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spk04: Welcome to the InVivid second quarter 2023 business and financial results update call. I will now turn the call over to Gabriela Linville-Engler, Director of External Communications.
spk07: Thank you for joining us today. Before we get started, I want to tend to a few housekeeping items. I invite you to review our press release discussing our second quarter 2023 financial results and business updates, which can be found on the investor section of the InVivid website. I would like to remind you that during today's discussion, we will be making several forward-looking statements. Forward-looking statements include statements concerning, among other things, the future of the COVID-19 landscape, our ongoing research and clinical development plans, including the timing of these plans, our regulatory and commercialization plans, strategies and opportunities, our expected cash runway, and other statements that are not historical fact. Forward-looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially from those expressed or implied in the forward-looking statement, including those described under the heading Risk Factors in our filings made with the U.S. Securities and Exchange Commission, including our most recent Form 10-K. It is now my pleasure to introduce the InVivid management team to the call. I am joined by Dave Herring, CEO of InVivid, and Dr. Pete Schmidt, Chief Medical Officer. I will now turn the call over to Dave.
spk09: Thanks, Gabriella, and thank you to everyone joining us today on our quarterly update call. In Q2, in the recent weeks, we've made significant progress towards our goal of commercializing BYD 222 in the near term and advancing our mission to protect vulnerable people from serious viral threats. Since our last call, we have announced positive initial safety data and robust serum neutralizing titer data from our ongoing VYD222 Phase 1 clinical trial. We believe that the initial Phase 1 results are very encouraging and speak to the potential for VYD222 to provide vulnerable people, such as immunocompromised, with robust protection from symptomatic COVID-19. Shortly, Pete will provide additional color on the initial Phase 1 clinical trial results and our plans to rapidly initiate a 750 participant pivotal clinical trial of BYD222 for the prevention of symptomatic COVID-19 referred to as the CANOPI trial. With the compact size of CANOPI and a primary efficacy endpoint based on the analysis of serum neutralizing titers at day 28, the same biomarker used in our phase one clinical trial, we believe that we can swiftly enroll the trial and generate the clinical data necessary to enable a potential emergency use authorization or EUA submission. We look forward to initiating the Canopy trial in the near term and expect to have initial primary endpoint data by approximately the end of 2023. In Q2, we also announced that we reached general alignment with the FDA on a pathway to a potential EUA for VYD222 and anticipated follow-on candidates designed to prevent symptomatic COVID-19. We are very encouraged by the rapid development pathway outlined by the FDA and the opportunity it provides to leverage our previous work developing Intrabimab to accelerate the development of VYD222. We believe we are one of very few companies positioned to potentially meet the criteria that the FDA outlined for this streamlined development pathway. Importantly, with this pathway, we see a near-term opportunity to bring much needed protection from symptomatic COVID-19 to immunocompromised people. Before I hand the call over to Pete to talk about our plans for the transformational period ahead, I want to briefly underscore three important points. First, the need to protect vulnerable populations from COVID-19 remains as urgent as ever. immunocompromised people continue to be at higher risk for severe COVID-19-related outcomes, and more broadly, COVID-19 continues to be a deadly threat. Roughly halfway through 2023, before we have even entered the fall and winter months, the CDC estimates that more than 43,000 deaths in the U.S. are attributable to COVID-19 this year. That is more than 43,000 deaths where COVID-19 was listed as the underlying cause or a contributing cause of death on the death certificate. For context, consider that RSV is estimated to cause roughly 14,000 deaths per year in the U.S. among the groups at highest risk for RSV, and that pre-COVID levels for flu-related deaths have fluctuated between 23,000 and 52,000 deaths per year in the United States. COVID-19 remains a substantial driver of morbidity as well. The National Center for Health Statistics estimates that roughly one in seven adults in the U.S. have experienced long COVID at some point, which adds to the unique and unacceptable burden of this disease. While many have accepted the status quo and are trying to live with COVID, we continue to argue that all are not living well, particularly vulnerable populations. Second, we believe that protecting immunocompromised people from COVID-19 is a large ongoing need and opportunity. In the U.S. alone, there are an estimated 8 to 18 million immunocompromised people who may not generate robust protection from vaccines. To our knowledge, Invivid is one of very few companies in the clinic now with a monoclonal antibody candidate in development for the prevention of COVID-19 in this population. Consider that Evusheld alone captured $2.2 billion in total revenue in 2022 with strong growth prior to its removal from the market when it lost activity against emerging SARS-CoV-2 variants of concern. In a recent survey we conducted with nearly 200 US physicians who treat different types of immunocompromised patients, 76% of respondents said they would be extremely likely or somewhat likely to use Evusheld for the immunocompromised patients if it were still available and relevant to circulating COVID-19 strains. In the coming periods, we look forward to sharing more insights from the market research we've conducted to further refine our understanding of the different immunocompromised populations and the views of the clinicians who care for the different types of patients who may be chronically or temporarily immunocompromised. Third, we believe that InVivid is uniquely positioned to rapidly and perpetually deliver MAD therapies that can keep pace with viral evolution and protect the vulnerable. our company and our discovery platform are built on the premise that serial innovation will be required to provide vulnerable populations with continuous access to MAP therapies that protect against serious viral threats, a strategy that is similar to the approach used to periodically modify vaccines in response to viral evolution. To anticipate and quickly respond to viral evolution, we are leveraging state-of-the-art viral surveillance predictive modeling, and advanced antibody engineering techniques designed to generate a pipeline of optimized MAP candidates that could be deployed in the future. We see COVID-19 as the optimal starting point for InVivid due to the speed with which products can be brought to the market using the EUA pathway. From there, we believe that our platform could also be applied to protect vulnerable people from other viral threats, such as influenza, an area where we have an early discovery stage program. I will now pass the call to Pete Schmidt, our chief medical officer, to discuss in more detail our initial phase one data, pivotal clinical trial plans, and regulatory pathway.
spk11: Thank you, Dave.
spk09: Excuse me.
