Alright, hello everyone, and welcome to H.C. Wainwright's Fourth Annual Kidney Conference. My name is Matthew Caulfield, I'm a Senior Biotech Analyst here at H.C. Wainwright. We next welcome Akebia Therapeutics, and we're glad to welcome Nick Grund, Chief Commercial Officer at Akebia. Welcome, Nick. Great to see you this morning. Thanks for having me. Yeah, of course. Maybe to start off, could you provide a brief overview of Akebia and its commercial products for CKD patients that are on dialysis? Yeah, absolutely. Akebia is a fully integrated biotech company. We got founded in 2007. We've got two commercial products. Importantly, we've got a sales team that has deep renal experience. We've got an R&D team that's demonstrated the ability to develop compounds and bring them through to clinical studies and eventually approval. We've got a pipeline of early-stage assets. Importantly, we're focused on really bettering the lives of people with kidney disease. Mm-hmm. Our two assets are Auryxia, first off. It's about a 10-year-old phosphate binder. Its first indication is for the control of serum phosphorus in those patients that are on dialysis. Its second indication is for iron deficiency anemia in adult patients in non-dialysis. Not our first roadshow with anemia. There's about a 90% overlap between Auryxia physicians and Vafseo physicians, target physicians. That brings us to Vafseo. We launched Vafseo back in January. It's indicated for the treatment of anemia due to chronic kidney disease in adult patients receiving dialysis. You know, it's an oral HIF-PHI, a new mechanism of action. It stands for hypoxia-inducible factor prolyl hydroxylase inhibitor, so a mouthful. Really quickly, that mouthful really means that it stimulates the body's natural response to hypoxia, which enhances the body's natural production of erythropoietin to control anemia. No, that's great. Considering that kidney patients can otherwise rely on erythropoiesis-stimulating agents or ESAs and iron supplementation therapy, for example, what do you think are the greatest unmet needs facing CKD patients, you know, based on standard of care that they've been accustomed to? Yeah, Matt, you'd be surprised. You know, ESA agents have been on the market 30 years. Despite this, nearly 25% of patients are struggling to hit their hemoglobin targets and falling in and out of the range. Despite this large percentage of patients not quite getting to goal, there's been very little innovation in this area until Vafseo. Nearly 30% of those patients who are on ESAs are on high doses of ESAs. With those higher doses of ESAs come increased risks of major cardiovascular events. Additionally, as an oral therapy, patients can conveniently take Vafseo at home, which is ideal, particularly for those patients who are getting their dialysis at home. Though broadly indicated, those two populations, which physicians think of first, represent about 40% of the dialysis patients. That's very helpful. I mean, to kind of drill in a little bit more to what you described, so Vafseo is unique as an oral tablet. You mentioned it's the HIF-PHI inhibitor, sort of a novel mechanism of action, treating anemia, CKD, dialysis patients. Are there any other main points, or can you discuss a little further the relevance of this differentiation within the CKD market? Yeah, thanks. You know, it's really interesting. When you give an ESA, you see these large spikes in hemoglobin with a reduction, and then they give the next dose, it's another large spike in hemoglobin and a reduction. With Vafseo, given its unique mechanism of action, you really see really small changes in EPO over time. That lower level of EPO changes results in a gentle rise in hemoglobin for those anemia patients. Secondly, since it's working upstream from where ESAs work, we also note that we're seeing iron mobilization, which may be linked to more efficient use of iron, which is important for creating red blood cells. In the pivotal INNO2VATE study that led to our approval, it demonstrated also lower dose titrations for the product. You're not having to titrate patients as often, which is a benefit to the clinic staff. Absolutely. Being oral, I think that's a very helpful therapy as well. You mentioned Vafseo launched commercially very recently back in January of this year. Maybe you could tell us a little bit of how the launch has progressed, any early trends you're observing among uptake, enthusiasm, kind of where things stand for the initial launch stages. Yeah, so we're still working to close out Q2. Really, when I look at the first quarter of launch, we launched back in January. Overall, super pleased with how the initial launch went. When I think about a launch, I think about kind of breadth and depth of physicians writing. You know, breadth is how many are writing, and over 640 had written Vafseo in the first quarter of launch, which is super good. Most of those physicians are within U.S. Renal Care. They were the fastest to move. We have great advocacy at U.S. Renal