IVVD - NASDAQ

Good day, and thank you for standing by. Welcome to the Q3 2024 Invivyd Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. [Operator Instructions]. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Katie Falzone, Senior Vice President of Finance. Please go ahead.

Thank you, operator. A short while ago, we issued a press release announcing our Q3 2024 financial results and recent business highlights. That press release and the slides that are being used on today's webcast can be found in the investor 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 of Invivyd's Board of Directors and Chairman of the Executive Committee of the Board. He is joined by Tim Lee, Chief Commercial Officer; Bill Duke, Chief Financial Officer; Dr. Robert Allen, Chief Scientific Officer; and Dr. Mark Wingertson, Senior Vice President of Clinical Development and Medical Affairs. During today's discussion, we will be making forward-looking statements concerning, among other things, our corporate and commercial strategies, our research and development activities, our regulatory plans, certain financial guidance, 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 10-Q, which are also available on our website. I will now turn the call over to Marc.

Good morning, and thank you for joining us. The third quarter at Invivyd was marked by a promising start and then an unusual commercial headwind that Invivyd has been managing through since. This headwind is rooted in the academic virology complex, the U.S. FDA, and unfortunately, as a result, reached HCPs in vulnerable populations that can benefit from more protection from symptomatic COVID-19. As a reminder, Invivyd is discovered, developed, and is now commercializing a monoclonal antibody against SARS-CoV-2. This virus is now in its endemic phase, following a pandemic that raged through the immunologically naive human population, but now, in its endemic phase, still causes a shocking quantity of death, illness, and long-term damage even among the young and healthy. While the backbone of population health for COVID-19 remains vaccine boosts, contemporary data from CDC very consistently reveals the limitations of vaccine boosts in terms of the level of protective efficacy a boost can achieve in a human already experienced immunologically from prior vaccination or infection. These limits are universal among humans, although the immunocompromised population who may receive less benefit due to an inadequate immune response to vaccines are more vulnerable and bear an even greater burden requiring additional protection. Fortunately, Invivyd has conducted randomized clinical studies on monoclonal antibodies in both the pandemic phase and now the modern endemic phase of SARS-CoV-2, and the results are unambiguous. A monoclonal antibody can render a major step change in protective efficacy against symptomatic COVID-19 compared to placebo. Unlike modern vaccine boost epidemiologic studies, which reveal about a 40% to 50% reduction in the likelihood of a COVID-19-related hospital stay or urgent care visit for about 60 days, after which benefit fades rapidly, exploratory efficacy data on pemivibart from our CANOPY Phase 3 clinical trial demonstrated in an immunocompetent population an 80% to 90% reduction in the risk of getting symptomatic COVID-19 in the first place, over twice dosing during a six-month period. Invivyd recently shared long-term follow-up data from CANOPY showing that indeed robust protection remains even at low residual drug levels after six months following cessation of dosing, consistent with prior publications and indeed consistent with our overall corporate thesis for scaled monoclonal antibody protection at potential low doses and via attractive routes of administration. Against this backdrop remains SARS-CoV-2 virus genetic variation, a source of fascination and consternation for the academic and regulatory communities, and a major focus of our work internally at Invivyd. SARS-CoV-2 has displayed remarkable genetic mutability, and there exists a substantial cottage industry devoted to describing and considering those mutations. From Invivyd's point of view, as a pharmaceutical company, variation is why we have made a major investment in technology designed to understand and address that variation, and why we select the molecules we select with barriers to resistance in mind. We're all incredibly proud that so far, Invivyd stands alone in both attempting and accomplishing this goal in the contemporary context of a post-Omicron era, utilizing rapid approval pathways in concert with FDA. Pimivibart's longstanding and continued antiviral activity to date is a remarkable scientific accomplishment and one we are eager to repeat with an improved drug profile. Alas, applied virology is an inexact science, all the more inexact outside of an industrial, highly controlled context, and there are many labs globally that seek to understand our molecules using processes and systems of unknown quality and reagents of unknown characteristics. One of those systems and labs has presented an unusual headwind that cast doubt on the activity of our molecule against contemporary lineages, notably KP.3.1.1 observations made at Columbia University over the summer and into the fall. That KP.3.1.1 susceptibility doubt made its way into the U.S. FDA, and disappointingly, the agency broadcast that doubt into the HCP and vulnerable populations via not just fact sheet updates but also email blasts and tweets, or whatever tweets are called now. While the PEMGARDA fact sheet was corrected in late September with robust neutralization data generated through Invivyd's industrial virology effort, Invivyd's opportunity to drive utilization in the late third quarter and into the fourth quarter infectious disease season was badly damaged. Invivyd has been seeking to repair this damage in the end market up to and including News Today, in which the New England Journal of Medicine has published not just a letter to the editor from Invivyd, but also a second piece from this laboratory describing their neutralization results against a lab-made antibody, which had to be corrected at the 11th hour by New England Journal, as you can see online. The piece now describes, “Research grade” pemivibart which is a critical and sadly late emerged distinction. Prior to the New England Journal of Medicine's correction, it was implied that authentic pemivibart manufactured by Invivyd was used in these systems. Invivyd is a science-based company and therefore has a deep respect for the scientific process, but we are also in the business of trying to save lives and believe that the researchers and regulators considering scientific claims ought to exert real caution in making claims about authorized medicines for human use on the basis of rapidly emerging science that may lack appropriate rigor and appropriate control. Meanwhile, Invivyd remains working to drive awareness of a medicine among HCPs that we believe disrupts disease pathogenesis and has been shown to protect vulnerable Americans who are in need of protection against symptomatic COVID-19. Tim Lee, our Chief Commercial Officer, will describe our ongoing efforts and our thinking about building this important category of medicines, and our SVP of Clinical Development and Medical Affairs, Mark Wingertson, will touch on recent CANOPY data that points the way to scaling our work far beyond what we can do with pemivibart as an intravenous medication. More generally, our great hope at Invivyd is that these recent events, our strong and consistent data and upcoming government transition can all present an opportunity for regulators to consider an impressive and growing totality of data that shows quite clearly, one, the test-boost-treat paradigm championed by the current administration as having “Ended the pandemic” has left behind extraordinary ongoing human misery. Two, monoclonal antibody protection, especially when deployed in the contemporary human population on top of immune experience from vaccination or infection, can be a substantial unlock in terms of high levels of protection from symptomatic disease itself. Three, protection at low serum virus neutralizing antibody titers has now been demonstrated by monoclonal antibodies in both the pandemic and modern endemic phase of SARS-CoV-2. And such data can be leveraged to make products that would look and feel rather like a vaccine, for example, intramuscular or similarly convenient administration, but which could be distinguished by high efficacy and durable equitable protection, all without forcing human subjects to encounter the SARS-CoV-2 spike protein in vaccine form and experience associated reactogenicity. And four, companies like Invivyd have been and remain prepared to action these initiatives as soon as key governmental stakeholders are ready. Despite the extraordinary recent circumstances surrounding this company and our ongoing PEMGARDA launch, we have been gratified to see a recent return to product growth. We are pleased with the durability of pimivibart and our next generation antibody VYD2311 in the face of virus variation, and we stand prepared to radically scale the impact of our work near term. With that, I will turn the call over to Mark Wingertzahn, Senior Vice President of Clinical Development and Medical Affairs.

