Hello everyone and good afternoon. Welcome back to H.C. Wainwright's 28th Annual Global Investment Conference. I'm Patrick Trucchio, a Senior Healthcare Analyst at H.C. Wainwright. It's my pleasure to introduce our next speaker, Marc Elia, CEO and Chairman of the Board of Invivyd. Invivyd's INVYMAB platform pairs viral surveillance and predictive modeling with deep B-cell mining and monoclonal antibody engineering. The pipeline spans Pemgarda or pemivibart, next generation COVID-19 candidate, as well as next generation COVID-19 candidate VYD2311, which is in the phase III DECLARATION program with top-line data expected by the end of the third quarter, as well as a measles candidate VMS063 and an RSV candidate VYD222. Marc, with that, welcome. Thank you so much for joining us.
Thank you. It's a pleasure to be here.
Maybe just for those who are not as familiar with Invivyd, if you can talk us through the platform and the pipeline and where the company is today.
Happy to. Okay. Why don't we start then in the biggest picture? When most of us think about preventing an infection, especially from a virus, we will commonly think about vaccines. Indeed, America is in possession of a great number of vaccines. Some of them are extraordinary. Some of them are maybe more marginal in terms of their overall quality, say how well they protect you, for how long, and with what safety profile, so on and so forth. You'll notice that even though monoclonal antibody technology is inspired by human immunology, we actually have precious few monoclonal antibodies to prevent similar diseases. The ones that have been around the longest, and indeed some of the most economically and medically important, remain just in pediatric RSV or neonatal RSV.
Well, COVID came around, and it looked to many of us at the time, and I think was well demonstrated to be a virus that would be highly responsive to a monoclonal antibody. I think that's something to do with the match between what kind of neutralizing power a good company can put into the human serum and the requirement of that virus to essentially access cells in the epithelial tissues of your let's call it mouth, nose, and eyes, but then also your endothelial tissues, which are central to cardiovascular function, but where COVID likes to live and work. Invivyd began as a company devoted to monoclonals for COVID, and we've done that, and we're doing that. That is the main basis of our work daily, and I'll get into how we do it.
I would just point out, we exist as a company to start to right-size some of that relative dependency as it goes to American infectious disease medicine. We believe there's a lot of places where a monoclonal can play beautifully out past the limit of vaccinology. In COVID, many of you may remember from the height of the pandemic, Regeneron, which famously saved President Trump's life, or Evusheld, which was an AstraZeneca product for immunocompromised persons. Well, now the world is down to the work of Invivyd. We today make and sell Pemgarda, pemivibart, which is a preventative monoclonal antibody for use by moderately to severely immunocompromised persons. But more importantly, it makes a point. We built an entire company and an entire tech platform to deal with the particulars of this and perhaps other viruses, those things that move around a little bit.
We believe we are experts at finding pieces of those viruses that don't move, that are highly druggable, and we built a tech platform to exert that. Pemgarda, pemivibart, was kind of our warm-up act. I mean no shade. It's a beautiful antibody from the point of view of demonstrating longitudinal control over a virus that has escaped pretty much every other, in fact, actually every other pharmaceutical company. It has not escaped us. What's particularly compelling about that from an Invivyd standpoint, we think, is that we ourselves are aiming to replace Pemgarda, pemivibart, with something much more scalable. Because of the particulars of pemivibart, it's an infused product. It requires an hour-long infusion with a two-hour monitoring, which is about the most burdensome vaccine ever invented by a good amount. Then we do you one better. It is only available under EUA.
It has a box warning for anaphylaxis. This is a highly imperfect medicine. Like I say, though, it expresses a really important fundamental point and allows us to iterate ever so slightly to make VYD2311, which is the molecule we are currently wrapping up pivotal on right now. That medicine we would expect to essentially embody the same properties, very strong ability to disrupt infection at a level way past what a vaccine can conjure, we believe these days. Likely to last much longer than a vaccine, we believe, and likely, we believe also to be safer and more tolerable.
That's a pretty good setup for a company like ours, we think, because, again, go back to the beginning, our observation has been consistently, this is a virus that will respond well to a monoclonal, and we're in the business of taking our technology and now making a medicine that we hope will be scalable to much larger populations. The way we've designed VYD2311 is to essentially make it functionally interchangeable with a vaccine. They will both be IM. We would hope over time we would acquire equal standing in terms of ability to get dosed at a pharmacy or at a minute clinic or any setting where you might otherwise think to get a vaccine. In sum, and then I'll pause, we see deploying our technology as offering a better way to do business with this particular virus and then perhaps others going forward.
Maybe you can talk more about the phase III DECLARATION trial, which is now complete, as well as the LIBERTY trial. We're expecting data. What data will you release at that time?
