Good morning, and welcome to Moderna's conference call. At this time, all participants are in listen-only mode. Following the formal remarks, we will open the call for your questions. Please be advised that this call is being recorded. At this time, I'd like to turn the call over to Lavina Talukdar, Head of Investor Relations at Moderna. Please proceed.
Thank you, Catherine. Good morning, everyone, and thank you for joining us on today's call to discuss data and updates to our booster strategy against Omicron. You can access the press release issued this morning as well as the slides that we'll be reviewing by going to the investor section of our website. Speaking on today's call is Stephen Hoge, our president. Joining Stephen during the Q&A section is Stéphane Bancel, our Chief Executive Officer, Paul Burton, our Chief Medical Officer, Jacqueline Miller, Senior Vice President and Head of Infectious Disease, and 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 provisions of the Private Securities Litigation Reform Act of 1995.
Please see Slide 2 of the accompanying presentation and the 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. On Slide 3, please see the important indication and safety information for our COVID-19 vaccine, which has been authorized for emergency use as a primary series vaccine and booster vaccine in the United States and in many other countries around the world. I will now turn the call over to Stephen.
Thank you, Lavina, and good morning and good afternoon, everyone. On Slide 4, I'd like to remind you of our strategy on the Omicron variant and present some of the recent data we have received on the performance of our various booster strategies against this emerging variant of concern. First, Moderna has had a three-part strategy for addressing all emerging variants of concern since the early part of 2021. Those three elements are first testing the prototype vaccine, mRNA-1273, both at the authorized booster dose of 50 µg and at a higher dose. Multi-valent booster candidates that incorporate mutations from previous variant of concerns, again, both at 50 and 100 µg dose levels. Third, we advanced variants of concern-specific booster candidates to address emerging threats, including against Delta and Omicron.
Now, today we're sharing an update on some preliminary data from the NIH VRC Duke pseudovirus neutralization assays or pVNT ID50. It confirms robust Omicron neutralization activity of all the current booster candidates that we've tested. The authorized booster, which is 50 µg of mRNA-1273, increased neutralizing geometric mean titers to 850, which is an approximately 37-fold boost over pre-boost levels. The higher dose of mRNA-1273 increased to 228, which is approximately 83-fold higher than pre-boost levels. The multivalent candidates demonstrated neutralizing antibody activities that were similar to the high levels of both the 50 and 100 µg. We will speak more about this towards the end, but based on the strong boosting of mRNA-1273, Moderna will focus its immediate efforts around Omicron on advancing the prototype vaccine, mRNA-1273.
We're going to continue to advance an Omicron-specific booster into clinical trials in early 2022. We'll continue to assess the potential of the multi-valent candidates for both durability and breadth of variant concern over the months ahead. I'd like to now move to Slide 5 and some of the emerging clinical data that we have. First, on Slide 5, I wanna present a comparison of our most advanced booster candidates in the validated assays against the D614G viral archetype, the Beta variant of concern, and the Delta variant of concern. On this slide, you'll see the archetype booster, the archetype titers in the first row, the Beta titers in the second, and the Delta titers in yellow at the bottom.
I'm comparing here on the far left primary vaccination, the contribution of pre-dose after dose one and dose two in the three columns, as well as two different booster candidates for which we have this full set of data. mRNA-1273 at the 50 µg and 100 µg level. On the far right, the multi-valent booster candidate, mRNA-1273.211, which includes both the Beta variant and mRNA-1273, again at both 50 µg and 100 µg dose levels. As you can see, a booster dose of mRNA-1273 in the top row significantly increases the neutralizing titers and achieves neutralizing GMTs one month after boost that are higher than the GMT seen one month after primary series, reaching geometric mean titers of 1,951 as compared to the 1,131 after primary vaccination series. This is the basis of the authorization of the mRNA-1273 booster at 50 µg.
Now a higher dose, 100 µg of mRNA-1273, does lead to numerically higher geometric mean titers, and that is true for both the mRNA-1273 booster and the multivalent booster to the right. The same is also true that a higher dose will lead to higher neutralizing titers when you look at the two assays involving variants of concern. The Beta variant for the multivalent booster, we have that data now, and you'll see numerically higher geometric mean titers with the higher dose. Similarly, for mRNA-1273 in the bottom in yellow, you'll see that a higher dose 100 µg does lead to higher neutralizing titers against the Delta variant of concern as well.
Overall, the multivalent candidate, as you'll see, achieves similar geometric mean neutralizing titers against the D614G archetype virus in the top row, and further testing is already underway against a panel of variant concerns to understand whether there's a difference in performance against these variants. Now moving to Slide 6. Here's the preliminary data now adding to that more substantial data we have on Slide 5 on the Omicron assays. Now, briefly a word about the assays. These are the National Institutes of Health Vaccine Research Center assays established at Duke Medical Center and are pseudovirus neutralization titer assays based on ID50 standard. These remain research assays, and they have not yet been clinically validated, but they are run in the same labs and following the same protocols as the validated assays I presented on the previous slide.
