Welcome everybody to the Leerink Partners Global Healthcare Conference. My name is Roanna Ruiz. I'm one of the senior biotech analysts here at Leerink. It's my pleasure to host Akebia Therapeutics. With me, I have CEO, John Butler, and CFO, Erik Ostrowski. Thanks so much for joining me today. Hope you're doing well. Thanks for the invitation. Yeah. Great. For people in the audience who might be new or visiting this story, wanted to just ask you to walk us through, you know, the main focus areas for, you know, your overall capital allocation strategy, some of your top clinical and commercial goals for the next couple years. Could you just frame like how is this year setting up? Sure. You know, as a commercial company with a pipeline, we really have to be thoughtful how we, you know, go about spending our money. For strategically, we have three key strategic areas. First is our commercial product, Vafseo, it's to drive that become standard of care. In addition to the commercial investments that we make there, we also have a number of phase IV, 3b type trials ongoing now also, which we think will generate the kind of data you need to become standard of care, and I'm sure we'll talk more about that. Second is build on our commitment to kidney disease. We are very much a kidney disease company and I see that, you know, continuing for the future, and that's building out our pipeline. Praliciguat, AKB-097, AKB-9090 in acute kidney injury. The third, which is by far the smallest bucket of spend, is to build the future beyond kidney disease. Right now that's things like the investigation of Aduhelm and in ARDS that we're doing with UT Health to really prove the mechanism. 10108 in retinopathy of prematurity, where we have tox work going on now. Small investments, but potentially really meaningful business areas. Yep. I hear you. That's interesting. Maybe to dig into the lead commercial product, Vafseo, 'cause that's where I got a lot of questions recently. Yes. Just thinking about, you know, targeting the dialysis segment and pursuing, and also the fact that you pursued non-dialysis for a little bit too, could you just talk about, you know, what's the value creation strategy for Vafseo going forward? Where do you see it going this year? Yeah. You know, Vafseo, which is our HIF-PH inhibitor for anemia in chronic kidney disease patients on dialysis, this is a product that, as I referenced before, we believe is gonna become standard of care in the space. Now, patients have been treated, you know, since 1990 with ESAs, and this is a whole new mechanism, a whole new way of driving red blood cell increases and managing anemia. You increase hemoglobin, it's much more gradually, you have fewer excursions above target areas that physicians are looking at, you have fewer dose titrations. Generally, it's easier for physicians to use. Much more importantly is the data that's starting to, you know, become more clear now and is really building. In November, we presented data at the ASN meeting, the large nephrology meeting, that showed. We did this win odds analysis of our Phase III study, looking at mortality and hospitalization, two prospectively collected hardest endpoints that you have, and looked at that. Again, this win odds analysis allows you to generate a lot more statistical power. It was a 3,500 patient trial, so it was a large trial, but with this analysis, you get over 3 million data points. When you look at that data, you showed a statistically significant reduction in the risk of dying or being hospitalized with Vafseo. Those are the two outcomes that patients care about, physicians care about, dialysis providers care about. That was just presented. It is been accepted by a top-tier nephrology journal, we think that will be published very shortly. It gets in the hands of our medical folks who can go around and educate physicians on it. Now, just not this weekend, the weekend before, at the annual dialysis conference, we presented data. We took that data and did an economic analysis on the hospitalization particularly. There was about an 8% decrease in hospitalization when you use Vafseo. The hospitalization decreases based on cardiovascular and infection-related hospitalizations, both clearly explained by the mechanism difference. Well, that 8% difference in hospitalization also had a 16% difference in length of hospitalization, so people got out sooner. Between them, that translated into about a 15% cost reduction when you use standard Medicare costs. In other words, about $3,700 per patient per year. If you put all eligible patients who are treated with an ESA onto Vafseo, that would be about $0.9 billion savings. This is the kind of data, and we just presented this data, so we're working on the publication now. This is the kind of data that's building that says this is a drug that's gonna become standard of care. You know, we're seeing more and more access to the product. It's dialysis. It always moves more slowly than I would like to see. You know, you keep thinking it's gonna move faster, but dialysis providers are like ocean liners. They move slowly. We're really pleased with the momentum that we're seeing, and you know, most pleased with the data because the data at the end of the day is gonna drive the adoption. Yep. I hear you. You've highlighted, I think in the past, the TIW dosing as a key lever to improve adherence. How are you thinking about that broadly going into the