Hello everyone, and welcome back to the second annual H.C. Wainwright BioConnect Conference. My name is Patrick Trucchio. I'm a senior healthcare analyst at H.C. Wainwright, and it's my pleasure to introduce our next speaker, Marc Elia, Chairman of the Board of Invivyd, a biopharmaceutical company whose mission is to rapidly and perpetually deliver antibody-based therapies that protect vulnerable, vulnerable people from viral threats, starting with SARS-CoV-2. So maybe first, if we could start with some background on Invivyd, tell us a little bit about the history of the company.
Sure, Patrick, thank you for having me. People may or may not remember the global SARS-CoV-2 pandemic, which is the time in which our firm was originally born. Interestingly, even then, our mission was focused on endemic SARS-CoV-2, okay? So after the enormous wave of infected burden rolled through humans, among other species, we anticipated that humankind would be left with an unmet need, and that unmet need we see expressed every day still in the form of too much death, too much morbidity. After all, this is a multisystem virus that lives at high titer in your serum when infected and can exert damage, not just in sort of the classic deep lung and pneumonia, but also, of course, neurologic damage, renal damage, cardiovascular damage, and so forth.
What we really felt strongly about then, we still feel strongly about today, which is that human beings are not dying from inadequate access to mRNA boosting or inadequate access to small-molecule protease inhibitor treatments. They are dying in part because it is a tough fight immunologically. The difference in the, let's call it immune experience or antiviral titers one can generate following an infection or a vaccine is different than perhaps that titer one needs to be not just alive, but safe and well.
And so, of course, we, launched into this journey, like many others, with an eye toward delivering a monoclonal antibody directed against SARS-CoV-2, because it seemed clear then, and is now very clear today, that such medicines can dramatically shift, either one's ability to, experience symptomatic infection in a PrEP or a prophylactic setting, and can potentially also change the outcome of an active infection in a treatment setting. So Invivyd really only, modified its strategy, along with, I think, the virus itself, which is we all learned over time that there was sort of a two-dimensional problem to solve. One didn't just need to worry about how the virus would access ACE2, one also had to worry about immunologic evasion.
And so what we have built with Invivyd is designed to be a machine that connects up the safety and efficacy of monoclonals in these use cases with a compositional evolution of your pharmacophore that we borrow, in effect, from the vaccine industry. If you've ever gotten a boost for a COVID vaccine or a flu vaccine, it is not the same composition every year. It is updated.
Our belief is we can rapidly generate novel antibodies that exert, you know, these very attractive properties and do so at a pace that keeps up with or gets ahead of evolution if we're, you know, lucky and having a good day, and if our technology works in the way that we think, and that will allow us very uniquely to provide protection and possibly treatment to those people in our society, and there's, depending on who you count, between 500,000 and 10 million Americans who are frankly at high risk of very adverse outcomes still from SARS-CoV-2.
So that is our broad mission and history, and I would just note, at this point, we're very proud to have earned already, an emergency use authorization for our first sort of serial monotherapeutic antibody, which we-- it has the trade name Pemgarda, and we are working very quickly to both commercialize that and bring forward novel molecules that improve on that use case, and in effect, I think, validate the bigger thesis for the company and its existence, which is to, drive, the rapid generation of these high-value medicines in a fashion that is, I think, both apace with the overall scientific challenge and very unique in the field, so.
Yeah, that, that's all really helpful, and maybe you can expand a bit on Invivyd's antibody platform. What makes this differentiated?
Sure. Sure, so look, we leverage at our very core technology that's really only available through a private company called Adimab. We have in-licensed their technology, and that's a company with which we're very familiar as they're our founding tech partner. But what's unique about it is that, unlike, most companies that need to go out and source an antibody, we do not rely on a mammalian immune system, meaning we're not hunting in experienced serum for an antibody to pluck from an experienced patient. We're not, you know, ritualistically torturing mice, trying to get antibodies out. We leverage a very, very massive suite of combinatorial diversity that we can interrogate at very high speed.
