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Good day, and thank you for standing by. Welcome to the Invivyd First Quarter 2026 Earnings Conference Call. At this time, all participants on listen only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please note that today's conference is being recorded. I will now hand the conference over to your speaker host for today, Katie Falzone, Senior Vice President of Finance. Please go ahead.

Thank you, Livia. A short while ago, we issued a press release announcing our Q1 2026 financial results, and recent business highlights. That press release, and the slides that are being used on today's webcast can be found in the Investor Section of the Invivyd website. Under the Press Release, and Events, and Presentation sections, respectively. Today's discussion will be led by Marc Elia, Chairman of Invivyd Board of Directors. He is joined by Dr. Michael Mina, Chief Medical Officer, Dr. Robert Allen, Chief Scientific Officer. Tim Lee, Chief Commercial Officer, and Bill Duke, Chief Financial Officer. During today's discussion, we will be making forward-looking statements concerning, among other things. Our corporate, and commercial strategy, our research and development activities, our regulatory plans, certain financial expectations. Our future prospects, and other statements that are not historical facts.

These forward-looking statements are covered within the meaning of the Private Securities Litigation Reform Act, and are subject to various risks, assumptions, and uncertainties. That may change over time, and cause our actual results. To differ materially from those expressed or implied today. These forward-looking statements speak only as of the date of this call, and Invivyd assumes no duty to update such statements. Additional information on the risk factors, that could affect Invivyd business. Can be found on our filings made with the U.S. Securities and Exchange Commission. Including our most recent Form 10-K, which are also available on our website. I will now turn the call over to Marc.

Thanks, Katie. Good morning, and thank you all for joining us. It's an exciting time for Invivyd, and an exciting time for the future of infectious disease medicine. The first quarter of 2026, and the current quarter have been very busy here. And we'll use this time today to remind you of our news, and put it into the broader context of our mission. I'll start by recapping some recent events. First, our pivotal program continues at high speed. As you may remember, we triggered our DECLARATION study upsizing in early April. And the recruitment speed into this additional upsized cohort, occurred well faster than our internal expectations. Given the lull in COVID-19, and overall respiratory disease burden in April. We actually slowed recruitment, to stretch our upsized patient exposures. Into what we would expect to be a normal summer COVID wave.

We've resumed full speed recruitment, and believe we will finish up imminently. Keeping the program on time with our previous estimates. Next, we have substantially increased our government affairs activity of late, and I'll share some general observations. About what we are seeing, and hearing in Washington, D.C. The overall landscape from the Invivyd point of view is highly positive. But we are very focused on making sure policymakers are aware of the potential of our medicines. And so have no intention of slowing down our work. We recently published a manuscript, a preprint we call Safety First. That we think is perhaps more profound than it may seem at first glance. Our colleague, Dr. Michael Mina, will walk through some of the implications of our work in more detail in a moment. And describe how the analyses we are performing bear, on potential overall American wellness.

Finally, we're happy to announce that, as we expected. We formally confirmed virus neutralization of our medicines against Omicron BA.3.2. A COVID virus variant that may reveal more about overall evolutionary trends, than posing any particular clinical challenge. Dr. Robert Allen, our CSO, will describe those findings in a bit more detail. Where does all this leave us in the big picture? We are seeing continued growth in our monoclonal antibody revenues while COVID vaccine utilization, and revenue declines. We see overwhelming demand for our antibody study at the recruitment level. While recently we read another company in the field abandoned a major vaccine study for lack of demand. We think this means we're onto something good.

Beyond the centerpiece of our company in COVID-19 prevention, and treatment. We recently disclosed our early discovery pipeline in a presentation given by Dr. Allen at the World Vaccine Congress. You can find the link on our website, you will note that beyond the measles antibody program we've already described. There are several vaccine-preventable pathogens on the slide. Including mumps and rubella, the other components of the MMR pediatric vaccine. As well as Lyme disease, and several other burdensome pathogens. That may benefit from immune supplementation or treatment via monoclonal antibodies. That can operate beyond the limits of vaccinology. We believe that at Invivyd, we've created the premier industrial platform. For the discovery, development, and commercialization of monoclonal antibodies for burdensome viruses. With major associated public health benefit, and potential shareholder value creation.

Going forward, we think investors, and the broader medical community. Will be pleased with the scope of our technical capability, and the unique role. Our molecules can play in improving health outcomes, by adding to or synergizing with vaccination. On government affairs, we've taken the opportunity to introduce Invivyd in our work to portions of the new administration. And key advisors, and influencers in that space. Without going into too much detail, we're happy to share some impressions that may surprise investors. First, our observation has been that a great many people within, and the leadership of the MAHA movement. Often demonstrate a superior technical understanding of basic, and translational immunology than we commonly encounter. Second, and perhaps less surprising, these same people often have a much more clear, and detailed understanding. Of both the randomized, and observational data around COVID-19 vaccinology than much of the medical establishment.

It actually appears that the data on COVID-19 vaccines. Presented by the CDC over the last five years has been taken up, and understood more clearly. By elements of the MAHA movement, than even the traditional infectious disease medicine establishment. That was unexpected, and welcome news to us. More, consistent with the wide range of various sources on this slide. We have observed consistent, direct, and clear support for the concept of monoclonal antibody immune supplementation. Not just from the medical establishment, but also from this new segment in modern medicine. Whether you are President Trump opining on the value of monoclonals, or Anthony Fauci or even Joe Rogan. It doesn't appear to matter what political or scientific perspective one holds. The concept of supplementing human immunity, by adding the power of monoclonal antibodies appears to be regarded as a universal positive.

Some investors of ours have raised concern that, quote, vaccine-skeptical, unquote. Or hesitant communities may not appreciate monoclonal antibodies. I'll take this opportunity again to disagree. Our clear experience is that to the contrary. People who describe themselves, as vaccine-skeptical are telling a precise truth. They're not medicine-skeptical, and they're not confused. To assume they are is to risk missing the point, and inflaming the overall debate. Finally, consistent with now years of experience. We have actually shared these impressions with multiple media outlets. Have authored multiple op-eds about the shared common ground. Across this polarized modern infectious disease medicine complex. But have enjoyed almost no traction or uptake. The apparent fighting about vaccines, and health playing out in the media will continue. So long as the public continues to click on ads, and find conflict more interesting than resolution.

Meanwhile, we're excited to continue to work for a better way forward. We're thrilled with the level of understanding of, and appreciation for our work we've encountered. By working in COVID-19, and infectious disease generally, we have a duty to the public. That begins with educating our leadership on the scientific, and medical landscape to the best of our abilities. Expect that to continue. We're also beginning to educate the public at scale, on the role antibodies play in basic human immunology. The last few years have, of course, created all manner of misunderstanding, and misapprehension in the public. Thanks to the strange circuitous relationship, the public has enjoyed with vaccinology. We think a better future starts with simple, basic immunology education. That could be found on pages one through three of any immunology textbooks.

Who better to inform the public on these issues than Lindsey Vonn. Who is, we can assure all of you, the real deal genuine article. And perhaps the single most inspiring human being many of us are likely to encounter. It is clear from our personal experiences at Invivyd, that you don't want to race against her. You don't want to tell her that she cannot or should not do something. On the flip side, you actually might want to dare her, that she can't possibly do scientific education for the American public. She appears to be undertaking this challenge with real vigor. We've partnered with Lindsey on our Antibodies for Any Body campaign, and are very pleased with the attention garnered in our initial rollout.

As we move forward as a company, it's essential that we keep our eye on the basics. That investors may take for granted, but on which most consumers. And many healthcare providers are not actually all that clear. Accurately identifying the role of antibodies in human immune physiology for the general public. Will be an important contributor to the value of our work long term. I'll now turn the call over to Dr. Michael Mina, our Chief Medical Officer.

