Hello, everyone. Thank you for joining today's HCW @ Home Fireside Chat with Invivyd. I'm Patrick Trucchio, Senior Healthcare Analyst at H.C. Wainwright, and we're pleased to be joined by Marc Elia, Chairman of the Board. Invivyd's developing monoclonal antibody therapies for serious viral infectious diseases, beginning with COVID-19. Invivyd currently has one commercial product, PEMGARDA, or pemivibart, which is authorized under emergency use authorization, or EUA, for COVID-19 pre-exposure prophylaxis in certain immunocompromised patients. Wh ile key near-term catalysts revolve around VYD2311, a next generation intramuscular monoclonal antibody being evaluated in phase III program called Declaration, with enrollment complete and top-line data expected in the third quarter of 2026. Invivyd's also building a broader infectious disease pipeline, including programs in respiratory syncytial virus, or RSV, measles, long COVID, and additional vaccine-preventable pathogens. Just to start, for investors who perhaps are new to the Invivyd story, maybe you can give us an overview of Invivyd today. Sure, Patrick, thanks so much for having us. I apologize, there's, I think, a firetruck going by, which is not a metaphor, in fact, but just an inconvenience. Invivyd is, as you note, a monoclonal antibody company. We are thrilled to focus our tech and our modality on infectious disease because, of course, the human response to pathogens inspired this entire modality, right, which has proven an extraordinary boon to human health in multiple therapeutic areas. Ironically, though, monoclonal antibodies are arguably highly underdeveloped against especially viral pathogens. There just aren't many of them out there. We've had, I believe, the first approval was in 1998 with Synagis for RSV, then there was really not much to speak of in the space until this blush of authorized antibodies during COVID, okay? We are, of course, happy to be one of the companies with an authorized monoclonal for the prevention of COVID-19. Now, I say all that because it does turn out that there's some technological tricks you have to get pretty good at to start to tangle with targets, drug targets, that can evolve, that can move around. We built an entire platform, technologically speaking, to do that, because we felt to accomplish such a task would be just an extraordinary opportunity to advance human health, to advance the public health, and of course, to build a huge amount of shareholder value. I say that because I think we've all gotten used to vaccine franchises that can be mega blockbuster categories. Indeed, in monoclonal antibody land, even nirsevimab or Beyfortus, right, which is a Sanofi's current medicine for the prevention of RSV just in neonates, is now a blockbuster drug growing beautifully, okay? It is accomplishing meaningful change in the early childhood relationship to RSV. We built an entire company around this concept and are thrilled to be in late-stage development with a COVID antibody we believe could become standard of care in the prevention of COVID-19, which we believe can have many advantages over the current vaccines, which remain a blockbuster medical category. We don't plan to stop there. Our pipeline, I think you will see, comprises a host of pathogens, some of which, for example, measles are actually highly vaccinable, and you could argue that the measles vaccine is one of the best vaccines out there. Doesn't mean it does everything for everybody, and in fact, we think there are really interesting ways to look at most any vaccinable virus and make something that can either complement, add to, or even synergize with vaccines. We see a lot of work ahead of us for this company as we build out a modality that has just required a little innovation to unlock. We cannot wait to move from a more specialty medicine, which is PEMGARDA, right, it's authorized under EUA, it has some certain burdens associated with it, to something like VYD2311, which is, of course, highly scalable and built for big populations. It's a pretty exciting time, I think, both at our company and in infectious disease as we navigate these issues. Right. Terrific. Maybe you can talk a little bit more about the scientific rationale for monoclonal antibodies, specifically in infectious disease prevention and treatment. Sure. I'm going to keep it simple, and that, of course, will leave me open to reactions of nuance, but I feel pretty good about dealing with the nuance as well. The reality is that in a preventative setting, and certainly this is true for COVID-19, the monoclonal antibodies that get elicited by vaccination really are the mechanism of transducing protection. I remember back in the pandemic, people would say things like, "Well, what about the T compartment?" By the way, in managing an active infection, of course, things like CD8 T cells are critical. Actually in the prevention, the interruption of pathogenesis from that first contact with the virus, an antibody is doing almost all, if not all of the work. There's now a lot of empiric evidence for that, including data from our own controlled studies of an antibody that generate protection on the order of 94%, 95%, equivalent to the best data ever generated from the vaccines back in the pandemic era. I say all that because I think people sometimes wonder what is the advantage we expect to confer over a vaccine. It's pretty simple. We operate at Invivyd a much better immune system than any human being or mammal can operate. When we make an antibody, we're making something we believe that is highly advantaged over anything you can get out of a vaccine. Then for the even stupid simpler party trick, we simply dose you with that antibody before you get sick, right? Commonly in vaccinology, you would get your vaccine, your antibody titers would rise, they would fade fairly quickly, and unless you saw the inoculum, the attack from the virus right at that optimal time, you may not have a whole lot of antibody floating around to interrupt the disease. Whereas when we use something like VYD2311 or