Good afternoon, everyone, and thanks for joining us for the Guggenheim 6th Annual Healthcare Talks. Thank you for joining us for this fireside chat with Invivyd. I'm Evan Seigerman, one of the biopharma team senior analysts, and I'm joined by Invivyd CEO Dave Hering. Dave, just to set the stage for those unfamiliar, can you give a brief intro on Invivyd and your approach to tackling COVID with monoclonal antibodies? Yeah, great. Thanks, thanks for having me. We're a company focused, a-as you said, on bringing monoclonal antibodies to vulnerable populations, starting with COVID. Our focus is driving serial innovation through our platform approach, and so we really see the ability to meet the ongoing, evolving nature of, you know, viral infection as one that you can do by continually updating the antibodies. And so I'm sure we'll, we'll get into it and talk about it, but that's really our approach, both with our current antibody, which we submitted for an emergency use authorization, which is sitting with the FDA, as well as our, you know, sort of broader pipeline. Great. Can you just walk us through something of the, like, I guess, the engine around your serial approach? You know, I guess your antibody, you know, modification capabilities, your discovery work there. Yeah, so it all starts first, you know, in the discovery platform component. We leverage technology from Adimab, their yeast-based approach and platform that allows us to generate antibodies very quickly. Our original antibody came from a SARS-CoV-1 survivor, which also put us in what we think is a privileged real estate spot, in terms of where we're looking for, you know, targeting in the receptor-binding domain of the spike protein. So it's that as the starting point, but then really what we've done is evolve that into, first, an ongoing set of surveillance and predictive modeling for where we think SARS-CoV-2 as a virus is going. We've mined the GISAID database, which has all the sequences, and we use that plus wastewater plus this modeling to really start to look at where the virus is, like, testing new mutations. That's what we use then to inform the antibodies that we're making in our labs. So those are the ones then that we're modifying and tweaking, and then we apply that through our manufacturing and development arms and then, hopefully our commercial side. Great. Then just in terms of your, you know, approach with your, I guess, 1st-gen and your 2nd-gen, VYD222, I know you've been focused on, you know, an RBD direct antibody. I know there's some differences in approaches now going on, but you're leveraging, your antibodies that you've developed in the past to kind of move your platform forward. So can you just talk about, I guess, your approach there versus some of the competition? Yeah, so our approach, as I said, is really a serial approach. We want to be able to do this continuously and repeatedly. So think just like you get a new flu vaccine every year or you get a new COVID vaccine every year, if we can effectively always stay ahead of the virus by continuing to meet it where it's going, that's really the desire. And so we know you can find, you know, RBD type antibodies that work, provide activity, provide effectiveness, and efficacy against the virus. And so our approach, like I said, is to do this rapidly. And we've been able to do it a couple of different ways. One, we're leveraging the original set of studies from the original antibody. We worked with the FDA, and they've set in motion this bridging approach, and so we're using that bridging approach to leverage the next generation antibody, 222, which is the one that we submitted for an emergency use authorization request, and leveraging it back to the original antibody and that set of studies. And so that's really been our approach. Instead of looking for this sort of unicorn mAb that people think might last indefinitely, which is what some of our other competitors are still looking for, our approach is, hey, we don't need to try to find that needle in the haystack. Let's just leverage our internal capabilities and platform to be able to do this repeatedly. Great. You know, just to put it in context, when you said rapid, you guys went from clinic to submission in nine months. Yep. Can you just walk through the steps there in terms of, you know, designing VYD222 and the clinical development? Yeah, for sure. Exactly. I mean, the ability to do this rapidly, and as I've said, we're preparing to do this as quickly as, you know, every year. We'll see how often we need to do it going forward, but if you sort of look at how it's been done in vaccines, you could at least envision a timeline that would be on a sort of yearly basis, and we'll go from there. So we started the phase I study of 222 in March, and then, as you said, you know, we had an EUA submission announced by the first week of January. To do that, it's a very compact phase I study design, which we kicked off in Australia. We then used the information from that phase I into our phase III. Importantly, with the phase III, we had been working with the FDA and had dialogue with them about what a study design could look like. We announced, in alignment with them on this immunobridging using titers as a surrogate marker. That allowed for a very rapid and compact phase III study, 750 subjects. And because you're not waiting for people to have gotten, you know, symptomatic COVID or waiting for those events, you're just getting people enrolled and then taking, you know, serology and testing titers. It's a study that you can enroll quite quickly and then generate the data quite quickly, which we did. We used an interim set of data from that study then as the basis for our EUA request. Great. Can you talk about that, you know, cohort A portion where you used that immunobridging