Thanks, Marc. As most of you know, the pivotal program for VYD2311 is well underway. A quick update on our ongoing DECLARATION study. We are pleased that the Independent Data Monitoring Committee, or IDMC. Recently recommended that post-dose subject monitoring be reduced from two hours to 30 minutes. After review of unblinded VYD2311 safety data. We have modified the DECLARATION study accordingly, and believe this update may reflect an encouraging indicator. Of product safety, and tolerability post-administration. In addition to DECLARATION, we aim to have the LIBERTY study open, and recruiting shortly. To assess the safety, and immunology of COVID-19 vaccine combined with monoclonal antibody. And to assess in a direct, prospective fashion the safety, and tolerability of monoclonal antibody. Approaches to immunization against COVID-19 mRNA vaccination.

This comparison should go a long way to providing a direct view on. What we believe is the first advantage of an antibody approach is infectious disease prevention, high safety and tolerability. Our view is that symptomatic vaccine reactogenicity, is a major driver of people's willingness. To get vaccinated, and agree with data from CDC. And recent statements from Sanofi indicating the same. On that point, I was pleased to recently work with other Invivyd authors. And Dr. David Putrino of the Icahn School of Medicine at Mount Sinai, on a recent manuscript that evaluated adintrevimab. An old investigational antibody from Invivyd, that completed a placebo-controlled pivotal study. For the prevention of symptomatic COVID-19, similar to the DECLARATION study. Adintrevimab is highly similar to VYD2311, differing by only a handful of amino acids in the variable region. And was administered intramuscularly at a similar dose to VYD2311.

Upon seeing results from Sanofi's COMPARE Phase IV study, comparing protein-based COVID-19 vaccine. Against mRNA-based COVID-19 vaccine. Which demonstrated a statistically significant difference, on early systemic reactogenicity symptoms. Such as headache, fever, chills, and fatigue over the first seven days post-vaccination. We undertook an analysis of the same symptoms from the adintrevimab EVADE study over the same duration. The results of our analysis are presented on the slide, as they can be found in our manuscript. There are real methodological differences in how these symptom data were collected in the COMPARE study, versus the EVADE study. And so, we will have to wait for LIBERTY for an apples-to-apples direct evaluation. Nonetheless, the comparative results are striking. We see as we'd expect that while COVID-19 vaccination, relies on immune education and re-education. With its associated inflammatory response, monoclonal antibodies do not.

As an epidemiologist and physician, there are implications to these data. That go beyond a competitive or comparative profile, and get to issues. We must grapple with at the level of public health. If it's true that people's experiences with immunization, directly influences their willingness to get immunized in the future. Then systemic reactogenicity is itself, an important consideration in public health. A vaccine that generates an 80%-90% probability of three to 3.5 symptom days. Actually, represents a meaningful portion of the symptom burden, of an actual breakthrough COVID-19 infection. It's not surprising that we see declining vaccine utilization, and therefore declining protection from a virus in SARS-CoV-2. That is still inflicting a substantial medical burden on humanity. We can calculate the cost to society in symptom days per million immunizations given.

Logically, if a person starts with a high probability, of a few days of real burdensome systemic symptoms from the vaccine itself. Then the vaccine will have to be very protective against symptomatic disease for quite a while. To generate a net benefit in overall symptomatic patient days. Recent COVID vaccine efficacy data, does not make a particularly compelling case on that dimension. With estimated protection from symptomatic disease peaking at approximately 50% for a relatively short duration. By contrast, VYD2311 data look like adintrevimab safety data, and do not start patients with a meaningful symptomatic burden. A monoclonal can be essentially minimally protective on the order of 10%-15% protective of symptomatic disease. While still generating a net benefit in symptoms.

We'd expect any monoclonal antibody we generate, to have much more meaningful protection. But the point remains, the more reactogenic the vaccine. The higher the public expectation will be for consequent strong, and durable protection. The results of our modeling are presented here on slide 11. We expect to make this point with more refined modeling, and present it to relevant policymakers. And regulators as much as we can in the coming months. The big picture is clear, I want to be clear that. This is not some form of anti-vax statement, but rather the reality of the data. Our major concern at Invivyd is protecting people, and doing so in a way. That allows vulnerable populations to stay safe, and well.

Because low-dose intramuscular COVID antibodies, appear to confer very low levels of systemic reactogenicity. We believe that intramuscular monoclonal antibodies can address these experiential problems. And can exert meaningful population-level benefits at scale. Obviously, we'll look to our DECLARATION of LIBERTY studies. To provide high-quality prospective, and controlled data. On these safety, and tolerability issues near term. I'll now turn the call over to Dr. Robert Allen, our Chief Scientific Officer.

Thanks, Michael. We can turn to slide 15 very quickly. As we expected, we continue to see attractive neutralization data for our medicines against relevant SARS-CoV-2 variants. This is consistent with our hypothesis, and industrial process for drugging immutable targets like the SARS-CoV-2 spike protein. More, we continue to believe that our medicines engage important territory on the RBD. And as usual, we have no expectation of future activity concern based on the virus variant landscape we see today. On slide 16, beyond COVID-19, in our early pipeline, we have disclosed. What we view as potential best-in-class antibodies to treat, and prevent critical virus threats in measles, and RSV. As Marc noted, we are expanding our early discovery across a host of viruses. Including vaccine-preventable viruses such as mumps, and rubella. And key threats to chronic health in America, such as Lyme disease or Borrelia burgdorferi.

We see monoclonal antibody technology, as underutilized across infectious disease medicine. Both for prevention, and treatment in many diseases. And are looking forward to using our technology to open up new cases. New use cases that meaningfully improve our ability to keep people well. In the face of both established, and emerging viral threats. I'll turn the call over to Lee, our Chief Commercial Officer, to discuss our commercial progress.

Thanks, Robbie. We were pleased that PEMGARDA once again grew year-over-year, now at 22% over 1Q in 2025. Traditionally, the first quarter is a bit weaker in the pharmaceutical industry. And indeed in infectious diseases, and preventive medicine. One traditionally sees a major seasonal drop-off from the third, and fourth quarters to the first and second. Interestingly, we are not seeing nearly so much of that same seasonal change. As you would expect from a seasonal respiratory vaccine. We attribute our relatively more stable P&L, to the fact that SARS-CoV-2. Has periodic waves, including the anticipated coming summer surge, and even at low levels. Is a ubiquitous, and ever-present threat. Vulnerable populations, and their care teams appear to be making more rational decisions. That reflect the nature of this viral threat.

Elsewhere, our leading indicators are showing good ongoing growth. We are preparing for, and looking forward to transitioning. Forward into an entirely new kind of COVID antibody. We believe that can be game changing in the form of VYD2311 if approved. Although the distribution model will be entirely different. We are pleased that much of what we have built for PEMGARDA, already is going to be leveraged and expanded for VYD2311. Turning to slide 19. We are also increasing our exposure to new mechanisms. By which healthcare providers access information about medicine. Including the leading AI platforms. These tools promise to dramatically increase the efficiency. By which companies like Invivyd, as well as much bigger companies. Can disseminate appropriate information about our medicines to healthcare providers. Our expectation is to continue to think differently about how we design, and deploy our resources.

Our expectation is that these tools will help us, to differentiate from more traditional pharmaceutical companies. Who historically have relied solely on feet on the street. We'll be focused, and nimble with our sales force. As well as the resources we bring to market. So far, our early efforts with AI tools appear to be encouraging, and we will meter our investments in these tools appropriately. Over the coming quarters with our PEMGARDA business. Turning to slide 20. Finally, we have increased our direct-to-consumer efforts. Which, although still in its infancy, are beginning to generate greater disease, and brand awareness. This is another efficient channel, that we'll expect to ramp up if VYD2311 is approved. With that, I'll ask Bill Duke to cover the financials.

