Introduce Akebia Therapeutics and joining us for a fireside chat, we have CEO John Butler, Chief Financial and Chief Business Officer Erik Ostrowski. Close enough. Chief Medical Officer Dr. Steven Burke. Thank you for joining us for the fireside chat. This is meant to be an informal format, so if anyone in the audience has any questions, feel free to raise your hand. Before we jump into Q&A, we just want to level set for investors. John, can you just give a quick overview of Akebia, the story, the setup into year-end and into 2026? Great. I think we're going to cover a lot of that. But first, thank you so much for the invitation. It's really a pleasure to be here. Akebia really is a unique company. We have a clear therapeutic focus. We are a kidney disease company, and we think a very exciting company because we're a commercial company first and foremost. We have two commercial products on the market. The second product, Vafseo, just launched at the beginning of this year in a billion-dollar market opportunity where we believe we have the opportunity to become the standard of care. And beyond our commercial products, we're super excited, particularly today, to talk about our pipeline. Because yesterday, we just announced the establishment of our rare kidney disease pipeline with two assets, praliciguat, which we're just initiating a phase II study for FSGS, focal segmental glomerulosclerosis, and just acquired a second asset yesterday, AKB-097, which is a complement inhibitor for multiple potential rare kidney diseases. So I look forward to talking more about that. So it's really quite an exciting story. Very strong balance sheet, commercial revenue-generating company with a really interesting pipeline of assets. Absolutely. There's a lot of topics to touch on today, so why don't we start with the Vafseo launch? So can you walk us through the Vafseo launch progress thus far with regards to prescriber growth and dialysis organizations coming online and standardizing protocols? Yeah. So we're making very good progress on the Vafseo launch. We started the year with access to really just the U.S. Renal Care, which is the third-largest dialysis provider, about 36,000 patients, and a number of smaller providers. So we really only had access to about 40,000 patients, but got out of the chutes really quickly. In U.S. Renal Care, the clinical folks there have very strong support for the product. They really believe in the difference that a HIF-PHI can make in managing anemia in their dialysis patients. So got off to a great start there, and we've continued to expand the number of patients who potentially can access the product. We had our earnings call on November 10th. That was the same day that DaVita, who is one of the largest dialysis providers, rolled out from a pilot program to their village, as they call it, so their entire organization, which is about a 200,000-patient dialysis organization. So as of middle of November, about 260,000 patients had access or potential access to get the product. Now, dialysis is a complicated market, a lot of operational issues to kind of work through, which we're working through, I think, quite successfully, but it never goes as quickly as I'd like it to, I have to say. Right. That actually is a great lead into my next question. You talked about this on the Q3 call, but for the folks who are tuning in right now, can you talk a bit about some of those operational issues that have come up and the different strategies that Akebia is employing to successfully address them? Yeah. So again, a lot of it is just the nature of dialysis. Dialysis organizations normally think, "Oh, you launch a drug, the physician writes a prescription, goes to the pharmacy and fills it." Maybe you've got to make sure that the payers are paying for it. But with dialysis, what happens in the dialysis center for the dialysis patient is really controlled by the dialysis organization. The physicians make the decisions that they make around prescribing, but all within the context of what's available in the dialysis organization. So DaVita did a pilot, for instance, of about 100 dialysis sites and immediately had issues on the operation side. With one system, they would write the prescription, but that system didn't talk to the system that had to confirm that the patient had reimbursement, TDAPA or reimbursement. So it just went slowly. You talk to the folks at DaVita who've been incredibly supportive of the product, and they're very happy that we run pilots so that all of these issues come out and they work through them, and they really have worked through them. I think now that they're going from 100 sites to 4,000 sites, even though they've worked through some of those, we've also heard about other just kind of operational systems issues that physicians have to overcome to get the drug. Because remember, the drug is on formulary, but it's on formulary on an exception basis because you've got to ensure that the patient has that TDAPA or reimbursement, so it adds a step for the doc. I'm hoping that through the fourth quarter, because they really moved to that full rollout a week earlier than they had told us originally they were going to, so that means they were happy with how things went. But I'm sure that you go from 100-4,000, you're going to have some more of these issues. So if we enter 2026 with those issues ironed out, physicians know how to get the drug, and we can operationalize it quickly, I think we'll be in a great position to start off 2026 strong. Great. That's a good segue into my next question. You've