Sure. We were inspired by the American Revolution, given a lot of the, let's call it socio-medical churn happening around COVID-19. And so yes, our REVOLUTION program includes DECLARATION, which is our placebo-controlled two active arm pivotal study, which asks the question, does the Invivyd antibody VYD2311 reduce the incidence of PCR positive symptomatic COVID compared to placebo? This is essentially our third time running a similar study with a functionally identical antibody. Our first one adintrevimab was long ago in seronegative people, about a 71% reduction. Pemivibart, PEMGARDA, put up about an 84% to 94% reduction compared to placebo in modern populations against Omicron viruses. That brings us to 2311. We'll see how we do.
What we've said about it is we were desirous and have spent the last year running that study, and when one does infectious disease prophylaxis studies, the major unmodifiable risk is your so-called attack rate. Do you see enough disease in the study to give yourself statistical power that would substantiate your treatment effect at better than P of 05, because that is the typical intellectual framework we operate in. We upsized our study back in April and were able to disclose at the time that we had acquired some good statistical power for the upper end.
All we have been facing over the last few weeks is, it is safe to think, for those of you that are following our story, and we don't disclose the particulars, but I think it's safe for you to conclude the bottom end of our target VE may not be super well covered by the statistical power we've acquired so far. We have some decisions to make in the very near term, and we've been working very hard over the last year to provide pathways forward we think will allow us to operate well even in that setting.
We will either in the coming weeks, make the decision to fully unblind the study and file the drug on a normal pathway, traditional approval pathway, or we will make the decision to partially unblind, meaning safety, pharmacokinetics that allow us to measure the antiviral activity of the medicine and file for accelerated approval. That is, I think something that would be new in COVID antibodies, okay? But I would say we are inspired by and have been working closely with the federal government because today, or at least very soon, there will be XFG vaccines in your pharmacies that are either mRNA or protein encoded. You will know nothing about those vaccines from any kind of formal testing. You won't know how well they work. You won't know how long they'll last. You won't even know how safe they are.
We are all hoping that those things remain true from a nine-week field study conducted in fall of 2020 in humans that no longer exist against virus that no longer exists. In the old days, when we would bring those sorts of issues upward through the federal government, I think it's safe to say the last administration would shrug and go, "Who cares? It's an amazing vaccine."
Well, the new administration, I don't want to shock anyone here, but they have a slightly different attitude as it goes to infectious disease prophylaxis, and I think we have made some resonant points with some of the people that are responsible for the American public health, and we feel pretty good about should it become necessary, partnering with them to accelerate access to 2311 in large part because remember, we are selling today under EUA, a monoclonal antibody we view as functionally identical. And back in June, Secretary Kennedy ended EUAs, and so come mid next year, immunocompromised people will be left without an option, and all of us will be left without an option other than the vaccines, unless maybe Invivyd finds a way forward.
That is what we have been working on over the last year with the knowledge that we knew we might always face some degree of statistical uncertainty. The question facing our company that we will look forward to updating you on is how much play of chance do we think we want in this readout, and what do we do as a consequence? Stay tuned. We are really excited to get to that. You asked about LIBERTY. I will just say very quickly, LIBERTY is a study that arose from an FDA desire initially, actually, to see what would happen if you combined vaccine and antibody. Regeneron ran that experiment many years ago. The results were neither surprising nor frankly, particularly interesting. We are going to ask it again.
We also took the opportunity to construct an endpoint whereby we compare the first seven days of safety and tolerability between monoclonal and vaccine. We are looking forward to those data because I think that will be an opportunity for HCPs, for vulnerable people, for, say, decision makers at ACIP and CDC to see in one study after the ouch part of your deltoid meeting either the mAb or the vaccine, what happens? Most of us are probably aware that the COVID vaccines run what we would, I think in the vaccine industry call a little hot. They are reactogenic. You have a cytokinemia. That is, after all, you are the manufacturing facility for the immune response that it makes, and in the case of mRNA, congrats. You are also the manufacturing facility for the antigen.
With an Invivyd antibody, of course, we simply give you what we think is your target final product, and we do not expect too much of an inflammatory penalty, so we are delighted to, I hope soon have access to a direct comparison.
What will determine whether you choose to go ahead with the accelerated route to approval?
Right. So obviously the single biggest contributor will be the statistical power accumulated and our sense of the modeling for target VE. Even that is not enough. Of course, there is ongoing dialogue with various regulatory authorities. Indeed, there's sort of other logistical considerations that go to study conduct to ensure that we can do this in a sort of seamless way. As soon as you, of course, are in an accelerated approval context, should we choose to go that way, you have an obligation on the other end to conduct confirmatory studies. One of the things I think we meant to convey in our press release a couple weeks ago was the good news is the DECLARATION framework sits there.