Thank you, Marc. We can turn our attention to Slide 6. The efficacy results from the immunocompetent arm from the ongoing 12-month CANOPY study, as well as the major COVID-19 variant waves during that time are depicted on the current slide. As you may recall, the CANOPY study is an ongoing 12-month clinical study designed to evaluate safety, tolerability, and efficacy of pemivibart for pre-exposure prophylaxis of COVID-19 in adults aged 18 years and older. Participants received two doses of pemivibart infused 90 days apart and then were followed through month 12. The study was conducted from fall 2023 through winter of 2024, making this study one of the few, if only, COVID-19 studies conducted in the contemporary population. Over the entire one-year period, an impressive rate of relative risk reduction from symptomatic COVID-19 was observed with PEMGARDA versus placebo. Strong protection was observed with PEMGARDA over multiple variant waves and lineages of SARS-CoV-2, not only during the active dosing period, but also during the six-month follow-up washout period. During the active treatment period, an 84% relative risk reduction from confirmed symptomatic COVID-19 versus placebo was observed in the immunocompetent arm of CANOPY, also known as Cohort B. A substantial degree of protection remained over month 7 to 12 after cessation of drug during a KP.3 and KP.3.1.1 wave with an overall 76% relative risk reduction versus placebo observed in this cohort over the full 12 months. Reassuringly, the safety profile for pemivibart remained consistent with PEMGARDA fact sheet. The strong protection observed during the washout period is particularly impressive given the low residual titer levels, and while there are no head-to-head trials, we believe that protection can follow from fewer doses of antibodies than the doses of vaccine boosts that would be required to get protection for immunocompromised persons who are unlikely to mount an adequate immune response to the COVID-19 vaccine. If we turn our attention to Slide 8 and take a look at our pipeline, as you know, we've identified VYD2311 via affinity maturation of pemivibart against XBB lineage viruses in an effort to improve on the biophysical properties, including in vitro measured potency. Potency improvements in measured IC50s for an antibody can translate directly to lower doses that are required to achieve meaningful levels of sVNA titer, the Pharmacodynamics variable that drives protection and efficacy for a COVID-19 antibody. These lower doses may in turn allow for the development of routes of administration that are more patient and system-friendly than intravenous approaches. The first in-human study with VYD2311 began at the end of August and is interrogating intravenous, intramuscular, and subcutaneous dosing to provide flexibility and optionality for achieving titers from one antibody could be suitable for both COVID-19 prevention as well as treatment. We are currently assessing authorization pathways and plan to discuss thresholds in light of the CANOPY 12-month clinical efficacy and safety data with regulators and look forward to reviewing our progress with VYD2311 at our next earnings call. I will now turn the call over to Tim Lee, our Chief Commercial Officer. Tim?

