All right. Looks like we're on. Thanks for joining, everyone. Really happy to be here with the Vera Therapeutics team. Set for a really exciting 2026, actually. Off a big 2025. Maybe just to start off, we have Marshall, John, of course, and Rob. Maybe to start us off, Marshall, you just give us an overview of the company, big 2025, where things stand today, what you're looking forward to next year, then we'll get into it.
Thanks so much, Gavin. It's been an awesome year for Vera this year. So far in 2025, we're still going, just getting into December. This is the year that we read out our phase 3 results. Most recently, in November, we were able to present the atacicept phase 3 results in IgA nephropathy at the American Society of Nephrology, the biggest kidney meeting of the year in Houston. We were the opening plenary session. We got to publish in the New England Journal of Medicine simultaneously. We've been off to the races preparing for U.S. commercial launch in 2026. We did file our BLA on November 7th. With expected priority review, that would give us a potential approval date in the middle of 2026. That's where we are today. I started Vera nine and a half years ago. It was a fantastic time in biotech.
We had a thesis that we could take a fusion protein, the natural receptor, to BAFF and APRIL, fuse it to Fc, and be able to reduce the autoantibodies that cause IgA nephropathy, as well as many other autoimmune diseases, and do that in a dose-dependent way such that you would not get immune suppression at the same time as efficacy. We would like to do that in a convenient dosing format. Those are three big asks. Here we are at the end of 2025. I think we have really checked those boxes. We now have a best-in-class molecule poised for U.S. launch next year. Importantly, efficacy is the most important thing. Efficacy in kidney disease in these young patients with IgA nephropathy is measured by eGFR, estimated glomerular filtration rate. We are the only program to have two-year eGFR stability.
That's published in JASN, where the slope of eGFR in patients taking atacicept is - 0.6, so close to -1 , which is the general population, as opposed to these young patients who are on a track to lose their kidney function before the age of 50. That's a massive effect size. That really has big implications for our clinical program. Efficacy is driven by eGFR. That's well recognized. We're the leader in efficacy in this space. Safety is comparable to placebo. We've seen that now in two randomized control trials in phase 2 and phase 3, both peer-reviewed and published, and now under review by FDA. That's really what we were shooting for is the Goldilocks therapeutic window where we saw clean safety but transformative efficacy. Finally, the dose and convenience. We're the only ones on track for a low-volume autoinjector.
That's been a tremendous amount of work. I am so proud to represent the Vera team in delivering that. Vera has built a commercial leadership team. We are very well poised in preparing ourselves for U.S. commercial launch next year. Great time for Vera. Thanks for the opportunity to talk today.
Awesome. All right. Lot to talk about. Let's just do a couple of questions on the clinical data side of things. Not too much time there. I guess first, on the ADA side, it's become a recent topic after seeing the sibeprenlimab label. I guess just to be clear, have you seen any ADAs in your phase 2 OLE on the neutralizing side, any sign that's impacting efficacy?
Yeah. Rob?
Yeah. Thanks, Gavin. It is common with biologic therapies, protein-based therapeutics, to see the development of antidrug antibodies. What is not common is to see antidrug antibodies that neutralize the impact of that therapy. I think what all of us are reacting to is what we saw in the sibeprenlimab label, which is that there was both a reduction in the exposure to the drug or a lower PK in patients who had some of these antidrug antibodies. It was associated with an attenuation of the efficacy, reduction in the proteinuria, raising real fundamental questions around the long-term sustainability of an impact on kidney function. As Marshall says, given the fact that we've published two years of eGFR stability data, it's a real open question as to if we'll see that from the competition.
In contrast, atacicept, as a human protein, has not been one where we've seen any evidence of neutralizing antidrug antibodies. We would not expect to see that when we get to full approval.
All right. Makes sense. I guess we'll need to see the review documents to see what exactly the correlation of the UPCR impact is. If there's a correlation to eGFR beyond that, I think we'll see some of that in the review docs. Maybe we'll talk about that in another month or so.
Yep.
All right. Hypogammaglobulinemia side also become a topic after ASN. What's your current take on this? Do you think this is going to be a differentiator for any of the therapies? What did you see on hypogam in your phase 2 OLE and in the phase 3?
Yeah. I think people have been talking about this because of data that was presented by Vertex back in Houston at the American Society of Nephrology Kidney Week. We noticed it. That was from a small phase 1b uncontrolled experiment. We will have to see what happens when they do their randomized experiment with a different approach to kind of recording for hypogamma. We have not seen evidence of hypogammaglobulinemia associated with infection in the atacicept program through this point in phase 3. We have a lot of confidence that the profile of atacicept really lends itself well to chronic administration, where you would simply look for evidence of infection. Across the phase 2 and phase 3 program, we have not seen a difference in the rate of opportunistic infections in patients treated with atacicept versus placebo.
Awesome. I guess it was really good to be at ASN this year. You guys have presented metrics on this before. I'm curious to kind of get your most updated feedback. Provider awareness of atacicept within the BAFF APRIL class seems like it's really high. That's something we definitely picked up. What are you seeing on that front?
