Hey, everyone. My name is Allison Bratzel, one of the senior biotech analysts here at Piper. So thanks for joining us for our 35th Annual Healthcare Conference. It's my pleasure to introduce Akebia for our next session. So joining us, we have John Butler, CEO. So this is meant to be informal, so if anyone in the audience have questions, feel free to just, you know, raise your hand, speak up. And, yeah, before we do jump into Q&A, John, maybe just to, you know, level set for investors, give us a quick overview of Akebia, you know, the story, what you've accomplished this year, what's the setup into, to your end and into, more importantly, into 2024. Great. Well, first, thank you so much for the invitation. It's great to be here again this year. So Akebia is a company that has a purpose to better the lives of people living with kidney disease, and it really is an exciting time for us now. We are on the verge of bringing our second product to patients with kidney disease next year, and that's vadadustat, our HIF-PHI, for the anemia of chronic kidney disease. So we are working towards our PDUFA date, which is March twenty-seventh of next year. We then work towards enhanced Medicare access through TDAPA in October of next year. That's really the... When you think about the launch of the product, is October of next year. Of course, that's product we're bringing, as I said, our second. We already have product Auryxia, that's generating, I think about $170 million in revenue this year. A great base for us. We have the commercial organization in place who's selling Auryxia today, so we'll get great leverage from that organization as we add vadadustat there. You know, we have the product on the shelf. Remember, we were planning on launching vadadustat last year, so product's on the shelf ready to go. When you think about the 2024 and launch, you know, we think about incremental investment in the launch. You know, this is a billion-dollar-plus market opportunity and, you know, we think the HIF-PHI pathway and vadadustat really can deliver for some significant unmet need for patients. So we're excited about what the future holds. Great. No, that's a good, good place to start. Maybe just before getting into some of the vadadustat, you know, launch or pre-launch questions—can you just remind us, you know, you recently had the NDA resubmitted. Can you remind us, you know, what exactly FDA wanted to see in that resubmission? I think the real-world safety data from Japan was pretty influential or as a key component of that. You know, kind of talk about what they wanted to see, what—and overall, just what gives you confidence in an on-time, you know, positive FDA decision come, you know, March 27th. Yeah, I mean, I really don't think we could be more confident. So you know, you mentioned the Japanese data, right? I mean, the most significant issue in the CRL to deal with was the feeling that there was a DILI risk, a Drug-Induced Liver Injury risk with the product. And, you know, as we pointed out to Dr. Stein during the dispute resolution process, the drug's been on the market now for three years in Japan. Tens of thousands of patients have received the drug. The Japanese do a phenomenal job of post-marketing surveillance, and there's been no severe DILI that's been seen. So, you know, what FDA wanted to see was that data, right? We talked about that data, but we hadn't presented it. So, we have submitted that data along with, you know, you kind of have to update all of your safety data. So it's a significant resubmission, but a very focused resubmission as well. You know, we sat down with the division in a Type A Meeting after the letter from Dr. Stein, a very collaborative meeting, very technical. Just here's how we're going to present the data, et cetera. But you know, the clinical reviewer from our original submission is no longer at FDA, so it's a new clinical reviewer, so no baggage from the original review. But you know, it was very collaborative. They're actively asking questions now. So, I mean, look, it's the FDA, so timing and, you know, you can never say 100%, but, but we've given them the data that they've asked for. I think we've answered the questions very clearly. And of course, you've got that vadadustat approved on the market, as well. So, you know, I think we feel incredibly confident. Okay. Maybe thinking about a potential label. You know, I think you brought up daprodustat. I think there's some maybe nuances to the daprodustat label. You know, can you just frame your base case expectations on what vadadustat label could look like? You know, with, especially with respect to daprodustat, and ultimately, if any of that matter, is going to matter for uptake. Yeah. I mean, I always like to point out that, you know, although people want to compare to daprodustat, the