Good morning. My name is Kevin and welcome to Moderna’s Fourth Quarter 2022 Earnings Call. [Operator Instructions] Please be advised 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, Kevin. Good morning, everyone and thank you for joining us on today’s call to discuss Moderna’s fourth quarter and full year 2022 financial results and business update. You can access the press release issued this morning as well as the slides that we will be reviewing by going to the Investors section of our website. On today’s call are Stephane Bancel, our Chief Executive Officer; Stephen Hoge, our President; Arpa Garay, our Chief Commercial Officer; and Jamey Mock, 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 our SEC filings for important risk factors that could cause our actual performance or results to differ materially from those expressed or implied in these forward-looking statements. With that, I will now turn the call over to Stephane.

Thank you, Lavina. Good morning or good afternoon everyone. Welcome to our Q4 2022 conference call. Today, I will start with a quick business review of 2022. Stephen will then review our clinical programs before Arpa gives an update on our commercial progress and plans. Jamey will then present our financial results and I will come back to share some posts on where we are heading. We are pleased to report today revenues of $19.3 billion for fiscal year 2022, GAAP net income of $8.4 billion, and GAAP diluted earnings per share of $20.12, cash and investment balances of $18.2 billion at the end of the year. We continued our disciplined capital allocation policy, reinvesting first in our company. In 2022, we invested $3.3 billion in R&D, our highest level of R&D investments ever. We invested $1.1 billion in SG&A and $400 million in capital investments. We made investments in Metagenomi for access to new gene editing enzymes and Carisma in oncology. We announced an investment in CytomX and the acquisition of OriCiro in Japan to continue to streamline our manufacturing processes. And just yesterday, we announced the collaboration with LifeEdit. $3.3 billion was returned to shareholders through a buyback of 23 million shares. I am proud of the strong results by our team in 2022 as we made history with a number of outstanding accomplishments for patients. In respiratory vaccines, we developed new products with remarkable speed, getting the mRNA-1273.214 against Omicron BA.1, the strain recommended by WHO and mRNA-1273.222 against Omicron BA.5, the strain asked by the U.S. FDA. We developed 1273.222 in less than 2 months. We are able to protect millions of people from potentially severe disease resulting from new COVID strains. Our RSV vaccine went from Phase 1 start to Phase 3 data in 24…

Thank you, Stephane. Good morning or good afternoon, everyone. Today, I will review our progress against our key clinical programs. I will start with our respiratory vaccines. We have approved our Phase 3 development programs against the big three respiratory viruses, COVID-19, RSV and influenza. I will share some additional data on these in a moment, including some presented this morning on our older adult RSV Phase 3 trial. We are also advancing a portfolio of next-generation programs against these viruses, including mRNA-1283, which is a next-generation COVID-19 booster that is referred to as rather stable. We also have multiple next-generation flu programs. We seek to increase the breadth of coverage against influenza by adding additional antigens that are not present in currently-available flu vaccines. Lastly, our respiratory portfolio includes a large number of combination vaccines to provide protection against multiple respiratory pathogens which has advantages for many stakeholders, including healthcare providers, payers and consumers. These include combinations of COVID, flu and RSV as well as two pediatric vaccines that include additional viruses that are important in children, including hMPV and PIV3. As we prepare for endemic COVID in 2023 and beyond, we wanted to briefly recap the recent VRBPAC committee discussions and recommendations. At the January VRBPAC meeting, the committee voted to harmonize the primary series and booster dose vaccines, which is an important step to simplify future guidance. The FDA also indicated that it expects to convene VRBPAC to determine vaccine strain composition for the ‘23/24 season in the second quarter of this year. We believe that our mRNA platform has demonstrated its ability to deliver variant match vaccines on accelerated time horizons and we believe we are therefore well positioned to deliver whatever composition update the FDA and other public health agencies recommend. And moving to RSV,…

