We're ready to start. Welcome everyone. Joined by Marc Elia, Chairman of Invivyd, amongst a number of other hats that you wear, but this is probably the one that's keeping you most busy lately. Give us a snapshot of the company and maybe some of the upcoming milestones we have to look forward to. Sure, happy to, and thank you. So, Invivyd is a antibody company with an authorized antibody for the prevention of COVID-19 disease, about which we're very happy and very proud. And indeed, also a technology company with an antibody technology platform that we have, for the moment, devoted to the concept of generating serial high-quality medicines that can either prevent or treat SARS-CoV-2. Which, I think despite all of our best efforts at both innovation and then, you know, perhaps, psychosocial denial, remains a pretty important medical burden. And so we have, over the last few months, launched our first authorized molecule, PEMGARDA. We also announced full 180-day efficacy data for that molecule, which showed an 84%-85% reduction in the risk of symptomatic COVID for those all-comer individuals who were in the PEMGARDA arm of our registrational study. And of course, we are in the full throes of our commercialization program. So, in effect, what you are contemplating when you look at Invivyd is an only-in-class, hopefully for us, first-in-class, and best-in-class molecule for prevention and treatment of a disease that has not had meaningful innovation, really, since the birth of Paxlovid. And our goal as a company is to continue to innovate, to broaden access to molecules like these, until such time as people like, frankly, some of us maybe in this room, can access high-quality protection with a relatively low burden. That's where we're going, in the disease generally, and with the company generally. So the preceding history to this, from going from a multiple antibodies approved under emergency use authorization to only PEMGARDA is quite interesting. Maybe you can kind of share what enabled PEMGARDA to achieve what others weren't able to? Sure. So I think it's a combination of technology, acumen, and intentionality, and I mean this. At the beginning of the pandemic, it was pretty clear, thanks to some really great early work by a lot of scientists, that one could disrupt pathogenesis, right? You have a virus with a spike protein, you have an entry receptor, an ACE2. And if one deployed antibodies, generally, whether those antibodies are polyclonal from a vaccine or whether they're recombinant monoclonals, like PEMGARDA, like Evusheld, et cetera, these things have been effective in a prophylactic setting. Now, everyone back then really conceived of a single dimension that would determine the barrier to resistance and effectiveness of your molecule. How well could an antibody bind and disrupt ACE2 interaction between spike and ACE2? What I think we all learned as a community and as a field, and what led to now our company as it's constituted, is that the ACE2 spike interaction is a little permissive. Virus will routinely acquire and give up a little ACE2 axis in favor of its more interesting determinant of fitness today, immune evasion, right? So we've been in an Omicron phylogeny for now a couple of years, and I would suspect there's a reason for that. The reason being, back then, mammals, including humans and all of us, were immunologically naked. We had no prior exposure to this virus. As it ripped around this population, and the deer, and the mink, and the pangolin, and so forth, and as we all vaccinated with Wuhan lineage spike, we all acquired an immunologic backdrop. That host-pathogen interaction, therefore, creates a second axis of fitness. We not only need to disrupt ACE2, we need to do it in a way that countenances, that accommodates evasive motion. So what did Invivyd do? Well, it was either an act of madness, or genius, or luck, or I don't know what. We simply said: "Well, if it's a two-dimensional problem, perhaps we can, with our tech platform, accommodate that." So we took our original antibody, and we affinity matured it. It's a form of sort of combinatorial mutagenesis. You get new species out of these sorts of discovery efforts, and we optimized an old SARS-CoV-2, old in, you know, sort of recent terms, against an Omicron lineage virus. And when we did that, we drugged a piece of spike that has been quiescent. It's been quiet. It doesn't change and hasn't changed since Omicron. And that may well be because most antibody developers, us included, the progenitor company, experienced a violent shift event that we think of as Omicron. But that shift event, really, I... at least in my mind's eye, represented more of an immunologic event than a virologic event. It sort of happened at the time at which all of us acquired antibody pressures. And once you walk through that door as a species, you cannot walk back out. We are now all immunologically experienced. We generate antibody titers in response to fewer and fewer boosts, but more and more infections, and the virus moves around a little with those pressures. It's probably why we see these, this periodicity, right? Virus comes along, we all generate an immune response. If we're lucky enough to survive and flourish, the virus moves a little, and it all happens again. Across that whole arc, because of our technology platform, we have consistently drugged certain territory that is what you would call immunorecessive or cryptic. It's quiet, because there has not been a fitness benefit to any structural exploration around that