This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk03: Thank you for standing by and welcome to the InVivid 2022 year-end financial results update call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question at that time, please press star 11 on your telephone. As a reminder, today's call is being recorded. I will now turn the conference to the host, Kira Faircloth, Vice President, Advocacy and Corporate Communications.
spk02: Please go ahead.
spk14: Thank you for joining us today. Before we get started, I want to attend to a few housekeeping items. I invite you to review our press release discussing our full year-ended December 31st, 2022 financial results, 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 including the expectation of its continued evolution and emergence of new variants and sub-variants, our ongoing research and clinical development plans, including the timing of these plans, as well as the technology and resources to develop therapeutic or preventative options for COVID-19 and other infectious diseases, our regulatory and commercialization plans and opportunities, and 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 statements, including those described under the heading risk factors in our filings made with the U.S. Securities and Exchange Commission, including our most recent 10-K filed earlier today. It is now my pleasure to introduce the InVivid management team to the call. I am joined by Dave Herring, CEO of InVivid, Dr. Pete Schmidt, Chief Medical Officer, Dr. Lucas Dillinger, Interim Head of Discovery and Preclinical, and Fred Driscoll, Interim Chief Financial Officer. With that, I will turn the call over to Dave.
spk10: Good afternoon, and thanks for joining the call. We are looking forward to sharing with you financial results from this past year, along with highlights of significant progress we made during this past quarter. For those who may be new to the InVivid story, We are on a mission to rapidly and perpetually deliver antibody-based therapies designed to protect vulnerable people from the devastating consequences of circulating viral threats, beginning with SARS-CoV-2. The foundation of our mission is based on three key factors. One, COVID is here to stay and represents an unacceptable medical burden on humankind. Two, the medicine cabinet to protect humanity from COVID is alarmingly limited. And three, we are uniquely positioned to keep pace with viral evolution and provide therapeutic options to people who urgently need them. We have reached a stage where SARS-CoV-2 is circulating unchecked amongst the broader population with as many as 85% of people in the U.S. having been infected. The vaccination rate for boosters is exceedingly low compared with rates of the primary series. Recent reports highlight that only 28% of the eligible people have now received the most recent COVID-19 booster. People are being infected and reinfected while the virus continues to evolve. Every day, 250 to 400 families in the US lose a loved one to COVID-19. And COVID remains the third leading cause of death behind only heart disease and cancer. While most of society has accepted the status quo and are trying to live with COVID, We would argue that all are not living well, particularly vulnerable populations. Although the immediate impacts of COVID-19 on many healthy adults appear mild, the long-term consequences remain unknown. Preliminary data reported by the Mayo Clinic show that COVID-19 infections are linked to long-term complications that impact numerous body systems, including pulmonary, renal, neurological, and gastrointestinal complications. Additionally, vulnerable populations remain at an increased risk of severe disease, resulting in hospitalization and even death. Immunocompromised patients alone in the U.S. represent between 8 and 20 million individuals, depending on how their status is classified. The threat we are facing from COVID-19 is constantly changing as viral evolution has continued through Omicron sub-lineages. In fact, hundreds of new variants have been identified in the U.S. in the last five months. This continual viral evolution mandates that drug discovery and development must keep pace. However, as of January 2023, there are no longer any monoclonal antibodies for the treatment or prevention of COVID-19 authorized in the U.S. We consider this market an open opportunity for InVivid to target near term. For reference, the last full quarter with all antibodies authorized in the U.S. and or approved globally represented approximately $1.1 billion in revenue. Importantly, we see this category growing because although many populations have been served by vaccination and treatment with antiviral medication, as we referred to, there are many populations who have not benefited from these approaches and which will require ongoing protection and treatment outside of the major options. Monoclonal antibodies for COVID-19 alone generated almost $8 billion in revenue in 2022. While the bad news is there are no monoclonal antibodies available for treatment or prevention and an ongoing high burden of disease, the good news is we believe in Vivid is uniquely positioned to respond to this need, having generated a pipeline of multiple next generation engineered antibody candidates for COVID-19 designed to keep pace with viral evolution. Our pipeline assets are engineered to be broadly neutralizing antibodies effective across multiple members of the coronavirus family to support their prolonged utility. Earlier this month, we announced plans to advance VYD222, our next pipeline candidate, into the clinic for SARS-CoV-2. VYD222 is one of the components of NVD200, a MAB combination candidate that Vivid previously elected to advance in development. The company chose to prioritize the clinical development of VYD222 monotherapy instead of NVD200 combination product because we believe this strategy will enable us to provide patients with a much needed therapeutic option as quickly as possible in a capital efficient way. Importantly, we had selected a combination drug candidate prior to the emergence of potential expedited regulatory pathways which may allow InVivid to develop multiple new antibodies staggered in time to take advantage of data from new SARS-CoV-2 variants. We see VYD222 as a highly attractive candidate for clinical advancement for several reasons. VYD222 targets the spike protein of SARS-CoV-2, a well-understood mechanism with a safety profile established by multiple FDA-approved antibodies which we feel reduces clinical risk. Additionally, BYD222 is an engineered version of our first monoclonal antibody product called Intrevimab, which demonstrated clinically meaningful results across its three primary endpoints in large global Phase III trials. Our strong data package from Intrevimab has the potential to support accelerated development of BYD222. Importantly, In standardized in vitro assays, BYD222 showed neutralizing activity against multiple currently circulating variants of concern, including those that led to the obsolescence of products previously authorized in the U.S. that have since been pulled from the market. We continue to plan to initiate a Phase I clinical trial in Q1 of 2023. And assuming positive Phase I data, we anticipate rapidly initiating the Phase III pivotal trials that could support regulatory filings globally. Recently, there have been several positive external developments that indicate momentum for faster development of next-generation COVID treatments, including VYD-222. We are often asked about the White House's decision to end the COVID-19 public health emergency and how this could impact the FDA's emergency use authorization for COVID and the development of monoclonal antibodies like VYD222. We do not see this impacting our development strategy. Soon after the Biden administration announced that the public health emergency will end on May 11th, the FDA confirmed that existing EUAs for vaccines, tests, and treatments will not be affected and confirmed that it may continue to issue EUAs for new products that meet the required criteria. Additionally, the industry remains hopeful that alternative Efficient regulatory strategies to support the development of novel monoclonal antibody therapies will be utilized for this critical unmet need. While we are optimistic about BYD222's potential to serve the critical need for therapeutic options for COVID-19, continued viral evolution dictates that we also continue to evolve our assets and further add to our pipeline. Leveraging our proprietary discovery platform approach, we are perpetually monitoring emerging viral threats, discovering engineering and evaluating new monoclonal antibodies for their ability to neutralize SARS-CoV-2. In addition to VYV222, we have three other COVID-19 candidates in our pipeline at the preclinical stage. The message is clear. There remains a large, persistent medical and commercial opportunity. Outside of COVID, I am not aware of any other opportunity in biotech that is larger, offers a faster path to authorization, and has a higher probability of meaningful clinical results given our mechanistic understanding of the virus. We believe we are well positioned to capitalize on this opportunity time and time again with our proprietary discovery technology. I will now turn it over to our Chief Medical Officer, Pete Schmidt, to review our recent pipeline progress and ongoing discovery and development activities.
