Invivyd - Q1 2023

Transcript

Gabriela Linville-Engler (Director of External Communications)

Welcome to the Invivyd First Quarter 2023 Financial Results update call. I will now turn the call over to Gabriela Linville-Engler, Director of External Communications.

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 first quarter 2023 financial results, which can be found on the investor section of the Invivyd website. I would like to remind you that during today's discussions, 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 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 Form 10-K. It is now my pleasure to introduce the Invivyd management team to the call. I am joined by Dave Hering, CEO of Invivyd, Dr. Pete Schmidt, Chief Medical Officer, and Fred Driscoll, Interim Chief Financial Officer. With that, I will turn the call over to Dave.

Dave Hering (CEO)

Welcome. Thank you for joining us today on our quarterly update call, thank you for your continued support of Invivyd. Since our last update call, we've made significant progress on the development of our lead candidate, VYD222, as well as great strides advancing our early pipeline and discovery capabilities and our overall mission to rapidly and perpetually deliver antibody based therapies designed to protect the vulnerable from the devastating consequences of circulating viral threats. We are making swift progress with VYD222, a broadly neutralizing monoclonal antibody candidate in development for the prevention of COVID-19 in vulnerable populations such as immunocompromised people. At the end of March, we announced the dosing of the first participants in our phase I VYD222 clinical trial being conducted in Australia. Now, roughly a month and a half later, we are pleased to share that we have finished dosing all 30 participants in the trial.

We remain on track for initial data readouts from that phase I trial in the second quarter, with additional clinical readouts from the VYD222 program anticipated in 2023. We also recently announced that the FDA has cleared our investigational new drug, IND, application for VYD222, an important step in our efforts to rapidly develop a therapeutic to protect the millions of immunocompromised people in the U.S. who are still under threat from COVID-19. Before I hand the call over to Pete to provide an overview of our VYD222 program and our regulatory strategy, I will provide a brief overview of the patient population we are focused on and cover recent developments in the field that speak to the strong unmet need for new therapeutics for COVID-19.

As you are aware, we are primarily focused on COVID-19 as it continues to remain a serious problem and a significant unmet medical need, particularly for immunocompromised people who remain vulnerable to the virus. People with dysfunctional or suppressed immune systems may not be able to mount an adequate response to vaccination and generate protective immunity. Therefore, immunocompromised people, which are estimated to number between eight and 18 million people in the U.S. and 14 million people in the E.U., require a different approach to COVID-19 prevention that does not rely on a healthy and functioning immune system. This population includes, for example, people who take immunosuppressive drugs, including organ transplant recipients, and people with autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, or inflammatory bowel disease.

This population also includes patients with hematological cancers that affect the immune system, like leukemia or lymphoma, as well as patients with forms of cancer that require treatments that weaken the immune system, such as chemotherapy. Immunocompromised people are at increased risk for severe COVID-19 outcomes such as hospitalization and death, and are in urgent need of new therapeutic options. As SARS-CoV-2 has continued to circulate and mutate, what clinicians have to offer these individuals in the global medicine cabinet has become extremely limited at present. For instance, there is increasing real world evidence that suggests the bivalent mRNA boosters offer marginal protection against symptomatic disease caused by emerging variants of concern, even in people with normal immune systems. Now more than ever, immunocompromised people need the rapid protection provided by monoclonal antibodies.

With the previously authorized anti-SARS-CoV-2 mAbs losing activity against variants of concern and being removed from the market in the U.S., there remains a significant unmet need. With COVID-19 still threatening millions of people, we are pleased to see that COVID-19 is still a priority for the U.S. government. The recently announced Project NextGen and $5 billion of associated funding is evidence of the government's continued commitment to supporting the advancement of vaccines and therapeutics that provide more durable protection and address future variants with new monoclonal antibodies identified as one of three priorities for the initiative. We are encouraged by the government's recognition that there remains a need to advance improved tools that provide better, broader and more long-lasting protection.

We agree that multiple approaches beyond vaccines are needed to address the prevention and treatment of COVID-19. Filling this gap in the product landscape represents a significant market opportunity for Invivyd. Consider that Evusheld 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 variants of concern. Additionally, the first quarter of 2023 in the biopharmaceutical industry has featured stronger than anticipated utilization of vaccines and drugs for which, while counter to some who think COVID-19 is over, aligns with the vast unmet need that still exists.