territory. So I tend to look at it as suggesting to ourselves first and then to the rest of you, that the initial hypotheses were correct and incomplete, which is different than wrong, right? So the completeness comes from hopefully a conception of host pathogen that looks more like equilibrium, and therefore, that our structural analysis can yield sort of consistently druggable target space. That's what PEMGARDA, pemivibart, is. It has sat on what we see as consistently druggable target space, and it's how we think about our pipeline. So nobody else in the field has that tech platform, and nobody else brought that intentionality, to my knowledge. So you, you'd framed some of the phase III observations earlier. A couple of interesting signals from that program. One, there were no cases of hospitalization in that cohort. Was that a surprise to you? You know, does that in any way kind of shape or alter your perception of the unmet need? I think we saw something similar in Atea's phase III trial. They just didn't really even have hospitalizations. Yeah. I don't think it changes the perception of the unmet need. I mean, let's just say this, there are a great many medical conditions which do not routinely result in hospitalization, for which people, you know, routinely deploy high value medicines. Okay, so you know, we don't talk a lot about the acuity of rheumatoid arthritis or your propensity to decompensate with HIV, so on and so forth. SARS-CoV-2 is knowably a different beast today than it was when we were all immunologically naive. But the sheer burden of it, the magnitude of the burden is extraordinary. Something like... And I, you know, again, I wore a mask on the train this morning because something like 2.5% of Americans have SARS-CoV-2 today. Obviously, 50% of them are not gonna end up hospitalized. But what we have focused on in partnership with FDA is immunocompromised people who bear a very disproportionate burden, right? And I just look at this and I kind of go, "If we were to power for those kinds of observations, I would carry a very high confidence that we would modulate those sorts of endpoints," right? Because of the simple biological plausibility. If you do not get symptomatic disease, it is very difficult to go to the hospital, right? It is very difficult to then die, so on and so forth. I think this is a matter of the powering. Nobody would imply today that the burden, the outcomes burden, is the same sort of proportionality as it was in 2020. I don't think that makes it less of a key health headwind for a goodly portion of Americans. Was it a placebo-controlled trial? Remind me. So in effect, both. CANOPY, our registrational study, had two cohorts. Cohort A was in immunocompromised people. That was a single arm, open label cohort. Cohort B was, in effect, all comers. So if you read the entry criteria, it was, a human who is at risk for symptomatic disease because they take routinely face-to-face meetings, so it's us, cohort B. That is placebo-controlled. That is where we noted the 85% reduction in one's ability to, achieve symptomatic COVID-19. Okay, so that was a healthier population then, or- I wouldn't call it healthier, actually. Right. If you look at it, it was fairly comorbid. I wouldn't call it elderly, but aged to elderly. It was more all comers. Mm-hmm. When you do that in a trialing population, you know, I would surmise you are probably not signing up for clinical trials routinely, just guessing. It's a personal question, but you don't have to answer. Medical confirmation. But you do get, Yes ... a relatively representative high risk American population. Kind of. It's just small. The other interesting observation was the efficacy even at lower exposure levels of PEMGARDA. So, you know, I guess maybe help us understand first, why you think you're seeing that. Yeah ... and how that informs your strategy going forward. Sure. Because part of that strategy is coming up with new versions of- Yeah ... the product, optimized iterations. I think the reality of the field is the following: there is a curve somewhere out there to be determined, and that people have taken stabs at already, that dictates the, quote, "correlative protection." Okay? How much titer, how much drug in effect, but antibody neutralizing titer is required to generate what quantity of clinical benefit? Because we did an accelerated pathway with our partners at FDA, the FDA carried some very strong views about the need to parse and target very, very high titers. In effect, the logic is, look, if we're concerned about the safety of this airplane or its effect, we'd like you to fly it at 200,000 ft above ground, not 35. And we go, "Okay." That is why, for example, pemivibart is given at the dose it is given. So low drug exposures is a relative statement. We effectively threw the titers and the dose very, very high, so that as it came down, it would land at high. And so I don't know that we've actually interrogated what are, to us, the more interesting parts of that curve, and the parts of that curve that I think would get very interesting as the clinical community starts to see more work that we're gonna do and share publicly that describes some of that. Because the key to democratizing that access to a medicine like this is, in fact, trying to understand those dose response relationships and, in effect, how low we can allow a titer to fall before protection starts to decline. I don't know that we're close to that area today. So that's a great boon if you're receiving medicine, but it is also a rate