been clear in the past about expectations post-TDAPA, about Vafseo pricing coming down to about ESA levels, parity. But that price decrease is expected to be offset by increasing volume beyond the TDAPA eligible population. So can you just help us understand these factors and kind of how you expect the Vafseo trajectory in dialysis to look in 2027 and beyond? Great question. Great question. So you talked about volume offsetting price declines. I'm not sure it's going to offset. I think it's important for people to recognize that there could be a drop in revenue in 2027 as we transition from TDAPA to non-TDAPA, to being part of the dialysis bundle. So if you think about it today, we have a WAC of about $15,500 per patient per year. Now, no one pays that. All of our dialysis contracts have an off-invoice discount and a volume-based rebate. So as our volumes grow, our net price will decline, but never down to the average price that you see today for ESAs, which is roughly $2,500, somewhere between $2,000 and $2,500 per patient per year. The big providers pay a little less, the small guys pay a little bit more, but it's around $2,000. So we're going to see that drop. In order for them to be comfortable using it during the TDAPA period, they have to know that their price post-TDAPA will be no more than what they're paying for ESAs today. And that's the commitment that we've made to dialysis providers. Now, what does happen, as you referenced, is you go from having access to only people who have a TDAPA payment, which is 40% of the patients who are on fee-for-service and some percentage of Medicare Advantage, not 100%, and certainly no access to commercial or Medicaid. Post-TDAPA, we have access to all of those patients. But when you think about it, the price decrease happens immediately. The volume increase happens over time. So we've always taken the perspective of $2,000-$2,500 per patient per year. This is a blockbuster market. This is a billion-dollar market. And we want to be standard of care in that market. During TDAPA, there's an attractive economic opportunity for the dialysis providers, but our mind has always been focused on the long term. I'm happy to sell as much as we can, as quickly as we can, take advantage of that opportunity for a higher price. But we really want to have that. We're generating data to support the long-term growth of the product, which would be at that lower price in dialysis. Great. That makes sense. Another great segue into ASN, where you guys showed clinical trial designs for VOICE and VOCAL. Maybe just at a high level so we can get into the pipeline a bit, but just at a high level, can you characterize the kind of feedback that you were getting around these trials and any of the key takeaways that you're hoping to see in terms of the outcomes of these trials? Yeah. No, that's a great question as well. So the first piece of data from ASN that I want to reference, though, is the analysis that was presented by Dr. Glenn Chertow that was an analysis of our INNO2VATE study, which was our phase III study, where we in INNO2VATE, we saw about a 1% decrease in mortality versus darbepoetin, the long-acting ESA that we compared to. We had about an 8% difference in hospitalization in INNO2VATE, but neither of those were statistically significant. And when we did this hierarchical analysis called the Win Odds analysis, where we looked at mortality is worse than hospitalization, time to mortality matters also, we did this analysis and really supercharges the statistical power. You saw that we actually had a statistically significant lower risk of death or hospitalization in the Vafseo, the vadadustat group. When you looked at an on-treatment analysis, the p-value was like 0.0001, so highly statistically significant. We're super excited about that. Now, that's a post-hoc analysis on very objective measures. You're in the hospital or not, you're either alive or dead. We want to get that published. We think that'll be incredibly helpful. But that is now the primary endpoint for the VOICE study that Jeff Block at U.S. Renal Care is doing in collaboration with us. And that will be a prospective confirmation of that benefit. And that study will wrap up at the end of next year. We'll have data early in 2027. And then VOCAL is a study we're doing with DaVita. And that one is interesting also. Probably the most interesting part of it is the small sub-study that we're doing looking at red blood cells. We always talk about the difference in this physiologic approach to managing anemia. Here, and Steve can talk more about this, we're looking at the quality of the red blood cell. I think that will show physicians, "Look, this physiologic difference that we talk about with this HIF mechanism is manifesting. These are 'better' red blood cells." That's probably a non-scientific way to say it. I don't know, Steve, you want to talk about that? Yeah. We've published this already, and red blood cells made under the influence of vadadustat are larger. They have more hemoglobin, and they have a more narrow distribution of widths, which hematologists tell me is a good thing, so we're looking at the underlying physiologic mechanisms, and we're looking at things like the ability of the red blood cell to deform, to resist oxidative stress. We're looking at the proteome, the metabolome, even the lipidome, so I think we're going to see some very significant differences, and we think that's going to ultimately translate into an increase in the red blood cell lifespan, which is very reduced in patients on dialysis, so that'll