Well, thank you everyone for joining us today. I have Mark Elliott from InVivid with me. Mark, thank you for joining us.

Thank you for having us. It's great to be here.

I think we're really excited to get to talking about InVivid so we can just get to it. I want to start with maybe just a softball question to talk about your views about passive versus active immunity and why you believe InVivid can really revolutionize the treatment of infectious disease.

Sure. It's very soft, but I'll swing away. So I think, look, we're in year 300 of the vaccine, right? And we're in about year 40 of the monoclonal antibody gap, maybe 50 if you count really, really early stuff. And what's been surprising about the journey of the antibody, given that it's just a replicate of native human effector biology, is that it's been so almost exclusively devoted to self-targets, right? It's a wonderful pharmacologic modality, but it's been really under leveraged in virology and infectious disease, particularly if you think about how it works and where it's from, right? So some of that is because viruses can be very challenging to target with a monoclonal. That's why the human immune response is, you know, polyclonal and complex. But what has been interesting about the last 10 or 15 years of monoclonal technology in the pharmaceutical industry is it's allowed us to start to ask and answer tougher questions, including how do we think about deploying molecules like monoclonal antibodies against infectious diseases, which have the unfortunate habit of moving around a little bit, right? These are live, well, they're not really alive, but you get it. They're targets that can be in motion, and we built InVivid to do that. Our thinking was both around COVID-19, which we can talk about, but also a great many other diseases. If you could solve those kinds of problems, and then use modern engineering to make long-lasting antibodies that are really potent, you could actually start to drive a whole new vertical that would be totally complementary to vaccinology. So think about every disease for which you are familiar with a vaccine. There may well be a role for a monoclonal to either treat that disease if you get a breakthrough infection, to complement a vaccine where the protection is inadequate, too short-lived, maybe too dangerous or unpleasant to acquire, or maybe to use instead of a vaccine where a vaccine really can't get, right? Classically, you would see this having played out in RSV or respiratory syncytial virus, right? So you have a lovely monoclonal antibody called nersevumab sold as Bayfortis. You can't vaccinate a neonate against RSV. You can try, but it's not great to vaccinate a pregnant mother. So what do you do? You turn to nature's toolkit, you grab a monoclonal, you make a good one against RSV, and what do you know? You have a blockbuster. So InVivid was built to try to solve that problem in a bunch of different verticals, starting with COVID, because that is a place where, and I don't want to shock you, Josh, the vaccines may not be all that great. So there's a real room for an extraordinary new vertical that builds on normal human immunobiology, little sprinkle of modern pharmaceutical tech that we rolled together into InVivid to make new objects that I think over 20 years are going to suddenly look obvious in hindsight, right? Why weren't we doing this more the whole way? If you'd invented monoclonal antibody technology in the year 1750, it would have taken a long time for someone to come up with something as sort of different and weird as a vaccine, right? To train you to respond, right? If you could actually just go to direct protection injected into you with some regular and low burden consequence. I just think we are at a moment in infectious disease medicine where people are starting to think more constructively about this stuff. And we are thrilled to provide the medicines that I think are gonna offer a lot of people a lot more protection than they can get from just a vaccine.

Yeah, I mean, thank you very much. I think that's a great overview. And I really wanna dive more deeply into some of the expansion opportunities and maybe we'll start with COVID. and let's start with, let's start with your 2311 program and, and maybe a comparison to your currently approved product PemGarda, which I think a lot of people forget about. And I want to talk about that as well.