Thanks, Tim. Turning to slide 22. The first quarter of 2026 included, meaningful clinical spends to support our DECLARATION clinical trial. This is a very substantial investment compared to our ordinary clinical, and SG&A spending. One we feel has extraordinary commercial potential. Our cash position remains very strong, especially considering the additional cash raised in April. From long-term investors who wish to increase their position. Through our at the market offering facility. We are looking forward to continued PEMGARDA growth, and as the pivotal trial for VYD2311. Winds up over the coming quarters, a return to more normalized R&D spending. Turning to slide 23. You can see the effects of VYD2311 spend, on our overall burn via this chart. That provides a bridge from Q4 2025-Q1 2026. You will note that we have also made targeted investments, to prepare for VYD2311 commercialization if approved.

Although it is reasonable to expect that some of these investments in personnel. And commercial infrastructure could benefit our current PEMGARDA business as well. With that, we are happy to take your questions. Operator?

Thank you. Ladies and gentlemen, as a reminder, to ask a question at this time. You will need to press star one one on your telephon, and wait for your name to be announced. To withdraw your question, simply press star one one again. Please stand by while we compile the Q&A roster. Our first question coming from the line of Josh Schimmer with Cantor Fitzgerald. Your line is now open.

Great. Thanks so much for the updates, and taking the questions. First for the 30-minute post administration monitoring time for VYD2311. Do you anticipate that would be ultimately included in the label? If so, how might that impact adoption? Second, the last I checked in terms of the wastewater monitoring for COVID, it's still at a nadir. But do you from your vantage point, see any indications of the new or a summer wave starting to emerge yet? Thank you.

I think just to go in order. Hey, good morning, Josh, by the way. On the 30-minute monitoring, I think it's a little premature. When we go out into the field, and you will all. I'm sure, remember from the pandemic, different medical interventions administered in different settings. Will carry with them some obligation, typically, right? Particularly, if I recall back in 2021, I wandered the hallways of a Walgreens for about 12-15 minutes. Before a pharmacist told me I could leave. I think to us, which really looking at is the evolution of a clinical program only at this point.

It's, I think as we go through FDA, and then out into the field. We would hope that something that has a profile. That we would expect to be relatively, you know, modestly burdensome barring the administrative ouch. I think, let's see. I certainly don't think of it as something, a variable that we are concerned about. In terms of adoption, and uptake bigger picture. I'll just invite anyone else from Invivyd to have a view or.

Yeah. Hey, Josh. I think that's Michael Mina. Certainly, you know, what the wave winds up saying. You know, that's going to be based on the studies, and our discussions. We anticipate from what we know, in particular from EVADE. That we're going to see high tolerability, low reactogenicity. You know, overall, we would anticipate, that as we move into the future with an IM monoclonal. That, you know, practice is going to start to look more like the way, that people currently wait following a vaccine. You know, which will probably, as people get more comfortable. Physicians get more comfortable, we would expect that, you know, concerns. That would lead somebody to stick around for two hours would certainly fall by the wayside.

You know, as I reflect, I would also just add, remember early on in. The people would often wonder what would be the biophysical relationships between, say adintrevimab, pemivibart, and then VYD2311. We would have always reminded folks, that when we deal in pemivibart. We are dealing in extraordinarily high doses of monoclonal antibody delivered via IV infusion. As we moved into the DECLARATION program. I think people were, you know, perhaps justifiably wondering. Would there be meaningful peri-administrative issue like for example hypersensitivity, and allergic reaction. That is, you know, common at some low rate with protein-based therapeutics, and monoclonal antibodies.

Again, going back to my remark about the evolution of a study. I think again, we don't know what the IDMC is looking at. But it is to a large degree to us reassuring, and we would expect that there will be very little. To talk about on this front, as we get through the final data. Of course, there's one way to find out, and so shall we all in time. On the wastewater, I think again, I'll ask Robbie in a minute if he has anything to add. But I think what we essentially know boils down not in terms of variant perception. From what most people can see, although different wastewater services, and sites have differing levels of latency. Okay.

All of us, depending on what source we're looking at, are looking some number of days in arrears. I think there is something reassuring, to the simple arithmetic of exponential growth. COVID is a little unique among the more classically seasonal respiratory diseases. COVID, it appears to us since now six years. To either be declining or to be rising. And it certainly appears to have radically slowed its level of decline. Albeit now down to low levels. Typically, that would portend a relatively predictable rise. The critical thing from an Invivyd standpoint, is to make sure that we have. The maximum number of patient exposures out there, when that rise occurs. Again, maybe a little bit of inside baseball from a practitioner standpoint.

I think, you know, it's, it's in some ways unfortunate the DECLARATION started about two weeks only. You know, later than in hindsight could have been ideal relative to a December-January wave. Is that a, a big problem or a big issue? No, certainly not. It does go to how finally we try to map these things, and tune these things. To the benefit of event rate accumulation. Look, all I think I'm saying is at a certain point, we start to get conviction. That a turn is either of upon us, and not yet detected. Or imminent to a point where a forward three-month lens. Feels like a very attractive place, to place our patient exposures. Can't be a guarantee. It's just the experience of six or so years of watching this stuff.

We're all gonna, like we say, you know, find out together unfortunately on this point. I think we feel pretty good about our setup going into this summer, and then the wrap up of the study.

Great. Thanks very much.

Thank you. Our next question coming from the line of Patrick Trucchio with H.C. Wainwright. Your line is now open.

Thanks. Good morning, and congrats on all the progress. Just a couple of follow-ups on DECLARATION. The first is, you know, I think you mentioned that. You know, even low efficacy antibody, monoclonal antibody could generate symptomatic benefit. We're expecting much stronger protection,. I'm wondering, though. What point estimate or lower confidence bound would you consider clinically meaningful, commercially viable, and supportive of a BLA? Separately, how should we think about the single-dose versus multi-dose arms? You know, how is the, I guess, the statistical hierarchy structured, and commercial read-through, you know, that we should see between the single-dose, and monthly dose arms?

Okay. Thanks for that. Good morning. Let me, let me start, and then I know some others are gonna, are gonna weigh in. Okay. On your first question, you know, in some ways you posed the considerations. In what I think are a really interesting, and important order, okay? I'm gonna, I'm gonna go backwards in effect. In terms of, what would be required for BLA? Recognize that that's a determination made by a small group of people. Who work for the federal government, and they make the rules, and we all follow them. We will all end up being in receipt, of whatever it is the U.S. FDA deems. You know, a positive risk-benefit for the American public. We certainly, of course, expect much better VE.

We're certainly, of course, providing antiviral titers. That we would imagine would carry much higher VE. I'll get to your other points. What is commercially viable? Well, you know, today there's $3 billion or so in U.S. revenue. Of something that would appear, to not have a particularly impressive nor a particularly durable VE. So your mileage may vary on that point. In terms of what is clinically meaningful, I think actually. Whether or not you mean it, of course you are getting at the heart of the analysis we're providing here. Which is the goal of clinical medicine, and infectious disease practice is to keep people well. I think the point we're trying to demonstrate here. Is just that it's we're all operating against a very high proposed bar, of overall profile when we deploy these mAbs.

We're looking for very, very high protection. At a very, very low symptomatic penalty or tolerability penalty. That's our goal. If you asked us what was clinically meaningful, and you were talking to. Let's say, a vulnerable person, and here I'll just use myself as a fun example. Because I happen to be here, and I'm speaking. I would be thrilled if I could routinely access something, that at very low penalty. Modulated my risk of symptomatic disease. The reason I say that is, because symptomatic disease is gonna define, yes, my day-to-day experience. Typically one would imagine it is also a predicate, for derivative follow-on benefits, right? Such that if I don't get sick, it's probably unlikely I'm gonna go to the hospital. If I don't get sick or go to the hospital, it's probably unlikely I'm gonna die.

Again, I would just point out, you actually did all of this. These waterfalls of consideration that suggest to us, and we're very comfortable doing this. We are operating with the aim of delivering a very exciting new medicine. That proposes to ask very little of patients or subjects. That in terms of tolerability, and return something really meaningful. Which would be relatively very high protection over a very long term. We think that is awesome. All we mean to point out is that indeed, let's say we were in a dialogue over time or at some point in the future. With a group of people who have been designated in our social contract. To decide whether or not these are useful objects.

