Good morning. I'm Patrick McCormick and from the banking team here at Wells Fargo. I will like to welcome John Butler, who's the President and CEO of Akebia Therapeutics. Akebia is a Boston-based commercial stage company that's focused on providing novel therapeutics to patients with kidney diseases, in order to improve their outcomes. So John thank you for joining us here today. Patrick thanks for the invitation. Appreciate it. Awesome. Maybe we just jump right into it. Yeah. You know starting off could you provide us with an overview of Akebia's two commercial programs, as well as you know some highlights into your recent progress and upcoming near-term events? Yeah, sure. Absolutely, I'm happy to so Akebia really is a unique company in that, you know we have this clear focus in kidney disease, and we now have two commercial products available. Auryxia has been a phosphate binder for patients on dialysis. Yesterday was Auryxia's tenth birthday, so it- Congratulations. Thank you. It's clearly a mature product, but has been an important product for us. Did just over $170 million last year. It's really unique in that it's moving into the dialysis bundle starting next year. So while there is a loss of exclusivity in the end of the first quarter of next year, we've really in a great opportunity for, you know for the product to maintain significant revenue for us in the, in you know over the next year or so. Really interesting as we go to the end of this year, you know we've talked about revenues this year being in line with last, and you know the underlying demand certainly supports that, but it's really interesting. Going into the bundle, you're completely changing the distribution channel, you kno way from wholesalers and into, you know, more directly to dialysis providers. So, you know, we're seeing that shift, and we think that'll probably have a somewhat negative impact on revenue over the back half of this year. Not because there's any change in demand, just because of the shifting supply kind of supply chain distribution channel. But those revenue have been very important for us, and it's a great product for patients. But we're really excited about a new product, Vafseo. Vafseo is our hypoxia-inducible factor prolyl hydroxylase inhibitor for the anemia of chronic kidney disease in patients on dialysis, and this was approved at the end of March. We are launching it now into dialysis. The product will be available come January of next year. The launch dynamics today is that we're working on securing reimbursement. In dialysis is a very unique marketplace, and they have this wonderful reimbursement system called TDAPA, Transitional Drug Add-on Payment Adjustment, and that creates an opportunity for dialysis providers and nephrologists to gain experience with innovative products outside of the bundled reimbursement that you have in dialysis. Now, it takes six months to secure that reimbursement, so we submitted that application shortly after approval, and we'll have that TDAPA designation come January 1st, so you know, now we are incredibly busy putting contracts in place, creating protocols with dialysis providers, driving that demand from physicians, so it's the team's really energized by what's going on, and we're really, really pleased with the progress we're making there. That's fantastic, and it's, you know, so rare for us to see a company that already has a commercial stage project that's about to launch with a second product on its own. Maybe just circling back to Vafseo for just a second, but, you know, obviously been through a number of clinical trials. What are some of those key benefits that patients are gonna see, and what did you demonstrate in those clinical trials for Vafseo, that supported its approval by the FDA earlier this year? What's unique about Vafseo is the mechanism of action. You know, this. People have been using erythropoiesis-stimulating agents, ESAs, since 1990. And you know, they you give the product, you see this very quick increase in hemoglobin levels. You see excursions above where their targets are. What you have with Vafseo is you have a much more gradual increase in hemoglobin. At the end of the day, the mechanism of action is a more physiologic mechanism of action right? This is about how the body responds to changes in oxygen levels. You know, if you or I were to get on a plane, we're here in Boston today, we went to Denver, you get off the plane, you immediately, your body immediately recognizes that you're in a lower oxygen environment because of the altitude. You have HIF that you're constantly making, that's constantly being destroyed by these enzymes, prolyl hydroxylases. That's inhibited. HIF is stabilized. It goes to the nucleus of the cell. It binds with HIF beta. This is what turns on the bone marrow to make red blood cells. That's exactly what Vafseo does. It inhibits the prolyl hydroxylases, allowing HIF to stabilize. So you see this nice gradual increase in hemoglobin. You see fewer excursions, a more gradual increase, you know fewer dose titrations for physicians. You know, all of these things is about ease of use and, you know potential safety benefits as well. That's, that's extremely helpful for me. Maybe you could spend just a minute reviewing the market opportunity for Vafseo, both in the currently approved labeled indication and then potential expansion opportunities. And specifically, are there any patient segments that you plan to prioritize during this initial launch? Yeah. So if we focus on the launch in dialysis, the dialysis market for ESAs is about a $1 billion market today. There's about 550,000 patients on dialysis. 