We believe that among all of the choices a vulnerable person and their healthcare professional can make relative to COVID-19, reducing the probability of having symptomatic COVID-19 that is not getting sick remains the strategy that is likely to lead to the lowest overall burden of disease and lowest negative health outcomes. Vaccines have done incredible work to keep us alive, there remains substantial work to keep vulnerable populations well. Monoclonal antibodies are well suited to meet this gap by augmenting the human immune system and helping to protect vulnerable populations from COVID-19. COVID-19 is transitioning into an ongoing endemic disease, it remains a massive disease category. Immunocompromised people who will continue to be at high risk could benefit significantly from monoclonal antibodies.

Given the enduring need for these patients and the unique value proposition for mAbs, we believe this market has the potential to become a high-growth, multi-billion-dollar opportunity in this space for many years to come. Among the companies developing antibody-based therapeutics, we believe we are positioned to have a significant impact for vulnerable populations because of our differentiated approach, an approach that is grounded in a commitment to serial innovation and is designed to anticipate and quickly respond to viral evolution. Our approach to perpetual innovation has two key pillars. The first pillar is a cutting-edge viral and epidemiological surveillance. With these capabilities, we aim to predictively model and target future SARS-CoV-2 variants. The second pillar is our discovery engine, which includes industry-leading B-cell mining and antibody engineering capabilities through our internal expertise and collaborations, such as their partnership with Adimab.

We leverage B-cell mining to isolate broadly neutralizing antibodies, but we do not rely alone on the repertoire of antibodies naturally produced by humans in response to viral exposure. We take our work one step further by continually leveraging our antibody engineering capabilities to improve the potency, breadth, biophysical properties, and developability of the antibody candidates we discover through B-cell mining. With our discovery engine, we have generated multiple monoclonal antibody candidates for COVID-19. The first candidate from our engine, adintrevimab, we advanced from IND to pivotal clinical trial data in 16 months. Our second candidate, VYD222, is in clinical development now. VYD222 is unique because it is engineered from our previous candidate, adintrevimab, which demonstrated clinically meaningful results in global phase III clinical trials and has a robust safety data package.

As Pete will discuss shortly, we aim to leverage insights from our experience with adintrevimab, including our recently published landmark research on monoclonal antibody correlates of protection to move much faster with the development of VYD222. Beyond VYD222, we have multiple anti-SARS-CoV-2 monoclonal antibodies in discovery and recently nominated an additional monoclonal antibody candidate for further preclinical characterization. This robust discovery pipeline reflects our strategy to predict and respond to variants before they become variants of concern and continuously discover and engineer new antibody candidates that can be leveraged to keep pace with viral evolution. I am proud of the tremendous progress we have made to advance our work in the recent months, I look forward to continuing to drive our mission forward with the urgency and speed that these vulnerable populations deserve.

I will now pass the call to Pete Schmidt, Chief Medical Officer, who will provide an update on our VYD222 clinical program.

Pete Schmidt (CMO)

Thanks, Dave. As Dave mentioned, we are pleased to report that we have completed dosing all 30 participants in our phase I clinical trial of VYD222. VYD222 is a broadly neutralizing monoclonal antibody candidate in development for the prevention of COVID-19 in vulnerable populations such as immunocompromised people. VYD222 has demonstrated in vitro neutralizing activity against variants of concern, including Omicron sublineages up to and through XBB.1.5. We continue to actively monitor emerging variants of concern and VYD222's in vitro neutralizing activity against these variants. VYD222 was engineered from adintrevimab, our first investigational monoclonal antibody, which demonstrated clinically meaningful results in global phase III clinical trials and has a robust safety data package. Our precision engineering resulted in only eight amino acids that differ in the variable region of VYD222 compared to adintrevimab.

This is our first example of re-engineering one of our monoclonal antibody candidates to adapt to a viral shift. The ongoing VYD222 phase I clinical trial is a randomized, blinded, placebo-controlled dose-ranging trial to evaluate the safety, pharmacokinetics, tolerability, and serum virus neutralizing activity, or sVNA, of VYD222 in healthy adult volunteers. The trial will evaluate three different doses, each administered as a single IV push. All doses are designed to provide durability in the face of viral evolution and flexibility at the time of regulatory submission. We are on track for initial readouts from the phase I clinical trial in the second quarter, including initial insights into VYD222 serum virus neutralizing activity, which may provide an early look at anticipated clinical efficacy.