spk11: We are pleased to recently share positive initial data from our ongoing phase one clinical trial of BYD222, which enrolled 30 healthy volunteers across three different dosing cohorts. Each cohort, participants were randomized 8 to 2 to BYD222 or placebo. The initial phase one clinical trial data showed that a single administration of BYD222 was generally well tolerated at all three dose levels tested with no serious adverse events reported. As expected, we saw a dose-dependent increase in serum neutralizing titers against Omicron XBB1.5. At the lowest dose tested, 1500 milligrams, the geometric mean serum neutralizing titers were 3,245 against Omicron XBV1.5 at day seven, a geometric mean 39-fold rise from baseline. At the 2,500 milligram dose, the titers were 9,647. At the 4,500 milligram dose, the titers were 16,865. As a point of reference, even the lowest VUID222 dose tested resulted in higher serum neutralizing titers against Omicron XBV1.5 than the titers shared at the recent Vaccines Advisory Committee meeting from investigational, XBB-targeted vaccines that were administered to adults who were not on immunosuppressive treatment. Higher BYD222 doses resulted, as expected, in higher titer levels that were well above those reported vaccine titer levels. Serum neutralizing titer data are meaningful because COVID-19 vaccine and MAP clinical trials including our past Phase 2-3 adentrovimab clinical trial for the prevention of COVID-19, referred to as EVADE, have demonstrated that serum-neutralizing titers are correlated with the prevention of COVID-19. This correlation has also been observed in immune-compromised individuals receiving Evusheld, a MAD that targets the spike protein receptor binding domain of SARS-CoV-2, like VYD222. Based on this correlation, we believe that the serum neutralizing titers seen in our Phase I clinical trial are highly encouraging and support the potential for BYD222 to provide clinically meaningful protection from symptomatic COVID-19. With positive initial Phase I data in hand, we are pleased to have now solidified the design of our canopy trial of BYD222 for the prevention of symptomatic COVID-19, which is geared to support a potential EUA submission. We plan to enroll approximately 750 participants total across two cohorts in parallel. In cohort A, we expect to enroll approximately 300 participants who are significantly immune compromised. This cohort may include, for example, people who are actively being treated for solid tumors, people with hematological malignancies such as acute leukemia or multiple myeloma, regardless of treatment status, as well as other groups of people who have weakened immune systems as a result of a medical condition and or immunosuppressive treatment. All participants in cohort A will receive VYD222 administered via IV infusion, and the co-primary endpoints will be safety and tolerability and serum neutralizing titers at day 28. In this cohort, the primary efficacy analysis will use an immunobridging approach, comparing data obtained in Canopy for VYD222 to certain historical data from our previous clinical trial of adentravimab, in which serum neutralizing titers correlated with observed clinical efficacy. In cohort B, we plan to enroll approximately 450 participants who are at risk for exposure to SARS-CoV-2, which is essentially anyone who has regular unmasked interaction with others. Participants in cohort B will be randomized two to one to receive VYD-222 or placebo administered by IV infusion. In cohort B, the primary endpoint will be safety and tolerability. Secondary and exploratory endpoints will include serum neutralizing titers and clinical efficacy. We plan to initiate the CANOPI trial with a 4,500 milligram dose of BYD222. While we believe that all three doses tested in the phase one clinical trial have the potential to provide clinically meaningful protection against symptomatic COVID-19, We have decided to initiate the canopy trial with the dose that provided the highest serum neutralizing titers against Omicron XBB1.5. This decision was informed by the FDA's preference for a conservative serum neutralizing titer benchmark and the 4,500 milligram dose. We believe this dose has the potential to provide a significant duration of protection while also providing protection against the potential loss of neutralization activity as SARS-CoV-2 evolves over time. For context, based on our own data from Avaid and other clinical studies of COVID-19 maps and vaccines, we believe there is strong clinical evidence that antibody mediated protection against symptomatic COVID-19 may be achieved even at relatively low serum neutralizing titers on the order of 30 to 100. While we believe the 4,500 milligram dose of BYD222 is likely to provide titers well above the minimum level observed to provide clinically meaningful protection for a significant period of time, we are excited to continue rapidly advancing the VUID-222 program while exploring in parallel possible opportunities to leverage other doses in the future. As currently designed, all participants in the Canopy trial will receive a second dose of VUID-222 three months after the initial dose. We plan to use the observed pharmacokinetic data from the trial in combination with the neutralization potency of the UID222 against relevant circulating SARS-CoV-2 variants to modify our redosing strategy as appropriate. With the size and design of Canopy, we believe that we can quickly enroll the trial, given the strong interest we have seen from trial sites and immunocompromised people. To facilitate enrollment in Cohort A, we have established a registry of recruitment-ready immunocompromised individuals for potential enrollment. We now have more than 1,000 potentially eligible individuals in our database, which we believe speaks to the strong unmet need. With clinical sites selected, study drug available, and many other activities already completed, we are pleased to be on track to initiate the Canopy trial in the near term. Shifting to the regulatory pathway, as Dave briefly mentioned, the FDA has indicated that the use of a correlative protection or a surrogate of clinical efficacy in an immunobridging approach to a pivotal clinical trial may be a reasonable approach to support an EUA request for new MAB candidates when certain criteria are met. Specifically, when clinical efficacy data from a prototype MAB is available, provided that one, the new MAB candidate is similar to the prototype MAB, such that it leverages a consistent manufacturing platform and has limited structural and functional differences. And two, the new MAB has supportive non-clinical data, such as favorable in vitro neutralization data against currently circulating SARS-CoV-2 variants. We plan to leverage this immunobridging pathway in the U.S. to accelerate the clinical development of BYD222 and anticipated follow-on MAP candidates, with our previous MAP candidate, Adentrevumab, or future proprietary MAP serving as the prototype MAP. We believe we are one of very few companies that can potentially meet all the criteria and utilize this accelerated development pathway for the prevention of COVID-19. The use of Adentrevumab as the potential prototype MAP is proprietary to InVivit, and enabled by the data from our previous Phase 2-3 clinical trial of Adentrevumab, for the prevention of symptomatic COVID-19, which had clinical event endpoints. In addition to utilizing previously generated adentrevumab data, we plan to use day 28 serum neutralizing titers from the immunocompromised cohort of Canopy, along with safety data from both Canopy cohorts, to enable the clinical data package for a potential EUA submission for BYD222. Looking outside the U.S., we continue to engage with global regulatory authorities regarding the BYD 222 Clinical Development Program. In closing, I'm very pleased with all the progress our team has made, and I'm optimistic about the opportunity we have to make a meaningful difference in the lives of some of the most vulnerable people in our communities. Viruses that typically cause minor illness in immunocompetent people can have devastating consequences for the immune compromise. which leads many of these individuals to self-isolate from their loved ones and miss out on many important moments and activities. For the immune compromised, MAPs have the potential to provide the robust protection from viral threats that they require and deserve. With that, I will turn the call over to Dave to provide an overview of our financials before we open up the call for Q&A.