be the next study. Excellent. I wanted to really quickly touch on non-dialysis just because you had a recent regulatory update, so it was pretty surprising, at least on our end, about the phase III PRO2TECT study, and you're not going into CKD, NDD. You're not pursuing a broad label for Vafseo. So really quickly, can you just walk us through FDA's feedback and any next steps for the NDD population, just given the sheer size of the market opportunity? Yeah. No, we were obviously very, very disappointed. This is a market that patients need access to the product. Physicians want to use the product there. We certainly had some very unhappy folks, not with us, but more with FDA at the ASN meeting. But it was clear we really thought we were engaging in a way that we could get to an alignment with the FDA. But in the live meeting, it became clear that they wanted a study that was just larger and would take longer than it made sense for us from a business perspective. And the patient groups understood this. The physicians understood this. You can't get the data a year before your IP expires. So when we did engage with the FDA, and they engaged with us, was on subpopulations. We're not really talking yet about the specifics around that because it was more just chatting, I guess. We are going to follow up with them. Again, it would be a much smaller population, but we think it would be important. Physicians want to use the product there, and any evidence we can get in the label that they're able to use the product in some non-dialysis population will be helpful. Stay tuned. We probably won't update on that until we've had some more engagement with the FDA, which I don't expect for some period of time. Okay. Great. Now, let's get on to the pipeline because you had a really exciting update yesterday. So you disclosed an important update to establish a rare kidney disease pipeline with two core products, AKB-097 and praliciguat. Both products are going to be studied in phase II clinical trials with patients dosed in 2026. So first on AKB-097, tell us a little bit about the asset, which was acquired from Q32 Bio. What makes it a next-generation complement inhibitor? Yeah. So we are very excited about the product. The strategic fit is clear for us. I think I'm going to turn it over to Steve to talk about why we're so excited about it. Sure. Thanks, John. The product's actually quite exciting. It's very different than the complement inhibitors that are on the market today. And it's principally due to the fact that it's a fusion protein that targets the sites of complement activation in the tissues. So it's administered intravenously or subcutaneously. It spends not a lot of time in the circulation, but homes to the site where C3d is deposited on the surface of cells, for instance, in the cells in the glomerulus where patients are experiencing damage to those cells. It then also has, in essence, two chains of Factor H, which is a complement inhibitor, and it causes dissociation and degradation of the C3 and the C5 convertases. So those are the things that amplify the cascade and lead to the formation of the membrane attack complex, which damages the cells. And because of its unique properties, we do not expect it to have systemic complement inhibition like the existing products. It also requires a lower dose because, again, it's going to the site of complement activation. It's not going all over the entire body. And that will lead to a more convenient administration schedule. We expect to have a subcutaneous self-administered injection maybe once or twice per week, which is a significant advance over some of the other injectables, most notably a pegylated compound, which must be administered over 1,000 mg twice a week using an infusion pump. So we hope to be as good as the best complement inhibitors out there with a better dosing regimen and, most importantly, not inhibiting the complement system systemically, which puts patients at risk for serious bacterial infection. So we're very excited about this product. I think it's wonderful we could get our hands on it. Great. Quickly, can you walk us through the financials of the acquisition and why an acquisition like this makes sense right now? Yeah. So we're really happy with the financial terms of this transaction. The upfront payment was $7 million. There's another $3 million due six months post-closing. And then there's a $2 million payment when we start the phase II. So in the scheme of things, relatively modest payments for what we think as an asset can drive potentially a lot of value in the future. In addition, your typical development clinical commercial milestones with royalties on the back end. Yeah. And why the timing's right? I mean, clearly, we are experts in kidney disease. As John mentioned, this is right in our wheelhouse. We know the space. We know these diseases. I think one of the benefits from a Wall Street perspective is that we'll be generating data from the trial, which I think Steve will talk about a little bit later, which is an open-label basket trial. We will have the ability to show investors data over time. Great. I also wanted to touch on praliciguat, which is an sGC stimulator. And this was licensed back in 2021. What have you done since then? And can you just walk us through some of the data that suggests it can work in FSGS? Yeah. We're excited about this product as well, and we identified FSGS as a potential indication for it back in 2021 when we did the study before some of the work that's been done to really clarify the regulatory path in FSGS, which