Remember what DECLARATION is first designed to do. I think we would argue, establish safety, and tolerability relative to placebo. I say that because we all know the calculation of protection in VE. Is gonna be dependent to some extent on infectious disease attack rate in the study, so on and so forth. That is a probabilistic thing. Again, as we've disclosed previously, we feel like we're in great shape. And looking forward to completing this study. It's critical people not lose sight of the fact, that if we are able to generate. A highly active anti-SARS-CoV-2 antibody, that is scalable and highly safe. It's a really good thing for society viewed through any one of those lenses you proposed.

Now, in terms of the single, and multi-dose, I'll just remind everybody. We first embarked on a multi-dose cohort principally. Because the FDA asked us to demonstrate multi-dose safety. Which is a perfectly reasonable request we're happy to provide. The reason we picked the increment of one month, was to afford future subjects of these medicines. The maximum reasonable flexibility in their dosing regimen, right? Such that if somebody wished to take a medicine like this monthly. I suppose if we're so fortunate as to demonstrate safety, and efficacy, and we're so fortunate to earn a BLA. They could do that on the basis of that multi-dose arm in DECLARATION.

The only reason we didn't pick, for example, an increment of one day. Is because if one were to take VYD2311 monthly, given the antiviral potency we see now. That human being would be carrying around a fairly extraordinary quantity of antiviral power. Not to suggest more couldn't be a tiny bit better, there's a limit. I think, to how much somebody is going to end up wanting to sort of giga-MAB themselves on the way, to maximum potential protection. It's not to say we couldn't have done a day, it's just that we picked a month. Because that felt like a reasonable quantum that affords some flexibility. In terms of expectation, what you're asking is really about, you know, the probabilities of study conduct in this regard, right?

Meaning if we could run DECLARATION 10,000 times, like a Monte Carlo simulation of outcomes. You would of course imagine you'd see some level of potentially low. Breakthrough infection in the single-dose arm, and then some much lower level of breakthrough infection in the multi-dose arm. Consistent with the modeling we provided in our correlative protection analysis. That went into the literature just a couple months ago. You know, the math ought to math, as it were, as you go through these things. Of course, this is a clinical trial. It has its own contours, and we're all gonna find out what the answer is together. I only lament we can't run it 10,000 times. Because I think we would all feel very, very comforted by the mean outcome, and then the tails.

Nonetheless, as we're doing it in sort of real time, and operational space. We still feel great about our progress, and what we think we're gonna demonstrate. Anyone else want to add to that or we're fine?

I'd just say, you know, in getting to one of your first questions. This really comes down to, you know, risk versus benefit. Certainly we know that COVID causes significant symptoms, and we expect the tolerability. And the symptom profile of our mAb to be very, very low. Similarly, you know, what Sanofi's COMPARE study recently showed, and I discussed it. But to be very clear, it showed effects of upwards of 90% of individuals or more with an mRNA vaccine. Or over 80% with a protein-based vaccine directly getting three or so days of symptoms, as a result of that vaccine. That's a real effect on, and on the benefit, you know, versus detriment scale of getting a biologic that's currently on the market.

We expect our overall safety, and tolerability profile. To be substantially better is our expectation. As we look at risk-benefit, the point of what I said earlier is that. We anticipate it'll be significantly better than 15% efficacy. Even at something as extraordinarily low as a 15% efficacy. We'd still expect our medicine, to provide a positive benefit risk ratio. I think that that's really, where we're gonna be focusing a lot of our discussions as we move into the future.

I can't help myself just because I've worked on the buy side. For sufficiently long, to know that I want to remind everyone. The dose justification we selected for VYD2311, and the corresponding antiviral titers. Would conceptually generate a 70%-90%, protective benefit on symptomatic disease. Just because we're spending time contemplating it. What happens at much lower levels, don't mistake that for a second as something we expect. We don't. We expect something much higher, and that's how we dose the medicine. I think we think this is a really important concept for a whole lot of people. Not just our investing partners or capital partners. But also, you know, our counterparties across both infectious disease medicine, general medicine, and policymakers to really think through.

This is a really important moment, not just for our company. But hopefully for the future of this, and potentially other diseases. As we start to really understand the unique merits, of an emerging modality. That hasn't been deployed at particular scale. We aim to do that, and we think it's really, really important to double underline. And educate what we see as a really substantial benefit set that's available here to the public. If we're so lucky to have the good luck we hope, and earn a BLA. Does that all make sense? I know that was a lot.

Yep. No, that's very helpful. Thank you so much.

Thank you. Now our next question coming from the line of Shrader with BTIG. Your line is now open.

Good morning. Thanks for taking the questions, and congratulations on a nice quarter. Couple of quickies on safety, then I have a monitoring question. The surveillance time, what is that for a vaccine now? Has that gone away? My memory is you were supposed to sit for a while, in that case too, so maybe 30 minutes isn't differentiating. I apologize if you said this, but the AEs you see. Do you describe them blinded? Have you seen anaphylaxis? If you mentioned it, I apologize. I have a monitoring follow-up.

On post-vaccine dose monitoring, I will say I don't believe any of us in the room. Understand the current labeling off the top of our heads. I shouldn't understand. I mean, remember. The practice of medicine, of course, out there. Runs very different depending upon, which provider someone runs into. In what context, and what that subject is or is not, right? I'm gonna defer because frankly, I suspect that what was very clear in 2021. You will take this vaccine, and then you will wander around or sit quietly for 15 minutes. I don't know the extent to, which that is actually queued to out in clinical practice today anymore. Stay tuned. Again, I think we would imagine, that if we're successful in our work. We would be given equivalent consideration, if not superior, right?

Let's just see how the profile of the medicine plays out. You know, in terms of monitoring our blinded pooled safety data. I'm just going to decline to answer that question. Mainly, Because while it's a fun thing to contemplate. We are of course, running a ongoing pivotal study. I think, you know, doing exercises such as you're suggesting raises the potential for type one error. That we really don't need in our lives at this point. I think all we see is that going back to adintrevimab, which is again. A highly structurally related antibody, delivered at an approximately equivalent dose. There was not much to write home about. You'll see that in our analysis of the EVADE study.

As we have DECLARATION unfold in real time. We can only make the loose inference. That a change in monitoring time, may well reflect some measure of comfort that the IDMC would also have. We don't know that. It's just a supposition, we can make on the basis of their representation. I apologize. I just don't wanna get too into fun, but dangerous looks at ongoing studies that we're not doing.

It's a fair point, and a good reminder to keep the trial clean. On the monitoring front, where is that these days? Is it as robust as it was years ago? Do you have good surveillance? I'm curious, given you have essentially instant protection, you could in fact be used to respond to outbreaks. The question is, does the infrastructure exist that you know, maybe the antibody is appropriate for highly at-risk people all the time. But maybe the bar drops if you realize, that suddenly there's an outbreak in an area. Where is the surveillance now relative to where it was? And what kind of data do you get? Thank you.

Tom, thank you for that. And I'm gonna apologize in advance, because you've asked a question I love so much. You're gonna have to sit a little longer than usual, because I'm just too excited to answer it. The monitoring is more than sufficient for the purposes you're describing. You know, just to answer the question plainly, of course there's less sequencing going on out there in the world, than there was in 2021. If you ever sit with us at Invivyd, and you look through some of the analytics. That Robbie, and his team routinely study, back in 2021. You could identify clinical, and wastewater variants at such comically low frequency.

I'm not sure that the sample in the sequencer wasn't the only variant. That existed like that on Earth at the time, meaning it was an extraordinary resolution, wildly unnecessary, right? Akin to counting the individual fleas on one dog. It was stunning. What you still have very clearly, is you can roughly know when, and where COVID is, and is not? By the way, you can do it with flu, you can do it with RSV. There are now a whole host of services, again, mainly that focus on the fecal shedding into wastewater. Which is a perfectly wonderful way, to measure the overall sort of location, and timing of the burden.