dialysis organizations and where do you see possible variability across different customers? Yeah. Yeah, the TIW dosing or observed dosing, that we're calling it is, now it's not in our label yet. I mean, this is a conversation we're planning to have with the FDA. You know, QD dosing worked beautifully. Like, the daily dosing worked beautifully. I think the thing that surprised me was, you know, you've been giving someone a shot in the chair for the last 30 years. As soon as you saw, you had to send the drug home, there was a real concern about patient compliance and the like. The idea that we had done studies knowing that, you know, being quite confident that the drug would work well in TIW dosing, and it does, you know, that this would be an option for physicians to confirm that, you know, the patient's taking the drug. I think this has really proven to be most important for the anemia managers, the nurses, who have the day-to-day responsibility for managing the patients. We've done study FO2CUS, smaller one modify, where we demonstrated that you could dose TIW. There's two studies ongoing now, VOICE and VOCAL, both using TIW dosing. You know, Geoffrey Block, who's the physician running the VOICE trial, this is a collaborative trial and he's really the, you know, running the trial. He's the one who decided to move at U.S. Renal, move patients to TIW dosing or recommend that to the physicians in, at U.S. Renal. By the end of the quarter, we expect they'll all be doing TIW dosing. You know, anecdotally, we hear from physicians, you know, they still have to go through the titration phase. Once they get through that, you know, the patient just maintains their hemoglobin, you know, really, really well. With ESAs, you're constantly dabbling with the dose to keep them within a range. I would say never underestimate the power of making a busy nephrologist life easier, you know, and how much that means to them. At the end of the day, you know, the data we hope to generate from VOCAL and from VOICE obviously will be about more than just it's easier to use, right? You're really gonna keep building on that evidence that this should be standard of care. Yep. I hear you. Speaking of VOCAL and VOICE and just thinking about Vafseo going ahead, there are a few different things happening. Thinking about the data from both those trials and also your TDAPA period also. Mm-hmm. Is going to expire, how do you think about the transition for that product going through that, and then the data coming through as, you know, if all goes well. Yeah. V ery positive results? Yeah. Thinking about the trajectory going forward for Vafseo. You know, we've always had the perspective of looking at the long haul here, right? We're, you know, we're in it for, you know, changing standard of care. You know, the thing that we're so fortunate about with Vafseo versus other TDAPA products is that there's a meaningful amount of money within the dialysis bundle to treat anemia, because almost every patient needs to be treated, well, 90-plus% of patients need to be treated for anemia. You know, there's real money within that bundle. We could take the long view. I mean, we always thought of TDAPA as a wonderful opportunity for the dialysis provider to, in a no financial risk way, as a matter of fact, you know, they could make some money to use the product, and we could charge a higher price. We could benefit for some number of years. We always, you know, recognized that long term, we would need to be pricing around ESA pricing. You know, again, we try to keep it very simple. There's two years of TDAPA. After that, there's this payment that goes on for three more years, but that gets peanut buttered over every dialysis provider. The idea that you're gonna get one to pay more for your drug while the other one takes that money and puts it in their pocket, we just don't think that way. You know, we think about this is how, you know, we have to price in and around the ESAs. Now, when you have, you know, data that supports that you're saving significant money, about half of dialysis patients are fully capitated for the dialysis provider. You know, saving that kind of money that you're gonna get for basically free does give us some leverage in the negotiation. You know, 80% of dialysis patients are managed by 2 dialysis providers, so most of the leverage lands on their side. We know what the pricing for ESAs is, and that's a price, you know, in this kind of $2,000-$2,500 a year. That's something that Vafseo can be a very pro-profitable product for Akebia. Yep. If we develop all of this data. The other thing to remember is TDAPA, not every patient has TDAPA, right? The day TDAPA ends, while the price comes down, it comes down substantively from where we are, as we expected, your patient population grows to everyone is available. You know, as you build this data that supports, you know, that this is a different way to treat patients and the pricing, you know, is relatively consistent with the ESAs, with all of this data that says you're saving money, the opportunity is there to become standard of care. Yeah, just to reiterate, that post-TDAPA market opportunity is $1 billion at that ESA level of pricing. Yeah. Thanks, Erik. That's exactly right. Yep. Makes sense. Just to help frame it, I mean, how much do you think investors are used to thinking about this dynamic with TDAPA expiring, et cetera, and versus your expectations? Like, where