Thank you, Stephen and good day to everyone. I will start with a review of sales on Slide 20. In the fourth quarter, total product sales were $4.9 billion. In the U.S., our sales were $1 billion, sales in Europe approximated $2.2 billion, and sales in the rest of the world were $1.6 billion. We ended the full year strong, with total product sales for 2022 of $18.4 billion. Sales in the U.S. for the full year were $4.4 million, sales in Europe were $6.7 million, and in the rest of the world were $7.3 billion. We are reiterating approximately $5 billion in COVID sales for delivery in 2023 from our currently-signed advanced purchase agreements and deferrals. And we do expect additional sales from key markets such as the U.S., EU and Japan. Slide 21 summarizes the current composition of sales for 2023. We have advanced purchase agreements from Canada, Kuwait, Switzerland, Taiwan and the United Kingdom. We expect these sales to be recognized upon delivery of vaccines in the second half of 2023. Additionally, we expect further sales from deferrals from 2022 contracts. These deferrals are from the countries listed on the slide and are expected to be mainly recognized from deliveries in the first half of 2023. Together, these advanced purchase agreements and deferrals totaled approximately $5 billion in sales for 2023. We do expect additional sales from key markets, including the United States, EU and Japan, as well as Australia and other countries in Asia and Latin America. In the U.S., contracting discussions with commercial customers are ongoing and we will provide visibility into expected U.S. sales at a future date after we complete these discussions. In our discussions with commercial customers in the U.S., it is clear to us that our customers recognize that COVID is…

Thanks, Arpa and hello everyone. This morning, I will cover our 2022 financial performance and provide a framework for our 2023 financial outlook. Moving to our fourth quarter results, starting on Slide 29, total product sales decreased by 30% year-over-year to $4.9 billion. The decrease in 2022 was mainly driven by lower sales volume compared to overall higher demand in the prior year. Cost of sales was 39% of product sales compared to 14% of product sales in 2021. The key driver of the increase in cost of sales as a percent of product sales was a catch-up royalty payment to the National Institute of Health, or NIH, of $400 million, representing 8% of product sales in the fourth quarter. In December 2022, we entered into a non-exclusive patent license agreement with the National Institute of Allergy and Infectious Diseases and institute or center of the NIH to license certain patent rights concerning stabilizing prefusion coronavirus spike proteins and the resulting stabilized proteins for using COVID-19 vaccine products or 2P technology. Pursuant to the agreement, we have agreed to pay low single-digit royalties on future net sales of our COVID-19 vaccines. Our cost of sales also includes a charge of $297 million for inventory write-downs related to excess and obsolete COVID-19 products and expense for unutilized manufacturing capacity, and CMO wind-down costs and related charges of $376 million, and a loss on firm purchase commitments and related cancellation fees of $281 million. These charges other than royalties are driven by costs associated with surplus production capacity, overall lower demand and a shift to our most recent Omicron BA.4/5 targeting COVID-19 bivalent booster. Research and development expenses were $1.2 billion, which increased by 87% versus prior year. The increase in R&D spend continues to be driven by our clinical trial expenses,…

Thank you, Jamey, Arpa and Stephen. Let me now share some thoughts about where we’re heading. I’m really excited to see our mRNA platform and the investments we have made in science over the last 11 years leading to such a promising pipeline. We anticipate a number of important developments. Let me start with our first franchise, respiratory vaccines. In COVID boosters, we are working for the switch to U.S. commercial market, and we anticipate being able to quickly meet the full 2023 market needs for updated vaccines after VRBPAC and the FDA make this transaction in the spring of 2023. We plan to submit RSV vaccine for regulatory approval in the first half of 2023, and as you heard from Arpa, we will be ready to launch the RSV vaccine in late ‘23 or early ‘24. In flu vaccine, for Northern Hemisphere, mRNA-1010 Phase 3 trial, the Data and Safety Monitoring Board is expected to complete its interim efficacy analysis in the first quarter of 2023 of second franchise latent virus vaccine. It’s progressing very well with a broad spectrum of programs. In our large CMV Phase 3 study, we look to complete the enrollment. For EBV, HIV and VZV programs, our next milestone will be Phase 1 data. Turning to Slide 37, let me review the milestone for mRNA therapeutics programs. For personalized cancer treatment, we expect to start our Phase 3 study in partnership with Merck in adjuvant melanoma, and we expect to rapidly expand to additional tumor types, including non-small cell lung cancer. Full Phase 2 data will be presented at an upcoming oncology meeting and published in a top-quality medical journel. In PA, we plan to select those and begin the expansion arm of our Phase 1/2 study. MMA, we will have Phase 1/2 data.…

[Operator Instructions] First question comes from Salveen Richter with Goldman Sachs. Your line is open.

Good morning, thank you for taking my questions. Could you speak to the regulatory strategy for flu, given the miss on the B strains for immunogenicity? And if you are confident into the interim efficacy analysis, given the abominating prevalence of [indiscernible]?