So look, appreciate it. And we say authorized in our world, right? We have a medicine PemGarda, which is a COVID-19 antibody that prevents symptomatic COVID-19. And it's authorized under EUA for the prevention of COVID in immunocompromised persons, okay? Moderately to severely immunocompromised persons. People forget about it because it's not designed to be a big population medicine. It's a little bit nichey. It's an IV. You can think of it as a Gen 1 antibody, right? So whatever your favorite thing is, a Model T Ford or, you know, the first ever cell phone, right? It's sort of bulky and difficult to access, but it makes a really important point. And I'll give you the really important point. First of all, it's both by design and then empirically through experience, it is actually doing the job we asked it to do, which is drug a target that is regarded as in high motion and do so durably, stably, and without regard for the variant flow. So every year with COVID, we debate which vaccine variant we're going to go with. We don't worry about that in Vivid. We just go, well, you use PemGarda because it works, right, in that way. So we see it as proof of concept, and we're thrilled that it's doing, you know, whatever it's going to do in revenue. It's been, you know, at the 50, 60 million in revenue growing at around 20-some-odd percent, and that's great. But it's really just a very modest warm-up act because we don't need to change all that much to suddenly migrate the same science, the same backbone, the same idea set to the new medicine you referred to, VYD 2311, which is in a pivotal right now, for a much broader population. And we would expect it to be essentially identical or equivalent to Pemgarda in protection, but not an infusion. And I am a straight intramuscular, just like the vaccine, a low dose with a very, what we hope and expect to be an attractive safety and tolerability profile, a very high protective rate along the lines of Pemgarda. And therefore, you know, when we look at that profile, we are excited to bring the world something that we think would render a COVID vaccine, which I would just point out is a multi-billion dollar global franchise right now, essentially a distant second-line option for people who maybe can't get a monoclonal antibody that we would expect to deliver higher protection, more durably, and with much more attractive safety. So look, COVID is a place that, you know, elicits a lot of sort of social emotion these days, but if you just zoom out from any experience you've had and recognize there is a sitting vaccine franchise. It's very valuable. It can be disrupted. And the way in which it can be disrupted, we think, is well-validated in our own hands with prior antibodies and our current antibody, but also others. We're not proposing something revolutionary in the medicine. We just have a lot of fancy tech that allows us to accomplish something at the level of the interaction between our antibody and the virus that other people don't have. So to the extent that that's, I think a really, really important, it's the main act of this company for the next few years as we build that out. We are absolutely chomping at the bit to get people really high quality protection from a modality. We think they're actually going to grow to love. One of the most rewarding things about studying this marketplace and interacting with it is you realize how little people know and how ready they are to learn. If we go out and we survey people When we say, here is, you know, a vaccine and here is an antibody, which would you choose? People are deeply intrigued by an antibody because they intuitively perceive this is something that looks like what I would be doing otherwise, right? It's sort of natural, for lack of a better word, right? We might produce it, but it's a natural way of getting protection from a disease, maybe in contrast to a vaccine that way. So, yeah, we're looking forward to delivering Pivotal data later this year, moving as expeditiously as we can towards market, and we think there's an enormous opportunity right here for this company to go grab.

And so maybe, why don't we just talk a little bit for a second about the design and the, you know, our expectations for the declaration phase results, which is the Pivotal that you're talking about. And how do we expect the design and maybe the results to improve upon, you know, the TPV of the vaccine?

Sure. So declaration is in some ways, it's just a very simple study with a couple of twists that we think are, you know, useful or clever or whatever you would you would say. I say it's simple because it's asking such a simple question. Does our antibody lower the risk of symptomatic PCR positive COVID? It's just, do you get sick or don't you, compared to placebo? Now, over the last five years, no one's really had a great ability to ask and answer that If you think about vaccines, they're typically obsessing over, do we lower hospitalization? Do we keep you alive? Because it is perceived that, and I think accurately, they may not be so effective anymore at actually just stopping you from getting sick at a high rate. We believe we're in a position to demonstrate a pretty high level of reduction in just getting sick. that's your sort of apex endpoint, right? If you deliver on that, I think it's pretty unlikely that if you're not getting sick, you're going to the hospital. If you're not getting sick and you're not going to the hospital, it's pretty unlikely you're gonna die, right? So we love operating at that high level. Declaration is a pivotal clinical study that asks in three arms, how well do we do that? First, you just do placebo. Then you do one dose of our antibody and you measure the reduction from placebo from one dose over 90 days. It doesn't mean the protection is only going to last 90 days. It's going to last much longer, we believe. However, we're measuring it over 90 days for a whole lot of reasons, including it's actually quite a bit longer than the vaccines for COVID-19 were ever studied in a controlled fashion, but that's neither here nor there. We're looking forward to delivering those data. Then the third arm is a repeat dose. So we actually administer the antibody monthly, mainly because the FDA has asked us to interrogate repeat safety. So we're doing that in one arm. But there's also something fun about it, which is one arm is a dose where, of course, you inject the antibody, the serum levels rise and then gently fall. In the other arm, they rise, and then they rise more, and then they rise more as we deliver multiple doses. So you're actually going to see if we have enough power in the study to see it, or we'll just demonstrate it out in the world someday. You can actually sort of choose at some level however much protection you want. That's a really important nuance that gets beyond the study, and it goes to our social posture. What do we do with vaccines? Well, if you read the COVID vaccine label, it actually says use once or no more than every two months. That is on those labels. That's all the information you're given. How long does it last? How often should I do it? I don't really know. What we're trying to do is move from a centrally mandated posture to something more resembling choice. do it once a year or do it when you want. For example, if someone in this room sneezed on me and we had an approved antibody, wouldn't it be fun to toddle on down to Dwayne Reed and have somebody give me a little antibody boost because I don't like the look of this Josh Sands and I don't know if he's harboring COVID-19 and you know, I don't want it, right? So we're actually going to try to maneuver the intersection between public health and individual choice and wellness, which is, I think, really, I don't even think it's like a strategic option. I think it's a necessity in 2026. I think we've all gone through this incredible decline in the public trust, and I think our medicines are designed to empower individual wellness. That's how declarations actually designed. I know that sounded like a socio-political statement, but it's actually the design feature of declaration, and it's why you might imagine we sort of branded it and named this program the way we branded it and named it. We're trying to exert meaningful change at the population level. That study is step one.