Here I'm presenting the mRNA-1273 data at both 50 µg and 100 µg. You'll note in black we've included for the samples that were included in this test the D614G validated assay results as well as in red the Omicron neutralizing titers. On the left under each group, you'll see the booster day 1 pre-boost titers, and on the right you see the booster day 29 or one month after booster neutralizing titers. First, drawing your attention to the 50 µg dose level. The 50 µg of mRNA-1273 led to a 37-fold boost of Omicron-specific neutralizing titers in these assays. 850 was the geometric mean titer one month after boost. This still represents a 2.9-fold lower titer against Omicron than against the archetype virus D614G, but nonetheless is a significantly higher result in GMT.
On the right you see the 100 µg dose titers, and again, you'll see an 83-fold boost after 100 µg of neutralizing titers against Omicron to levels of 2,228. Consistent with the 50 µg, we still see a 3-fold lower titer level against Omicron than D614G. Now moving to the multivalent booster candidates on Slide 7. Again, the same format presented here and two different multivalent booster candidates are illustrated. On the left you have the mRNA-1273.211 multivalent which includes the Beta variant and the Wuhan-based mRNA-1273 sequence. On the right you see mRNA-1273.213 which includes Beta and Delta. We have 50 µg, 100 µg data for the 211, and 100 µg from early data for 213.
Now again, as you saw before, there's a substantial boost at the 50 µg dose level of mRNA-1273.211, a 39-fold boost in Omicron titers, and a slightly numerically lower difference in the level of Omicron titers versus D614G, only 2.2-fold lower relative to the 3-fold lower that we saw with mRNA-1273. 100 µg shows a consistent result, which is higher levels of boosting, 141-fold in this case, of Omicron titers. And a consistent result as well in the approximately 2.3-fold lower titers for Omicron versus D614G. We only have partial data for the 213 candidate at 100 µg, which shows a generally consistent 77-fold boost of Omicron titers after 100 µg of mRNA-1273.213.
We also have announced some data on safety from the 100-µg dose level of mRNA-1273, which is broadly representative of what we've been seeing across our booster candidates. That data is presented on Slide 8. First looking to the solicited local adverse reactions through day seven, we're comparing here the mRNA-1273 primary series in labeled P301 after dose two against a 50-µg booster previously reported as the authorized dose, and the new 100-µg booster dose of mRNA-1273. On the left you see pain, and then erythema, swelling, and axillary swelling or tenderness on the right. Grade 1, Grade 2, and Grade 3 events are reported in the shaded colors. There were no Grade 4 events in these studies.
Overall, there's a consistent profile across these different nature and frequency of events with a trend towards increased frequency of axillary swelling and tenderness, mostly mild or Grade 1, for the 100 µg booster dose relative to the 50 µg dose in primary series on the right. There's a general trend towards more frequent adverse reactions in the 100 µg dose, as you'll note, as opposed to the 50 µg booster dose, but they are generally consistent with the 2 with primary series dose 2. On Slide 9, we have the solicited systemic adverse reactions through day 7, again with a similar layout and presentation of the post-dose 2 from phase III, 50 µg boost and post 100 µg results.
As you'll see on the chart, systemic adverse reactions are generally consistent with the dose two of the primary series, and there is a generally higher frequency of adverse reactions reported for the 100 µg booster as opposed to the 50 µg booster. On Slide 10, I'll briefly summarize our emerging perspective across these data on Omicron booster strategies. First, the mRNA-1273 results in a significant boosting of Omicron neutralizing titers, both at the 50 µg authorized dose and at the 100 µg higher dose level, suggesting good potential cross-protection from the current vaccine against the Omicron variant concern. Conversely, given the strong boosting we've seen with mRNA-1273 to 37- 80 fold boosting at the two different dose levels, the opportunity for significant additional benefit against Omicron from multivalent boosters is consequently diminished, particularly in the short follow-up tested to date, which is day 26.
Moderna will therefore focus its near-term efforts on the mRNA-1273 booster as the first line of defense against Omicron. The higher dose of mRNA-1273, 100 µg versus 50 µg, did result in dose-dependent increases in Omicron neutralizing titers, which is consistent with what has been seen and reported previously against the ancestral archetype virus D614G and both prior variants of concern, Beta and Delta. Moderna is gonna continue to evaluate an Omicron-specific booster in early 2022, given the concerning immune escape features demonstrated by this variant of concern as part of a more midterm strategy to address the ongoing pandemic. With that, I'd like to turn it over back to the operator to address any questions.
Thank you. If you would like to ask a question, press the star, then the one key on your touchtone telephone. To withdraw your question, press the pound key. Our first question comes from Salveen Richter with Goldman Sachs. Your line is open.