do you see the street being, and where do you think there might be a disconnect, if there is one? Yeah. No, I think there is. I mean, well, it I don't know if it's a disconnect, it's just that there's so few TDAPA drugs, right? I mean, you know, you've got the DefenCath from CorMedix, whose TDAPA's expiring in the middle of the year and us. You know, you had Korsuva, you know, which again, difficult because there was no money in the bundle. How do you use that product? We're just really a unique product from that perspective. You know, the idea that, you know, it's a math equation as you think about 2027, right? How fast can you grow volume? Can you grow it enough to offset the revenue decline? You know, we've been really clear. We don't think we can. You know, we think we can continue to grow volume. If you look at the volume, slope, we expect that to sort of be a straight line. Revenue, you're gonna have this divot of revenue. Again, between growing based on the data that's available and growing based on more patients being available for treatment, you know, you ultimately gain our share. You know, we say standard of care in a $1 billion market is a $500-plus million product. I mean, that's our belief about what the product can be. Yep. Got it, got it. Great. Since we were talking about VOCAL a little bit, I wanted to sort of double-click into that and think about, what would be a clinically and commercially meaningful result from VOCAL? Mm-hmm. Especially because you're, I think you're comparing to ESAs as well. Yes. How are you thinking about what's the bar or what would be a really great result? Yeah. look, VOCAL is 350 patients, are running that at DaVita centers. You know, it gives DaVita the opportunity. Now we're the sponsor of that trial, so that's data that we can use for a regulatory filing around TIW as well, if FDA wants it. It gives DaVita a clinical experience with it. You know, we've already proven that we're non-inferior. That's what you're looking for there, right? Non-inferiority from a, from a hemoglobin management standpoint. The thing that's really interesting and VOCAL from my perspective is the sub-study that we're doing, with a small number of patients, about 30 patients, that is, looking at red blood cell characteristics. You know, this has been seen before, but, you know, this idea that, you know, you're talking to physicians, you know, you're showing them this data, our phase III, you know, you were non-inferior, right? Now we're showing them this data with the Win odds analysis and it's kind of a why. You know, the why is this differential mechanism. One of the places where you can really demonstrate that there's a different. That this mechanism leads to a different way, this more physiologic way of managing anemia, gives you a more physiologic red blood cell, and that's what we hope to show. We've seen this in other data, but other studies, but not with dialysis patients. The idea that you have a red blood cell that's larger, that carries more oxygen, that moves through the capillaries more clearly, all of these omics, metabolomics, et cetera, that we're gonna be studying, I think this is gonna be really interesting data for physicians. You know, you have to give them a why. You know, you get in front of VOICE, which, you know, is the beginning of 2027, where we'll see that, you know, about a year from now, less than a year from now, I hope, where we'll see that data. You know, you're showing them this is why you're seeing this clinical difference. You're not just getting the same number of red blood cells, you're getting a better red blood cell. You know, we're gonna follow up with a study that looks at red blood cell lifespan, right? Dialysis patients have red cell lifespan that's about half what yours and mine is. The idea that you're also extending that, and again, this has been seen, some data out of China showed you almost double the lifespan of the red blood cell. To show that again in U.S. dialysis patients, this is how you build that evidence. Mm-hmm. that physicians say, "Yeah, this is the drug that I need to use to manage anemia. Yep. Tagging on to that, you're alluding to VOICE. How are you thinking about the possible hospitalization and mortality endpoints coming out of that, and how could that influence real-world clinical practice? Yeah. Well, I mean, I think we're getting that now from the data that we presented at ASN. You know, this was a post hoc analysis, but it was very prospectively collected data, right? It's not, you know, like we're just data mining. You know, but this is basically the same endpoint. You know, fewer patients. You know, what I expect to see from VOICE is the same magnitude of difference. You know, the same magnitude of difference in mortality, same magnitude of difference in hospitalization. Now, the things that led to hospitalization and MACE rate in the INNO2VATE trial were excursions above a hemoglobin of 12, which we always were better than an ESA, but the second was ESA rescue. How often did the patient have to get an ESA rescue? In the INNO2VATE trial, it was about the same between us and ESAs because you had that dip based on the way you were dosing in INNO2VATE. That doesn't exist anymore in the VOICE trial. In FO2CUS, which was a TIW study, we had half the ESA rescue. If you layer half the ESA rescue on top of, you know, the benefits around keeping people in the target range, et cetera, you know, we