Hello everyone. My name is Alex Buckley from the Healthcare Investment Banking Group at J.P. Morgan. And it's my pleasure today to introduce John Butler, CEO of Akebia Therapeutics. There'll be some time at the end for questions, but in the meantime, let me pass over to John.
Alex, thank you so much, and I appreciate the invitation to discuss Akebia with everyone today. I'm always excited to talk about Akebia, particularly today. Akebia is a company that is mission-focused, and our mission is to better the lives of people impacted by kidney disease. And I think we're well on our way as a company to doing that. And I just want to remind you before I begin that I'm going to be making forward-looking statements, so please refer to our SEC filings for more information. I think this is a great place to start. Our first Vafseo vadadustat shipments were one week ago today on January 9th. This has been an incredible effort from an incredible number of people to bring this product to market. People who are at Akebia now and were at Akebia previously.
I'll say over the last two years, I think we describe as more of a fight to get this product to be available to patients. So it's incredibly gratifying to be able to talk to you today about the launch of Vafseo in the U.S. And I think we'll spend a lot of time this morning talking about the launch of Vafseo, but I think that is a central part, but only one part of the reason that Akebia is such an interesting and compelling investment. The dialysis business is a $1 billion market opportunity, a very substantive market that we believe we're on the cusp of disrupting with Vafseo, bringing a new way of treating anemia to patients. But beyond the dialysis market, the non-dialysis market is even larger.
It's a multiple of the dialysis market, and we are now pursuing label expansion for Vafseo into that late-stage CKD population. We'll talk a lot about that process here today. So just alone, those two things are incredibly compelling for the company. But we have more than that. We've really developed this expertise in the company around HIF biology, and we're really the only company pursuing HIF-PHIs, prolyl hydroxylase inhibitors, as a therapeutic solution. And we're really starting to see the fruits of that as we have the first products of that internal research that we're now bringing into the clinic and expect the first to enter the clinic in 2025. And these are assets that are both in kidney disease, and we're excited that we're also starting to look for opportunities outside of kidney disease in rare diseases that are significant unmet medical needs.
Finally, we're doing all of this from a position of financial strength. Our cash on hand and our cash from operations will fund our current operating plan for at least the next two years. Just to be clear, we're talking about the VOICE trial, we're talking about the NDD trial during the presentation today, our new products going into the clinic. We consider all of those as part of our operating plan, and we believe that our cash on hand and the sales of both Auryxia and Vafseo will allow us to move forward with all of those programs for at least the next two years. Let's jump into talking about the launch. Again, it feels like it was a long time coming. As you know, we had FDA approval in March of last year, but we're in dialysis.
Dialysis is a very unique market with a particularly unique reimbursement system. And that reimbursement system creates incredible opportunity for us over the next two years. We needed to secure this transitional drug add-on payment or TDAPA payment, which we received in October of last year, and it kicked in January 1st of this year. And then, of course, we talk about this nine months that we've been working to get to the place where we're launching the product. But I'll tell you, we used that nine months incredibly effectively. And one of the things we need, we need access. You need access, and to get access in dialysis, you need contracts in place with the dialysis provider. That's just step one, but it's the most important step is to get that contract in place.
And we're incredibly proud to say that we have nearly 100% of U.S. dialysis patients who are being treated at a dialysis provider where we have a contract for them to be able to access Vafseo. We signed the last contract with a major provider just at the end of last week. I truly appreciate their partnership and making sure we were able to stand up here today and talk about the level of access that we have. As I said, that's only step one. You've got to put protocols in place, and you've got to pull through from the physician perspective with our commercial organization. Obviously, with the contract signed last Friday, we're just starting that protocol process now. But for all the others we signed earlier, we have those protocols in place, and the commercial organization is excited and active.
The first prescriptions having been written just Monday of this week. So I'm going to step back for just a second. I'm going to say, here's this great execution that we've done. I mean, everything we said we were going to do this year in 2024, we've done, and we're proud of that. But some people ask, and I've heard this question, well, but people have been using ESAs in dialysis for the last 30 years. What's the opportunity for Vafseo? And it's significant. And I think nephrologists, and you see from my research, nephrologists agree it's significant. I'll start with the fact that simply 25% of patients just do not achieve the hemoglobin target that physicians want for them. There are about 20% of patients who you'd consider true hyper-responders to ESAs. They have higher hospitalization rates. They have higher one-year mortality rates.