Based on research we and our collaborators published in March 2023 in the peer-reviewed journal Science Translational Medicine, which relied heavily on data from our adintrevimab clinical trial, we believe that serum virus neutralizing activity is the optimal biomarker for predicting clinical efficacy and potentially accelerating the clinical development path for VYD222 when combined with associated pharmacokinetic safety data pending input from regulators. Our recently published paper establishes a quantitative relationship that defines a correlative protection for monoclonal antibodies, demonstrating protection from symptomatic infection even at relatively modest antibody titers, which speaks to the potential to have an extended period of time before needing to redose mAb therapies with extended half-lives. The research indicates that antibodies, whether polyclonal or monoclonal, are mechanistic for protection against symptomatic disease.

This groundbreaking work suggests that clinical efficacy of monoclonal antibodies against the SARS-CoV-2 spike protein is a predictable phenomenon that can be modeled. We see this publication as transformational towards accelerating the clinical development of monoclonal antibodies for the prevention of symptomatic COVID-19. On the regulatory front, we continue to be encouraged by the evolving regulatory landscape following the joint FDA EMA workshop in December of 2022, where alternative surrogate marker-based strategies for development of novel monoclonal antibody therapies for COVID-19 were discussed, including a presentation by Invivyd about the potential use of sVNA titers as a surrogate marker for protection against symptomatic COVID-19.

Since that meeting, we have seen other companies in the COVID-19 mAb space refer to rapid development plans and the use of sVNA titers as surrogate endpoints in their clinical trials, which may suggest that the FDA and other major regulatory bodies have agreed in principle to such a trial design for next-generation mAb candidates. We intend to work closely with global regulators to ensure our clinical trials are designed to provide the data they require as they establish regulatory frameworks that reflect the pace of SARS-CoV-2 viral evolution. We have had constructive interactions with the FDA and EMA regarding our VYD222 development program, and pending feedback from regulators, we plan to share an update once the design of our pivotal VYD222 clinical trial is finalized.

We did with adintrevimab, our intention is to initiate the pivotal trial of VYD222 as quickly as possible on the heels of early positive data from our phase I trial, including sVNA titers. To help ensure that we are well-positioned to support rapid recruitment into our planned phase III trial, we have established a database of recruitment-ready immunocompromised individuals for potential enrollment into the pivotal clinical trial. As the regulatory landscape evolves, one thing that remains the same is our belief that emergency use authorizations, or EUAs, continue to be an attractive pathway for authorization in the U.S., continuing past the end of the state of emergency around the COVID-19 pandemic. The FDA has confirmed that existing EUAs for vaccines, tests, and treatments will not be affected and has further confirmed that it may continue to issue EUAs for new products that meet the required criteria.

In fact, just last month, a host-directed monoclonal antibody received emergency use authorization for the treatment of COVID-19 in hospitalized adults receiving mechanical ventilation or artificial life support. As we look ahead, we look forward to constructing in partnership with global regulators a future paradigm where viral-directed monoclonal antibodies have a standard rapid development pathway that is similar to the platform-based approach used for the periodic modification and approval of flu and SARS-CoV-2 vaccines. We are optimistic about our path forward from here and our ability to address the significant need for novel therapeutic approaches for the prevention of COVID-19, particularly for immune-compromised individuals. With that, I will turn the call over to Fred Driscoll, Invivyd Interim Chief Financial Officer, who will discuss our financials.

Fred Driscoll (Interim CFO)

Thanks, Pete, good afternoon, everyone. With respect to operating expenses, R&D expenses, including in-process R&D, were $28 million for the first quarter of 2023, compared to $92 million for the comparable period of 2022. This decrease is attributable to lower contract manufacturing costs driven by adintrevimab commercial manufacturing in 2022, with no comparable commercial manufacturing costs in 2023 and lower clinical trial costs due to the wind-down of adintrevimab clinical trials. Our SG&A expenses were $11 million for the first quarter of 2023, compared to $8.7 million for the comparable period of 2022. This increase is attributable to lower stock-based compensation expense in 2022, partially offset by reduced consulting costs, professional fees, and public company costs in 2023.

