Well, thank you, guys. Super excited to have management team from Invivyd join us. And I'm sorry, Mark, couldn't make it, but I'll let you kick things off, and I feel like there's a lot to talk about since it's weekend.
There is. You know, it's a very exciting time at Invivyd. And for those who don't know us, we are a monoclonal antibody company. We have a drug, via EUA that we are commercializing called PEMGARDA. And so we are continuing to sell that product. It's a one-hour-long infused product for the prevention of COVID for the immunocompromised population. What we're really excited about right now is that the next-generation asset, 2311, for COVID prevention as well, is gonna be entering the clinic in a pivotal trial for an EUA. Excuse me, for a BLA, fully licensed approval product. And we're really excited about that. It's gonna be a stepwise change, we think, if we're proved that we think that we can change the product profile from a one-hour-long infused product with PEMGARDA to something that's delivered via intramuscular injection.
And so that stepwise change, we think, is gonna be better for patients, easier for prescribers, and we think that it's gonna be, could truly be an alternative to vaccine. So we are very excited about that program. And then we've also recently announced an RSV candidate that we are looking forward to working towards and then having something that would be ready for IND later in 2026.
Excellent. Excellent. So I guess maybe let's start with some of the emails going around from this weekend. In fact, even before that, do you guys see yourself as a vaccine or not?
We do not.
Does FDA see you as a vaccine?
They do not. So we are a monoclonal antibody, and they recognize that. They look at us as a tool to prevent COVID. With regards to PEMGARDA, we are, you know, we have the EUA issued for that immunocompromised population, and so we truly are differentiated from a vaccine.
Apologies. Got it. Sorry.
No problem.
Sorry. Okay. So you were saying, okay. So they don't necessarily view you guys as just a. They don't view you as a vaccine either.
Correct.
Okay. So with some of the questions that are going around on flu vaccines, broadly, the strain selection efficacy, how do you envision that impacting both the clinical development as well as commercial recommendation for Invivyd?
So we are really pleased about the pathway that we have towards BLA. You know, when we were looking at PEMGARDA, we were informed that the EUA pathway was what would be most applicable, that we weren't really gonna be eligible for a BLA at that point in time. So the fact that we have been able to work with the FDA now and actually design a BLA-enabling trial, something that we are looking to launch imminently. We're already working on that with site selections and working towards starting that as soon as later you know by the end of the year or in Q1 with first patient. And so we're quite pleased about that. Robbie, I don't know if you wanna add anything else to that one.
I think the path to commercialization here is the difference is with active immunization with a vaccine, you have to pick a strain or a variant at some point. In our case, we have an antibody that the epitope for that antibody is present on all of the variants to some—to one degree or another. It turns out that our epitope is very well conserved among all of the variants that have occurred since the Omicron break, and even before that, we have good activity against viruses before that time. The other thing that we can do is look at all of the current variants for any of the antibodies that we're pushing forward into commercialization and make sure that we have adequate activity against all of those variants as we're moving through the clinic, which is a big difference, right?
We have the ability to look at breadth actively throughout the process of both development and also the clinical trials and then further on into commercialization. And then, you know, in the background, we're always making improvements to our antibodies through a process that allows us to optimize in the background and get ready for the next commercial candidate, right? So we can hedge in that way against variability and dynamism.
Excellent. Makes sense. So maybe let's start to get a little more specific then. The new program you have, 2311, compare that to PEMGARDA because those are two very different constructs. We can go sort of step by step on indications, but dose, etc., if we can go through that.
Sure. So with PEMGARDA, we have an antibody that is administered through intravenous route, and it's administered the recommended population or the population for which we have authorization are immunocompromised individuals. We would look with 2311 at maintaining that activity in those recommended populations, but also including people that were considered to be at risk, either based on their age or some other predisposing factor that would put them at risk for COVID to potentially expand the population beyond the immunocompromised. You know, all of this depended upon the readout from the study itself. So again, we're going intramuscularly now, so it's still a parenteral route, but intramuscular is a much—it basically is thought to increase access for patient populations, be they immunocompromised or people that are at risk.
And then this allows for a shorter period of time for the actual dosing event itself, and then should be a fairly brief amount of time in terms of the follow-up as well, so fundamentally different in terms of access for patients to 2311 versus PEMGARDA.
Right. What's the dose level? So PEMGARDA is 4-4.5 g IV. The dose level expected on 2311 is what?
What are we gonna go?
Something that fits in an autoinjector.
Yeah.
And so sub-300 mg, presumably.
Presumably.
Yep.
Yeah. So I guess maybe just, and I remember doing this exercise with Mark the other day as well. So if it's four and a half, 4,500 mg on the current construct versus, let's say, sub-300 on the new one, you have to assume there's a very significant potency increase to be able to deliver something equivalent. So is that a reasonable conclusion?