spk09: Thank you, Pete. The details of our second quarter financials are included in the press release issued earlier today, So I won't reiterate all of the details here. And Vivid ended the second quarter of 2023 with $298.4 million in cash, cash equivalents, and marketable securities. Based on our current operating plans, we expect that our cash, excluding any potential revenue associated with BYD 222, will enable us to fund our operating expenses into the fourth quarter of 2024. As you may recall, in past quarters we guided to the second half of 2024 on runway, but have refined our guidance now that we have finalized the size of our canopy trial. We believe that we are well capitalized to execute on our strategy and create value for our stakeholders. With that, operator, please open the call for questions.
spk04: Thank you, ladies and gentlemen. If you have a question or a comment at this time, please press star 11 on your telephone. If your question has been answered and wish to move yourself from the queue, please press star 11 again. We'll pause for a moment while we compile our Q&A roster. Our first question comes from Maxwell School with Morgan Stanley. Your line is open.
spk03: Hi. Thank you for taking my questions, and congrats on the updates. Just can you elaborate a bit more on the profile of cohort B? Will these patients be vaccinated, unvaccinated, boosted, and how do you plan to evaluate clinical efficacy? Also, did the FDA provide guidance related to how long you have to follow these patients to fulfill the safety requirements? Thank you.
spk11: Hey, Max. Good questions. In terms of cohort B, this is what we call an all-comers cohort. So we really aren't concerned with their vaccination or exposure status. And the clinical endpoints for that cohort will be as they were in evade, so symptomatic disease, anyone who gets symptomatic COVID. In terms of follow-up, we haven't really stated. We'll put those details up on clinicaltrials.gov when we initiate the trials.
spk05: Great, thanks. One moment for our next question. Our next question comes from Evan Wang with Guggenheim. Your line is open.
spk12: Hey, guys. Great to see all the progress for Phase 3. I had some follow-ups on the trial design. It does seem significantly smaller compared to the supernova trial, and I know there's a focus on generating FC data. from FDA. So, you know, is this smaller trial really just driven by the platform? And if you could share more color on, you know, generating some of those FC data. Second, you know, on enrollment and data by year end, can you talk about, you know, what's remaining to get the trial started, confidence in enrollment, and whether you need both cohorts to file for approval? Especially, you know, it seems like it positions you pretty well versus AstraZeneca with their, you know, data by year end. And then, you know, third, just thoughts in terms of the commercial opportunity of this immunocompromised and all-comers. I know the focus there has been on immunocompromised recently, so just wondered if you have updated thoughts on, you know, some of the all-comers commercial opportunity. Thanks.
spk09: So, I'll take the first part of this, and then, Pete, you can, you know, Hang on. So as it relates to the size of the study versus, you know, supernova, I mean, I can't, you know, comment specifically on, you know, why their trial is the size that it is, not knowing that. But I think what's key is, you know, we have started and had these conversations since that December FDA meeting where they had a joint FDA EMA session talking specifically about how to accelerate MAD development in, you know, against COVID-19. And that's where they first started bringing up this prototype concept. You know, and then certainly as we were into our phase one study, we got further detail, which we, you know, put forward in a press release talking about this immunobridging concept and being able to utilize specific data from intramumab. I think, you know, SupraNova has gone through a variety of iterations and clinical trial design, which may have impacted that. I don't really know, but specifically when we look at this, cohort A allows you to get this titer-level data quickly in a small subset of the overall trial, and then cohort B gets you the necessary safety and that you need to pull together to put together a package for a potential EUA. You can talk a little bit, Pete, about starting and enrollment, some of the other pieces that Evan asked about.
spk11: Yeah. And to clarify in cohort B, it's exactly what Dave said. I don't think there's necessarily an intent to pursue a commercial opportunity there. That's really just to provide the supportive safety database. As you can imagine, it's easier to enroll all comers than specifically the immune compromised. And in terms of recruitment and what we expect, I think it goes to what I was saying about this registry we created. So every individual in that registry has identified as immune compromised and has expressed interest in an interventional trial. So we are very pleased to have that ready database of over 1,000 individuals, and we think that a large proportion of them will be very interested in rolling quickly.
spk09: Yeah, the only thing I would add, Evan, is it relates to the commercial opportunity. I mean, we are focused on the vulnerable population, which could be argued to be just about all of us, given the current state of protection and where we are with variants. But that said, our initial focus has always been on this immunocompromised group, folks who have been contraindicated against vaccines, etc., those who are at highest risk for severe outcomes from COVID-19.
spk11: And in terms of activities necessary to initiate canopy, it's largely just the box checking stuff that you have to do before you start a trial. I think we've passed all the major hurdles. We haven't provided specific guidance on when we're going to start, but you can see that we did say we'll release some preliminary primary efficacy endpoint data by around the end of 2023.
spk04: Thank you. One moment for our next question. Our next question comes from Michael Yee with Jefferies. Your line is open.
