Day, and thank you for standing by. Welcome to the Invivyd Topline LIBERTY Data and VYD2311 Next Steps, September 29, 2026. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star one one on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Katie Falzone. Please go ahead.
Thank you, operator. A short while ago, we issued a press release announcing an update on our LIBERTY phase III study and VYD2311 regulatory submission plans. That press release and the slides that are being used on today's webcast can be found in the Investors section of the Invivyd website under the Press Release and Events and Presentation sections, respectively. Today's discussion will be led by Marc Elia, Chairman and Chief Executive Officer of Invivyd. He is joined by Dr. Michael Mina, Chief Medical Officer and Chief Epidemiologist of Invivyd. During today's discussion, we will be making forward-looking statements concerning, among other things, our 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 and 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 and Form 10-Q, which are also available on our website. I will now turn the call over to Marc.
Good morning, and thank you all for joining us. Today marks the beginning of a new chapter for Invivyd, and we hope for vulnerable people at risk of COVID everywhere. We are very pleased today to report the top-line data from our LIBERTY phase III study and to provide you with an update on our development and regulatory plans for 2311 going forward. I'll ask Dr. Michael Mina, our Chief Medical Officer, to walk you through the highlights from LIBERTY, and then I'll discuss our next steps for VYD2311. But first, let me provide a little bit of background for today's discussion. If we can move to slide four. As you all know, Invivyd has been in the business of making monoclonal antibodies for COVID for now six years.
We're currently commercializing the parent medicine to VYD2311, pemivibart or PEMGARDA, which is authorized under Emergency Use Authorization for the prevention of COVID among certain immunocompromised persons. PEMGARDA, you may recall, is a high dose of antibody delivered via one-hour infusion, includes a two-hour post-infusion monitoring time, carries a boxed warning for risk of anaphylaxis, requires quarterly dosing, and is overall a bit too burdensome for easy, routine access. All of that is poised to change for the better. The promise of monoclonal antibody technology in our hands was not intended to result in a burdensome medicine. The promise of our technology has been to allow most any human being, and especially the vulnerable, such as immunocompromised persons, children, and the elderly, to access immune power that is improved compared to what their own immunobiology can summon, and to do it safely, simply, and easily.
The goal of such products is to help people who choose them to stay well, and to do so without incurring some of the hardwired intrinsic downside of requiring the inflammation and antigen exposure from infection or vaccine to get an immune education that may only offer low-level short-term protection. Remember, all human beings are born immune-compromised and full of monoclonal antibodies we get from our mothers. Pharmaceutically, however, to this day, only babies have reliable access to monoclonal antibody supplementation to prevent infectious disease through nirsevimab or Beyfortus. In our view, it's time for that to change. Allowing humankind routine access to direct immune supplementation can be a revolution in the prevention of important viral diseases. While LIBERTY is the first and the smaller of our two clinical studies that are driving VYD2311 toward commercialization, it's an important first step. Next slide, please, to five.
Today's LIBERTY data provide an important new window into the clinical profile of VYD2311, a low-dose intramuscular monoclonal antibody that is designed to prevent COVID-19. We remind everyone listening that VYD2311 previously underwent long-term first-in-human evaluation, the results of which we reported last June. That first human clinical experiment stress-tested safety and tolerability at doses far above those we believe are required to confer protective immunity, and the results were very reassuring. It also followed subjects over the long term of 180 days in order to generate a robust assessment of pharmacokinetics and estimated half-life. Today's LIBERTY data build on those initial findings and set the stage for the more definitive placebo-controlled DECLARATION data coming soon.
Before Michael discusses the LIBERTY data, I'll remind everyone what the study is and is not designed to show, as I know many listeners who are also investors may be trying to make inferences about DECLARATION or other topics from today's LIBERTY data. The LIBERTY study had a specific purpose, in part informed by questions posed to us by the U.S. FDA with joint input from CDER and CBER. First, we wanted to compare the COVID-19 vaccine safety and tolerability to VYD2311, and we are very pleased with our highly positive and statistically significant results. Note, there is no placebo arm in LIBERTY, and the study collected adverse events in a solicited manner, different than our prior studies and different than DECLARATION, which is designed similarly to the AE collection methods of our previous EVADE and CANOPY studies.
Because of LIBERTY's specific design, we do not know the adverse event profile associated with ordinary life in the study that would typically be seen in a placebo arm. However, our earlier work with VYD2311's similar low-dose intramuscular monoclonal grandparent molecule, adintrevimab, was very encouraging on this point, and we are looking forward to our DECLARATION data so we can all see that comparison. We are feeling very confident based on all of the data we have seen so far. Second, we and the FDA wanted to understand whether combining VYD2311 and COVID-19 vaccine would present any new safety challenge. Clearly, it does not. Indeed, by contrast, appears to drive clinical safety and tolerability outcomes in a much more favorable direction, maybe more favorable than many of us would have dared to expect, and we are very pleased with those results as well.