even pemivibart, right? We are putting the antibody you most want into you in an extended half-life time at a dose that can last many quarters. Again, we've demonstrated all of this in controlled studies already. Essentially what you're doing is you're taking the best of the immune system and putting it where you want it in advance. It's essentially just asking our antibodies to put out a match instead of a raging fire, which would be sort of the actual fulminant infection. We look at this as kind of wonderful because it's very simple and beautiful because it's totally inspired by and borrowed from Mother Nature. We're just kind of advancing her art a little bit and time-shifting it forward. When you look at some of these respiratory pathogens like COVID, for which the vaccines may not be particularly great, may not last particularly long, we actually look at it and think this is the optimal way to interact with a virus. All that was required to unlock it was the sort of tech we built that you'll notice other players that were sort of prominent names during the pandemic phase just didn't build around. That's okay. In fact, from our standpoint, that's great. We are sort of enthralled with the interruption using monoclonals early in a lot of different disease states, and we're thrilled to see our COVID data upcoming. Right. Before we get to VYD2311, I did want to ask a few PEMGARDA-focused questions. Sure. Just from a clinical development perspective, what did you learn from the PEMGARDA development that you can then apply forward? As well, what have you learned from the commercialization? Yeah. Whether it's the sort of the real-world need for COVID-19 prophylaxis, or just in terms of identifying patients, payer education- Yeah. ...payer access, et c. Sure. Clinical first was a pretty simple statement. We learned to get, I think, some margin more confident, meaning when we started with pemivibart, back when it was called VYD222, and it was in sort of first in human. You could look across all monoclonal antibodies, and you can rattle them off and it will jog memories, sotrovimab, bebtelovimab, REGEN-COV, and so on and so forth. You could start to look at those datasets as a meta-analysis that asked and answered a question, does an antibody of dose X create a clinical benefit of Y? Okay. It was a bet, right? When we set forth on our immunobridging study in collaboration with the FDA, we at Invivyd had some very clear views about what we thought would happen. The FDA had some open questions about what they thought might happen. Gratifyingly, over the course of our CANOPY study, I think our view was borne out. Our antibodies do transduce algorithmic protection, such and such activity to such and such clinical benefit. Now, it is easier to say today, having executed CANOPY, than it was going in, right? On the way in, we believed that was the case, and we were hopeful that it was the case, but no one had ever done the experiment in a post-Omicron seropositive world, right? Our current world, kind of endemic COVID. Now having done it, we feel really good about essentially the clinical and scientific arithmetic that dictates our dose justification, our clinical designs. We feel like we have a good basis. Again, these are clinical trials, anything can happen, at first principles pharmacologically, we feel like we can understand and control these medicines for the long term and can use that knowledge to really build a big franchise that'll be, I think, at least a little hard to replicate elsewhere. On the commercial front, I think we've learned some things about human behavior that we're going to use for VYD2311, and I'll touch on that in a second. I would also note, I hope very little of what we've had to do with PEMGARDA will bear on VYD2311, meaning pemivibart, PEMGARDA, is a logistical problem. You have infusion centers distant from HCPs. You have patients looking for reimbursement, which blissfully has been a non-issue, I think, eventually for people, but as an EUA medicine, right? That means it's not approved, it's a long infusion, it's got a box warning, it has all these sort of logistical problems. We've had to exert, I think, a lot of effort for a not wholly impressive commercial return. Although, look, we're pleased to have a medicine doing whatever it is, sort of the $60 million run rate growing at 20%. That's not nothing. What we're excited to do is take that same basic science and then translate it commercially at scale in a way that makes counterparties sort of indifferent as to whether or not it's a mAb or a vaccine other than our hope would be VYD2311 is like a vaccine, but one that works better, lasts longer, and is much safer and more tolerable. That's a pretty good setup. What I think we found that has been interesting is, a lot of people, I think, don't always intuit this, certainly I didn't, is that you would imagine risk tolerance for seeing infectious disease runs 100% along the lines of immunocompromised acuity, meaning like you would think that the most vulnerable people, say if you're carrying a solid organ transplant and you're highly immunosuppressed, or you're undergoing deep ablation associated with a hematologic malignancy or something. It turns out that's not always the case. Indeed, the people who seek protection mainly turn out to be the people who want protection. And so p emivibart, for example, is used disproportionately by the rheumatology community. Why that is, we can speculate on. A lot of it, to our belief at least, from having a lot of conversations and dealing with a lot of our physician counterparties, is it's possible those HCPs are simply more holistically involved in their patient's health journey. What I think is going to end up happening as we move into bigger and bigger populations is a lot of people are going to end up, as soon as they are in effect "on label," coming to Invivyd and beginning a dialogue about wellness. I think we're looking forward to that sort of bigger population, more self-activated, more so than trying to knock down doors at busy heme/oncs