spk08: Hi, good evening. Thanks for taking our questions. This is Jenna on for Mike. We have two questions, if we may. First question is, at this upcoming year-end readout of initial pivotal data, what are you looking to show and what is the bar? Are you looking to replicate the phase one results, which was already great, or are you looking to show even higher titer levels? And then second question is, from that point forward, What are the key milestones afterwards? And how soon could you expect to be on the market? Thank you.
spk09: Yeah. So, yes. So, from the preliminary data that we're talking about around year-end, it would be similar to what we saw in the phase one. It's the titer values. That said, it will be, you know, based on an analysis for day 28. So, it's, you know, slightly different than the day seven phase one data that we provided there, but similar in terms of we're looking for high titer values. They don't have to be equivalent to the Phase 1s, but based on everything we saw from Phase 1, it's repeating that in this Cohort A and getting some of that preliminary data. And so that would confirm what we've seen in Phase 1 and what we're expecting to see in Canopy. Key milestones after for an EUA submission. You need the clinical data. You need a preclinical set of activity, CMC, et cetera. We believe we can assemble all of that quite rapidly and certainly will provide more information and guidance as we get closer to this clinical information, et cetera. But certainly it's something that we're looking to do as quickly as possible, especially as we're starting to see you know, an uptick in COVID cases, an increase in hospitalizations, et cetera, even prior to the fall and winter season. And so, certainly, it's not lost on us that time is of the essence and, you know, in a situation where there are nomads on the market, one that we're, you know, looking to rectify as quickly as we can.
spk08: Great. Thank you so much.
spk05: One moment for our next question.
spk04: The next question comes from Patrick Truccia with HC Wainwright. Your line is open.
spk13: Thanks. Good afternoon and congrats on all the progress. I have a couple of follow-up questions. The first is just I'm wondering if you can talk about the new COVID variant EG5. What have we seen so far with these cases of COVID-19? How different or similar is this variant to XBV1.5? And would you expect CYD222 to retain activity against this variant?
spk09: Yeah, on the first piece, right, I mean, we continue to see viral evolution. That's, you know, I guess one of the most critical components of the InVivid strategy, right, which is we expect the virus to continue to evolve, which is why we see serial innovation as the answer, continuing to update antibodies, et cetera. As it relates to EG5, we're looking to pull in and get in vitro data on it. But based on what we've seen so far, our belief is that it wouldn't cause a significant activity reduction to BYD222. And so we'll take a look at that now that it's the predominant variant and do some additional confirmatory tests, et cetera. I do think we've seen a progression from the summer into now, which is, like I said, not unexpected. we continue to do a variety of surveillance and predictive modeling on our side and look at mutations specifically, so even before they become specifically designated variants. And so that's how we continue to look at what do we see coming, which ones would we like to start to test against, how we start to bring in assays against those and prepare for different eventualities. That's really, like I said, embedded into how NVivid is structured in our strategy and looking to assess and then respond to the different variants as they emerge.
spk13: Great. And then just a clarification question. Is the expectation to have primary endpoint data from both cohorts A and B at the end of 2023? And, you know, can you talk to us about the potential for government contracts for BYD222, or would this be primarily be commercialized through sort of traditional channels and methods? And then just lastly, can you talk about advantages of BYD222 compared to some of these other antibodies in development for COVID-19? And, you know, what are some of the advantages, you know, perhaps of the dosing schedule or other that you can point to relative to those approaches. Thank you very much.
spk09: I can take government contracts. You want to take first the preliminary data we're expecting from the primary endpoints at the, you know, around the end of the year?
spk11: Yeah, that was a good question. So, our understanding and plan is actually that we don't need the serum neutralizing titer data from cohort B. that group just serves to increase the safety database, the exposure needed for an EUA.
spk09: So the preliminary data you'll see will just be from the immune compromised cohort, which is cohort A. Yeah, and then related to your question about government contracts, based on the current environment and transition, we are not anticipating government contracts as the primary source or really putting much in terms of our commercial readiness related to government contracts. We're preparing for a traditional market, you know, your activities related to reimbursement and payers and, you know, market access, etc. And so that's really the focus of the team now, you know, as we're preparing for a potential launch and being ready for that in a traditional market. That said, a variety of the different acts that Congress took during the pandemic do provide different reimbursements and things, coverage for Medicare, et cetera. And so we continue to look at all of those. So even without government contracts, as we saw during the pandemic, there still is a variety of support that has been put in place for COVID-related products. As it relates to advantages of UID-222, one of the things that we've been saying for quite a while is 222 is a re-engineered version of our original antibody, ADG20. And we did this through an affinity maturation process and did it, you know, looking at the BA1, BA2 backbone of Omicron. And so with a set of slight changes, eight amino acids, we were able to, you know, reestablish binding where ADG20 has lost. came from a SARS-CoV-1 survivor. And so we continue to see that 2, 2, 2 has broad neutralizing activity and is one that we really see as an antibody that to date has not occurred in a natural setting. And so we feel that it provides us a higher probability of duration of activity. And so that's what we continue to look at and test, but we think that's probably the most critical advantage, which is being able to have prolonged activity as our hypothesis for 222. You know, beyond that, we continue to see that by utilizing the adentrovimab, the ADG20 data, that allows this platform as well to be quite a significant advantage. As we said, we see That InVivid is one of a few companies who could utilize existing data that was done previously, and that's quite an advantage as it relates to pursuing EUAs in a much faster fashion than running full clinical endpoint studies, especially given the current environment and looking to recruit patients.
spk02: Great. Thank you so much.
spk04: And I'm not showing any further questions at the time. I'd like to turn the call back over to Dave for any closing remarks.
spk09: Well, thank you all for joining the call today. It's a very exciting time for InVivid as we get closer to milestones that we believe would be quite impactful for patients, our organization, and shareholders. We thank you for your continued support and interest in InVivid, and we will look forward to catching up with any of you individually over the coming days. Thank you so much.
spk04: Well, ladies and gentlemen, that concludes today's presentation. You may now disconnect and have a wonderful day. Hello. We'll be right back. Bye. Welcome to the InVivid second quarter 2023 business and financial results update call. I will now turn the call over to Gabriela Linville-Engler, Director of External Communications.