Thank you, Mark, and good morning. Turning to Slide 10, the third quarter began commercial transformation. It is my first full quarter at Invivyd and I'm excited to share some of the foundational work that we've built to serve the immunocompromised community. I came to Invivyd because of our mission to serve people who are immunocompromised. This community is made up of fighters, people who are battling cancer, people who have received an organ transplant or bone marrow transplant, have a primary immunodeficiency, advanced HIV, and are actively being treated with high-dose corticosteroids. These are all conditions that can lead people to being vulnerable to an opportunistic virus that causes systemic damage and is why in 2024, approximately every nine minutes, a person in the U.S. dies with COVID-19. COVID-19 continues to be the leading cause of hospitalization and death from respiratory infection in the United States. Protecting this community is a noble mission and I'm proud to be a part of it. Turn to Slide 11. Data from the CDC shows that ICU admissions for all Americans are greater this season than last, clearly demonstrating that COVID continues to have a lasting impact. Turning to Slide 12, you can see that COVID can cause systemic damage with no organ system spared from its impact. Turning to Slide 13, it is with the immunocompromised community in mind that we are building our commercialization plans. We fought through real headwinds through the month of September as the PEMGARDA fact sheet was updated to include reference to third-party data that was not reflective of PEMGARDA's neutralization activity for the immunocompromised community as Mark alluded. Clinicians and patients, more importantly, were confused by these data. Putting this behind us, we have focused on our mission to serve the immunocompromised community at scale. We're partnering with community and independent infusion centers along with academic centers and integrated delivery networks to increase sites of care for this community. We're developing a digital presence and recently conducted our first speaker program during IDWeek in Los Angeles. We're bringing the sales team from a contract field force to direct hire and believe it's the right decision to serve this community. We believe now is the right time to structure this team and it will better serve our future growth. We're excited to be investing in patient support programs to ensure there's a smooth access for patients who are prescribed PEMGARDA. We're investing in field reimbursement management team and building a federal account team with a focus on immunocompromised veterans and their families. We've also added an inside sales team with a focus on rheumatology and are impressed by the early results. Turn to Slide 14. Those actions along with, as you can see, growth across all launch metrics are positioning us to serve the appropriate immunocompromised community at a larger scale. With that, I'd like to turn the call over to our Chief Financial Officer, Bill Duke, for final remarks prior to Q&A.