approach? I guess, how translatable are some of these titers to efficacy? I guess, what, what is the researchers' research there? Yeah. So the first thing we did in our phase I was to show that we could generate high titers. It's, you know, you know, not that there was really much question, right? If you give someone an antibody and then you test the titers in their blood, you would expect to see that you have, you know, in effect, actually generated high titers, which we did. In the phase III study, the first part, as you said in cohort A, we wanted to again show that it doesn't matter whether these are, sort of normal healthy adults or immunocompromised patients that you can have a similar impact, which we showed that you could in the cohort A component. And then cohort B was an all-comers. That was placebo-controlled, predominantly for safety. That was one of the main goals, is again to be able to show a safety profile that was generally favorable for the antibody. And so that was the main component of cohort B. Great. Then I think that cohort B portion has that efficacy component, I guess. Yep. How does that add to the story on VYD222? Does that get included in the EUA package? Is that supportive? This goes to your previous question, which is, so there's a lot of evidence about titers and higher titers supporting higher efficacy. Getting into what specific titer values then translate to specific efficacy still has a lot of questions and, you know, ongoing studies. We published a paper back in March of last year where we really identified that, you know, this correlate of protection existed between these serum virus neutralizing titer values and efficacy. And we used both monoclonal antibodies and vaccine titer values to generate that curve. We still feel that that's the best indication of how this relationship exists. However, it's one of these situations where we can continue to build to it. The FDA hasn't allowed us to use the entire curve. Instead, they wanted us to bridge back to specific data points from the original study. And so to your question, since we were running this cohort B and doing placebo versus drug arms, we're using it also as an opportunity to test actual differences in symptomatic disease. We weren't sure when we started the study, given the population and the size, how many cases we would end up with and whether, you know, you would be able to generate a statistically significant finding. Since we started the study and because of the waves of COVID in particular, as we were going into the fall and winter with JN.1, we have seen a significant number of cases, and we do anticipate being able to put out some of that efficacy data later this year. It's not required or necessary for the EUA submission, but it is data that we are generating and looking to, again, supplement. All right, here's the bridging data based on titers. Here is what the efficacy then looks like in these specific populations and how those things relate. Great. And then I know you guys already have submitted, but just in terms of clinical updates that we'll see through the rest of the year, you mentioned efficacy data later this year. I guess what other kind of clinical updates could we look forward to? Yeah, we're still, you know, working through all those different pieces, but we are expecting a publication based on the CANOPY data. And so that could be either the dataset we use for the EUA submission or perhaps a broader dataset. We're still looking at that. And so, we are looking for a publication in the first half of this year as the target for those, those data. And then, again, we're continuing to look and see what else we can provide throughout the year. Great. And then, you know, the EUA submission itself, you know, I think under a month since you reported top-line data there. So I guess you have general alignment from FDA on, you know, the whole design. I guess how confident are you in, I guess achieving EUA? Yeah, I mean, listen, we're really confident in the package we put together. It includes clinical, non-clinical, CMC, the whole component. We feel like one of the major linchpins in our submission is this in vitro data for JN.1, the potency that we have there. JN.1 is now 90% of the cases in the U.S., and so we think that activity and that benefit is a huge selling point for the product. Yeah, we're, I think, I mean, we announced that we had submitted the first week of January, so yeah, we're right around, you know, a month from, from when we put it in. And we continue to have an ongoing dialogue with the FDA, both about the submission as well as, you know, the broader goal in terms of being able to license the platform. And so that, that dialogue continues to be positive. Great. And then, you know, that's the US. I guess has there been any progress internationally? I know there's been efforts and, like, discussions, but. Yeah. So our priority and focus right now is the U.S. We have gotten some questions and inquiry from ex-U.S. regulators, certainly with putting out the press release about submitting the EUA. That has generated, as you can imagine, some inflow of questions and requests. The EUA pathway that exists is a relatively U.S.