Third, we and the FDA wanted to understand whether the combination of VYD2311 and COVID vaccine would somehow reduce or interfere with the immunogenicity results one could achieve from vaccination alone. It does not, and as you might imagine, our highly positive results on that front are also very gratifying. What LIBERTY was not designed to do is to provide an early read-through to DECLARATION. The design of LIBERTY does not provide quite the right data, either virologically or pharmacokinetically, because of course it was built for a different purpose. Fortunately, what we do see is very encouraging, and we should have the data we want from DECLARATION very soon. A last caveat, LIBERTY also cannot be used to determine any clinical meaning about the vaccine immunogenicity results, either from the vaccine alone or the combination.
We in the field lack the necessary clinical correlates in this assay, and indeed in others, to make confident estimates of vaccine efficacy on this basis. However, it is readily apparent that however well the neutralizing antiviral titers from the COVID vaccine work clinically, adding VYD2311 in combination sure makes for much higher neutralizing titers. Someday, we hope both VYD2311 and the COVID vaccine can be broadly available, and either we or other groups can do the clinical research necessary to find answers to these fascinating questions about relative clinical protection or head-to-head efficacy. What we do know is that VYD2311 has generated what we see as an extraordinarily attractive comparative profile relative to the widely used standard of care used in millions of Americans annually, which is currently selling billions of dollars in revenue.
We believe our LIBERTY data point clearly to advantages VYD2311 can have in helping humans at risk for COVID acquire immune supplementation via a new mechanism that operates beyond the limits of vaccinology. Finally, with these data, along with data we anticipate near-term for the DECLARATION study, we are looking forward to bringing VYD2311 to vulnerable Americans as fast as possible. To that end, we have been working hard with regulators and the federal government, including up until recently, to articulate the pathways required to move VYD2311 forward to vulnerable Americans, which I know we will discuss much more shortly. Some of these conversations and associated processes are behind the requirement to modestly delay our DECLARATION results on the order of weeks from our original guidance, and we hope you will bear with us as we move forward in our work to accelerate the program more broadly.
We are very excited to share the results of LIBERTY with the FDA and the broader scientific community. Beyond all of our interest today in the mechanics of moving VYD2311 toward approval and market, today's data underlines some of the unique and positive attributes that we think can underpin a whole new field of preventative medicine in infectious disease based on Invivyd monoclonal antibodies. With that, I will turn the call over to Dr. Michael Mina, our Chief Medical Officer, to walk you through the top-line data.
Thanks, Marc. We will move to the next slide. Let me begin by quickly reviewing the design of the LIBERTY study, because as Marc noted, it is critical to remember what findings the study was designed to support. Next slide. Here is the general scheme of the study conduct. We randomized 210 healthy adult subjects into a double-blind, active- controlled study such that each subject received one of 250 mg of VYD2311, a standard mRNA-based COVID-19 vaccine, in this case COMIRNATY, or the combination of the two. Subjects in the single-arm studies received a volume-matched placebo injection, such that every subject received two intramuscular injections in the study on opposite arms. Next slide. As a healthy adult volunteer population, the baseline characteristics are unremarkable.
Next slide. The co-primary endpoints we measured are described in more detail here and capture the key safety and tolerability profile of VYD2311 versus mRNA vaccine over the short term, specifically the first six days, which is of course the period most associated with burdensome vaccine reactogenicity. We also show the key secondary endpoints that describe safety and tolerability of each approach over a longer term of 56 days. Of note, and as we disclosed, there is no incidence of hypersensitivity or anaphylaxis in any of the study arms, consistent with our expectations for a low-dose monoclonal antibody.
Some of you may recall that FDA asked Invivyd to monitor for incidence of myocarditis or pericarditis associated with the COVID-19 vaccine arm. We did not expect to see any in this study given its small size, and indeed, there was no incidence of myocarditis or pericarditis in any arm of the study.
What we do observe here is a significantly more favorable profile for VYD2311 compared to COVID-19 mRNA vaccination. At the top level, VYD2311 administration presents a much lower overall burden of adverse events than COVID-19 vaccination over six days. Further, VYD2311 presents a much lower burden of systemic symptoms than vaccination, such as headache, chills, and fatigue, over the same six-day follow-up period. Finally, the overall safety and tolerability advantage of VYD2311 compared to COVID-19 vaccine holds up over the full 56-day evaluation period. We note that all of these comparisons are associated with strong statistical significance. These data do not include a placebo arm, and any comparisons of VYD2311 versus placebo will have to wait for upcoming DECLARATION data. But these, in addition to our prior phase III studies, leave us feeling very confident going into that readout.