spk21: Thanks, Dave. As Dave mentioned, we recently nominated BYD222 to advance to the clinic as a new monoclonal antibody candidate, or MAB, against SARS-CoV-2. As you know, BYD222 will be our second MAB candidate to enter clinical testing. After a phase one dose ranging trial to evaluate safety in pharmacokinetics, or PK, we intend to initiate what we expect to be a larger, registrational phase three clinical trial to assess the efficacy of BYD222 to prevent COVID-19, specifically in immune-compromised individuals. BYD222 has demonstrated in vitro neutralizing activity against SARS-CoV-2 variants of concern, or VOCs, including the current dominant Omicron sublineage, XBB1.5. BYD222 is an engineered version of aditravimab, our first investigational map. Adentrevumab has a robust safety data package and has demonstrated clinically meaningful results in global phase three clinical trials for both the prevention and treatment of COVID-19 during the Delta and Omicron BA.1 waves of SARS-CoV-2, but subsequently lost in vitro activity against Omicron BA.2. Utilizing our expertise in protein engineering, we were able to restore in vitro neutralization activity against BA.2 and other Omicron VOCs while maintaining activity against previous VOCs. Our precision engineering resulted in BYD222 differing from aditravimab by only eight amino acids in the variable region. The regulatory landscape around COVID-19 is advancing, and there has been considerable movement with the US Food and Drug Administration and the European Medicines Agency as they work to establish regulatory frameworks that consider the rapidity of viral evolution. The agencies are looking for ways to accelerate development of MAPs as well. On December 15, 2022, a joint EMA-FDA workshop entitled Efficacy of Monoclonal Antibodies in the Context of Rapidly Evolving SARS-CoV-2 Variants was held to discuss alternative strategies for the development of novel MAP therapies, including those based on prototype products that have demonstrated safety and efficacy in clinical trials. InVivid was asked to present alongside Eli Lilly and Regeneron at this workshop to discuss ways of accelerating MAP development against COVID-19. As part of the joint industry presentation and utilizing data from our adentropamab prevention trial debate, neutralizing antibody titers were proposed as a surrogate marker of protection. It is our belief that these neutralizing antibody titers, combined with associated PK and safety information, could be used for a streamlined development pathway in the prevention of COVID-19. Encouragingly, we have seen other companies in the COVID-19 MAP space refer to the use of biomarker surrogate endpoints to expedite their clinical development, which may suggest that the FDA and other major regulatory bodies have agreed in principle to such a trial design for a next-generation MAP product. We see this as an important advancement, not only for BYD222, but also for future MABs we anticipate generating against SARS-CoV-2 to allow us to rapidly shift from one MAB to another as the virus mutates. After demonstrating clinical development success with edentropamab by generating clinically meaningful results, we are leveraging and applying this expertise to new therapeutic candidates. Furthermore, targeting the SARS-CoV-2 receptor binding domain, or RBD, is a well-validated mechanism of action for MAPS, with robust safety and efficacy data generated across the class. We expect that these data supporting the broader class of RBD-targeted antibodies will also enable regulatory authorities, including the FDA and EMA, to apply surrogate endpoints as a correlative protection in future clinical trials. I know many of you want more details about our clinical trial design and timelines. For VUID-222, we are planning a standard phase 1 PK and dose rating trial. This trial, which will be conducted in Australia, is on track to dose the first patient this quarter. Consistent with the Aditrabab program, we are planning to initiate phase 3 pivotal trials that could support global regulatory filings rapidly on the heels of completing this phase 1 trial. With regards to CMC, to support manufacturing of our clinical materials and commercial drug product, we have a partnership with WUSHI, which has FDA-approved manufacturing facilities and has delivered 100% of our drug substance lots on time. Through this relationship, we have already manufactured the drug substance needed for clinical trials of BYD222 in support of an EUA. I am confident in our ability to work with speed, agility, and efficiency to reduce traditional clinical timelines and to get to top-line data as quickly as possible. I will now pass the call over to Lucas Dillinger, eVivid's interim head of discovery and preclinical, who will discuss our ongoing surveillance and antibody discovery screening and engineering efforts.