Physicians are always concerned when they have to increase the dose of ESAs. It's well known that there's increasing MACE risk as ESA doses increase. Of course, for the home population who don't want to come into the dialysis center to get an injection, an injectable product is suboptimal. Once-a-day oral product is ideal for that population. For all of these reasons, this is why more than two out of three nephrologists say there's clearly an unmet need for a new treatment for anemia. Let me talk a little bit about how we're positioning Vafseo in the market. To be clear upfront, we're not positioning Vafseo for a niche opportunity just for your home patients, just for your high-dose ESA patients. That may be where they start. To be clear, we're positioning Vafseo as an opportunity to create a new standard of care for patients with anemia due to CKD.
And frankly, our expectation is that it will be a new standard of care for all patients with anemia due to CKD. Today, we're focused on dialysis. The basis of that positioning, that focus is around this new mechanism of action, this HIF -PHI mechanism of action, this Nobel Prize-winning science. Why is this different? It stimulates the body's natural response to hypoxia. In other words, it's a much more physiologic way to manage anemia. It enhances the body's natural production of EPO. When you give an ESA, you're giving a super physiologic dose of that protein. You're seeing spikes in EPO levels. When we measure EPO in our studies, you hardly see a change in EPO levels, yet you see that hemoglobin response. When you need to make red blood cells, it's not just about EPO. It's also about iron. The HIF mechanism, you also activate iron mobilization.
Again, a more physiologic approach to managing anemia. So what does that mean? It means hemoglobin is controlled. The levels increase over time. It's a more gradual increase that allows you to get patients in the range and keep them in the target range. We saw fewer overshoots. Patients stayed in the range of 10 to 11. This is what physicians are looking for. And they're looking for it in an area where they can use. It's a simple titration of the drug, fewer dose modifications. Never underestimate the power of a product that can make a physician's life easier. These physicians spend a tremendous amount of time, frankly, tinkering with the ESA dose to keep people within a target range.
We saw in our studies fewer dose modifications, and it's a simple titration and allows patients to stay within the target range, all in a convenient oral dose for patients. So we think there's a very strong value proposition for Vafseo for the dialysis patient. So you want to become standard of care, but you do have to start somewhere. Physicians have to say, where is it I want to initially use this product? There are two areas that have come to the fore. And we've been talking about these for some time. And I think as we're out in the field, we're seeing that play through. Out of the 500,000 dialysis patients in the U.S. who have or treated for anemia, the home patient is, I think, the number one area that we hear from physicians that they want to use the patient.
It's just clear to them that they hear patients complain about having to come into the center maybe a couple of times a month to get a shot. And the idea that they can write them a prescription and have them take that at home once a day is very attractive for the physician and for the patients. There's about 80,000 patients of the 500,000, and it's a very fast-growing segment of the dialysis market. Now, the second area is maybe even more intriguing. And this is the higher dose ESA patient, which we estimate to be about 150,000 of those dialysis patients. As I mentioned earlier, physicians are concerned when they have to continually increase the dose of ESAs to achieve a hemoglobin response. They don't want to increase that risk, and they're looking for another option.
So there's a really strong clinical rationale for why they want to use a product like Vafseo in the patients who have a higher dose of ESA. But there's also a significant reason from the dialysis operator's perspective that those patients are ideal. Remember, dialysis is a capitated environment. For a fee-for-service patient, they get $274 a month. About $16 of that is what, on average, they pay for an ESA. If a patient's on an ESA dose that's two or three times higher, they could be spending $40 or $50 on ESA alone. And they still have to provide dialysis three times a week and still only get $274. So the idea that these high-dose ESA patients could get Vafseo where it's reimbursed outside of that bundle on an ASP basis is very, very attractive for dialysis providers.
