Hello and welcome to Oppenheimer's 35th Annual Healthcare Conference. I am Chang Li, one of the biotech analysts here at the Oppenheimer team, and it's my pleasure to welcome our next presenting company, Invivyd. Today we have Marc Elia, Founder and CIO, Bill Duke, CFO, and also Brian Korb from Astr Partners. With that, I will turn it over to you, Marc and Brian. Great. Thanks so much, Chang. Great to be with my former Oppenheimer colleagues in this exciting virtual format, which is actually perfect, I think, for this company, given the topic. We wanted to keep things a little bit, you know, I think, more investor-focused and a little bit more open and flexible on the presentation format, especially given some of the recent news that the company's had. I also think, particularly given Marc's background as the Chairman, also a big investor, and I think personally very invested in the space. Maybe I'll turn it over to Marc just to give us a little bit of a background on the company and the strategy and vision, and then we'll dive into the programs. Thanks. Happy to do it. You know, thank you, Chang, and thank you, Oppenheimer, for hosting us. I'll ask Bill to keep me on the straight and narrow as we go through some of this, as I am prone to wandering from time to time. Thanks, everyone, for tuning in. Invivyd is a company focused on viral infectious disease. That is for one big reason we're all aware of, I think, but we talk about maybe not quite enough, given the magnitude of the burden we all face, meaning Americans and indeed the world are awash right now in respiratory pathogens and other important viruses that bedevil us and make us sick and make us die. We're also awash in vaccines and vaccine boosts that purport to keep us safe from those pathogens. They do, I would say, on balance, an okay job at keeping us alive. They do not do a terrific job at keeping us well. The reasons for that are really not particularly surprising. It's very difficult to make a sterilizing vaccine for any pathogen. For a respiratory pathogen, it's near impossible. For COVID-19, which is our first area of focus, it's, I think, been observably impossible and will remain that way. We, as a technology company and an antibody technology company, looked at that problem many years ago and began to work on what we thought would be high-quality solutions to that, namely monoclonal antibodies that are highly potent, highly specific, that interrupt disease pathogenesis. All of us who remember the pandemic a little bit may remember that these agents were deployed to quite some good effect. The Regeneron was a treatment paradigm, right, brought to us by our friends at Regeneron. AstraZeneca had, for a year or two, a prep, a so-called prophylactic antibody named Evusheld. These are agents that were highly effective in the prevention or treatment of SARS-CoV-2 disease or COVID-19 disease. Invivyd takes a somewhat different technological approach and has tried and so far succeeded at staying in the game and providing those medicines to people in need because of our central premise, our central observation, that we can use these molecules to exert a step change in protection for vulnerable populations, and that our technology is allowing us to move through and hopefully well ahead of the fundamental challenge in the field, which is virus evolution. There is a whole lot of technology packed inside of Invivyd that we deploy, unique in the industry, to address that central problem. You know, it's one of these problems that could never be fully extinguished as a risk factor, but we feel awfully good about our differentiation to date. We obviously have an authorized pharmaceutical product called PEMGARDA, pemivibart, our first antibody. It's only in class. I suppose, as a consequence, it's best in class, whatever its properties. We are very proud of that fact, given the number of very enabled, very sophisticated pharmaceutical competitors whom we have beaten to get to that place. We'll talk a lot about that, I'm sure, and there's been some recent news, and we're hard at work every day on growing that commercial franchise. I think I regard it as effectively a demonstration and a warm-up act designed to provide us with, yes, operating capital, but more importantly, a regulatory pathway, a paradigm, and a demonstration of what we can do with tools like these. The future, I think, does not look quite like the present, meaning our goal is to move this technology into broader and broader populations in more and more scalable forms. That is a dance that we are effectively dancing at all times between our tech and the FDA and other global regulators and what their, you know, appetites and inclinations look like from time to time. One thing I will just double underline before I pause and consider where we want to go next is this: if you actually look at Invivyd and you look at our randomized controlled study that enabled the authorization of pemivibart, you'll see it's called the CANOPY study, and it was divided into two cohorts for what it's worth. The primary efficacy endpoint that we analyzed in our double-blind randomized cohort was the occurrence of