So let's talk about, let's dive a little bit more into declaration.

And so you recently announced that you upsized the trial, and maybe what was impetus for that does it give you stronger conviction in the results so so here's the deal with our antibodies they change very minimally one to the next this is our third placebo controlled rct in five years and so we tend to feel pretty good hopefully we're not over confident but we tend to feel pretty good that when we change an antibody such a tiny amount and i mean it's a handful of amino acids down in the binding domain it's nothing different we are able to determine a dose that we think will deliver a clinical benefit of about 70 to 90 percent of a risk reduction relative to placebo. That's our expect out of the study. So if we feel good about that and we feel like we have a good handle so far on the safety of these medicines, they're all highly similar, and indeed 2311 went through a first in human with stress-tested high doses, and we saw lovely and attractive early safety and tolerability data. So we, let's just say we're feeling good about the overall profile, it leaves the last question. In infectious disease trialing, you need disease events, so-called attack rate, to show up in your study. That's what we are designing declaration and operating it to do. We're trying to be conservative while being responsible with capital and time and so forth, because you can try to solve these problems with sort of infinite money and infinite time, but you're better off designing a study that you think will work. So we built the base declaration study, and we inbuilt an upsizing algorithm such that, you know, kind of in the early mid phases of the study, if we didn't feel as though the study were already reasonably powered, it would automatically trigger an upsize that would allow us to catch maybe a piece of a wave because COVID works periodically. So we kind of do the base bit. And if we feel like we need more power, we wanted to time shift and add a little bit of patient exposure to catch COVID events that come in these kind of sine waves through our population. So that was triggered in early April and in our communication to the street. We pointed out that even though we were upsizing, we had already accumulated some real meaningful number of events that could actually power the upper end of the efficacy estimate for our drug. So look, as we sit here today in early June, we're feeling pretty good about how this summer can play out, what the profile of the drug will be elaborated. Late 3q is our target and you know again people will have to bear with us i'm sure people will be counting the days but unfortunately the sausage requires some grinding and making but that is around when we think we'll be in a position to tell the world what has happened here and again based on everything we know we're we're just uh excited to see the data of course and let's talk about these covid waves a little bit so based on based on the current wastewater monitoring data you know what are the current dynamics in covid what are the current dominant variants how does the design of 2311 give you confidence that you'll see a strong coverage.

Yeah.