-unique focus at the moment. There are some accelerated approval pathways in some of the other markets that we continue to explore. And it's, you know, one of the things we continue to talk about as well is, as you start to think about potential partnerships or other areas, are there other companies that might be in better position than us to look at some of these ex-U.S. markets? So it's something we continue to explore and look at. But as I said, our focus right now is really getting ready for this potential launch and then working through the details of a U.S. launch. Yeah, yeah. That makes sense. I know we've seen some actually international markets have some compassionate use for some antibodies. Yep. I guess longer term, you know, you've emphasized that this is kind of a platform approach. So I guess how could clinical development in the future look, I guess, compared to VYD222? Yeah, we really see VYD222 as the foot in the door, the sort of launching-off point for the approach. And so, as we said, we've now demonstrated the speed that you can go from phase one to EUA submission. And our goal would be to do that repeatedly in the short term. And so we already have a pipeline of antibodies that we're working through in discovery, and we'll provide more information about them soon. But, you know, we now feel like that blueprint exists, and it's something that we could do again and again. And that is, again, the step towards the longer-term goal, which would be to license the platform and be able to move from one antibody to the next under either, you know, sort of a supplemental BLA or equivalent kind of approach. And that, for us, is what, you know, the longer-term goal is and what we've started having conversations with, externally, about how to do that. And so in the near term, you know, it's the milestones for 222, which is, you know, fingers crossed and, and get through the EUA authorization, do a successful commercial launch, and then have the next antibodies ready so that we can move from this one to the next one. And then the longer-term goal, which would be licensing the platform, which would increase efficiency and, allow us to do this, we think, even more rapidly. Great. And then how are you thinking about maybe ways to get from EUA to an approval of the platform? I guess could you get there with real-world data? Would you need a clinical study? Yeah. There's a whole host of things that we're considering. It could be, you know, an additional, efficacy-type study where we're looking at different titer values, higher and lower titer values. Taking the efficacy data from the current study is one way that we're contemplating bringing this together. It's really getting a sense, too, for, you know, how CBER looks at this from an FDA perspective and CDER and marrying those two together and, you know, really getting some more information from the agency on how they see this going forward. Because, as I said, our goal is that you would have a, single sort of, marketing authorization, a brand name, a INN number, and then you would be able to switch from one mAb to the next as you are, matching them to new variants that come along. I think I mean, that, to me, is where this, you know, from our perspective, would make the most sense for how we're going to deal with, unfortunately, what seems to be a virus that's not going away. And so that, to us, is the best approach for being able to manage that. Great. So just transitioning to commercial, I guess, how are you thinking about the commercial opportunity for an antibody now? I know we haven't had one for a while. Yep. You guys have done pretty extensive market research here. What has that kind of shown? Yeah, no, we've done a significant amount of market research. First, we see that the unmet need for prevention as well as treatment, but in particular, prevention is significant, and it will remain, you know, perpetually there. And so this isn't a situation where we think, "Oh, there's only a near-term need. There's a longer-term goal." We've talked about vulnerable populations, and those include people who either don't mount a response to vaccines or can't take vaccines or don't take vaccines and still are looking for prevention. We've narrowed that down for our initial launch into what we've classified as the most severe immunocompromised patients. These are folks who are, you know, recent or upcoming solid organ transplants, stem cell, you know, hematologic blood cancer folks. And so that's about 485,000 people from our research that we've identified as the ones most at risk for severe outcomes from COVID-19. And so that's really what we're targeting in this first phase of the launch and really working, again, with a commercial organization, field force, etc., to target them. Great. And when you talk about, like, this high-risk population, I guess what level of utilization do you kind of expect there? Yeah, so we're triangulating, too. It's a little bit tricky. So we've looked at how these patient populations utilized Evusheld. That was the most recent prevention product on the market. The only tricky thing there is, during that period of time, the U.S. government was the sole purchaser and distributor. So you didn't always end up with product exactly where it needed to be. But we still saw a very high utilization of the product in those places, and we continue in market research to see this. I mean, I think these are folks that are all in need. So from my perspective, you know, all of them of the 485,000 are certainly in need of such a product. How that utilization will work, I think it's, you know, you know, like any launch. You're going to start, and you'll continue to drive utilization, and you need to do that through awareness and all of the sort of blocking and tackling that occurs. But certainly, I would see a high percentage of this group in particular that would be both receptive and utilizing the product. Great. And then, so assuming you know, assuming EUA here, I guess, how are you preparing for a successful launch? Yeah, so we get this question a lot about, you know, what can you and can't you do under an EUA versus a license. There is still marketing allowed under an EUA. There are specific regulations, as you can imagine, and there's certainly approvals that you need from the FDA in your materials. But you can utilize disease awareness, and you can utilize, you know, your traditional sales force models to go