Thank you, Tim. Turning to Slide 16, as you may have seen, at the end of October, we pre-released our Q3 results, including PEMGARDA net product revenue of 9.3 million in Q3 2024 and September ending cash of approximately 107 million, which is consistent with the results reported this morning. Further, we noted that we expect to finish 2024 with 65 million or more in cash and cash equivalents. At the same time, we went through the guidance of 150 million to 200 million of net product revenue, and we guided to earlier this year, citing recent headwind from U.S. FDA late Q3 2024 warning on potential for substantially reduced activity of hemorrhoids through the PEMGARDA fact sheet and other media based on a contested third-party preprint reflecting biologic activity data from a non-pneumothorax antibody, as has been noted. As Tim mentioned, we are excited about PEMGARDA's potential to reach appropriate immunocompromised patients. As such, we are targeting near-term profitability with existing cash and cash equivalents, anticipated growth of net product revenue, and various operational efficiency improvements underway. The good news is that we previously recorded as research and development expense a significant amount of inventory in preparation for the emergency use authorization submission. As we have managed the significant supply of PEMGARDA and do not plan for significant further manufacturing expense in the near term, with continued modest net product revenue growth, we expect that we will return profitable by the end of June 2025. I will now turn the call over to the operator to open the call for questions.

Thank you. [Operator Instructions]. Our first question is going to come from the line of Maxwell Skor with Morgan Stanley. Your line is open. Please go ahead.

Great. Thank you, everyone. Can you provide any additional color on the treatment EUA for PEMGARDA if you received any feedback from the FDA? And also, the reason I understand for pulling guidance, but what would give you confidence in providing guidance again? Should we expect it at the end of the year, early next year? If you can walk us through the thought process there, that'd be great. Thank you.

Hey, Max. Good morning. Why don't I start? This is Marc, and then I'll see if anyone from Invivyd else wants to chime in. Firstly, on the treatment EUA application, we have been in the process of updating it timely. This is a bridging analysis, as defined by the FDA, and so we have taken our opportunities, as our virology has evolved, to update analytics and make sure that those analytics are in front of them. We've not heard anything explicit about it, other than, I think, a general statement that the FDA is aware of our perspective on all of these various issues, and we'll be rendering some feedback and thoughts to us on that and a multiple of topics soon, so we shall see and stay tuned. On the topic of confidence and guidance, I think, look, we are forced to project into the future. When we project into the future, we draw heavily on the recent past, and I think if PEMGARDA revenue were to grow in a fashion consistent with the recent past, inclusive of a very, very difficult period in the late summer, early fall, we feel very good about our prospects for meeting that, and indeed, of course, it involves two dimensions, right? The rate of revenue growth and our ability to manage our expenses, which is part of what Bill was alluding to. So, I think in this case, what we are indexed toward is that the guidance conception doesn't require some, bolus, as it were, of seasonally driven revenue. It would now embrace the simple continuation of trend. So, we obviously feel as though we have exited the majority of the period embracing confusion, certainly on the activity of PEMGARDA against KP3.1.1, and feel good about our ability to drive from here forward, and I guess, just to add to that, I would ask Tim to comment a little bit on what he has seen over recent weeks.

Yes, thank you, Marc. I think we're very pleased with the trend and the growth that we're seeing, and I think that's all in light of kind of the checklist that I presented of all of the things that we're doing right now up to and including bringing in our sales team, increasing a digital presence, and working to increase access at independent infusion centers, as well as academic infusion centers and integrated delivery networks. And so I think as I look at where we are, in the activities that we're putting into place right now, very excited about what that will mean.

Great, thank you.

Thank you. And one moment as we move on to our next question. Our next question is going to come from the line of Michael Yee with Jefferies. Your line is open. Please go ahead.

Hi, good morning. Thanks for the updates. Two questions on revenue. Can you help us understand while you expect steady growth or growth based on the metrics you're disclosing, are we talking about significant stepwise increases month over month, or are we talking about modest growth? And to that extent, how does that change in the first quarter and the second quarter? I think there's a perception of seasonality, but maybe you think differently because of the population and whatnot. So help us understand the fourth quarter and then what that looks like in first and second quarter. And then on the OpEx, of course, the natural question is that has to change as well in order to hit profitability. So is that expected to be significant declines in R&D over the next few quarters? Because I think what you said was that you don't expect a significant manufacturing campaign. Thank you.