PCR-positive symptomatic COVID-19. In that study, pemivibart exerted an 84% reduction in symptomatic PCR-positive COVID-19 compared to placebo. For those of you that don't think about these endpoints commonly, I would just observe this: that really reflects your ability to get sick from COVID while on this medicine. Now, if you are really deep in the weeds of vaccinology, you might follow the semi-annual reviews by the Advisory Committee on Immunization Practices, ACIP, and their recommendation to CDC about the COVID vaccine. Long discussions occur, levels of protection are asserted, and in the end, the most relevant data shows that a COVID vaccine boost gives you about a 50% reduction in your likelihood of visiting an urgent care or becoming hospitalized for about 60 days, after which the benefit wanes rapidly. When we talk about step change, sometimes we forget to double underline the endpoints. Our goal is, in Invivyd, to scale medicines that stop one from getting sick. We've all gotten used to America in which, oh, you're going to get sick over and over again. And if you boost, yeah, you can reduce the propensity that you might become hospitalized. Indeed, there are still many hundreds of thousands of COVID hospitalizations every year, more deaths than there are in breast cancer, and this unthinkable and growing toll of long COVID, none of which today we're in a position to present you with randomized data on. I just want to underline the power of the pharmaceutical-grade monoclonal in this context is night and day. Our aim is to scale a level of protection that actually allows humans to transit the world without getting sick. That's the goal of the company. If we are successful in doing that for COVID, I think our technology, which involves a lot of proprietary stuff, would allow us to exert that playbook against some other pathogens, some of which, you know, for example, like RSV, already are supportive of blockbuster, growing to mega blockbuster category antibodies, and even, you know, sort of more recently emerging viruses that exert similar tolls. I'm thinking of human metapneumovirus, thinking of potentially influenza, so on and so forth. That is the aim of the company, in a nutshell. We are looking to try to keep the most people well we possibly can. What you see today is sort of the opening round of that that has emerged over the last basically 18 months to 24 months. No, that's a great intro. I think you touched on it a little bit. You know, I guess on the flip side, and I'm sure it's one of the things, you know, Chang probably hears from investors, we certainly hear it from investors when we're reaching out to folks, you know, that people are kind of having maybe the COVID fatigue in terms from an investment perspective. You touched on it a little bit, but maybe just thinking, you know, why should investors care? We obviously saw your preliminary earnings last week, which were great. Like, why should investors care when you think about it from the patient perspective in terms of hospitalizations you mentioned? Also thinking, you know, real-world market, like, what are the vaccines doing and the current therapies doing on the market? Yeah. So look, it's an important point. And, you know, as an equity investor myself, right, my day job is indeed doing long, short biotech investing. I'm familiar with the phenomenon. You know, the issues, I think, are fascinating. Again, I don't think most people have focused on the actual numbers that describe the ongoing toll. So 60,000 or so deaths last year is maybe not a pandemic with hospital shifts, but, Lord, it is an incredible burden. About 600,000 hospitalizations is more than RSV and flu combined. Long COVID is estimated to today affect somewhere between about 14 million and 40 million, depending on the numbers, you believe, Americans. And that number is growing. So what is fatigue? Well, I guess I look at it as emotional and psychological. We all went through something terrible, and we wish it would stop, and I understand that. I look at it as quotational. There are probably people who wish Moderna stock would stop going down and start going up. That is sometimes fatiguing to people. You know, there are entrenched players in the therapeutics category, like I'm thinking of our colleagues at Pfizer and Gilead, who report earnings, and they exclude, as if to imply revenues that are non-recurring, of extraordinary and recurring magnitude. I think, you know, Gilead, I want to say, reported this morning that they did $1.8 billion in remdesivir sales in 2024. That is largely an inpatient COVID drug designed to keep you off of a ventilator or get you out of the hospital. I'm going to miss the Paxlovid number because it's been a few days since Pfizer, but I want to say they did something like $7 billion in Paxlovid in 2024. You know, we're all entitled to whatever level of fatigue or enthusiasm we want. I would just say this: the people that are really fatigued are the people who are continuously getting sick. An extraordinary number of us, including some reasonable percentage of the people both appearing on and listening to this call, are either already in