Hey, good morning, and thank you for taking our questions. This is Elizabeth on for Salveen. Just given your strategy and the emerging data that we're seeing play out, you know, what does this mean for the prevention of infections and against severe disease and hospitalization? Thank you.
Thank you for the question. I think, first of all, the level of neutralizing titers in these assays has not yet been correlated with clinical benefit, because these are still research assays, and so we need that important caveat. However, we do know from the correlative risk work and prior published epidemiologic studies that the mRNA vaccine and the high neutralizing titers we have seen in it have generally predicted or correlated with benefit against symptomatic infection, even asymptomatic infections, and certainly severe disease and death. Seeing that a third dose of the mRNA-1273 vaccine at the authorized dose level can achieve these high numerical titers is quite reassuring that we'll be able to rely on this vaccine to address the near-term surge of Omicron cases.
Ultimately, we'll depend upon emerging public health data to confirm that effectiveness in the real world.
Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. Your line is open.
Thanks for taking the question. This is Charlie Young for Matthew. So I guess my first question is, you know, whether you have tested the sera at a time point beyond 29 days, and you know, you have any sense in terms of the durability of the boost against Omicron, and or if the titers may decay faster than, you know, against the Omicron strain. Thank you.
Yeah, great questions. The booster studies, we are collecting long-term samples. One of the things that we're gonna look at for sure is whether or not there's a difference in durability as we look at the different booster candidates. You can, in particular, imagine that the multivalent boosters, as you look at six months or 12 months, might start to show a difference in the type of affinity maturation, type of durability, therefore, you'd see against variants of concern. We do not have that data at this time, though. We only have right now through day 29, which is a relatively short window.
I think it is reassuring, you know, per the prior question, if you look at the day 29 neutralizing titers that we see, for instance, you know, post a 50 µg boost, against Omicron, numerically, they're coming in at about 850. That is consistent numerically with the types of neutralizing titers that we saw against the Delta variant of concern, and I presented on the slides today, approximately 800. That is encouraging because we do know that the mRNA-1273 vaccine and booster has held up relatively well in terms of effectiveness, against Delta, even in the face of that, you know, very infectious variant of concern.
I think we're cautiously optimistic given the data presented here that, if additional labs and additional assays confirm these magnitudes, which should happen over the coming week or two, that the authorized booster dose of 50 µg should provide good protection, we would hope, against the Omicron variant of concern, because these levels have been correlated or have been consistent with that kind of protection against other variants of concern.
I guess just a quick follow on that. How about in terms of the decaying speed, whether there's any thought on that front? Thank you.
Oh, great. Thank you for reminding me. Generally we have seen, and previously presented data across all the variants we've tested through about six months. The thing we have generally seen is after primary series, the decay curves are not significantly different between variants of concern. Now, put another way, the slope of the decay is the same over time. It is really the altitude of neutralizing titers, the height of neutralizing titers you get to immediately after vaccination that determines how long you're gonna be protected. That is true post dose two. We do not have data post dose three yet, but there's reason to believe that it may even do slightly better. The slope may be slightly different after dose three.
What is clear is that, you know, when you have a substantial decrease in neutralizing titers, you generally will fall below what we think might be a protective threshold more quickly, you know, perhaps over months instead of over a more desirable year. We just don't know at this level what to expect though, because post dose three, we still don't have a view of those slopes. I do think it's encouraging that the level of neutralizing titers we're seeing here today in the pseudovirus neutralization assay conducted at NIH Duke is sufficiently high that we think we're comfortably above what for other variants of concern was a correlative breakthrough risk.
Now the durability of that, I think it's too early to speculate on how long it'll last, but again, I think the data, the magnitude of boosting we're seeing here is quite reassuring.
Great. Thanks so much.
Thank you. Our next question comes from Michael Yee with Jefferies. Your line is open.
Hi. Good morning. We had maybe a two-part question. Following along some of the data you just presented and some of the questions you just answered, it seems that 100 µg boost is significantly higher than the 50 µg boost, and so logically perhaps that conveys more protection but longer protection for the decay, which was just asked about. My question is first, would there ever be any thoughts around that as a boost? Related to that, don't you just think that there would be significant decay over six, eight, nine months like we've been seeing previously, and therefore we would just need another boost next year for whatever variant that would be next year? That would be perhaps your strategy requirement for annual boosting.
Maybe just put some of those together and make a comment about the thoughts for annual boosting. Thank you.
Great. Thank you for the question, Michael. Both very astute. First on the 100 µg dose level, we are encouraged that you do see, you know, higher titers. You know, 2000 is actually, if that is validated in other assays, is a quite high titer level that we would hope would provide significant protection. However, the decision of whether to deploy 100 µg or a higher dose is really one for public health agencies at this point. We are just providing the data, and obviously we'll share it with everybody so that they can make that determination.