As I said, fundamentally, and this is incredibly important, there's a strong clinical rationale for why those patients make sense. I've talked about our operational execution. It has been on point for the last nine months. We talked about, from a commercial standpoint, two things we needed to do, sort of mom and apple pie, create access and drive demand. We've done that over the last nine months. Again, we are, I think, the first TDAPA drug that has entered the market with 100% of patients covered by a contract with a dialysis provider. We say nearly 100% because there's some patients who may be dialyzed in a hospital in a long-term care facility. Virtually all of the patients are covered by the contracts we have in place or the GPO contracts for dialysis providers. We established a price.
Remember when we talked about pricing first? We talked about how we're thinking about not just dialysis, but non-dialysis as well. At a starting dose of $15,500 annually, this creates a significant opportunity for Akebia and a significant opportunity for the dialysis patient. And it's clearly supported by the value that the product brings. We secured that TDAPA reimbursement. And this is the first time in my career. I've been doing this an awfully long time. You do not have the opportunity to talk about a product from its approval for nine months before a physician actually has to write a prescription. And our commercial and medical team has really taken advantage of that opportunity to educate physicians and prepare them to prescribe. In the time since the approval, we've had over 20,000 interactions with potential customers for the product.
So again, the team has just done a magnificent job of execution, and what has that translated into? This is nephrologist feedback from market research we did towards the end of last year on would they be willing to prescribe and in what timeframe would they be willing to prescribe, and this is a cumulative look, and you can see that by the time you get out to 12 months, virtually 99% of physicians are willing to prescribe Vafseo, and you can see that that ramp-up is quite significant as well, and I have to say, market research never translates into what happens in the market, but I also have to say, I have never started with numbers this high before, that this level of interest is this significant.
Even if half of these physicians do what they say they're going to do, we're going to have an unbelievable launch of this product, and we're incredibly excited about that. As I said, we're in day four today now of physicians actually being able to write prescriptions for patients, so we certainly don't want to get out over our skis, as they say, but the feedback that we're getting from the field is incredibly exciting for all of us who are here today talking to you. I've been talking over the last nine months about three legs to the stool. There's driving demand. There's contracting, and the third is continuing to build evidence, and a centerpiece of that desire to build evidence is the VOICE trial, and the VOICE trial is a study we're doing in collaboration with U.S. Renal Care and Dr. Jeff Block.
This is a very important outcomes trial targeting 2,200 patients to enroll. The endpoints are all-cause mortality, all-cause hospitalization. 2,200 patients gives us the power if we show a 10% reduction in hospitalization that that would be a significant reduction. That is how you become standard of care, is to build evidence like that. We're excited about that opportunity to deliver on that promise. One of the things I wanted to point out here is that Dr. Block started to enroll this study just after Thanksgiving, so maybe the very beginning of December. As of last Friday, he already had 650 subjects enrolled in the study. That is an outstanding performance. Again, I think this is an important clinical study, but I think it just generally speaks to the interest level in the product.
I just got a report this morning that he's now consented, and this is what, four days later, he's now consented 865 subjects for this study. Again, I mean, Dr. Jeff Block is an amazing trialist, but this really speaks, I think, to the interest that clinicians have in understanding where Vafseo can make a difference for patients. We believe that we are incredibly well-positioned in the dialysis market, and we're excited about delivering on that opportunity. I want to spend a significant amount of time now talking about our opportunity to capitalize on a significantly larger market in the non-dialysis population. You've seen me present this slide before. Anemia is simply not optimally managed in CKD non-dialysis patients. If patients start dialysis with a hemoglobin that's below 10 or below 9, they have a significantly higher mortality rate.
And the graph on the left, I think, is stunning. At three months, they have a higher mortality rate. At six months, they have a higher mortality rate. At 12 months, they have a higher mortality rate. When they start dialysis, their anemia is managed. But if you start dialysis with anemia, you never catch up. You never catch up. And these patients have poorer outcomes. Physicians understand this risk. They understand this consequence. Yet this is data that comes from Spherix, outside market research. This is actually chart review data. This is actual use of the product. You see over the years, the use of ESAs is actually declining in this patient population, even though physicians understand this significant risk. Why is it declining? Well, patients simply don't want to give themselves a shot. They don't want to come in for an injection.