who yes, appreciate the medicine and yes, want to do it, but their first concern is actually the refractory DLBCL, right? I think because PEMGARDA is such a specialty medicine, because it's burdensome, we have no choice but to have the HCP be a very real participant in the decision to deploy. When we move to something that's IM, can be done certainly at a minute clinic and if we're fortunate and effective, perhaps just done at a pharmacy. A lot of that activation energy can just dissipate. We can move to just competing with the current COVID-19 vaccines, which are, I think certainly one is available at my local pharmacy, and I'm pretty sure I'm not going to have to have a 15-minute consult with an HCP to get it. I'm not suggesting that medicine isn't practiced well in that channel. I'm simply saying there's a much lower activation energy there. We're looking forward to rolling together everything we've learned and going much bigger, much broader right out of the gates. Right. VYD2311, this is the key near-term value driver. I'm wondering, as you're developing this product, what is the ideal product profile that you're trying to establish in terms of potency, durability- Yeah. ...safety, tolerability, as well as the IM administration, which we just discussed, and how- Yes. ...I suppose, how would this also compare to PEMGARDA's IV infusion model? Yeah. Well, like I say, we're hoping the compare to PEMGARDA fades pretty quick because, again, while it's built on the same science and we are very proud of PEMGARDA, it's I would say apples and oranges, but I don't think of oranges as particularly burdensome. Maybe it's like grapes versus a pineapple or something you really have to work at a little bit. I don't know. I'll leave the fruit analogies to someone more clever. The point is, I think for VYD2311, it's hand-built and hardwired to be quite potent, and we really haven't seen a whole lot of meaningful change in any post-Omicron phylogeny virus. We think we're onto something pretty special in that medicine. There may be someday we can make something more potent than VYD2311. I don't know that we need to, but we certainly could. What you then end up with is a medicine you can pencil out as hopefully being very, very high VE in comparison to a vaccine. Okay. As I think most people know, our target, our dose justification was built around a 70%-90% reduction in symptomatic disease. Just your ability to get sick reduced by 70%-90% versus placebo. In the same needle gauge and the same mode of administration as the vaccines. We would expect protection to last a substantial turn longer than a vaccine. Really when we think of the three competitive drivers, we're really asking how well does it work. How long does it work. What does it feel like/how safe is it. We're hoping and certainly we're planning to win on all three. Right. We hope that that'll make a really compelling case out at the vulnerable person/physician interface, or just intuitively appeal to the tens and tens of millions of people who still seek protection via a vaccine. Not to mention, probably the almost 50 million or 100 million who actually might seek protection from a COVID vaccine if they weren't afraid of it. Right. That's an enormous market opportunity. Of course, we're only ever going to serve a fraction of it, but it's objectively massive and I think unlocked by that profile. I'll just pause for a second to note, going forward, there may be some interesting opportunities to even just keep innovating a little bit on the margin. You may have noticed that Americans have acquired this habit of injecting themselves subcutaneously at home, like all the time now, in service of a better image in the mirror, and that's wonderful, right. It's possible that we can certainly, and have explored subQ dosing in our own work down the road. Maybe we actually give people the opportunity to protect themselves from the comfort and safety of their own home. It's certainly not beyond the reach of our tech. I think we see ourselves as building out a really attractive potential for the consumer. What's kind of fun about this field is that you got to remember, HCPs are consumers too. They're just people and actually deal with, shockingly, sick people all the time. We are hopeful, I think, that there's sort of a virtuous growth in appreciation for what's possible through this thing. Right. That's really interesting. With the DECLARATION program now complete, the top line data is on track for the third quarter, and you upsize the trial by 500 subjects following that pre-specified blinded sample size re-estimation, how does the upsizing impact powering, if at all, the trial? Can you help us understand the decision framework- Sure. ...against potential COVID wave over the summer? Yeah. Upsizing is of course, in and of itself, always a seek for more power. In an infectious disease trialing, right, where you don't know the VE. We know, like I say, what we're targeting. There's no scenario where we wouldn't want more power. It really comes down to feasibility and cost, right? You can approach these things by deploying $1 billion, or you can approach them, hopefully with a little more thought in advance, by looking at the sort of sine wave of COVID attack in America. What we did with DECLARATION, and all of this was designed almost a year ago today, was to make a study that we thought would catch events during a winter wave. You might infer from our public statements, particularly at the time of the upsizing, that indeed, we've caught some very meaningful events during the winter wave in which the main body of DECLARATION was open. Now, why did we design a pre-specified upsize? Because we always want more events if we can get them, and our thought was we needed a mechanism such that, you could ask the question, well, why not add 500 people more then? The answer would be, well, not knowing where we would be when we designed the study, you would risk just putting more non-productive exposures out there during a COVID lull, which is indeed where we've been for around