limiter. on how broadly we could ever democratize such a therapy. So, and we have talked about kind of next generation type strategy- Right -and program. I know there are a number of variables you're thinking of working through, but, you know, where are you in terms of honing in on what that next product iteration is likely to look like, and how it may differ from the current? Right. So, so because this field is relatively nascent, right? We all have seen antibodies, and we're familiar with COVID, but this process we're engaged in with the FDA is new. We tend to advance it by innovating assets with a certain profile and then getting into a dialogue. So when we, when we made pemivibart, now PEMGARDA, there was no pathway whatsoever. Now, there is a pathway, and we are moving on. I mean, we're not moving on in the sense that we dislike or worry about pemivibart. We're, we're simply innovating in an ongoing way to try to drive more patient system-friendly medicines. There's a couple of ways we can do that. We can make them more potent. Our next gen molecule is a good, good step change, more potent, which should translate immediately into dose, which then, of course, opens up different routes of administration, potentially. Okay, so doing a quarterly IV might be a little more burdensome than doing a quarterly IM. But in the end, what is unusual about Invivyd is that we don't spend most of our time concerned about whether a molecule will be safe or whether it will be effective. We feel very good about those dimensions at first foundational levels, right? Preclinical. What we think about is the arithmetic that governs that titer relationship and where those trip points are clinically that we've got to get something to. And so, for example, for the next molecule, 2311, once we see some initial safety data, which should be later this year into early next, and some initial in vivo pharmacokinetic data, that is to say, what is its half-life? We can have a pretty high-resolution picture of the medicine that could result from that. So when we have those types of data, we can go to different regulatory authorities and say, "Well, this is what could be. What would you like us to demonstrate in what order?" And I think the benefit of a platform-style approach and our leadership in this field is that those cycles should get a little shorter and a little quicker, because the first time was, you know, a little involved. The questions are getting easier, right? The dimensions are getting more known, and so our this sort of, I think, comports well with our strategy and our goal as a company. We don't want to sit around ideating the world's perfect medicine and then going on a torturous ten-year journey to get it. We're gonna iterate and move these regulatory bodies together with our innovative process towards, I hope, destinations that start to look like medicines we all might contemplate. So, PEMGARDA also has the black box warning around anaphylaxis. So maybe you can talk about a few, the dynamics there. Number one, you know, what, if anything, can be done to further mitigate that? Yeah. Number two, how are the institutions kind of responding to that in terms of their willingness to prescribe? And then number three is, you know, ultimately engineering that out in future product cycles. Right. So... So a lot can be done to not worry about it in the future, because I think from a ClinO ps, you know, trialing standpoint, there were some certain things that were not prosecuted that could easily be prosecuted, okay? So you know, for example, through our reporting systems, we're not aware of any anaphylaxis post-market, and that may well have to do with the fact that unlike in our pivotal program, facilities may be pre-medicating routinely, for example, which is not unusual. And they may be modulating infusion time, which would, again, not be unusual. These are things that we can certainly do if we are to be in an infused paradigm going forward, which would not be our preference, but it could be, and we would address it those ways. The other thing I would point out, you asked about our pivotal study design. The observations of anaphylaxis occurred in an open-label, single-arm, immunocompromised cohort. If you go look at the randomized cohort, there was no observation of any note, and I think hardly any hypersensitivity, which would really align better with how you might consider a monoclonal antibody in a modern context, right? They're not... There's always a little infusion hypersensitivity shock to navigate in these things if you trial big enough, but I don't think it's anything that is intrinsic to our molecule, intrinsic to our platform. I think it's a by-product of design choices, and we would certainly not make some of those same design choices again. Moreover, if we can advance our profile to the point where we're an IM drug, I just don't know that we would ever contemplate those kinds of outcomes again. So at the start of the year, the company provided guidance for- Mm-hmm ... PEMGARDA launch, $150-$200 million in 2024, which means in the second half, you're looking to generate $147 to- Yes ... $197 million. Yes. How are you feeling about those numbers, and what might the adoption curve look like? Yeah. Well, so I think those of you following the narrative thread would observe that shortly after authorization and guidance the leadership of the firm was rapidly changed, and indeed, the commercial leadership of the firm. Now, as it goes to giving guidance, I think what we've said publicly is, it's not clear