Care. Certainly, expanding beyond U.S. Renal Care is important. The second I think about is depth of prescribing. That's the number of prescriptions a physician writes. On average, in Q1, we saw about 12 prescriptions per physician. You know, that range was super broad. We have still folks in the, we'll call it trial phase, one to five prescriptions. On the other side of that spectrum, we have physicians that are over 100 prescriptions, which is really tending towards full adoption. Obviously, full adoption is where we want to get to. That 12 would demonstrate there are still, most folks are still in what I'll call the trial and early adoption phase, as opposed to complete adoption. Understood. That kind of parlays into the next question. You know, we know uptake in the kidney space has some nuances. Can you talk a little bit about the path from initial small and mid-sized dialysis organizations? I know you mentioned U.S. Renal Care and how that can progress ultimately into the large dialysis organizations or the LDOs. That's kind of a unique component to the kidney space. Yeah, you used kind of two words that are often put with dialysis: nuanced and unique, right? When we think about the dialysis space, though it is unique, it's actually unfolding really closely to how we thought about it. As we thought about the launch, we always anticipated that the small to mid-sized dialysis organizations would go first. They would be faster through the launch process. That segment is about 150,000 dialysis patients, so a large segment, but they were going to move faster. We saw that. U.S. Renal Care being the most, you know, they're the third largest dialysis organization with about 36,000 patients, so not small by any means, but certainly not the size of an LDO. An LDO, or a large dialysis organization, is roughly 200,000 or above; that's Fresenius and DaVita. They go a little bit slower. They've got more systems to integrate. They've got more decision-making layers between top to bottom. Certainly, while we expect it in Q1 to be small to mid-size, that's to fuel our growth into Q2. We anticipate in the second half of the year, LDOs will start to become a more major player in that second half growth. That's great. Another important component to therapy adoption and access in the kidney space is the TDAPA component. Can you explain how that factor plays into the launch, patient access, and the timeframes related to that, and how that's impacted initial launch? Yeah, TDAPA, you know, another unusual nuance of dialysis. It stands for Transitional Drug Add-on Payment Adjustment. What it is, is first a drug has to qualify for TDAPA, which Vafseo has done. It is under the prospective payment system, which applies to all ESRD products. Why they developed TDAPA at CMS was they were worried that having one flat bundled rate per session would disincentivize dialysis organizations from giving innovation a try. What they did is they set up this reimbursement mechanism known as TDAPA that really calls for a payment in addition to their bundled rate. It's a payment they receive for qualifying drugs in addition to that bundled rate. It really is there to incentivize folks to figure out how to operationalize innovation into normal treatment. It lasts about two years. After that, there's a whole convoluted mechanism of what happens for the next three, et cetera, et cetera. The long and short of it is to be successful, not only do you have to have good economics during TDAPA, you have to provide dialysis organizations with certainty post-TDAPA around pricing. We've done that. We've contracted and worked with dialysis organizations to have their price post-TDAPA be at approximately the standard ESA price at about $2,500 a year. Importantly, while that is a price reduction from our initial starting dose price of about $15,500 per year, this is a billion-dollar market at $2,500 per year. Obviously, to be successful, we need to do that to provide that predictability. Understood. Could you tell us a little bit more about the upcoming pilot program for Vafseo with the large dialysis organizations? What expectations could look like for that development? I know you just mentioned the second half, 2025. Yeah, kind of overall for the LDOs. Can you tell us a little bit more about sort of that evolution there? Yep, that's kind of what we've talked about. We've had one of the LDOs is going to be doing a pilot program. One of the reasons that LDOs take a little bit longer is sometimes they want to test the myriad of systems that they have in order to operationalize a new product. One of the large LDOs is going to initiate a pilot in Q3. It's a substantial size pilot between 75 and 200 clinics. If you think about 200 clinics, the third largest dialysis provider has about 700 clinics in total. 