Hello, everyone. I'm Maxwell Skor, biotech analyst with Morgan Stanley, and before we get started, I need to read an important disclosure. Please note that all important disclosures, including personal holdings disclosures and Morgan Stanley disclosures, appear on the Morgan Stanley public website at www.morganstanley.com/researchdisclosures. And with that, I would like to welcome Dave Hering, CEO of Invivyd. Welcome to the conference. Excited.
Thank you.
Thank you. And for those in the audience who are either new to or revisiting the Invivyd story, I was hoping we'd kind of discuss COVID in general, what the current status of the pandemic, and then we can dive into the programs, if that's all right.
Yeah, I mean, thankfully, I think COVID sort of introduces itself. Everyone understands the disease. We all lived at home for a while. I think the key piece here, though, is where COVID is going forward. There was this conversation, of course, about the pandemic. Is the pandemic gonna end? Where is COVID gonna go? Invivyd as a company is really focused on driving solutions for this ever-present threat from COVID disease, and so the company is focused on monoclonal antibodies. We're using a platform approach to really deal with viral evolution.
We've all seen all these different variants, and in order to keep track of those and keep ahead of those, we're really focused on driving monoclonal antibodies as a platform, using them in prevention first, specifically in immune-compromised populations, groups that aren't getting optimal benefits from vaccines, et cetera, because their immune systems aren't acting the same way as normal, healthy adults are. And so they have a critical unmet need. They're also, unfortunately, the ones who are at the highest risk of severe disease. So that's really the focus of the company. We do think the platform could be extended to other viral infectious diseases, influenza, RSV, et cetera, but the first priority is COVID-19.
Okay, great. Thank you for that background. And then broadly speaking, overall, what's your view on the variants? And, I mean, there's different variants that are popping up currently, EG.5, BA.2.86. We can talk about these variants first and then potentially how it applies to your lead program.
Yeah, so I'll talk about the first two that are in the news. They're the news of the day because we have gone through a whole litany of different variants over the months and years. These are the ones that people are talking about now, though I can almost assure you that three or six months from now, we'll be talking about some new variants. But as it relates to the EG.5, comes up 'cause it's one of the most prevalent variants right now in terms of causing symptomatic disease, et cetera. It is basically one mutation different from XBB.1.5. That's relevant because XBB.1.5 is the variant that was used in our phase I testing, as well as the vaccines that recently just got approved this week from the FDA.
It has this one mutation difference called F456L, and so we haven't tested EG.5, but we've tested another variant that has that mutation in it in vitro and continued to show activity in our lead asset, which is VYD222. The other one, 2.86, has gotten a lot of news because it had a lot of mutations, a lot of change, and so whenever that happens, people kind of take a pause and take notice of, "Oh, okay, what is the virus doing?" That one, since it arrived on the scene, there's quite a few preprint publications stating that its sort of fitness level, et cetera, is not expected for it to continue to be any kind of, you know, major variant of concern.
We'll keep monitoring and taking a look at it, but again, some of these flash on the scene and peter out, and then some of course take a little bit more of a fire and expand globally. So we'll take a look at it, but that's the other reason that one's in the news.
Okay, so let's move on to your lead program, VYD222. If you can kind of just frame data to date what gives you confidence in moving this program forward, and then we can move into the CANOPY trial and the first patient dose.
Yeah, one of the things that's really unique about our lead asset is it's actually quite associated with our first asset. So our first asset, ADG20, we took through, you know, significant clinical testing in prevention, in treatment, in post-exposure prophylaxis, all of that, met the endpoints in those trials. And that's important because where we are now with 222 is we've done a phase I study, and in that phase I study, we started pulling what are called serum virus neutralizing titer values. And that's just a big mouthful to say, right? It's, you know, how your... If I take your blood, what are the neutralizing titer values against a specific variant? And so we did that in our phase I study.
We put out that information, and then more critically, what we said is we have alignment with the FDA to use that type of endpoint in a pivotal study. And so that's important because it's obviously much more efficient, much faster, much easier to do titer value testing versus, you know, waiting for people to get COVID and then testing, you know, how many people got it in a placebo arm versus, you know, the actual drug arm. And so we're using that approach in our CANOPY study.