spk07: Thank you for joining us today. Before we get started, I want to tend to a few housekeeping items. I invite you to review our press release discussing our second quarter 2023 financial results and business updates, which can be found on the investor section of the InVivid website. I would like to remind you that during today's discussion, we will be making several forward-looking statements. Forward-looking statements include statements concerning, among other things, the future of the COVID-19 landscape, our ongoing research and clinical development plans, including the timing of these plans, our regulatory and commercialization plans, strategies and opportunities, our expected cash runway, and other statements that are not historical fact. Forward-looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially from those expressed or implied in the forward-looking statement, including those described under the heading risk factors in our filings made with the U.S. Securities and Exchange Commission including our most recent Form 10-K. It is now my pleasure to introduce the InVivid management team to the call. I am joined by Dave Herring, CEO of InVivid, and Dr. Pete Schmidt, Chief Medical Officer. I will now turn the call over to Dave.
spk09: Thanks, Gabriella, and thank you to everyone joining us today on our quarterly update call. In Q2, in the recent weeks, we've made significant progress towards our goal of commercializing VYD-222 in the near term, and advancing our mission to protect vulnerable people from serious viral threats. Since our last call, we have announced positive initial safety data and robust serum neutralizing titer data from our ongoing VYD222 Phase 1 clinical trial. We believe that the initial Phase 1 results are very encouraging and speak to the potential for VYD222 to provide vulnerable people, such as the immunocompromised, with robust protection from symptomatic COVID-19. Shortly, Pete will provide additional color on the initial phase one clinical trial results and our plans to rapidly initiate a 750 participant pivotal clinical trial of BYD222 for the prevention of symptomatic COVID-19 referred to as the CANOPI trial. With the compact size of CANOPI and a primary efficacy endpoint based on the analysis of serum neutralizing titers at day 28, the same biomarker used in our phase one clinical trial, we believe that we can swiftly enroll the trial and generate the clinical data necessary to enable a potential emergency use authorization or EUA submission. We look forward to initiating the Canopy trial in the near term and expect to have initial primary endpoint data by approximately the end of 2023. In Q2, we also announced that we reached general alignment with the FDA on a pathway to a potential EUA for VYD222 and anticipated follow-on candidates designed to prevent symptomatic COVID-19. We are very encouraged by the rapid development pathway outlined by the FDA and the opportunity it provides to leverage our previous work developing intravimab to accelerate the development of VYD222. We believe we are one of very few companies positioned to potentially meet the criteria that the FDA outlined for this streamlined development pathway. Importantly, with this pathway, we see a near-term opportunity to bring much needed protection from symptomatic COVID-19 to immunocompromised people. Before I hand the call over to Pete to talk about our plans for the transformational period ahead, I want to briefly underscore three important points. First, the need to protect vulnerable populations from COVID-19 remains as urgent as ever. immunocompromised people continue to be at higher risk for severe COVID-19-related outcomes, and more broadly, COVID-19 continues to be a deadly threat. Roughly halfway through 2023, before we have even entered the fall and winter months, the CDC estimates that more than 43,000 deaths in the U.S. are attributable to COVID-19 this year. That is more than 43,000 deaths where COVID-19 was listed as the underlying cause or a contributing cause of death on the death certificate. For context, consider that RSV is estimated to cause roughly 14,000 deaths per year in the U.S. among the groups at highest risk for RSV, and that pre-COVID levels for flu-related deaths have fluctuated between 23,000 and 52,000 deaths per year in the United States. COVID-19 remains a substantial driver of morbidity as well. The National Center for Health Statistics estimates that roughly one in seven adults in the U.S. have experienced long COVID at some point, which adds to the unique and unacceptable burden of this disease. While many have accepted the status quo and are trying to live with COVID, we continue to argue that all are not living well, particularly vulnerable populations. Second, we believe that protecting immunocompromised people from COVID-19 is a large ongoing need and opportunity. In the U.S. alone, there are an estimated 8 to 18 million immunocompromised people who may not generate robust protection from vaccines. To our knowledge, Invivid is one of very few companies in the clinic now with a monoclonal antibody candidate in development for the prevention of COVID-19 in this population. Consider that Evusheld alone captured $2.2 billion in total revenue in 2022 with strong growth prior to its removal from the market when it lost activity against emerging SARS-CoV-2 variants of concern. In a recent survey we conducted with nearly 200 US physicians who treat different types of immunocompromised patients, 76% of respondents said they would be extremely likely or somewhat likely to use Evusheld for the immunocompromised patients if it were still available and relevant to circulating COVID-19 strains. In the coming periods, we look forward to sharing more insights from the market research we've conducted to further refine our understanding of the different immunocompromised populations and the views of the clinicians who care for the different types of patients who may be chronically or temporarily immunocompromised. Third, we believe that InVivid is uniquely positioned to rapidly and perpetually deliver MAD therapies that can keep pace with viral evolution and protect the vulnerable. Our company and our discovery platform are built on the premise that serial innovation will be required to provide vulnerable populations with continuous access to MAP therapies that protect against serious viral threats, a strategy that is similar to the approach used to periodically modify vaccines in response to viral evolution. To anticipate and quickly respond to viral evolution, we are leveraging state-of-the-art viral surveillance predictive modeling, and advanced antibody engineering techniques designed to generate a pipeline of optimized MAP candidates that could be deployed in the future. We see COVID-19 as the optimal starting point for InVivid due to the speed with which products can be brought to the market using the EUA pathway. From there, we believe that our platform could also be applied to protect vulnerable people from other viral threats, such as influenza, an area where we have an early discovery stage program. I will now pass the call to Pete Schmidt, our chief medical officer, to discuss in more detail our initial phase one data, pivotal clinical trial plans, and regulatory pathway.
spk11: Thank you, Dave.
spk09: Excuse me.