market is ESAs now. I mean, 100% ESAs. So, you know, when we want to switch patients or start new patients, they're patients who are on an ESA today. So, you know, our ability to differentiate there, you know, with our publications and our label, I think is incredibly important. But, you know, FDA does like to, you know, think about class labeling to a significant extent, and so, you know, we do expect that there'll be things that will look similar. Mm-hmm. You know, one area that we've talked about in the past was, you know, daprodustat has in their label that you can't start the drug till they're on dialysis for four months. And again, I'm not saying that that won't land in our label, you know, at the end of the day, but we really shouldn't. You know, the data from our phase III program, when you look at patients new to dialysis, remember in the PRO2TECT study, our non-dialysis study, we had 1,000 patients who started dialysis during that study, and we continued to monitor them. So we're able to do the analysis of those patients, all the patients from our dialysis program who were new to dialysis, and, you know, there's no increase in MACE. I mean, the hazard ratio is just about 1.99, something like that. So, so we don't think that should be in the label. Can't say it won't be, but we've put that data into our resubmission, very proactively- Okay. to have that conversation with FDA. I mean, even with that in the label, I still believe dialysis providers are looking at, you know, the product for what it is, looking at the whole safety package. So having that data published, you know, which we're working on now, as well, proactively, I think will be very important to update if that lands in the label. Okay, excellent. Can you talk about like, you know, launch readiness? You know, what, what are the launch readiness activities, you'll be working on, you know, between now, March 27th, you know, be it, you know, doc education, working out protocols with dialysis organizations, you know, publishing additional data analyses? You know, just frame that and, and what's most important to help kind of pave the way to a successful launch once you secure TDAPA designation in October. You're answering the questions for me. So, you know, you did say it. I mean, there's a tremendous amount of work to do between now and March and now and October. You know, the physician education is very, very important, you know, Dapa sets on the market. We just came back from the ASN meeting in early November. So, you know, we kind of saw. We got the opportunity to talk to physicians about how they're thinking about HIF. I have to say, I was a little bit nervous about what the perspective there was, you know, given the CRLs that there have been. But we found is physicians are pretty excited about the opportunity to try something new. Now, I guess I had a hope that GSK maybe was gonna be doing more of that education. They don't seem to be doing significant investment there. That's fine. We'll do that. You know, we understand the dialysis market extraordinarily well. We're very focused on it. You know, we believe that we have relationships there that will make a huge difference. So we need to do two things, right? We need to drive the practicing nephrologist to want to use this product. So we've got to drive demand from the bottom. But, you know, as you referenced, you need to have protocols in place with the dialysis providers. So, you know, at ASN and, you know, before ASN and, and since, you know, we've had multiple meetings with the leadership at the clinical leadership and business leadership at the dialysis providers. You know, I get frustrated about the idea, "Hey, we got a PDUFA date in March, but we don't get TDAPA until October, and it's six months, and why does it take so long?" They've made it clear that they actually need that time to build the protocols, build the, the, the ability to bill for the- Mm-hmm. the product and, you know, be ready for for launch really in October of next year. So that sort of pre-TDAPA period, post-PDUFA period is kind of going to be time well spent, kind of- Yeah. So you can hit the ground running. Well, that's exactly right. Okay. I mean, I really want to make sure we're setting expectations that we don't expect significant revenue- Right. During that 6 months, right? They are waiting for TDAPA. Now, TDAPA, you know, every patient has access to the product now because of, you know, whatever their reimbursement is. TDAPA enhances that access for, you know, for patients who are all part of PPS, and it really allows. That was why this was created, was so that, you know, CMS said: We want dialysis providers to be able to get experience with innovative drugs, and so we'll allow you to bill outside of the bundle for those two years. Mm-hmm. That