the last month and change, right? We decided to create a trigger that was relatively conservative, meaning if we didn't feel like it was overpowered, we were going to conduct this upsizing. Indeed, that trigger was triggered, for lack of a better word, in early April. What you have now is an incremental cohort of 500 patients, which is about the size of CANOPY Cohort B back when we did that, right? Obviously, but that was 450 people actually. This cohort now, this upsize cohort, will exist time shifted into a period of the calendar in North America here, in which there is typically a COVID wave. Indeed, at least at our end, and I know we have access to sometimes a little more or a little different data than some of the street has, there appears to be some COVID attack re-picking up as we go into summer and air conditioning indoor season, particularly across the south. Of course, we have the World Cup and a bunch of other interesting things coming up, that tend to be drivers along with immunologic waning, of some more COVID in America. Look, we're just always going to be in the market for more statistical power. It is possible, as we've disclosed, that the study's already well powered. We just can't know that, right? We're always going to be in the market for more power up to some certain point. Right now, sitting here in June, we feel great and we're just excited to, again, it's never fun to hear that someone gets COVID, but if someone violently coughs or sneezes on television into someone's face during the World Cup, we'll be very happy and hope that they are adjacent to someone in our study, and they can go out there and get some COVID. Right. That's helpful. I think you've discussed in the past VYD2311 as being the design to support 70%-90% protection against symptomatic COVID-19. What are the key assumptions behind that range, and what data should we be looking at or should investors focus on when DECLARATION reads out? What would be sort of a clinically meaningful and then also a commercially meaningful result for DECLARATION? Sure. Well, I think the assumptions underneath it are pretty well elaborated in two places. The first, easiest, and most proximal is a paper from Invivyd authors, Yalcin is the first author, Y-A-L-C-I-N, which is a statistical immunologic correlative protection analysis of pemivibart. Because pemivibart is nearly identical to VYD2311, and again, VYD2311's a little different, and certainly it has way better properties, but structurally and in terms of its interaction with the spike protein, these are very, I think we call them minimally evolved molecules, one to the next. We draw a lot of inspiration from the work we did with pemivibart, and that paper lays out the so-called antibody titers or SVNA, serum virus-neutralizing antibody titers. And for those of you that are numerate, all that number represents is the serum concentration divided by its antiviral potency. Okay. You can actually back-calculate what you think our SVNA titers are at any given moment by looking at disclosed IC50s of VYD2311 against certain variants, and where you believe someone is in their PK curve, okay, of 250 mg of antibody divided by a blood volume. Okay. And the nice and interesting thing about that curve, and those of you who look up that paper will notice that the Y-axis is linear and the X-axis is logarithmic. So it's actually a very flat sigmoid curve, where a little bit of antibody helps a lot. We see meaningful protection on the order of 50% at titers as low as one in 50, and very, very robust protection, meaning 80%, 90% at titers up at the, call it one in 2,000 level. All right. That's how we built our dose justification, and the virus backdrop looks about the same. We're in an XBB dominant world for the most part, so we don't anticipate those assumptions changing particularly. That's how we derive our target VE. Again, that's based on the arithmetic. We're of course, running a clinical trial, which is why we always want more power, right? The statistics are just sort of the consequence of having enough events to really know with high confidence where on that curve you're landing. We're pretty confident we're going to land in some interesting territory on that curve. I say two places to look because that paper, and pemivibart is place one. I would just suggest that place two is data from most any other antibody you'll ever see, going back to REGEN-COV, going back to adintrevimab, our prior molecule in the EVADE study. The sorts of correlate curves I'm talking about, they're a little unique to different lineages of antibodies. Meaning, I think Invivyd antibodies are a little different and have slightly different numbers than others' antibodies. If you zoom out, they're very similar. You got to think of us as drawing inspiration not just from the particulars of our own work, but also, of course, we operate in a genus. That's a little like asking, "Well, will this statin lower LDL and have such and such an outcome event?" Yes, they're different. They're not so hugely different that it defies predictability. We think of our 70%-90% as being extraordinary. That's well above where we see vaccines sitting today. If you go back to the beginning of the pandemic, the FDA actually called a 50% reduction clinically meaningful. As the vaccine efficacy declined, I think good old dearly departed Makary and Prasad decided 30% was meaningful. Of course, we're hoping to be manyfold above that. Sure. That makes sense. Recently also, the IDMC recommended reducing post-dose monitoring from two hours to 30 minutes. How important is that change for trial execution for a potential real-world administration profile of the VYD2311? I don't think it's particularly important for either. That is a trialing feature that we imported from CANOPY, and candidly we would've imagined nobody would consider much about the minutia of the trialing other than the inference. The inference we took was that if one were worried about potential anaphylaxis or hypersensitivity, which is or can be a feature of IV administration of