But more significantly is this frustration that physicians have with using ESAs. The way ESAs labels are written, it's basically rescue therapy. And that's how payers are managing it. A patient comes in, has a hemoglobin below 10, they can give them a shot of ESA. They come back in the following month. If their hemoglobin is 10.1 or 10.2 or 10.5, they can't get another shot. They have to wait until their hemoglobin drops below 10. Basically, the label and the way that payers have it used, it creates this hemoglobin instability, this up and down of hemoglobin, which is actually a risk factor for increased cardiovascular risk. So physicians recognize that maybe treating patients that way is doing more harm than good. And so they wait until the hemoglobin is below even eight, we see sometimes, that that's where they'll start using the product.
They understand the risk, but they feel like the solution may not actually be helping the patient. And that's why they're so excited about the opportunity that Vafseo can present for them. This is more research from Spherix. And to focus you on the middle panel, they asked nephrologists about their agreement with the statement that their treatment of anemia in CKD NDD will increase substantially if HIF-PHI are FDA approved. 87% of physicians agree that their use will increase substantially. 57% strongly agree with that statement. That's an amazing number, but not surprising when you look at their frustration with using ESAs. And even where they do use an ESA, in six months, two-thirds of them said they will have their patient switched within six months. Frankly, that's the less important market.
It's that market of patients who are not being treated today in NDD that's so critical for patient care. And it's an incredible business opportunity for Akebia as well. I spent the first 10 minutes of this presentation talking about dialysis. Dialysis is a billion-dollar market opportunity where we believe Vafseo can be standard of care. It's an incredibly important market for us. It's about 500,000 dialysis patients who are anemic. If you look at the stage IV and stage V, so later stage CKD patients, there's about 550,000 who are anemic, so about the same size as the dialysis market. But because you don't have this bundled payer, you have a significantly different opportunity. Remember, we've talked in the past about how once we get through TDAPA, the average price per patient in dialysis will be about $2,500. Remember, our WAC price is about $15,500 for the starting dose.
The average dose from the PROTECT study in non-dialysis patients would be about $20,000 a year. Even when you take your normal gross-to-net discounts and take a discount for compliance as well, you're still talking about an opportunity that's maybe four to five times as large. We have to pursue this because patients need it. But the opportunity here from a business perspective for Akebia is incredibly massive. And so why do we think we can take advantage of that opportunity? If you recall the PROTECT study, our non-dialysis phase III, we missed that primary safety endpoint of MACE. I just want to remind everyone that the U.S. population, we stratified on geography. So it was a stratified population. It was a pre-specified analysis. We were treating U.S. patients with a different hemoglobin target of 10-11, which is the target here in the U.S.
And when you analyze that population, which was 1,700 patients, about half of the study, you saw no increased MACE risk. And treatment of non-dialysis is homogeneous within the U.S. When you get dialysis anywhere in the world, once you get to dialysis, you're basically treated very, very similarly. Non-dialysis is not the same. We saw very significant differences in ways patients were treated outside of the U.S. in the non-dialysis study. The FDA is regulating for U.S. patients. And in the U.S. patients, we didn't see that increased MACE risk. But we still have to answer that broader question. So we've engaged with the FDA on this. And I'm very encouraged by the way the FDA is approaching this. In correspondence with the company, they acknowledge an unmet need for safer and orally available therapies to treat anemia due to CKD in certain non-dialysis patients.
We're focusing on those stage IV and V, later stage non-dialysis patients. Orally available therapies. The only orally available therapy in development today for the non-dialysis population is Vafseo. We submitted a protocol to the FDA. We received their feedback on that protocol. We're incorporating that feedback as appropriate. The design is an outcome study. We're expecting to begin the study by the middle of this year. This is going to be 1,500 U.S. patients, stage IV and V CKD, not on dialysis. Very importantly, the comparator in this study is going to be standard of care. There'll be a significant number of patients on an ESA. When you look at those chart reviews and you see how few patients are actually treated, that's what physicians want to understand. They want to understand how this product will perform vis-à-vis standard of care.