As the vaccine is currently approved in many markets authorized under EUA in the United States, it is in many places where it is approved up to now, recommending bodies to determine whether or not a higher dose is appropriate for high-risk individuals. You could imagine that those that are at high risk of exposure, for instance, healthcare workers or those that are at high risk of severe disease, even from Omicron, even if it tends to hopefully be more mild than Delta, that it would make sense to provide a higher level of neutralizing protection. Again, that is a decision principally now for public health officials. The authorized dose that we have today is the 50 µg of mRNA-1273. Of course we'll be answering questions on that and providing them.
Now as far as the question of decay and does a higher dose leave you with longer protection? Again, we still don't really know the slope, but it is true that we expect that with this coronavirus, SARS-CoV-2, like you see really endemic coronaviruses and other respiratory viruses, we do expect that there's gonna be waning neutralizing protection over time. As a result of that and what we think will be a continued series of evolutions of variants from through this variant from the SARS-CoV-2 virus, we do expect that there will be a need in the future for seasonal boosting. Principally that will be because as we all come in northern latitudes in the winter months indoors, respiratory viruses, not just SARS-CoV-2, have an opportunity to repeatedly infect people.
They do over our lifetimes repeatedly infect, and they can have severe consequences in particular in older adults and immune-compromised. For that reason, you know, we often boost with respiratory vaccines like influenza annually, and we think a similar picture will likely emerge over time with SARS-CoV-2. The question is, you know, will that frequency be seasonally every year? We think probably yes. The other question is, you know, who will benefit most from that booster? We think it is most likely to be those that are at highest risk of severe complications if they develop a SARS-CoV-2 infection. Ultimately it will fall to recommending bodies, including, you know, groups like the CDC, to decide what is recommended broadly for use.
As a sponsor, Moderna is focused on developing that data following the neutralizing titers now post dose three out, as you said, six months and 12 months to determine when they do fall to a level that we think would be a concern and will justify further boosting. We are preparing for a seasonal booster market that would protect those at least at high risk of severe COVID-19.
Yep. Thank you.
Thank you. Our next question comes from Gena Wang with Barclays. Your line is open.
Thank you for taking my questions. I have three. Maybe the first one, you know, when we look at the Pfizer, they also using pseudovirus, and when we look at the GMT numbers, what they are showing is a 398, and then Omicron is at 154, one month after third dose. Can you first maybe, you know, give us a little bit more color regarding your pseudovirus testing, if we try to do some comparison GMT level the flu number, how should we think about your number versus their number? The second question is, do you have the data for dose level three, versus dose level two, at a similar timeframe, post the dose?
Then lastly, you know, when we look at the Omicron compared to wild type, maybe that's more like a better comparison. Like Michael Yee mentioned, you know, we also saw that 100 µg when we look at the Omicron level, it's 2,115. That almost similar or even higher than the 50 µg 1,799. I assume you've done all those experiments at the same time, so it could be very good, you know, comparability there. Wouldn't that suggest that 100 µg at the third dose, that boosting the protection should be equivalent to 50 µg with the wild type against the Omicron?
Thank you, Gena, for the three questions. All excellent. Let me try and work through them, and please, catch me if I get anything wrong, or I miss anything. First comparison of the GMTs to other vaccines, specifically the Pfizer vaccine in your question. The Pfizer-BioNTech data is also a pseudovirus neutralization assay data, but we do not know very much or anything really about that assay. Ours is run in the same lab, the NIH VRC Duke lab, that is also running our validated clinical assays against the other variants of concern in D614G. We do know more about that and do believe that at least methodologically it is very consistent with our other data.
I do not think it's easy to directly compare because these are ultimately different assays. I would make the comment that there is, you know, broad previously published data showing that the higher dose of Moderna's vaccine over the Pfizer-BioNTech vaccine does lead to higher neutralizing titers, whether in a primary series or in a booster context. You know, for instance, the recently published COV-BOOST study out of the U.K. shows, you know, higher neutralizing titers, including against variants of concern and higher T-cells as well from the Moderna booster.
The NIH Mix and Match study, which was presented, you know, a couple of months ago and is a preprint online, again, in head to head assays, what you see is higher neutralizing titers or several fold higher neutralizing titers usually, for Moderna, both pre and post-boost. It would be entirely unsurprising that what has been true for the primary vaccination and booster series for archetype virus and for prior variants of concern including Beta and Delta when you do head to head, that it would also, you know, be true. You would also expect it to be true for Omicron.
It's possible that what we will ultimately see when head to head data comes out is that with Omicron as with other variants of concern, mRNA-1273 is seeing higher neutralizing titer data. For now, I just don't feel I can make a direct comparison between their assays and ours. You really need to wait till they're tested with the same results, and same study, and same assays, I should say. Second part of your question or second question, which is do we have data for dose two versus dose three? Some of that data, we do, and we are actually preparing a preprint that will include all of this data and posting online. As you can imagine, there's much more data overall.