a ton of antibody, okay? You saw some in CANOPY with pemivibart, that we wouldn't expect to see it in VYD2311. I don't think clinical monitoring time is going to be a particularly big feature of the practice of medicine for this antibody if the safety and tolerability data look as we expect. Now, we don't know what the IDMC sees at any given moment, but it's hard to be anything other than really encouraged by that feedback. Today, I think there is guidance from CDC that someone should wait 15 minutes after you give a COVID vaccine to watch the subject. I'm really not aware that that particularly happens anymore. Certainly in 2021, I did it in a Walgreens somewhere in suburban Connecticut, but I may have just walked out after 11 minutes. That was during passports and all the rest, and blah, blah. I don't expect it to be a particularly meaningful feature of our commercial work at all. Right. That's interesting. Also, how should we think about the single-dose and monthly-dose arms in DECLARATION- Sure. ...just in terms of statistical hierarchy, how could different outcomes across the two arms influence- Yeah. ...the BLA labeling, et c? Yep. We haven't fully disclosed our SAP. I can just comment on the idea that either arm can constitute a win statistically. We are more interested in the single-dose arm for a whole lot of reasons. Firstly, given the half-life of VYD2311, we would expect a single dose to confirm meaningful protection for a year, maybe more, depending on, again, what you call meaningful. The multi-dose arm really has a different purpose in mind, okay? Meaning we don't imagine a commercial product that comprises people injecting themselves monthly. Although, I suppose if somebody wants to and the data support it, they are free to do so, and we would probably earn more revenue, and they would be very well protected from COVID. Actually, that arm was built to answer a question from the FDA, which is demonstrate the safety of repeat dosing, and it was designed to substantiate, again, if the data look favorable, labeling language that would look very familiar to anyone who's ever read a COVID vaccine label. The usage directions on SPIKEVAX and COMIRNATY both say use once or no more than every two months. You'll notice they give you no information other than that. How long will it last? Don't know. How will it feel? Eh. What we did was we built a paradigm in DECLARATION that would allow for the labeling language of use once or no more than every month. We're not really imagining anyone using it monthly, I think what it does substantiate or may help people with is if they, from time to time, want to go grab it, meaning let's say you were so kind and you follow our company, you want to use it, and you do it in September, and then you realize, oh God, you're going to San Francisco in January and there's a COVID wave, it should allow you to deal with an HCP, and be able to access antibody more or less on demand. That was our thought behind it. Again, we would expect to see not much of a change in safety and tolerability, from a monthly dose other than the actual ouches themselves. It's built with maximum flexibility for the end user in mind. Right. That's helpful. Assuming a positive DECLARATION outcome in the third quarter, what are the key steps between top-line data and BLA submission? Those principally consist of every employee who's relevant at Invivyd pulling all-nighters until a massive amount of documentation is in the hands of your favorite regulator in mind. I think, look, we are going to move with all haste, with a winter in front of us at that point, to put the federal government in a position to provide an option for vulnerable people who may wish to not get COVID and may also wish to not vaccinate, and that looks like a goodly number of people. We are going to be working very hard. Again, we should be in possession of some LIBERTY data, which is another companion study we can talk about that has to do with a head-to-head and combination evaluation of vaccine and antibody. Those two would constitute the bulk of an expected filing, and we think that the combination is going to be really useful and attractive. We're going to be working. It's going to be a very unchill fall at Invivyd. Not that it's particularly chill right now, but it'll be extra un-chill as we move to action all this as quick as we can. Yeah. That's helpful. Maybe on the LIBERTY trial, I think this trial is expected to initiate this month. Maybe you can just- Well, we said midyear. We've never said this month. Okay. We said midyear. Oh, okay. Gosh, we are awfully close to the, what is it? The summer equinox? I don't know what that one's called. We're on it. We're getting close, and stay tuned. That study also arises from an agency request to characterize the safety and immunologic profile of combining antibody and vaccine. Again, it's a little more than a purely academic question because you might imagine there are people who may wish both, for example, and you'd like to know what that entails. Our colleagues and competitors at Regeneron actually ran a version of this experiment long ago in seronegative people, and the consequences were not particularly interesting to look at. There was, when you deploy the antibody about at the same time as the vaccine, you would see a modest reduction in the neutralizing antibodies generated by the vaccine antigen. It sort of goes to the beauty and redundancy of the immune system. We would expect you to still have a vaccine result. I don't think there'll be much remarkable on the safety side about combining, and in the end, I think with vaccine uptake as low as it is, we're not particularly wound up one way or another about what the combination looks like. We're just going to be interested to see the translational immunology play out. What's fun about LIBERTY is, of course, it also involves a head-to-head comparison of early safety and tolerability. Okay? One of the central attractive bits about deploying a monoclonal is they don't engage the immune system, and they mainly just sit