spk16: Thank you, Pete, for this update on our new trim outlook. As Dave discussed at the beginning of the call, InVivid's approach to R&D for COVID-19 is one of perpetual innovation. InVivid was created to continually develop candidates and not rely on any one candidate. The pace of viral evolution demands that our candidates need to keep pace and have the potential to address emerging viral threats. This unique perpetual discovery engine is fueled by cutting-edge viral epidemiological surveillance, identification of broadly neutralizing monoclonal antibodies, and industry-leading detail mining, protein, and antibody engineering, as well as screening capabilities through our internal expertise and collaboration. With regards to monitoring viral evolution, we continuously maintain and improve our in-house surveillance system for new and upcoming SARS-CoV-2 variants, before these become variants of concern. Furthermore, by pinpointing dominant spike glycoprotein sites targeted by human antibody repertoires and mapping common mutation escape routes, we aim to predict and target future SARS-CoV-2 variants. We have industry-leading antibody mining, engineering, and developability screening capabilities built with our internal expertise and enhanced with our fully operational vet lab facilities that we moved into in December. This is further supported by our partnership with Adima, our industrial and academic collaborators, and the Council of our world-class scientific advisory board, comprised of leading researchers and key opinion leaders in immunology, virology, epidemiology, and the COVID-19 space. Our innovation engine leverages beta mining capabilities to isolate broadly neutralizing antibodies, followed by antibody engineering to improve the potency, breadth, biophysical properties, and developability of our candidates we seek to advance into non-clinical development and IND-nating studies. For example, where applicable, we specifically engineer our antibodies to extend the half-life modify their FC-mediated innate immune effector function, or to introduce alternative formats, such as single-domain or bispecific molecules. Our established platform and key learnings from our work without intravimab help to accelerate our path to the clinic and beyond. Through this approach, we are generating not just VYD222, but the robust pipeline of discovery-stage candidates with potential for use in both prevention, and or treatment of serious viral diseases starting with COVID-19. From there, we are expanding discovery efforts into high-need indication, including influenza. Beyond VYD222, we have already initiated new antibody campaigns that target reengineering and definitive maturations of our current molecules against the most recent COVID-19 variants of concern, such as XBP.1.5. We are currently evaluating several of these candidates in preclinical studies to support nomination of additional candidates for IND-enabling and clinical development. We envision further product development opportunities emerging from SARS-CoV-2 discovery efforts for the prevention and or treatment of COVID-19. We believe the discovery of additional broadly neutralizing monoclonal antibodies that target new viral epidemics both within and outside the RBD will support durable products for COVID-19 as new variants of concern continue to arise. In conclusion, our strategy is to predict and respond to variants before they become variants of concern and continuously discover and engineer antibodies with neutralization breadth and potency. such that patients in need may have access to high-quality protection even in the face of rapid viral evolution. We do not rely on a single molecule targeting a single epitope that may experience viral escape. We believe our integrated discovery platform, linked to our drug development and manufacturing expertise, offers a unique, competitive advantage in this effort and the potential to provide a distinct benefit to patients in need, caregivers, and global health authorities searching for durable solutions to the ongoing burden imposed by COVID-19. With that, I will turn the call over to Fred Driscoll, InVivid's Interim Chief Financial Officer, who will discuss our financials.
spk11: Thanks, Lucas, and good afternoon, everyone. Let me begin by providing an update on our 2022 fiscal year P&L results. as compared to the comparable 2021 period, and an update on cash guidance. With respect to operating expenses, R&D, including in-process R&D, was $183.6 million for the year ended December 31, 2022, compared to $190.4 million for the comparable period of 2021. This decrease is attributable primarily to wind down of adentrevumab clinical trials, partially offset by an increase in contract manufacturing, including adentrevumab commercial supply for a potential EUA and to support our pipeline programs, including VYD 222. This decrease in R&D was further offset by an increase in personnel-related expenses. Our SG&A expenses were $47 million for the year ended December 31st, 2022, compared to $36.5 million for the comparable period of 2021. This increase is attributable to higher personnel-related expenses, professional fees, and costs to support our operations as a public company. In the fourth quarter of 2022, the company incurred a $17.4 million expense attributable to a one-time charge associated with warrants issued to population health partners or PHP as compensation for consulting services to be provided by PHP to the company. The net loss for the year ended December 31st, 2022 was $241.3 million compared to $226.8 million for the comparable period in 2021. Basic and diluted net loss per share was $2.23 for the year ended December 31, 2022, compared to a net loss of $5.32 for the comparable period in 2021. The net loss of $241.3 million for the year ended December 31, 2022, included a one-time charge of $17.4 million related to the fair value of the warrants issued to PHP. We finished 2022 in a strong balance sheet position with cash, cash equivalents, and marketable securities of $372 million. Based on our current operating plans, which reflect the completion of a bottoms-up departmental analysis that we highlighted on the Q3 earnings call, our cash guidance has improved from our previous guidance, and we now expect our cash will enable the company to fund its operating expenses, excluding any potential revenue associated with VY222, into the second half of 2024. With that, operator, please open the call for questions.
spk03: Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please press star 11 on your telephone. Again, to ask a question, please press star 11. One moment, please, for our first question. Our first question comes from the line of Evan Wang, of Guggenheim, your line is open.
spk09: Hi, guys.
spk08: Thanks for taking my question. Can you highlight, you know, what's remaining before the VUID 522 trial start and then expand a little bit more in terms of how you guys are thinking about trial design, both, you know, dosing, timelines, et cetera?
spk10: Yeah, thanks, Evan. Pete, you want to talk a little bit about what remains as we're getting ready towards the end of this quarter?
spk21: Yeah. As we stated previously, we're still anticipating dosing our first-in-human study this quarter. We haven't released a lot of details about that study, but as you heard from the call, it's a pretty traditional dose-ranging PK and safety study. Beyond that, we'll continue to release details as appropriate on our subsequent studies.
spk10: Yeah, and you asked, Evan, a little bit about timing, right? You know, as Pete mentioned, we still anticipate the first study starting by the end of the month, just getting, you know, clinical trial material to the sites, you know, getting the recruitment done, et cetera. And then our plan is to continue to have, you know, ongoing data releases throughout the year.
spk08: Got it. Thanks. And then in terms of a phase three, I know you guys put out the paper the other day in terms of correlates. How are you guys thinking about primary endpoints And secondly, you know, BYD 222, you know, adapted from ADV20, how does that kind of benefit in terms of if you can provide some maybe a framework in terms of how that may reduce the trial size? What kind of scope of trial are we looking at here?