Next slide. Of note, we observed that the addition of VYD2311 dosed concomitant with COVID-19 vaccination, which we describe as the combination of the two, may actually be improving the tolerability of vaccination itself. Such a finding is particularly impressive and might be of real clinical significance, particularly if VYD2311 is improving the tolerability of the vaccine without negatively impacting the expected vaccine-derived neutralizing titers. I will get to that important finding in just a moment. Next slide. This slide provides a visual overview of the relative performance between the arms on multiple endpoints. The story is remarkably consistent across these top-line data cuts. I would like to draw your attention to the overarching pattern that is on display here. Firstly, each row is a categorization of adverse events from any events, including the most mild up towards the top, moving down to grade three and above at the bottom.
On the x-axis is the proportion of individuals with those categories of adverse events. As you can see, across all cuts of adverse events, including by severity, the monoclonal antibody skews to the left, sometimes very far to the left, compared to the vaccination alone. This is particularly notable for injection site reactions, which remarkably had a risk difference of greater than 60% in the vaccination-only arm compared to the monoclonal. While ISRs might seem a minor consideration, for those contemplating immunization receipt, the experience is important for willingness for redosing in the future. Also, I draw your attention to a very interesting, significantly lower proportion of participants with systemic events within the combination monoclonal plus vaccine arm compared to the vaccine-only arm, whereby it appears that VYD2311 may actually be drawing down the systemic adverse events associated with the vaccine.
Next slide. You might be asking if the improved tolerability and safety of the combination vaccine arm plus monoclonal is happening at the expense of an appropriate vaccine response. For example, an immunological interference by the monoclonal. We anticipated this question. To measure the potential for immunological interference, Invivyd performed a very elegant experiment. We developed an approach to very selectively and efficiently remove VYD2311 from a human blood sample, thereby enabling the third-party laboratories we work with to isolate and measure specifically the relative immunological contributions of vaccine in VYD2311 to virus-neutralizing titers. For the curious among you, we used an anti-idiotype antibody that complexes with VYD2311 and pulls it out of solution. Next slide. The results of the interference experiment are presented here both in quantitative terms and as a visual depiction of the resulting immunogenicity change when VYD2311 is dosed concurrent with vaccination.
As you can see on the left side, the addition of VYD2311 to COVID-19 vaccination substantially adds to the vaccine-induced neutralizing titers, driving a very impressive fold increase in total neutralizing titers compared to COVID-19 vaccine alone. This is exactly as we would predict, knowing that Invivyd's goal is to provide humans with more immunological power than a vaccine could elicit. To ensure that the vaccine, in the presence of VYD2311, works as designed without interference from the antibody, on the right side, we removed VYD2311 using the approach I just described and reanalyzed all of the samples. The result is exactly what we would expect from no interference. Essentially identical curves from the immunogenicity elicited by vaccine and immunogenicity elicited by vaccine when in combination with VYD2311 after removal of the antibody.
Combined with the safety and tolerability data, the net of these data highlights an intriguing result with potential clinical importance that subjects receiving both COVID vaccine and VYD2311 monoclonal antibody together could, simply from having a second intramuscular injection, ultimately experience a safer and more tolerable COVID-19 vaccine immunization with very high combination titers. Indeed, our experience at Invivyd has been that there are many, many people who do not wish to become sick with COVID, who are pleased to be able to access and use COVID-19 vaccines, and who may indeed wish to pursue such an option. We'll look forward to discussing these data with regulators as we move forward. As we mentioned in the press release, our VYD2311 monotherapy immunogenicity results are underpowered and preliminary and therefore not well reducible to formal analysis.
Nonetheless, when we look at the results, they are entirely encouraging, and we are excited to review them in the context of DECLARATION data coming just around the corner. Next slide. To summarize our findings from LIBERTY, the results demonstrate a substantial advantage for VYD2311 compared to mRNA vaccine. Such a result is highly encouraging, and indeed it is a rare privilege to understand how an investigational medicine compares on safety and tolerability to current standard of care so early in the product life cycle. Our hope is that data such as these can better inform vulnerable people, healthcare professionals and care teams, regulators, and policymakers on the importance of novel immunization strategies. With that, I'll turn the call back to Marc to discuss our progress on regulatory.
Thanks, Michael. I'll now turn to our next steps of VYD2311. As we've said publicly, we've been working now for over a year to build a regulatory pathway suitable for our work that has never existed before, but perhaps such a pathway is overdue. Let me begin this way. COVID-19 is the first opportunity we are aware of in which the two different centers within the U.S. FDA may contend with alternative routes toward achieving immunization in the same population. As many of you know, in 2003, the FDA moved therapeutic or so-called in vivo antibodies from CBER over to CDER, while leaving the vaccines at CBER. So now two different centers regulate products intended for the same preventative purpose in identical populations. CBER covers vaccines, which are more complicated biological objects, and CDER covers monoclonal antibodies.