In general, though, some of that data has already been presented publicly, and so there was even Dr. Fauci at a briefing presented some data out of VRC on what things look like post-dose two in a research version of this assay. It is generally consistent with those results, and so there's you know post-dose two, you do see some neutralizing titers against Omicron, but they are substantially lower than against the D614G comparator neutralizing titers. Post-boost, you see that substantially closes the gap down to this roughly 3-fold difference.
In the preprint, we will put that data out there, but I'll just tell you that it is broadly consistent with what has been previously reported and presented even last week by Dr. Fauci from the NIH's data. In terms of Omicron versus wild type, and in particular, what do we think about the neutralizing titers of a 100 µg? I think you point to the key question, which is that, you know, it is reasonably clear that a 100 µg dose leads to higher neutralizing titers against Omicron.
That the levels, at least numerically, start to exceed the levels that you see against ancestral variants at a 50 µg booster dose, which you would think provides a good degree of confidence that a 100 µg will perform well against Omicron, perhaps as well or even better than we saw against other variants of concern. I think the big challenge in that conclusion is that we still are learning so much about Omicron that, you know, we wanna be cautious about drawing too many parallels back to what we saw with Beta and Delta. They are also variants of concern for sure, and the Delta data is perhaps more predictive.
It is just a conclusion that, ultimately we as a company do not have hard data on, and so we need to be cautious about the conclusions we draw. What we can say for sure is that the neutralizing titers are higher, that the safety and tolerability profile looks acceptable, and that it would be appropriate, we think, for public health authorities to consider that. I would also just say the other part of that statement, which is it is also clear that a 50 µg dose of mRNA-1273 gets you to quite reasonable, quite respectable titers. It's 850. Titers that are numerically the same as what we saw against Delta after a 50 µg dose of mRNA-1273 as a booster as well.
For many people, it may not actually be necessary that you push titers even higher, maybe for all. Therefore, I think it really is a judgment that public health officials need to make about the relative risk benefit for different populations. Because the data we present today on the authorized dose 50 µg of mRNA-1273 really looks quite encouraging as well. Could higher be better? Absolutely. Do we have data on that today that allows us to make a conclusive recommendation? No. Do we recommend public officials have a look at that? Of course. I know they are.
Thank you.
Thank you. Our next question comes from Simon Baker with Redburn. Your line is open.
Great. Thank you for taking my questions. Two, if I may, please. Firstly, late last week, WHO published some preliminary data on T-cell cross-reactivity for the Pfizer vaccine, which showed that comparing Omicron with ancestral CD8 response was pretty similar, slight decline in CD4 response. I just wonder if you have any data at this admittedly early stage for mRNA- 1273. A broader question, I just wonder if you could update us, given the very fast-moving situation we've been in the last few weeks on the order book and capacity situation for 2022. Thanks so much.
Of course. I'll leave the second question to Stéphane. But the first question, there has also been presentations from a number of labs of the cross-reactivity and T-cell for mRNA-1273 as well as the Pfizer vaccine and others. Generally, you would expect those to be consistent. I will note that, if you look at the COV-BOOST study that was published out of the U.K., Moderna has had numerically higher T-cell and cellular responses against the Delta, Beta and the ancestral virus relative to those published, but directionally quite similar. You would expect that there's really not gonna be a big difference between the vaccines in this.
The reason I would say that is that at the end of the day, we are expressing, you know, largely the same spike proteins, in fact, identical in many cases between the different, first wave vaccines that have been deployed, including between the Pfizer-BioNTech vaccine ourselves. In fact, if you look at epitopes, and there's been quite substantial publication on this, and presentation on this, if you look at the T-cell epitopes, they are largely preserved, almost 90%, consistent between the, ancestral vaccine antigen, which is the base of the vaccine and the new Omicron spike protein. For that reason, you absolutely do expect T-cell responses to be, quite reasonable and robust. I think that has been what the early data published by others or presented by others has started to show.
If you look at what we're seeing here in terms of neutralizing titers, the data we do have, the day 29 response that you're looking at here, it's quite rapid responses, and these titers are getting to quite remarkable levels. Again, we're talking about, you know, 1,000-2,000 or 800-2,000 fold. That kind of rapid boost ability really does depend on, cell health, and we would say T-cell health, and does, we think, generally correlate with broad cellular immunity responses. I think you are seeing indirect evidence in the data we're presenting today. I think some other, academic labs and others have presented some emerging direct evidence.
I think, mechanistically, you would absolutely expect, given a degree of sequence preservation that's still quite high for T-cell epitopes, that there's really gonna be reasonable T-cell responses against Omicron. Now, Stéphane, do you wanna take the second question?