I’ll take that. Thanks, Salveen for the question. Look, I think the honest answer is we’re still having incomplete information to provide guidance on the regulatory strategy. At this point, we are looking to the efficacy results from the P302 study that I described, which will guide us on that filing strategy. It’s important to note that efficacy, ultimate demonstration of non-inferior efficacy against an approved vaccine was always going to be required for full approval, and that the only thing that you could do with immunogenicity would be an accelerated approval path with an obligation to subsequently demonstrate efficacy. And so right now, we are actually very encouraged that the data that we’ve seen from our immunogenicity and safety study, which is running the Southern Hemisphere, P301, shows superiority on three out of four endpoints for the influenza A strains, which drive the overwhelming majority of disease, and the population of interest here are older adults, and account for over 99% of the cases in our efficacy study. And so that first interim efficacy analysis that we’re conducting now in P302 will evolve over 200 cases and 99% of them are influenza A, and it will be our first chance to really see the performance of the vaccine in terms of prevention of influenza-like illness from flu A. That is the first interim analysis. And so it’s quite possible, as you would expect in any efficacy study, and we’ve all got some experience now with these respiratory efficacy studies, that we may end up – need to go to a second subsequent interim analysis and accrue even more cases to demonstrate either non-inferiority or superiority in that study. And so what we will do is we will wait for the results from the DSMB, the independent DSMB, and gauge from that. Based on those results, obviously, if we do see efficacy, that is the gold standard for proceeding with regulatory filing and full approval. If we do not yet meet that threshold, then we will be looking forward to subsequent interim analyses in that study.

Great. Thank you.

[Operator Instructions] Our next question comes from Gena Wang with Barclays. Your line is open.

Thank you. Just quickly follow Salveen’s question. Do you need to show superiority in order to receive approval regarding the efficacy study? And then quickly on the revenue. Did I hear correctly the existing contract of $5 billion mainly will be in the second half ‘23? If that’s the case, is it fair to say that total COVID revenue in 2023 should be around $7 billion? And then regarding the $2 billion in the first half ‘23, how much will be from the U.S. market, i.e., out of estimated 100 million doses in the U.S., what could be your market share?

I’ll take the first question. Thank you, Gena for that. So first on superiority. You do not need to demonstrate superiority to get a flu vaccine approved. That’s well precedented. Non-inferior efficacy is the threshold. Our goal, though, over time is absolutely to develop a superior influenza vaccine. And so if we don’t see it with the first-generation product, which is mRNA-1010, I would note that we have four other programs – flu programs in development, different stages of clinical trials, that are looking to do even better than perhaps flu mRNA-1010. And our goal over time would be to demonstrate that we have a superior influenza vaccine. But it is not actually required for approval. Non-inferiority should suffice. I’ll turn it over to Arpa, I think, for the other questions?

Sure. Yes, I can take the second question. In terms of the total sales, we are anticipating about $2 billion of the $5 billion in the first half of the year, and none of that $2 billion is coming from the U.S. market. The remaining advance purchase agreements that we have of $3 billion will be coming in the second half of this year. Now, that $5 million is just the total that we have from advanced purchase agreements as well as deferrals from 2022. We do anticipate additional sales from the U.S., Japan, EU and other markets, and we believe the majority of these sales will be in the second half of 2023.

And then your market share regarding the U.S. market?

We continue to believe in the strong, differentiated profile of our products. We do not have any updates on market share projections as we are currently in discussions with customers right now for fall 2023 contracting.

Thank you.

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

Great. Good morning, thanks for taking the question. I was hoping to ask about the regulatory strategy for PCV, and specifically, how you’re thinking about the potential for filing off the Phase 2 data set, as well as how you’re thinking about the time lines for enrollment in the Phase 3 program and how that may impact the time line for potentially filing off the Phase 2 data set? Thanks.