It's been rare for these centers to contend with products and processes that would appear to so overlap, and therefore, to contend with what can be divergent habits and practices with regards to immunization. For now years, we have argued to CDER that accelerated approval based on antiviral titers is the most appropriate mechanism for approving novel monoclonal antibodies from Invivyd. Why? There are three elements worth discussing. First, to achieve timely patient access. Accelerated approval does not lower an evidentiary bar. It changes the sequence of evidence generation. Accelerated approvals rest on the effects of a surrogate that is reasonably likely to predict clinical benefit. A sponsor like Invivyd is then required to confirm that clinical benefit, and the FDA has the authority to withdraw approval if that benefit is not confirmed. This allows vulnerable people to access safe and effective medicines timely rather than waiting for them.
The pathway exists for serious conditions in which waiting for clinical event data, for example, could leave vulnerable populations unprotected. Of note, use of the accelerated approval pathway has recently been used for an mRNA-based flu vaccine. Indeed, CBER today maintains a guidance that describes accelerated approval as a route for COVID vaccines on this basis. CDER has never developed such guidance for monoclonal antibodies. Second, the accelerated pathway addresses the vagaries of COVID attack rate, the one risk in infectious disease trialing that is outside of sponsor control. Moving confirmation of clinical benefit via clinical event accumulation to a post-approval setting allows for much more focused, rational accumulation of clinical events in the face of variable epidemiologic conditions. Therefore improves the overall feasibility of acquiring sufficient disease events for well-powered demonstrations of clinical outcome benefits.
Third, we have available to us right now a dispositive, functional, scientific surrogate that we can use with high confidence to consider for accelerated approval in this context, our serum virus neutralizing antibody titers. This surrogate marker has, in Invivyd's hands alone, characterized quantitatively clinical benefit across multiple placebo-controlled RCTs, including in prophylaxis, post-exposure prophylaxis, and even treatment of COVID. When we say functional with regards to the surrogate, we mean that not only is the surrogate quantitatively correlated to clinical benefit, we mean that we are directly measuring the actual driver of clinical benefit, the ability of our medicine to neutralize virus. As many of you know, PEMGARDA was authorized under EUA, which carries the evidentiary standard of "more likely than not" to confer clinical benefit. Such authorization rested on exactly similar immunogenicity concepts.
In the time since, of course, Invivyd and FDA have both monitored the antiviral titers created by pemivibart through all of the virology data Invivyd generates, transmits to the FDA, and which is presented on the PEMGARDA EUA fact sheet. Not only is the surrogate functional and dispositive of pharmacologic effect, the surrogate we are interested in is in daily clinical use, is used by the FDA to monitor and steward our medicines, and would be used by the FDA to remove our medicines if activity was abolished. Therefore, is already in their minds a functional surrogate in ordinary daily use. For many of the foregoing reasons, as mentioned, CBER actually created a guidance for COVID-19 vaccines that includes accelerated approval for all of these reasons.
We see that the logic underneath that guidance holds even more for monoclonal antibodies, which are not just simpler, better characterized medicines than a vaccine. They are indeed in large part the biologic effector species one is trying to get from a vaccination itself. Next slide. Our view is that our monoclonal antibodies are functionally identical at the level of virus neutralization and therefore clinical benefit. VYD2311 is just the latest in a series of closely related monoclonal antibodies from Invivyd. Adintrevimab, pemivibart, and VYD2311 share the same epitope and the same binding and neutralization interface. They differ by only a handful of amino acid residues we evolved to optimize performance as SARS-CoV-2 evolves, and they are otherwise identical.
We also note that by contrast to the COVID vaccines, Invivyd has generated controlled data demonstrating reduction in PCR- positive symptomatic COVID-19 versus placebo in both ancestral seronegative populations from the 2020 timeframe against pre-Omicron viruses in the EVADE study, but also in modern seropositive American populations against Omicron lineage viruses in CANOPY. The CANOPY result matters a lot to us because it demonstrated the value of monoclonal antibody prevention of COVID in exactly the virus and population backdrop we see today. Seropositive Americans facing Omicron lineage virus. DECLARATION will of course add yet more data for this unique antibody lineage. You will note that these X-ray crystallographic images of our different antibodies shown with each study are actually all bound to different virus variant RBDs, from original Wuhan virus through Omicron XEC.
In other words, these images look as different as we can make our antibodies look when bound to target. What do they look like superimposed? Next slide, please. Here are all three superimposed. You can see from this image the same thing we see at Invivyd when we think about our antibodies. We are very hard-pressed to tell them apart geometrically, functionally, or indeed even visually when bound to target. While we modestly evolve just the parts of the mAb that drives the binding and neutralization interface, the remainder of the antibodies are identical. Their measured neutralization across now dozens and dozens of virus lineages are consistent, and indeed, their binding geometry and interaction with target is identical structurally and visually. In short, the structural basis for why we believe the clinical benefit from one of our antibodies carried over to the next is embedded into these images.