The reason I love your question so much is, of course. We named our program REVOLUTION, we named our studies DECLARATION and LIBERTY. Because I think the kind of data you're describing, is the kind of data that can actually rationalize prophylaxis. Meaning, why would I go get a COVID vaccine, let's say? That may only confer short-term protection, if I don't reasonably anticipate a meaningful burden of COVID anytime soon. Say, if I'm on the downslope of a recent wave, and appear to be approaching a nadir, well. It wouldn't be particularly rational for me as a consumer. To take on the side effect, and tolerability burden at that time. If what I'm exchanging it for is a pretty low probability, of earning a benefit back in protecting me from disease, right? Look, some of those habits are well worn.

Some of them are sort of cemented by, typical public health guidance of, "Hey, it's fall, go get your vaccine suite." It turns out that might not be the best way to skin the cat, so to speak, in 2026. When we do have access to all these data. If you look at that chart, which I will concede is not the most intuitive concept in the world in our earnings slides. You will notice that part of the point of that is to note, if you want to go through a tolerability event. You really want to protect your way back out of future sickness. In a future that a monoclonal antibody at scale can unlock. It would be our vision, and hope that it's used rationally.

Meaning that individuals, in concert with their care teams. In concert, we hope, with the federal complex, and using big data. Can actually start to allocate prophylactic medicine across space, and time. In a way that resembles the underlying community attack rate, right. You know, that is a really substantial shift, in infectious disease medicine prophylaxis thinking. But I think it would be welcome. Again, I apologize that was too long, and I'm saying all this in front of an epidemiologist physician. Who specializes in infectious disease prophylaxis. Once again, Dr. Mina, surely you can clean that up.

Well, I just wanted to mention there was a question about. About the duration that somebody might be anticipated to have to sit around. Currently on the vaccine labels, there's no longer any, any suggestion. Or specificity given to the clinicians around waiting time after administration of the vaccines. We are expecting that will fall in a similar category, you know, on our labels. Regarding the I don't have too much more to offer, than what Marc already mentioned.

Well, at any rate, spread the word Tom. I think you're thinking in the right way, and I think what you're talking about. Could be a meaningful step change for the overall burden of disease in our society, if we can pull this off.

Okay. Thanks a lot.

Thank you. There are no further questions in the queue at this time. I'll now turn the call back over to Mr. Marc Elia for any closing comments.

Thanks, operator. Thank you all for joining us this morning. I hope it's clear, that we believe we are onto some pretty important, and big things. And these event sets are coming your way within months. Stay tuned. Thanks so much for joining us today. We're gonna look forward to your questions throughout the rest of the day. Bye-bye.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

Good day, and thank you for standing by. Welcome to the Invivyd, Inc. Fourth Quarter 2025 Earnings Conference Call. At this time, participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Katie Falzone, Senior Vice President of Finance. Please go ahead.

Thank you, operator. A short while ago, we issued a press release announcing our Q4 2025 financial results and recent business highlights. That press release and the slides that we are using on today's webcast can be found in the Investors section of the Invivyd, Inc. website under the Press Releases and Events and Presentations sections, respectively. Today's discussion will be led by Marc Elia, Chairman of Invivyd, Inc.'s board of directors. He is joined by Timothy Lee, Chief Commercial Officer; William Duke, Chief Financial Officer; and Dr. Robert Allen, Chief Scientific Officer. During today's discussion, we will be making forward-looking statements concerning, among other things, our corporate and commercial strategy, our research and development activities, our regulatory plans, certain financial expectations, our future prospects, and other statements that are not historical facts. These forward-looking statements are covered within the meaning of the Private Securities Litigation Reform Act and are subject to various risks, assumptions, and uncertainties that may change over time and cause our actual results to differ materially from those expressed or implied today. Forward-looking statements speak only as of the date of this call, and Invivyd, Inc. assumes no duty to update such statements. Additional information on the risk factors that could affect Invivyd, Inc.'s business can be found in our filings made with the U.S. Securities and Exchange Commission, including our most recent Form 10-K, which are also available on our website. I will now turn the call over to Marc.