spk11: We are pleased to recently share positive initial data from our ongoing phase one clinical trial of VYD-222, which enrolled 30 healthy volunteers across three different dosing cohorts. Each cohort, participants were randomized eight to two to VYD-222 or placebo. The initial phase one clinical trial data showed that a single administration of BYD222 was generally well tolerated at all three dose levels tested with no serious adverse events reported. As expected, we saw a dose-dependent increase in serum neutralizing titers against Omicron XBB1.5. At the lowest dose tested, 1500 milligrams, the geometric mean serum neutralizing titers were 3,245 against Omicron XBV1.5 at day seven, a geometric mean 39-fold rise from baseline. At the 2,500 milligram dose, the titers were 9,647. At the 4,500 milligram dose, the titers were 16,865. As a point of reference, even the lowest VUID222 dose tested resulted in higher serum neutralizing titers against Omicron XBV1.5 than the titers shared at the recent Vaccines Advisory Committee meeting from investigational, XBB-targeted vaccines that were administered to adults who were not on immunosuppressive treatment. Higher BYD222 doses resulted, as expected, in higher titer levels that were well above those reported vaccine titer levels. Serum neutralizing titer data are meaningful because COVID-19 vaccine and MAP clinical trials including our past Phase 2-3 adentrovimab clinical trial for the prevention of COVID-19, referred to as EVADE, have demonstrated that serum-neutralizing titers are correlated with the prevention of COVID-19. This correlation has also been observed in immune-compromised individuals receiving Evusheld, a MAD that targets the spike protein receptor binding domain of SARS-CoV-2, like VYD222. Based on this correlation, we believe that the serum neutralizing titers seen in our Phase I clinical trial are highly encouraging and support the potential for BYD222 to provide clinically meaningful protection from symptomatic COVID-19. With positive initial Phase I data in hand, we are pleased to have now solidified the design of our canopy trial of BYD222 for the prevention of symptomatic COVID-19, which is geared to support a potential EUA submission. We plan to enroll approximately 750 participants total across two cohorts in parallel. In cohort A, we expect to enroll approximately 300 participants who are significantly immune compromised. This cohort may include, for example, people who are actively being treated for solid tumors, people with hematological malignancies such as acute leukemia or multiple myeloma, regardless of treatment status, as well as other groups of people who have weakened immune systems as a result of a medical condition and or immunosuppressive treatment. All participants in cohort A will receive VYD222 administered via IV infusion, and the co-primary endpoints will be safety and tolerability and serum neutralizing titers at day 28. In this cohort, the primary efficacy analysis will use an immunobridging approach, comparing data obtained in Canopy for VYD222 to certain historical data from our previous clinical trial of adentravimab, in which serum neutralizing titers correlated with observed clinical efficacy. In cohort B, we plan to enroll approximately 450 participants who are at risk for exposure to SARS-CoV-2, which is essentially anyone who has regular unmasked interaction with others. Participants in cohort B will be randomized two to one to receive VYD-222 or placebo administered by IV infusion. In cohort B, the primary endpoint will be safety and tolerability. Secondary and exploratory endpoints will include serum neutralizing titers and clinical efficacy. We plan to initiate the CANOPI trial with a 4,500 milligram dose of BYD222. While we believe that all three doses tested in the phase one clinical trial have the potential to provide clinically meaningful protection against symptomatic COVID-19, We have decided to initiate the canopy trial with the dose that provided the highest serum neutralizing titers against Omicron XBB1.5. This decision was informed by the FDA's preference for a conservative serum neutralizing titer benchmark and the 4,500 milligram dose. We believe this dose has the potential to provide a significant duration of protection while also providing protection against the potential loss of neutralization activity as SARS-CoV-2 evolves over time. For context, based on our own data from Avaid and other clinical studies of COVID-19 maps and vaccines, we believe there is strong clinical evidence that antibody-mediated protection against symptomatic COVID-19 may be achieved even at relatively low serum-neutralizing titers on the order of 30 to 100. While we believe the 4,500 milligram dose of BYD222 is likely to provide titers well above the minimum level observed to provide minimum clinically meaningful protection for a significant period of time, we are excited to continue rapidly advancing the VUID-222 program while exploring in parallel possible opportunities to leverage other doses in the future. As currently designed, all participants in the Canopy trial will receive a second dose of VUID-222 three months after the initial dose. We plan to use the observed pharmacokinetic data from the trial in combination with the neutralization potency of the UID222 against relevant circulating SARS-CoV-2 variants to modify our redosing strategy as appropriate. With the size and design of Canopy, we believe that we can quickly enroll the trial, given the strong interest we have seen from trial sites and immunocompromised people. To facilitate enrollment in Cohort A, we have established a registry of recruitment-ready immunocompromised individuals for potential enrollment. We now have more than 1,000 potentially eligible individuals in our database, which we believe speaks to the strong unmet need. With clinical sites selected, study drug available, and many other activities already completed, we are pleased to be on track to initiate the Canopy trial in the near term. Shifting to the regulatory pathway, as Dave briefly mentioned, the FDA has indicated that the use of a correlative protection or a surrogate of clinical efficacy in an immunobridging approach to a pivotal clinical trial may be a reasonable approach to support an EUA request for new MAP candidates when certain criteria are met. Specifically, when clinical efficacy data from a prototype MAP is available, provided that one, The new MAB candidate is similar to the prototype MAB, such that it leverages a consistent manufacturing platform and has limited structural and functional differences. And two, the new MAB has supportive non-clinical data, such as favorable in vitro neutralization data against currently circulating SARS-CoV-2 variants. We plan to leverage this immunobridging pathway in the U.S. to accelerate the clinical development of VYD222 and anticipated follow-on MAP candidates, with our previous MAP candidate, Adentrevumab, or future proprietary MAP serving as the prototype MAP. We believe we are one of very few companies that can potentially meet all the criteria and utilize this accelerated development pathway for the prevention of COVID-19. The use of Adentrevumab as the potential prototype MAP is proprietary to InVivit, and enabled by the data from our previous Phase 2-3 clinical trial of Adentrevumab, for the prevention of symptomatic COVID-19, which had clinical event endpoints. In addition to utilizing previously generated adentrevumab data, we plan to use day 28 serum neutralizing titers from the immunocompromised cohort of Canopy, along with safety data from both Canopy cohorts, to enable the clinical data package for a potential EUA submission for BYD222. Looking outside the U.S., we continue to engage with global regulatory authorities regarding the BYD 222 Clinical Development Program. In closing, I'm very pleased with all the progress our team has made, and I'm optimistic about the opportunity we have to make a meaningful difference in the lives of some of the most vulnerable people in our communities. Viruses that typically cause minor illness in immunocompetent people can have devastating consequences for the immune compromise. which leads many of these individuals to self-isolate from their loved ones and miss out on many important moments and activities. For the immune compromised, MAPs have the potential to provide the robust protection from viral threats that they require and deserve. With that, I will turn the call over to Dave to provide an overview of our financials before we open up the call for Q&A.
