Hello everyone, and good afternoon and welcome back to H.C. Wainwright BioConnect Investor Conference in partnership with Nasdaq. I'm Patrick Trucchio. I'm a senior healthcare analyst at H.C. Wainwright. It's my pleasure to introduce our next speaker, David Hering, CEO of Invivyd, a clinical stage biopharmaceutical company focused on delivering antibody-based therapies to protect vulnerable people from devastating consequences of circulating viral threats, starting with SARS-CoV-2 and then expanding to flu and other high-need indications. Maybe we can start first with just some brief background on Invivyd, including the history of the company. Sure thing, Patrick, thanks for having me here. Invivyd was created during the pandemic. It's only a few years old with the goal, exactly as you said, of bringing products to market, starting with COVID and going from there. Originally we had an additional initial compound, ADG20, which we took into clinical trials and got through pivotal data. I'm gonna use this instead. Use that. We took it into clinical trials and delivered against all of our endpoints in record time. That was the impetus and start of this. Now really what we're envisioning for the company is a serial monotherapy approach to delivering products against COVID-19. What we've seen is one single antibody or combination of antibodies is highly unlikely to remain active against a virus like SARS-CoV-2 that continues to evolve. We've geared the company directly to address that ongoing threat of the virus and that's really where we are today. Can you talk more about, which patients Invivyd is gonna focus on? Where is the unmet need at this stage of where we are with the disease? Yeah, I mean, interestingly, you've got this case where vaccine efficacy in prevention of symptomatic disease has plummeted against the current variants, which is, you know, unfortunate for where we are. That plummeting efficacy is due to the viral evolution and change in variants. The most recent bivalents that were boosted have the ancestral, you know, Wuhan strain and BA.4/5. We're now into BQ.1s and XBBs, some of the new data shows that there is limited to no efficacy in preventing symptomatic disease in the XBB Omicron sub lineages. This has also led to continual waves of disease and, unfortunately, also emerging evidence of reinfections and what the potential long-term impacts could be. That's to people who mount an immune response to vaccines and need prevention. When you talk about immune compromised people, in particular vulnerable populations, they don't even have the benefit of, you know, a minimal response or use of vaccines. Monoclonal antibodies are designed for prevention, treatment, and post-exposure, and they were, you know, instrumental part of the fight against COVID-19 that has been eliminated. I know we'll talk about it some more, but right now we are where we were in 2020, which is there are no monoclonal antibodies on the market for prevention. You have immune compromised people with a significant unmet need. We talk to them every day with our patient advocacy groups, and while the rest of us have more or less gone back to leaving our houses and going back to where we were, these are folks who feel trapped and nowhere to go. That patient population in particular is one that we're targeting as a preventative approach and to give them a product that provides them hope. Right. Maybe talk a little bit more about Invivyd's antibody platform. What's differentiated about this platform and the approach? Yeah. The antibody platform comes from our own internal discovery as well as partnerships. The company utilizes a technology from Adimab for yeast display. What we then do is something differentiated from other antibody manufacturers, which is we do engineering of antibodies, which is affinity maturation. This allows us to find antibodies that wouldn't be just naturally occurring. So yes, we do B-cell mining and look for those, but this engineering approach gives us, as I said, antibodies that we see should have less immune pressure. Hence, the goal is to increase the probability of higher durability, higher duration in the market. That to us, is one of the differentiating factors of our platform. Right. Maybe you can also give us an overview around the partnership activity, how some of these came about, what's the strategic importance of the current partnerships in your operations? Yeah, as I said, I mean, I mentioned the work we've done with Adimab. We have an existing relationship with them. That really has been one of the foundations and building blocks of the antibodies. We've now continued to evolve that partnership. We're in the process of transferring in some of the technology into our own internal labs, which is then again, what we could be using for both COVID as well as other infectious disease down the road. We have a strong partnership with WuXi, which is a manufacturer which allows us to rapidly produce antibodies both for clinical trials as well as for commercial production. Those two are really critical in terms of our goals to be able to move through development rapidly, find antibodies perpetually, and deliver them and have products on the market sustainably. Recently the FDA cleared VYD222 for an IND. I'm wondering if you can talk about the VYD222 program. Where did this kind of how did it come about? Some additional details around kind of where you see this program going from here. Yeah, 222 is very exciting. It's our re-engineering strategy in action. 