to me that a new management team would give that guidance, but it is not necessarily a number that caused us great fear, consternation, or greed. We were effectively agnostic, and I think to some extent remain that way. I say that because of the following. The PEMGARDA fact sheet that describes the target population for this medicine embraces a pretty impressive swath of Americans today. Something like eight or nine million people technically fall underneath that, what you would think of as an indication, right? Immunocompromised people, and so the math on the guidance is that roughly 30,000 infusions would have to be given. There are millions of boosters given out in this fall. I mean, we'll see what the actual number is this year, but it doesn't. There's enough leverage in the model, for example, that at the sort of tactical planning level, it's not an intimidating hill to walk up. Will we fall short? Will we beat it? Will we come right in? I genuinely don't know, but I do know that at any given moment, our goal is to take whatever number we're at and make it bigger, and build a durable category around medicines like this, and I think I don't know that most of us would contemplate giving pre-launch guidance on a new category again. But I do think, I do very much think, the size of the opportunity speaks to the unmet need and our ability to serve it with some real economic consequence for shareholders. Maybe you can talk a little bit about the TAM, the price point. Mm-hmm ... and the addressable population. Yeah, so I think you can think of PEMGARDA right now as roughly for Invivyd, you know, a patient that is on therapy and durably on therapy would generate about $18,000 a year in net revenue, on that order. And that number may move around as we look for volume and seek contracting if we were to do those things. Now, that's a reflection of a bunch of factors, which I was just explaining we would like to democratize. So right now, we have a relatively high dose infused therapy designed to be highly effective for a relatively small slice of America. But I look across an immunologic gulf over toward COVID vaccine boosts, and I think to myself: Hmm, okay, well, that is an intramuscular injection that, according to ACIP in June, confers about a sixty-day benefit in the form of a 40% or 50% reduction in your ability to get symptomatic COVID, after which it wanes rapidly. And I kinda think to myself, well, there's a lot of space between here and there, and a lot of humans who could benefit between here and there. And so the innovative mission, I think, is going to be to not orphanize COVID, right? There would be no point in getting involved in something where we are seeking to sterilize you, right, for $100,000. I don't know how much you're worth, but whatever it is- Not much ... we'll take it in exchange for a huge quantity of drug. But I think the better strategy is, why don't we use our innovative engine to try to democratize access? Because I do think humans and Americans are relatively rational about their healthcare. They are seeking, in some limited way now, a proposition in the form of boost that's low risk and maybe low return. What if we can step into that space with something low risk and relatively high return? Obviously, I think perversely in pharmaceuticals, that would imply we would bring the price down, and we would seek to democratize access. So we see a big category, and we want to, over time, become a scaled company that delivers real value, right? To do that, you have to start to think about price now around a profile that would allow for that kind of uptick. Maybe we can describe some of the activities thus far this year on the commercial front, and- Yep ... what the gating steps have been to driving adoption. Sure. So we onboarded fresh commercial leadership in early June of this year, and the goal was to move from a more pandemic posture, which was really about creating an innovation and putting it in effect in a catalog or in the channel and sort of passively waiting for people to come in, to more of a modern biopharmaceutical commercialization posture. So that has involved building a team that spent the summer really doing the logistical plumbing around access, around infusion center capacity, building relationships, formulary, all that good stuff. That work is never done, but enough has been done, and we have issued publicly some statements about the breadth of ordering activity we have seen so far, which has been gratifying and positive, and now it is time to move into the next phase, in which we try to draw through that machinery a real activation of both vulnerable person and HCP, in effect, demand, and that is the work that is now beginning. We're in the very early innings of that. Some of you may have seen our hopefully charming little digital campaign- Mm ... to start to talk about what is available, that is new and, represents additional protection, and I hope you will shortly see much more from us. So having built in effect over the past few months, a machine, now the goal is to see how fast and hard it can run over these next three, four months and, then beyond, of course. In terms of the frequency of administration, especially after the finding from the phase III that suggests maybe you could go longer between administrations, what's kind of the recommendation or evolving recommendation? Certainly from a commercial standpoint, we prefer to have people read the fact sheet and make the decision that the fact sheet and the FDA suggest for the medicine. Now, if