What that unlocks is the ability, I think, to ask very interesting, unique questions, as in we might, for example, wish an antibody that, say, neutralizes JN.1, that also neutralizes, I don't know, BA.2.86 in the past, and which specifically avoids, for example, interaction with residues that we see on the spike undergoing real exploration, real motion. So we're using this technology, combined with a whole suite of analytics, to in effect, find, let's call it more stable territory, and then drug it at higher speed, and hopefully with more evolutionary sophistication than, others in the field.
... Right. So you alluded to it earlier that you have the emergency use authorization on Pemgarda. On May 8th, you had the first shipment of the drug in the setting of pre-exposure prophylaxis. Maybe you could talk a little bit about the pathway to approval in the prep setting for Pemgarda.
Sure. So this was all very novel and something we were very proud to partner with the U.S. FDA on. The, the, the, the approval pathway for Pemgarda goes all the way back to December of 2022, in which a variety of sponsors, Invivyd included, and a variety of academics convened with the U.S. FDA and EMA to talk about surrogate approaches to licensure or authorization of COVID antibodies. And the general gestalt was, hey, look, when these things work, they are highly effective and highly safe, and the problem is time. And I think regulators around the world recognize that. Some of our thinking and their co-ideation about how we might handle this issue resulted in not just our pathway, but an actual issued FDA guidance, in December of 2023, that describes an approach called immunobridging, which simply relies on a measurable laboratory surrogate.
So we know ancestral antibodies, including our own, can be highly effective, can be highly safe. Great! How do we take that body of clinical evidence and move with it through space-time a little quicker? Well, we rely on a, you know, I think, a serum surrogate with emerging validation, which we simply call serum viral neutralizing antibody titers. It's a lab measurement you take. So our authorization docket, if you will, really was safety, PK, and serum titers that we measure in a lab. And if you zoom out and consider the broad arc of what has happened here, we had a prototype antibody, adintrevimab, that went through a full clinical outcomes program involving thousands of people.
Pemgarda, okay, went through this bridging pathway and involved total exposures of about 700 people over a much shorter period of time, call it weeks to months. And then on a go-forward basis, I think what we all can appreciate is that, regulators and people like Invivyd are deeply interested in how we can continue to make more compact the human exposures that a regulator or any reasonable HCP can look at and say: Yeah, I get it. The belief is this is safe and works.
And so that's really the bridging EUA pathway, and gratifyingly, recently, we announced that we and the FDA had aligned on an approach to using the same principles to address the treatment of symptomatic COVID-19, which again, sounds like something that maybe people don't need new options for, but I assure you, when we look at the death and the morbidity, new options are very much, very much, appreciated. So we're looking forward to using this general principle set, because our goal is, I think, a little bit, maybe more ambitious operationally than other firms, is to very rapidly and with high capital efficiency, generate high-value medicines on a very tight schedule. And it's not a burden, it's a gift, right? It's a real advantage. And so we will be looking to do that as fast and well as we can.
Right. No, that, that makes a lot of sense. Just in terms of the approval pathway for Pemgarda in the prep setting-
Mm-hmm.
Do you think this is a pathway that will remain available to Invivyd, you know, for next generation antibodies and for the foreseeable future?
Certainly, that is the understanding that we have, but I can't speak for the U.S. FDA. What I think I can say is that, it's a gratifying question to get, because up until a year ago, the question was: Why would anyone ever do this at all? So we have already gotten the move from, why would anyone ever do this, to, are they gonna do it again? And if they do it again, which I think we have every reason to believe they will, given that we just PR'd alignment on a treatment EUA pathway that looks like this, I think the more interesting question is: Okay, where does this field go over the long term? Meaning, if we expand the aperture of our thinking to just forever, right, what do we need forever?
I think it is clear that in order to live well, we, as a society, would benefit from this kind of protection. What do we do about it right now? Right now, you do rather what I think it looks like Invivyd is doing, which is working with the FDA to articulate and then execute these pathways that are sufficiently rapid and sufficiently efficient, that we can knock these things out and stay in effect in the commercial channel, serving highly vulnerable people. So will they do it again? Gosh, they're gonna have to do something, or else a lot of people end up, unfortunately, having their last or worst day on Earth-
Right
... all too often. So none of us have a crystal ball, none of us know what it looks like exactly, but we feel very comforted by all of the interaction we've had so far, and I can assure you, you won't hear Invivyd, you know, complaining about the behavior of global regulators. They have been extremely leaned in, extremely aware of the issues, and highly motivated, which is great.