We announced on Monday of this week that we had started dosing that study, and so where we are in terms of development is, you know, having started that pivotal study, and, what we've continued to guide to is that we're looking at preliminary endpoint data from that study by the end of this year or early next.
Okay, great. And so in the phase I study, you evaluated three doses.
Yep.
You decided to move forward with the highest dose?
Yep.
Rationale behind that? Any, I mean, overall, safety data has looked encouraging. Basically, there is no major safety concerns.
Correct.
So why go with the highest dose?
Yeah, it's a little counterintuitive, right? Normally, when you're doing drug development, you say, "Let me use the lowest possible dose," right? 'Cause you're concerned about potential side effects, et cetera. The safety profile of monoclonal antibodies has been very strong from, you know, the beginning across, you know, a whole host of manufacturers. That's because these monoclonal antibodies are targeting the virus itself, and, as such, they're interacting right with the spike protein of the SARS-CoV-2 virus. We decided to go with the highest dose with input from the FDA, looking at where we are to get the highest starting titer value, right? Not surprising, if I give you a bigger dose, you have a higher initial titer value, and then over time, that decays, right?
So we've done a half-life extension, et cetera, into the product, but over time, you're gonna get that decay. So, in order to give the longest possible duration of protection, as well as to give ourselves protection against potency changes that could happen from different variants, we, again, with input from the FDA, decided to go with the highest dose.
Going back to 2.86, have you tested VYD222 against 2.86?
Not yet. So each of those variants, when they come out, you have to get assays up and qualified, et cetera, and so we've done a lot of that. But, you know, one of the critical things that we've continued to invest in in the company is this set of tools really looking at surveillance, viral evolution, predictive modeling, et cetera. And so we have mapped and drawn out the crystal structure of our monoclonal antibody, and then when these new variants come out, we take a look at them and see, you know, are they in an area close to where we bind? And when I mean close, we're looking at whether it's, you know, five angstroms or less.
That's one of the areas that we look at, in terms of, you know, getting a sense for whether there could be, you know, a potential challenge, et cetera. And so our preliminary look on all this continues to have us believe that we would have activity against it, and then we'll confirm it once we get the assays in place and can test them in vitro.
Okay, great. And in regards to the design of the CANOPY study, it's you have two cohorts. Could you walk us through both cohorts and what you're looking to get out of that data?
Yeah, of course. So right, it's a very compact, clinical trial design, 750 subjects overall. Cohort A is 300, cohort B is 450. Cohort A is immunocompromised, so that population is looking to, that we can see the same result that we saw in the phase I. So the endpoint there is a day 28 serum virus neutralizing titer value. And so that's what really what we're looking at for that cohort, as well as safety. Cohort B is an all-comer study that is predominantly just to build the safety database and show any potential differences between placebo and the drug.
Okay, great. And for cohort A, if I understand correctly, the FDA is asking for a second dose three months later. What rationale behind that?
Yeah, so we're doing it for both cohorts, but we've added a three-month redosing component to the protocol, really because we want to be able to show that you can boost. So, it's intuitive that you would, but this way, we can demonstrate it. So as I said, you do your first dosing, you start with a titer value, it'll decay over time. You then go in at, you know, day 90 redose and see what that fold increase, that fold rise is from where you were, and showcase then that you have that data.
When people start to think about this in real-world implications, you could think about, okay, when we get to certain titer values, we have confidence that we could redose if necessary, or if new variants come along, we could look at those and say, "Ah, okay, we know what we can do," and we've demonstrated that in these studies.
Okay. And so, best-case scenario, if we look at the CANOPY study, we have the interim readout coming end of the year, early next year. What potentially are the gating factors to apply for either EUA or any other strategies in regards to communicating with the FDA?
Yeah, I mean, to put all of this together into a package, right, you have a non-clinical, clinical, and manufacturing component. We have written an EUA document before. We did one for our initial asset, so we're comfortable with, you know, all the different elements that are there. We're really waiting on getting the endpoint data, which is based on this day 28. We don't need the redosing as a part of the package for the EUA that we're looking to submit, but it would be pulling all of that together.
