Invivyd, Inc. (IVVD) Earnings Call Transcript & Summary

Hello, everyone, and good afternoon, and welcome back to H.C. Wainwright BioConnect Investor Conference in partnership with NASDAQ. I'm Patrick Trucchio. I'm the senior health care analyst at H.C. Wainwright. It's my pleasure to introduce our next speaker, Dave Hering, CEO of Invivyd, a clinical-stage biopharmaceutical company focused on delivering antibody-based therapies to protect vulnerable people from devastating consequences of circulating viral threats, starting with SARS-CoV-2 and then expanding to flu and other high-need indications.

So maybe we can start first with just some brief background on Invivyd, including the history of the company.

Sure. Thanks, Patrick, and thanks for having me here. Invivyd was created during the pandemic. It's only a few years old with the goal, exactly as you said, of bringing products to market, starting with COVID and going from there. And originally, we had an initial compound ADG20, which we took into the clinical trial and now pivotal data -- I'm going to use this instead and use that. We took it into clinical trials and delivered against all of our endpoints in record time. And so that was the impetus and start of this. And now really, what we're envisioning for the company is a serial monotherapy approach to delivering products against COVID-19. And so what we've seen is one single or a combination of antibodies is highly unlikely to remain active against a virus like SARS-CoV-2 that continues to evolve. And so we've geared the company directly to address that ongoing threat of the virus, and that's really where we are today.

Can you talk more about which patients Invivyd is going to focus on? Where is the unmet need at this stage of where we are with the disease?

Yes. I mean, interestingly, you've got this case where vaccine efficacy in prevention of symptomatic disease has plummeted against the current variants, which is unfortunate for where we are. That plummeting efficacy is due to the viral evolution and change in variants. The most recent bivalence that were boosted have the ancestral Wuhan strain and BA.4, .5. We're now into BQs and XBBs. And some of the new data shows that there is limited to no efficacy in preventing symptomatic disease in the XBB-Omicron sublineages. This has also led to continual waves of disease and, unfortunately, also emerging evidence of reinfections and what the potential long-term impacts could be. And that's to people who mounted immune response to vaccines and need prevention. When you talk about immunocompromised people in particular, vulnerable populations, they don't even have the benefit of a minimal response or use of vaccines. Monoclonal antibodies are designed for prevention, treatment and post exposure, and they were an instrumental part of the fight against COVID-19 that has been eliminated. So I know we'll talk about it some more. But right now, we are where we were in 2020, which is there are no monoclonal antibodies on the market for prevention. You have immunocompromised people with a significant unmet need. We talk to them every day with our patient advocacy groups. And while the rest of us have more or less gone back to leaving our houses and going back to where we were, these are folks who feel trapped and nowhere to go. And so that patient population, in particular, is one that we're targeting as a preventative approach and to give them a product that provides them hope.

Right. And then maybe talk a little bit more about Invivyd's antibody platform? What's differentiated about this platform and the approach?

Yes. So the antibody platform comes from our own internal discovery as well as partnerships. The company utilizes a technology from Adimab for yeast expression. And what we then do is something differentiated from other antibody manufacturers, which is we do engineering of antibodies, which is affinity maturation. This allows us to find antibodies that wouldn't be just naturally occurring. So yes, we do B cell mining and look for those. But this engineering approach gives us, as I said, antibodies that we see should have less immune pressure. Hence, the goal is to increase the probability of higher durability, higher duration in the market. And that to us is one of the differentiating factors of our platform.

Right. Maybe you can also give us an overview around the partnership activity, how some of these came about? What's the strategic importance of the current partnerships in your operations?

Yes. As I said, I mean, I mentioned the work we've done with Adimab. We have an existing relationship with them. That really has been one of the foundations and building blocks of the antibodies. We've now continued to evolve that partnership. We're in the process of transferring in some of the technology into our own internal labs, which is then, again, what we could be using for both COVID as well as other infectious disease down the road. We have a strong partnership with WuXi, which is a manufacturer, which allows us to rapidly produce antibodies both for clinical trials as well as for commercial production. And so those 2 are really critical in terms of our goals to be able to move through development rapidly, find antibodies perpetually and deliver them and have products on the market sustainably.