spk10: Yeah, I'll take the first part, and then, you know, Pete, you can take the second. As we've said and shown before, ADG20, our original antibody, we went from IND to pivotal clinical data in 16 months, and we utilized both treatment and prevention studies that used event-driven clinical endpoints. And what we continue to look at as a possibility is whether there's an opportunity to use correlates, surrogates, immunobridging, et cetera. And so those discussions continue. As Pete mentioned, you know, as a part of the upfront on the call, this was really articulated during the December 15th joint FDA EMA meeting. And, you know, we alongside academics and, you know, other stakeholders really commented about the need for these types of approaches, especially given the dynamic environment that we're in you know, really going against a virus that continues to evolve at such a rapid pace. And so, you know, we continue to have those conversations and, you know, as we previously mentioned, as soon as we have outlined and confirmed exactly what those clinical parameters would be for pivotal studies, we plan to share, you know, more details about that. Pete, any, you know, other comments?
spk21: Yeah, great question about the relationship to ADG20, the molecular relationship. And, you know, we're still in conversations with global regulators around this, of course, but we do believe that it is an advantage to have a robust safety data set and also efficacy data from our previous phase three studies in a molecule that was generated on the same manufacturing platform and is so closely structurally related to VYD, to ADG20, I'm sorry.
spk20: So lots of potential there.
spk04: Great. Thanks, guys.
spk03: Thank you. One moment, please. One moment, please. Our next question comes from the line of Siddharth Mehta of Jefferies. Your line is open.
spk06: Hi, this is Siddharth from Michael Yee at Jefferies. So two quick questions. First one being, you know, AstraZeneca and other big companies, while they made a lot of money in 2022 on antibodies, have noted that they see the market going significantly down in 23 and beyond as we move to an endemic market. So how do you guys think about that as you move your antibody forward? And my second question is, you know, although you've mentioned having these kind of correlates of protection for phase three studies, has there been any discussion or definitive evidence Answers from the FDA on whether or not you can use that as a part of your phase 3 studies. Thank you.
spk10: Yeah, I'll take the 1st question and so our estimates that in 2022, the sort of overall market across vaccines. oral antivirals, monoclonal antibodies, with almost $100 billion. And yes, I think that a lot of folks are predicting that that will come down, but it's still an incredibly sizable market. Monoclonal antibodies did $8 billion. about in revenue in 2022. And that was with, you know, predominantly Bebtolovumab and Evusheld. And Evusheld did, you know, 500 and some million dollars in Q3 of last year. And what we see is with a similar indication, really targeting immune compromised, vulnerable populations, you know, they only touched really a fraction of that population. And we continue to work with These groups talk to patient advocacy groups, speak with these individuals, and they still are really clamoring for products. In particular, I spoke to a physician who works at the Mayo Clinic and said he had never been in a position that these types of patients come in and ask for products and there's nothing available. And so based on that, we see the market for monoclonal antibodies continuing to be incredibly significant and a huge unmet need in this patient population. As it relates to your other question in terms of where regulators are and what the status is, we'll provide additional updates when we get them. We continue to be in dialogue with the FDA and other global regulators. As I said, as soon as we have confirmed what that trial design will look like, we plan to provide that information.
spk02: Thank you.
spk03: Thank you. One moment, please. Our next question comes from the line of Matthew Harrison of Morgan Stanley. Your line is open.
spk05: Hi, this is for Matthew. Thanks for taking our questions. I have two questions. Is there any update on adding kind of regulatory thresholds for new antibody therapy for COVID, given the change of the pandemic setting? Could there be any flexibility in potential approval? The second is, do you have any updates on your potential progress on flu antibodies therapy development?
spk10: Sir, no, thank you for the question. So on the first one, in terms of regards to thresholds, You know, as you're likely aware, at least in the U.S., none of the antibodies have been fully licensed and gone through BLAs. They've all been authorized through EUAs. And there currently are no monoclonal antibodies on the market. And so we have not seen any specific changes in thresholds. In particular, what we continue to look at is in vitro data ahead of time and as what we've seen on VYD222 is consistently strong activity against a variety of variants, including the most recent on .1.5, and so we see that that is really important information as it relates to getting the products into clinical trials, et cetera. And as I mentioned through the presentation, while the public health emergency is ending, that does not remove the potential for the FDA to utilize the EUAs, and so we still see that as an open possibility for BYD22 or our additional other candidates that we have in the pipeline. As it relates to the flu component, I'll turn it over to Lucas. You can provide an update on the status of where we are with the flu program.
spk16: Yes, thank you, Dave. So we've identified several interesting molecules in the flu program already.
spk15: These molecules are currently being further characterized in in vitro assays and other studies, and we will be releasing the data as soon as we have them available.
spk03: Okay, thank you. Thank you. I'm sure no further questions at this time. I'm going to turn the call back over to Dave Herring for any closing remarks.
spk10: Thank you so much. So thanks everyone for joining. It was a fantastic quarter and a great 2022. So I'm very excited for where we are. And as I alluded to at the start of this discussion, I'm extremely pleased with our progress in the fourth quarter and our start to this year. We have multiple monoclonal antibody candidates that have shown in vitro neutralizing activity against multiple current lineages of Omicron. I believe in the company's ability to bring to market a product for COVID-19 as fast and efficiently as possible to meet this continued large unmet need in patients and to capitalize on the significant market opportunity and create value for shareholders. Given the rapid pace of viral evolution and the ongoing regulatory environment, we are positioning the company to pivot as necessary to deliver on that goal time and time again. So that concludes our meeting for today, and as always, we'll be happy to follow up with analysts or investors one-on-one after the call tonight and tomorrow. Thank you.
spk03: Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day. Music. Thank you. Thank you.
spk00: Thank you.