So COVID right now appears to be slightly returning from a lull. There are periodic lulls. And many of you who have experienced the last six years of a pandemic and then an endemic virus will remember as long as COVID has existed every two months, it's over for a month. And people just go, that was it. We flattened the curve. It's gone. And then oops. So it's like kind of wild how bad we are at watching something that comes cyclically right it's like you're sitting in New York in December and you're like what summer anyway I don't even believe it exists right and then what do you know like magic it comes around right so right now we are exiting a lull and we would anticipate we're obviously we're not in control of these things but we look at the trends we would imagine there is a normal summer wave of COVID mainly because there usually is and some of those waves are actually quite meaningful epidemiologically. So right now, the dominant variants are what we call, you know, XFG lineage virus. It's just, you know, a part of the alphabet soup of COVID virology, but it is not something that is particularly worrisome to us. This is garden variety variants against which our medicines, we're thrilled, work very, very well. So look, that's the fit game in town, and it's what we would expect would be substantiating a wave over the next six months to a year so we feel again we feel pretty good about where we are we are just we're in that part of the calendar we're again in new york in december if you measure the number of mosquitoes in the air it's going to be pretty light but just wait they're out there so uh let's see if it let's see if it turns on schedule great and and maybe just to switch gears for a second and maybe talk about liberty yeah and and maybe how you know what is the design of liberty trial and and how do you expect that it'll validate 2311 as a viable vaccine alternative yeah thanks for asking after it because it's a it's a fun trial we think so this is something we would expect um should be should be live relatively shortly and it is actually it has its roots in an fda request to assess immunologic and safety interaction between the monoclonal and the vaccine if you were to administer them together now gratifyingly regeneron actually did a version of this study years ago, and it didn't show a whole lot to write home about. There's not that much that happens for a whole series of interesting immunology reasons that we don't need to go into. But as we satisfied that ask, we realized, of course, it was also an opportunity to provide, in one study, a head-to-head. If we're going to study mRNA vaccination, let's also study single-arm antibody, single-arm vaccination, and ask the question, is the antibody safer and more tolerable. We would expect, based on all of the data we have seen and some of our own experiences with these things, we would expect to be substantially more tolerable as a function of lacking vaccine reactogenicity. It's not rocket science. It's just embedded into the modalities themselves. Now, that turns out to be, I think, relatively important data because most of the time companies are reduced to cross-trial comparisons and sort of making assertions, and we wanted to have in one place in a relatively compact fashion, hey, here's the data. It's either going to be, I guess it could be ambiguous, or it could be relatively unambiguous. What is the experiential journey of someone getting one of these medicines? Because if your vaccine doesn't last very long, doesn't protect you very well, and is sort of a drag to go through for a few days, a fever, chills, malaise, lethargy, however you want to characterize constitutional symptoms, and all the antibody shares with it is essentially the ouch part. There's no getting around the ouch. You suck it up and you get your boop and off you go. We would expect very little from a monoclonal antibody after that ouch because it is simply a human IgG joining a massive pile of IgGs in human serum at all times. We all have them. We don't imagine much of consequence here. I think that's going to be really important as we bring data forward, not just to the FDA, but to other, you know, stakeholders, both in the federal complex and the HCP complex. We want what you can almost think of as almost like phase four data right now to make a really important point, okay? There might be a better mousetrap here, a better way to accomplish the job of protecting people at scale. And I think, you know, at some point in one of our press releases, as I think we pointed out, this might really help a public health challenge today in which we are asking people routinely to feel sick so that later on they might feel less sick. It's not a great trade. And when you look at the data from this U.S. CDC on why people don't use the COVID vaccine, a big, if not the biggest reason is they're worried about the safety and the side effects.

So let's just get that out of the way if we can up front and move on to trying to drive utilization to a place where people don't have to make these trade-offs let's talk about maybe one of these trade-offs and it's the post-administration monitoring time and so we recently recently announced that you know with your trial you will be reduced or with 2311 you're reducing the monitoring time from two hours to 30 minutes and do you think that'll be included in the final label and how do you think it'll impact market adoption you know I I don't I don't know that we think it'll be in the label as such, okay?

Typically, with a vaccine administered in an office or a pharmacy, there is guidance, and okay, there was very clear guidance early in the pandemic. Everyone who got an mRNA vaccine in a pharmacy was going to hang around for 15 minutes. Now, in our case, what we disclosed was a clinical trials feature. I don't know that it really will bear on clinical practice or labeling, okay, as such. What we meant to convey was, as a holdover of our canopy study, we imported the same feature set of a monitoring because this is, in the end, a clinical study of a new biologic. And we were gratified when the Independent Data Monitoring Committee made the recommendation to us on the basis of reviewing unblinded safety data, hey, this monitoring time can be way shorter. So to us, that was encouraging. And we would imagine there may not be too much peri-administrative things to worry about. So classically, with a new biologic, you might worry about hypersensitivity reactions. You might even worry about anaphylaxis. It's a feature of some protein medicines. But we don't know what they were seeing that led to the recommendation. We just infer from that recommendation, hey, there may not be so much of consequence to think about. So how is that going to play out commercially and in the practice of medicine? I suspect like most intramuscular antibodies, there's not going to be a whole lot. for physicians, caregivers, administering nurses, and so forth to really worry about.

All right. Great. So maybe now we can move on from COVID. And I want to understand your plans to expand the pipeline. And you've already announced candidates for RSV and measles. And let's talk about that. What are your plans for RSV, for measles?