Hi, Mike. Good morning. And I'll ask Tim to comment a little bit more on revenue and Bill on OpEx. But let me just start by saying what you might have read already in our press releases is that we have begun the process already of modifying our base burn. And clearly, those areas on which we will not ever compromise and indeed might allocate incremental spend would be our commercial presence. R&D is a topic that has to, by definition, flex with what is occurring with the company clinically. We are coming off of CANOPY spend. We are not yet arriving at a registrational spend for 2311. And as Bill alluded to in the past, we have expensed manufacturing largely through R&D. So you would have seen organically or rather would see organically anyway some change in our overall burn. We're simply looking to tighten that up and accelerate that reduction in burn. But why don't I ask Bill to comment a little bit further on that and then turn it over to Tim.

Sure. I think Marc highlighted the key points here. With regards to manufacturing spend, of course, we've manufactured at risk a significant amount of PEMGARDA prior to EWA and then continued to produce PEMGARDA throughout this year. At this point in time, we've substantially completed the manufacturing runs and the expenses associated with that, which will not necessarily be repeated as we go forward in 2025. I think that's one of the most significant elements that you can look at from a reduction of spend. With regards to 2311, we have also continued. We have also done manufacturing for 2311 in 2024. Those expenses have flowed through R&D expense for this year as that has not yet been submitted for EWA. So as a result, as that winds down, we will also see relief to the P&L through R&D as we go forward in 2025. Just other streamlined expenses, of course, we are investing heavily in commercial. We will continue to invest on commercial. But that being said, I think the largest thing that you can see is the drop on the R&D expense side.

Yes. Great question. I think as we look at our recent activity at IDWeek in Los Angeles in the conversations that we've had with the infectious disease clinicians in their community, as well as individual meetings, seasonality is not a construct that I think is something that we're hearing even from some of the largest independent infusion networks across the country. People who serve those fighting cancers and other conditions that I mentioned earlier. And so as we look at the opportunity to serve this group, seasonality doesn't affect those people who are on different therapeutic regimens that will impact their immune system. I think as we look at who our core is, it is people who are fighting for their life because of cancer therapies, because of an organ transplant, because of a hematopoietic stem cell transplant, and others. And those conditions and therapeutic regimens don't know seasonality. And I think protecting them is what we're gearing up towards. And excited to say from a breadth in account utilization, we're pleased with that. Our opportunity is to drive depth through increased access. And that's what the team has been. One of the many things in the checklist that I went through earlier that the team has been solely focused on is fighting for this community to have access to something that will protect them, as I said, from a virus that is looking to cause systemic damage.

It's probably worth my adding, Mike, just for the clarification of all of our vocabulary, right? We use terms like seasonal because there is a perception in the HCP community that infectious disease and certainly respiratory infectious diseases have, you know, “season”. And certainly back in the summer, we were looking to take advantage of that dynamic as we went to large scale. COVID-19 disease, SARS-COVID-2 is not seasonal at all. It's ever present, pervasive, and presents with periodic waves, right? The periodicity of the wave, it might be biannual or triannual or frankly, we may have yet to see what a true equilibrium looks like. I think a part of what Tim is getting at is that at the scale we are reaching right now, which in our view is very small, I don't know that we would see any particular effect of seasonality because we are so early in our growth. But I think it's also fair to say that as we scale a business, it would be natural and rational to have some relationship to at least periodicity. And while it may be confusing, we may from time to time, and certainly HCPs and the vulnerable may refer to seasonality, but I think it's too early to worry or wonder about Q4 into Q1. I think the point that Tim is trying to convey is that from a growth standpoint, we feel so young and so early in our penetration into the highly vulnerable population. I don't think we believe we've yet achieved the scale where those kinds of dynamics will come to the fore, but we'll all have to find out together.

Thank you.

Thank you. [Operator Instructions]. Our next question is going to come from the line of Jason Kolbert with D. Boral Capital. Your line is open. Please go ahead.

Good morning. Thank you very much. Yes, I saw the R&D number came in very high, but it corresponds, I'm sure, almost one-to-one with the inventory bills which showed up on the balance sheet. My question is, what is the real -- what is the commercial value of that inventory on the balance sheet? It's obviously substantially higher than what you're carrying at.

Yeah, Bill can comment a little bit. In general, I don't think we want to get into the level of specifics that would reveal sort of temporary net pricing by implication, but let's just say it this way. Invivyd has produced or is wrapping up production of well in excess of hundreds of millions of dollars of product inventory in revenue terms, and the accounting of that I think will flow through in the coming quarters as diminished spending. Bill, would you add anything to that?