90% of them are treated with an ESA, so let's call it 500,000 patients on ESA therapy. And at an average cost per patient per year of about $2,500, that's about a $1 billion market opportunity. So, you know, we do think with this TDAPA reimbursement, where dialysis providers today pay for their ESAs and are reimbursed as part of an overall bundle. So with TDAPA reimbursement, they're able to bill for Vafseo outside of that dialysis bundle on an ASP basis. So instead of paying $2,500 a year for an ESA, they can pay for Vafseo, bill for that separately, and not incur that cost. So you have a cost avoidance, and you have the contractual benefit of Vafseo as well. So there's a great economic incentive for dialysis providers to allow physicians to use the product. You know, as we talk about the launch, we really talk about three buckets of things we need to do well, like kind of a three-legged stool, if you will. Mm-hmm. We've got to drive demand at the physician level, and that's talking about those benefits I talked about before: avoiding excursions, a gradual increase, differentiated mechanism of action, fewer dose titrations, all of those things that get physicians excited about using it. We've got to contract effectively with the dialysis providers. That is critical. You know, there's two dialysis providers who treat 80% of the patients. You know, we have great relationships there. We've been working in this space. I've been working in this space since nineteen ninety-one. You know, we think that's a real competitive advantage for us. We're putting those contracts in place now. Very pleased with how that process is going. We have a target of having every patient provider under contract by the end of the year. And then the third leg of the stool is we got to keep generating new data. And just yesterday, we put a press release out announcing the VOICE trial, which is a collaborative trial that's being run by Dr. Geoffrey Block out of Denver with US Renal Care, the third-largest dialysis provider in the country. And this is looking at using the product three times a week when they get dialysis. You know, we're looking at all-cause mortality, non-inferiority there, but we powered it to show a benefit in hospitalization, a superiority for hospitalization. We saw about a 6% benefit in our phase three program, but it wasn't statistically significant. Now, we started at a much lower dose, people had hemoglobin instability. We think that given what we've learned about dosing and dialysis, avoiding excursions and avoiding what's called ESA rescues, where hemoglobins drop, and you have to give them an ESA- Yeah. Those are the things that were really closely associated with MACE. If we can remove those, which we believe we can, we demonstrated that in another study, in FO2CUS, maybe we can show this benefit in hospitalization. If we can show that benefit in hospitalization, then we get to continue to grow this, this product well beyond TDAPA. It's not just an economic or a convenience advantage. Now you're making a really significant benefit for patients. And of course, keeping people in the dialysis center, in the chair dialyzing, is also a revenue stream for the dialysis providers. So those are the three legs of the dialysis stool. You know, we're driving that demand today. We're getting those contracts in place. Really pleased with the progress we're making there. And then, you know, now we've kind of shown these are the kinds of studies we're going to do to help generate new data to keep the product growing in dialysis. And that's a billion-dollar market. But you referenced non-dialysis as well. Yep. Of course, non-dialysis is a much larger market opportunity. About the same number of patients, about 500,000 patients who are not yet on dialysis, Stage four, Stage five, but have anemia. Mm-hmm. The difference from dialysis, where 90% of patients are treated, in non-dialysis, it's really only about 23-24% of patients who are treated with an ESA today. When I'm talking to physicians about where they're going to use the product in dialysis and, you know, they talk about home patients, because an oral product, we can use it at home, high-dose ESA patients, those are the ones I want to try the drug on. They'll always end with, "But I'd really like to use it in non-dialysis." You know, we agree, right? This is a once-a-day oral product where patients aren't being treated today. We'd love to get the product to them. You know, when we got the CRL from FDA two years ago, part of it, you know, FDA said, "Come back and talk to us about a population where the benefit-risk is positive." So we know we're going to have to do more clinical work to assess that in our label, and we're working on that now. We will. We expect that we'll have feedback from the FDA before the end of this year, so we'll be able to kind of talk to the street about, you know, this is our path forward to include non-dialysis in our label. But if you think about the way the market's set up, we're now contracting with dialysis providers. We're providing, you know, discounts. After TDAPA, our