And what is the plan to expand the platform beyond that yeah so obviously just to to to say it for the sake of saying it our covid uh program is job one right now so i just don't want anyone listening to think that we're we're spending a whole lot of our time and money on this today okay because we want to make the main thing the main thing and and do a lot of good uh in the covid world but i appreciate the question mainly because it ties back to the first set of comments right if we think this modality disease, under-deployed, underutilized, if it can be a complement in a lot of interesting places, well, you can look at what we've done and consider where we might be going. And I'm sure we'll have much more to say about this over the coming few years, because I think there's actually a little more fun and electricity in this space than even in the COVID space, okay? And by that, I mean the following. When you do infectious disease, you are classically worried about the very young, the very old, and the immunocompromised, okay? Most pathogens don't bother people as hale and hardy as you, right? So we don't think about you first, I'm sad to say. We do think a lot about elderly people and babies. And I pointed out early, Bayfortis, Nersevumab, this drug from Sanofi, is an absolute boon to pediatrics, meaning early childhood, especially under two years, RSV used to be a major, major driver of hospitalization and real cost. And indeed, I'm suspicious that as we eliminate it by using nircevumab in most appropriate live births in America and in Europe, you're not just going to see the reduction of RSV burden, you're going to see a reduction of RSV in the community. You're probably going to see a decline. I'm speculating on this point, but I would imagine Sanofi might agree. You're going to see a decline in pediatric asthma. You're going to see a whole lot of derivative benefits that go along with stopping these pathogens from infecting very, very vulnerable, including kids. So we're obviously thinking about COVID among the very young similarly, because it's actually a real problem. And why would we make our own RSV antibody? Well, we think we're really good at making antibodies. So maybe, maybe we can offer something even a little better than nircevamab, which is today a blockbuster, which is great. Why did we do measles? Well, there's a short answer and then a longer answer. The short thing is measles turns out to be a problem again, and there really is no indicated treatment. There's no consensus way to respond to an outbreak, right? Some people use IVIG. Some people redeploy vaccination. Some people use supportive care. The world could use a specific treatment, right, or a specific way to respond to an outbreak that is highly potent, highly specific, engineered, a really nice medicine, okay? That's our measles antibody in our mind. But the fun part is, in the future, you could even imagine using such a tool to really re-underwrite, re-evaluate major pieces of the pediatric vaccine schedule. So today, most American kids get the so-called MMR, measles, mumps, and rubella, at age one. There's good data that shows you if you try to vaccinate too much earlier, you don't get a very good response. And if you can wait longer, you get an even better vaccine response because babies are not born with much of an adaptive B suite. So you're really working to get some kind of vaccine response out of a one-year-old, right? So why do I bring up an antibody? Well, if we had a sufficiently long half-life, sufficiently potent antibody, you can imagine a totally different world in which actually you remove the inflammation and the sort of clinical course of a live attenuated measles vaccine from a kid, bridge them much deeper into childhood development. So maybe they've undergone real immunologic development. Maybe they've undergone real neurocognitive development. Maybe they can even independently report an adverse event. Instead of being, you know, I don't know if you've ever been a new parent or if any listeners have been a new parent, you take your precious object to the pediatrician, and oh boy, do they vaccinate. And by the way, my children were all vaccinated. Of course. But I didn't have a choice either, right? And you super don't want your kid to get measles. So we can use an antibody just like a Bayfortis, just like a 2311, and start to actually pull inflammation back out of the early calendar, maybe do vaccination later, and the best consequence may well be that with additional immunologic development, the vaccine improves, meaning you can either get a much better vaccine response or use less of it to get the same response. So we're thinking into the future about that complementarity. There's going to be diseases we can treat. There's going to be vaccines we can actually synergize with or even improve upon. I don't think of it as competing with a measles vaccine. The measles vaccine is awesome. It gives you durable, very impressive titers. But can we make it even better and keep kids safer earlier and offer parents a choice to maybe not engage the early immune system, maybe not deploy early inflammation, I think we might be able to do all those things. And I don't think measles is the only one we can do. So stay tuned on this point. I think as we build out the core of the company through COVID, I wouldn't want anyone to think we are out of ideas or short of ideas on how to keep running a bespoke platform that is the only game in town as far as I can tell, that is operating in these green fields of medicine all alone and uniquely enabled with this technology. Right. We can do these things. I think we can do them better than anyone. And I can't wait because 10 years from now, maybe we look back and we think, why were we vaccinating so heavily at six months, at nine months, at 12 months? The answer will have been because there was no alternative. And if we can come up with a better alternative, I think that can be extraordinarily powerful for generating both medical and then shareholder value.

Great. And I think just maybe the last question is, you know, with your platform, just to be clear, I think it's really compelling. Can you develop antibodies for all of the diseases on the pediatric vaccine schedule?

I'm not going to say all of them, but maybe a lot of them. So, you know, send us your target ideas. All right? Like, we're open-minded cats. But I think what is true is that a lot of these viral targets look extremely tractable. And generally speaking, if you can make a vaccine that generates a good neutralizing antibody response, we at InVivid can look at that neutralizing antibody response and ask the question, can we beat that? Sometimes the answer is going to be yes. And that could be extraordinary, I think, for the future of American health.

All right. Well, with that, I think we'll end it there. And thank you, Mark. I really appreciate your time and for taking the time to come out here.

Thank you.