What that also does is it allows us to enroll this trial much more quickly and in a much more cost-effective manner. So we're excited to get this study started by the middle of this year, sorry, the middle of 2025. And we look forward to updating you on that. This study is an incredibly important study, but I do want to point out that it will only be one part of a very robust data package that the FDA will have to approve this product for the non-dialysis population. We have the U.S. PROTECT study, which is 1,700 patients. 1,500 patients in this study. It'll be over 3,000, over 3,200 U.S. patients, non-dialysis patients treated as part of a clinical program. On top of that, the drug will be available in the U.S. for dialysis for at least two years, maybe more.
For non-dialysis patients in Japan, they'll have five years of in-market experience by the time they're reviewing this data. We feel very, very confident in the strength, the robustness of the data package that will support the non-dialysis market opportunity and regulatory review. Hopefully you're as excited as we are about the opportunity both in dialysis for Vafseo as well as in non-dialysis. I'm going to spend just two minutes talking about our pipeline. I think most of the focus from investors will be on how we execute the launch. We are very focused on that as well and look forward to giving you updates on it. We're excited about our pipeline. We think later this year, once we have a couple of quarters of revenue under our belt, we'll do a more in-depth look at our pipeline.
But as I mentioned at the beginning of the talk, we've really developed an expertise in HIF biology. We have a very small discovery research team who have been incredibly productive. And the fruits of that labor is really coming to the clinic now. AKB-9090 will be the first product from our own internal research that enters the clinic. We expect by the end of this year. We think the first indication will be cardiac surgery-associated AKI. But we still may choose ARDS, high on medical need, as a first indication. We're actually planning, and I believe it'll be starting very soon, a phase II-A study with vadadustat in collaboration with the University of Texas in ARDS to prove that the mechanism works in that disease. AKB-9090 is probably a better compound than vadadustat to move forward and certainly will have a longer patent life.
But we'll really prove that you can use a HIF-PHI for ARDS. I'm really excited about the compound that's following right behind AKB-10108. This is our first true foray into areas outside of kidney disease. This is a rare disease, retinopathy of prematurity, where there's no approved treatment today. And we're looking at a preventative treatment. Babies born prematurely, this is the leading cause of blindness. And the idea that this disease is all about oxygen and managing that with a HIF-PHI makes sense. Our preclinical data is incredibly impressive. This is behind 9090, so it won't be in the clinic this year. But we're obviously moving this forward as quickly as we can. And we're excited to update you on it more in the future.
When you look at all of these opportunities, I think very conservatively we're saying this is at least a $5 billion set of opportunities here within the U.S. And obviously, we look forward to telling you more about that. So here we are in January of 2025. Our transformation as a company began really Monday of this week as physicians were able to write prescriptions for Vafseo, a product that the company's been working on for many years and we believe can truly disrupt the care of patients with anemia on dialysis. And that's what we'll be talking to you about this year. Executing the Vafseo U.S. commercial launch, initiating the phase III trial in non-dialysis by the middle of this year, fully enrolling the VOICE trial at the rate that Dr. Block is going. That will happen quickly.
Updating you on the advances of our pipeline as well. We look forward to talking to you over the course of the year about all of these catalysts. With that, I think we'll move to Q&A. I have in the room with me as well, Erik Ostrowski, our CFO CBO, Nik Grund, our Chief Commercial Officer, and Steve Burke, our Chief Medical Officer, to help me with the Q&A. Alex, we get started?
Yeah, great. Thanks, John. So if you just want to raise your hand and there's a mic going around, otherwise I have some on the screen to get us started. Maybe to start, John, do you have any other early feedback you can share from prescribers?
Nik, do you want to take that?
Yeah, thanks so much. Yeah, four days in or day four today, our field team has been out there. Early in quarter four, we started moving away from broad-based education to patient identification, and that patient identification, we're in the populations that John previously went through, the home patient, the high-dose ESA patient, and so the sales team was effectively filling the funnel with patients identified for start in early January, and what we're seeing is those physicians who told us they were going to start patients are starting patients. We don't love to take four days and draw a straight line, but we're really, really encouraged by the first four days of the launch.