just makes it easier for them to use the product. That's why they'll wait until they have that kind of access. Yeah. One thing on TDAPA that I hear from investors a lot is just, why isn't Korsuva a good analog? You know, I think there's a lot of skepticism about how TDAPA will actually incentivize uptake of HIF in light of the KORSUVA experience. So can you just, you know, compare and contrast for us why that launch experience is not necessarily a good analog for that at least? I mean, I think there's some really clear fundamental differences in anemia versus pruritus treatment. But yeah, just- Yeah. Walk us through that. You've hit one of the main things. I completely understand the question. I mean, there haven't been that many TDAPA experiences, and that one has not gone well. But the fundamental difference is, there's no money today in the bundle for pruritus. Yeah. Well, there's actually $0.25 for Benadryl, so there's no money today in the bundle, whereas there's money for an ESA, right? There's significant dollars. About $16 of the bundle payment is considered to be towards the ESAs, and people aren't treated for pruritus today. 88%, 90% of dialysis patients are treated for anemia, and they have to be treated for anemia because there are quality measures to ensure that patients are being treated for anemia. So, you know, when you think about TDAPA, where I know I have to treat the patient, I have dollars in the bundle today, 'cause, you know, the Korsuva experience wasn't about them not getting paid during the TDAPA. It was the concern about what happens after TDAPA. Right. Right. It's like the, I think the average selling price, ASP, is about $133 a session for Korsuva. The dialysis bundle payment is $270 in the final rule, $271. So if you think about, hey, when this ends and no real dollars go back into the bundle, it was about $0.25 that was going back into the bundle, I'm getting paid $270. I can't add a $163 drug and make any money. They'll be out of business. Whereas with vadadustat, you know, we'll clearly have to think about our contract pricing post TDAPA, but they have to treat the patients, and there's money in the bundle. As long as they're not losing money, we want, we want to create an environment where they can be successful, continuing to treat people with vadadustat, and we'll figure that out over the course of the TDAPA period. Okay, and that kind of segues right into the next question, just, you know, on pricing. You know, can you give us an update just on your thoughts on pricing for Vada? Mm-hmm. You know, especially, and I don't want to always bring it back to daprodustat, but, just, you know, and can you compare it to, to, to GSK's, you know, pricing for, for daprodustat? How does that factor into your thinking? And, yeah, how should we be thinking about net pricing, you know, pre- and post-TDAPA as we, as we model out the launch? Yeah. So, you know, so of course, we're doing a lot of work to understand pricing. So we don't have, you know, I, I want to be careful not to try to guide anyone here, but because we're really trying to understand in the environment where you have TDAPA for, you know, 50% of the Medicare population, Medicare Advantage patients, you have to work harder to get more access. And then you have commercial and Medicaid, where there's easier access outside of a bundled payment. You know, we want to put all of those things together and think about, you know, what's the... You know, titrate to the price. We've been saying for years that there's potential upside to the current pricing. I mean, the average price today for three ESAs is in the $2,500-$3,500 range. Daprodustat, if you look at their phase III, their average phase III dose and their per milligram price, it's about $8,500- Mm-hmm. -that they, that they price it at. Now, we don't know what their contract pricing is, but, you know, where in there is the right place for us to drive broad adoption? Remember, we expect a label fundamentally to say all patients can, can access this product. Now, we know there'll be places where they want to use it first, highest dose ESA patients, home patients, things like that. But ultimately, we expect that, you know, we want to work towards making vadadustat standard of care for anemia and chronic kidney disease patients on dialysis. So how do you think about pricing within that context during the TDAPA period and then post-TDAPA? You know, we continue to work on CMS. You know, we thought that the rule this year was going to have more dollars follow the patient, put out an RFI suggesting that. Their final rule didn't reflect that. But we're working both with CMS and on the Hill, you know, through things like Kidney Care Partners, where, you know, we're members, and I chair the organization, because the whole community wants