So it is entirely possible that as we move forward, we simply leverage that same infrastructure, add a cohort. I think as capital allocators on behalf of shareholders, our desire would be, if we are to go out there and seek additional statistical power, why don't we try to do it while either making very clear progress toward market or being in market and actually earning revenue? Because I'll remind everyone, Pemgarda does, let's call it on a $60 million- $70 million annual run rate, growing 20%-25% per annum. That is a highly burdensome medicine. If we transition from that to an IM scalable antibody, I think we like the effect that such a transition could have on shareholders, and we are highly desirous given all the science we have done.
I think we presented a slide recently to those who make these kinds of decisions, that at a certain point, there is a scientifically, medically, morally responsible way to move protection forward, right? I think we're reaching that point.
How do you think about the efficacy bar? What do you think would be sort of practice changing and I guess what range should we be looking for as well?
Sure. Very quickly to dispense with the numbers, we've always maintained, and we are unmoved, our target is about a 70%-90% reduction in symptomatic disease versus placebo. That's what the math tells us we should be aiming at and we should be getting. But the actual number, we'll see, that is subject to what we think of as clinical assay sensitivity, right? The smaller the number of events, the lower the resolution and the more chance is in there. Okay.
Right.
That remains our target, and I think it's perfectly valid. I think almost anything would be practice-changing, meaning humans have never had the ability to routinely opt for immune supplementation that sits in excess of what any of us can produce ourselves. Most medicines, we're hoping for a return toward normal physiology when we're sick, and in the case of prevention, we're mainly interested in holding the line. With a vaccine, you get the most you can create. I think we're fond of saying to people, if you want to know what the limit of any vaccine is, look in the mirror. Well, at Invivyd, we believe we run essentially the world's biggest immune system ex vivo. That's our tech platform. And we're actually able, we believe, to offer you something you can't otherwise summon. Right?
You can't get the antibody we make, or maybe some of us can at some vanishingly small level, and we don't know at what probability. You can't get it in the quantum that we give you, and you can't get it on time. Right? Typically, your B-cells re-energize and begin to produce neutralizers after your infection has started. So we see this as such a beautiful evolution of our overall posture in infectious disease. It's about taking a step that I think technology has started to unlock in the last few years. Remember, vaccines are 300 years old. Monoclonals are about 40, 50 years old, but the tech to do it the way we do it's realistically only about 10 years old and has never been run the way we're running it.
To us, we look at COVID and think, what a beautiful opportunity to finally offer humankind a level of immunity that may be the difference between that which keeps us mostly alive, and maybe in the future, if we are successful and we scale, which might keep us mainly well. That is a pretty powerful concept, and one that I think we might be able to sort of scale across some different pathogens.
How should we think about the single dose and monthly dose arms in terms of statistical hierarchy and label, and what duration of protection evidence beyond three months do you expect to have to support either annual or semi-annual?
Okay. We have never actually made it hierarchical. They are endpoints with equal standing, and therefore there is a measure of alpha spending, so you can imagine what that looks like. While we have never disclosed our SAP, it is pretty straightforward. Why? Well, the why behind all of this is a little more labored, but only because of the journey we have all been on with COVID and with these vaccines. The FDA was very clear that they wanted a demonstration of repeat safety, and we love that. Okay? Of course. Why? Well, the single dose is how we built our protection math, 70%-90% for a single dose over 90 days. Of course, the protection would and will extend beyond that, but that is the first formal measurement. Why would we do a multi-dose, and why would we do it monthly?
Well, if you open the labels for the COVID vaccines currently, you will read the indication, use once or no more than every two or three months. Now, what do people do out there? Most people will take it once. Some people who feel very vulnerable will take it over and over again. What we can do with a mAb, if the safety and tolerability works out the way we think, is we can offer even more flexibility. Do it as much as you want in effect, right? If you are me, I might want to do it once a year because I am, at least to my knowledge, I am immunocompetent and I am sadly 50, but I am not at some extremely heightened risk. However, I have dealt with long COVID, and I do not want to get COVID. I might do it once, I might do it twice. Let us see.
I might come to a room like this, eyeball somebody and kind of go, they look a little peaked. Maybe I will go downstairs and grab another one, right? If, however, you are undergoing CAR T therapy, or you are carrying around a transplant, and maybe you got your first dose in the fall and you have a wedding or a trip or a something, the design and part of our inspiration of the REVOLUTION was the idea of choice and freedom. We are in year six of a federal centralized health complex applying recommendation, and I think America has grown a little uninspired, right? We are all supposed to get our flu shot and our COVID vaccine in the fall. We are not really given any information about how long it works, how well it works, and so forth. Our answer to that is to build a program that celebrates choice.