pricing has to look a lot like ESA pricing today, so $2,500 a patient. Again, that's a billion-dollar market. You know, we can be very profitable there. But our WAC price today for the starting dose is about $15,500. When you think about a more traditional gross to net in a non-dialysis market, will be substantively higher price per patient for a market that's about the same size. So to say that it will at least double the market opportunity, I think undercalls the opportunity when you think about that pricing difference. And again, it's much more of a kind of a blue ocean, right? I mean, these are patients who aren't being treated today. So, you know, we've got to get today's launch right, and, you know, the team is focused on that. But the clinical folks are really very focused on what's the study we can do effectively and quickly to move the non-dialysis market opportunity into our label? ... And there is, obviously, there's a huge market for dialysis, and there is for non-dialysis as well. And so you touched on it just a little bit, but why are patients not currently being treated effectively? Is that from formulation of existing drugs and sort of what benefits might Vafseo have, in that, in the future? Yeah, I mean, in dialysis, about 25% of the patients are not in the target range of hemoglobin. So, these are the patients who are getting the highest doses. That's why one of the areas where physicians are looking at. You know, anytime, you know, you have people who aren't achieving goal, you know, if you have something that's got a different mechanism of action, let me try that there. And, you know, if you think about in dialysis, you keep jacking up the dose of ESA, well, those are also the most expensive patients for the dialysis providers, and they're not getting the outcomes that they're looking for. So, you know, trying a new product where you're increasing hemoglobin via a different mechanism makes a lot of sense. And you know, our goal is to become a standard of care. But you've got to, you know, get there over time, and like, where do physicians want to use the drug? Well, home patients, oral drug, don't bring them into the center to give them a shot. That makes sense. That's low-hanging fruit. That's 80,000 patients. And then these high-dose ESAs, that's maybe another 150,000 patients. So that's where we think, you know, we'll get that penetration. In non-dialysis, again, you know, ESAs demonstrated that there was some increase in MACE risk, and that, you know, I think that's hung on. But really, it's about... This is an injectable product. They have to go to an infusion center to get it. In insurers, you'll, if their hemoglobin is below 10, they'll let them get a shot. They come back to the doctor the next time their hemoglobin is over 10, they can't get another shot. With a once-a-day oral product, you write a prescription, you have refills. It's just, it's an outpatient setting. You know, it's an oral product. It just makes more sense, and when I see how excited physicians are about the opportunity to use it in the non-dialysis population, you know, we clearly have a responsibility to get that in our label. I completely agree, and it's a wonderful opportunity for you guys, excuse me, to track down in the future, especially from a patient dosing, patient convenience, and the ability to treat them more adequately than they are currently being treated right now with existing therapies. When you look at it now, there's so much data that shows that these 75% of patients aren't treated, and when they start dialysis, if they start dialysis with anemia, their mortality rate is higher than someone whose hemoglobin is managed three months later, six months later, twelve months later. In other words, you never catch up, you know, even though they're being treated. So if they start dialysis with anemia and not as well managed, they're going to do poorly on dialysis. So physicians really do want to treat these patients, and you know, we believe we have a solution. That's, that's fantastic. Maybe, you know, obviously, the product was approved in March. You guys been doing a lot of work to prep for commercialization. So, you know, maybe you could give us an overview of what the sales force has been doing to prepare for launch in advance of that, and you know, how you've been utilizing your resources and staff that you have on hand to get ready for twenty twenty-five. Yeah, sure. Of course. So this goes back to the three legs of the stool, right? Yeah. And the sales force is one leg. It's the driving physician demand. And, you know, it's the first time in my thirty-plus year career where you have a product approved, and you have nine months before you actually are selling it to prepare the market. And, you know, the example I keep using is, you know, we're trying to compress a spring down, you know, get people excited about using it, and then have the product available in January and kind of release that and, you know, kind of have as steep an adoption curve as we can. Because in nephrology, traditionally, launches are slow. Mm-hmm. I mean, nephrologists are not as There's a lot of inertia with them. There's a lot of inertia, right? I mean, oncologists move quickly, right? Right. Nephrologists don't. So hopefully, we're spending that slow time over the next nine months, kind of generating that demand. What's