Right. That's a very reasonable assumption. I mean, we've seen, you know, depending on the variant, anywhere from 15- to 17-fold increases in potency for 2311 versus 222 against the same variant. So those types of increases allow for the efficacy at a lower dose that you're, you know, you're sort of calculating in your head.
Is the epitope identical?
It's you know, so it's overlapping. The epitope between 2311 and 222 is overlapping. Yes.
Got it. The COGS would be what?
So what we said is that we expect to achieve pharmaceutical-like margins. So think about, you know, the 80%+ margin is what we're targeting. So we're talking.
But the price point would come way down on it.
Will come well down, so we're comparing ourselves, you know. What we have said to date is that we're expecting the price point to be somewhere in the hundreds as opposed to thousands of a dose for PEMGARDA.
Right. What's the PEMGARDA price right now?
Right now, it's approximately $6,500 gross.
Oh, is that right? Okay. So PEMGARDA, $6,500. And this would be, let's say, sub-500.
We're saying in the hundreds right now.
Got it. 2311 in the hundreds. Is it possible that the 2311 COGS could be below $50, below $40? Like, are those possibilities?
I think possibility is below 100 for sure. We feel.
Okay. Makes sense. Makes a lot of sense. Future constructs that okay. And by the way, trial timelines, so it's starting phase one right now, 2311?
2311, we've already done a Phase 1. We're starting pivotal right now. Think of it Phase 2, Phase 3 trial for BLA, and that's imminent. We're already preparing for it. We've received the IND, which enables us to begin the trial, and so we're targeting end of this year, early Q1.
How important is it for Invivyd to get this product to the market in the three years remaining for the current administration?
I mean, I think it's important for the population and by and large to get it to the market as soon as possible. I think that this is. We look at this as a potential real alternative to vaccination. We feel like we are well positioned, based on our experience with predecessor mAbs, including what is now PEMGARDA, to get it through the clinic. We feel like we have a strong study design and are able to concisely put forward this data package. So we're targeting completion of a data package to submit to the FDA, in the, you know, around the halfway mark of 2026.
Around the halfway mark of 2026. Okay. Got it. The phase three design, this will be focused on, remind us that—and the primary efficacy endpoint, what would that be?
So this is PCR positive COVID, is the primary efficacy endpoint, right? So the number of PCR positive COVID cases in the placebo versus the treatment arms.
Right. What about the hospitalization endpoint? Could that be something FDA asked for or probably not? Because that was a harder endpoint to accrue.
Right. Based on our current communication with the FDA, we don't have any reason to believe that that's gonna be an endpoint they're gonna ask for, and so we're proceeding with the endpoint that I just described. Yeah.
Have there been conversations between Invivyd and CBER? Oh, sorry. Invivyd and Vinay, not CBER.
Specifically between Vinay Prasad and Invivyd?
Yeah.
In terms of as it relates to, well, I don't know. I guess it's difficult to say. I don't know of any conversations specifically.
But is that even a natural place? 'Cause that wouldn't—like, your primary point of contact would not necessarily be Vinay directly, obviously, right?
No.
It'll be a team within. So you're operating with the team you're speaking to.
Yes. Correct.
The team would be under whatever the standing instructions are, by Vinay.
Absolutely.
Okay. Makes sense. Makes sense. Okay. Great. And then, I guess, the other one I wanna also just, like, touch up on is, for true commercial success, what exactly is it that you guys have in mind? Do you need to have any hospitalization endpoint or anything along those lines? Or, showing that COVID positivity rate delta along with duration is really all that sufficient for successful commercial launch?
I mean, I think that we believe that's all that's required for successful commercial launch. It doesn't mean that there wouldn't be post-approval studies to actually, you know, gather other information. That being said, we do feel like this is gonna be a compelling product for people, given the fact that, you know, vaccination, you know, there's a hesitancy towards them. There's a safety concern. We feel like a lot of that can be avoided with a monoclonal antibody, and the fact that we're able to work towards changing the product profile over what is now PEMGARDA to 2311, we feel it'll be a stepwise change and would make it a very attractive product.
From a patient perspective, what does the commercial presentation look like? 'Cause I know right now the COVID shot is you just take it and you don't feel much, but then over the next day and a half, you do feel something, so at least in my case, I have to plan ahead for that day and a half down, then you still get headaches and fevers, chills. I guess could you speak to because it's an antibody, you wouldn't have those side effects on the back end, but during the administration, the volume, the experience, the pain, et cetera?
So in terms of the, you know, that's what we would look for with any sort of parenteral dosing. Modality would be injection site reactions would be one typical class of events that would occur, but we don't have any reason to believe that based on the Phase 1 study that there's anything extraordinary about the experience on the patient side when it comes to being administered antibodies at the doses that we're intending to use in this trial. We also know that with vaccine, you know, the reason for some of those post-injection feelings that people have to do with the actual active vaccination process. Whereas with a passive vaccination process, we wouldn't look for a whole lot of immunogenicity post-administration.
