Hello, everyone, and Welcome to the third annual H.C. Wainwright BioConnect Conference. I'm Patrick Trucchio, Senior Health Care Analyst at H.C . Wainwright It's my pleasure to introduce you to the management of Invivyd, Katie Falzone, Senior Vice President of Finance, and Robert Allen, CSO. Welcome. First, I think it would be good to start out with some background on Invivyd and on the platform and on the validation of this antibody platform.
Great. Yeah, Invivyd is a monoclonal antibody company and viral infectious disease company. Right now, we have a product on the market under emergency use authorization. We were authorized in March of 2024 and launched in April. Our product on the market is for the pre-exposure prophylaxis of COVID-19. Robbie will speak a little bit about the platform.
Yeah. So we have an antibody discovery platform that lends itself very well to establishment of an antibody relationship with a target and then optimization of that target over time with a dynamic target, such as we've seen with SARS-CoV-2. We also have now applied that to other virus pathogens that we consider to be not quite as dynamic as SARS-CoV-2, but are dynamic in their own right, that being RSV and measles. We have at Invivyd basically been able to move all the way from discovery through to commercialization under the same roof, utilizing outside resources, of course, but demonstrated that on a number of occasions with completion of clinical trials and completion of commercial scale manufacturing on a number of antibodies to date.
Great. Maybe just on PEMGARDA, maybe you can provide the background here on PEMGARDA, the road to approval, and then kind of the latest on the commercial launch.
Yeah. So the road to approval, as I mentioned, was through emergency use authorization. Our first quarter was Q2 of last year. We had sales of about $2.3 million. In Q3, it was $9.3 million. In Q4, $13.8 million. We did, at the end of last year, decide to make the decision to internalize the sales force. With all transitions, there is a learning curve there. We did anticipate that there would be some headwind. In Q1, we did have sales of $11.3 million. We are really excited about what we are seeing with the sales force that is now in place. Most of them are onboarded in January, February of 2025, and then fully trained up and out in the field by the end of the quarter. We are really pleased with sort of the return on investment we are seeing to date and our return to growth.
We really took the long-term view here, really thinking that internalizing the sales force would really position us for a rapid acceleration.
Are there some specific metrics you can point to within the sales force that are giving you this confidence?
Yeah. I mean, of course, we get really excited when we see new accounts ordering, when we see existing accounts that continue to order. During our Q1 earnings call, we also presented some other metrics, including highlighting certain interactions with HCPs, the amount of calls we have with them, et cetera. All of those are trending really nicely from January to April. As I mentioned, Q2 to date, we're really pleased with what we've seen.
Can you talk a little bit about the engagement of payers, payer reimbursement, what you're seeing on that side of things?
Yeah. Thankfully, under EUA, CMS is statutorily obligated to reimburse for Medicare and Medicaid. We are covered by both Medicare and Medicaid, and then the commercial payers did follow. I'm pleased to report that we've also had really positive outcomes with some of the larger plans, including UnitedHealthcare, Aetna, Cigna, and certain regional Blue Cross Blue Shield plans as well.
Is there an opportunity to sort of streamline or expand access and infusion, expand the infusion capabilities in various geographies?
Yeah. Right now, our sales force is geography-based and really focusing on some of the larger academic institutions and then also sort of the other networks, HCPs, et cetera, that are associated with those hospitals. In addition, just to sort of think about the COVID-19 market in general, last year, the therapy market was about over $9 billion. Right now, we, from a market share standpoint, are still reaching the thousands, not sort of the hundreds of thousands of patients that are potentially eligible for PEMGARDA. We feel that there is definitely a big opportunity for our sales force to sort of educate healthcare providers. We look forward to that. We also sort of feel that there's a great momentum that we have right now, just with PEMGARDA being recognized as a standard of care.
We were recently added to the NCCN guidelines for certain B-cell lymphomas. That is in addition to the IDSA guidelines that we were added to in the fall. We are really happy with the momentum, and especially heading into the summer months with the summer surge. Typically, there is a surge during the summer months, especially as people start to travel, go inside, and air conditioning. We will have sort of a digital marketing campaign that will be kicking off related to that.
Can you talk a little bit more about that market and just sort of your, you mentioned your market share, and just sort of how should we think about this, the COVID treatment and COVID prevention market?
Yeah. The COVID prevention market is sort of the market that I was just speaking about. For COVID treatment, that is not something that we're currently indicated for. We do think that there is potentially a role for monoclonal antibodies in the treatment of COVID-19. We do think that especially in the immunocompromised population, where maybe they have more limited, they don't have the same response to a vaccine that somebody who is not immunocompromised would have, there's definitely patients that are in need.
Maybe we can talk a little bit about the regulatory and EUA framework. I'm just wondering, I guess, just sort of what's the latest on FDA's response to PEMGARDA treatment EUA request? Are there additional data submissions planned?