Do what you want will be our message, and there will be arithmetic and some degree of demonstration initially and then ongoing about what that might do for you. I do not expect DECLARATION to be the final word on this. It will not be big enough, it will not be long enough. As we go, recognize if you are doing monthly with the half-life we have, we would not expect you to get to terminal concentrations for many, many months. You would be carrying around a lot of antiviral power. That will translate into a higher protection. Or you can do it once and watch it gently fall over the course of, say, a year. By the end of that year, you might still be in better shape than the best you could get from the COVID vaccine over a short term. We will have to find out, right?
Right.
That is what the math tells us. Stay tuned. We wish to get on base, and then as we go, we think it is a sufficiently big idea that we are looking forward to partnering with all kinds of institutions that do evidence-based medicine to fully elaborate what this profile will look like.
Can you talk about the commercial preparations that have been underway, and also the learnings from the Pemgarda launch you can bring forward?
Yeah. Look, with the limited time I suspect we have, although I'm watching the clock with less anxiety, or more anxiety maybe than you, I would just say we are in the commercial channel, right? You must imagine that over two years we've learned a lot. I think all of us have learned a lot about infectious disease prophylaxis over the last few years just by being American. There's been a lot of churn in this space. So it turns out that it's not always the case, for example, that people seek protection with some strict liability in mind. There are people who feel very comfortable and safe, even though they might be profoundly immunosuppressed with a new kidney or a new lung.
There are people who may be only mildly immunosuppressed or moderately, I guess, because maybe they're on, I don't know, I'm speculating, HUMIRA, something like that, but they just don't want COVID. Whether that's because they've lost a loved one or had a bad experience, I think what we're learning is that behaviors and decisions in the preventative wellness space are a lot more nuanced and individualized than decisions, for example, if you learn you have BCR-ABL transformed CML. Under those circumstances, you're probably going to go get GLEEVEC or something that looks a lot like GLEEVEC without a lot of nuance. To the extent that Invivyd is learning, I think what we are learning is we are, in many ways, a consumer products company. You have to want what we sell you because you are well. You might be medically complex, right?
You might be undergoing a journey somewhere else, but you need to want to do what we offer you, and I think that's giving us a very different corporate voice, a very different corporate posture. It's why we do things like the partnership we have with Lindsey Vonn. We're going to try to educate Americans on this idea that there are objects in this wellness preventative medicine field that are extremely high tech, absolutely cutting edge, and if we make them accessible and desirable, I think we all sort of win in that circumstance. So that's a little window into what we've been experiencing.
Just maybe as a final question, what do you think investors are missing about the story?
Well, we have so little time, Patrick, and there's so much. But I guess I would just say, I think Invivyd has been low profile and under followed for most of its corporate existence, so we're always thrilled to come out and talk a little bit more about our work. I think investors sort of bifurcate into those persons who are very interested in the exact particulars of what will happen next, and we do our best to serve that interest set. I suspect that as we get through the next steps, to the extent that they happen positively and productively, investors are going to get a chance to spend time in much bigger ideas. And that, I think, is not really entered the conversation yet, because there are particulars that relate to our work that don't rely on precedent, right?
We can't say we're inspired by Kagocel, but trust us, ours is different, right? That's like an easy pitch, and that allows people to bet science within a well-established regulatory and commercial framework. I think we're offering people the ability to bet science, but in a very dynamic, somewhat chaotic public health and regulatory space without a lot of precedent. Now, we see that as just deferring what could be an extraordinary story as that all resolves and clarifies, because remember, we're a commercial company now. Our interest is in building shareholder value, and the best and most reliable way to do that is by selling objects people want, creating a huge amount of medical value, and then rationally transferring as much of that as we responsibly can to shareholders.
So we are a company that is, I think, a little bit different and people are going to realize you can ask us all you want about our tech and our platform, and we can talk epitopes and variation, or we can talk about the same things you talk about with a lemonade stand. What is the growth profile? What are the prices? What do you see as the efficient frontier of volume? How are you thinking about the federal complex? We're really looking forward, candidly, to getting to those conversations because the world has been left very much out of position. Okay? There are many vaccine companies. There are not any Invivyd's other than us.
In fact, there was a brief time where there was one Sidara, and that went away real fast because I think what we're all figuring out is there may be these better ways to do business in this really dynamic, overtly massive field. The number of people who could benefit from these medicines, we believe is really extraordinary. Even when people say, "Well, what if it were just," quote, "just immunocompromised persons?" And you think, well, there's 10 million- 13 million of those in America. Those are extraordinary numbers. So look, we have a lot that we are aiming at, and we're really excited to let investors kind of partner with us to get through the very persnickety and new details and get to the really exciting part.
Terrific. Marc, thanks so much. Thanks so much to Invivyd, and thanks for everyone for being with us. Have a great rest of your conference.
All right. Thank you.