You know, you could have reactions, but they would be, you know, of a different origin, I think, potentially than the types of reactions you would have post-vaccination.
What's the needle gauge for this?
Oh, that's a good question.
Oh, and that can evolve too, I would imagine.
Yeah.
With time. But right now, is it in the low 20s or high or is it in the mid-20s?
That's, I don't know the answer to that question.
Okay.
That's a good question. But on the ground level, I think that typically you're dealing with a fairly, you know, high-gauge needle, right? Like in terms of the 20s or in the high teens with this type of administration. So I would look for something, you know, typically.
Around 20, not 27 is what you're saying.
I mean, typically that would be a reasonable expectation.
Okay.
Yeah.
Is a sub-Q possible or is that even needed? 'Cause I know IM is a plan right now.
I mean, sub-Qs with antibodies are always possible. It's something that, you know, that we've thought about. Right now, it doesn't seem to be needed based on the dose level that we're administering, and we feel like we have protective efficacy well within range with the IM-administered dose. Yeah.
Okay. Got it. Okay. Makes a lot of sense. And then I guess the only other one is who administers this? Is like, if I walk in, like, in five years from now, if I walk into the pharmacy, could the pharmacist just give me a shot or is this something that would have to be done by a, in the hospital setting?
So, we're thinking that this could be a combination of in the pharmacy setting or in the doctor's office as well, is what we're contemplating right now. So, you know, whether it's at your annual physician appointment, whether or not you can get it dosed there or an appointment similarly to the way that you would schedule a COVID vaccination or a flu shot at your local pharmacy.
Got it. Okay. Makes sense. Great. And then, so buy and bill and those types of models, those are not necessarily the base case plans.
Correct.
Okay. Excellent, and then I guess sort of towards the end, as we think about the future optionality and where things are heading with this program, we've seen constructs come up for other indications like flu, also using antibody-like approaches. We've seen prophylactic antibodies for RSV as well now. So one thing I always think about is on immunology, we're seeing bispecifics. On anti-infectives, we're not seeing bispecifics yet, but maybe not even bispecifics, but multipurpose antibodies, which deliver, let's say, a COVID in the base antibody, I don't know, conjugated to something which can deliver a flu effect, perhaps one arm delivering RSV. Like you could have a multipurpose respiratory super respiratory antibody shot, which then makes a proposition almost so compelling that it's hard to avoid. Is that a consideration or active consideration internally?
So absolutely. I think, you know, the way this goes from a regulatory perspective is you have to have that first product through before you can add to it. Even if you're talking about a cocktail of antibodies that each of the antibodies had a different target, they typically would go through as a singleton first.
Sure.
If you wanted to conjugate to an antibody with an active against a second target, that also would be, on the back of having done the antibody first, in most cases. But, I think it's, if you're talking about prep, the more prep that you can bundle into a given administration, the better. Because prep is sometimes a bit of an abstraction. I think that if you can provide people lots of prep for lots of different pathogens, it's very compelling. And we would look to achieve that. We talk about, you know, those types of outcomes a lot when we think about where to go next with our.
Right.
Existing products, and how best to address the market in prep. I think that's it makes a lot of sense.
Got it. Maybe in the last minute or so, could you remind us what's the half-life and what's the realistic expected, protective period once you take the shot?
So, we're basically, have we gone out with the half-life specifically in terms of numbers?
We've provided, you know, the latest.
Yeah. So the half-life here is, you know, superior to that for VYD222 PEMGARDA. We feel like with the half-life in the range that it's at, which is in that sort of 60 to 70-day period, that's gonna be more than enough to provide protection with a single dose across the three-month period of the trial. And because the dose level basically allows for the titers to be protective with that consideration. So we're, you know, we're very confident with the dose level and basically the protective potential of this dose going into this trial.
Okay. Has a minimum threshold for effectiveness been established?
You know, when we looked at the washout period in CANOPY for VYD222, you can see in that data, and that data has been published, that there is protection across a very wide range of titers. The powering of that study was insufficient to give you an absolute minimum effective titer. But from an anecdotal perspective, informing yourself with all of the cases that are present within that study, it's very evident that at low levels, there is still significant protection afforded by the antibody.
Makes sense. Excellent. I think we'll wrap it up right there. Good luck into the registrational data. So the readout would then be the next big clinical update is 2027 then. Is that reasonable? 'Cause you're starting the study now.
We're starting. We think that we will have a data package into the FDA, mid-next year, mid-2026. So we think that this is a trial that we can actually enroll rapidly.
Oh, wow.
Into that data package. So we are looking to get a data package into the FDA middle of next year. And so, you know, depending upon review cycle time, that would obviously, you know, could find ourselves on the market, you know, within a year.
Oh, fascinating. Very interesting. Excellent. Good luck. Thank you again.
Thank you.
Thank you.
Thank you so much.
Thanks so much.
I didn't realize mid-2026.