222 is a re-engineered version of ADG20, which was our original compound. We shifted eight amino acids in the variable region that targets the spike protein of the virus. Basically what we did is take, you know, those connection points and just pivot them slightly so that we could recreate activity with the antibody against the Omicron sub lineages. To date, in vitro, we've shown activity against all of them through XBB.1.5, and that's what we continue to monitor. We're excited about this for a variety of reasons. One, you know, you talked about the IND. In December of this past year, there was a FDA EMA meeting. In that meeting, they specifically talked about this prototype concept where if you have a prototype product, you could then use that to either accelerate or, you know, augment your, you know, package for regulatory. By starting with ADG20, which I mentioned, we already have conducted clinical trials extensively across, you know, prevention, post-exposure, pre-exposure. We are hoping to utilize that as a part of the 222 development program, both in terms of safety and, you know, totality of data. That's the exciting part there. We also see this as the scaffold that we can utilize going forward. That is important because, as I've said, we expect viral evolution to continue, unfortunately, with the SARS-CoV-2 virus. We are continuing to put new antibodies into our pipeline to address that going forward. Yeah, that's helpful. Then a couple of follow-ups, just the first around the regulatory framework that you mentioned. Yep. How has this evolved? I mean, I think all of us are familiar with kind of how COVID drugs were approved previously. How is it evolving now? Is there, kind of a precedent being set for accelerated regulatory pathways for COVID drugs? Yeah, I mean, it is an evolving landscape as you can imagine. Even for our original ADG20 product, we saw that as more and more people got vaccinated, that changed the paradigm. Then you had oral antivirals that came to market, and that changed it. So you could no longer run placebo-controlled trials in the U.S. for treatment, right? That was a big change. The original studies in most monoclonal antibodies were clinical endpoint event trials, meaning, you know, you were testing placebo and drug and testing who got symptomatic COVID-19, right? You are looking to find areas around the world with high disease incidents to be able to get at this data quickly. What's evolving now is this approach using surrogate and biomarkers in order to do these studies much more rapidly. There is a recognition globally amongst regulators that the pace of what I call human nature or the regulatory side isn't keeping up with mother nature. That's why we continue to have these gaps where we have no products on the market like we currently have. The approach here continues to look at how to use surrogate and biomarkers in order to do trials more effectively and efficiently. That's really our approach with 222. We recently published a paper specifically talking about correlates of protection in utilizing serum neutralizing titer levels and comparing that to efficacy data. You could also see with AstraZeneca and their new SUPERNOVA trial that they are using a bridging study. Again, you can see this shift away from clinical event endpoints to biomarker surrogates correlates of protection, which we see is, you know, a great step in the right direction for how we as society are going to be able to stay ahead of the variants. Just back on VYD222, can you talk about some of the preclinical data that you've generated so far and how you would expect that to translate as you bring this program forward to phase I? The preclinical data, right, we have, we can continue to conduct both, you know, pseudovirus assay in vitro testing, which shows IC50 in activity levels with those data. Looking at a variety of PK modeling, you can start to get a good estimate of duration of protection against the current variants. It's a space like no other than I'm aware of in biotech, where already in preclinical and doing in vitro work, you already have a good sense of what the potential efficacy could be of your drug. Before you've done phase I, before you've done phase II or III, you're starting to get that, you know, early read. We continue to do that. You do your normal panel of, you know, rat tox and TCR and the rest. You know, we've continued to conduct those. I think, like I said, the most important are these early views of how the product's gonna work well before you're doing these large scale trials. Right. Now, the original timeline for antibody development that you went through is around 16 months. Yep. I think you mentioned the goal is to do it much, much quicker, much faster and cheaper. How should we think about this, you know, condensing of the timeline, particularly around the use of these surrogates and biomarkers? How much quicker could this timeframe become? I mean, today we see this ability to go faster, right? That's really the goal, just as you said. Part of that is because recruitment of trials can happen much quicker. We're currently working on the design for our pivotal trial. We're in discussions with regulators. Once we have that finalized, we'll certainly communicate, you know, broadly what that trial looks like. If you want to look at, you know, proxies for speed and time, you can look at what AstraZeneca is doing. They have started their combination of phase I, phase III, this trial. They continue to put out guidance that they're looking to be in the market before the end of the year. The pace of development in this space is like none other that I'm aware of. Yeah. Just in terms of, you know, the timeline for VYD222. I think in the Q2, we're gonna get the first phase I data. How important is that data as you're looking to design the phase III trial? Presumably, you take that data to the FDA or what does that look like? You know, what is the ideal scenario for Invivyd as you go forward, as you're looking at the phase III? Yeah. The phase I data is safety tolerability. Dose ranging is what we're looking at there. In Q2, we'll have preliminary data that we plan to read out. Interestingly, not only would we get information on the dose ranging piece, but we would get this initial read on, again, you can get this, you know, serum neutralizing, you know, virus titer levels, and then using the curve in the publication that we put out in March, you get this early read on what the efficacy is gonna look at. That's an important indicator for us. The data there will then support which dose we want to take into the phase III. Really, it's less about looking at that from a safety and tolerability, but more getting some of the PK information, the half-life data, from the phase I, which then will inform really the dose selection for the phase III, and while we're doing that, finalizing the design with the FDA. I mentioned earlier just the Astra program is a phase I, III combined program. I think they're looking to bring that product to market in the H2 of this year. Yep. Maybe you could talk a little bit about what does that look like? Is that an emergency pathway, you know, emergency authorization pathway? When the public health emergency ends in this month, what does that look like? Is that still available? Would you expect