Yeah. So the treatment request was denied by the FDA for PEMGARDA. We now have a new FDA, and we have a new opportunity for conversations around treatment for PEMGARDA. Also, more importantly, I think the feedback that we did have on PEMGARDA guides us a bit in terms of how we would approach with next-gen antibodies, so VYD2311, how we would approach a treatment indication with that antibody. That antibody is attractive in many ways because of its potency. It's around 15-fold more potent than VYD232 or PEMGARDA and opens up the door to other parenteral routes, including something like sort of an IM route or sub-Q route. With all of those things in hand, we'd look to engage the FDA very soon with documentation around these issues of treatment.
We also have a general desire to look for alignment on the FDA's part between the expectations with respect to monoclonal antibodies as they relate to the expectations for vaccine. We have had a citizen's petition recently that argues for that parity. All of that points in a direction to the future that we feel pretty strongly that we have a good plan and a good opportunity to engage with the agency around treatment.
Is there any indication under this new administration how they're going to, I guess, sort of view antibodies with this EUA framework?
I think that in general, we've had very good responses from the agency around antibodies in general. I think that right now, we would not anticipate that on the basis of this being a monoclonal antibody, that there would be any need to adjust course.
I think we will find out more. I think in terms of the vaccines, I think later today, sort of the FDA is going to be unveiling sort of the new plan for vaccines. As Robbie mentioned with the citizen's petition, we think that will sort of help inform the path forward. What we anticipate is it will probably align very much with what we've already done for PEMGARDA, which is we conducted a placebo-controlled clinical trial as part of Canopy.
Right. And so do you anticipate submitting a full EUA for PEMGARDA in prevention, or would you shift to VYD2311?
At this time, I think we're focusing our resources really on 2311 going forward, of course, maintaining all of our requirements for PEMGARDA. For any kind of treatment indication or potentially pursuit of a BLA, that would be for the next generation 2311 candidate.
For 2311, we have the phase one readout expected this quarter. What do you need to, I mean, presumably, it's a similar platform, so we would expect safety data and tolerability data to look similar. What are you looking for there? Is there anything that you'd want to see there as far as gating factors to moving forward phase two?
Yeah. We are anticipating, we did already release an early preview of some of the data in early February. We would expect that hopefully, it is not too much of an update coming as when we release the updated data, except we will be more informed on sort of the half-life as we have not yet reached a half-life when we initially reported that data. In addition to that, we will also be reporting safety data.
How are you thinking about dosing and route of administration? I think you mentioned possibility for intramuscular.
Yeah. The half-life and the potency together go into the consideration of what we call the titer, right, which is how much antibody is on board at the time when a given variant is encountered. And the potency of 2311, along with the half-life and the overall PK, is very attractive when it comes to intramuscular routes and sub-Q routes, which we think are going to be sort of well received by the immunocompromised population over that consideration that we have with VYD232, right? That is kind of the direction that we'd like to go. We have no reason to think that we can't pursue that direction based on the physical chemical properties of the antibody.
Is it still the expectation to target the immunocompromised population, or what might you look to sort of expand?
I think that immunocompromised is a place that we've come to know through this commercialization effort. We think that there is still a lot of space in that population to introduce antibodies for COVID. There are also other at-risk populations that go beyond the immunocompromised. Those could be people that are healthcare workers that are facing COVID on a regular basis. People that are at risk is a population that we'd like to basically explore with the agency as a potential second consideration beyond the immunocompromised.
To what extent can the data from the PEMGARDA program support 2311 as you look to advance this?
Yeah. I think that remains to be seen. That really is going to require a conversation around assumptions with the agency. We have a number of readouts from the Canopy trial that really speak to the potency of this approach as it relates to protection against the complications from COVID. That conversation is going to decide how that data can be used going forward with 2311.
Just as far as with SARS-CoV-2 kind of continuing to evolve, I guess, what gives you confidence that the epitope targeted by PEMGARDA and VYD2311 will remain relevant?
We've spent a whole lot of time looking at variant monitoring and surveillance. We look both in the wastewater as well as in clinical sequencing data. Everything that we know about where PEMGARDA binds to the target tells us that that particular epitope has been very quiet in the wake of the Omicron shift. That has now been three years where we see quiescence at that epitope. That also is something that we can look at with respect to all the changes that have occurred in the target and make what we call synthetic antigens or synthetic pseudoviruses to future-proof against those changes that we have seen that fall outside of our epitope as well.
All of those together have created an empirical approach that gives us a great deal of confidence in the quiescence that we see at the epitope and the fact that if we do not see changes within that epitope, we have reason to believe that this is going to result in basically continuity of the neutralization activity that we have demonstrated to date, all of which has been clinically meaningful as held in light of the Canopy trial, right?
Right. And so how has your surveillance capability evolved, whether it's wastewater sequence monitoring? How does this sort of inform your discovery and prioritization?
Right. I think the first thing that everybody started out with was variant-level data that allowed them to say, "This is the variant, and this is the change at the amino acid." What we've gone back and looked at is all changes that have occurred across every amino acid in the target, right? Looking at the RBD equally-weighting change. We have developed what's called a residue plasticity index that looks at plasticity over time as an accumulated factor, but also in any particular time period, how much change is occurring. We then can map that based on cryo-EM and X-ray crystallography onto the target. We can see that our epitope with regard to this plasticity has remained sort of aplastic, right, whereas other aspects of the target have been very plastic.