Thank you, Katie, and good morning, everyone. I will make a few quick remarks by way of executive summary, and then we will discuss our clinical progress. Of note, this morning, you may have seen that we have brought an esteemed physician-scientist into the Invivyd, Inc. fold to serve as our Chief Medical Officer. Michael was unable to join our call this morning; I am sure many of you will enjoy hearing from him going forward. After the clinical discussion, Timothy Lee, our Chief Commercial Officer, will review our work with PEMGARDA, and some of our pre-commercial preparation for VYD2311. William Duke, our Chief Financial Officer, will touch on our financial results for Q4, then we will be happy to take your questions. Now on to the highlights. Our Revolution clinical program is well underway, with the aim of providing Americans with an option for what we believe is needed protection from symptomatic COVID disease. We know investors have many questions about our progress, and we will provide as much detail today as we can. Our commercial work with PEMGARDA continues, and we were pleased to demonstrate growth in the fourth quarter. Commercial activities are establishing an attractive basis for broader commercialization of VYD2311, if approved, by demonstrating the power and durability potential of Invivyd, Inc. monoclonal antibodies. We are continuing to build awareness and understanding of our work with monoclonal antibodies among HCPs, professional societies, vulnerable populations, and government public health entities. We believe that the ongoing American experience with COVID vaccination has left an extraordinarily high medical and economic value opportunity to advance standard of care via monoclonal antibody prophylaxis. In the pipeline, we are excited to begin clinical exploration of our antibodies in long COVID and post-vaccine syndrome as disclosed earlier this quarter. We are very interested that the Advisory Committee on Immunization Practices, or ACIP, a group which advises the U.S. Centers for Disease Control, has recently announced that they are having a full discussion on both topics. The ACIP meeting is currently scheduled for March, and we will be watching with interest. Our collaboration with key academic thought leaders in this space, the SPEAR study group, has yielded a clinical trial design we are moving with all haste to action in light of the substantial unmet need for millions of Americans suffering from long COVID and vaccine injury. In the fourth quarter, we were pleased to share our identification of a highly potent, potentially best-in-class RSV antibody. As you may know, there are today two RSV antibodies approved and recommended for the prevention of RSV in certain neonatal and pediatric populations, and we believe the properties of our antibody are highly competitive with standard of care. As we advance our work across multiple infectious diseases, you may notice a special interest in pediatrics. RSV, COVID, and indeed other viruses exert substantial medical burden on both the elderly and the very young, as well as immunocompromised persons. Finally, as previously guided, expect us to update the Street on our measles program in the first half of this year. In light of the substantial and rapidly growing burden of disease, we are excited to share our progress with you, as well as describing what we see as the potential medical value of such an antibody, which we hope can be both first and best in class. Slide five. Moving on to our clinical update. On slide six, we know that there are investors who are new to the Invivyd, Inc. story, and so we would like to review quickly the medical and scientific background for our work with VYD2311, which hopefully will add context to the updates we provided on the Declaration study in our press release this morning. First, it is important to remember that SARS-CoV-2 has been an extraordinarily unwelcome and ongoing medical burden on the human species. As an ACE2 receptor accessing betacoronavirus adapted for high human virulence and transmissibility, it has exerted medical toll in two distinct phases. In the initial pandemic phase, the virus swiftly moved through the human population, exerting substantial morbidity and mortality, especially among vulnerable populations such as the elderly, and people with relevant comorbidities such as preexisting cardiovascular and renal disease. After vaccination and mounting seropositivity, we see a predictably less violent mortality but still extraordinary medical burden from this virus generally in the same populations. As a vascular, prothrombotic, immunomodulatory virus that circulates pervasively, we now see accelerated human aging and broad health effects in Americans from acute infection, with attendant risks through the substantial growth in long COVID prevalence. Even American economic data collected by the Fed appears to show an unwelcome, impressive growth in American disability since COVID entered our population. We must be less tolerant of this burden. Second, given all of the relevant sociopolitical and medical aspects of this controversial field, we must touch on the evidentiary and regulatory history we have in COVID prophylaxis. The mRNA-based COVID vaccines were each formally studied in a single placebo-controlled clinical trial in 2020. These studies assessed vaccine safety and efficacy versus placebo in a seronegative American population against highly immunologically responsive Wuhan-derivative virus variants, for about seven to eight weeks before unblinding. These studies demonstrated high short-term protection and short-term safety. However, these original datasets also reflect the last opportunity we had as a species to assess absolute safety in randomized, placebo-controlled trials. Given the broad vaccine mandates and rapid virus spread, we as a human species are now all routinely exposed to SARS-CoV-2 and its spike protein, which we see as a type of toxin. And absent a new medical option, we as a species have no real opportunity to avoid exposure to spike protein chronically going forward. Shortly after those original vaccine studies and rollout, our entire species became immunologically educated or seropositive, either through the original campaign or circulating virus, all while undergoing excess morbidity and mortality. Omicron phylogeny virus arose quickly following an evolutionary acquisition of population immunity. Omicron viruses are defined by immune evasiveness or the functional avoidance of human immunologic pressure, whether vaccine-induced or natural. One major consequence of Omicron virus was a natural, predictable, apparent reduction in COVID vaccine efficacy, which has been reliably estimated by epidemiologists at CDC over the past years, and was directly measurable in diminished vaccine titers when vaccine manufacturers updated COVID vaccine compositions from Wuhan-variant virus to Omicron BA.4/5 virus. These analyses can be seen in the relevant vaccine labels, and we see them as predictive of diminished efficacy. COVID vaccine boosts have undergone five structural updates since Wuhan virus vaccines, just on the basis of immunologic comparison. Ongoing new placebo-controlled vaccine studies should provide us all with more insight into these issues in the coming quarters. By contrast, Invivyd, Inc. is now conducting its third randomized, placebo-controlled trial for a COVID monoclonal antibody in five years. Our antibodies change one to the next, rather like the vaccines, to make allowance for virus evolution, although we hope to stay ahead of virus variation rather than chasing it from behind. On a percentage basis, our antibodies change by about the same tiny amount as vaccine antigens, but in contrast to COVID vaccines, we see our antibodies as a much more natural, welcome approach to prophylaxis than serial exposure to spike protein in vaccine form. To us, given the apparent short duration of vaccine-induced protection and the potential risks of administering spike protein in either mRNA or protein form, it is natural to now move to supplemental immune support via monoclonal antibody to exert protection. From an evidentiary and regulatory point of view, our antibodies have undergone more extensive placebo-controlled characterization than the COVID vaccines, including now multiple placebo-controlled clinical trials and, in our recent CANOPY study, long-term characterization of pemivibart in a modern seropositive population and against Omicron virus variants. That brings us to our latest antibody, VYD2311, designed as an alternative to COVID vaccination. VYD2311 is much more potent than pemivibart in vitro, and has a longer measured half-life—properties which we believe may combine to deliver equivalent protection to PEMGARDA, but in a much more scalable and convenient intramuscular form. You can see on slide eight a reminder of the initial pieces of the Revolution clinical program. The Declaration study is a triple-blind, randomized clinical trial once again evaluating the safety of VYD2311 and its ability to reduce the risk of symptomatic disease versus placebo. Our target enrollment for Declaration is approximately 1,770 human subjects, randomized 1:1:1:1—three active arms, one placebo arm. We were recently notified that the Declaration clinical trial has reached target enrollment, and indeed, as is normal in these situations, may modestly over-enroll as sites are given permission to complete any ongoing screening and enrollment before closing. Of note, recently, the Declaration Independent Data Monitoring Committee, or IDMC, conducted a prespecified review of unblinded safety and tolerability data associated with initial experience of Declaration subjects. While the IDMC is completely separate from Invivyd, Inc., we are pleased to relay their written communication to us following that review, which included three recommendations. First, that pregnant and breastfeeding women may now enroll in the study. Second, that women of childbearing age enrolled in the study are no longer required to use contraception. And third, that prespecified safety visits at days 8, 38, and 68 post dosing are no longer required. Finally, Declaration is a study designed to assess the performance of VYD2311 in lowering the risk of symptomatic, PCR-positive COVID-19 versus placebo. In every infectious disease prophylaxis study, a sponsor like us faces an unknown so-called attack rate, or the rate of infection observed in the study, to power our efficacy assessments. Because monoclonal antibody technology in COVID has typically involved a very high efficacy hazard ratio or VE traditionally, it has not taken more than a high single-digit or low double-digit number of events in a study to generate statistical significance. As you may recall, alignment with the FDA on the VYD2311 clinical development pathway included recognition that in our CANOPY clinical trial, pemivibart’s placebo-controlled arm demonstrated robust exploratory efficacy with strong statistical support on the basis of nine total COVID events at three months. America is in the middle of a COVID wave, and we are pleased with the speed of our study recruitment. The majority of our recruitment has occurred only in the past few weeks, and COVID events have begun to appear in our study. We see Declaration event accumulation as on track to date, and on a projected basis, we anticipate suitability for robust assessment of VYD2311 effectiveness if the clinical performance of VYD2311 matches our modeling and prior experience with COVID antibodies. Of course, attack rate in the community and in our study is outside of our control and could change going forward. As a result, Declaration includes a prespecified upsizing algorithm to allow for additional patients in the trial should our event rate projections indicate that Declaration would benefit from more statistical power. This resizing feature is dependent on overall progress, and at this point, our best estimate is that such an analysis would take place in approximately April. We will make an announcement to the Street about our next steps one way or the other at that time. However, depending on overall recruitment rates, with which we have been very pleased so far, a modest upsizing to add statistical power may not meaningfully delay our achievement of “mid-year” timing guidance for Declaration, which we consider as Q2 or Q3 2026. Of course, any upsizing would have some level of timing impact, but we would endeavor to stay within our original guidance boundaries. When we get to that point, we will be happy to provide any updated timing estimates. Irrespective of the overall number of COVID events, we are looking forward to data and believe that it may be a profound next step for our company and for infectious disease medicine if Declaration can demonstrate attractive VYD2311 safety, high antiviral titers, and a demonstration—for the third sequential time—of the vaccine-free protection that an avid monoclonal antibody can provide. With that, I would like to turn the call over to Timothy Lee to discuss our commercial update. Tim?