This picture alone provides a striking contrast to what we are able to know and understand about vaccine responses from one antigen to the next. We believe that we are offering regulators and the scientific and medical community far more information and clinical context about our updates to our antibodies than could ever be derived from a vaccine. Next slide. In this slide, you can see how we've used our clinical data to develop the quantitative link between our neutralizing titers and clinical benefit that define our predictive surrogate. Our antibodies have provided us with data we have peer-reviewed and published as quantitative correlates of protection analyses that we see as predictive of clinical benefit for a new, functionally identical antibody such as VYD2311. This sort of material, among much more, was the focus of a recent Type C meeting with the U.S. FDA.
Next slide. That meeting addressed all four considerations that bear on the suitability of accelerated approval for VYD2311, and indeed, in that meeting, we asserted that the standard had been met and exceeded. Given the calendaring of that meeting, we are not yet in possession of the FDA's final minutes, but as is customary, we have submitted our own minutes, and in those, we faithfully recorded that we could not identify an area of scientific disagreement between the U.S. FDA and Invivyd. What comes next? Next slide. Well, in light of all this, we are moving forward with all speed possible toward vulnerable Americans at high risk for progression to severe COVID-19.
As we previously described, to us, what lies immediately ahead is the DECLARATION study, which we believe will offer yet more definitive placebo-controlled safety and immunogenicity data that we expect to provide a very attractive basis for regulatory consideration of accelerated approval. With DECLARATION in hand, if supportive, we will therefore submit our BLA as soon as possible. Stay tuned for more refined estimates on process and timing as we move forward. Third, we will continue our commercial preparation for VYD2311 so that, if successful, we can provide Americans with an option once the PEMGARDA EUA winds down next summer. We hope you will stay tuned as we move through that result in the coming weeks, and we will now look forward to taking your questions. Operator, you can open the line for Q&A.
As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile our Q&A roster. Our first question comes from the line of Josh Schimmer of Cantor. Your line is open, Joshua.
All right. Congrats on these great results. Thanks for taking the questions. Have three. If I may first, are you going to be able to comment on the blinded event rate in the DECLARATION study when you report the immunogenicity and safety study? Number two, can you elaborate on the potential use of the combination therapy VYD2311 with the vaccine in the real world? What are the implications in your mind of these findings, and why would anyone want to add a vaccine to VYD2311? Last, commercially, with PEMGARDA annualizing around $55 million per year, can you talk about some of the headwinds that that product faces? How do you expect VYD2311 to perform commercially on a relative basis, particularly if it winds up with a similar indication for immune-compromised patients? Thank you.
Thanks so much, Josh. Let me start, and I may invite some colleagues to add and help out. I guess I will go a little bit backwards in order. You think of the PEMGARDA journey as maybe containing headwinds. We see these as just hardwired facts of product form. We are in the unusual position of having a new antibody that can look, at the molecular level, almost identical, but carries a vastly different product profile associated with it, right? There are probably 100-year-old cars that have four wheels and a steering wheel, but they bear very little resemblance to what you can go out and buy today. I think the jump from a PEMGARDA to a VYD2311 is a step change in a category that I do not think anyone has really had the privilege to contemplate in quite a long time.
From administration to the time associated with administration, the setting associated with administration, the fact that it is not an approved product, pemivibart is under Emergency Use Authorization and is therefore investigational. It has, as we noted, a boxed warning for anaphylaxis. We would expect all of that to invert rapidly, and for VYD2311, by contrast, to be functionally interchangeable, in effect, with mRNA vaccination if we are so fortunate to achieve regulatory success. I could not see it as more night and day, and perhaps after I finish, some of my colleagues or Dr. Mina will jump in, but I think we could not be looking forward more to moving to something as straightforward as an intramuscular injection. As we establish the regulatory pathways and the correlates that we are working on, of course, down the road, we are tantalized by other possibilities, right?
There is no reason we cannot consider a subcutaneous version of VYD2311, you could do at home. We actually trialed subcutaneous VYD2311 in our first in-human. It has been on our minds. I think this is a process as we build a category, we are going to try to prize, I think what I said just now on the call, is ease and simplicity. That is the goal. On the use of the combo in the real world, I think we are just in the early days of even contemplating that. Our CCO, Tim Lee, is actually here in the room with us, although he was not introduced, unfortunately, so he will remain silent until he cannot take it anymore, and then he will jump in.