spk03: Thank you for standing by and welcome to the InVivid 2022 Year-End Financial Results Update Call. At this time, all participants are in listen-only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question at that time, please press star 11 on your telephone. As a reminder, today's call is being recorded. I will now turn the conference to the host, Kira Faircloth, Vice President, Advocacy and Corporate Communications.
spk02: Please go ahead.
spk14: Thank you for joining us today. Before we get started, I want to attend to a few housekeeping items. I invite you to review our press release discussing our full year-ended December 31st, 2022 financial results, 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 including the expectation of its continued evolution and emergence of new variants and sub-variants, our ongoing research and clinical development plans, including the timing of these plans, as well as the technology and resources to develop therapeutic or preventative options for COVID-19 and other infectious diseases, our regulatory and commercialization plans and opportunities, and 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 statements, including those described under the heading risk factors in our filings made with the U.S. Securities and Exchange Commission, including our most recent 10-K filed earlier today. It is now my pleasure to introduce the InVivid management team to the call. I am joined by Dave Herring, CEO of InVivid, Dr. Pete Schmidt, Chief Medical Officer, Dr. Lucas Dillinger, Interim Head of Discovery and Preclinical, and Fred Driscoll, Interim Chief Financial Officer. With that, I will turn the call over to Dave.
spk10: Good afternoon, and thanks for joining the call. We are looking forward to sharing with you financial results from this past year, along with highlights of significant progress we made during this past quarter. For those who may be new to The Invented Story, We are on a mission to rapidly and perpetually deliver antibody-based therapies designed to protect vulnerable people from the devastating consequences of circulating viral threats, beginning with SARS-CoV-2. The foundation of our mission is based on three key factors. One, COVID is here to stay and represents an unacceptable medical burden on humankind. Two, the medicine cabinet to protect humanity from COVID is alarmingly limited. And three, we are uniquely positioned to keep pace with viral evolution and provide therapeutic options to people who urgently need them. We have reached a stage where SARS-CoV-2 is circulating unchecked amongst the broader population, with as many as 85% of people in the U.S. having been infected. The vaccination rate for boosters is exceedingly low compared with rates of the primary series. Recent reports highlight that only 28% of the eligible people have now received the most recent COVID-19 booster. People are being infected and reinfected while the virus continues to evolve. Every day, 250 to 400 families in the US lose a loved one to COVID-19. And COVID remains the third leading cause of death behind only heart disease and cancer. While most of society has accepted the status quo and are trying to live with COVID, We would argue that all are not living well, particularly vulnerable populations. Although the immediate impacts of COVID-19 on many healthy adults appear mild, the long-term consequences remain unknown. Preliminary data reported by the Mayo Clinic show that COVID-19 infections are linked to long-term complications that impact numerous body systems, including pulmonary, renal, neurological, and gastrointestinal complications. Additionally, vulnerable populations remain at an increased risk of severe disease, resulting in hospitalization and even death. Immunocompromised patients alone in the U.S. represent between 8 and 20 million individuals, depending on how their status is classified. The threat we are facing from COVID-19 is constantly changing as viral evolution has continued through Omicron sub-lineages. In fact, hundreds of new variants have been identified in the U.S. in the last five months. This continual viral evolution mandates that drug discovery and development must keep pace. However, as of January 2023, there are no longer any monoclonal antibodies for the treatment or prevention of COVID-19 authorized in the U.S. We consider this market an open opportunity for InVivid to target near term. For reference, the last full quarter with all antibodies authorized in the U.S. and or approved globally represented approximately $1.1 billion in revenue. Importantly, we see this category growing because although many populations have been served by vaccination and treatment with antiviral medication, as we referred to, there are many populations who have not benefited from these approaches and which will require ongoing protection and treatment outside of the major options. Monoclonal antibodies for COVID-19 alone generated almost $8 billion in revenue in 2022. While the bad news is there are no monoclonal antibodies available for treatment or prevention and an ongoing high burden of disease, the good news is we believe in Vivid is uniquely positioned to respond to this need, having generated a pipeline of multiple next-generation engineered antibody candidates for COVID-19 designed to keep pace with viral evolution. Our pipeline assets are engineered to be broadly neutralizing antibodies effective across multiple members of the coronavirus family to support their prolonged utility. Earlier this month, we announced plans to advance VYD222, our next pipeline candidate, into the clinic for SARS-CoV-2. VYD222 is one of the components of NVD200, a MAB combination candidate that Vivid previously elected to advance in development. The company chose to prioritize the clinical development of VYD222 monotherapy instead of NVD200 combination product because we believe this strategy will enable us to provide patients with a much needed therapeutic option as quickly as possible in a capital efficient way. Importantly, we had selected a combination drug candidate prior to the emergence of potential expedited regulatory pathways which may allow InVivid to develop multiple new antibodies staggered in time to take advantage of data from new SARS-CoV-2 variants. We see VYD222 as a highly attractive candidate for clinical advancement for several reasons. VYD222 targets the spike protein of SARS-CoV-2, a well-understood mechanism with a safety profile established by multiple FDA-approved antibodies, which we feel reduces clinical risk. Additionally, BYD222 is an engineered version of our first monoclonal antibody product called intravimab, which demonstrated clinically meaningful results across its three primary endpoints in large global Phase III trials. Our strong data package from intravimab has the potential to support accelerated development of BYD222. Importantly, In standardized in vitro assays, BYD222 showed neutralizing activity against multiple currently circulating variants of concern, including those that led to the obsolescence of products previously authorized in the U.S. that have since been pulled from the market. We continue to plan to initiate a Phase I clinical trial in Q1 of 2023. And assuming positive Phase I data, we anticipate rapidly initiating the Phase III pivotal trials that could support regulatory filings globally. Recently, there have been several positive external developments that indicate momentum for faster development of next-generation COVID treatments, including VYD-Q22. We are often asked about the White House's decision to end the COVID-19 public health emergency and how this could impact the FDA's emergency use authorization for COVID and the development of monoclonal antibodies like VYD222. We do not see this impacting our development strategy. Soon after the Biden administration announced that the public health emergency will end on May 11th, the FDA confirmed that existing EUAs for vaccines, tests, and treatments will not be affected and confirmed that it may continue to issue EUAs for new products that meet the required criteria. Additionally, the industry remains hopeful that alternative efficient regulatory strategies to support the development of novel monoclonal antibody therapies will be utilized for this critical unmet need. While we are optimistic about BYD222's potential to serve the critical need for therapeutic options for COVID-19, continued viral evolution dictates that we also continue to evolve our assets and further add to our pipeline. Leveraging our proprietary discovery platform approach, we are perpetually monitoring emerging viral threats, discovering engineering and evaluating new monoclonal antibodies for their ability to neutralize SARS-CoV-2. In addition to VYV222, we have three other COVID-19 candidates in our pipeline at the preclinical stage. The message is clear. There remains a large, persistent medical and commercial opportunity. Outside of COVID, I am not aware of any other opportunity in biotech that is larger, offers a faster path to authorization, and has a higher probability of meaningful clinical results given our mechanistic understanding of the virus. We believe we are well positioned to capitalize on this opportunity time and time again with our proprietary discovery technology. I will now turn it over to our Chief Medical Officer, Pete Schmidt, to review our recent pipeline progress and ongoing discovery and development activities.