great for the company as well is having Auryxia, we already have that commercial footprint. Mm-hmm. There's about 96% overlap between Auryxia prescribers and potential Vafseo prescribers. So, you know, we literally have added a handful of sales reps, gone from 36 to 40 sales reps. So, it's not, you know, for a small company, not making a huge investment in, you know, spending a lot of cash on building a commercial organization. They're there, they have relationships, and we're focusing them now on the growth product. Mm-hmm. That's another reason why, you know, we kinda have, you know, Auryxia being a ten-year-old product, has a very stable underlying demand. There's no sense in deploying sales effort to that. I want them talking about Vafseo. Yeah. That's what's gonna be the future of the company. So that's, you know, where they're transitioning now as we get into the fourth quarter to 100% talking about Vafseo. So that's the one leg. There's a lot of medical work here as well, you know, the medical affairs side of the world. Right. Because dialysis providers need protocols in place for, you know, their nephrologists to to know where and how they can use the drug. So our medical affairs folks are working with the dialysis providers on, on putting those protocols in place. And then we have the team of people who are working on, on putting the contracts in place as well. So it's, it's an incredibly active, time for us. You can really feel the momentum of the company as well, you know, as we have successes, you know, with things like VOICE. You know, we talked about, you know, putting contracts in place. You know, the company just gets, incredibly, jazzed about, you know, what we can accomplish for patients here. I think that's one point that I didn't really appreciate until we spoke earlier today, was around the ability to leverage the existing- Mm-hmm ... sales force that you have. And so they have both an inherent knowledge of nephrology and of the needs of patients that are either on dialysis or-... trending towards dialysis. And so I think the education level to that group of people that will be existing, incrementally, it's not a huge leap for them to be able to, to move another product that's gonna fit well inside of their bag. 100%. That's exactly right. It's the same people, and, you know, having been a sales rep very early in my career, you love a launch, and you love something new to talk about. And you can see that when we interact with the sales organization, I mean, how excited they are about it. And then maybe, you know, moving on to that next, that last leg of the stool. We talked a little bit about payer contracting. How does the environment and dialysis centers, how does that impact you guys? And how do you win, get to a win-win situation for both Akebia and for payers? Yeah, it is a unique market, and this is why I said it's really a competitive advantage for us to have the kind of expertise there that we have, you know, on staff, from myself on down. You have to understand how to make it a win-win for the dialysis providers. You know, it's not... You have a new product come out, and you say to a physician, "You know, I'd like you to use this product," and they say, "Okay." You know, you put payer contracts in place, and they write a prescription, and they're off to the races. It doesn't work that way in dialysis. Everything is done by protocols. You know, they have the things that they want to use. So, and they're, you know, especially once you get outside the big ones, they run on very thin margins, right? 85% of their patients are Medicare patients under this bundled reimbursement system. So you want to introduce a new product like Vafseo, you have to create an economic reality for them, where, you know, kind of the juice is worth the squeeze. Mm. You know, there's a lot of operational work that they have to do. They take on bad debt, and, you know, we hear about all of it as we go through contracting. So, you know, we created a price point at $15,500 on the starting dose that, you know, we then contract with an off-invoice discount and a volume-based discount. So, you know, our net price will drop as volume increases, but during this two-year TDAPA period, that creates opportunity for margin for them. Now, the physicians have to want to do it. That's why there's three legs to the stool. If there's no demand, there's no margin, but if the physician demand is there, you want them to be able to access the product. Creating contracts that allow for that is what is what we need to do. Now, TDAPA is not the entire dialysis population. It's roughly, call it 40-ish% of the dialysis population. That's the target for us initially. Then you get outside of TDAPA, you get people excited to use the product, you generate new data. After TDAPA, you're now going after the entire five hundred thousand dialysis patients. So you kind of take this stepwise approach, create an opportunity for the dialysis providers to actually look at this as a positive from an economic standpoint, avoid the cost of an ESA and make a margin on Vafseo. It does what TDAPA is supposed to do, which is to allow physicians to try innovative drugs and see how they fit in the practice. Mm. So that's what CMS set out to do by creating TDAPA. And, you know, understanding all of those pieces, I think, is what's gonna allow us to be successful. How