The net loss for the first quarter of 2023 was $35.3 million, compared to $100.7 million for the comparable period in 2022. Basic and diluted net loss per share was $0.32 for the first quarter of 2023 compared to $0.93 for the comparable period in 2022. We exited the first quarter well capitalized with cash equivalents, and marketable securities of $333 million. Based on our current operating plans, we expect our cash will enable the company to fund its operating expenses, excluding any potential revenue associated with VYD222 into the second half of 2024. With that, operator, please open the call for questions.

Operator (participant)

If you'd like to ask a question at this time, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Evan Wang with Guggenheim Securities.

Evan Wang (VP of Equity Research)

Hi, guys. Congrats on the progress and completing enrollment. Just wondering, you know, in terms of recent interactions with regulatory agencies, how is that progressing? Have you proposed a phase III design? I guess how quickly can you approach them with phase I data? I know you highlighted some aspects of potential phase III preparation that's currently ongoing, but how quickly could you move into phase III once a design is finalized? Thanks.

Dave Hering (CEO)

Yeah. Thanks, Evan. Great to hear from you. Yeah, we're really excited about the quarter and the news that we have, you know, finished dosing all of the phase I cohort participants. A little bit more, right? As a part of the IND, we submitted our design for the phase III pivotal study. We're certainly excited about that and waiting for that. As I've mentioned previously, we've done a considerable amount of work to be ready and prepared for that clinical trial. As Peter Schmidt mentioned in the call, we've even got this database of immunocompromised individuals that we're looking to utilize for that potential trial and to be able to enroll rapidly instead of, you know, sort of waiting and then starting from ground zero at that point in time.

So that plus the, you know, clinical trial material all being made, all of the different elements in place, CROs lined up, et cetera, is a part of our underlying approach, which is to do this as quickly as possible, seeing the need that still remains in vulnerable populations and the EUA pathway that continues to be open. That's all supportive of our desire to do this as quickly as possible and to be smart about these different preparations and be at the ready so that really, once everything is, you know, completed and all the I's are dotted and T's are crossed, we can, we can start. Pete, anything more from your side on the clinical preparation?

Pete Schmidt (CMO)

I think completing dosing is a big milestone here because, of course, we will have to provide some data from the phase I to initiate the phase III, but we have no concerns about that happening quickly as well as Dave said.

Evan Wang (VP of Equity Research)

I had one follow-up. I guess how quickly will you be able to decide on a dose? Will this initial read in 2Q, you know, give confidence in a go forward pivotal dose? How are you thinking about dosing for the phase III? Thanks.

Pete Schmidt (CMO)

Yeah, it's a great question. you know, we have two decision points on dosing. The answer to the first part is yes, we'll be able to decide on clinical dose from the early read from phase I that you'll see later this quarter. There's also the concept of having dose flexibility at the time of submission. That's why we studied this dose range because as we know, the virus is evolving, the potency of the antibodies against the virus changes over time. We may be able to go with a lower dose at the time of submission than we decide in the pivotal trial. We're kind of leaving the door open, for multiple discussions there.

Dave Hering (CEO)

I think the only other thing I would add there that's really exciting about this initial read that we're talking about for the phase I is the sVNA data, which gives us a view based on the paper that we published to get, you know, an early readout where we would fall on that curve, which as you know, would give us this correlative protection and these titer levels related to predicted efficacy of what they would be. That will also greatly influence us as well as looking at whatever new variants of concern are circulating throughout this period of time. We can apply those back into the model and make some determinations and assessment on which is the most appropriate dose.

Evan Wang (VP of Equity Research)

Thanks. We'll jump back into queue.

Operator (participant)

Our next question comes from the line of Patrick Trucchio with H.C. Wainwright.

Patrick Trucchio (Managing Director of Equity Research)

Thanks. Good afternoon. Just a first question to follow up on the phase I data for VYD222. What serum virus neutralizing activity are you looking for in this initial data readout? Is there comparable data from earlier programs that would be good for us to look to? You know, would that earlier data be less relevant given the new variants and it's a new antibody?

Pete Schmidt (CMO)

Yeah, it's a great question. We anticipate the data will be against contemporary, variants of concern. Looking back at previous, variants or previous programs is probably not as valuable.