Thanks, Marc. It is a pleasure to update you all on our work. As we see it, more and more clinicians are turning to monoclonal antibodies. And, frankly, it is common sense. Thomas Paine once wrote that common sense is often the most powerful kind of reasoning. In health care, when evidence accumulates and risk is clear, the logical course becomes difficult to ignore. Our goal is straightforward. It is not simple. We want to give people a choice as they seek protection against COVID. We believe that choice has significant potential because there are still millions of individuals who remain vulnerable and underserved. The medical community increasingly recognizes the importance of antibody therapy, and the long-term consequences of COVID continue to be serious. From in utero exposure risk to children, neurological effects, cardiovascular complications, and more, avoiding infection matters. That perspective is reflected in clinical guidelines. Leading organizations, including the Infectious Diseases Society of America and the National Comprehensive Cancer Network, recommend monoclonal antibodies for prevention of SARS-CoV-2 infection in appropriate high-risk patients. This inclusion of PEMGARDA in the NCCN guidelines for B-cell lymphomas underscores that recognition. We are encouraged to see growing interest and utilization across hematology, oncology, rheumatology, infectious disease, transplant, neurology, and other appropriate specialties. The adoption curve is expanding, and that momentum reinforces our belief in the long-term value of this platform. There is a great deal reflected here on this slide. Many of these data points we have discussed on prior calls. I am pleased that we continue to grow PEMGARDA to serve certain adults and adolescents who are moderately to severely immunocompromised, thus leaving them vulnerable to infection from SARS-CoV-2. What you are seeing is Invivyd, Inc. is building a category. This category has served to expand upon the foundation that is PEMGARDA. Nationally, we see continued growth of accounts who have utilized PEMGARDA, clearly understanding the benefits of protection offered by antibody therapy. We have created this durable foundation with a high degree of accounts reordering PEMGARDA at 77%. We continue to increase available sites of care nationally and across multiple specialties, showing a high confidence for repeat utilization. Our GPO sites of care continue to grow, and the team has been busy providing education at conferences across the nation in hematology, oncology, rheumatology, neurology, pulmonology, transplant, and more. As a team that is defining a treatment paradigm, we are in the right places talking to the right audiences, and our position is strengthening after each engagement. We secured more than 15,000 contracted GPO sites, significantly expanding our commercial footprint. Taken together, these milestones position us to evolve beyond serving a more limited patient population that we have today with PEMGARDA. With our next-generation monoclonal antibody, we see the potential to redefine COVID prevention, moving toward a vaccine-alternative strategy designed to protect broader populations against viral infection. Invivyd, Inc. is proud to partner with Lindsey Vonn because she exemplifies the power of disciplined preparation as the foundation of enduring strength. In her memoir, “Rise: My Story,” Lindsey writes, “Preparation is the one thing I can control, so I have always controlled it to a capital T.” Lindsey prepared at an elite level to always perform at her best, and that requires foresight to minimize anything that can get in her way. That mindset really mirrors our approach. Invivyd, Inc.’s monoclonal antibody platform is built on the belief that proactive immune protection—preparing the body before viral exposure—is the most effective way to preserve performance continuity and long-term health. Viruses should be kept in check to allow everyone to give their best performance. Staying well helps you continue showing up for the moments that matter, and antibodies can help a person stay well. For this reason, Lindsey is an amazing partner to help educate on the importance of antibodies in all of our well-being. With that, I will turn the call over to William Duke to discuss our financials. Bill?

Thank you, Tim. I will quickly review our financials, and then we will open the line for your questions. Our PEMGARDA net revenues continued to grow in the fourth quarter, up 31% over third quarter 2025 and up 25% over fourth quarter 2024. Full net revenues in 2025 totaled $53.4 million, reflecting our continued efforts on driving awareness in the market. After raising over $200 million in 2025, we ended the year with $226.7 million of cash and cash equivalents. This leaves Invivyd, Inc. well capitalized through anticipated pivotal data for VYD2311 in mid-2026 and, depending upon continued PEMGARDA growth and continued operational discipline, potentially well beyond. With that, operator, please open the line for questions.

Our first question comes from the line of Patrick Trucchio with H.C. Wainwright. Your line is now open.

Thanks. Good morning, and congrats on all the progress. Just a couple of follow-up questions from us. Just curious, I think it was mentioned that the potential trial resizing decision in the Declaration program could occur around April depending on event rates. Can you talk a little bit more about that, what the specific statistical criteria would be that would sort of trigger that decision, whether enrollment expansion may be needed? And then just separately, I think, beyond symptomatic PCR-confirmed COVID, I am wondering if you are collecting secondary endpoints such as viral load, symptom duration, or health care utilization, and how that could help the clinical benefit profile that is emerging.

Sure. Thanks for the questions, Patrick. Happy to do my best to enlighten. So on your first question on the resizing, everything we do related to powering is, of course, effectively a two-by-two matrix. Right? You have to understand both the expected VE for which you are powering and then the number of events that accumulate that would allow you to project a final study power. And so right now, as we sit here, we feel pretty good about our progress in the study. All of these algorithms are essentially prespecified, of course, to avoid the potential for bias. And so I think the way I would look at it is like this. And again, I am speaking in concepts because, of course, we are not at that resizing yet, and we do not know what the next few weeks will hold. I think if we were to not trigger the upsizing trigger, it would be because we are highly confident in our ability to statistically assess even a lower-than-anticipated VE, or hazard ratio. And if we do, it really could not even be read as a concern about underpowering as such. It would be simply because the way the trigger is designed it would serve to potentially add power in case the target efficacy is lower than we might otherwise anticipate. So we think of it as really a safety mechanism to ensure, to the best of our ability—which, again, is unfortunately subject to that—the best of our ability to support the power of the study in case VE pencils out as lower than our modeling would suggest. Now the good news in all of that is actually related to the speed of our recruitment. The upsizing target is not particularly onerous. Okay? So you can imagine, in your mind’s eye, approximately another 30% of the study or so as an upsize target. And importantly, of course, that cohort would be time-shifted, right? A little deeper into the spring and then into the summer, which you might imagine collectively would add to the probability that you accumulate more cases, for example, in a future COVID wave. So while perfect is unavailable here and we are not endowed with godly insight into the future weeks, what we can confidently say is we are very pleased with what we are seeing, and we truly do not know whether such a resizing would be triggered. I think what is nice to consider is that if it is, we would simply be in a position to feel better about ultimate study powering. And I think, stepping back way back to reflect on this endeavor, our goal is to have a successful study, if that is what the clinical profile of 2,311 allows. And so to the extent that such an upsizing might incur a relatively modest timing and overall financial penalty, I think we would rather “make the mistake” of having upsized and then only later find out we did not need to, than do it the other way around. So I hope that adds some level of color around the design and thinking. I think it will be very difficult for us to elaborate much more because we speak to the Street only periodically. And, of course, these things occur semi-stochastically. Right? We have just recruited up the bulk of the study. We just have most of the exposure out there, and so far, things are looking great. So we will make sure to update you as we go forward. In terms of secondaries, of course, you can imagine in a study like this, we will be recording all manner of interactions between participants and, for example, the health care complex, which is behind one of the questions you asked. And I am sure a great deal more will always come from this study as it did from CANOPY. I think I would caution on expecting meaningful powering of low-frequency clinical events, e.g., hospitalization or death. I think that would be well beyond the intended power of this exercise. But I think that is also for a reason. Meaning, at this stage in the game, I think we see pretty clear linear biophysical truth—if not, you know, that is sort of a level beyond plausibility, but let us just say it like that—that if you do not get sick from SARS-CoV-2, it is pretty unlikely for you to be hospitalized with SARS-CoV-2 or die from SARS-CoV-2. And so our progress as a species, I think, over these last six years has demonstrated that one of the best ways to stay well is to not get sick. And that is really what we are fixated on trying to demonstrate here. I think that is an evergreen principle. I think it has been well elaborated in all manner of these studies. I think those relationships are pretty clear in all of the data, even from the vaccines. And so our primary focus is really on, I guess, a revisit of what was an earlier-in-the-pandemic message: do not get sick. Most good things, we would think, would follow linearly and logically from that. I think that is the regulatory paradigm in which we are pleased to operate. And I would suspect that if we are successful going forward, there will be many, many opportunities, as our antibodies move into bigger and bigger populations, to demonstrate these kinds of things in, you know, classically post-approval registry and other-type situations in which we will all look eagerly to make sure that we are right—in effect, that not getting a symptomatic infection following virus is just a globally good thing. So, again, not trying to be coy or not answer. I think we will collect a lot of stuff. I do not know how meaningful many of those endpoints will be from a quantitative empowering standpoint, but they will certainly be collected.

Yeah, that is really helpful. If I could, I would just like to ask about the measles antibody program. I think there is an update expected in the first half of this year. Can you give us a little bit more detail on what the envisioned use case is? Is it outbreak prophylaxis? Is it sort of a pediatric bridge therapy, you know, before newborns could get the vaccine? Or are we looking at more of a broader prevention strategy?