should we be thinking about the ramp during the two-year TDAPA period? Well, we're all gonna see. I mean, it's nothing. Again, I don't wanna oversell how quickly it can go. Yeah. But, you know, once you have protocols in place and physicians want to use the drug, you know, it, it can move. Now, interestingly, about 20% of the patients are at small and medium-sized providers. You know, that's where there's a lot less distance between the people who are putting contracts in place and the people who are writing the drug. And as I said, they're the ones who work on the thinnest margins. And I think we've seen with other TDAPA drugs, that's where you get the traction fastest. Mm. And so, you know, I expect that we'll see the same thing. You know, the early days, it'll be more kind of small, medium providers who move quickly. And then, you know, the larger ones who just have more, you know, kind of the wheels have to turn, will come along, as well. But if you create the right incentive, and the demand is there from the physicians, because it doesn't matter what the incentive is, if the physicians don't see it as a benefit for the patients, they're not gonna use it. They're not gonna use it. But you've got two years to take advantage of this. And you know, it is dialysis providers look for every opportunity they can to increase their per treatment margin. So you know, we do think it can go quite quickly. That's how we're focusing, though we have not guided on revenue. Sure. And does having both Auryxia and Vafseo in its TDAPA period beneficial to the company? You know, it really is. And it's the fact that Auryxia is going into the bundle. I talked about, you know, the complexity of the supply chain that we're working through this year, but, you know, that has, particularly when you think about contracting, they have to contract for the phosphate binders. So it's not us calling up the dialysis providers and say: Hey, we want to talk about Vafseo. It's basically them calling us saying, "We need a contract for Auryxia. Yeah. And, oh, by the way, we have this other product that we wanna contract as well." So, you know, we knew that there was gonna be a benefit to that, you know, before we started this, but I'm really pleased with how much access that's given us to the dialysis provider. And, you know, they are, you know, they're very focused on getting those binders in the bundle, and then when you can kind of talk about, you know, the benefit they'll get from Vafseo as well, it's really a really impressive one-two punch for us. Mm-hmm. No, that's really beneficial for you guys and for the patients, too. You know, maybe this is the time just to segue just a little bit. I know that there was an agreement in place with CSL Vifor that you guys have recently restructured. Maybe you could talk about how the restructuring of that agreement benefits Akebia going into the future, and you know, how that might simplify commercialization? I mean, look, at the end of the day, our fate is in our hands, in our own hands, and you always want that. You know, Vifor has been a very good partner, you know, for a number of years. You know, they put a lot of capital into the company. They were there for us. But the way the relationship was structured, it was just operationally very clunky. Mm-hmm. You know, Vifor also has a competing product in Mircera that has a large part of the market. They were responsible for doing contracting. It just made more sense for both of us to change this from the profit-sharing relationship that it was to a royalty agreement. You know, it gives them. You know, they only had access to the dialysis market. Now, it's on all sales, so you know, into non-dialysis. So there's some you know, opportunities for them. But truly, this just gives us control of our own fate. We're contracting with everyone in the dialysis market. At the end of the day, our sales reps were the ones who were gonna be out there pulling it through anyway. Right. So that's what I mean about it was just kind of clunky the way it was constructed, and this just simplifies it, and I think it truly was a win-win, and I really appreciate you know with Vifor how they approached it and how we've partnered with them for the last five or six years. No, that's fantastic that you guys- Mm ... were able to simplify that and straighten, you know- Yeah ... straighten everything out and still provide a benefit. You know, we touched a little bit on non-dialysis CKD patients, but just wanted to double back and, you know, talk about how that drug might be reimbursed for those patients, if there's a little bit more detail we could go into. Yeah. Well, Again, it's a much more traditional reimbursement for an oral product. I mean, I think the non-dialysis market. Whereas dialysis is 85% Medicare, and, you know, some MA and, and about half MA and half fee-for-service, non-dialysis is, again, much more traditional. About half, probably a little bit of a moving target, but about half is commercial insurance, and, and the other half is, more Part D and, and some Medicaid. But that really creates that, that greater opportunity. It's not that you're negotiating with dialysis providers and contracting and discounting. It is, contracts that you put in place with, with Part D providers, and I. I mean, you, you have a much more traditional kind of gross to net in that