But I think we do have some fairly good market research data that we have been considering on this point, in which if we were to present people with target product profiles of what we think VYD2311 is, and what we think a COVID vaccine is, about 85% of respondents choose the monoclonal antibody. Let us just start there. We see this as intrinsically attractive on its own. We think we have very good data, both clinically and from a consumer preference standpoint, that highlights what an attractive option VYD2311 is on its own. But we are highlighting this potential for combination because, A, it is scientifically very interesting, and B, because of a comment that Dr. Mina made on the call, which is this.
You are going to be surprised, I think, and I think persons who run disproportionately young and healthy are sometimes surprised the lengths to which people will go to avoid becoming infected with COVID-19. Those people are not irrational. They are vulnerable. Some of these people have either been hurt badly by the virus themselves. Some of them have lost loved ones, including recently to the virus. Some people are suffering from long COVID themselves. While that may seem like a very small portion of the overall American population, I think we are all going to be surprised by how many people actually want the most protection they can gather. Let us see how it plays out. It is very early for us to suggest that there is some consumer preference we can understand, but I think we are intrigued by the data.
Finally, when we've been in a position to comment on a blinded event rate overall, I think that has been in the context of a formal analysis on powering. Should those circumstances present, we would of course be tempted to communicate as we normally do. But right now, we don't have the ability to commit to it as it is an ongoing study, and particularly that cohort will remain a blinded ongoing study. I think what we have said in the past absolutely still stands. If you'll recall, the lead-up to this call was really about what is the delicate balance we're trying to walk here between moving toward definitive data as fast as possible and not wanting to make a decision that's both irrevocable and unknowable going into it. Once we unblind that cohort, those are the numbers, maybe forever associated with VYD2311.
We have seen from time to time, persons and companies trialing an infectious disease live with results that are even just a bit marginally underpowered, and it forever colors the journey of that medicine. I think we are a little bit averse to taking those sorts of risks, mainly because when we look at VYD2311, we see an extraordinary opportunity for providing protection to the vulnerable, for moving a whole field of medicine forward, for adding rigor and quantitative discipline to a field that is a little bit, I think, desirous of that. In short, there are actually big important things to keep in mind that relate to the future of this medicine. We don't want to jeopardize those needlessly. Now, just very quickly, I would point out we are pretty experienced trialists in COVID. I think our company now in its third RCT.
I think it is very clear to us experientially that when there is a wave of COVID around, events accumulate duly. When there is not a wave around, they do not. Such an observation is the furthest thing from surprising. But I think what you will notice about the pathway we're choosing is it is built to accommodate uncertainty. That doesn't mean it's designed to put off definitive results. It simply means we want to navigate the accumulation of evidence in the most efficient way possible. Let's see how the next fall, winter unfolds. There may be real opportunities to acquire statistical power very quickly. There may not be. What I think we're saying is we don't want to ask vulnerable people to wait for those circumstances to present in order to access what we see as a very high-quality potential medicine.
I guess, Dr. Michael Mina, since you're here and contemplating all that that I just said, anything you would add on the clinical commercial side?
Yeah. I think we know that individuals' response to the vaccine portends their willingness to be in receipt of vaccines in the future. I think the only piece I want to reemphasize as we think about why people might want to get both products in the future, if what we have found in LIBERTY continues to hold, and we expect it will, where an individual in receipt of both products actually has a reduced reactogenicity profile to the vaccine. I think that that is going to really pique a lot of people's interest to be able to be protected on two different fronts. You may have noticed that in the slide with the neutralizing titers, we saw significant enhancement of neutralizing titers when in combination of our mAb plus the vaccine neuts.
I think people are going to be looking at the label and looking at the type of data that will come out in the future, and say, "Why not gain greater protection?" Especially if it doesn't come not just not come with a toll of additional reactogenicity, but actually improves the side effect profile of the vaccine. I think that there will be many, many individuals who are looking for added protection, though we are also confident that the monoclonal alone will be great.
Thank you very much.
Our next question will be coming from the line of Tom Shrader of BTIG. Your line is open.
Good morning. Congratulations on all the data. I am not sure if I am being a little dense here, but the confirmatory trial is just to follow DECLARATION longer and not add patients? If that is correct, what does it do to your endpoint? They are only going to hit 30 days once. I understand it would argue for efficacy, but does it change your endpoint, or am I missing something?
Well, Tom, I am a little worried you might be missing something, or at least inventing something new. I think you referred to the confirmatory study, which sounds fascinating, but we do not operate it, and I am not aware of what that is. Give me another shot [crosstalk]
Confirmatory trial underway. So, is confirmatory trial underway?
Oh. Okay. No. The confirmatory cohort that we have in mind is simply, you can view it in your mind's eye as a continuation of the blinded clinical part of DECLARATION. Recall, DECLARATION is actually a 90-day period.
Yeah.
What I think we will do, and it is a little early, we are sort of finishing up these ideas right now, is we would simply create the circumstances under which we feel as though we can have that cohort available to deploy in the face of real epidemiologic attack. Go back in time a year, or a little bit more even. When we designed DECLARATION, we designed it to catch all the events we would want pre-regulatory filing, right?