Great. Thank you, Matt for the question. So we’re obviously really pleased yesterday to announce that we received FDA breakthrough designation therapy for the PCV program. And what that allows us to do is very rapidly accelerate our conversations with the FDA and other regulators on the path forward for filing 4157. As you noted, the Phase 2b study that we’ve run is a randomized study compared against, really, the standard of care with KEYTRUDA alone, and has already shown a quite significant benefit of 44% reduction of the rate of recurrence and – or death. And that study is ongoing, and so we’re continuing to follow over time and conduct additional interim analyses. And it’s possible that those – in fact, we would hope that those data mature and continue to get stronger and stronger. And so it is entirely possible that in our discussions under breakthrough with the FDA and others that we will come up with a path forward for beginning the filing process based on that Phase 2 and potentially proceeding with accelerated approval. Now as you know, in this country, and I think it’s where your question is coming from, as well globally, if there is a path forward there. We haven’t yet engaged with the FDA on because the breakthrough happened yesterday. But if there is a path forward there, it would require us to rapidly enroll a confirmatory Phase 3 study. And in fact, there is more and more attention on perhaps requiring that those Phase 3 studies be enrolled prior to an accelerated approval. And so for that reason, ourselves and Merck are working really quickly now to try and stand up that confirmatory Phase 3 melanoma study and enroll as fast as possible. Now we’re not ready yet to guide on how quickly that will be, but we are fully aware of the fact that in fact, if there is a path forward for accelerated approval, the enrollment of that Phase 3 may be gaining, and therefore, we want to have it enrolled as quickly as possible. So at this point, we’ve just received the breakthrough designation, we’re engaging with regulators, and we’re going to try and develop that path forward. But it is theoretically possible that there is an accelerated approval path and that we would need to enroll that Phase 3 study based on recent regulatory guidance, more generally to the industry. And working hard to make sure that we can do that as fast as possible here, while continuing to conduct the additional interim analyses and see the maturity of this data continue to proceed, and hopefully, the strength of the benefit provided by the combination to be further validated.

Thank you. [Operator Instructions] Our next question comes from Edward Tenthoff with Piper Sandler. Your line is open.

Great. Thank you very much. And thanks for all the detail on the call today. My question, I had to go back to flu for a minute and just with respect to the follow-on candidates, including I think the one that’s pentavalent hemagglutinin and then fixed hemagglutinin and then also into the neuraminidase, the candidates at that neuraminidase, what should be our expectation both in times of timing for data here? And how do you ultimately see your seasonal flu product offering kind of evolving? Thanks.

Thanks for the question, Ed. So let me start with the most advanced program, obviously, is our 1010 program, which we’ve talked about. And we have done an update to that vaccine that we think will increase the B immunogenicity for those populations for whom that matters, and we expect to advance that in clinical study quite quickly. That, in combination with the efficacy data that we were just talking about with P302, probably is the most important information for guiding our next step on the second-generation products. Our multiple – sorry, penta and hexavalent vaccines as well as the 1020, 1030 programs, which include neuraminidase, as you said, are all in various Phase 1 studies. And as we have shown repeatedly hopefully over the last couple of years, we can proceed very quickly in the subsequent Phase 3 in pivotal studies once we select one of those candidates to move forward. But the really important gating information is understanding how is our first generation product performing in terms of efficacy as a first mRNA flu vaccine. And so we are waiting for that information before proceeding forward. But we do expect that at least one, if not multiple, of these second-generation products would move into subsequent pivotal studies, Phase 3 studies. And in those cases, because we would be looking to demonstrate some form of superiority either against a broader range of influenza strains or better protection against influenza-like illness because we have included additional antigens, we would expect those studies to include both immunogenicity and safety and efficacy end points as we move forward. And so we will make a selection on which ones we might move forward based on the ongoing interim analysis of efficacy from our 1010 program. We don’t have another way to update at this point on which we will move forward.

Great. Thank you very much.

[Operator Instructions] The next question comes from Michael Yee with Jefferies. Your line is open.

Hi. Thanks. Good morning. A couple of follow-up on the flu vaccines and also a PCV question for Stephen. I guess could you clarify – do you have a hypothesis around why these strains were not non-inferior and what the ramifications are for that, either for this flu vaccine, but also for the infection study, and what that would mean for combinations? So first of all, just to clarify what’s going on there with the B strain, the ramifications for flu vaccine? And then my second question is on PCV. Obviously, we are excited about the adjuvant data. There is also a competitor reading out in metastatic melanoma this summer, so I wanted to understand how we should compare and contrast that and if you could walk us through how to think about metastatic and what competitors might show? Thank you.

