Invivyd, Inc. (IVVD) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to the Invivyd CANOPY data update conference call. [Operator Instructions] Please be advised today's conference is being recorded. I would now like to hand the conference over to your speaker today, Katie Falzone, Vice President and Corporate Controller. Please go ahead.

Thank you, operator. A short while ago, we issued a press release announcing our Canopy data update. That press release and the slides that are being used in today's webcast can be found in the Investors section of the Invivyd website under the press release and Events and Presentations section respectively. Today's discussion will be led by Marc Elia, Chairperson of Invivyd's Board of Directors and Chairperson of the Executive Committee of the Board. He is joined by Dr. Mark Wingertzahn, Senior Vice President of Clinical Development and Medical Affairs; Tim Lee, Chief Commercial Officer; and Bill Duke, Chief Financial Officer, will also be available for Q&A. During today's discussion, we will be making forward-looking statements concerning among other things, our corporate and commercial strategy, research and development activities, our regulatory plans, our future prospects and other statements that are not historical facts. These forward-looking statements are covered within the meaning of the Private Securities Litigation Reform Act and are subject to various risks, assumptions and uncertainties that may change over time can cause our actual results to differ materially from those expressed or implied today. These forward-looking statements speak only as of the date of this call, and Invivyd assumes no duty to update such statements. Additional information on the risk factors that could affect Invivyd's business can be found in our filings made with the U.S. Securities and Exchange Commission, including our most recent Form 10-K, which is also available on our website. I will now turn the call over to Marc.

Good morning, and thanks, Katie. Before we walk through the CANOPY clinical trial exploratory results in detail, I want to add a few remarks about the overall context for this trial and today's data. If you're following our slides online, please turn to Slide 3. First, remember that CANOPY was designed as a safety and immunobridging trial in collaboration with the U.S. FDA, not as a clinical outcome study. Back in 2022, academics, sponsors and FDA all agreed that executing COVID-19 outcome trials before antibody authorization would likely take up too much precious antibody equity time and faster pathways to authorization based on surrogates were needed, such as the immunobridging approach that led to the EUA for PEMGARDA. Also, back in 2022, no one knew what attack or rate at which study participants would experience ambient virus would be likely with COVID-19 at the time this framework was generated and CANOPY was designed. As in a side, I'm sure many stakeholders hope then, that by now, there would be less COVID-19 around following broad initial vaccine uptake and seemingly endless waves of disease. But clearly, that hope is not borne out. We see a surprising magnitude of ambient COVID-19 and the CANOPY data from 2023 into 2024 that we will discuss today. And indeed, we see a substantial magnitude of Ambient COVID-19 today. Whatever it is we've all been doing to mitigate COVID-19 disease burden, it is clear that we need to do more. Given these clinical trial design elements, efficacy analyses like those we are discussing today are exploratory. Still, given the major wave of JN.1 virus earlier this year and the substantial attack rate displayed in CANOPY, the results we are presenting today are of great interest to us, the FDA and we believe the broader scientific medical and immunocompromised populations generally. We saw from the 180-day data analysis, an impressive rate of protection with PEMGARDA from symptomatic disease across CANOPY. The 84% relative risk reduction from confirmed symptomatic COVID-19 versus placebo