Patrick Trucchio (Managing Director of Equity Research)

Just assuming that, you know, the phase III program kind of progresses as you would expect, I'm wondering if you can clarify for us the use of the emergency use authorization. Specifically, what would that submission process look like, you know, from the time of submission to a potential authorization, and if or when a BLA would be needed to ensure continued access?

Dave Hering (CEO)

The first part, right? You know, we continue to see timelines. We don't have, you know, information on exactly when other companies have filed EUAs. You know, certainly we've seen that that review period from the FDA doesn't fall under any specific clock, but that it is done in the past quite quickly. That's a part of being in the emergency use piece. Unlike, you know, the PDUFA dates and BLA timelines, which have a very set clock, the, of course, good news, bad news about the EUA is that doesn't exist. We've seen it in, you know, months in the past. You know, certainly, you know, the idea is to be in continued conversations with regulatory authorities and providing them data along the way.

They would have an understanding of what's coming in that package. I don't know, Pete, any other insights?

Pete Schmidt (CMO)

No.

Dave Hering (CEO)

I mean, there's certainly no, you know, hard and fast, pieces from them. With no antibodies on the market, it certainly is not lost on them or others, the need for products like this. That to us is certainly indicative of why there would be a quick review.

Pete Schmidt (CMO)

Yeah, I completely agree with Dave. In terms of the BLA, you know, as the EUA criteria are currently written, you need to intend as a sponsor to continue to develop towards BLA. Our trials are designed as you know, we have a long-term safety follow-up. Our trials are designed to potentially support a BLA as well.

Patrick Trucchio (Managing Director of Equity Research)

Yep. That's helpful. Just one last one, if I may. What additional data... You know, appreciate the earlier comments about the openness of regulators on the approach with the surrogate endpoints. You know, what additional data might they ask for, might the FDA or EMA ask for, or what would they wanna see maybe from trials that are already running to give further confidence in this surrogate endpoint approach for approving new antibodies in this COVID-19 setting?

Pete Schmidt (CMO)

Yeah. That's another good question. There will always be this clinical endpoint portion of all of our studies. The difference here is that it's not the primary endpoint anymore. I do anticipate that we and others will continue to generate in a secondary endpoint supportive clinical data to confirm our primary endpoint surrogate markers.

Patrick Trucchio (Managing Director of Equity Research)

Yep. Terrific. Thank you so much.

Dave Hering (CEO)

Thanks, Patrick.

Pete Schmidt (CMO)

Thank you.

Operator (participant)

Our next question comes from Michael Yee with Jefferies.

Speaker 7

Hi, good afternoon. Thanks for taking our question. This is Jenna on for Mike. We wanted to follow up on the sVNA biomarker. Could you talk about what are your expectations on the biomarker? What level of reduction would you want to see for a different doses? Thank you.

Dave Hering (CEO)

Yeah. What we've talked about in the past is really right from a target product profile, and our goal is to provide at least six months of protection. Now, these are highly vulnerable groups who are currently receiving infusions and are in a variety of, you know, outpatient and inpatient care. With what I said earlier as well, I mean, the bivalent vaccines in terms of emerging data are showing, you know, limited, you know, protective properties against symptomatic disease, and that's in folks who have fully functioning immune systems. In these vulnerable populations, they're really looking for, you know, anything that can help them with prevention, and we speak with the patient populations frequently.

What we really see here is getting a look at where we would be providing, and you can make some trade-offs between dose in terms of higher or lower and predicted, you know, duration of protection. Those are the types of things that we're looking at. Again, in the publication, we've specifically linked and shown that this correlate between these sVNA titers and efficacy from previous clinical studies is what has made that curve. You can see where you are on that curve and, you know, that's really what we're comparing those against and looking to provide, again, very usable products to people who currently have none.

Speaker 7

Got it. Thanks so much.

Operator (participant)

Showing no further questions in queue at this time. I'd like to turn the call back to Dave Hering for closing remarks.

Dave Hering (CEO)

Thank you all for joining the call today. We are entering a transformational period that we believe has the potential to establish near-term and long-term success and value creation by realizing the potential of our strategy and technology. We thank you for your continued support and interest in Invivyd, and we look forward to catching up with any of you individually over the coming days. Thank you so much.

Operator (participant)

This concludes today's conference call. Thank you for participating. You may now disconnect.