possession of or due for, at some point, material damage. You know, people who are interested in Wall Street, you know, run disproportionately young and healthy, that's great. Even the young and healthy have a way of experiencing COVID over and over and over again, and it exerts a very real toll. The basic literature is, you know, it's a little bit disturbing if you start to look at essentially what is a transmissible, you know, thrombotic endothelialopathy with neurologic manifestations, all of which is a great way of saying we are all passing around at high speed a pretty ugly little pathogen, you know, not so different than polio before a vaccine. Polio before a vaccine was 70% asymptomatic, 20-some-odd% kind of a fever. For this small number of people, you would get a really bad meningitis and potentially a paralysis. The difference, of course, was we had extraordinary vaccines, thanks to legends in the field. I guess I'm aware of the phenomenon, but I think there's a reason why we ran the studies we did with the molecules we did and why, even though it almost feels countercultural sometimes from a Wall Street perspective, it's why I think we see encouraging early utilization and strong growth. I mean, maybe the fatigue I think we are actually focused on is it's not that interesting to point out a problem over and over and over again until you have a solution. Because just saying to someone, you know, hide indoors and eat your vegetables is less interesting than, here's a tool. Now you can do something about it. Yeah, I think we're familiar with the dynamics, but I think here, five years in, it's an interesting time to kind of sit back and re-underwrite, why do these dynamics exist? What makes us think arbitrarily that in year six, everything will magically change? I think we're basically in this pattern forever. We can end a pandemic, we just can't end transmission, and we cannot end toll. Invivyd was built, right, to try to address the endemic forever of this, you know, remarkable-seeming designer virus. I mean, you know, you mentioned Paxlovid, you know, and kind of the vaccines. Like, how has PEMGARDA differentiated, you know, kind of where does it fit in today? You know, obviously, you announced preliminary numbers last week, but like, where is it today and where is it going? Yeah. PEMGARDA is authorized for a very specific use case, the prevention of COVID-19 among certain mild to moderate immunocompromised persons. These people express a pretty wide swath of American medicine today, and depending on how one reads our fact sheet, could embrace, for example, 89 million Americans or so. These are people who investors may be familiar with or probably interacting with some other therapy we all know, right? Maybe their B suite is depleted by anti-CD20 for MS. Maybe they've undergone CAR-T for a refractory DLBCL, and they have total ablation of their immune system. These are people who are profoundly vulnerable to all these kinds of viruses, COVID-19 especially. That's the use case. We have a pending application for the use of PEMGARDA as a treatment of mild to moderate COVID in an outpatient context for essentially that same population. This, of course, makes all the sense in the world. You know, antibodies, of course, have both been used for prevention and treatment, and naturally, as you know, we all are humans, our antibodies do double duty, right? They prevent and treat our natural diseases. You know, long term, I think our goal would be to operate very firmly in both contexts. As compared to a vaccine, I think we would regard an antibody as effectively a somewhat premium product, but hopefully in the future, you get what you pay for, right? Our aim would be to have a product out there at a more achievable sort of price point for big populations, think kind of low thousands of dollars, which is, you know, just a bit of a turn lower than where PEMGARDA sits today. Similarly, our vision would be to have either of our next molecule be two roles or start to divide up treatment and prophylaxis. Because one thing is clear, back in the times of the pandemic, the power brought to bear by monoclonal antibody therapy was, I think, pretty noticeable among the HCP community, right? Paxlovid is a terrific drug, right? It's a very, very potent protease inhibitor. It has a lot of nice properties, but it requires ritonavir boosting. It has drug-drug interactions. It's not appropriate for a lot of people who are on polypharmacy. Let's remember, it's a five-day treatment course, and there is a substantial quantum of rebound. You know, we are very interested in the potential role of a long-acting antibody to exert meaningful antiviral activity for weeks and months after a single dose. You know, all of these things can have their place, right? I think so far we have now seen over years the incredible power that a monoclonal can play in both domains. If you are at risk, our view would be in the future, we'd like to offer you something much more than what a vaccine can offer you. If you're young and healthy, perhaps it's not of interest. Totally get it, no problem. In a treatment context, if you are not at particular