Yeah, I mean, I think Nik pointed out that we took our commercial, remember, we had a commercial organization in place already. So this is incredibly important to getting that launch to go quickly. I mean, I've used in previous presentations the analogy of the coiled spring that we were kind of compressing over the course of the last nine months. We took all of our commercial organization and took them off of focusing on Auryxia, our phosphate binder, and 100% on Vafseo over the last quarter of the year to fill that funnel, as Nik pointed out.
And we are three or four days in, so I don't know whether the spring is fully sprung yet, but we're actually quite encouraged. And I think it was absolutely the right decision to have them focus on Vafseo.
Excellent. And what gives you confidence in a path for approval in the non-dialysis patient population?
Yeah, I'll just reiterate. I think that the confidence in the non-dialysis plan is the robustness of the data set that we'll be submitting. Quite frankly, the recognition from the FDA that this is an important patient population to treat who don't have an available oral therapy today. 10 years ago, I sat with the FDA and they didn't have that belief that a non-dialysis patient has a significant need to be treated. I think all of the data that's been generated over the last decade, some of which I shared today, they're in agreement that these are patients where there's a high unmet medical need.
We recognize that we missed the primary safety endpoint in the PROTECT study, but that U.S. data is compelling. I think during the review, FDA agreed that that is very interesting data. We've always known we would have to do another study to support that and move that forward. Obviously, over the last two years, we focused on getting the dialysis approval.
With that in hand, now we can think about non-dialysis, and that robustness of data, those 1,700 U.S. patients in PROTECT, 1,500 U.S. patients in this new study, as well as years of experience in the market, both in the U.S., Europe, and in non-dialysis in Japan, I think give us incredible confidence that with the results of this new study in hand, that we'll have the opportunity to help patients with non-dialysis anemia.
Right, and it sounds like HIF has potential beyond the kidney. Could you comment a bit on that and potential pipeline?
Yeah, this is the opportunity to talk more about our pipeline, and if Dr. Burke wants to add anything here, I'd encourage him to do so. Our team, we really had focused on we want to build a company that's a kidney disease company. But when you recognize that there are these really significant unmet needs, I mean, ROP is a great example. I mean, it was probably close to 10 years ago, we were contacted by a physician at the Cleveland Clinic, a pediatric ophthalmologist who believed that there was an opportunity for HIF in retinopathy of prematurity. And this is how science works, right? It's not a fast endeavor most of the time. But our team picked that up and worked on it.
I mean, the idea of preventing blindness in a newborn baby is a pretty hard to get anyone who doesn't want to be part of that. And the team created the compounds targeted towards this disease. And the preclinical data that we've been able to produce is incredibly compelling. We had an advisory board with a number of pediatric ophthalmologists, pediatricians, neonatal physicians.
It was a virtual advisory board. I remember texting Steve during it, "We got to move this faster. We've got to move this faster." I mean, the level of excitement from these physicians was amazing. We recognize this is a preclinical asset and people want to focus on the launch, and so do we. I mean, we want to see this successful. But we're really excited about what opportunities lie in other therapeutic rare diseases and kidney diseases with HIF.
Excellent. Is the NDD trial and other programs fully funded at the moment?
Yeah, I made a point of that. I want to make another thank you for giving me the opportunity to just kind of put an exclamation point on that. We talk about that our cash on hand and cash from operations, which means revenue from Auryxia and Vafseo, will fund our operating plan, which includes the non-dialysis trial, the VOICE trial, other smaller ISTs, our early pipeline, moving that forward, our continued research efforts, as well as our SG&A.
It will fund that for at least the next two years. So we feel very confident that we're operating the company from a financial position of strength. And again, having gone through the two years post the CRL, we became very disciplined from a spending perspective, really investing in the things that matter to shareholders and matter to patients. And I think we are maintaining that discipline. Eric, who's here, is overseeing that effort. And we're quite confident in our financial position.
Great. Thank you. I'll open up again to the room for any final questions. If nothing, then I think we can wrap. And thank you, John. Thank you all for attending.
Thanks, Alex.
Thank you.