Thank you, Michael for both questions. So, first on the flu, on the B, we are still looking into the data, and we are going to develop a more complete picture of what we think happened in the influenza B immunogenicity study. I would note a couple of things that are important. The first is these are active comparator studies. And so when you look at non-inferiority on zero conversion or titers, it’s important to note that we are going at the standard-dose influenza vaccine active comparator. And between the Phase 2 study and the Phase 3 Southern Hemisphere study, there were changes in the composition of those active comparators and the comparator use, and so that can drive some difference. The second thing I would note is that they were different populations, and so we went from a Northern Hemisphere to a Southern Hemisphere. And obviously, that can drive some differences in background history of influenza illnesses. But the third and perhaps maybe most relevant is we did expect that the influenza B neutralizing titers were lower. As you remember, we shared with the Phase 2 data about a year ago. We did have lower neutralizing HAI titers for the influenza B strain. And for our older adult influenza vaccine, we thought that was acceptable because at the end of the day, our goal was only to achieve non-inferiority, not to demonstrate superiority. Whereas for the influenza A strains, we really wanted to maximize those neutralizing titers and potential for benefit because influenza A really is what drives the illness in older adults, which is our first generation product. So, we did focus heavily on the influenza A. We were aiming at non-inferiority on the influenza B. And as you said, we did not make non-inferiority on those, and…

Thank you. [Operator Instructions] Next question comes from Tyler Van Buren with Cowen. Your line is open.

Hey guys. Good morning. Thanks very much for taking the question. For RSV, a few years from now, do you expect it to be a 2-player, 3-player or perhaps a 4-player market when including J&J? And how do you believe that the tolerability profile compared to others based on the full data presented this morning?

Sure. I can maybe – I will take the first portion of that question. At this point, there are obviously three companies that have wrote out their Phase 3 pivotal efficacy studies and are proceeding right now to filing. I think – I don’t have a specific view on J&J, maybe Arpa can offer perspectives on that, but it is an adenovector virus [ph] program, and otherwise still unclear about their regulatory path forward. Now on the question of reactogenicity and tolerability profile, as we presented today or as our collaborator presented today at RSVVW, we do see, we think a favorable tolerability profile. Grade 3 adverse reactions, whether local or systemic, were all below 2% for any of the individual symptoms. And actually compared relatively favorably with a placebo in that arm, often maybe 1.5x as frequent as what we are seeing in placebo, which we think is a compelling overall reactogenicity profile. We then think the other parts of the benefit of the product are obviously efficacy. We are incredibly pleased. If you look at the most common definition of cases, or RSV, lower respiratory tract disease involving two symptoms, which has been relatively consistent across the different products. We have seen high efficacy 83%, which I really think is among the best. And as we presented today, that efficacy actually holds up beautifully as you look at older populations, those over the age of 70, as well as those with higher comorbidities. Those would drive the majority of the expense associated with caring for patients, older adults with respiratory disease from RSV. So, overall, it’s very difficult, obviously, to do cross-trial comparisons. And ultimately, it will fall for public health officials to make those decisions, but we are really encouraged by both the efficacy and tolerability profile of 1345, and look forward to filing and ultimately to the commercialization of that product. Arpa, would you like to add anything in terms of your perception of the market going forward?

Sure. So, I would say we do anticipate it being at least the 3-player market with Moderna, Pfizer and GSK. There is a possibility of a 4-player market if J&J has a regulatory path forward with their adenovector virus vaccine. Nothing more to add there.

Thank you. [Operator Instructions] Our next question comes from Jessica Fye with JPMorgan. Your line is open.

Great. Good morning. Thanks for taking the question. Following up on flu or mRNA-1010, just to be very clear, if you hit on non-inferiority in the efficacy Northern Hemisphere study, do you think that mRNA-1010 would be approvable in spite of missing on non-inferiority on the B strains? And related to that, would you envision the approval only being for older adults? And on RSV, can you comment on the expectation for dosing frequency for your RSV vaccine? And how do you think about the value and potential pricing of that vaccine, maybe benchmarking off of other vaccines for that age group? Thank you.