spk09: Thank you, Pete. The details of our second quarter financials are included in the press release issued earlier today, So I won't reiterate all of the details here. And Vivid ended the second quarter of 2023 with $298.4 million in cash, cash equivalents, and marketable securities. Based on our current operating plans, we expect that our cash, excluding any potential revenue associated with BYD 222, will enable us to fund our operating expenses into the fourth quarter of 2024. As you may recall, in past quarters, we guided to the second half of 2024 on runway, but have refined our guidance now that we have finalized the size of our canopy trial. We believe that we are well capitalized to execute on our strategy and create value for our stakeholders. With that, operator, please open the call for questions.
spk04: Thank you, ladies and gentlemen. If you have a question or a comment at this time, please press star 1-1 on your telephone. If your question has been answered and wish to move yourself from the queue, please press star 1-1 again. We'll pause for a moment while we compile our Q&A roster. Our first question comes from Maxwell School with Morgan Stanley. Your line is open.
spk03: Hi. Thank you for taking my questions, and congrats on the updates. Just can you elaborate a bit more on the profile of cohort B? Will these patients be vaccinated, unvaccinated, boosted, and how do you plan to evaluate clinical efficacy? Also, did the FDA provide guidance related to how long you have to follow these patients to fulfill the safety requirements? Thank you.
spk11: Hey, Max. Good questions. In terms of cohort B, this is what we call an all-comers cohort. So we really aren't concerned with their vaccination or exposure status. And the clinical endpoints for that cohort will be as they were in evade, so symptomatic disease, anyone who gets symptomatic COVID. In terms of follow-up, we haven't really stated. We'll put those details up on clinicaltrials.gov when we initiate the trials.
spk05: Great, thanks. One moment for our next question. Our next question comes from Evan Wang with Guggenheim. Your line is open.
spk12: Hey, guys. Great to see all the progress for Phase 3. I had some follow-ups on the trial design. You know, it does seem significantly smaller compared to the supernova trial. And I know there's a focus on generating FC data from FDA. So, you know, is this smaller trial really just driven by the platform? And if you could share more color on, you know, generating some of those FC data. Second, you know, on enrollment and data by year end, can you talk about, you know, what's remaining to get the trial started, confidence in enrollment, and whether you need both cohorts to file for approval? Especially, you know, it seems like it positions you pretty well versus AstraZeneca with their, you know, data by year end. And then, you know, third, just thoughts in terms of the commercial opportunity of this immunocompromised and all comers. I know the focus there has been on immunocompromised recently, so just wondered if you have updated thoughts on, you know, some of the all comers commercial opportunity. Thanks.
spk09: So, I'll take the first part of this, and then, Pete, you can, you know, Hang on. So as it relates to the size of the study versus, you know, supernova, I mean, I can't, you know, comment specifically on, you know, why their trial is the size that it is, not knowing that. But I think what's key is, you know, we have started and had these conversations since that December FDA meeting where they had a joint FDA EMA session talking specifically about how to accelerate MAD development in, you know, against COVID-19. And that's where they first started bringing up this prototype concept. You know, and then certainly as we were into our phase one study, we got further detail, which we, you know, put forward in a press release talking about this immunobridging concept and being able to utilize specific data from entremumab. I think, you know, SupraNova has gone through a variety of iterations and clinical trial design, which may have impacted that. I don't really know, but specifically when we look at this, cohort A allows you to get this titer-level data quickly in a small subset of the overall trial, and then cohort B gets you the necessary safety and that you need to pull together to put together a package for a potential EUA. You can talk a little bit, Pete, about starting and enrollment, some of the other pieces that Evan asked about.
spk11: Yeah, and to clarify in cohort B, it's exactly what Dave said. I don't think there's necessarily an intent to pursue a commercial opportunity there. That's really just to provide the supportive safety database. As you can imagine, it's easier to enroll all comers than specifically the immune compromised. And in terms of recruitment and what we expect, I think it goes to what I was saying about this registry we created. So every individual in that registry has identified as immune compromised and has expressed interest in an interventional trial. So we are very pleased to have that ready database of over 1,000 individuals, and we think that a large proportion of them will be very interested in rolling quickly.
spk09: Yeah, the only thing I would add, Evan, is it relates to the commercial opportunity. I mean, we are focused on the vulnerable population, which, you know, could be argued to be just about all of us given the, you know, current state of protection and where we are with variants. But that said, our initial focus has always been on this immunocompromised group, folks who have been, you know, contraindicated against vaccines, etc., those who are at highest risk for severe outcomes from COVID-19.
spk11: And in terms of activities necessary to initiate canopy, it's largely just the box checking stuff that you have to do before you start a trial. I think we've passed all the major hurdles. We haven't provided specific guidance on when we're going to start, but you can see that we did say we'll release some preliminary primary efficacy endpoint data by around the end of 2023.
spk04: Thank you. One moment for our next question. Our next question comes from Michael Yee with Jefferies. Your line is open.