spk21: Thanks, Dave. As Dave mentioned, we recently nominated BYD222 to advance to the clinic as a new monoclonal antibody candidate, or MAB, against SARS-CoV-2. As you know, BYD222 will be our second MAB candidate to enter clinical testing. After a phase one dose ranging trial to evaluate safety and pharmacokinetics, or PK, we intend to initiate what we expect to be a larger, registrational phase three clinical trial to assess the efficacy of BYD222 to prevent COVID-19, specifically in immune-compromised individuals. BYD222 has demonstrated in vitro neutralizing activity against SARS-CoV-2 variants of concern, or VOCs, including the current dominant Omicron sublineage, XBB1.5. BYD222 is an engineered version of adentravimab, our first investigational map. That Entrebimab has a robust safety data package and has demonstrated clinically meaningful results in global phase three clinical trials for both the prevention and treatment of COVID-19 during the Delta and Omicron BA.1 waves of SARS-CoV-2, but subsequently lost in vitro activity against Omicron BA.2. Utilizing our expertise in protein engineering, we were able to restore in vitro neutralization activity against BA.2 and other Omicron VOCs while maintaining activity against previous VOCs. Our precision engineering resulted in BYD222 differing from aditravimab by only eight amino acids in the variable region. The regulatory landscape around COVID-19 is advancing, and there has been considerable movement with the US Food and Drug Administration and the European Medicines Agency as they work to establish regulatory frameworks that consider the rapidity of viral evolution. The agencies are looking for ways to accelerate development of MAPs as well. On December 15, 2022, a joint EMA-FDA workshop entitled Efficacy of Monoclonal Antibodies in the Context of Rapidly Evolving SARS-CoV-2 Variants was held to discuss alternative strategies for the development of novel MAP therapies, including those based on prototype products that have demonstrated safety and efficacy in clinical trials. InVivid was asked to present alongside Eli Lilly and Regeneron at this workshop to discuss ways of accelerating MAP development against COVID-19. As part of the joint industry presentation and utilizing data from our adenotrevumab prevention trial, EVADE, neutralizing antibody titers were proposed as a surrogate marker of protection. It is our belief that these neutralizing antibody titers, combined with associated PK and safety information, could be used for a streamlined development pathway in the prevention of COVID-19. Encouragingly, we have seen other companies in the COVID-19 MAP space refer to the use of biomarker surrogate endpoints to expedite their clinical development, which may suggest that the FDA and other major regulatory bodies have agreed in principle to such a trial design for a next-generation MAP product. We see this as an important advancement, not only for BYD222, but also for future MABs we anticipate generating against SARS-CoV-2 to allow us to rapidly shift from one MAB to another as the virus mutates. After demonstrating clinical development success with entropomab by generating clinically meaningful results, we are leveraging and applying this expertise to new therapeutic candidates. Furthermore, targeting the SARS-CoV-2 receptor binding domain, or RBD, is a well-validated mechanism of action for MAPS, with robust safety and efficacy data generated across the class. We expect that these data supporting the broader class of RBD-targeted antibodies will also enable regulatory authorities, including the FDA and EMA, to apply surrogate endpoints as a correlative protection in future clinical trials. I know many of you want more details about our clinical trial design and timelines. For VUID 2-2-2, we are planning a standard Phase 1 PK and dose rating trial. This trial, which will be conducted in Australia, is on track to dose the first patient this quarter. Consistent with the Atta Trevabab program, we are planning to initiate Phase 3 pivotal trials that could support global regulatory filings rapidly on the heels of completing this Phase 1 trial. With regards to CMC, to support manufacturing of our clinical materials and commercial drug product, we have a partnership with WUSHI, which has FDA-approved manufacturing facilities and has delivered 100% of our drug substance lots on time. Through this relationship, we have already manufactured the drug substance needed for clinical trials of BYD222 in support of an EUA. I am confident in our ability to work with speed, agility, and efficiency to reduce traditional clinical timelines and to get to top-line data as quickly as possible. I will now pass the call over to Lucas Dillinger, eVivid's interim head of discovery and preclinical, who will discuss our ongoing surveillance and antibody discovery, screening, and engineering efforts.