Yes. Thanks for those questions. So, let me take the flu stuff first. So again, the full approval of standard is a head-to-head efficacy study. And so if we demonstrate non-inferior efficacy against an approved vaccine in the population which we are studying and which in this case in P302 is 50-plus adults. We do believe that could form the basis of an approval. At the end of the day, immunogenicity results, and in particular, are only surrogates for efficacy, and ultimately, efficacy is the gold standard. That’s what’s required for traditional approval, and that’s why we are running the P302 study. So, it will depend upon how a conversation with regulators around that data package, but it is certainly plausible. And in fact, one might say likely that if we meet efficacy in the efficacy study that that would be sufficient to move forward for a full approval. It doesn’t mean that there may not be questions about demonstrating non-inferior immunogenicity with influenza B strains or other things in subsequent studies, but we do believe there is a possibility there. But at the end of the day, it will be dependent upon data and discussions with regulators, including the FDA. And so we will wait until we have that data and have those conversations, but I think it’s certainly a possibility. Now, as it relates to age for approval, we are currently studying mRNA-1010 only in older adults. And so as I have said, the P301 was in 18-plus, P302 is in 50-plus, and that’s really where we see the broadest recommendations for seasonal influenza vaccine and where we have been most focused initially on building out our respiratory portfolio. We will evaluate our influenza vaccine, in fact, many of our respiratory vaccines in younger populations over time. But we will have to do age de-escalation, dose finding and then bridge down from an immunogenicity perspective, very much like what we did with COVID. And so our initial filings for approval, if they proceed based on data, would be in adults and older adults principally. And then eventually, we would follow-on with pediatric populations. And as I said a moment ago in response to Michael’s question, that may involve using updated B antigens to increase immunogenicity in that population. But again, that’s subsequent studies that we would do in children. Could you remind me of the second question?

For RSV, what are you thinking for dosing frequency and how do you think about value and potential pricing of that vaccine, maybe benchmarking off of other vaccines for that age group?

Sure. So, I will let Arpa take the second part of that question. First on frequency, it is not yet clear on how frequently people will need an RSV vaccine. It’s a seasonal virus, a seasonal epidemic of disease that shows up. Most of us have been exposed to RSV all over a dozen times over the course of our life. And what really happens from a biology perspective is as we get older, our ability to maintain high neutralizing titers to protect us goes down, and what we have is breakthrough disease and ultimately, a disease leads to substantial cost and morbidity and even some mortality in older adults. We do not – we have not yet had approved vaccines, and so what we don’t yet know is what’s the frequency of vaccination, is it going to be seasonal every year, or is it going to be less than seasonal every couple or few years. But what’s pretty clear, based – from my perspective, based on the epidemiology of RSV infection, is that we do see RSV fairly regularly as adults, and unfortunately, over time, it breaks through more frequently, and so there probably will need to be repeated boosting to protect against RSV. At the end of the day, the initial recommendations will come from ACIP as well as from regulators around that frequency, and we will have to defer to them on how they want to administer and roll out the RSV vaccines, whether they want to follow a flu model, which would be annual to make sure that we get the broadest amount of protection, or that they want to initially roll out RSV vaccines and then follow over time for the durability of that efficacy. At this point, none of us, none of the three products that have read out in Phase 3 have a clear answer on the durability of that efficacy, although we would expect it to wane as it does against natural RSV infection over time in those results. Arpa, do you want to take the next part of the question?

Sure. Yes. I can take the question on pricing. So overall, from a pricing philosophy perspective, Moderna is committed to pricing that reflects the value of our vaccines. In terms of what they deliver to patients, to societies and the healthcare systems, while also ensuring full access for patients regardless of their ability to pay. So, with that broader principle around pricing, we will be looking at the full recommendations that come out of ACIP as we get the filing and the ACIP recommendations to look at what the full value that could be provided back is based on things, as Stephen mentioned, around dosing frequency, and their pricing will be based on both value and access. I am not able to share any additional details on what sort of range that pricing might fall into, but it will be consistent with our overall pricing philosophy.

Thank you. [Operator Instructions] Our next question comes from Ellie Merle with UBS. Your line is open.

Hey guys. Thanks so much for taking the question. Just another on flu, just – any more details on the titer level specifically that you saw or when we will get more details on the titer levels? And then how should we think about the importance of having titers above that 40 benchmark versus demonstrating non-inferiority. Like I guess what is the comparator vaccine titers in your Phase 3, did very well and were well above 40? How should we think about the implications then, say, you are at 30 or near 40, what that would mean from a regulatory standpoint as well as a commercial standpoint in interpreting the immunogenicity idea? Thanks.