So I understand we're, you know, at the early days of the launch, but maybe you could give us a sense of how is the launch going, what has the kind of reception to it been, where is payer reimbursement?
Sure. So we're gonna stay a little bit cautious about just how much detail we put out there, because the simple and should be sort of obvious truth is that at this phase, we're about kind of six weeks in, and really about four weeks in, 'cause, you know, no one knows when you're gonna get an EUA, so it kinda drops in out of the clear blue sky, and you sort of start rolling. We are very pleased with how things are going, meaning we now have our institutional field force out. Okay, as you know, we have sold drug. We are very pleased with what we see as robust organic demand, meaning sort of reverse inquiry and/or highly organized, motivated people seeking therapy today, and it is on us to generate sort of the materialization, actualization pathways.
That is to say, if a vulnerable person and their caregiver or their care team decides they are a great candidate for Pemgarda, well, obviously, it is a brand-new object in the world, and so people have to determine the logistical steps that are associated with, you know, acquiring drug, we have a drop ship model, finding infusion capacity. So you might imagine that out there as we speak, is all of that logistical education occurring between Invivyd and between institutions and, in effect, you know, infusion centers and other logistics partners that will get drug into patients. So that is, I would say, going great.
In terms of how we think about the arc of the year, I think what we are very eager to do is make sure that we have the maximum quantity of information and rhythms established, because I think, you know, here in May, in the Northern Hemisphere, probably indoor COVID risk is not top of everyone's mind, but that changes awful quick. So we feel the time pressure of establishing all of this infrastructure so that these fairly impressive numbers of potential subjects, when they come in or when they have that appointment, all of this infrastructure is established so that they can get drug, and we can experience, in effect, the commercial pull-through.
So look, it's very, very encouraging that CMS came out very early, that we have the HCPCS codes for 50% of the covered lives, as you know, and that, that it represents a zero out-of-pocket expense for patients and an attractive, I think, proposition for everybody involved. Commercial payers are right now, in effect, both talking to us and we know well dealing with early prescriptions moving through their architecture. So it is all happening at a pace that is simultaneously gratifying, I think, for us to observe, and infuriating, because, of course, we'd all wish it would go faster, and why isn't everybody canceling their personal plans and making arrangements to deal with Pemgarda access, right?
So that's the tension we're in right now, and we're, you know, watching it carefully and learning a lot and pivoting wherever we can, whenever we can to make it all go faster.
So at the outset, you mentioned the EUA and the treatment setting. I'm wondering if you can talk about this in greater detail. What's the status of that EUA, and how do we think about, kind of the side of the market?
Sure. So that is, as now, a probabilistic exercise. It is a question long posed to FDA. I think for whatever reason, subject to some discussion, they at least see that in effect, the math is identical, meaning back in the old days, you generated an antibody, you put it into the PrEP context, it, quote, "worked" in a big clinical study. You took the same antibody at the same dose, it, the same route of administration, it, quote, "worked" in the treatment setting. So the math is identical, right? And as we look at Pemgarda, we see the opportunity to very quickly put that same arithmetic back in front of FDA for their consideration.
Now, I think we said in our press release on that, that work was underway, and we expected at least our part of the deal to be done, quote, "imminently," which I think you could interpret as sort of weeks and not quarters, right? Now, what happens from then? Welcome to EUA land. There is no ability to tell, and that is not a complaint, right? EUAs don't have PDUFA dates, so there's no statutory obligation to work backwards from some point on the calendar. What I would point to is simply that, throughout this entire process, I think certainly FDA has been very attuned to the unmet need, and I think they're very aware of some of the cyclical calendaring dynamics within this.
And so I have no reason to believe that it would be a process that would be, you know, longer per se, than our PrEP EUA. But I would also say something else, which is this: It might even be more important in the big picture for new molecules than it is for Pemgarda, and the reason I say that is this: Pemgarda had to go through CANOPY. This is our study, a day 90 and then a day 180 endpoint. That's PrEP. You are holding somebody safe for almost a half a year or more. In treatment, the relevant endpoints are about day 7 and day 28. So if we believe that bridging to treatment is a repeatable pathway, it is very compact in time. And I'm sure, you know, other biotech investors like myself always enjoy higher rather than lower speed.