Great. So thanks for asking, and I hope it does not diminish your interest when we are in a position to more formally update. So I will just stay in concept land for a little while. Look, you have hit upon the use cases, I think, quite nicely in large part. Right? One of the things we very much like about this modality is that there is not a pharmaceutical premise that we—or use case we—prosecute separate from what native human immunobiology prosecutes. So why do we all have antibody suites? It is to prevent the presentation of symptomatic disease, to treat and knock down viremia once an infection is established, and yeah, as you know, that means we could use such an antibody theoretically for treating active disease. It means we could use—and by the way, that is, we have noted in the past, I think, something that sometimes we will use intravenous immunoglobulin, or IVIG, to do. You could imagine, of course, responding to outbreaks with essentially ring immunization via monoclonal antibody, which might be, you know, an enhanced way to look at the kinetics and potency of what we are able to put on board relative to vaccination. And then more generally, you highlighted something there that I think we have been putting a lot of thought into, which is—I think you used the concept of bridge to vaccine. We think about it almost more in the sense of vaccine enhancement. Meaning, I would just observe, and I think this is noncontroversial, children—babies—are born without a fully developed adaptive immune system, especially the B suite. And so there are data demonstrating that delaying vaccination actually has the ability to improve the profile of vaccination, meaning higher, more durable titers from vaccinating older and older kids, and potentially lower possibility of seronegativity or failure to seroconvert after vaccination, not to mention the potential benefits associated with allowing for early childhood neurocognitive, motor development, all these other things. So look, we are going to be in a position, we hope, to contemplate a lot of things that really, I think, the medical complex has not been in a position to contemplate before, and that is because, justifiably, absent other tools, I think that pediatric schedule is thoughtfully assembled in order to try to have the least vulnerability possible beginning with vaccination at an early age. Well, certain antibodies, especially, you know, nirsevimab (Beyfortus) and others, have demonstrated the benefits associated with passive prophylaxis in the very young. There may be other benefits we can explore going forward, but look, it is premature to say more, although Robert Allen is leaning in, and that usually tells me he wants to add something. So I am going to stop in a second. But I guess I would just say stay tuned because I think we are really intrigued by the potential for some use cases, as you put it, that just have never been contemplated before. And I think our view is there is a potential substantial quantum of medical and potentially economic value to create.

Yeah, I would agree with that answer. And I think that the main thrust of this has come from inbound requests from HCPs for something to provide them with a solution in cases where they have a need for treatment or for post-exposure prophylaxis for measles. And this antibody has been designed with those use cases in mind, as well as some of the potential future use cases that Marc mentioned. So that is really where we are headed with this antibody at this point.

Terrific. Thanks so much.

Thank you. As a reminder, to ask a question at this time—our next question comes from the line of Tom Schrader with BTIG. Your line is now open.

Good morning. Congratulations on the progress. I think you are making positive event comments, and certainly the safety news is fantastic. We have talked a little bit, Marc, about your ability to sculpt the trial a little bit to try to hit hot-spot areas. If you could talk in broad brushstrokes about how well that has gone, and is that in fact self-enforcing—that the people who enroll are, in fact, they know they are in areas where it is a big deal? And then a more specific question: On the myocarditis monitoring, is that going to be clinical myocarditis—yes/no—or is that a more detailed study where you are looking at, I do not know, muscle protein, things like that? Or is that a deeper study, or is that just the rare clinical myocarditis event? Thanks.

Hey. Good morning, Tom. Thanks for the questions. Happy to give you some view here. So, okay, listen. With respect to the Declaration study, the what we have been discussing is, on the margin, our ability to have sites that are in areas that are, we believe, undergoing some level of community COVID attack rate. Right? Now you can see some of that in the ways that we see it—whether it is clinical sequencing, whether it is wastewater sequencing, or sometimes whether it is, for example, emergency department or, you know, sort of one of those things called the sort of, like, low-acuity walk-in clinic kind of census data on where people are reporting symptomatic, positive COVID. So, look, we operate a U.S. study with a relatively broad catch area because a lot of this was designed in October, November, December timeframe, and we were not in possession of such a map. But, you know, we have some ability on the margin to try to place exposures where we see COVID. I think it is also a risk to over-interpret the map because these things move. And they move fast. And so, for example, over the next few weeks or months, to the extent that air conditioning goes on across the U.S. South, the map can move. But we feel pretty well prepared and pretty well configured to hopefully keep seeing event accrual. Now is it self-reinforcing? I could not even begin to answer because I have never even contemplated such a thing. So I guess I will leave it as I do not know. But we will see, in hindsight, whether there is any discernible behavioral aspect to it. On myocarditis, I think at first pass, this is going to be a yes/no exercise mainly because the LIBERTY study where we are looking for that is small, and I think the risk of overt myocarditis or pericarditis following vaccination is relatively low. Now, like all clinical studies, we gather samples. We will look at data. There can always be room for more detailed exploration or follow-up. And again, if we were to see such an event following vaccination, I think we would become very—I will not speak on behalf of the broader scientific or academic community or regulators—but I imagine a lot of people might be interested in that. I just want to double underline: myocarditis/pericarditis is not something we see with antibodies. Right? This is a function of studying mRNA-based COVID vaccination in our comparative and combination LIBERTY study. So, look, we will see. Right? LIBERTY is certainly not powered, or even close to powered, to detect events that we would imagine are at that lower frequency. But let us all find out together.

And if I can ask a quick follow-up, you apparently have an RSV antibody you like. That would seem to be a high bar. That has been a very active area for a long time. Can you give us any detail on maybe what you are improving or how hard you think it would be to have an antibody that was good enough to take on what is a pretty entrenched competition? Thanks.

Sure. And now I really saw Dr. Robert Allen’s body language change, so I know he is going to have some thoughts on this topic. But I would just say this. You know, the RSV antibody field goes back, I believe, to 1998 with palivizumab, or Synagis, and was really only updated at the molecular level, I want to say—and forgive me if I am wrong—in 2023 with the arrival of nirsevimab (Beyfortus). Now nirsevimab is a lovely antibody. We think ours is a lovely antibody, and I think it has some properties that we see as quite compelling. And so, you know, typically in the pharmaceutical industry, when we look at a blockbuster, high-growth antibody space, it is hard to sit back and conceive of the fact that that will be the one thing forever and only and always. And indeed, at the molecular level, we really like what we are seeing and expect to have the ability to compete. I will let Robert elaborate in a minute, but I would also just note we look at RSV as a really attractive component of an emerging strategy. You might well notice now as we go from COVID to RSV, perhaps to measles, perhaps onward to other viruses in which having a commercial portfolio and a real presence in pediatrics has the potential to open or expand on a field that is, I would argue—by contrast to your assertion—in its infancy, no pun intended. Nirsevimab, in year three now, is early. I think its dramatic commercial success is a function of the quality of the medicine. And so, to the extent that we feel great about the quality of our medicine, I can say we are very much looking forward to competing. And now that is a long way off, but we have opportunity in front of us to be clever in clinical trial design, to be clever in, you know, some other aspects that might define our overall profile. And now that Robert is good and warmed up, why do you not add color as you see fit?

I think, you know, what you can know is that we learned a lot in the era of generating COVID antibodies about trying to be upfront about addressing evolutionary drift. Drift represents a change in context that deserves to be addressed periodically. When we look at RSV, in the time since the screening was done for the two known actives that are in the market now, there has been a considerable amount of drift, and really the design of our program was meant to address that. And with that drift, also address some of the known liabilities for the two known actives and overcome those liabilities by design. And so this is where we find ourselves with a very high-quality antibody that is contextualized by the recent evolutionary past of that virus. And I think that, as we see with RSV, we can depend on it to drift—not as much as SARS-CoV-2, rather—but it will drift, and so we will continue to address that as it comes up. It is really the overall strategy that we have with our antibodies: to be very upfront about updating antibodies periodically to match the environment that we find ourselves in. I hope that helps.

Yeah. That is perfect, thank you.

Thank you.

And I am currently showing no further questions at this time. I would like to hand the call over to Marc Elia for closing remarks.

All right. Well, thank you very much, all of you, for joining us this morning. We will look forward to having, I am sure, some follow-up calls throughout the day. Have a great day. Thank you.

This concludes today’s conference. Thank you for your participation. You may now disconnect.