spk16: Thank you, Pete, for this update on our new-term outlook. As Dave discussed at the beginning of the call, InVivid's approach to R&D for COVID-19 is one of perpetual innovation. InVivid was created to continually develop candidates and not rely on any one candidate. The pace of viral evolution demands that our candidates need to keep pace and have the potential to address emerging viral threats. This unique perpetual discovery engine is fueled by cutting-edge viral epidemiological surveillance, identification of broadly neutralizing monoclonal antibodies, and industry-leading detail mining, protein and antibody engineering, as well as screening capabilities through our internal expertise and collaboration. With regards to monitoring viral evolution, we continuously maintain and improve our in-house surveillance system for new and upcoming SARS-CoV-2 variants, before these become variants of concern. Furthermore, by pinpointing dominant spike glycoprotein sites targeted by human antibody repertoires and mapping common mutation escape routes, we aim to predict and target future SARS-CoV-2 variants. We have industry-leading antibody mining, engineering, and developability screening capabilities built with our internal expertise and enhanced with our fully operational VETLA facilities that we moved into in December. This is further supported by our partnership with ADIMA, our industrial and academic collaborators, and the Council of our world-class scientific advisory board, comprised of leading researchers and key opinion leaders in immunology, virology, epidemiology, and the COVID-19 space. Our innovation engine leverages beta mining capabilities to isolate broadly neutralizing antibodies, followed by antibody engineering to improve the potency, breadth, biophysical properties, and developability of our candidates we seek to advance into non-clinical development and IND and 18 studies. For example, where applicable, we specifically engineer our antibodies to extend the half-lives modify their FC-mediated innate immune effector function, or to introduce alternative formats, such as single-domain or bispecific molecules. Our established platform and key learnings from our work with Arden Trebemont help to accelerate our path to the clinic and beyond. Through this approach, we are generating not just VYD222, but a robust pipeline of discovery-stage candidates with potential for use in both prevention, and or treatment of serious viral diseases starting with COVID-19. From there, we are expanding discovery efforts into high-need indication, including influenza. Beyond VYD222, we have already initiated new antibody campaigns that target re-engineering and definitive maturations of our current molecules against the most recent COVID-19 variants of concern, such as XBP.1.5. We are currently evaluating several of these candidates in preclinical studies to support nomination of additional candidates for IND-enabling and clinical development. We envision further product development opportunities emerging from SARS-CoV-2 discovery efforts for the prevention and or treatment of COVID-19. We believe the discovery of additional broadly neutralizing monoclonal antibodies that target new viral epitopes both within and outside the RBD will support durable products for COVID-19 as new variants of concern continue to arise. In conclusion, our strategy is to predict and respond to variants before they become variants of concern and continuously discover and engineer antibodies with neutralization breadth and potency. such that patients in need may have access to high-quality protection even in the face of rapid viral evolution. We do not rely on a single molecule targeting a single epitope that may experience viral escape. We believe our integrated discovery platform, linked to our drug development and manufacturing expertise, offers a unique, competitive advantage in this effort and the potential to provide a distinct benefit to patients in need, caregivers, and global health authorities searching for durable solutions to the ongoing burden imposed by COVID-19. With that, I will turn the call over to Fred Driscoll, InVivid's Interim Chief Financial Officer, who will discuss our financials.
spk11: Thanks, Lucas, and good afternoon, everyone. Let me begin by providing an update on our 2022 fiscal year P&L as compared to the comparable 2021 period, and an update on cash guidance. With respect to operating expenses, R&D, including in-process R&D, was $183.6 million for the year ended December 31st, 2022, compared to $190.4 million for the comparable period of 2021. This decrease is attributable primarily to wind down of adentrevumab clinical trials, partially offset by an increase in contract manufacturing, including adentrevumab commercial supply for a potential EUA and to support our pipeline programs, including VYD 222. This decrease in R&D was further offset by an increase in personnel-related expenses. Our SG&A expenses were $47 million for the year ended December 31st, 2022, compared to $36.5 million for the comparable period of 2021. This increase is attributable to higher personnel-related expenses, professional fees, and costs to support our operations as a public company. In the fourth quarter of 2022, the company incurred a $17.4 million expense attributable to a one-time charge associated with warrants issued to population health partners or PHP as compensation for consulting services to be provided by PHP to the company. The net loss for the year ended December 31st, 2022 was $241.3 million compared to $226.8 million for the comparable period in 2021. Basic and diluted net loss per share was $2.23 for the year ended December 31, 2022, compared to a net loss of $5.32 for the comparable period in 2021. The net loss of $241.3 million for the year ended December 31, 2022, included a one-time charge of $17.4 million related to the fair value of the warrants issued to PHP. We finished 2022 in a strong balance sheet position with cash, cash equivalents, and marketable securities of $372 million. Based on our current operating plans, which reflect the completion of a bottoms-up departmental analysis that we highlighted on the Q3 earnings call, our cash guidance has improved from our previous guidance, and we now expect our cash will enable the company to fund its operating expenses, excluding any potential revenue associated with VY222, into the second half of 2024. With that, operator, please open the call for questions.
spk03: Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please press star 11 on your telephone. Again, to ask a question, please press star 11. One moment, please, for our first question. Our first question comes from the line of Evan Wing, of Guggenheim, your line is open.
spk09: Hi, guys.
spk08: Thanks for taking my question. Can you highlight, you know, what's remaining before the VUID 322 trial starts and then expand a little bit more in terms of how you guys are thinking about trial design, both, you know, dosing, timelines, et cetera?
spk10: Yeah, thanks, Evan. Pete, you want to talk a little bit about what remains as we're getting ready towards the end of this quarter?
spk21: Yeah. As we stated previously, we're still anticipating dosing our first-in-human study this quarter. We haven't released a lot of details about that study, but as you heard from the call, it's a pretty traditional dose-ranging PK and safety study. Beyond that, we'll continue to release details as appropriate on our subsequent studies.
spk10: Yeah, and you asked, Evan, a little bit about timing, right? You know, as Pete mentioned, we still anticipate the first study starting by the end of the month, just getting, you know, clinical trial material to the sites, you know, getting the recruitment done, et cetera. And then our plan is to continue to have, you know, ongoing data releases throughout the year.
spk08: Got it. Thanks. And then in terms of a phase three, I know you guys put out the paper the other day in terms of correlates. How are you guys thinking about primary endpoints And secondly, you know, BYD 222, you know, adapted from ADV20, how does that kind of benefit in terms of if you can provide some maybe a framework in terms of how that may reduce the trial size? What kind of scope of trial are we looking at here?
