think is the questionable scientific relevance overall to that response relative to a CD4 Th1 phenotype than a robust antibody response.

Working my way backgrounds, I am not sure what you’re alluding to. There is — these three subjects who had high levels of neutralizing antibodies I believe also had clear evidence of neutralizing antibodies in the pseudoviral. So perhaps I missed something. I’m happy to go back afterwards and double check that and I’ll follow-up with you if I got it wrong. But I believe that you have a consistent level for two of them sort of between the first and second quartile. For the third, it seems to be between the third quartile and fourth quartile, if you look at that.

Finally, your first question about the PRNT50. I think you’re spot on. We expect that if you had tried to calculate PRNT50 here that numerically that should be a little over twice the number that you see. So I would concur with your assessment, that’s just an estimate. I think the relevant point here is what I had alluded to in terms of that which is in the FDA guidance, FDA believes that donor plasma that has neutralizing activity at a titer of 160 or higher is sufficiently good that one could use it to try and treat and prevent the exacerbation of disease in somebody who is already sick.

Now here’s an interesting bit of math for you, since your questions revolve around this math. If you take somebody with a titer of 160 as a donor plasma and you inject it — say you inject the unit or two of that plasma into a recipient, you’ve actually now diluted that titer by five-fold. So the effective neutralization titer that you find yourself in the recipient on top of whatever that recipient may already have that what you hope will actually help ameliorate their disease is now actually an effective titer of 130 to 160, right, because you’ve taken that 160 or higher, you’ve diluted by giving just the unit into the total plasma volume of that recipient.

So if you kind of start with that math and then you go back and say, well, our vaccine is able to elicit in a live viral assay a geometric mean titer that’s at a PRNT80 of 640, and as you say, we may be can get to extrapolate that it should be over 1,200 if we were to look at PRNT50, I think that gives us a good degree of confidence that we’re eliciting a robust immune response.

Jonathan Miller — Evercore ISI — Analyst

Thank you very much for that.

Operator

Thank you. And this concludes the question-and-answer session. I would like to now turn the call back over to Stephane Bancel for closing remarks.

Stephane Bancel — Chief Executive Officer

Well, thank you very much everybody for joining and for all your questions. We look forward to speaking with you at the latest for our Q2 call in early August. Stay safe, and have a nice day. Bye.

Operator

[Operator Closing Remarks]

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