risk of an adverse outcome and you take your Paxlovid and you have a great, great result, great. If you are at risk of being one of the hundreds of thousands of people that ends up with an average 11-day hospital stay, we'd like to offer the world the opportunity to, in effect, you know, break the glass and deliver overwhelming antiviral activity to forestall that progression from viremia to that sort of end-stage inflammatory, you know, basically hospital COVID-19, which is, you know, still going on at sort of an extraordinary rate. That would be the vision, right? Just within the COVID domain is to continue to scale and democratize access to both of those sorts of use cases. I guess, you know, so you guys did announce some preliminary earnings last week and gave some guidance in terms of hitting, you know, cash flow break-even. I guess that's based on the current authorization. And then, you know, if there is a, you know, I guess it could be just upside to that if you get the other authorization come through from the FDA. Yeah, I'll let Bill comment so that way I can hold him accountable to it later. Yes, we did release our preliminary Q4 results where we showed quarter-on-quarter growth at the top line level of almost 50% on that front. At the same point in time, dropping our OpEx to the tune of more than 50% as well. We are on this path towards profitability. We have guided that we believe that we can get there by the end of the first half of this year. Month on month by June, we feel like we can turn the corner to profitability and then extend that through the rest of the year. That does not necessarily contemplate treatment. We were able to do that on the backs of the currently stated EUA, which is for prevention only. We do look at treatment as a great potential for patients, but also that we think it can be a net positive for Invivyd, not only with currently PEMGARDA, but also as we move forward with VYD2311. Great. I mean, and then I guess, you know, on VYD2311, Marc, do you want to kind of talk about some of that new data and some of the recent findings? And maybe how quickly can you kind of move it forward with the FDA given the experience you have with PEMGARDA? Yeah, the last question is great. I hope there's some FDA people on the line with us that can lob in some thoughts and questions because that discussion is going to be fun. Look, I think, as I said at the beginning, pemivibart is sort of where we started because it had some very attractive properties in the year 2022. There's a little trick about Invivyd antibodies that are different than others. Most people, if they want an antibody, particularly for an infectious disease, you know, they might mine human serum, right? You might go find someone who survived norovirus or this, that, or the other and do a down selection of their B cells, find yourself some antibodies. You know, again, there are a great many people in industry who will inoculate a mouse and then squeeze whatever interesting antibodies a mouse or a humanized mouse is willing to give them. We do things a little differently in a synthetic sort of form. The reason for that is really critical. The reason is we actually started with serum back in 2020 from a SARS-CoV-1 survivor. Then affinity matured. Basically, we exert sort of combinatorial mutagenesis in a directed fashion. You start with an antibody and then you start to change it, the binding site, the variable domain combinatorially, directing it towards Wuhan lineage SARS-CoV-2. The idea there is you're using the sort of ortholog or the homolog to get more variation resistance, more evolutionary resistance, right? That worked great until it didn't. The way in which it didn't was rather interesting. It didn't at the level of Omicron. Most people think about Omicron as a virologic event. I don't think of it that way. I think of it as a population event. Omicron marks the virus phylogeny whereby evasiveness of human immune pressure was the central driver of fitness, right? Before everyone got either infected or Wuhan vaccine, you would have seen these big sweeping changes, alpha, beta, delta, gamma, whatever. Afterwards, we're in this soup because of our host-level ecology. All of us got imprinted, I mean, all of us that lived probably now are imprinted. There are very few humans remaining who got neither vaccinated nor SARS-CoV-2. We looked at parent molecule adintrevimab that got knocked out and re-affinity matured it against BA2. That gave us pemivibart. Now, pemivibart biophysically, it's a pretty meh antibody, okay? It's got some warts on it. I think of it kind of like a dump truck in a world where you want a sports car. It doesn't have the flashiest potency. It doesn't have the flashiest half-life. Like a dump truck, it sits on a very interesting territory for some very interesting reasons. Indeed, it's approaching its third birthday, which is pretty extraordinary in antibody land. To get the next one, we thought, geez, this has been fun, but why don't we turn up the heat? We are going to once again combinatorially evolve pemivibart against more contemporary lineages. That gives us VYD2311. By the way, we're doing this