No, I think that's very well stated. Part of the reason for that discrepancy between what Marc has said for the market value and what we're carrying at is don't forget that we expense a large amount of PEMGARDA costs prior to EUA granting of the EUA. So, costs that were incurred as we led up to the EUA to the point that those inventory amounts have not yet been sold through remain on our balance sheet. So, that's a piece of why the discrepancy between our inventory balance on the balance sheet and what the market external value would be as those inventory amounts are sold through.

Thank you very much. I just want to ask you kind of a probing question. When you look at how to engineer a more potent or next generation formula of PEMGARDA and even potentially moving from IV to IM or sub-Q, what do you scientifically have to do? How do you make those changes? Can you give us some insights into your process?

Yes. And look, this is Marc. Your bad luck is that -- wait. Actually, Robby is logged in. So, he will be able to rapidly clean up whatever I tell you that he feels is off base. But the reality is we've already done that work and it's well manifested in our next generation molecule VYD2311, right, which is in – it's first in human study right now. What we effectively do is avail ourselves of a vast combinatorial library that can interrogate spike protein and offer up hits almost in the manner of if you're familiar with small molecule chemistry screening, right? And so, we can select antibodies with enhanced biophysical properties by screening combinatorial libraries against spike protein that is, let's say, more and more contemporary. And in doing that, what we discover is that we are able to substantially enhance our potency with very modest changes to the overall structural identity of pemivibart, and which is indeed itself not so, so different structurally than adintrevimab. So, you might even think of it as a process of directed molecular honing in which we are continuing to interrogate what appears to be a pretty enriched site on the spike, which should not be surprising given the foundational hypothesis of the company, right, that there are these territories on spike that are essential for ACE2 access and therefore essential for viral fitness, and we wish to exploit that via monoclonal antibody. Now, that is easier said than done and involves a lot of technological tricks and sort of trade secret, as it were, in our approach. Other companies do not have access to those sorts of technology stacks and approaches. So, we feel particularly proud of having done this work now on our third cut. But to the extent that I've glossed it over in simplistic terms, feel free to follow up with Robbie, or Robbie, by all means, correct anything --

So, I think that the description that you provide embraces the answer to the question that was asked, definitely, in terms of how we go about doing this. The one thing I will add is that we are equipped in the laboratory to do this at any time, and we do it all the time. And so, we are constantly updating our working knowledge of how antibodies are acting against current variants and looking into future space using the technologies that we have to assure ourselves that antibodies will maintain activity to meet the target product profile that we've described and enabled through PEMGARDA and will enable through 2311 and on. So, hopefully, that helps with your question.

Yes, you actually answered my follow-on question, which is, it sounds like the platform is going to ultimately show utility beyond PEMGARDA and COVID.

Yes, I think that particularly in situations where we have dynamic targets that have conventionally required a great deal of a periodic vaccine effort, or even a monoclonal antibody effort, we have an ability to address those types of dynamic targets that is borne out through the work we've done in COVID. So, that's very true.

Great update. Thanks so much, everybody.

Thank you. [Operator Instructions]. Our next question comes from the line of Patrick Trucchio with H.C. Wainwright. Your line is open. Please go ahead.

Good morning, team. This is Luis Santos standing in Patrick. I would like to ask a follow-up question also on VYD2311 regarding the regulatory authorization paths and lessons learned. So, would there be a need for separate trials for treatment or prevention, or based on the PEMGARDA fast track, would there be a possibility that a new way could be approved for both treatment and prevention? I'm just thinking about if there's an accelerated path for 2311? And then I have a follow-up question.

