My name is Lisa Bayko. I'm one of the SMIDCAP analysts here at Evercore ISI. Welcome to HealthConX. We're starting off our last day with Vera. Vera is a company that is working in an area that I care deeply about, which is IgA nephropathy and renal disease. They've done a great job in really moving the field forward. We're really excited, as 2025 will bring about their phase 3 study, which we think is in good shape to support an approval. With that, I want to turn it over to the team. Maybe we can do some brief introductions. Sean, I'll turn it over to you and go through.
Thanks, Lisa, for having us. Sean Grant, Chief Financial Officer.
Good morning. Rob Brenner, Chief Medical Officer.
Good morning. I'm Marshall Fordyce, the founder and CEO.
Great. Well, let's start just to make sure everyone's on the same page with the company overview. I think I'll turn it over to you, Marshall.
Sure. Lisa, thanks so much for your work in the area. And I want to give you credit first for probably being one of the few analysts to interview patients in the patient organization.
Thank you.
Being passionate about an area of medicine where there's an opportunity to change the standard of care means that you have to find champions. And this doesn't happen on its own. So appreciate your leadership on that. Vera Therapeutics has been a public company for three and a half years. 2024 has been a fantastic year for us. We've been now revealing for the first time in a phase two trial that our development candidate, atacicept, can stabilize kidney function in these young patients over a two-year period. And we're the first and only to show that in the field. That's really what's been so outstanding. And we've initiated a phase three trial long ago. And that trial has fully enrolled its primary endpoint cohort. And we'll be reading that out in Q2 of next year, enabling a BLA filing in the second half of next year.
Vera is now preparing, of course, for commercialization in 2026. That gives us the opportunity to really expand our potential impact by opening up new studies. Rob, our CMO, presented back in October at R&D Day for Vera an expansion of our development program to include phase two studies in further populations in IgA nephropathy in our PIONEER study, as well as looking at adjacent autoimmune kidney diseases where we think atacicept could have a substantial impact. Really, as an overview, I'd say the data that we've shared has been very well received. We're talking about a disease that affects young people. About one in 10 of us has an autoimmune disease, whether it's the US or globally. IgA nephropathy, from a developer's perspective, is in some ways ideal. We really understand what causes the disease, the pathophysiology. It's caused by B cells.
B cells are overstimulated by two cytokines, BAFF and APRIL. Atakicept is a dual inhibitor of BAFF and APRIL. We really have demonstrated that at the dose and frequency that we are administering, we're normalizing that B cell function. We have not seen evidence of immune suppression. Even during the time of COVID-19, when if you took steroids or Rituxan, you were at high risk of being hospitalized or dying from COVID, we did not see that in our phase two trial. This is really opening up an opportunity with atacicept to move from immune suppression to immune modulation, not just in IgA nephropathy and autoimmune disease in renal disease, but autoimmune disease generally. That's the opportunity ahead of us. We've got a great team, great momentum this year. We're really looking forward to 2025.
OK, great. Let's dig into, I think, maybe the market a little bit and start there. And then we'll get it back and come back to the clinical trials. Maybe I'll turn it over to Sean, I guess. He'll probably crunch a bunch of the numbers. Kind of characterize the market for us in terms of how many patients there are, I mean, maybe even globally. And then let's break it down to how many are actually diagnosed, how many you think would be eligible for treatment, maybe with accelerated approval, maybe later on when you get a label expansion with full approval, that kind of thing.
Thank you, Lisa. Broadly, we see it as a very large market, as a $6-$10 billion potential market, and the majority of that being in the United States. We see roughly 160,000 patients in the U.S. alone, and within our ORIGIN 3 indications, we think it's roughly half of that, and this is really why PIONEER is a portion to really tackle the other portion of the patients as well to really capture 160,000 of those patients.
OK. And when you talk about half the patients, do you expect your label to have any qualifications of a certain level of proteinuria or eGFR function? Or is this really going to be a broad label for anyone with IgA nephropathy?