Yeah.
But we are left a little short after a summer in which COVID decided to misbehave, so we do not feel overpowered for the low end of our efficacy range or indeed below. How do we handle that going forward? What we do is we add more subjects. You might recall, we performed one upsize in April--
Yeah.
--of earlier this year. All we really think about it, meaning to us, and maybe we are not being sufficiently clear externally, all we are thinking about is in effect what you could imagine as another upsize that goes into the exact same infrastructure, the exact same trial, has the exact same considerations, but allows us to consider without sort of a clock being stopped, meaning we are able, we believe, to go get those exposures while we are moving toward the commercial space and indeed in it. Right? So what we are trying to do is to accomplish that powering within the same study structure with a larger N. Just to be clear, it would be another quantum of subjects. We have not decided how many yet. We are still working on those final details.
But the plan would be to use the immunogenicity and safety to move forward towards filing and towards commercialization, and then in parallel, get the events we require to feel very, very good about statistical powering. Right? So actually, you would find this is a concept that is not unfamiliar, for example, in, of all places, vaccinology, right? Where certain companies, and indeed our treasured colleagues to the northeast who operate an mRNA platform, are considering right now how to think about an accelerated approval for a flu vaccine on the basis of immunogenicity that they will then go confirm in a clinical outcome context. The advantage Invivyd has is, I think, just the feasibility tailwind of already operating that study, already having it stood up. So to us, it is an opportunity for another cohort of DECLARATION. That is all we meant. Does that make sense?
Yeah. I got it. Yeah. Through the ongoing randomized means the same plan, not the same trial. I was confused. I can ask a follow-up. Slide 13 is beautiful. It is really amazing result. Does it give you the ability to estimate your efficacy? Your fall-off is the same as the vaccine. You know how good the vaccine is. There is published data. You have 2.5x as many antibodies. Can you predict your efficacy, and is it quantitative enough that you think you can say what they see at two months, we would see at five months? Do you think you can extract that kind of data, or is it not quite that quantitative?
Yeah. I think we have far better sources than these data to do exactly the analysis you are proposing. Just to be clear, I do not know that we would ever say the fall-off is the same, nor do we think we can isolate VYD2311 from these data specifically. Let me say it a little bit differently. When we see full pharmacokinetics and both measured and calculated titers from DECLARATION, I think we will feel very good about doing that analysis that you are proposing, and we would do it actually not based on data like these compared to vaccine. We would do it on the basis of published correlates of protection. For example, the two analytics that are referred to, and forgive me, I have forgotten the slide title, but further on in the presentation are two different quantitative takes on exactly that.
Indeed, you might remember, numbers like those are exactly how we articulated our target product profile for VYD2311 of 70%-90% reduction in symptomatic COVID. Math like the sort of math we are able to observe, but maybe not formalistically infer from LIBERTY, it is all supportive of the thesis you are describing. But actually, we see far, far more robust sources already in the public domain.
I would say, as a general matter, and I am sure some of our enterprising and clever investors have already noticed this, if you are interested in calculating titers, you can use some certain numbers that have been public from Invivyd for a very long time to consider what is the dose, what is the measured half-life, what are the published by Invivyd or even estimated sometimes by other labs, although we do not really have a view on the reliability of those other values. What are the IC50s and what titers pop out? I think no matter how you look at the situation, what emerges is something really compelling. I think it is very reasonable to assert that very potent Invivyd antibodies delivered around the doses we deliver them are very likely to generate meaningful clinical benefit.
These curves don't actually add so much to that story, but I agree with you, they're very pretty, and a different point that they're making is extraordinary, which is wonderful to see. But I think all we're doing today is we're adding a lot of really critical information that's adjacent to the main point you're making, but in toto is, I think, remarkable, comforting, and I think bodes well for our progress and our next steps.
All right. Great. Thanks for all the details.
Our next question will be coming from the line of Patrick Trucchio of H.C. Wainwright. Your line is open, Patrick.
Good morning. This is Luis in for Patrick, and congratulations on all the progress. Thanks for taking our questions. The question that I have is a follow-up on the previous question on DECLARATION. Will it need additional enrollment or follow-up to function as a confirmatory trial? If not, what analyses will be disclosed in October that will support the filing? I have a follow-up.
Sure. No, I don't think it would need anything a bit longer. Again, 90-day demonstration of clinical benefit is, I would just remind anyone, in excess of any placebo-controlled demonstration from a COVID vaccine. It nicely embraces a very, very meaningful part of the pharmacokinetics while not being complete. Under most of the titer scenarios we calculate from circulating viruses recently, you would expect clinical benefit from our antibodies probably out to a year. In a multi-dose context, certainly more. I don't want us to get too tripped up on how this is all going to play out. Not much will change, but for our need and our desire to add more human subjects to catch more clinical events. The rest is pretty consistent.