to see patients be able to access innovation more broadly. So it's too early to say, you know, where we'll land post-TDAPA, but in a worst-case scenario, you're talking about something similar to that $3,000- Yeah. a year. Okay. Somewhat related to that, QD versus three times weekly dosing. Mm-hmm. Walk us through what, you know, your current plans on getting that, you know, three times weekly dose on the label. Is that even necessary? Do dialysis organizations have all the data they need to be able to adopt, you know, the three times weekly? Mm-hmm. And then, just from a pricing standpoint, you know, is there any reason to think a patient dose three times a week is gonna, you know, have a different net revenue than one dose, you know, every day? A lot of questions there, and all of them important. So, so we have three times weekly data. I mean, the FOCUS Study, which we presented at the ASN last year, demonstrated that you can use vadadustat three times a week. And remember, you know, dialysis patients come in three times a week. It's convenient to be able to give them the drug, and they can ensure compliance with those patients. You know, particularly in FOCUS, there was a 600 and a 900 milligram starting dose, and 900 milligrams did extraordinarily well. Nobody got transplanted, very few rescues, you know, maintained hemoglobin beautifully. The data was very, very compelling. At the same time, you know, once-a-day dosing, you know, does a lot for dialysis providers. They have huge staffing issues. People have to go and give ESA dosing, now, you know, once a month, twice a month, every day, depending on which drug they're using, and they're having these significant staffing issues. You give people once a day, give the drug outside, provide it for them. You know, there's great opportunity for once-a-day dosing. We have to work with them. You know, their billing is different. Mm-hmm. You know, there's lots of things to work with them on, but again, we know dialysis. We have great relationships there. You know, we think we can be quite successful. Obviously, home patients, you know, once-a-day dosing is much better for them. So we're gonna work to get three times weekly on the label. You know, we haven't... You know, obviously, we'll get approval, then we'll go talk to FDA about that. We don't know if they'll need more data than what we've provided. Mm-hmm. We'll certainly publish that data. Then each dialysis organization will decide whether they want to use the once a day, or, you know, that they have enough data to support using three times weekly dosing. We'll work with each of them. You know, obviously, our label, you know, we'll only be promoting once a day because that's what will be on our label, but they can choose to use three times weekly if they, if they feel it's supported by the data. Got it. Oh, and you asked about pricing. So, when you look at the data from FOCUS, it would suggest that you take your daily dose, and you deliver it three times a week, you know, kind of three times. Mm-hmm. So it would be slightly lower, net price for a three times weekly patient, because instead of giving someone 300 milligrams a day, you know, for seven days, you're giving them 900 milligrams- Yeah ... three times a week. Okay.... Maybe just real quick on, on non-dialysis. You know, I know a label in that setting is, is likely a no-go with this FDA. I guess, as you talk to docs, you know, what, what are their thoughts on, on the potential for, for off-label use? You know, are there any kind of, segments of the non-dialysis population that, that, you know, might benefit from, from this, you know, from VADA or HIF? Just wanted to hear from you. Well, look, I mean, we still feel that vadadustat could play an important role in non-dialysis, and I—we certainly haven't given up on it at all. And I don't want to comment on off-label use. You know, the distribution's reasonably controlled into dialysis- Mm-hmm, yeah. So there might not be huge opportunities for that if physicians wanted to do it. And of course, payers, they'd have to jump through hoops there. But we do think that, you know, as you interrogate the data, that there's a real rationale for certain patient populations. We want to focus today on getting the dialysis, getting the drug approved. I mean, that is critical for the company, and launching it well, and then going back to FDA to have that conversation. And EMA, I mean, I think given our conversations with the European Medicines Agency, I mean, we thought right till the end that there was a real chance that we could get- Mm-hmm. non-dialysis in the label. And, you know, it's funny when you talk to physicians and you explain the data from PRO2TECT, where we missed the primary endpoint. I mean, they still... They still like, "Work to get this approved. This