over a 6-month period in Cohort B is a step change in protection from that estimated to be available from vaccination. And indeed, in an unusual reflection of the power of a long-acting antibody versus traditional vaccine technology, we believe that such protection can follow from fewer doses of antibody than the doses of vaccine boost that would be required to get protection for immunocompromised persons. As a reminder, the CDC recommends vaccine boosting no more than "every 2 months" or no more than 6x in the year for the immunocompromised population. Clearly, the traditional roles of active prophylaxis via vaccine versus passive prophylaxis via antibody are somewhat reversed in COVID relative to what one might expect or wish for. To us, these CANOPY data underline that a long-acting antibody can be a critical increment to the protective or momentary. We believe this field requires rapid scaling so that more people can benefit from antibodies, and we look forward to discussing that with the FDA and other global regulators. Meanwhile, these exploratory efficacy data are critical addition to the PEMGARDA fact sheet that may help vulnerable populations and their caregivers make more rational data-driven decisions about their care going into the fall and winter season. Turning to Slide 4. Importantly, CANOPY, along with the SUPERNOVA data, we expect to see shortly from our colleagues at AstraZeneca relates to data on antibody prophylaxis that we, as a scientific community are now seeing for the first time in a human population that has had some level of prior immunologic experience from prior vaccination or both. You can see clearly the evolution in our population over the last few years in the inclusion and exclusion criteria for these studies in a modern, endemic virus world. We had Invivyd wonder whether the medical job to be done for an antibody in the modern population might be a critical increment on top of the immune-experienced people already have from vaccination or prior infection. Now pemivibart, even at the dose interrogated in CANOPY does not provide quite the same level of sVNA titer as the parent molecule adintrevimab because pemivibart is not as potent as adintrevimab was. You can see that quantitative relationship in the PEMGARDA fact sheet, where the FDA describes the range of bridging values in a sensitivity analysis down to levels as low as 35% to 70%. So a bridge only in the sense that if you are interested in crossing about half of the immunologic river, the FDA suggested to Invivyd, pemivibart will get you there well. Further, adintrevimab in the EVADE study drove a 71% reduction in symptomatic COVID-19 from much higher calculated tires whereas pemivibart appears to drive 80% plus protection even at these lower titers. We see robust protection in CANOPY, and we, at Invivyd, have been confident in CANOPY and pemivibart for now 2 years. Why? There are at least 2 distinct possibilities explored by the underlying immunology. First, it is entirely possible that the cellular bioassays that describe antibody antiviral potency can be highly variable and poorly reliable and the collection of numbers imagined to describe both adintrevimab and pemivibart are subject to error and leverage underpowered mean value estimates instead of ranges, driven by confidence intervals. I might imagine we might return to this point during today's Q&A. Second, and we believe more intriguing an immunologically experienced population may have a higher baseline of protection on top of which an antibody offers a critical functional increment that builds towards more complete protection. We should all be grateful for the vaccination campaign that helped us gain this baseline level as a population. From here, however, an antibody has the potential to finish the job and move titers to the point at which people have an easier time staying well, not just staying mostly alive. With that, I'd like to turn the call over to Mark Wingertzahn to talk through today's CANOPY data update.