around in your and my serum, just like an ordinary native IgG to you or me, until there's target to engage. Our expectation, based especially on some recent data from Sanofi comparing one vaccine to another, a protein versus mRNA, is that, of course, the COVID vaccines are relatively notorious for giving subjects a reasonably rough reactogenicity or immunologic tolerability profile over the first few days, and we would expect to not see a whole lot with antibodies. We are formally doing that experiment to really buttress the profile and prevent anyone from needing to make cross-trial comparisons and to kind of hand wave about it. We just figured let's go get the data at reasonable cost, and quick time hopefully, so that HCPs, vulnerable populations, and indeed policy people can see, "Hey, there may be a better way to solve this problem." We're looking forward to getting that up and running soon. Did you say that you needed the data from both DECLARATION and LIBERTY for the BLA? I would suspect we certainly need the immunologic interaction for the BLA. There's a little more in DECLARATION than is, I think, on the critical path, but our anticipated plan would be filing it all. I guess so if everything sort of went to plan, when would we expect to have VYD2311 available on the market, and how does fast track, how does that play into this? Yeah. Yeah. I don't think we've been a little coy about exact timing on commercial, but I think you can imagine if we're working very hard to bring it to the FDA in kind of late 2026, or certainly second half, post fourth quarter 2026, it'll be more about them. I would offer one authentic and a heartfelt compliment to our friends in Silver Spring, Maryland, at the FDA. In the case of COVID, and certainly with our work at Invivyd, they have been extremely responsive and rapid. Let's see. Certainly with the kind of timing we're talking about, it's a 2027 event, we believe. I also notice there has been just a touch of, let's call it, political heat around this issue of the COVID vaccines, it wouldn't surprise me if they moved very quickly indeed. Yeah. That makes sense. There's also the DRUMMER trial, which I believe is expected to assess the safety and immunogenicity in children. Yeah. This is age 0-11 years. Correct. I was wondering how this data is going to play into the BLA. This is not on the critical path for the first filing. This is something we will action if and when we are in possession of positive DECLARATION data that shows us an attractive VE that has us thinking we have a great commercial product on our hands. Actually, kids are pretty impressively burdened by SARS-CoV-2, and of course, the younger you are, the riskier it is to see. I think we look at pediatrics as a really interesting analog to the work Sanofi has done with Beyfortus and RSV, right? When you dose three of 3.8 million live births in the U.S. with a $500 antibody, which is roughly where Beyfortus is, you end up with a blockbuster medicine pretty quickly, number one. Number two, you protect really, really vulnerable infants beautifully as they develop, right? I don't know how many of you out there have studied nirsevimab closely, but there's some really lovely data around it that show you, number one, infants can actually be a pretty impressive contributor to overall disease transmission because they are so naked, so to speak, immunologically. Number two, that you can turn off a lot of RSV in a community, therefore, by deploying nirsevimab. Again, if you read into the data a bit, it would not surprise me if we learned five or 10 years from now that abrogating RSV in infants meaningfully impacts, for example, childhood asthma rates. Not a one of these viruses is benign. When you start to talk about infants, they become even more problematic. Look, when you look at our pipeline, you might imagine we're doing a lot of this work with pediatrics and the elderly in mind. DRUMMER is something that is a safety and immunologic bridging study, meaning it's not an efficacy study. It'll refer to whatever was generated in DECLARATION, but we're pretty well looking forward to establishing a pediatric footprint. As you know, we do have what we believe is a best-in-class RSV mAb. We have what we believe is a best-in-class measles mAb. Those are both sort of under construction right now, awaiting clinic next year. Don't be surprised if Invivyd ends up with a pipeline of really important, interesting antibodies that are designed, in effect, to complement Beyfortus and actually make the pediatric journey and maybe even the pediatric vaccine schedule better- Yeah. ...five or 10 years from now. That's really interesting. Just back on VYD2311, assuming that the drug is approved. What's the initial commercial target population? How large could this addressable population be? How do you segment sort of the immunocompromised patients, older adults, vaccine-intolerant individuals? Yeah. Those who are hesitant to vaccines, then as well, we were talking about pediatric patients- Yeah. ...I know there's a lot of groups here, so There's a lot of groups. Look, I think no matter how you slice our work, the answer is the sort of total addressable market can be considered as quite large. By that I mean even just moving through the population we are beginning to serve with pemivibart, PEMGARDA, that's on the order of 10 million-13 million Americans, depending on how you count moderately to severely immunocompromised persons. Of course, by virtue of having a commercial footprint in that population, you might imagine it's the natural place to start, and indeed, it's the natural place to start. We will be hard at work, simply migrating our book of business from something that is burdensome and therefore constrained to something we hope is not at all burdensome and relatively unconstrained in that population, and we'll be working there. The FDA, actually, and the medical complex define our target population as those Americans at risk of progression to severe COVID-19. When you read that population, let's say from the Prasad Makary 