The precedent in this disease is that the FDA uses an approach where companies are able to achieve initial approval, accelerated approval, based on nine-month readout of proteinuria. And then with two-year follow-up of eGFR or glomerular filtration rate, sponsor is able to achieve full approval. At the time of accelerated approval, the history has been the indication statement and label talks about the proteinuria threshold that was used in the clinical program. At the time that there's conversion to full approval, the proteinuria threshold evaporates. And patients are eligible if they've been diagnosed with the disease and are considered to be "high risk." The reality is all patients with IgA nephropathy are at high risk of requiring dialysis or transplantation during their lifetime. So in my view, I think everybody with this disease is at risk.
So I think if the cadence of what has happened in the past would play forward, it's possible that we'll have a proteinuria threshold at the time that we have accelerated approval and that will disappear at the time of full approval.
What do you think that would be, that level?
It's been in the neighborhood of about a gram, gram and a half of proteinuria a day.
OK. It seems like those thresholds are lower now.
They are. And in many ways, I think the data that the FDA has been exposed to and that we've shared during the course of 2024 starts to raise some fundamental questions about the relationship between proteinuria and GFR. Because of the general relationship and the academic community's narrative about this, the FDA adopted this approach to using proteinuria as a surrogate endpoint for accelerated approval. But now we know, based on the results of our program in comparison to others, that the story is a little bit more subtle. And it turns out that you can have many mechanisms of action in this disease that achieve relatively comparable levels of urine protein reduction. However, the impact on GFR, the measure that's most tightly correlated to the need for dialysis or transplant, is very different.
You can achieve a 30%-50% reduction in proteinuria with endothelin receptor antagonism, with SGLT2 inhibition, with steroids, even maybe with a complement inhibitor. But none of those therapies get the eGFR profile to what has been called for by guideline authors as the goal, was to get the eGFR rate of loss to less than 1 mL/min/year. Why is that important? For healthy people without biopsy-proven kidney disease, we're all losing about 1 mL/min/year of GFR. Because IgA patients are usually diagnosed relatively late in their disease, their lifetime risk of dialysis or transplant is very high. The vast majority will progress. Only by achieving a GFR rate of loss that's comparable to the healthy population can you have a real impact on that lifetime risk.
And in our clinical program, now at two years of follow-up, we've shown an eGFR rate of loss of minus 0.6 mL/min per year. That kind of GFR profile is distinct from what we saw with other modes of intervention where you had a robust antiproteinuric effect. Therefore, I think the FDA is starting to think about how do we want to have labels that help provide a little bit more guidance to practitioners as we think about trying to intervene in this disease.
You're one of the few companies that has this kind of long-term eGFR data. And you're going to go forward with proteinuria for accelerated approval. Is there any chance that that could support actually a full approval from the get-go and have a broader label, which would allow access to patients in a way more quickly?
Yeah, I think it's possible. However, I respect the fact that the agency has outlined a roadmap for how they approach this disease today, and that uses the paradigm of accelerated approval followed by full approval. There may come a time where that changes, and there may be a data set that prompts them to change, but that is certainly our corporate base case. And in our conversations with the agency, we haven't dived into that kind of discussion at this point. It would be premature. I will say I know the agency is very engaged with us. In May, we received breakthrough designation based on the results of our 72-week experience prior to having the full 96-week, so they see the potential benefit for patients, and that allows us to have a very open and frequent dialogue, which we're taking advantage of.
You've got your phase three ongoing, as we talked about. We're looking for data in the June time frame. What new do you think we're going to learn in this study? Is there any sort of new analysis? I mean, as I see it, most of the studies are de-risked by your phase two B study already. But any new analyses or any sort of interesting twists or data you can cultivate doing any biopsies, anything that may kind of even give us further insights into the benefits of B cell modulation?
I like the question. I think I would use that as a way to highlight the phase two trial that Vera ran was robust and ran for two years and was a global double-blind placebo-controlled trial that did proper dose exploration. That gives us high confidence that that will translate into phase three. As clinical scientists, as a corporate entity, we respect the need to reproduce that data and reproduce that data with a larger footprint and with the single to be commercialized dose. That's been our approach. That's a standard drug development approach. It is just differentiating within the competitive space.