Thanks, Marc. We turn our attention to Slide 6. The CANOPY clinical trial included 2 cohorts and was primarily designed to assess safety and immunobridging. Cohort A is a single-arm uncontrolled cohort comprising approximately 300 immunocompromised subjects. Cohort B is a 2:1 randomized, double-blind, placebo-controlled cohort comprising approximately 450 all-comer immunocompetent subjects who are at risk for SARS-CoV-2 exposure due to regular unmasked indoor interactions. CANOPY trial participants received 2 doses of pemivibart infused 90 days apart. Today, we are sharing the safety and exploratory efficacy results from the full 180-day analysis. Next slide. The baseline demographics are shown on the current slide. The average age was what you would expect in a trial such as this with the immunocompromised cohort being somewhat older than Cohort B and having a greater proportion of subjects greater than 55 years of age. The majority of subjects in both cohorts were white or Black/African-American. Next slide. The medical histories of subjects enrolled in CANOPY are shown on the current slide. As expected, given cohort A subjects are immunocompromised, they were medically more complex than cohort B participants due to the concomitant medications or preexisting conditions that led to their immunocompromised status. Next slide. As noted previously, dosing of pemivibart or placebo in the CANOPY trial occurred from fall 2023 through winter of 2024. As it can be seen on the current slide, interestingly, the majority of subjects who received their second infusion of pemivibart did so during the major JN.1-dominant COVID-19 wave that moved through the United States in winter of 2024, making this study one of the few COVID-19 studies conducted in a contemporary population. Next slide. As the CANOPY clinical trial was designed as a safety and immunobridging trial, safety was of paramount importance. Reassuringly, the updated safety analysis from the second half of the 180-day assessed time period is consistent with the previously described profile of pemivibart. It includes no new adverse events of special interest. Additionally, we are pleased that as of this date, we have received 0 reports of anaphylaxis in our post-authorization experience with pemivibart. Next slide. In addition to safety, the CANOPY study also assessed COVID-19-related events as part of the analysis plan. In this regard, we will present 2 key analyses described on this slide. First is the A priority defined exploratory composite endpoint of RT-PCR confirmed symptomatic COVID-19, COVID-19-related hospitalization and all-cause mortality. Second, we will present an analysis of those events known to be caused by COVID-19 alone to provide greater context. Next slide. The current slide depicts the exploratory clinical efficacy endpoint of RT-PCR confirmed symptomatic COVID-19, COVID-19-related hospitalization and all-cause mortality for the modified full analysis set of Cohort B., analogous to an intent-to-treat population. This analysis showed an 84% relative risk reduction of RT-PCR confirms symptomatic COVID, COVID-19-related hospitalization and all-cause mortality. The nominal p-value associated with this finding is p equals 0.000061. Of important note, there were no COVID-19-related hospitalization or all-cause deaths in either arm of Cohort B. Next slide. The current slide depicts the Kaplan Meier for the composite exploratory clinical efficacy endpoint of RT-PCR confirmed symptomatic COVID-19, COVID-19-related hospitalizations and all cause mortality. The placebo arm in the curve demonstrates the strong attack rate presented by the JN.1 virus in the second half of the 180-day assessment period and further substantiates the strong protection confirmed by pemivibart through that COVID-19 wave. Next slide. The current slide depicts the exploratory composite endpoint of RT-PCR confirmed symptomatic COVID-19, COVID-19-related hospitalization and all-cause mortality in the single-arm immunocompromised Cohort A group. What we see here is we've observed encouragingly low rates of symptomatic COVID-19 and COVID-19 related outcomes in the Cohort A immunocompromised patient population. Although as a medically complex population, we were set to note, as previously disclosed, 2 deaths in this cohort. One death was due to suicide and one was due to unknown causes. Both patients suffered from an advanced HIV infection at baseline. Next slide. Similar to what was seen with Cohort B, the Kaplan-Meier presentation on this slide for Cohort A shows that the immunocompromised arm had an encouraging levels of protection as evidenced by the relatively low rate of COVID-19 throughout the entire 180-day period, including during the JN.1 wave of COVID-19. Next slide. As we sum up and reflect, we all should be reminded that COVID-19 is the most damaging and deadly of prevalent respiratory viruses and still remains the leading cause of hospitalization and death from respiratory viruses over the 2023 to 2024 data period. Moreover, COVID-19 remains a critical unmet need, especially in the immunocompromised. We, at Invivyd, are highly encouraged by the exploratory clinical efficacy data from CANOPY and the role pemivibart and follow on antibodies can play in diminishing the unacceptable burden of COVID-19 disease outcomes going forward. With that, I'd like to turn the call over to the operator for questions. Operator?