Yeah. I would say it's a little too early to give you solid numbers. We do have immediate post-ASN share of voice that's at the top of the top of the class in terms of B cell modulators. I think that's been a result of the exciting data and important that we're out there. We're talking about the data. That's clearly had an influence.
Awesome. All right. Let's switch gears. Let's go over to PIONEER next. We'll come back to the commercial side later and again. For PIONEER, I think the guidance is still for Q4 for this update. What's going to be included within that?
Yeah. So just a little background. PIONEER is a phase 2 trial that we announced last year. We started earlier this year. And it's got two basically distinct objectives. One is we're looking to study atacicept in all comers with IgA nephropathy. Historically, the clinical trials in this space have been limited to only a fraction of patients with biopsy-proven IgA nephropathy. The PIONEER program is designed to study everybody else, so those who would not be eligible for the phase 2 or phase 3 inclusion criteria. Second is the same physicians who care for patients with IgA-mediated disease care for patients with other forms of autoimmune glomerular disease, like membranous nephropathy, FSGS, or minimal change disease associated with specific autoantibodies. We have cohorts of those patients in this program as well. We've been thinking a lot about when to share these results.
Given the focus that we had on IgAN at ASN, we decided not to share results there. Now we're thinking about, is it going to be Q4? Are we going to wait into 2026 to align with one of the earlier academic conferences to share some of the results.
Gavin, I want to pick up on one thing that's pretty important. That's in our phase 3 program, similar to others in the space, we focused on biopsy-proven IgAN patients who are at "high risk of disease progression." Despite being on background CKD therapy like an ACE-ARB SGLT2 inhibitor, they still had over a gram of protein in the urine. What was remarkable, I think, last week is that the competitor program from Otsuka had no proteinuria threshold in their initial accelerated approval label. That really was a first in the space. I think represents a lot of excitement for this class. PIONEER, as a study that Vera is running, is exploring the benefit, the potential benefit of atacicept in patients with lower proteinuria. It's, of course, awful to end up on dialysis or need to transplant before the age of 50.
It is also awful to end up on dialysis before the age of 60 or 70. I get a lot of that feedback. So does the whole team at Vera. When we are out talking to nephrologists in the United States, they are saying, look, it is not just those with high proteinuria. It is others who I am worried about losing their kidney function. That is what PIONEER is all about.
Yeah. Very important point. All right. When you do give the next PIONEER update, what's going to be included within that? Is it just going to be data? Is there going to be updates on registrational path? You kind of alluded to it being at a medical conference. I'm just trying to get a sense for kind of how comprehensive it's going to be.
Yeah. I think at an academic conference, we'll focus on the data itself. I think as we get into 2026, we'll have a lot more to say about our registrational strategy for some of the new indications. Team's hard at work at it. We look forward to doing that more in a corporate setting.
Yeah. OK. That makes sense. I guess we have other supportive PMN data already. There's some link to, with that being an IgG autoantibody, there's some link to the nephrin side. So we have some pieces of evidence to believe in those indications already from a clinical data perspective.
Yeah. The membranous nephropathy opportunity is predicated on this being an autoantibody-driven disease, first identified to one target kidney antigen called PLA2R. Patients, about three quarters of the patients with membranous have detectable anti-PLA2R antibodies. Other sponsors have shown that they're able to reduce the circulating level of those autoantibodies. That's associated with a reduction in proteinuria. We're studying those patients today. I look forward to sharing some of the results. We're very keen on that indication.
Yeah. I guess I would also add, Gavin, that inhibiting BAFF and APRIL with atacicept 150 weekly captures a lot of things. It comes back to that original thesis that I just shared. Getting the therapeutic window correct, especially in IgAN, where the efficacy is where it is, the safety is where it is, allows us to think very strongly about accelerating more quickly into what Rob presented at R&D day back in October of last year, which was, let's go into additional glomerular nephritides, membranous nephropathy, FSGS, MCD that are driven by autoantibodies, as well as other areas outside of kidney.
Yeah. All right. One question on the FSGS nephrin side. It's not really a standardized test fully in terms of the titer cutoffs. How big is this population relative to the FSGS population?
Yeah. We've estimated that the size of the population is comparable to the anti-PLA2R positive membranous side, so in the neighborhood of 35,000 patients in the U.S. You're right that the status of the maturation of the assay in terms of being available for clinical use differs between the two diseases. We have a commercial-grade assay available for anti-PLA2R. We don't have that yet for FSGS and minimal change disease as it relates to the anti-nephrin assay. I like that we're ahead of the curve. I like that we're leading. I like that we're studying both a disease like membranous where we have an established assay, as well as a disease where that is coming in the future. Vera can do two things at once.
Awesome. All right. A couple of questions on monthly dosing before kind of going commercial, which will be a big focus for next year, of course. When you do give the monthly dosing update, is that going to be just clinical data? Or are you also going to be outlining kind of the registrational path to bring this to market?