market. And, and as I said, where you're talking about $2,500 per patient post-TDAPA- Okay ... for Auryxia, for Vafseo, in the non-dialysis market, you're taking a more traditional gross to net off of this $15,000-$20,000 WAC. That's very helpful for me. You know, obviously, two products that are gonna be commercialized, obviously the focus of the company, but there is an earlier stage pipeline that you guys continue to develop. Is there any information that you might be able to share about sort of what the plans are that you have for it and sort of what that might look like? Sure. I mean, we're obviously so focused on the launch. We know we need to get that right, but, you know, once you have that product out, it's always, "What's next? Yeah. Right? And, Biotech. Yeah, biotech. Exactly. And, you know, we think the HIF pathway is a really fertile ground for, you know, kind of finding new opportunities, frequently in more acute care settings. And so we have two early-stage programs that we're excited about both of them. AKB-9090 is an acute care product that we're targeting two indications. One is acute kidney injury, so right down our kind of strategic wheelhouse, and the other is ARDS, acute respiratory distress syndrome. Mm-hmm. We are, you know, in the process of doing our IND-enabling tox work, and our goal is to have that product in the clinic, you know, phase one next year. The second compound, AKB-10108, is just a little bit behind AKB-9090, but it's one that I'm incredibly excited about. Again, this is super early. It's preclinical. Sure. But this is targeted at retinopathy of prematurity. And you know, when a baby is born prematurely, your retina only starts to develop at week 24. And so when they're born, put into 100% oxygen environment, you know, they get this hyper growth of the. You know, first, it tells the, when they're in 100% oxygen, the retina stops growing. And then a free radical environment. Then you take them out, and it starts to grow, you know, kind of uncontrollably, and it leads to decrease in vision and ultimately blindness. It's the number one cause of blindness in premature babies. So, you know, very simply, we're looking at 10108 to, you know, again, fool the body into thinking you're still in that anaerobic environment of the womb and have the retina and the lungs, frankly, 'cause bronchopulmonary dysplasia is another issue that these babies face, you know, have that develop normally. And, you know, we had an advisory board with a number of these pediatric ophthalmologists just recently, a couple weeks ago, and they're very excited about this pathway. And, you know, my goal now is to find ways to accelerate this as quickly as possible. This is clearly an orphan-type indication and one that again it's super early, but you know we think this can make a massive difference. And it expands our footprint beyond you know the kidney disease footprint. Yeah, I think that's what's the most exciting part of that. And I was gonna ask about total addressable market, but I understand it's an, it's an orphan disease, and obviously- Yeah ... going into pediatrics is an extension for the company, so... Yeah ... very, very exciting. Yeah, it is exciting. I mean, it's doing drug development in the neph, but it's a well-understood path also. Yeah. You know, obviously, you know, first, we'll be in normal volunteers before you go into neonates. But it's, you know, we're super excited about that, about the potential there. And, you know, as our launch starts accelerating, how can we accelerate all of our early stage programs, is a question we're already asking, as an executive team. I have no doubt that somebody's already following up on that. I think that's a nice segue into obviously, you've got a launch that's coming up. There's a lot of expenses with it. You've got a development stage pipeline. So what's the company's current cash position, and how do you guys think about cash runway into the future? We had about $40 million in the bank at the end of the last quarter. You know, we've talked about having cash for at least two years. Mm-hmm. Because remember, we have a $170 million revenue product from Auryxia. Yep. And we have the launch of Vafseo coming up as well. And, you know, as I kind of referenced before, we're really unique in having that revenue stream, but also, you know, we're a small company doing a launch, but we have a commercial organization in place. That's one of the two most expensive areas. Second expensive area is product and having product available, and we were ready to launch two years ago when we got the CRL. So the product's on the shelf. Our team has done a great job of extending our dating on that product, so we don't have to take on a significant cash expense to make more product for the launch today. It's there waiting for- Ready, yeah. for patients. So, you know, we feel very good about our cash position and, you know, we're just getting excited to start to see the revenue from Vafseo. Well, that's great. You know, we definitely appreciate you coming out to the conference today and for spending some time with us this morning. Excited to follow up, in the future, and looking forward to the launch of Vafseo, as well as the continued commercialization of Auryxia. It's great. Patrick, thanks for the invitation again. Thank you, John. Appreciate it. Yeah. Thanks. Great. Bye-bye.