work at all times, and it doesn't really cost us that much. What costs us a lot of money is making one into a drug, right? What our criteria for VYD2311 was, we wanted it to be even better suited to life in an Omicron world. I say that not thinking about the virus, because the virus has mutated plenty, as everyone knows. We wanted it to be best suited to an immunologically experienced host species, as in us and us plus the deer plus the mink plus the fictional pangolin that was supposed to have been the thing. The point is VYD2311 now is a much higher performance expression of the same approach. That means you get way more potency, which automatically allows you to confer much more antiviral punching power at less dose. It's the difference between, you know, tequila and Michelob ULTRA, right? You are way more potent. Encouragingly, it appears to have a very long in vivo half-life. Certainly, the reason we were able to announce what we announced is it is now well past what we observed for pemivibart. And while we don't know the final answer yet, at this point, it kind of doesn't matter to us, meaning it more would be great. And we'll see what the final number is. But the way the combo of those properties works out is now it becomes sort of math, right? The FDA knows what targets they have in mind and what data inform those antiviral titer targets. We know what targets we have in mind and what data inform those. And now we know, okay, subject to such and such a potency and such and such a dose and such and such a half-life, we can hit those targets or come near as makes no difference in more and more convenient form factors. Because prophylaxis is a, it's an eat your vegetables kind of game, right? You are selling a medicine to the worried well. They're not sick. They're well. They don't want to get sick. The more difficult you make that for them, as in the need for an infusion, the need for more periodic infusions, you know, the less inclined people may be on the margin to eat those veggies. If you on the flip side, make it very convenient, hopefully indistinguishable from a vaccine boost, but with the consequence of, okay, now you're going to get access to that much higher protection on a much more stringent endpoint with a much longer duration. And then critically, no immunologic engagement, right? You're not an active vaccine that is activating your memory compartment and forcing these titers and dealing with all the hair that, you know, is, I think, well understood to come along with vaccination. VYD2311, you know, I don't know if it's the best we can do, and I suspect it's not, but it's a substantial turn better. What we're going to do with it now is go to the agency and kind of say, you know, you've read our press release, you know the physical properties, here they are elaborated. We can now do a bunch of stuff. We can either run in effect the same sort of compact, low-cost, rapid pathway to destination A, B, or C. If they want to call it an EUA, fine. I don't know that there are puts and takes. If they want to consider it an accelerated approval, fine. There are puts and takes on all of that. I think we know we can do something here. The process will probably look a little bit like the process of getting pemivibart. It's a discussion. I think if there's anything encouraging about, I think if there's a reason we're looking forward to that discussion, it is that in the year 2022, the world was told by the White House to test, boost, and treat. There was really no room for discussing the limitations of vaccination in the political discourse. There was a sort of fascinating election recently in this country, and it would seem those winds are perhaps even blowing in the other direction. I don't know. It's not a political statement. It's a scientific statement. You know, ACIP and CDC broadcast well the strengths and the weaknesses of a vaccination-based backbone. You can see the toll it takes in the outcome numbers. VYD2311 is going to be our first next shot to bridge that gap and get into population, bigger population medicine with what we hope will be very attractive sort of pharmaceutical properties, right? That is the other piece of news we announced. The goal of the company, again, zooming way back out, is we are going to grow our PEMGARDA franchise best we can because our favorite source of capital to fund our operations is operating contribution. After that, we will have to see whether we would ever need to tap dilutive equity ever again in order to get VYD2311 going to its next phase. What we're proposing to the investing public, I guess, is we think there's a very attractive destination here economically and medically. We think Invivyd is highly advantaged and empirically differentiated. And, you know, we think we're underway and doing it. So, you know, hopefully some of this has been useful for raising awareness and, you know, happy to take any questions. Yeah, just to like maybe chime in here. I mean, you mentioned to improve the patient access. So just wondering if you're planning to have some like Sub-Q injection with your next generation to make it easier for patients to take. Yeah. What we