Yeah. It's a great question, Gavin. The way I've thought about it is I don't want to do kind of sequential haircut updates on this program. Earlier this year, we initiated a monthly dose range finding study where we're looking at three different possible monthly doses of atacicept, comparing that to weekly administration with 150 mg. Once we identify which the right dose is, we'll come forward with the integrated story that also lays out the time and events to get that on the label. Depending on the dose, the program may be a little different. I don't want to show just infinite possibilities. I'd rather be very specific. Here's what we learned. Here's what we're going to do. Here's what you can expect.
Yeah. I would add the VT-109 story to that as well, Gavin. This is part of Vera's ability to broaden the profile. The profile that we're taking to market next year is a once weekly. We're looking at monthly with atacicept. The VT-109 is really targeted to look at every three to every six months. You should know that we're playing a long game to really be the dominant player in the BAFF APRIL space.
Have you said anything about the VT-109 indication plans yet?
Not yet.
OK. Next year.
Possibly.
OK. Wait to hear more. I guess just high level back to the monthly atacicept side. The game plan is not to run a full phase 3 efficacy study. It's to bridge on some type of metrics. Is that fair to say?
I would say we want to be as creative as possible about the nature of the program that will enable us to achieve label claims for that dosing interval. Depending on the dose, I think it could be a more limited program versus a larger program. That'll be something we'll be able to talk about next year.
All right. Sounds good. Have you said the concentration you can formulate atacicept to?
We haven't commented on anything other than the formulation that we have, which is 150 mg in a 1 mL volume, is something that's working really well. While we're talking about the monthly program, I don't want to miss an opportunity to just share again that our confidence in a small volume, once a week, autoinjector-enabled administration with a small needle is a phenomenal presentation. Just after reviewing the sibeprenlimab label and their need to use a prefilled syringe, I think we're really differentiated in that regard. We are focused on learning more about monthly dosing. Our confidence in being able to launch effectively with atacicept with the presentation of an autoinjector delivered once a week is as high as it could be.
Yeah. All right. Let's talk about the launch then. That's going to be a big focus for next year. I guess first off on just kind of the pricing and access side, have we seen the sibeprenlimab price yet? I guess given the broad label, what's your guys' expectation for how some of the policies are going to start to shake out?
Yeah. It's hard to make a comment given today where pricing has a big range. There are four drugs approved. Three of them are in the $160,000 per patient per year range, several of them for chronic dosing, not all of them, but several. At the upper end, Fabhalta up in the $500,000 range. There's a broad range. We've certainly been planning on a variety of scenarios. This all comes down to value. What is the efficacy? What is the safety? As you can hear from us, we believe atacicept is positioned as best in class. That's driven by both efficacy and safety. We'll see what those dynamics play out. I think it's helpful that we have a competitor going first. We'll see how that unfolds in the near term.
We certainly believe that if you can stop eGFR decline and demonstrate that convincingly to regulators, and that makes it into your label ultimately, that creates more value than other programs that have not been able to demonstrate that. I think that's something to really focus on.
Just to add, I think as we look at the label that Otsuka has achieved, as well as the way the guidelines have been evolving, I think if access is not a barrier, these drugs are going to become the dominant approach to managing IgA-mediated disease. That is extremely exciting to be part of. That said, I do think there is some overhang in the label of the first approved drug in this class, which leads a lot of opportunity, I think, for a fast follower to come in and establish a leadership position.
Just on commercial preparedness, are you guys ready to launch? How much more investments do you need to make to be ready for that?
We are ready to launch. I think it's public out there how we've sized and structured our U.S. sales force. Sales leadership is in place and has been for some time. As we bring in that sales force, the people part is done. Preparation has been ongoing for a very long time. We're very ready to launch in the very near- term.
Awesome. I guess looking ahead too, you kind of alluded to additional indications. I'm not sure if that's kind of a separate discussion from VT-109 or kind of part of one of the same. What are you guys thinking about at the moment? Broad potential universe.
Yeah. Again, I think when you've got a molecule at this level of validation with both phase 2 and phase 3 efficacy and safety with the dose range finding phase 2 and phase 3 that is highly consistent and reproducible, that gives you a lot of confidence about the therapeutic window. Taking the same drug into different patient populations, of course, has differences. That requires some thought. Determining that that window exists and we've made it happen with atacicept 150 gives us broad use. I think you can hear from us we're being very systematic in building on the strengths that we've built at Vera, which begins in nephrology with membranous nephropathy, with FSGS, with MCD. It quickly can go into other areas.
We've certainly developed our thinking and have kept that current about all of the validation for this space, whether it's BAFF APRIL dual or APRIL alone, what kind of data we've seen in multinational trials, what kind of data we've seen in single-country trials. We're aware of all that. We analyze that. We keep our analysis up to date. We can count at least 11 additional indications beyond nephrology that have us eyeing really a double-digit billion-dollar market potential for this program.
Awesome. A lot more to talk about. We're just at time, actually. I think that's probably a good way to end it. Marshall, Rob, Shawn, thanks so much for joining, guys.
Great. Thanks so much.