is where we want to use the drug." So we're not going to give up on that. Got it. Maybe shifting now, we got a couple minutes left. I do want to touch on Auryxia. Sure. So maybe just, you know, I guess front of mind for us is, you know, the competitive setup, you know, now with the recent launch of Tenapanor, you know, how do you see that affecting the binder market? Is this going to be kind of a rising tide lifts all boats situation, where now there's, you know, increased attention on phosphorus control, new agents? You know, like, what, what, should we be expecting in, in 2024? I think you've kind of guided to flattish volume for the year. So, you know, what, what does that factor in, in terms of competitive? Yeah, I mean, you know, the Auryxia is a nine-year-old product. So, you know, our expectations of growth have been managed and we've really said, you know, we grow from exiting, you know, some payer contracts that, you know, really weren't providing the benefit that when they were signed, there was an expectation. The last one of those Part D contracts ends this year. So, you know, there's a substantial increase in the average selling price we'd see next year. And in Part D, you're still getting those prescriptions approved. I think Tenapanor is great, that it's available. It's available as an add-on to phosphate binder therapy, so we don't see it as competitive. We actually think, you know, that the Ardelyx folks will be out there making phosphorus control a front and center issue- Mm-hmm ... for people again, and that is a rising tide lifts all boats situation. You know, so if people are focusing on it, remember, we're also going to have reps out there, talking about Auryxia. In March, we'll have an approval. Physicians will want to see- Mm-hmm ... our reps to talk about vadadustat, and that gives us an opportunity to talk about Auryxia. So, you know, all of those things I think, set up quite well. The other thing I think dialysis providers are looking at is January of 2025, when the binders of phosphorus-controlled drugs go into the bundle and there's a TDAPA period for them and I think that's the expectation now. They're looking at, well, there's only three branded products, and those branded products are more expensive. And if you saw how they handled the cinacalcet Parsabiv TDAPA period, they want to use those drugs during TDAPA, and then they want to stop using them after. But, that's a great setup for us for 2025 and 2026. So it's, you know, we remember, LOE for Auryxia is March of 2025, so we're not pushing towards, you know, significant increase in growth. But those dollars that we maintain give us great leverage, and pay for a lot of our research and development activities. Yeah, and actually, I think that last point is kind of an important one. Just, can you kind of walk us through the mechanics of how we should be thinking about Auryxia and getting folded in, and binders getting folded into the bundle in 2025? You know, and what does that look like given, you know, the LOE is in March of that year. Can you just kind of walk us through the- Right. - kind of intricacies of that? Yeah. So, I mean, I think there's some of the detail will come out in the rules from CMS next year, but I think, you know, we've seen them do these TDAPA before. So basically, we're a Part D drug now. You'll become a Part B drug- Mm-hmm. and, you know, you'll have a separate billing code under Part B, and you-- they will bill separately for the phosphate binder that they use. And remember, phosphate binder is more complicated, right? There's a whole bunch of different drugs. They'll look at all of that utilization over the course of two years, and then they'll say, "The average per dialysis session was X dollars, $10, $15." I don't know what the number's gonna be. And then they'll add that to the bundle forever, right? So dialysis providers saw that. They got $9.93 added to the bundle after the three-year TDAPA for cinacalcet Parsabiv. They added that $9.93, and then they proceeded to use as little Parsabiv, and, you know, branded cinacalcet as they could, and, you know, to hold on to as many of those dollars as they can. Mm-hmm. So for us, no, no issues, right? There'll be a generic available. For 2025 and 2026, you know, we still think over the course of 2026, they'll probably start using the generics more liberally so that they're on a generic by the time they get to 2027. But the dollars, you know, under that curve for us, are really quite significant and could be really helpful. I mean, I don't want to be talking to you about this in 2025. I want to be talking about the vadadustat launch, but, you know- Thank you. Those dollars spend the same way. Excellent. Well, I think we are... Yeah, we're just about out of time, so we'll leave it there. But, thanks.