[Operator Instructions] Our first question comes from Michael Yee with Jefferies.

Congrats on the data. We had two questions. One was, I'm just thinking about these results is the plan to get this into the label. What is -- how does this contribute obviously to regular processes either here or around the world? Should that be the first question. And then the second question is, obviously, now we are, I guess, going into Labor Day weekend and peak start of the season, can you just tell us a little bit about your visibility around ordering patterns with a couple of months here left to go in the year and your current guidance? And how ordering patterns are looking as you go up against your guidance?

So just on your first question, these data are already in the updated fact sheet for PEMGARDA. And I think it is safe to say that translational immunology is always interesting, but RCTs and human clinical data are much, much, much more interesting. And so I think we are finally transiting the end of that period in which antibodies are a feature of COVID passed and new antibodies bear some unknown assessed immunologic relationship back to them, and we're entering a new period in which we can consider with much more robust and complete data sets, what benefit is conferred in a contemporary population by contemporary antibodies. And so we have as yet no express guidance for you or thoughts for you about what this augurs around the world. But one of the reasons we're very pleased to be speaking with you all today is, of course, unsurprisingly, we and the U.S. FDA appear to find these data rather interesting as they speak to the totality of evidence, and I think that they speak very strongly to the totality of evidence that suggests a real medical benefit set to antibody in the form of very high protection from symptomatic disease. So that's as much of an answer as I can give you. But I think overall, we see this as a little bit of a kick off to a much bigger, broader future, we hope to engineer for both pemivibart and then follow-ons. As it goes to the season, I noticed you noted there are a couple of months left in the year. I think there's more than that, but we are leaning forward in our seats just as we were when we spoke to you a couple of weeks ago. I think what I would ask is Tim Lee, who's on the call can talk about what we're maybe not what we're seeing in terms of ordering patterns because that's a little granular for a CANOPY data update call. But I'm sure he'd be delighted to tell you what he sees in the field and what the possible utility of these data might be in these coming weeks and months. Tim?

Yes. Thank you, Marc, and great question. I think as we look at this exciting data for the immunocompromised patient community who is in need of protection, we're excited to have these data within our fact sheet. I think coupled with the IDSA guidelines, which recently came out to update, we see this as a really important clinical story that we can go out to tell commissions around the country to serve this community. As we noted not that long ago in the Q2 call, we talked about the number of accounts who have ordered launch to July 31st, and I think we discussed that infrastructure and foundation that we're building is ready to serve these communities. And we -- I think we last spoke, we said over 208 accounts had ordered through the end of July in academics and infusion centers around the country. So we're pleased with the ability to serve this group. I'm very pleased with these data and our fact sheet in order to be able to go out commercially to educate clinicians around the country and couple that with IDSA guidelines. And I think we're very pleased, as you noted, that the season is upon us now.

Our next question comes from Patrick Trucchio with H.C. Wainright.

[indiscernible] in for Patrick. Congratulations on today. And it's great to hear that this day is already in the fact sheet. Are you doing any other steps to actually educate people about that potential and the choice -- that the choices that they have. So not just telling them you can refer to the fact sheet, but seeing -- actually explaining to them what we're seeing basically in this presentation. And another question is, what is the current variant -- the predominant variant? And how do you think this is going to -- do we have antibodies against that new variant because the JN.1 was basically seems like it's waning towards the end of May. So have you seen data -- have you shown data that we support -- that supports the protection against the new variant that is [indiscernible].

So why don't we go in reverse order? So as you know, to do rigorous high-quality virology, it takes some measure of time. And so by definition, we're always playing a little bit of catch-up. However, I think earlier in the summer, we press released and conveyed our confidence in our antiviral activity against KP3, which is a variant that's highly related to the, let's call it, soup, you can find either in the CDC Nowcast or in the wastewater data that is available for your perusal. So we tend to communicate with the Street indirectly because our results go to FDA first for updating through the fact sheet. But given the activity, we see against KP3. Right now, we have no reason to feel anything but confident about the activity of pemivibart against a great number of contemporary lineages. I don't think there's anything we could say as dominant at the moment. But there's sort of breadth available to look at and we feel pretty good when we look at that breadth. But of course, our data always evolve on this point. Pemivibart is designed to navigate variant evolution to the best of our scientific ability and right now to our knowledge, there is nothing out there that intrudes into the pemivibart binding site. So, the epitome, the target engagment in effect that we leverage appears to be intact and it has been largely intact I think in the sort of high 90s level plus since omicron. So, numbers are going to move around and come and go. And we can talk about that endlessly and indeed on some days, we would love to do that. But in general, right now, we feel pretty good. As it goes to education, I guess, Tim, why don't you once again talk about what we're doing in sort of a broad marketing and digital campaign starting shortly.