don't know what exactly. Obviously, you do the study to find out what the data says. Even if we see just the same magnitude, that's a huge win and a confirmation of what we saw in INNO2VATE when you put it along with all the other data that we've generated. Yep. We'll all see in about a year. Yeah. Looking forward to the data. Me too. I want to also have some time for pipeline stuff as well. Yes, please. I know you recently started talking more about AKB-097 and praliciguat. Maybe could you walk us through, you know, why you're excited about these programs, and what are the next drivers of growth? Yep. You know, so obviously as a kidney company, you know, you have to build a pipeline. Rare kidney is an obvious place for us to go. It's an area of significant interest, but it's an area of significant unmet need still. You know, we did the deal to bring praliciguat in 2021, you know, for a variety of reasons, including, you know, us having to work through the CRL and, you know, some issues that our partner had in getting us drug. We weren't able to start the phase II until the end of last year. You know, praliciguat we're looking first in focal segmental glomerulosclerosis or FSGS. You know, it is an area of high unmet need. You know, praliciguat had been studied in diabetic kidney disease by Cyclerion. You know, it clearly showed a reduction proteinuria, but not enough for them to go into that larger market opportunity. We believed that the product could be very effective in FSGS. We did a number of animal studies. We're very pleased with the results we showed there. With the PARASOL, this kind of FDA academic partnership looking at what should be the right outcome for or the right approvable endpoint for FSGS. Before that we were looking for a disease that moved quickly, so you could show a difference quickly, but PARASOL kinda gives a much clearer pathway for us. You know, we took that DKD data just as a pressure check, right? it was UACR not UPCR. You have to do some data manipulation, but, you know, we felt quite confident in our ability to demonstrate a benefit here. FSGS is such a heterogeneous disease. You know, there are gonna be other products that are gonna be approved there, which is great for patients, but, you know, we're gonna see how treatment moves in the future as these products are available. I mean, today there's nothing available, right? But, you know, we think the praliciguat will fit very, very well within treatment, and it's a unique mechanism of action. There's no one else developing a guat for FSGS. We're excited about that. That's just started its phase II. Happy with how it's enrolling. We haven't really guided on timing for that yet until we see a little more, you know, get more confidence in the line of enrollment. 097 we brought in in December from Q32 Bio. We're incredibly excited about that, and Erik and his team led that effort. I think that, you know, most of us looked at that and at first and said, "Oh my god, another complement inhibitor. Oh my god, IgAN. How many drugs do we need in IgAN?" As we dug in, particularly talking to the KMEs, the medical opinion leaders, we got incredibly excited about it. It's this tissue-targeted effect that makes it so interesting, right? I mean, you've got an efficacy profile that's potentially as good as the best complement inhibitor out there in a kind of the same pathway, which would be like an Empaveli. The difference being because it's this fusion molecule, it gets directly to the tissue of, you know, where complement's being produced, gets out of the bloodstream quickly. You know, the two benefits of that are, A, since it gets out of the bloodstream, you should be able to avoid the box warning for infections that you see with most complement inhibitors like Empaveli. Two, since you're going to the tissue of damage, you can use a much lower dose. Empaveli, I think has to do about 1 g infusion twice a week. We're starting our basket study, which we're gonna be starting shortly, or second half of the year. We're using 450 milligrams, I think it is, once a week as an infusion. We think maybe it can be even a lower dose than that or a less frequent dose than that. The ultimately getting it to an auto-injector, which would be phenomenal. You know, efficacy consistent with the best in class with an improved safety profile and a more convenient dosing regimen. I mean, that's a, that's a best in class potential drug. Basket study in IgAN, lupus nephritis and C3G will start as early as we can in the second half of the year. Because it's an open-label basket study, we expect to start generating data in 2027. Okay, great. On the topic of the basket study, I do get some questions about. You're testing a different indications and moving them all forward in parallel. How would you prioritize these indications, or what are you looking for to help you figure out which is the one to go forward with down the road? That's a great question. First and foremost, we're just looking to get as many of each as we can. You know, there are other indications. We may add indications to the basket as we go. You know, IgAN is the largest opportunity, so it may be the one where we see data first. I think for everyone, you know, we wanna see that efficacy data first, right? It's less about what are we prioritizing to go forward with and more, you know, at initially and more about, you know, show me the data, right? Let's see, let's see