spk08: Hi, good evening. Thanks for taking our questions. This is Jenna on for Mike. We have two questions, if we may. First question is, at this upcoming year-end readout of initial pivotal data, what are you looking to show and what is the bar? Are you looking to replicate the phase one results, which was already great, or are you looking to show even higher, tighter levels? And then second question is, from that point forward, What are the key milestones afterwards? And how soon could you expect to be on the market? Thank you.
spk09: Yeah. So, yes. So, from the preliminary data that we're talking about around year end, it would be similar to what we saw in the phase one. It's the titer values. That said, it'll be, you know, based on an analysis for day 28. So, it's, you know, slightly different than the day seven phase one. data that we provided there, but similar in terms of we're looking for high titer values. They don't have to be equivalent to the Phase 1s, but based on everything we saw from Phase 1, it's repeating that in this Cohort A and getting some of that preliminary data. And so that would confirm what we've seen in Phase 1 and what we're expecting to see in Canopy. Key milestones after for an EUA submission. You need the clinical data. You need a preclinical set of activities, CMC, et cetera. We believe we can assemble all of that quite rapidly and certainly will provide more information and guidance as we get closer to this clinical information, et cetera. But certainly it's something that we're looking to do as quickly as possible, especially as we're starting to see you know, an uptick in COVID cases, an increase in hospitalizations, et cetera, even prior to the fall and winter season. And so certainly it's not lost on us that time is of the essence and, you know, in a situation where there are nomads on the market, one that we're, you know, looking to rectify as quickly as we can.
spk08: Great. Thank you so much.
spk05: One moment for our next question.
spk04: The next question comes from Patrick Truccia with HC Wainwright. Your line is open.
spk13: Thanks. Good afternoon, and congrats on all the progress. I have a couple of follow-up questions. The first is just I'm wondering if you can talk about the new COVID variant EG5. What have we seen so far with these cases of COVID-19? How different or similar is this variant to XBV1.5, and would you expect BYD222 to retain activity against this variant?
spk09: Yeah, on the first piece, right, I mean, we continue to see viral evolution. That's, you know, I guess one of the most critical components of the InVivid strategy, right, which is we expect the virus to continue to evolve, which is why we see serial innovation as the answer, continuing to update antibodies, et cetera. As it relates to EG5, we're looking to pull in and get in vitro data on it. But based on what we've seen so far, our belief is that it wouldn't cause a significant activity reduction to BYD222. And so we'll take a look at that now that it's the predominant variant and do some additional confirmatory tests, et cetera. I do think we've seen a progression from the summer into now, which is, like I said, not unexpected. we continue to do a variety of surveillance and predictive modeling on our side and look at mutations specifically, so even before they become specifically designated variants. And so that's how we continue to look at what do we see coming, which ones would we like to start to test against, how we start to bring in assays against those and prepare for different eventualities. That's really, like I said, embedded into how NVivid is structured in our strategy and looking to assess and then respond to the different variants as they emerge.
spk13: Great. And then just a clarification question. Is the expectation to have primary endpoint data from both cohorts A and B at the end of 2023? And, you know, can you talk to us about the potential for government contracts for BYD222 or would this be primarily be commercialized through sort of traditional channels and methods? And then just lastly, can you talk about advantages of BYD222 compared to some of these other antibodies in development for COVID-19? And, you know, what are some of the advantages, you know, perhaps of the dosing schedule or other that you can point to relative to those approaches. Thank you very much.
spk09: I can take government contracts. You want to take first the preliminary data we're expecting from the primary endpoints at the, you know, around the end of the year?
spk11: Yeah, that was a good question. So, our understanding and plan is actually that we don't need the serum neutralizing titer data from Cohort B. that group just serves to increase the safety database, the exposure needed for an EUA. So the preliminary data you'll see will just be from the immune compromised cohort, which is cohort A. Yeah.
spk09: And then, you know, related to your question about government contracts, based on the current environment and transition, we are not anticipating government contracts as the primary source or, you know, really putting much in terms of our commercial readiness related to government contracts. We're preparing for a traditional market, you know, your activities related to reimbursement and payers and, you know, market access, etc. And so that's really the focus of the team now, you know, as we're preparing for a potential launch and being ready for that in a traditional market. That said, a variety of the different acts that Congress took during the pandemic do provide different reimbursements and things, coverage for Medicare, et cetera. And so we continue to look at all of those. So even without government contracts, as we saw during the pandemic, there still is a variety of support that has been put in place for COVID-related products. As it relates to advantages of EYD-222, one of the things that we've been saying for quite a while is 222 is a re-engineered version of our original antibody, ADG20. And we did this through an affinity maturation process and did it, you know, looking at the BA1, BA2 backbone of Omicron. And so with a set of slight changes, eight amino acids, we were able to, you know, reestablish binding where ADG20 has lost. came from a SARS-CoV-1 survivor. And so we continue to see that 2, 2, 2 has broad neutralizing activity and is one that we really see as an antibody that to date has not occurred in a natural setting. And so we feel that it provides us a higher probability of duration of activity. And so that's what we continue to look at and test, but we think that's probably the most critical advantage, which is being able to have prolonged activity as our hypothesis for 222. You know, beyond that, we continue to see that by utilizing the adentrovimab, the ADG20 data, that allows this platform as well to be quite a significant advantage. As we said, we see That InVivid is one of a few companies who could utilize existing data that was done previously, and that's quite an advantage as it relates to pursuing EUAs in a much faster fashion than running full clinical endpoint studies, especially given the current environment and looking to recruit patients.
spk02: Great. Thank you so much.
spk04: And I'm not showing any further questions at the time. I'd like to turn the call back over to Dave for any closing remarks.
spk09: Well, thank you all for joining the call today. It's a very exciting time for InVivid as we get closer to milestones that we believe would be quite impactful for patients, our organization, and shareholders. We thank you for your continued support and interest in InVivid, and we will look forward to catching up with any of you individually over the coming days. Thank you so much.
spk04: Well, ladies and gentlemen, that concludes today's presentation. You may now disconnect and have a wonderful day.
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