So really, you know, the gating items include, you know, getting that data, you know, making sure all the data is, you know, QC'd and, as you would think, ready for submission, making sure all of your CMC, which is the manufacturing side, all of those validation elements are in place, and that you can put all that data together and submit it to the agency.
Okay, and the FDA is looking at previous data from the monoclonal antibody that you developed before. How would this data package look overall? What would be... you're using serum-neutralizing antibody titers as a benchmark. What is clinically meaningful? Is there a specific number you would point to?
Yeah, so we don't have a specific number in terms of, like, okay, this is the, you know, absolute, you know, number that we're looking at. What we've shown in the phase I, so we were talking about the, you know, the 4,500 mg dose, we were seeing at day seven titer values close to 17,000, right? Which is a, you know, really significant number. We're comparing that back to some of the titer values we saw in our EVADE study. That was the prevention study we did with ADG20, and we saw different efficacy values for titer values from, you know, as low as 100 up to, you know, 3,000 something. And so we published that in a peer-reviewed journal in this curve that we did in April.
But what we're really looking to do is, as I say, target some of those titer values and see how they look, you know, again, over time and compare the data that we're generating from the new asset against some of those titer values that we saw before.
So what, would there be any reason why the titer values would potentially be lower than you would anticipate?
Well, the titer values are always associated with a specific variant, right? So in terms of testing them again against XBB.1.5, which is what we did in phase I, there isn't any reason we have to believe that they would differ, even using an immune-compromised population, because again, I'm not looking for your immune system to do anything. This is passive immunity. I'm giving you, you know, an infusion and letting that work its way into the blood. So, you know, each of us have different baseline titer values to start, but looking at the fold increases in where we can go, you know, we don't have a belief that there should be any difference.
Is there any unknowns around? So you said you have alignment-- you've gained alignment with the FDA on potentially what an EUA data package would look like. I don't want to put words in your mouth, sorry, but, is there anything, or is there uncertainty with these novel variants that keep popping up that would change course in your mind?
I mean, we'll continue. I mean, again, the whole basis of the company is the goal to license the platform at the end goal. So we're talking 222 as the first piece of this. Certainly, we have seen variability between assays, between variants on where the potency is. That could have some implication as we're working through it. But again, the goal of the company is to start with 222, and then continue to have conversations with regulators about how do you move from one to the other. So we're on the third iteration of the COVID vaccines. Those aren't each going all the way back to the drawing board and starting at phase I and going through clinical trials. They are getting licensed, basically supplementing the licenses that they have. It's similar to what happens with flu vaccines every year.
It's that approach that we're looking for in the long term. 222 through an EUA, you know, there's certainly a lot of leeway and flexibility that the FDA has when it comes to EUAs. That's both good and bad, right? Because it really is, then dependent on what the environment and situation looks like at that specific time. But we're very encouraged by the FDA and EMA continuing to have conversations like they did all the way back in December about how do we accelerate the development of monoclonal antibodies, as there are zero on the market and a huge continued unmet need, specifically in this population.
And so overall, it seems like you've achieved a potential accelerated path to getting to the EUA step. And the one factor, I guess, unknown, is the safety database. How much data do you need to compile, and for how long before you're potentially able to lock that?
Yeah, we anticipate that the safety data around the same time point of the day 28 is what we would be putting together to show that initial rate, right? Like, what you're really looking at in monoclonal antibodies is a safety profile in those first couple of days, right? Do you have a reaction to the infusion, et cetera? And so we will continue to monitor it, you know, going forward beyond the 28 days, but that's really what we're looking to include as a part of the data package.
Okay. I think I fielded questions from investors in regards to why other companies who are developing monoclonal antibodies are maybe not taking this accelerated path, or it may not be an option. SUPERNOVA comes to mind, for example. I know Regeneron's also reformulating their monoclonal antibodies. Could you speak to the competitive landscape and where you fit into that?