Sure. Good morning. We are providing no update today on the commercial sales for 2022. I would just note that as I'm sure you noticed, we announced recently a new partnership with the U.K. for products for 2022, as well as a firm order for 2023. We are having quite a number of discussions in the last couple of weeks with the rise of Omicron with countries around the world, and it was before this data was presented this morning. As you can imagine, we're gonna be quite busy in the coming days and weeks reaching back again to all the countries and partners we have to make sure that this data understood, which as you saw from Stephen's description, are very encouraging and very strong.
On the capacity, we confirm that we have, you know, the capacity to deploy 2 billion-3 billion doses in 2022. As we've said in the past, the swing between 2 and 3 will depend on the product mix between 50 µg doses and 100 µg doses. We'll provide more clarity in the next quarterly release.
Great. Thank you very much.
Thank you. Our next question comes from Tyler Van Buren with Cowen. Your line is open.
Hey, guys. Good morning. Thanks for taking the question. Can you talk about the potential timeline to get an approval of a 100 µg booster dose for the entire population given this data? The second question is, if there wasn't a large difference in GMTs between the multivalent booster candidates and mRNA-1273, then why do you think the Omicron specific vaccine heading towards the clinic will be significantly different?
Great. Thank you for both questions. First on timing for approval. We are not at present planning to file for amendment of the authorizations or approvals to include the 100-µg for a booster. I'll note that in many places it is 100 µg, well, in all places, 100 µg is approved or authorized as a primary series. We have the 50-µg booster. In many places those approvals, full approvals would allow public health authorities, for instance, recommending bodies, to recommend the use of 100 µg if they wanted to for high-risk populations.
Determination of whether some populations, you know, at high risk of severe disease or high risk of infection would benefit is one that we don't believe currently we have the data to make. We are providing this data to public health authorities so that they can make the best decisions in the face of the pandemic they can. Ultimately we will defer to recommending bodies, you know, such as the CDC or other or their analogs in other countries to determine if they wanna take any action with the 100 µg dose level. I will, as a final comment, note that 100 µg as a third dose is authorized for immunocompromised populations as a part of their completion of their primary series.
That the 100 µg dose here is the same dose that's used in the primary series, the first two-dose series. It's in the same presentation in vial. We have a 50 µg and a 100 µg dose in the same vial, already, in market. All that's different between the two dose levels is the volume of injection. From a logistical and operational perspective, we hope that the option is there. Again, it is now for public health officials to decide if there's any need or desire to use it. As I said a moment ago, the data that we show here today on 50 µg is really quite encouraging. It may be that the benefit isn't worth it.
We again will defer to public health officials to make that decision now. Now on the question of multivalent and Omicron, it's a great one scientifically. I think first of all, the positive surprise here I would point to is how strongly mRNA-1273 did. So the prototype vaccine against Omicron at a 50 µg boost level as well as the 100 µg being higher. We think that augurs well for the ability to cross-protect based on that variant of concern, cross-protect with the prototype. It does in some ways diminish the opportunity for additional benefit provided by the multivalent. What you see with the multivalent is they do quite respectable.
I think we would have all been very pleased to be looking at, you know, titers of a couple thousand a week ago. It is only because mRNA- 1273 continues to do quite well at 100 µg or 50 µg that that seems less necessary today. I think the fact that that gap isn't able to arise at day 29 sort of fits the picture immunologically. If you think about it, if mRNA- 1273 is able to drive this really, you know, this nice affinity maturation, this strong boosting neutralizing titers again after a third dose against Omicron, that picture would suggest that, you know, really that's a good, you know, inherent response of a memory response that already exists and is only slightly refined by day 29.
When you come back in with a multivalent booster, you're gonna basically see most of the immune response is that same, you know, anamnestic recall response from the original vaccination. That's I think why these numbers start to look so similar. It's important to also though say that that's true through day 29. What we do not know is what does that look like six months out? Because in the case of the multivalent or an Omicron specific booster, which is really your question, you may see different affinity maturation. Again, you're gonna present a slightly different antigen and, you know, maybe six months out, maybe twelve months out, you will see a broader, more diverse immune response or repertoire antibody response that's developed against that new antigen.
That may also, you know, change the affinity maturation and ultimately therefore the potential for durability or future boostability in that immune response. Now those are all speculative statements. That's a hypothetical of what we might see over the next six months. That's why we emphasize today that we think we need to continue to follow that multivalent platform. It is not needed to address the current Omicron surge. We feel very confident in mRNA-1273. We believe we're gonna be living with this virus and its strains and variants for forever at this point. We need to continue to think about the best ways to provide the broadest and most durable immune response against future variants of concern as well as those that are currently circulating.