Yes. Thank you, Marc. Yes, I think we're excited to launch multiple different channels of engagement to clinicians and the community at large. One of the things that this helps an awful lot just in a simplistic term, is that when there is data of this robust in the fact sheet, it allows us to be able to speak broadly to it to be consistent with regulations. So, the good news is we've teed up an awful lot of materials for our field teams to go out and educate clinically with are coupled with a digital strategy that we've engaged and built out rapidly over the last 4 to 5 weeks and continue to make investments where we see in the digital channels where we're seeing a real return in real time, which allows us to gate appropriately, but also really lead into areas where we're finding a high degree of reception, so it's -- these really important clinical data being and the fact sheet really do allow for us to lean forward a bit and educate clinically around this unmet need.

Our next question comes from Maxwell Skor with Morgan Stanley.

Congrats on the update. So two for me, just briefly, how did these data inform the path forward for 2311, your next-generation monoclonal antibody? Has it changed potentially your clinical trial design or time lines? And then second, in regards to the treatment EUA that is currently submitted any additional thoughts. I know I asked about it on the second quarter update, but any initial thoughts on when we can hear back from the FDA?

Great. Thanks. So we and the FDA, as you may have inferred have been rather busy together over these last weeks. And I suspect that the treatment EUA will come into focus for them shortly, but we don't have an update at this point for you. I think with respect 2311 and these data, they raised some intriguing possibilities that we are, I think, gratifyingly already seeking to parse clinically, meaning we talked about in the prepared remarks, this sort of evolving relationship or potentially, I should say, evolving relationship between titer conferred and clinical protection. And we have thought these thoughts, we simply haven't seen fulsome data that suggest that perhaps the remnant titer or the titer we need to add in an immunologically experienced population may not be quite so substantial is that -- that was imagined when we began CANOPY all those a couple of years ago. And so what you will see although 2311 is, generally speaking, a markedly more potent antibody than pemivibart, we might be intrigued in engaging with regulators on defining, let's call it, a more rational dose. One of the great benefits of antibody is that they appear sufficiently safe, that regulators and sometimes even sponsors just figure, well, if some is good, more is better. Keep pushing dose, keep pushing titers. And of course, while that's a strategy that can be prosecuted, I'm not sure that we believe it results in the most equitable or attractive medicine, right? It's one of the ways you might end up with gram quantities of drug in an intravenous infusion. And so I think stepping back a little bit and just looking at the field in its evolution, what these CANOPY exploratory data suggest to us is that perhaps that paradigm can be, in effect, re-underwritten from first principles immunologically. And all of that would comport I think, with our broader mission, which would be to try to get to form factors and routes of administration that would allow us to substantially broaden access to medicines like these. And as a consequence, you have already seen our intent to begin interrogating alternative routes of administration including IV but also adding intramuscular and subcutaneous routes of administration for future COVID antibodies, including 2311. So again, this is one of these situations where -- in which we can think prospectively all that we want, but data is sort of rules on and is much more compelling, I think, to other stakeholders in the field. We're pretty excited to rethink the field to the extent that our counterparties as global regulators are open to such a discussion around what the boundaries really ought to be here. So I hope you followed that answer. I think knowing you might have, but do follow up here, if it's not clear.

Our next question comes from Evan Wang with Guggenheim Securities.

Great to see this supporting clinical data. It looks like the vendor activity for JN.1 was resolved. Two for me. First, on the exploratory clinical efficacy data, understanding it's within the UA. Can you remind us -- are you allowed to comment on that in marketing campaigns to patients or in DTC campaigns? And then second, I understand that some of this work may be ongoing. But can you comment on the process for updating the fact sheet for anti-viral activity, just to maybe resolve the KP311 pending status. I know you mentioned some of the activity against flu, can you comment on some of the degree of confidence and maintaining sepal activity here given the recent preprint. And maybe if you could comment on some activity against variants we have seen with S31 dilution?

Sure. Happy to do it. So I guess, Tim, first, can you handle what it is we are going to say to whom in the near future?