2025 "New England Journal," you find that's about 170 million Americans. It's people with diabetes, who are obese, who have heart failure, who have asthma. There are so many people who are vulnerable. Gratifyingly, I think with that big of a counterparty population, you can start to imagine where we're going to focus, which is around where we currently are, and then we will hope to be in receipt of authentic demand from some of these other populations as people learn about the availability of our medicine. We're going to take a, I think, measured, stepwise approach because with an approved medicine, we're going to have some very real industrial mobilization to do, right? We've got to kind of build the category while we build demand, while we build supply, and so forth. I think we've been very clear about saying we have on the order of about 1 million doses ready to go right now. That's great, but it's not enough, and we are imagining down the road that indeed, if we did our work correctly going forward, there's no American that couldn't benefit. Meaning, at some level, we're all a little immunocompromised against SARS-CoV-2 because you can always get it, no matter who you are. We in the FDA have, and I think, I can't remember if we wrote this into our press release, but we happily share the FDA's guidance to us was, were we to double our safety exposures in DECLARATION, which is a pretty modestly sized study, the BLA could be expanded to just any American over 12. That's where this is going, we hope. I don't mean any American over 12 in that kind of SpaceX TAM sort of sense of like, "It's everybody and everything," but I do think we see out there a very meaningful burden of disease, a very meaningful unmet need in elderly, very young, and immunocompromised, and we're just looking forward to keeping as many people healthy as we possibly can. Yeah, that makes a lot of sense. Regarding the reimbursement pathway have you had discussions with payers, and what are you expecting as far as the- Yeah. ...is it likely to sit with medical benefit, pharmacy benefit, a hybrid model? If you've had those conversations, how have they been going with payers? Yeah. I'll answer in part because we're obviously in the thick of a lot of this, right? There's a lot of moving pieces here, including one giant swing factor that maybe I know you know about, but is embedded into all of this, which will be the role of the federal government in some of this. I'll come back to that. Of course, you must imagine not only do we have some of those conversations today around pemivibart, but we are doing our research and having some of the sort of opening conversations about the concept of VYD2311 as a next generation. I think it's safe to say the feedback has been great. It's easy to say. Let's find out how this all unfolds. I think you would not be surprised to learn that there are many people at stakeholders across the industry who are also themselves consumers and have some pretty pointed views about vaccinology, for example. I think are interested in advancing the art in infectious disease into more of a wellness play like a monoclonal antibody. I guess I'm just saying people are very willing and able to make nice general noises. Let's see how productively we can all partner together to deliver care. Actually, for pemivibart, which is a relatively quite expensive monoclonal antibody, at least from a prophylactic standpoint, there's really not been any kind of reimbursement pushback. There's logistics, but not a whole lot of you don't get reimbursed. The swing factor is, of course the federal government and the role of the Advisory Committee on Immunization Practices, or so-called ACIP, CDC, and the role that the recommended vaccine schedule has on the economics of infectious disease prophylaxis. Thanks to the ACA, the IRA, those recommended vaccines on the ACIP's schedule, and again, the COVID vaccines are still right there, recommended for those persons who are at risk. Those become free, essentially, with zero out-of-pocket to those persons who are federally or commercially insured. Certainly, I've enjoyed a nice couple of hearty handshakes and some very nice noises from the good Dr. Mehmet Oz, who controls America's reimbursement checkbook right now. I think their attitude at CMS is, "Hey, look, this is an investment in American health that's probably returning across populations." If we can keep America healthy, and whether you decide to put the again on it or not is really the only political tell here, I think there's a really strong interest in having high-quality prophylaxis around. Look, that's why if we're ever a little more vague than other companies, it's because stay tuned, there's about to be a lot of really interesting discussions with really important stakeholders. You can look to Beyfortus at Sanofi as a model for what is possible here. They went from a standing start to something like 75% or 80% of American live births in three years. That's extraordinary in commercial returns. I don't know where MedImmune would be trading if it were still a standalone biotech company with its only product as Beyfortus, but I suspect it'd be a very valuable asset. We're looking forward to some productive partnership along the same lines, but stay tuned. This is going to be fascinating because no one's ever done what we're trying to do, which is take a monoclonal essentially up against a sitting incumbent vaccine. Right. That's interesting. Maybe you can talk about the cash runway, and just the ability to sort of fund the program, the DECLARATION- Yeah, ...program, the eventual commercialization. Yeah. We're certainly very well capitalized through data and any host of catalysts, right? We feel good about that, and that's thanks to the contributions of very smart people we appreciate a lot who wanted to step up and fuel this program. I think, depending on how things unfold, we may well be well capitalized quite a bit beyond that and/or explore some interesting non-equity alternatives. Let's see. As we think about it, because certainly, I