It's in that context that we think it's appropriate to study an Omicron specific booster. Because it is quite possible, given what Omicron has shown us in its ability to escape pre-existing immunity, that the best way to achieve durable immunity to Omicron or any of its future progeny, will be to boost with Omicron or add an Omicron booster to a multivalent platform to try and continue to mature the immune response in individuals and across the population. It's for that reason that we're gonna test forward. We'll need to look at that data. It is also possible that Omicron continues to mutate and evolve.
We've seen this virus surprise us now an unfortunately large number of times in just the first year or second year of this pandemic. We do think it's, you know, the better part of valor. It's prudent to advance an Omicron-specific booster, given what the virus has shown us of this potential for immune escape. Hopefully that answers the question.
Yeah, very interesting. Thanks for the additional color.
Thank you. Our next question comes from Geoff Meacham with Bank of America. Your line is open.
Hi, this is Alex calling in for Geoff Meacham. Thank you for taking our call, our question. We just really wanted to understand how you're thinking about these variant boosters being approved, and can they keep pace with these variants as they arrive? Was there a regulatory bottleneck that you guys are encountering so far? Thank you.
I'll take a stab at this, and maybe Jackie can, you know, fill in. First of all, I think regulators are responding as fast as anybody could, as fast as we as a sponsor or other companies are to a very fast-moving picture. I mean, you know, let's just recall that a month ago, we weren't even talking about Omicron. Now we've, you know, got data and we're evaluating it, and we're trying to make a decision forward. It would be unfair to say that there's absolutely inaccurate, unfair to say that there's a regulatory bottleneck around these sorts of things.
I think the question for all sponsors, manufacturers, and regulators to engage in over the coming months and year is, given the virus is gonna continue to evolve, how do we wanna think about strain updates going forward. Now, there was very clear guidance on that from the early part of 2021. You know, we have heard global regulators start to point to the fact that when we start to get very comfortable with the mRNA vaccines, we have now a broad set of data against many different variants of concern, and we've provided increasing data across both multivalent and monovalent boosters that gives us some confidence that we can make, hopefully, these changes without needing to fully study them in the clinic.
That starts to approach a process or procedure that might look more like flu, where we do update vaccines every year, and do not do the full clinical programs around them. It's early days for those conversations. Again, the data has really emerged from manufacturers over the last few months. You know, we believe at Moderna that over time that will be a viable strategy to make sure that we can more rapidly respond to these variants of concern. In the case of, you know, right now, Omicron, like Delta before it, really can be addressed by the prototype vaccine mRNA-1273. You know, I don't think that there has been a need yet to provide an urgent strain update.
If you look at the, you know, operational challenges around that urgent or emergent strain update, you know, for instance, rolling out an Omicron booster, it would be quite substantial and something you'd only wanna do if it was absolutely necessary and if you know, didn't see the types of neutralizing protection that we've been seeing in these early assays from the prototype vaccine. Something that we don't think is necessary today emergently. You know, as you look forward as the, you know, prior question, it makes some sense that we're gonna continue to provide sequence updates, strain updates, try to broaden the immunity.
As we do that over time, we'll wanna develop a flexible regulatory strategy that, you know, aligned with global regulators that allows them to comfortably review those but ultimately doesn't maybe involve the same level of testing, and starts to look more and more like seasonal flu.
Thank you so much.
Thank you. Our next question comes from Joseph Stringer with Needham & Company. Your line is open.
Hi. Good morning, everyone. Thanks for taking our questions. Just a quick high-level question from us. You know, given the emerging data on Omicron here, how do you understand that, you know, we'll involve discussion with regulators and such going forward, but just in general, how do you think this recent data will impact sort of the sentiment on boosters in general, both from clinicians and sort of a public sentiment perspective? Thank you.
may defer to Paul. Do you wanna talk about your perspective on that and what you're hearing?
Thanks, Stephen. Thank you, Joseph. Look, you know, yesterday marked the one-year anniversary of the authorization of the Moderna vaccine. Vaccines as a whole, we know, have prevented 1 million deaths and 10 million hospitalizations. The clear message around the world now, Omicron has brought this home, you know, more significantly than we had ever imagined, is if you have not been vaccinated, get vaccinated. If you've been vaccinated, now is the time to get boosted. There's never been a better time. I think, Joseph, that sentiment is widely held. I think also the, you know, exceptional safety and efficacy of the Moderna vaccine and the vaccines in general, you know, think back to when the pandemic started, we had nothing, and now we have great vaccines.
The exceptional vaccine from Moderna, the efficacy it provides, you know, is really remarkable. I think there's definitely been an uptick, probably driven in large part by this latest fear and the surge of Omicron to get vaccinated again and to get boosted. I think, you know, we're definitely seeing that around the world.
Thank you. Our last question comes from Mani Foroohar with SVB Leerink. Your line is open.