to follow, you know, the path that Astra's taking? Is there any reason you wouldn't be able to follow their footsteps? Yeah. A bunch of good questions. First, in the U.S., yes, we continue to see emergency use authorizations as a pathway that's open. One was given to a product just recently in April for a very, you know, niche, you know, severely, you know, sick individuals that was recently granted an EUA. Everything that we've looked at, the FDA continues to have this authorization even after the public health emergency ends. As we've noted, there are no products on the market for immune-compromised individuals. All the monoclonal antibodies have been removed in the U.S. Ex-U.S., there are options outside of EUAs. We've seen EMA in particular also quite interested in this biomarker approach, so we have ongoing discussions with them. Yes, we see the EUA pathway continuing in the near term, and the longer term goal is to take the platform and look to get a licensure on the platform similar to what you would see in COVID vaccines or flu vaccines, where you have an approval, and you update them on some sort of timeframe, usually seasonally or, you know, yearly, etc. For those strain changes in vaccines, they don't go back and redo clinical trials. If you can use the scaffold, as I said, the manufacturing platform, etc, that to us is a good longer term approach for how we would be able to deal with continued viral evolution and have products continually on the market without these gaps. Just thinking about the competitive set, you know, and which has also been evolving, a number of the antibody developers have essentially dropped out. You know, AstraZeneca, of course, is moving forward, and Regeneron has a new antibody approach that they're taking forward. We have the small molecules on the market. How do we think about positioning of 222 relative to small molecules for post-infection treatment and then relative to having, you know, another Astra molecule on the market for prevention? Where does 222 fit in? Yeah. First, I mean, it's an interesting space because it's not like other drug development. You know, as I said, we haven't seen any other drug development that's faster, higher probability, bigger market opportunity than this, in terms of where we are. Where I think a lot of folks were is they saw this initial, you know, huge opportunity when all of us were locked home to develop drugs. You know, over time, that interest has shifted into other disease areas because what we see is the pandemic part of COVID has gone away, but what's left is the infancy of this new disease category in the endemic state. This opportunity is different from others in that, as I said, as an antibody manufacturer, you have the opportunity to work against, you know, the disease and treatment prevention and post-exposure. We see prevention in this vulnerable population as, you know, a huge unmet need, one that you can target the population specifically, you can get to the healthcare providers and find these folks. They're highly attuned to wanting the products. For a company our size in particular, looking at what a commercial model would look like, it's a very attractive market. You know, recently, AstraZeneca in their earnings a week or so ago still mentioned this as a blockbuster market opportunity for them. You know, we agree. I mean, it's still a, you know, multi-billion dollar market just looking at the prevention in immunocompromised. We see the biggest competition in this space really coming from the virus itself and how it evolves. There isn't a, you know, a situation here currently where it's going to be a, you know, one company takes all kind of piece. When you look at the almost certain evolution of the virus, we think that our strategy for the near and longer term to continue to have available antibodies in our pipeline to plug and swap in as the virus evolves is the one that will be the best approach. I think when Omicron came about, that was very surprising, to a lot of folks out there, and I'm wondering what is the probability that there's another Omicron-like event and what would you do? How quickly could you re-engineer? Yeah, that's a great question. What I would say is right now we've continued to add a great degree of surveillance into our capabilities. With that, we're looking at, you know, mutations, evasion to antibodies. That's what leads us to continue to be testing in the background, our different antibodies in our pipeline. With the current Omicron sub lineages, I mean, there are hundreds and thousands of these, many of which don't go anywhere. What we're tracking is ones that may have a fitness advantage, ones which may have a mutation that could cause a problem and tracking them, you know, globally. My long answer to that question is we have pretty good visibility in the Omicron sub lineages. If there's another major shift from Omicron to, say, Pi or Rho, that's much harder to predict and see. I think the approach is the same in terms of being able to quickly do this work. I think it's that threat that's also on the minds of regulators and the broader environment, because Omicron has had lesser severe outcomes, right? Less hospitalizations, less deaths. There's no guarantee that the next major change will do that. When we talk to governments, there's still a lot of, you know, concern about pandemic preparedness, et cetera. While maybe the rest of society has stopped thinking about COVID, certainly if you're a, you know, government health official, you're worried about what that could be and the fact that no one can really predict what the next Omicron is going to be. Right. Maybe just a question around cash and. Yep. cash runway, kind of the ability to fund the phase III and then potential launch. Yeah. We will provide updated guidance next week during earnings, but the last guidance we had was at the end of the year, we had $372 million of cash on hand. It's enough to fund the clinical trials that we have planned for COVID all the way up and through to an EUA or equivalent ex-U.S. We continue to monitor that. What we've said is that would take us into the H2 of 2024. As we get more precision on the size of the studies and, you know, broader regulatory commitments, we can continue to update those numbers. Great. Any follow-up questions from the audience? Well, great. Thank you so much. Thank you for having me. Thanks, Dave. Thank you very much.