you're asking me scientifically, where could it go over time? I think the issue is how do we get confidence in that relationship around a minimum titer you'd wanna bounce back up off of? There are publications in Science and Nature that suggest titers might be highly protective at levels well lower than what we are conferring. I think, you know, some more work we're doing might add to that body of knowledge. But in the end, I think what is most required is sufficient familiarity with the tools, and sufficient innovation on our part, that people can start to make up their own minds as they go, right? I don't know of anyone still, or maybe I guess I should say I don't think many people are doing appointment boosting, as in, "I have to go to the Cantor Global Healthcare Conference, maybe I should consider a boost." I don't do that. But I could easily foresee a future in which we do administer something that doesn't involve reactogenicity, and doesn't broadly engage the immune system with an antigen that maybe we don't like, which could allow for more periodic, habitual protection, right? You know, I'm going on a trip. I'm going to a wedding, right? So these things have to arise from good science that lays out those relationships. But I think you're hinting at something that I believe is deeply true, and has to be borne out in some form of research, which is, there is valuable protection to be earned, at maybe a less burdensome form. And it's really up to Invivyd, I think, and hopefully others, to make that clear. I had a great question on my mind, but it's, it's- Lay it on me, come on. ... fallen out of my head for a second. Oh, We don't have a- I was just asking about the size of the sales force you're planning. Where are you in terms of recruitment, and who is the target physician? 'Cause it could be a lot of them. Yeah. Well, okay, so, so we have a mix of a contracted and now growing in-house sales force. It's 20-some odd folks. Which is you know, calibrated to match the profile of pemivibart, okay? Which is not designed as an enormous population medicine. It is a relatively specialty medicine today. I think in terms of the physicians, we tend to believe in a sort of a two-by-two matrix, okay? There is your level of immunocompromise, your acuity, and you might, for example, think of a transplant recipient at the top of the acuity need as it goes to incremental protection. There is also another dimension, which is the familiarity with and use of prior biologics for prevention of SARS-CoV-2, general familiarity with infused biologics. When we sort that, we still see a relatively large group of practitioners, but they also tend to cluster in the handful of institutions that we all know the names of, in some very high-volume community practices, in the case of, for example, hematology and oncology, and so we are, every day, in that ground game of building familiarity, and hopefully building use and volume that begets use and volume. Because it is, after all, a reborn category, with a sort of a unusual registrational pathway, right? They were first shown a fact sheet that said, "Here is an immunobridged molecule," which you could be forgiven for looking at and going, "I don't know what that is," right? Now, gratifyingly, we have our CANOPY registrational data on our fact sheet, so one can look at it and say, "This is what this thing did in a controlled clinical trial." But all of those practices have the demerit of being big and diffuse. They have the merit of being big and diffuse, and so you do not have to imagine a very large crack opening in the utilization dam before very real volumes can manifest. So that's the game. It is the opposite of an orphan strategy of just hyper sub-segment and then attack. We are forced to do a broader ground game, but hopefully there's a consequence to that that is positive. One of the other antibodies still standing is Astra's sipavibart. What are the points of differentiation that you see versus- Is it still standing? Think so. I guess it's still standing. We'll say that it's still standing. So, sipavibart, I think, is a beautiful, beautiful antibody when it works. And when it doesn't work, it doesn't work. And, I think that AstraZeneca has been very clear about the molecular liability in sipavibart. They have been very clear, at least to us, about their intention to try to engage regulators, I guess, in a probabilistic sense, right? Meaning... But if something becomes susceptible, sipavibart would be lovely. I would agree. I am personally very much looking forward to seeing the detail from their SUPERNOVA pivotal, which met its primary endpoint, despite having an active that was inactive for some portion of that study. Which tells you, I think, how well these things work when they work. I think, look, from an Invivyd standpoint, it would actually be delightful to have a big pharmaceutical company in the channel, banging away at these practices and these HCPs, because then we could follow it and go, "Well, sure, you could do that one," right? Or, but in the meantime, I think most of the field has been hamstrung by a fundamentally different conception of how to drug the target, and what technologies are required to try to find territory evaded by the virus. Right? So I think Invivyd is structurally advantaged. That's been the case empirically so far. We don't see anything on the radar screen that's close. Got it. I think we're out of time, Marc. Thank you so much, as always. A great, engaging conversation. Thanks, everyone, for tuning in. All right.