confirmation about kind of how excited we are, what was seen in phase I, where it gets right to the tissue. IgAN may well be the first, you know, C3G is such a rare disease. There's only a few thousand patients. I'm very excited about the opportunity in lupus. you know, it's a less crowded space and, you know, I was just talking to a couple of physicians here this past week, down here in Miami and they were talking about having 30-year-old women who were starting dialysis from lupus, you know, and looking for any opportunity to impact that disease. you know, this would be a, this would really be a great one. you know, we'll do the work now to understand. Like even IgAN, where you say, "Well, goodness gracious, there's so many IgAN drugs," which was my initial reaction. When you think about, you know, the APRIL and BAFFs and what you're doing to people's immune systems for decades, you know, the idea of having a targeted complement inhibitor that you can manage disease early and, you know, kind of reduce the amount of time on an APRIL or APRIL/ BAFFs, you know, I think that some of these treatment paradigms are we're gonna learn about as this data comes forward. Where I thought, "Well, that's not really such an interesting area," the uniqueness of this compound, of 097, I think could lend itAnd to be a very, very important product in treating IgAN, even with, you know, it being as crowded as it is. We just have to see the data. Yep. I hear you. I'm gonna give John a break and maybe ask Erik a question. He never needs a break, you know. He can just keep going. Erik, wanted to also throw a question to you. How are you thinking about just for Vafseo and the commercial products and the portfolio, like any sort of metrics, like financially, that you're thinking about watching that could indicate good execution going forward to investors? There's a lot going on in R&D and commercially. How are you thinking about prioritizing these things? Great question. On the metrics for Vafseo, I know John kind of alluded to some of them earlier. We're looking to increase that breadth and the depth of the prescribing, so more prescribers prescribing more. I think the adherence rates are also really important to keep an eye on. We talked about, we're seeing those improve under the TI dosing, so I think that's important as well. From a capital perspective, I think we're taking a really balanced view. We want to continue to support the Vafseo launch. It's incredibly important to us, continue to generate the phase IV type data that John's talked a lot about. We really believe this can become a standard of care, again, in a billion-dollar market. At the same time, continue to bring this really exciting pipeline along, which we think has the potential for a lot of value creation for shareholders, so a lot of return. Yep. Great. I think in the last minute that we have, I'll zoom out again, and a bigger picture question for you guys in terms of, you know, what do you think the market still under appreciates about the Akebia story? What are things that we should be thinking about going forward? Yeah. I think that clearly dialysis reimbursement is complicated, and there are investors that, you know, It just becomes like peanuts, you know, wah, wah. You know, can we really understand that, what this is? You know, we do try to simplify with Vafseo that, you know, I mean, yes, we have this TDAPA, and we're enjoying a higher price now for a couple of years. Our market is unlike any other TDAPA drug in that there's dollars there, for use and we've known that from the beginning. I mean, look, I wish it was $5,000 a year, which it was when I started, you know, when we started the Phase III study. At $2,000-$2,500, particularly when you're demonstrating the savings that we're showing, you know, the opportunity to be standard of care in a $1 billion market, you know. Standard of care is 50% plus one, you know, we think we can be much better than that, right? That's, you know. This is a small molecule. I mean, this is, we have an opportunity for this to be a very, very successful product. I think people need to see the consistency of that launch growth, you know. Got out of the shoots very quickly, and because of these things like adherence and the complexity of these big dialysis organizations, you know, it flattened out from a demand perspective, which surprised us. We're seeing growth again, you know. We're clearly seeing growth again and, you know, we're seeing it beyond just U.S. Renal. We're seeing DCI, IRC, some of the, kinda the third, fourth and fifth largest are, you know, now using the product, and DaVita's starting to move, and eventually we're gonna get Fresenius too. You know, that opportunity is there. Once you see that revenue growth, you have to start to appreciate the pipeline that we have, you know. I understand that people can't spend a lot of time on that until they feel confident, you know, that the thing that's gonna fund it is there. I think we're doing an R&D day, shameless plug, on April 2nd. You know, we have some outside KOLs who are gonna speak at that. It'll be virtual. I think people will have the opportunity to really get excited about this pipeline. Okay, great. Looking forward to it. With that, I think we're at time. Thanks again, John and Erik, for joining us and covered a lot of great ground and looking forward to more updates. Thanks, Roanna. Thanks for the invitation. Appreciate it.