All very good questions and I think the short answer is we are looking into that data right now. And we will provide an update I am not exactly sure when we will have that, but we do have the Vaccines Day Investor Meeting coming up in April of the spring and then obviously, we will be looking to publish that data and share as it comes in and is it available. You have highlighted one of the key challenges in active comparator studies in influenza in particular, which is that you can see high titers, but actually because you are looking at a ratio, say for whatever reason, your active comparator does really well against one of the strains, that can impact your ability to non-inferiority statistically. And at the end of the day, the challenge is even more complicated as you look at older adults where, for instance, the influenza B strains are not a big driver of efficacy or disease. And so we will look at all of that as will regulators. I would note that it is well precedented. In fact, many of the currently approved influenza vaccines have, in the past, missed on non-inferiority for – and influenza B strain end point here or there and still have received full approval or accelerated approvals. And the reason for that is, as we have said sort throughout, that at the end of the day, influenza B is not a primary driver of concern and it is known to be among the different strains of influenza in the virus in the vaccines of lower import for disease in older adults. In fact, one of the four strains, there have been active debate about the B/Yamagata strain as to whether or not it’s gone extinct, and even should be removed from quadrivalent vaccines in many of the recent WHO and other debates. And so influenza B is a well-trodden path for many of these vaccines as well as now for mRNA-1010, where there is differential performance, and ultimately, there is precedent for moving forward where you do not technically need non-inferiority on immunity your sales [ph] conversion endpoints and still moving forward because of the lower concern about that disease in older adults. So, we will look at that data. We will develop our strategy. We will obviously engage with regulators with that data, and ultimately determine a path forward. The most important thing for us, though, in the near terms continuing with the efficacy study trying to establish whether or not we have non-inferior or even superior efficacy for mRNA-1010 in its current form against influenza A, which is really where we think payers and public health officials will have the most attention because it is prevention of that disease, not the immunogenicity endpoint, prevention of influenza-like illness, hospitalizations, that is the primary objective of the vaccine and that’s where we are focusing our attention right now.

Great. Thanks for the color.

[Operator Instructions] Our next question comes from Joseph Stringer with Needham. Your line is open.

Hi. Good morning. Thanks for taking my questions. Two from us, the first one on 4157-KEYTRUDA combo program. Just curious, if you could give us a little bit more color on how we should think about the cadence of the additional trial starts? Is it something that will be a more stepwise and measured approach, or should we expect sort of a full force kind of multiple trial starts approach? And then secondly, on rare disease, outside of your MMA, GSD and PA program, what is the next rare disease program that we can expect to enter the clinic? Thank you.

Thank you for those questions. So, on 4157, I think I will just reiterate our prior guidance, I don’t want to expand it, to say that we are trying to move into those pivotal studies, they are Phase 3 confirmatory studies for melanoma and non-small cell lung cancer, both adjuvant settings, this year. And we – you can look at the history of Merck and their ability to execute those studies, enroll quite quickly and now working together with us, we hope to be able to at least do that well. And we will look to enroll those at least as quickly as other confirmatory Phase 3 studies and similar populations have been run generally. But I don’t think we are going to provide more specific guidance on enrollment time horizon except to say we want to go as fast as possible. I will also clarify, too that from an accelerated approval perspective, if that pathway were to become available based on the current Phase 2 data, which again is subject to future conversations with regulators, that we would want to have started those confirmatory studies. We wouldn’t have needed to complete enrollment, but definitely, we want to be demonstrating that we are moving forward in those confirmatory studies as quickly as possible. And so we have double impetus. We are moving fast in enrolling them in the near-term. Now, in the rare disease space, programs moving out of pre-clinical and clinical. The first I would say is we do have a clinical program for MMA, which you referenced, but that MMA program is another place where we expect to see additional data following on, hopefully, the continued strong performance of the propionic acidemia PA program. And then in the pre-clinical development space, we have programs against OTC and PKU, so Phenylketonuria and a urea cycle disorder OTC, and those are both programs that we would hope to move into clinical testing in short order. We haven’t specifically guided on the timing of that yet.

Many thanks for taking our questions.

Ladies and gentlemen, this does conclude the question-and-answer portion of today’s call. I would like to turn the call back over to Stephane for any closing remarks.

Thank you very much everybody for joining us and for the many thoughtful questions. We look forward to hosting you for Vaccine Day on April 11. It will be live in Boston, for those of you who can join us, and also of course virtual. Have a great day. Thank you.

Ladies and gentlemen, this does conclude today’s presentation. You may now disconnect and have a wonderful day.