think our view at Invivyd is this is an undervalued company, and we can understand why that is and still work to try to optimize the compounding journey for common shareholders. Stay tuned, right? There's a lot of action, I think, not very far away, and we have more than enough capital to fuel that beautifully. Again, we feel pretty good and we're just working behind the scenes to make everything over these next handful of months go as smoothly as we possibly can. Right. Terrific. Then maybe you can talk to us about the SPEAR program. Sure. I believe in the long COVID and COVID-19 post-vaccination syndrome, I think this one is also supposed to start around the middle of this year. Yes. Just tell us what we are to expect from this program. Sure. Look, we look at this as an exploratory study to ask the question formally, does deploying a very real quantum, I mean, you can expect us to use a pretty high dose of VYD2311 to just not leave a lot on the table here. Does a very high dose of antiviral antibody help people with long COVID who have some evidence of antigen persistence? I say antigen because maybe that's a viral reservoir, and maybe it's protracted vaccine production. I don't know how many of those latter people are out there, but they appear to be out there. We're asking this question even though I think we acknowledge, and again, you may recall, I suffer to this day from certain manifestations of long COVID. It doesn't mean that it's a non-complex syndrome, right? It may be very complex. What moved us at Invivyd is this, there are people accessing pemivibart right now for long COVID off-label, and they have a funny habit of making their experiences very public. You will see a little bit of published literature on the effects people have earned from using pemivibart for their long COVID. If you are so inclined to dive down into Facebook or Reddit or some of these other places where people gather and kind of organize, what compelled us and the other SPEAR investigators were some very, very compelling anecdotes of either substantial improvement or clinical remission. Knowing that it's a complex phenotype, knowing that an antibody is a very specific intervention, but blissfully, our antibodies are highly active and broad. No one's done this experiment really with an active antibody since Regeneron did a little bit of long COVID work that got published, and people seem to find those antibodies very helpful. What I know to be true about long COVID is that while it may be complex, it's also huge. There's millions of Americans who either are suffering or certainly very much believe they are suffering from one of the two, right? Either long COVID or post-vaccine syndrome. We are doing a placebo-controlled study, and you should start to hear some details and see some details soon, to ask the question, okay, what do we see in a formalized, rigorous study context in which we're going to try to select for people we think may benefit, or at least who have some evidence, and again, here the assays are a little, let's call them academic, okay? We're going to do our best, and if we see a meaningful treatment effect there, I think we would move very quickly to demonstrating that in a pivotal and getting a drug on the market to treat long COVID, because it is an enormous problem that is continuing to grow. Right. That's really interesting. You sort of addressed some of these other questions I had earlier, but I just wanted to come back to the pipeline and just on both RSV and measles, if you can walk us through each of these compounds. Sure. Sort of the timing of when can we expect first in human trials- Yeah. ...for each of these compounds, what's sort of the patient groups who you'd be targeting for each of them? Yeah. They're very different programs on a very similar calendar. Both of these we expect in the clinic in 2027. The balance of the year may be a little quiet because we're in essentially production and IND enablement on both of those programs. In that way, they're similar. In other ways, they're quite different. RSV, of course, is a very well-characterized pharmaceutical market with a current market leader that's Beyfortus or nirsevimab. Then there's Merck coming along with influenza or clesrovimab. We designed our medicine, which is VBY329, we designed it to improve on the state of the art in terms of potency and variant coverage. [Break] Talked about flu since 1919, but that doesn't stop everyone from using a flu vaccine, and it certainly doesn't stop our favorite dearly departed Cidara from being an incredibly valuable asset. I think people tend to take the small view on COVID, whereas we would take the big one, it's our job to action that. I think when we get to a place that's characterized by more certainty and I think more revenue, people are going to be really, really pleasantly surprised, I think by the things that we, and right now pretty much only we, can do in other infectious diseases that can be blockbuster products in their own right. It's not crazy to sit down and pencil out a world in which Invivyd owns multiple antibodies that do pretty unique things, and that the public health and medical complex can actually gravitate to really rapidly. There's nothing particularly controversial about a monoclonal antibody against a pathogen. They're just hard to get. If we've built something that makes them a little bit easier to get, I think today we look at Invivyd as a very small company, but we have our eyes on someday being Gilead in effect, but in a biological context. I mean old Gilead, the HIV, Hep C, right? Sure. You really dominate the innovative space in some certain pathogens, and again, blissfully because COVID and other infectious disease antibodies are hard, we don't have a lot of company today, and I hope it stays that way. Right. Terrific. Well, thanks Marc, so much. It's always a pleasure to catch up. It's a very exciting time in Invivyd, I appreciate your time today. Thanks for everyone else for joining us. Have a great rest of your day and week. Patrick, thanks so much.