Hi, good morning. This is Rick on the line for Mani. Thanks for taking our questions. First, I was curious as to how the continued emergence of SARS-CoV-2 variants, and in particular, the speed at which they're arising, how that's influencing the thinking around the selection of a COVID vaccine construct for the pan-respiratory vaccine strategy? Secondly, just one more question on the topic of longevity of the antibody titer and speed of decay here against Omicron. Could you maybe go into a little bit more detail about the plans going forward for following this cohort of individuals from the boost study, how often you plan to assess the neutralizing titers against Omicron and, the timing for when we could see an updated data set?
Yeah, great questions both. Maybe I'll take the second one first. We have been following these booster strategies over time for quite, you know, for quite some time here. You'll know that the mRNA-1273 50 µg booster cohort, that is the authorized dose, those folks were actually boosted almost nine months ago now, in Q2 of last year, so six-nine months ago. Very shortly here, we will have the six-month samples, which will start to give us a sense of how the prototype vaccine is doing in terms of, you know, longevity against Omicron out to six months, which is one of the benefits of those studies and having, you know, conducted them and got them up and running earlier this year.
Some of the other variant booster, or sorry, multivalent boosters, as well as the 100 µg dose data sort of fills in, you know, in the interim over the course of those folks were boosted over the course of the summer, and so it's a little bit further out, maybe into early spring next year. We will provide updates as we get that data. In general, one of the challenges we have is that we, you know, obviously get these samples and we have something like Omicron happen, and we reprioritize work to make sure we produce this Omicron data.
I think the next update that we would wanna do, particularly on durability, would involve first wanting to get more experience with the Omicron assays, seeing as it compares to other assays out there, because those are still some questions that we face around this today, and then testing a higher number of samples so that we can have an even higher degree of confidence in terms of the performance of this. I don't wanna guide yet on what that timing will be, but I would expect in the early part of 2022 we would be able to look at least at the archetype, so the 50 µg of the authorized mRNA-1273, and then sometime a little bit after that, we might start to see the other booster data.
I think it is that six-month, you know, data for some of the multivalent candidates that might start to provide some understanding of whether or not expanding immunologic breadth here is of any value. The first part of the question is around the antigen selection. I think we're actively looking at whether or not there is an opportunity to design an even better antigen internally in the research space, because over time, we start to see the evolution of the virus for sure. Maybe there are gonna be opportunities to design a superior antigen or an antigen that provides broad protection against future variants of concern. That is something we're gonna evaluate.
For now, the thing that we believe provides that indirectly is a multivalent approach. We currently have multivalent candidates in the SARS-CoV-2 space, in the COVID space, of two different antigens that we are studying, as I said, in these clinical studies to understand is it helping us broaden that immunity, and we'll test over the six-month time horizon whether that actually is leading to any difference in terms of the durability or in terms of the performance against a full panel of variants of concern. Again, data that we'll be developing in the early part of next year. There's no reason we'd have to stop at two.
We obviously have the quadrivalent flu, and we're taking that quadrivalent to the hexavalent flu, and we have in our phase III CMV study, six mRNAs in that. It's quite reasonable for us to contemplate expanding beyond that. The question is just how many candidates do you add, how many antigens do you add to multivalent? Ultimately, that'll need to be guided by the emerging data on the performance of these initial bivalent vaccines. If what we find is a bivalent looks like it does really well, then maybe you don't need to go to a quadrivalent.
If you see a bivalent leaves a gap, somewhere in the, against emerging variants of concern across the panel or over time, then you could decide to add a third or a fourth, antigen, which might get you a trivalent or quadrivalent, COVID booster. That is data that really matters as we look towards the endemic market, because as we look towards that endemic market, we will think you'll wanna provide the broadest, neutralizing, protection and boosting as possible, to protect the largest number of people for the longest duration possible.
We're studying it both in the research space and in the clinical space, and I think as soon as we have data that helps clarify where we're heading in terms of that broad protection and possible multivalent candidates for seasonal boosting, we will certainly talk to you all about it.
Great. Appreciate all the detail here.
Thank you. There are no further questions in the queue. I'd like to turn the call back to Stephen Hoge for closing remarks.
Great. Well, thank you, everyone. I think I really appreciate the questions. I hope the data that we shared today helps reassure folks that the current boosters we have, mRNA-1273 specifically, can achieve really quite remarkable neutralizing titers, even at the 50 µg dose, and does present an interesting question about the potential of a 100 µg dose, for some high-risk populations. I would just emphasize the messaging that Paul said a moment ago, which is we believe all data we have suggests that the mRNA-1273 vaccine is highly effective in the real world, and will have benefit against the Omicron variant of concern, and we would, you know, we'll be providing this data to public health officials, to help reemphasize the benefit of vaccination and of boosting, with the mRNA-1273 vaccine.
With that, thank you all. Please stay safe, and have a happy New Year.
This concludes today's conference call. Thank you for participating, and you may now disconnect.