spk10: Yeah, I'll take the first part, and then, you know, Pete, you can take the second. You know, as we've said and shown before, you know, ADG20, our original antibody, we went from IND to pivotal clinical data in 16 months, and we utilized both treatment and prevention studies that used event-driven clinical endpoints. And, you know, what we continue to look at as a possibility is whether there's an opportunity to use correlates, surrogates, immunobridging, et cetera. And so those discussions continue. As Pete mentioned, you know, as a part of the upfront on the call, this was really articulated during the December 15th joint FDA EMA meeting. And, you know, we alongside academics and, you know, other stakeholders really commented about the need for these types of approaches, especially given the dynamic environment that we're in you know, really going against a virus that continues to evolve at such a rapid pace. And so, you know, we continue to have those conversations and, you know, as we previously mentioned, as soon as we have outlined and confirmed exactly what those clinical parameters would be for pivotal studies, we plan to share, you know, more details about that. Pete, any, you know, other comments?
spk21: Yeah, great question about the relationship to ADG20, the molecular relationship. And, you know, we're still in conversations with global regulators around this, of course, but we do believe that it is an advantage to have a robust safety data set and also efficacy data from our previous phase three studies in a molecule that was generated on the same manufacturing platform and is so closely structurally related to VYD, to ADG20, I'm sorry.
spk20: So lots of potential there.
spk04: Great. Thanks, guys.
spk03: Thank you. One moment, please. One moment, please. Our next question comes from the line of Siddharth Mehta of Jefferies. Your line is open.
spk06: Hi, this is Siddharth from Michael Yee at Jefferies. So two quick questions. First one being, you know, AstraZeneca and other big companies, while they made a lot of money in 2022 on antibodies, have noted that they see the market going significantly down in 23 and beyond as we move to an endemic market. So how do you guys think about that as you move your antibody forward? And my second question is, you know, although you've mentioned having these kind of correlates of protection for phase three studies, has there been any discussion or definitive evidence Answers from the FDA on whether or not you can use that as a part of your phase 3 studies. Thank you.
spk10: Yeah, I'll take the 1st question and so. You know, our estimates that in 2022, you know, the sort of overall market across vaccines. oral antivirals, monoclonal antibodies was almost $100 billion. And yes, I think that a lot of folks are predicting that that will come down, but it's still an incredibly sizable market. You know, monoclonal antibodies did $8 billion about in revenue in 2022. And that was with, you know, predominantly beptilolumab and Evusheld And Evusel did, you know, 500 and some million dollars in Q3 of last year. And what we see is with a similar indication, really targeting immune compromised, vulnerable populations, you know, they only touched really a fraction of that population. And we continue to work with these groups, talk to patient advocacy groups, speak with these individuals, and they still are really clamoring for products, in particular, I spoke to a, you know, physician who works at the Mayo Clinic and said, you know, he had never been in a position that these types of patients come in and ask for products and there's nothing available. And so, based on that, we see the market for monoclonal antibodies continuing to be, you know, incredibly significant and a huge unmet need in this patient population. As it relates to your other question in terms of where regulators are and what the status is, we'll provide additional updates when we get them. We continue to be in dialogue with the FDA and other global regulators. And as I said, as soon as we have confirmed what that trial design will look like, we plan to provide that information.
spk02: Thank you.
spk03: Thank you. One moment, please. Our next question comes from the line of Matthew Harrison of Morgan Stanley. Your line is open.
spk05: Hi, this is for Matthew. Thanks for taking our questions. I have two questions. One is, is there any update on adding kind of regulatory thresholds for new antibody therapy for COVID, given the change of the pandemic setting? Could there be any flexibility in potential approval? The second is, do you have any updates on your potential progress on flu antibodies therapy development?
spk10: Sir, no, thank you for the question. So on the first one, in terms of regards to thresholds, you know, as you're likely aware, at least in the U.S., none of the antibodies have been fully licensed and gone through BLAs. They've all been authorized through EUAs. And there currently are no monoclonal antibodies on the market. And so we have not seen any specific changes in thresholds. In particular, what we continue to look at is in vitro data ahead of time. And as what we've seen on, you know, VYD222 is, you know, consistently strong activity against a variety of variants, including the most recent on .1.5, and so we see that that is really important information as it relates to getting the products into clinical trials, et cetera. And as I mentioned through the presentation, while the public health emergency is ending, That does not remove the potential for the FDA to utilize the EUAs, and so we still see that as an open possibility for BYD22 or our additional other candidates that we have in the pipeline. As it relates to the flu component, I'll turn it over to Lucas. You can provide an update on the status of where we are with the flu program.
spk16: Yes, thank you, Dave. So we've identified several interesting molecules in the flu program already.
spk15: These molecules are currently being further characterized in in vitro assays and other studies, and we will be releasing the data as soon as we have them available.
spk03: Okay, thank you. Thank you. I'm showing no further questions at this time. I'm going to turn the call back over to Dave Herring for any closing remarks.
spk10: Thank you so much. So thanks everyone for joining. It was a fantastic quarter and a great 2022. So I'm very excited for where we are. And as I alluded to at the start of this discussion, I'm extremely pleased with our progress in the fourth quarter and our start to this year. We have multiple monoclonal antibody candidates that have shown in vitro neutralizing activity against multiple current lineages of Omicron. I believe in the company's ability to bring to market a product for COVID-19 as fast and efficiently as possible to meet this continued large unmet need in patients and to capitalize on the significant market opportunity and create value for shareholders. Given the rapid pace of viral evolution and the ongoing regulatory environment, we are positioning the company to pivot as necessary to deliver on that goal time and time again. So that concludes our meeting for today. And as always, we'll be happy to follow up with analysts or investors one-on-one after the call tonight and tomorrow. Thank you.
spk03: Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.
Disclaimer