What we are looking forward to very much out of DECLARATION is to see placebo-controlled safety, which again, for any novel antibody, is a really important contributor I would say, into its overall clinical profile and intended medical use, and I suspect regulators will be very interested in that data. From an immunogenicity standpoint, we're also looking forward to confirming something that is very well indicated here in LIBERTY, but not rigorously quantitated, which is this. If you know we have a highly active, highly potent anti-SARS-CoV-2 antibody that we routinely measure in vitro, is it surprising when we dose it in vivo and we find out, meaning we administer that antibody to patients and gratifyingly, we're still able to detect very high potent neutralization ability of that human clinical sample? I guess it depends on how much you know about this stuff to know whether that's surprising.
I think people who know more know that it's not surprising. We would expect when we dose a really potent antibody, we see really potent antiviral effects in human serum. That's great. If what people are thinking is, well, maybe not a lot of this sounds so controversial, and all we need to do now to finalize the entirety of the full forevermore regulatory docket is to assign a number to those values, a clinical benefit number, we would agree with you. In fact, we think this is about the least controversial conceit in modern pharmaceuticals in some ways because, remember, we are all encouraged to vaccinate justifiably. The basis on which we're asked to vaccinate for COVID-19 relates to very similar immunogenicity data generated in approximately cohorts of 10 mice a piece.
That's delightful data, and none of us have a particular issue with interpreting the immunogenicity of a vaccine. What I think Invivyd's point has been, both to the world, to HCPs, to vulnerable patients, and indeed to regulators as well, how gratifying and lovely it is to contemplate that same serum neutralizing titer in hundreds to thousands of real humans. That's the process we've begun. We intend to finish it pretty quickly. Net, we're thrilled that it's to people, I guess, obvious. I'm not implying that you've said that. I'm just saying I think we're commonly in receipt of that point from investors. We would agree. It's obvious and it really should be done. It's a job that should have been done, I think in our minds long, long ago. We're just thrilled to get going. But have I answered your question?
Absolutely. The follow-up that I had is what will determine the dose regimen or regimens that you are planning for the initial filing? Will you have to wait for that DECLARATION data, or you already have something in mind?
No. I think the dose regimen would be what it will be from base DECLARATION, and we would not expect that to change. Here is the way we designed DECLARATION with this in mind. We built the target doses based on two principles, the kinds of antiviral titers we want that we think can confer clinical benefit at level X, Y, or Z, and an ability to reach for more if vulnerable people want it. So recall, in DECLARATION, there is a single- dose arm, and then there is a multi-dose arm that involves three doses a month apart. We are not going to demonstrate this phenomenon in DECLARATION. However, you can imagine that what it begins to point to is what happens if you take an antibody more frequently, what happens if you take an antibody less frequently. If they are both safe approaches, you will get more protection.
Estimated, certainly, and if we had sufficient powering, we may see a between-arms difference quantitatively. I doubt it would achieve statistical significance in between the two active arms unless we were quite impressively overpowered, but I do not think we expect that. I think we are trying to make a broader point to people in the clinical and commercial space going forward. Today, you are encouraged to take a vaccine in the fall. You know it will last a couple of months. You do not really know when you are going to see COVID, and that every time you take that vaccine, you earn some measure of tolerability and safety penalty.
Well, we are going to try to dramatically lower the tolerability and safety issues associated with dosing, and we are going to try to elaborate all of the antiviral benefits of increasing the dose, right, which would be more protection.
If you want to know how much more protection, interestingly, you actually can go right to the literature to I always get this wrong. It is [Yalcin] et al., and I think it is called Immunologic Statistical Correlates of Protection for COVID-19 Monoclonal Antibodies or something like that. We did not have a really hotshot New York editor help us with the title to make it catchier. What it does do is it lays out the actual curve that you can use to calculate the titers we are going to get. So what we are really doing over the longest possible arc here is we are going to try to empower individuals with the ability to make whatever choice works best for them. So what will you see in October? Well, we believe you will see randomized, placebo-controlled safety of a single dose and repeat dose.
We believe you'll see some combination of calculated and possibly measured serum titers of a single dose and multiple doses. Those data alone provide you with extraordinary insight compared to standard of care. Extraordinary. We are actually bringing a level of quantitative rigor to this field that doesn't exist. It's asserted to sort of exist, and I think that's great, but I think we're going to advance the art substantially, and I think when you see all the data and you think about how you might behave, you'll get a pretty good portrait for how we believe people facing these options in the future might behave if these medicines are approved.
Excellent. Thank you so much, and congrats on the progress.
Thanks a lot.
We have no further questions. This concludes today's conference call. Thank you for participating. You may now disconnect.