I think makes it an even more important and kind of really interesting opportunity for us. Steve, do you want to kind of talk about what we've done? Yeah. When we acquired the compound, Cyclerion, the company that licensed the product to us, had done a very extensive package of non-clinical studies in kidney disease, both in vitro and in vivo. And so it was a very robust package. I think one of the things that jumped out at me personally was this drug, which basically amplifies nitric oxide signaling, had a very beneficial effect on the podocyte, which is that cell in the glomerulus that mainly is responsible for preventing proteinuria. So very strong package there. We did a really thorough assessment and decided that FSGS was a perfect disease for this product because it's a podocytopathy. It's rapidly progressive, and there aren't really effective treatments for it. But to confirm that, we did studies internally looking at two models which mimic FSGS. One is an Adriamycin model, and the other is a 5/6 nephrectomy. In both of the models, the drug performed beautifully and really gave us confidence that this could work in patients. We were about to start a phase II study, but then we had some issues. We were being supplied the drug product by Cyclerion, and there were some really just human errors that led to the drug not being usable, and we didn't have any drug substance available to us. So we put a pause on that and then have gone on to get some material produced into drug product, and we're ready to go. In fact, we're initiating sites. We started screening. We hope to treat our first patients in the new year. We're going to treat up to 60 patients in a randomized double-blind placebo-controlled trial, looking at change in urine protein-to-creatinine ratios from baseline to six months. At six months, patients on placebo will cross over to active, and at that point, the blind will be broken, and we can share information from that study. Got it. Just going back to ADX-097 or AKB-097, that is an open-label renal basket study. That study will be able to get data on a real-time basis because everyone's going to be on the drug. But praliciguat's a little different. Got it. So you also have an earlier pipeline of HIF-based assets to target unmet needs. We're getting more of a fulsome update during your next earnings call. But anything that you can say about the expansion opportunities for some of these earlier pipeline assets? I think the first product that will be going into the clinic at the phase I early next year, AKB-9090, obviously, it'll be a phase I in healthy volunteers, but that's for acute kidney injury. And again, I think there's a lot of reasons to believe that this mechanism really can be differentiated for AKIs. Steve, do you want to? Yeah. What's interesting about HIF-PHIs is they activate or stabilize HIF, which actually affects hundreds of genes, which are grouped into pathways. Some are related to anemia and correction of anemia. Others are related to inflammation, decreasing inflammation and activating cell survival pathways. And in our animal models of ischemia reperfusion injury, AKB-9090 was highly effective in preventing against ischemia reperfusion injuries. And I think, in general, HIF-PHIs have this property. We recently have published some data with people in Texas showing this in a myocardial infarction model. I'm glad to do that. It was very effective at reducing infarct size. So it's really a theme about HIF-PHIs. And we're very excited about this. And we're actually working with the FDA. I'm the head of the drug committee of the Kidney Health Initiative. And we're working with FDA to come up with intermediate and surrogate markers that would lead to accelerated approval for drugs for cardiac surgery, AKI. So I think there's a lot of promise in this area right now. And we have an even earlier stage program, AKB-10108, that we're directing towards trying to prevent complications of premature birth, many of which are due to oxygen toxicity. Our principal focus now is on retinopathy of prematurity, which is the leading cause of blindness in the world. But there are other potential benefits, such as bronchopulmonary dysplasia, that we're going to explore in those trials when we get there. While we have a clear focus on kidney disease, the opportunity you kind of have to follow the science, right? And the opportunity to deploy these assets potentially against non-kidney diseases like retinopathy of prematurity and with 9090, potentially ARDS. I mean, we do have the COVID paper was published with vadadustat recently. It really shows that this HIF pathway has an impact there. I don't know if Steve, you want to have a really quick on that. Yeah. No, we did a trial with people in Houston at five hospitals and 450 patients. We really actually significantly decreased inflammatory responses and lessened the severity of lung injury in people with COVID-19 pneumonia who were hospitalized and needed oxygen therapy. That was recently published in JCI Insight. We're doing our own internal screening using influenza models and mice to find other compounds that would have a longer patent life or might be more effective than vadadustat in that indication, so I mean, really, we are a unique company, right? I mean, we have two revenue-producing products, one early in the launch, and we think is a really exciting portfolio of products in the pipeline. Absolutely. Thanks for walking us through all of this and the story. We really appreciate it. Thanks for joining me. Thanks. Thanks for having us. Thanks. Great job.