We will be looking at that very critically as we think about next molecules and how to, let's say, sharpen the saw in terms of pulling down time, pulling down cost, and advancing new things, maybe even more attractive things, more rapidly.
Can you talk about the competitive dynamics, you know, with treatment, we have Paxlovid in this preventative setting, you know, Astra has a program, how does Pemgarda fit within these other treatments?
Sure. So, in the treatment setting, I don't think a bridged antibody would be, you know, in effect, indicated for anything other than those people for whom Paxlovid is either contraindicated or not clinically appropriate. Now, among the people who bear the lion's share of morbidity and mortality, not clinically appropriate can mean a lot of different things, and we'll have to see how that plays out if we are so fortunate as to receive EUA for treatment. But stepping way out, you know, at this point, if you are outpatient, Paxlovid is, of course, the drug of choice. If you are so unfortunate as to be hospitalized, you may see remdesivir, okay, which is a sort of multi-event, multi-infusion course.
And there is, I think, an opportunity and a need for something like Pemgarda or one of our antibodies, which can be a single infusion or perhaps in the future, you know, a potential intramuscular injection, that allows an HCP to see a patient who may be at risk of going downhill, administer the therapy, understand that that person is now de facto compliant, and send them home, rather than admitting for maybe more advanced measures. So we see a real opportunity, and certainly, you know, over time, the vast lion's share of the economic activity associated with antibodies has, of course, been in a treatment setting rather than prep. I mean, these are both, for small biotechs, very, very, very large, substantial markets. But treatment is certainly one that we look at with some real interest.
Right. So then just moving to VYD2311, can you tell us more about this program?
Sure. And I apologize, I didn't answer your question about AstraZeneca, which I would love to, because I'm not so sure they do have a program. But the point is, they, like others, have COVID antibodies, which, when they work, are spectacular, and what's uncertain is, will theirs work? So we'll see on that. In terms of VYD2311, it is the next one of what we hope will be an ongoing series designed to generate proof of concept of our ability to supply the channel, right? And what is nice about VYD2311 is that it has some improved biophysical characteristics that may present in, let's say, improved routes of administration, accessibility, dose, variant coverage, things like this.
Like, when you have an opportunity to outcompete your drug in the channel, you don't really want to shave it a little bit, right? We want to make a step change, because we have no reason to believe Pemgarda is going anywhere anytime soon. So we wouldn't necessarily perform the lift if we didn't take a look at the commercial profile, the actual biophysical profile and its commercial profile for Pemgarda and think, We can do better. That's what twenty-three eleven is, and we're really looking forward to pushing it forward.
Great. And then maybe just, just one on the cash position-
Mm-hmm.
and capital allocation. How do you, you know, your cash runway and-
Mm-hmm.
kind of your cash guidance and confidence in that? Yeah.
Yeah. So look, everything within Invivyd happens faster than other companies, right? Meaning we have gone from the lab to an EUA in a year. We are now launching. There are in the context of a launch, that I can assure you, on day zero or on EUA day, we sold zero drug. So that was quite terrifying, right? But as you look forward and things start to move through these large populations, you begin to get the sense for it. If you weigh and measure the economic activity associated with COVID prophylaxis and treatment, these numbers can get quite exciting. So what does that really mean? I think it means that the economic model of Invivyd over the near term is going to be sensitive. If we sell what we think we might sell, I don't think we have a care in the world.
If we sell something less than what we think we might sell, we might start to have some cares. But it is all too early to say, and what we want to do is both be mindful, okay, of margin of safety on the balance sheet, and also laser focused on per share value creation. I mean, I'm a big shareholder. I don't. We're not doing this academically, right? We don't want to simply dilute and dilute and dilute and create a huge amount of value without actually generating any per share compounding. So stay tuned. We're looking at this very closely, but, you know, so far, we're very encouraged by everything we see.
Great. Terrific. Mark, we've run out of time. Thank you very much.
All right.
Always a pleasure to catch up. Congrats on all the success so far.
Thank you.
Thanks for everyone for attending.
Thank you.