did in our first inhuman dose escalation safety study was we interrogated three different posologies or routes of administration. IV, because there might be an interesting role for IV in the future for certain treatment aspects, for example. We interrogated IM. Indeed, we have a subcutaneous cohort because prophylaxis is arguably optimal if you are able to execute it without accessing the healthcare infrastructure, right? Some of these people, you know, that do not want to go to a facility like an outpatient infusion center where they might encounter the unwell, we wonder if we can over time drive even in-home use. Again, some of that will depend on dose and properties and so forth. Certainly, we have the emerging proof of concept. It is certainly, you know, at a time in America where huge numbers of people are training themselves on Sub-Q administration of appetite suppressants. You know, there might be some interesting opportunities going forward there. Yeah, now we're like running out of time, but just maybe I can just squeeze one question. I think you recently announced the PEMGARDA activity against the most like recent dominant strain, which is XEC. Curious about how this, how important this and how that may contribute to your maybe the revenue growth in the coming quarter. Also maybe taking a step back. I mean, it seems like a powerful platform that you can apply to other diseases like RSV, especially like before this now a blockbuster. How are you thinking about additional opportunity here? Let me start at the back. If I go too long, cut me off and remind me about the front end of that question. The point about RSV is a great one because most people do not think about it this way, but RSV indeed is also in motion, right? Regeneron lost an RSV antibody due to evolution. Sanofi GSK, so far so good. Of course, they also have similar virologic commitments to the FDA that we do to make sure that their molecule exerts appropriate antiviral activity. I do think our platform is uniquely suited to this. Maybe we bid off the sort of higher speed version first. I think that gives us confidence when we look at some of these other opportunities. As we go forward, our goal would be, yes, indeed, to broaden to an area. RSV is absolutely toward the top of the list. The criterion would be we would like there to be an argument for best in classness, right? Because, you know, while there's always a role for another medicine, I think we would like to take the tech first a spin and see if we can offer the world something that, again, maybe it takes advantage of some of the same dynamics, right? There may be, as you point out, other pathogens where we could sort of run the same playbook. Again, that's going to be a function of access to capital, how we choicefully deploy and allocate capital inside the company. I want to point out, it is already occurring at some, you know, at some level. I'm sorry, what was the first bit? Yeah, first is the recent like data showing the PEMGARDA activity against XEC strain and how that may kind of contribute to our like revenue in the coming quarter. Yeah. You know, it's a sometimes not so fun topic because, of course, the whole world has virology labs of varying quality. There appears to be a like a low-grade debate about what are the properties of pemivibart. We feel great about all of the data we've generated so far. XEC really should be no surprise. Structurally, it's quite similar to predicate viruses like KP.3. You know, now we're going to get deep into the nerd weeds. Brace yourselves. Most people seem to believe that evolution occurs principally around RBD on spike. Actually, of late, most evolutionary pressure appears to be influencing more distal components of the spike, so-called N-terminus domain and so forth. It could be imagined that those things exert some epistatic effect or some allostery, but we don't see that. One of the things we're wondering about is, are those effects arising simply because there is some form of dynamic equilibrium between virus and host whereby the exploration of variation is occurring well away from our binding site? If true, you know, frankly, that's good news. We obviously will keep demonstrating and interrogating and so on and so forth. You know, we'll always have that, you know, okay, we need to show this and we need to figure it out. Right now, the overall co-evolutionary journey between humans and virus looks pretty favorable because pemivibart has now, I mean, if you go back to March of 2022, Omicron was brand new. You've had to sit through all manner of crazy stuff, BQ, BF, XBB, BA2.8. I mean, seemingly it never ends. Interestingly, that little dump truck, pemivibart, sits there doing its job. You can't make a perpetual promise. You can instead say, we feel great about what we're seeing. And if anything, the evolutionary backdrop looks more favorable to us than it ever has in the past. Got it. Thanks. We're out of time. I think we can wrap up things here. Thanks again, Marc, Bill, and Brian for joining us today and looking forward to future updates. All right. Thanks so much, Chang. Thank you. Thank you. Thank you. Bye-bye, guys. Thanks.