OK. Anything that you think you'll be able to articulate or highlight about your particular mechanism, which has both APRIL and BAFF? You'll be coming to the market around the same time as another B cell modulator that is APRIL only. And just wondering if that kind of portends any unique features that you might be able to spell out as well.
Yeah, maybe I'll start, and Rob, I'd be curious for you to add as well. Atacicept is a fusion protein. So it's a biologic therapeutic modality. It takes advantage of the natural receptor for the two known cytokines, BAFF and APRIL, which exist to cause B cells to survive and grow and differentiate into plasma cells, which become the factories for the antibodies that we need to fight infection. So this is a very well-known biology. That's what interested me in this mechanism as we contemplated what mechanism out there that we know in biology could help patients with autoimmune disease that is likely to be pretty solid biology that hasn't been adequately taken advantage of with therapeutics. And we think this is a good bet. It is unlikely we're going to discover a third or a fourth cytokine.
We know for sure that both BAFF and APRIL are important for B cell survival and differentiation. In fact, one side of the validation that we saw before we decided to develop this molecule is that inhibiting BAFF alone is approved as an approved product. It's a commercially successful product. If that's the case, then inhibiting both makes sense from an efficacy perspective. We're thrilled that we got the dose right. Because when you modulate B cells, it's not about maximizing potency. It's about Goldilocks. It's about getting the dose right. If you over-inhibit B cells, then you raise the risk of infection. And if you don't do it enough, you're not going to get the efficacy that you need. I think the phase 2 data that we're sharing supports the thesis that we've got the right Goldilocks approach here. That's true for really any drug.
Having the natural TACI receptor inhibiting both BAFF and APRIL is the most elegant, parsimonious way to inhibit the two known cytokines. The alternative approach of inhibiting one or the other, APRIL alone or BAFF alone with a monoclonal antibody, it's a different approach. And I think the biology needs to translate into substantial clinical evidence. And we haven't seen that yet. And we await that data so that we learn more about this pathophysiology and the way to treat the disease. But for example, inhibiting APRIL alone, I think, is confined to very few indications that one can address, whereas inhibiting both BAFF and APRIL opens up a world of autoimmune diseases that could be addressed by this mechanism. Rob, I'm interested in any other thing you would add here.
Yeah, I think it's very well summarized. In the nephrology community, we're not experts in B cell biology, and one of the opportunities that Vera has is to help this community become more facile in understanding this component upstream of the kidney involvement and how to think about it mechanistically and scientifically, and Marshall's absolutely spot on. There are two cytokines that are the predominant drivers of B cell activity, and what attracted me to the Vera story a year ago was using the native sequence of the TACI receptor, which is nature's solution of how to bind both BAFF and APRIL, to use that in a biotechnology reagent, fuse it to an activated Fc, have a soluble receptor with a 35-day half-life. Now, if we dive a little bit deeper, we know that BAFF and APRIL both circulate as monomeric proteins, monomeric cytokines.
But they also circulate as multimeric constructs. Some of those are actually combo BAFF-APRIL constructs. So there's a lot of elegance to think about harnessing the power of nature's evolved receptor for that full panoply of cytokine representation because we know that TACI binds BAFF monomers, APRIL monomers, and multimeric constructs. I think the jury's out whether a monoclonal antibody against APRIL actually binds all the APRIL that's in circulation if a portion of it is in a multimeric construct with BAFF. I don't think we know that. So I'm attracted to that story. I find it to be rather comprehensive. If you want to interdict against the B cell, you know there are these two main drivers of activity. You want to bind all the constructs that are fueling activity.
Tell us a little bit more about your commercial preparations. You'll have phase 3 data this summer that kind of puts you in line to submit a BLA in the second half. We'd look for approval in 2026. So a year from now, you'll be pretty much at the end of getting towards the finish line to prep for approval. So do you anticipate, for example, hiring a field force ahead of approval and for market preparation and formation, all that kind of stuff? And what kind of pricing research have you done? And if you can articulate any benchmarks there.