200 is pretty sizable. It's what they call an operational pilot. They're not there to prove safety or efficacy. They're really there to test the system. Can a doctor prescribe it? Does the patient get that prescription delivered to their home? Does the system indicate there's a refill? Does it help them control formulary of which patients have reimbursement for the product? Pretty much nuts and bolts of kind of how you get a new product prescribed to a patient. Since it is an operational pilot, we're thinking two to three months long for which they'll open up Vafseo use more broadly. Certainly, moving from 75 to 200 clinics to over 200,000 patients is a massive opportunity for us. We're likely to see that opening up in quarter four of this year. Excellent. Maybe if we could just change gears briefly to the other approved product, Auryxia or ferric citrate. That's used for hyperphosphatemia, as you mentioned. That's kind of the primary indication. With that product losing exclusivity in March, what's the best way to think about sales in the near term and then kind of transitioning to focusing on Vafseo moving forward? Yeah, when we think about Auryxia, frankly, we're really pleased with how Auryxia has done. It lost exclusivity back in March. At that time, the authorized generic launched, and so there's one generic, the authorized generic, on the marketplace today. What we've seen from Vafseo, from Auryxia, is really strong clinical demand for the branded product. That's one, due to its strong clinical profile. Physicians are well aware around what Auryxia can do for their patients. It's also the economic value proposition that we had in our contracting broadly with LDOs. You know, when we think about Auryxia, while we're really pleased with having that revenue, it could change at any moment. A second generic can enter that marketplace, which would have that market change really quickly. Internally here, we're really conservative for how we think about it. Every day that goes by is a day that we view as upside for the product historically. As we look to the future, we're not hedging Auryxia revenue. We're not keeping Auryxia revenue front of mind, if you will, in terms of what we do to be successful as a company. The only thing I'll say, Matt, is Auryxia, with over 10 years of experience, allowed us a foray into Vafseo. We no longer promote Auryxia despite its strong sales in quarter one, and we are 100% focused on Vafseo. Excellent. With Vafseo, you know, offsetting generic impact on Auryxia ultimately as we move forward, can you further discuss the market opportunity for Vafseo in dialysis? You've kind of covered that, but also thinking about non-dialysis patients and how that could be sort of a commercial evolution for the product? Yeah, absolutely. I mean, our intention with Vafseo is to have Vafseo become the standard of care. You know, in order to become the standard of care, you need things like clinical differentiation, which we already talked about with the MOA. You need increasing real-world physician experience. You know, physicians have to be using the product because as any new product launches in this space, it takes a little bit of time for physicians and staff to figure out how to use it. You need this kind of post-TDAPA transparency and contracting piece of it. The last piece you need in dialysis is continued data generation. Right? How do you build the profile of a product over time? An example of that would be the VOICE U.S. Renal Care is doing and Dr. Block. That program is, and that study is designed to show a 10% decrease in hospitalization and mortality. Now, it's pretty obvious hospitalization and mortality are benefits to patients. There are also benefits to dialysis organizations. You know, if you look at a 10% reduction in hospitalization, on average, a dialysis patient is hospitalized about two times a year, costs on average about $60,000 each time. It's $60,000 each time they're hospitalized. The dialysis organizations are on the hook for a large part of that. Saving 10% of that is a meaningful number per patient. Additionally, the patient, instead of being in the hospital, is in the chair receiving their dialysis, which they're earning revenue on. Continuing to increase data and the value proposition around Vafseo is going to be important in dialysis. No, I think that makes complete sense. Yeah. The best way to create a standard of care in dialysis is to actually have patients start dialysis on Vafseo. That's where MDD starts to be so important. When you look at a patient who starts dialysis with their anemia well managed, their outcomes are far better than those patients who start dialysis being anemic. Obviously, being well controlled in the MDD space through Vafseo is really important. MDD is a multi-billion dollar opportunity. It's got about the same number of patients as dialysis does, but the pricing is more traditional. It's Medicare Part B, it's Medicaid, it's commercial insurance. We expect pricing, instead of the $2,500 per year that we see in dialysis, will be four to five times greater than that. Therefore, if dialysis is a billion-dollar opportunity, non-dialysis is four to five times that. We as a company are working super hard there. We've received feedback