Yes. I think what we discussed is that we have a real opportunity to lead clinically with these important data being in the fact sheet allows us to educate broadly to the clinician community and couple that with the IDSA data, we can -- we are activating with immediacy right now. One thing we can't do is direct-to-consumer advertising. So you won't see any commercials as college football season opens up this weekend, but I think we're appropriately educating to the stakeholders who need to hear this very important clinical data for them. And as I said, we're doing multichannel marketing efforts are underway right now and look forward to all of that with the process of understanding what the consumption rate of that is and then doubling where we see opportunities and really being focused around this pivotal data for us.

Okay. So then on your second question, Evan. So to begin, the process in Invivyd typically looks like this. As the innovator and producer of pemivibart, we deploy any number of systems, but principally a large, well-known commercial-grade laboratory to do much of our antibody potency testing for us. And that process moves along at its sort of usual pace. And indeed, the virus you highlighted, KP3.1.1 is in that queue. And we would imagine having our own data from our own systems with our own molecule within weeks, let's just say. Now as to the preprint you raised, I guess I would just encourage anyone to consider some elements here. Number one, Invivyd doesn't provide pemivibart to these third-party laboratories. They make their own version, and then they utilize their own systems. Of course, we don't have any insight into in terms of quality, the calibration, the positive and negative controls, the lineal custody and series of observations that we have with our internal systems dating back months, quarters and indeed years. So it's always a little challenging to interpret the sort of data that pops up in non-peer-reviewed preprint type publications, particularly when a virus has sort of a retained binding site, but an interesting function, right? The S-31 deletion can manipulate the up-down configuration of RBD. But without going into that, I guess I would just say, one should probably exert a reasonable amount of restraint and caution in interpreting the meaning of these sort of ad hoc demonstrations. And I would just submit for your consideration, there is another preprint available in bioarchives. And by the way, a preprint can go into bioarchive if every author consents and if there is nothing obscene and content appears scientific. So Cold Spring Harbor is pretty clear about the bar required for putting a preprint in a nonpeer-reviewed format. This other preprint describing pemivibart comes from Institute Pasteur and the group of Olivier Schwarz and Institute Pasteur, as I'm sure you know, is one of the world's most renowned virology and microbiology institutions. It dates back to Louis Pasteur himself. In that preprint, shorts and colleagues described a potency level for pemivibart against JN.1 that we would consider on the border of having activity. It's roughly around the same levels described for KP3.1.1 by [indiscernible] colleagues. So in those situations, Invivyd has an opportunity to reflect on our own internal data from our own molecule and our own custodial assays contracted out to nonconflicted, independent third parties. And when we do that, we, for example, observed pretty robust JN.1 potency. It's viewable in the fact sheet, but I think we disclosed it now publicly any number of times. And then we consider that assessed potency estimate. And we can, in this instance, actually reflect against clinical activity. And so in the case of JN.1, my gosh, we feel pretty good about the activity of pemivibart in actual living humans. So bear in mind, all around the world, there are laboratories that are attempting to grow either pseudoviral constructs or authentic viral constructs and they try to get them to grow against the backdrop of the renal epithelial cell of an African green monkey, and they asked the question, well, if I make up some home group pemivibart, at what level of dilution does it approach IC50? That is an interesting experiment, and we're always enthused to read early results, but I think that is slightly different than the ongoing highly industrialized march that we engage on in collaboration with FDA. And so I would expect this series of types of observations to continue into the future and we find it of interest, but we really are much more comfortable indexing our own decision making, our communications to FDA and other regulators [indiscernible] that we view as having sufficient rigor to make decisions. And that's I think you will see that process play out here, hopefully over the coming weeks. Does that make sense? Is that a helpful answer?

Yes. I appreciate that they are enough.

I'm not showing any further questions at this time. I'd like to turn the call back over to Invivyd for any closing remarks.

Great. Thank you. Well, look, thank you to everyone for joining us today. We are thrilled with these CANOPY exploratory data and are very much looking forward to the fall season, and we will look forward to, I think, speaking to many of you with any follow-up questions shortly. Thanks again.

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect, and have a wonderful day.