Sure. We can share a little bit, but not too much at this stage, Lisa. And we haven't been public on when we plan to bring in a field force from a sales perspective. But we certainly have field directors on the medical affairs side. It's a pleasure, as you build a company, to move from clinical research, pick the right target, get the right drug, get the great fortune of strong clinical data, present that, engage with physicians and potential future prescribers. And we've really built in that way at Vera. So under Rob's leadership, we've really expanded our connectivity to the nephrology community. That's been a major push for us in the last year. And beyond that, we've had a core team on commercial planning for several years now.
That team, of course, has grown since the success of our phase two trial and our confidence in the phase three program as well. It's very much, I would say, on track, likely ahead of schedule in terms of our commercial build. What we like about IgA nephropathy is that it's an addressable market by a company like Vera. That's something that we're preparing for. There's a lot to build on at this stage. As you saw, throughout the year, we've announced bringing in new leadership. That team has been growing throughout 2024.
What are some benchmarks to think about for pricing? I'm sure you've been starting to do a bunch of work on that.
Sure. I mean, I think we can look to the currently commercialized products that are in IgA nephropathy that have not shown the stabilization of GFR at the $150,000-$170,000 plus per patient per year price range. We can look at those precedents and then imagine a valuation of a new product that delivers GFR stabilization. So I think we have a very different value story than what already is on the market. And we look forward to those discussions with payers.
Otsuka coming to the market probably a little bit ahead of you guys will set some sort of price. Do you sort of imagine parity pricing there? I mean, do they kind of set the agenda in a way that way?
Yeah, I can't really comment on that. Of course, we watch these launches carefully. We understand the competitive landscape in a pretty detailed way, and so we think that positions us very well.
Excited that you're working on life cycle management and as part of that once-monthly dosing option. When would we have any insights into that? Is that a 2025 story?
Yeah, let me just make a general comment that it's our belief in biotech that you have to out-innovate yourself. You can't just develop one product and expect to maintain that franchise over time. We've had that attitude from the very beginning. We love the initial commercial profile of atacicept that we're bringing to market in 2026. That's atacicept dosed at home, self-administered as a 1 cc injection. So patients take this on a Saturday morning. They remember it because it's every week. And we showed.
Is this refrigerated, by the way?
Yes, it is. Yeah. So you have to take it out of the refrigerator. And then it's less than 10 seconds to administer it. So this is very much like an Ozempic type of format for patients. The good thing is we've got data. We've got two years of patients doing this. And over 90% are continuing to do that over two years. So we've got data to say, look, this is a very acceptable Ozempic-like format. With that in mind, we know that the future might involve different formulations, different dosing intervals, next-generation approaches. Because we believe that getting the dose right and having the right approach to BAFF, APRIL, and inhibition, both for IgA and for other indications, is a huge opportunity. And we've been well at work on that internally.
What we've shared publicly about longer dosing intervals is that we are doing a dose exploration study in 2025, looking at a variety of doses in the monthly format. We don't see utility in looking at shorter intervals than that, and at this stage, we are looking at monthly.
OK. And then just to wrap up, because I know we're over time, maybe I'll turn it back to Sean again. If you could give us a view on cash runway. And then let's just wrap up with 2025 catalysts that we should look forward to.
Yeah, terrific. So we're well capitalized, currently $670 million in cash. That funds us through several milestones, including Q2 of next year, our phase 3 readout, BLA filing, and approval and launch. So we'll capitalize at this time.
Great. And just as a summary, 2024 has been fantastic. It's been all about game-changing data in patients and stabilizing kidney function over a two-year period with high retention at an at-home self-administered product. And phase three readout is expected in Q2 with a BLA filing in the second half of next year. And some of the other studies looking at adjacent indications, so in the PIONEER study, this is a basket study, open label. So we have a chance to share data throughout 2025. So that's to come as well.
OK, wonderful. Thanks, guys.
Thanks, Lisa.
Thank you. Thank you, Lisa.