Based on the distance between our epitope and those regions of plasticity that is now informed by a constantly updated database of sequence, we can have confidence that these types of changes, however distant they are from our epitope, are not going to result in changes in our binding capacity, right? We then come back to that. Like I said, we can reprove that with pseudovirus data. We use a sort of industry standard pseudovirus for all of our outgoing data with a third party. We can also look at binding with synthetic antigens that enjoy all of that space, independent of whether or not it's actually come out as a variant in the past or will come out in the future. That future-proofing is something that is relatively new based on our analysis of plasticity at the target.
Earlier brought up RSV. I'm just curious, can you talk about RSV, where you see the unmet need and sort of how your program is progressing?
Like SARS-CoV-2, RSV has demonstrated in the past in clinical trials some degree of plasticity. You have seen escape in some of those trials from antibodies that were used in that setting. We have now taken all of that data with respect to escape from other known actives and built that into our screening process for an antibody that is going to address, hopefully, those needs. We are still in the midst of the discovery process, and we would look to get more close to the preclinical candidate by the end of this year. This same approach to understanding plasticity is what is driving our desire to move into that space. We think that from a patient perspective, there is still a large unmet medical need that any one antibody is not going to be sufficient to meet.
Be that in the neonate population or in other immunocompromised populations, we think we're going to have an antibody that's unique and differentiated with respect to its breadth of protection and neutralization. With measles, we're sort of going in the same direction. The clades of measles are, this is something that's been well understood for a while. There are a few variants within the measles populations, especially if you look across North America. We will take that same approach, and we will be looking in the past for sequences, but also looking in the present at the clinical sequencing and the wastewater for signals related to each of these pathogens that help us to understand the underlying rate of change and which epitopes are best to sit within that change rate and also the geography of that change.
Right. The measles program was recently announced. I'm just curious on the decision to go forward, perhaps a measles program over something like pandemic flu threats.
Right now, the burden of disease with measles looks like it has a potential rate of increase that's a little bit different than H5N1 looks. We know that there's 20 million Americans that are not vaccinated for measles. We don't expect that number to go down. We expect that number to go up. We've seen cases that are at, in recent past, remarkable levels of cases that are occurring across North America. We also would expect that as vaccination rates fail to go down, that case numbers would not change or maybe even increase. The whole point here is to keep the disease burden down as low as possible. Ultimately, as a virologist, I look at this as an opportunity to eradicate a pathogen, right?
If we're going to eradicate, then we're going to need vaccines, and we're going to need monoclonal antibodies in order to achieve that. That's sort of where we sit with measles in terms of how it compares to H5N1. It's still a very important pathogen. We have the ability to address that pathogen at a certain time when the time is right. Right now, the time is right for measles for us.
How will you define success in the measles program? Is it as an acute therapeutic, a prophylactic, or sort of a stockpile-ready agent for outbreak control?
Go ahead.
I think we are open to various options. It sort of depends. Once we actually identify the candidate, we will determine sort of what next steps would look like. In terms of government stockpiling, that would be something that potentially would be up to the governments, sort of out of our control. That would be, of course, something that we would be open to having conversations about. Yeah, hopefully, within the future, maybe we'll be talking about potentially commercializing one of these, either RSV or measles.
With RSV and measles, what's sort of the cadence of next milestones for these programs? When should we expect sort of the candidates and the clinical?
Yeah. So we've publicly stated that we anticipate to have updates on both RSV and measles by the end of 2025.
Possibly have candidates named by the end of the year or by next year?
By the end of 2025.
End of 2025.
Is the timing, yeah?
Okay. I guess just have you started or have you had any discussions with HHS, ARNA, any of these other agencies around measles or sort of pandemic threats or any other viral threats?
Yeah. I think those conversations are best had when you've got that antibody in hand. We would look forward to that. Right now, we're focused on discovery.
As far as, I guess, the strategy around business development, how should we think about that? Are all of these programs, would you intend to keep in-house or would you look for out-licensing opportunities?
I think that currently, we would be sort of open to conversations, whether they were with the government or whether they were with potential other partners. We would be open to those conversations.
As we think about over the next 12 months, the key kind of milestones that investors can look forward to, it's more just sort of the continued ramp-up in PEMGARDA. We'll have a few additional, it sounds like a few additional candidates perhaps by the end of the year. Then possibly in next year, we should start to see maybe some additional clinical data as well.
Exactly. Also the 2311 data that we anticipate releasing later this quarter.
Right. So what do you think investors are missing?
I think that right now, COVID is something that people don't want to think about necessarily. I think it's been five years, and I think there's also sort of this time will tell of what the political environment will look like as well. We feel as though COVID's here to stay. We see us being active in the COVID-19 market, hopefully in both prevention and treatment at some point, and hopefully with a maybe more favorable product profile with 2311. Yeah, we think it's exciting times for Invivyd, so.
Great. Any other questions? Any audience? Thank you so much. Always a pleasure to catch up. Thanks, Katie. Thank you.