and provide information to folks. So we're still looking through all of that. We're also planning to utilize, you know, medical science liaisons, MSLs, like a national account team that will call on payers and make sure that we have reimbursement and, you know, formulary access into these different hospital systems. All of those sort of what I would call traditional elements will exist even under an EUA launch versus like a typical BLA launch. Mm-hmm. And I guess where are you with, you know, the buildout of MSLs, the national access team, or? Yeah, it's all in place. Some of those people we've already brought on. Some of them are in process of being brought on, working on training, creating materials. We have inventory here in the U.S., that we're looking to finalize artwork and get ready. And so we're doing all of those steps because our goal would be, from the time of a potential EUA to product availability is, you know, a very short, you know, time frame. We want the product to be available for patients as soon as we practically can, post, hopefully, a, you know, EUA timeline. Great. And as we think about, you know, this maybe in comparison to, you know, other drug launches, I guess are there any kind of references, or how are you thinking about, like, you know, the pace of a launch like this? Yeah. So I think some of this, like anything, is going to be charting some new ground. And there are certainly analogs, people who, we've seen how COVID products have been used. And so the, you know, the, the typical, like, "Do I have to explain the, the disease area?" I would think not. I'm guessing there's nobody in the world probably that hasn't heard of COVID or understands what the disease is. I think it's going to be more on the logistical components of this, making sure people know about, you know, reimbursement codes and making sure that the, you know, distributors all have the product available, people know how to order the product, they know how to get the product, that we can ship it. I mean, all of those sort of pieces which I've spent a lot of time in my past working on and making sure, and I'm a big believer in, you know, operational excellence, you know, really then drives these types of successful pieces. Because otherwise, you just have the leakage that occurs through all of the different chains, in the system. And so we really want to make sure that we can get product to the people who want it and need it and, can use it. And I think, you know, in the early stages, there'll be some time that it takes to sort of, you know, prime the pump, if you will, and get things all established and all that plumbing in place. But because we've already started working on all of that, I'm optimistic that we can do it very rapidly. Great. I guess just on that as well, you know, I guess part of the manufacturing side of things and, you know, just making sure and access logistics, what are the steps you know, I know you mentioned that you were kind of already working on it. I guess what are some steps that you're taking there? Yeah, so I mean, we've been thinking and preparing for a possible EUA for quite some time. It's a biologic product, so there is a lead time in making the product and having it ready and going through all of the quality steps, etc. And so we have manufactured, you know, a significant number of doses at risk. And that's what we've been putting in place and really have established that initial launch quantity. And so that's what we're working on to get completely, you know, released and final approved. And you know, that would be what would be used at first, and then preparing for that sort of next set of inventory that we would use to replenish, and looking through what that would be and the timelines for that. Great. And then lastly, I know there's some competition here. How are you viewing competition in this space? I know there's another phase three asset. Yeah, so from our perspective, we think we're uniquely situated in a couple of ways. One, we feel that we're one of two companies that have existing prevention studies that you could bridge back to. And so that puts us in a very unique position. We also feel that we could be on the market first, which also allows you some first-mover advantages and, you know, that sort of elements. That said, we do also see that there's significant need, and additional players in this space have the benefit of raising awareness and bringing more attention than we probably could as just a single small company. And so for us, competition isn't like perceived for us as like a, you know, devastating event. There's a "Okay, this is the set of parameters that we'd be focused on if we're by ourselves, and this is what we'd be focusing on if we're, you know, in the market with other people." But as you said, there's really only one other company that has, you know, a product anywhere near launch. And so, you know, we're not talking about, you know, being one of many. We're talking about either being one of one or, or likely one of two for a, you know, foreseeable future. Great. Just to wrap up, because we're right at time, can you remind us of Invivyd's cash position and, you know, what that does and doesn't assume? Yeah, so we're blessed with a very strong balance sheet. Q3 is the last update we had put out, $265 million cash cash equivalents, which we think really prepares us well for what we're looking to do. We put out cash guidance that said this would take us into the, you know, fourth quarter of this year. It really incorporates the budget that we have put together for the launch, etc. It excludes any revenue from commercial sale. And so again, we think it puts us in a really strong position to be able to execute on the activities that we have coming up in the near term. Great. Thank you so much. Thanks, Evan.