So recently, the FDA cleared VYD222 for an IND. I'm wondering if you can talk about the VYD222 program, where did this kind of -- how did it come about and some additional details around kind of where you see this program going from here.

Yes. 222 is very exciting. It's our reengineering strategy in action. So 222 is a reengineered version of ADG20, which was our original compound. We shifted 8 amino acids in the variable region that targets the spike protein of the virus. And so basically, what we did is take those connection points and just pivot them slightly so that we could recreate activity with the antibody against the Omicron sublineages. And to date, in vitro, we've shown activity against all of them through XBB1.5, and that's what we continue to monitor. We're excited about this for a variety of reasons. One, you talked about the IND. In December of this past year, there was an FDA-EMA meeting. And in that meeting, they specifically talked about this prototype concept where if you have a prototype product, you could then use that to either accelerate or augment your package for regulatory. And so by starting with ADG20, which I mentioned we already have conducted clinical trials extensively across prevention, post-exposure, pre-exposure, we are hoping to utilize that as a part of the 222 development program, both in terms of safety and totality of data. So that's the exciting part there. We also see this as the scaffold that we can utilize going forward. And that is important because, as I've said, we expect viral evolution to continue, unfortunately, with the SARS CoV-2 virus. And so we are continuing to put new antibodies into our pipeline to address that going forward.

Yes. That's helpful. And then a couple of follow-ups. Just the first around the regulatory framework that you mentioned, how has this evolved? I mean I think all of us are familiar with kind of how COVID drugs were approved previously. How is it evolving now? Is there kind of a precedent being set for accelerated regulatory pathways for COVID drugs?

Yes. I mean -- and it is an evolving landscape, as you can imagine. Even for our original ADG20 product, we saw that as more and more people got vaccinated, that changed the paradigm. And then you had oral antivirals that came to market, and that changed it. And so you could no longer run placebo-controlled trials in the U.S. for treatment, right? So that was a big change. The original studies in most monoclonal antibodies were clinical endpoint event trials, meaning you were testing placebo and drug and testing who got symptomatic COVID-19, right? So you are looking to find areas around the world with high disease incidents to be able to get at this data quickly. What's evolving now is this approach using surrogate and biomarkers in order to do these studies much more rapidly. There is a recognition globally amongst regulators that the pace of what I call human nature or the regulatory side isn't keeping up with mother nature. That's why we continue to have these gaps where we have no products on the market like we currently have. And so the approach here continues to look at how to use surrogate and biomarkers in order to do trials more effectively and efficiently. And that's really our approach with 222. We recently published a paper specifically talking about relative protection and utilizing serum-neutralizing titer levels and comparing that to efficacy data. You could also see with AstraZeneca in their new SUPERNOVA trial that they are using a bridging study. And so again, you can see this shift away from clinical event endpoints to biomarker surrogate correlative protection, which we see as a great step in the right direction for how we as a society are going to be able to stay ahead of the variants.

So just back on VYD222, can you talk about some of the preclinical data that you've generated so far and how you would expect that to translate as you bring this program forward to Phase I?

Yes. So the preclinical data, right, we have -- we can continue to conduct both pseudovirus assay in vitro testing, which shows IC50 in activity levels with those data. And then looking at a variety of PK modeling, you can start to get a good estimate of duration of protection against the current variants. And so it's a space like no other than I'm aware of in biotech, where already in preclinical and doing in vitro work, you already have a good sense of what the potential efficacy could be of your drug. So before you've done Phase I, before you've done Phase II or III, you're starting to get that early read. We continue to do that. You do your normal panel of rat TOX and TCR and the rest. And so we've continued to conduct those. But I think, like I said, the most important are these early views of how the product is going to work well before you're doing these large-scale trials.