Yeah, of course. So the FDA was very specific to use this path, and the path that we're talking about is using what they call a prototype mAb immunobridging. That's sort of the, you know, way that they've described it. In order to do that, you have to have a parent monoclonal antibody that has gone through double-blind, placebo-controlled, event-driven study, like we had in EVADE. The new antibody has to be on the same manufacturing platform and similar in terms of how it was created. So our VYD222 is eight amino acids different from our initial original, so we checked that box, and it has to have activity against current variants, and so that's why we continue to do the in vitro testing. So to meet all of those requirements, there is a very select few companies that have done this, right?
So as I said, the big, I think, owner's piece is have you done that initial study, right? Did you do an event-driven clinical trial for prevention, which we certainly have, but, you know, AstraZeneca has, you know, a few of us have, but we think that list is relatively small. Then you have to be targeting... Like, we're continuing to work on this, Fc region, the receptor binding domain of the spike protein. We use the same manufacturing platform. If you start to deviate and go to a different part of the virus that you're targeting, then, it's possible that you might not be able to use that clinical trial data that you had. So again, I think that has an implication.
So if you start to look beyond RBD and spike and, you know, into other areas of the virus that you're targeting, you might have to redo that. And you brought up SUPERNOVA. SUPERNOVA is AstraZeneca's trial. They do have a prevention trial, but their SUPERNOVA study was originally created before this conversation about prototypes, et cetera. SUPERNOVA really was announced sort of Q4 of last year. The meeting with FDA and EMA was December. They've made a variety of modifications, and we'll see what they do, but I think that's caused why they have so many iterations to the study design.
Okay. As you've said, you're targeting immunocompromised individuals. Could we talk about the market opportunity there, and not only in the U.S., but potentially ex-U.S., and what geographies you're looking to target?
Yeah. So the immunocompromised population, you know, depending on how you classify it, we've looked at it, it's about 8-18 million people in the U.S. alone. We've now started to subdivide it into different groups. So you can think about, you know, people who've gone through organ transplants, people who have a variety of, you know, hematological, you know, oncology disease, you know, people with cancer. Then you're looking at also folks on immunosuppressants, folks, maybe multiple sclerosis, dialysis, et cetera. We've now cataloged about 41 of these different potential conditions, and so that's now what we're focused on as we're thinking and being ready. So we're doing all of those sort of commercial-ready activities now to really think through what these target populations are, who are the ones that we can go and meet.
We started doing market research on the healthcare providers, their receptivity, who were the ones that were using AstraZeneca's Evusheld in 2022. And so really, you know, combining that in and looking at it. So we continue to see it as a very significant market. AstraZeneca generated about $2.2 billion of revenue in 2022, before they were pulled from the market in January of this year. And so we think that's just the tip of the iceberg. We really see that this group is highly motivated. They are a group of people through some of the patient advocacy work and others that we have talked to that are feeling left behind. We haven't talked about it yet, but, you know, most people have acknowledged we're in a new uptick in COVID.
Just about everyone I know knows somebody who either has COVID or just recently had COVID. And so these folks are the ones who are still masking on planes, afraid to go out in public because the potential implications to them are so much more significant than to your just sort of standard, you know, healthy adult.
Okay, that's helpful. I guess one question I have in regards to, I think, Regeneron, when they initially developed their monoclonal antibodies, they used two different antibodies to target two different regions. Would this prevent you from applying for the immunobridging approach to get the EUA, or have you put any thought into including another antibody in your cocktail to be able to deliver more efficacy?
Yeah, great question. I don't think it precludes it, though I think that would be a, you know, a different part of the conversation. I don't think it precludes... Right, if you had two antibodies that were similar, I think the challenge you would start to have there is, again, depending what you're bridging to and the titer values, are you able to, you know, effectively suss out which antibody was contributing which? And so I think you would- there's probably some nuances there, but conceptually, I think it seems possible. We've looked at combinations, and the, one of the main reasons for doing a combination is to give yourself more insurance, right? The idea being if you have two non-overlapping antibodies and one gets impacted by one of the variants, you have the second one to continue to drive.