from the FDA on a protocol. We're engaged with them around that protocol in MDD, and we're planning for a Type C meeting with the plan to initiate a phase III study in the second half of the year. Excellent. It's very exciting. Do you feel, you mentioned the exploration of decreasing hospitalization and mortality, do you feel those are the biggest levers to pull in terms of differentiating Vafseo? In terms of your mention of wanting to become standard of care, are those sort of the greatest components to focus on, or are there other aspects that could help push Vafseo into the forefront? Yeah, certainly in dialysis, you know, obviously hospitalization and mortality are the holy grails. If you can get those, that's great. In MDD, it's really interesting, every time I'm out with a physician, it's got a large unmet medical need. You know, only about 30% of patients actually receive treatment for their anemia in pre-dialysis. Right now, if you look at ESAs in that space, they're really used as rescue therapy. A patient's hemoglobin drops. In some cases, they wait to a hemoglobin of 9 or below to treat. They'll treat, they'll get them in the range, they'll wait till it comes back down to 9, they'll treat again. It creates what they call hemoglobin cycling, right? Hemoglobin cycling has demonstrated that it actually increases safety issues associated with anemia management. A lot of times physicians would rather not treat in that space. Every physician we've talked to has said that an oral therapy to help treat anemia in non-dialysis would be super, super important for patients. Mm-hmm. Very differentiated, obviously. Absolutely. Yeah, no, that's great. Kind of one nuanced question. For Vafseo, there's the distinction around dose titration once patients are on therapy. Maybe you could just briefly talk about how dose titration for optimum benefit could play into prescriptions, potentially refills at higher doses, or is that something that's kind of on the radar commercially? Yeah, no, it's a super, super important question. If you remember, the starting dose of Vafseo is 300 mg in dialysis. Then based on a patient's hemoglobin, they would titrate up or down from there. What we've seen in the first quarter of launch is about a third of our prescriptions were refills. What we saw in those refills is doctors titrating up. They were titrating up to a level that was very, very similar to what we saw in our INNO2VATE pivotal studies, which is about a 40% increase in dose. When we talk about an average price of $15,500 per year, that was at the starting dose. Imagine a dose where a patient is well controlled being about 40% higher than that. Excellent. That's very helpful. As we get closer to the end here, I wanted to make sure I asked you, what do you think are the most important near-term catalysts? I know you mentioned the LDO progress. What should be on investors' radars as we look to the next coming quarters? Yeah, it's really Vafseo, Vafseo, Vafseo. First, unlocking that additional DO, I think getting that pilot started successfully in the third quarter is critically important. Also, coming out of that pilot and making it broadly available is really important. The second thing is VOICE enrollment. That study at the end of Q1 was about 75% enrolled, and we've seen very strong enrollment since. Getting VOICE fully enrolled is important because the quicker you get it enrolled, the quicker you get an answer. That hospitalization and mortality is important. The last thing is progress on MDD, making sure that we've got a path forward with the FDA and can start the study as expeditiously as possible. Terrific. Maybe just to wrap things up, do you feel there are certain aspects of the Akebia platform or story that are currently underappreciated by investors or the market? Like any specific points that you'd like to help, you know, drill home for folks? Yeah, it's interesting because, you know, investors are really focused on Vafseo, and that's probably where they should be. We've actually got a pipeline of HIF assets out there. The first, AKB-9090, that should be in the clinic this year where we're studying acute kidney injury, you know, significant unmet need there. Quickly following on that, we have AKB-10108. That's HIF technology that we're studying for the prevention of retinopathy of prematurity. That's an orphan disease where we may actually be able to impact blindness in premature babies. Really interesting early-stage assets in our HIF platforms that we'd love to talk about more. Frankly, until we demonstrate continued success with Vafseo, it's hard to get folks to focus on any of those cool things going on in our pipeline. Sure. No, that's very helpful and very exciting. It's going to be great to see the progress with Vafseo and, you know, the evolution of the platform in the near term here. With that, I'd like to thank Nick and Akebia Therapeutics for a great discussion on their platform. This was really helpful. Thank you again, everyone, for joining us. Appreciate it. Thanks.