Thanks. So, the short answer is stay tuned. And these are topics of active consideration certainly at our end, and we believe at FDA as well. It's important to remember that the treatment EUA application discussed and submitted in collaboration with the FDA indeed drew upon the same clinical data generated for our PrEP authorization, right? At some level, a sVNA titer is a sVNA titer conferred by a given antibody. And, in vivid benefits from prior work with that intrepid map, which generated strong data from randomized controlled studies demonstrating high clinical efficacy in the both treatment and PrEP. And indeed, those clinical benefit signals were conferred by the identical antibody at the identical dose in the identical route of administration. So, we feel very confident scientifically that our work with pemivibart and certainly our work with 2311 represents the deployment clinically of very attractive antiviral titers. And you sort of step back and ask yourself, how controversial a concept could this even be pharmaceutically, right? I don't think there are many people left on earth who wonder whether or not having some measure of antiviral activity, either when you are worried about encountering viral inoculum out in the community, or when you are experiencing active infection, I think we universally regard that as a good thing. And so, I think we're in the business of passive prophylaxis with novel monoclonal antibodies generally, and we would eagerly await to be in the business of treatment of active SARS-CoV-2 infection, particularly among immunocompromised persons in an outpatient context. We believe we can do those things. Now, because we make novel antibodies, I think it is also safe to say that we and the FDA would jointly wish to assess the safety of these molecules in a reasonable and some of that data we have previously Press Released as a function of our discussions with FDA. And having done those things, we would look at the operative science and think to ourselves, well, my goodness, if we are bridging to predicate antibodies or if we are availing ourselves of more general concepts like a correlative protection, some of which you can read hot off the presses this morning in The New England Journal of Medicine, there are surrogates, which is, of course, the classical strategy for advancing rapid drug development and authorizations and or approvals. And so, I think what pens on 2311 is we are currently gathering our in vivo first in human experience. We wish to assess safety and in vivo pharmacokinetics in operative human subjects through a variety of routes of administration. And then we will very much look forward to discussing those data with the FDA and in effect dialoguing on how much residual uncertainty really remains in the category. I guess I'll pause there and ask Mark if you can add anything to that.

No, no, it was well said. I think that we enjoy the as you mentioned, we enjoy the fact that, the immunobridging concept that was employed for prevention is also directly able to be extrapolated to the treatment paradigm as well. So, it really is one effectively, as you can imagine, exposure study, getting PK levels as tighter levels and employing that versus the relevant variants at the time to make sure that, our monoclonal antibody has protection across, the current as well as, with our embedded tools within and vivid our future, the future variant landscape.

That makes a lot of sense. And regarding the follow-up question, it was, will this decision of a potential treatment and prevention rapid approval, will that depend on discussions of a tighter threshold? In other words, if the path to approval and say prevention reaches a very high convincing, compelling, tighter threshold, then maybe you can be more confident about an approval, rapid approval in treatment as well. And when can we have, when do you expect to have that first readout for titers?

Great. So, again, Mark can add some detail, but I think we are in the process, of course, of doing the clinical work required to generate that profile in human subjects right now at 2311. As it goes to tighter levels and confidence, I think our confidence is more or less unwavering for now about 2.5 years. Right? So, in vivid employees previously published a lovely relationship in science, translational medicine, showing antibody efficacy in a PrEP context down to very low titers. And you would have seen us very recently reminding ourselves and indeed the world and I think the FDA that that concept is generalizable. And I think we believe evergreen across all SARS CoV-2 variants because we see that relationship repeat itself in our long term CANOPY follow up. So, there's an aspect to the residual uncertainty here in which any reasonable person can say, well if some antiviral titer is good, more is always better. The challenge, of course, is that that's not necessarily the pathway to an equitable, scalable a category of medicine. Right? So, if we have a, a hunger problem this Thanksgiving, I can solve it by getting you a good meal or I can try to solve it by asking you to sit and eat three turkeys. You will be full and potentially satisfied either way. The latter strategy, which is the strategy of seeking a very high dose and a very high titer, may leave a little bit to be desired in terms of the scalability and advisability of that strategy. So, I think our view would be knowing that 2311 is, at least as we see it, a term maybe a good term, more potent than Cambodia part would be to assess the pharmacokinetic profile, see how long of a half life we have, calculate those titers and, really reflect those titers against the totality of evidence that we've seen so far, right? So, the pemivibart immunobridging pathway to a data point drawn from the EVADE study, that is one data point, and I think a total of 12 clinical observations from the year 2021. We now have a wealth of data, including data from a contemporary context, and frankly, we're looking forward to someday seeing a publication of the Astra

Thank you. That makes a lot of sense. Absolutely. Thank you.

Thank you. And I would now like to hand the conference back over to Marc Alia for closing remarks.

All right. Thanks everybody for joining us today. And indeed, it's an opportunity to reflect on what we hope has been a very unusual period in our corporate history. We are available all day for questions and answers. And again, we'll just get ourselves back to the business of trying to, grow our core business and scale protection as fast as we can to as many people as we can. Thanks again. Bye-bye.