I think it's a, you know, a reasonable approach, but we feel that the better approach is this sort of serial monotherapy design that we're talking about, which is if you're assuming that at some point, just like the vaccines, you're gonna need to update the monoclonal antibodies, then having two is unnecessary, right? It creates additional manufacturing challenges and the rest. It's better just to have one and then have the process in place to move from one to the next. So that's, again, one of the big focuses of the company now is, you know, certainly the near-term priority is getting 222 on the market, protecting patients. But the longer-term piece is really how do we execute on that?
Because we've added in the discovery and surveillance work, and once you have that regulatory path in place, and again, whether it's every year you update the monoclonal antibody, like it seems to be, what we're, you know, sort of gearing towards with in the vaccines, or you did it on a certain time point where you start to see something, or maybe you have multiple antibodies on the market. We're still working through what that transition will be, but I think that's the better solution than necessarily doing combinations.
In your mind, if we move into, or one could argue, an endemic phase where we're updating the vaccines yearly, potentially updating monoclonal antibodies yearly, do you think the vaccines surveillance approach, looking at what's moving around in certain hemispheres and then trying to design the vaccine based off of that, is that a good idea or a good approach that you're applying to your development process?
Yeah. So we have a whole host of tools, really looking at the epidemiology, looking at wastewater, looking at these different variants, and we're cataloging them by family, like lineage. So you've got, you know, sort of the BA.1s, the BA.2s. They all have a basic parent and lineage, the XBBs, the BQs, like, they all look like this. And so then we have folks looking at the specific mutations of these different variants. Someone reminded me the other day, there's more than 15 million sequences of SARS-CoV-2 right now on this GISAID database, and so we're using a variety of analytical tools to process through those. So when new ones get added, what does that look like? Where are they mapped to, et cetera? And so that's really the ability to try to be as forward-looking as you can.
I know a lot of people say, "Well, what happens if we move from Omicron to something next?" That's much more difficult to predict. We're in Omicron now, and all the sublineages of Omicron. You know, again, I think it's mostly a guess, but at one point I read, you know, some of the top scientific experts in the country estimated that there was a 10%-30% probability that at some point in the next five or seven years, we would move from Omicron to the, you know, sort of next backbone of the virus. No one knows.
That, like I said, would be more difficult to predict, but while we're in Omicron, you do start to get a really good sense of how these different branches continue to form and what the sort of points are and where the virus can mutate and still keep its, you know, different fitness, so that it can continue to do what it needs to do.
Okay, great. So I guess final question here: You're in a strong cash position, $298 million reported with 2Q earnings, provides a runway into the fourth quarter of 2024. What do you think investors are missing here? How do you, how do you view the stock price? Is it? Do you have enough money for one shot on goal? Is there another iteration, potentially, that could be supported? Any thoughts around that?
Yeah, I mean, listen, I always think that the stock is undervalued, especially at the current place where it's trading. I think it's an opportunity. We're trading below our cash value of the company, like a lot of other biotechs. I think where we are and the ability to get to market with the speed that you can still in COVID is one of the more exciting areas in drug development right now. We're still in what I think is relatively uncharted territories. This is a disease area that didn't exist three years ago. Prior to 2020, nobody had a model that looked at any revenue from a SARS-CoV-2 type of virus. And so that's both exciting, but I think what causes people some questions, people especially who like Excel and, you know, spreadsheets and models, how do you put the different inputs in?
And so that's really, I think, what a lot of people continue to have questions about. We think it's a relatively straightforward piece, like, do you think COVID is gonna be here to stay? You know, most emphatically, people say yes. Do you think there's gonna be a continued unmet need in these populations? The answer is yes. There are no products on the market. The opportunity is great, and so then it's figuring out from here to there how these different iterations are gonna take place. So I think that's one of the critical pieces that we keep communicating to people. I don't think you need to get lost in, you know, a lot of the different, you know, like, is it, you know, 2% or 6%, or is it, you know, these types of different elements?
But the high level, you know, order of magnitude that we're talking about is, it's a huge unmet need, with no, you know, like, with no products currently in the market. So that's really how we think about it, and that's what I continue to reiterate with investors.
Okay, great. With that, I really appreciate your time, and thank you very much.
All right. Thank you so much for having me.