Okay, let's go ahead and get started. My name's Ally Bratzel, a biotech analyst here at Piper. Thanks for joining us at our healthcare conference. It's my pleasure to introduce Akebia Therapeutics. Joining us today for a fireside chat, we have CEO John Butler. So this is meant to be an informal format, so if any of you in the audience have a question, just go ahead and raise your hand. So we'll get to Q&A in a second, but maybe John first. Give us a quick overview of Akebia, the story, the setup into year-end, and then 2025. Great. First, Ally, thanks so much for the invitation. It's great to be here with everyone. Always look forward to having the opportunity to talk about Akebia. We're at a really exciting moment for the company. We are a commercial-stage company with a deep expertise and focus in kidney disease. As you know, we are on the verge, we're within weeks now of launching our second product, Vafseo, for the anemia of chronic kidney disease in patients on dialysis, which is a billion-dollar market opportunity, and then we plan to expand the label for Vafseo into the non-dialysis market opportunity, which is honestly multiple of the dialysis opportunity. I think we'll probably spend most of our time talking about those two areas. We have an early-stage pipeline of products, both in kidney disease and not, based on the HIF platform that we're really excited about. Hopefully, once we kind of get through the launch, we can start talking more about the opportunities there as well. Great. So yeah, you're correct. I have a couple of topics to touch on today, but yeah, Vafseo is obviously the big one. So maybe just walk us through some of the launch readiness activities you've undertaken over the last year that really set you up to start off strong in 2025. I know you've talked about commercial supply contracts with dialysis providers and GPOs. Just talk to that. Sure. So the way we think about launch, you've got to drive access, you've got to drive demand, and you've got to create evidence. So driving access and dialysis is about dialysis provider contracts. So we've been very, very focused on that. Our goal is by the end of the year that we'll have 100% of dialysis patient lives under contract. As we sit here today, we're over 60%, which if you understand the dialysis market, about 35% are Fresenius and 35% are DaVita. So it would suggest we have one of the large providers under contract and we're working on the second. But honestly, with 65% or 60+% under contract, you're talking about over 340,000 patients. So again, our goal is to have everybody under contract this year, but we've got lots to keep busy on. Because first step is signing the contract, then you've got to get protocols in place. And as you referenced, you've got to drive demand as well. So that's the second leg of the stool is driving demand. Our sales force, remember, we already had a sales force in place for Auryxia. So we basically added a handful of folks. We've got 40 people in the field. They are 100% focused on the Vafseo launch now as of the fourth quarter, and they're driving demand. We're really excited about what we're seeing in market research and from the field. The last set of market research said 92% of docs are looking to use a HIF, 27% I think it was, in the first three months. Now, you've been involved in nephrology launches also. They're always somewhat slower than you expect, but I've never started with that high a number before. So even if we kind of see the normal kind of nephrology uptake off of that base, I think we'll have a really successful launch. Great. And then I know we saw each other in San Diego. Akebia had a huge presence there. So maybe coming off of that, just I guess talk more to doc expectations in terms of where they view the greatest unmet need and where you're likely to see early uptake. And if you have any kind of numbers around those different patient categories just to help us with the modeling side, that'd be great. Yeah, for sure. So ASN, which was in San Diego, was a great kind of coming out party for us. I mean, I was really pleased with the presence of the Akebia team, but the excitement that we felt from others as well. We had a reception early, one of the early evenings. And to see the excitement from the investigators, the KMEs, folks that we've been working with for years about having the product available, again, is one of those things that really makes you feel like you're well set up for a launch. And of course, we came back from San Diego, and as I said, our commercial group is, I mean, there is 96% overlap between Auryxia prescribers and Vafseo prescribers. So there's relationships that existed there already. But now they're really focused on day one of launch. They're looking for who are the patients that you're going to start day one and building that list. Now, we've talked about this before. I mean, when you talk to physicians about where they want to use the product, the low-hanging fruit is the home patient, which is about 80,000 patients of the 500,000-550,000 dialysis patients that are out there. The other area that keeps rising to the top is the high-dose ESA patient. And that is, I think there's a number of reasons for that. I mean, the clinical rationale for that, of course, is that MACE risk increases as dose of ESA increases. And you don't see that with Vafseo in our INNOVATE study or PROTECT. You didn't see an increase in MACE risk as you increase dose. So there's a good clinical rationale for that. Of course, from an economic perspective, the high-dose ESA patient is the most expensive patient for the dialysis provider. It's the one they'd be happy to try Vafseo. Now it depends on where you draw the line on high-dose ESA, but kind of reasonably high doses, you're talking about 150,000 patients. There's some overlap between that 80,000 and the 150,000 but you're still talking about half the dialysis population that are the places where physicians identify, this is where I want to use the drug first. Great. No, that's helpful. Then I guess, what's your expectation on the uptake split between daily and three times weekly dosing? Where I know you have the FO2CUS data, you also are working on the VOICE trial. Yeah, just kind of talk to expectations there. So I think early, so again, the label for Vafseo is once daily use. And you run into a mix of physicians. You have some who would love to take anemia management out of the dialysis center and use once daily with everyone. There are others who are more comfortable with observed dosing and using a TIW. Ultimately, we believe we have the data in FO2CUS that we can get TIW into the label, but it's published now. It came out about two weeks ago, I guess now. And it's a very robust study, about 450 patients, clearly showed that you can use the product successfully three times a week. And it really was one of the things that led us to want to do the VOICE trial with Jeff Block, which I'm sure we'll talk about. My expectation is that initially there'll be more use once daily. The home population, of course, that's exactly where they'll want to use it. And I think that's the very first place folks will use it will be in their home dialysis patients. But you'll talk to us, particularly some of the small centers, small dialysis providers, and they want to switch everyone who has TDAPA access to the drug. So I think we'll see a mix. My expectation is early, you're going to see once daily. As they get comfortable with the drug, they'll be more comfortable using a TIW. And that will be as you get to the back half of next year and 2026, I think you'll see much more TIW use. Okay. That makes sense. You brought up TDAPA. Just hoping you could just talk to what you expect the TAM to look like for the first two years of launch, basically pre and post TDAPA, and then kind of how we should think about the trajectory 2027 and thereafter. Sure. So when you think about TDAPA, 85% of dialysis patients are Medicare patients. About half and half are fee-for-service and Medicare Advantage. So when we talk about TDAPA, the patients who clearly have a TDAPA payment are the fee-for-service patients. Call it 40% of the overall market, plus or minus. Now, what we know is that Medicare Advantage patients, just because they're Medicare Advantage, doesn't mean they don't have a TDAPA or an innovation payment. As a matter of fact, this is one of the areas where phosphate binders really help Vafseo going into the bundle. In the final rule, which was two or three weeks ago now, CMS very specifically said that MA plans need to give patients the same level of benefits that fee-for-service patients have. It's the most discrete explanation that we've heard from CMS. Remember, there's a non-interference clause. They can't force people to do what they're doing for fee-for-service, but Medicare Advantage patients are supposed to get the same benefits. Remember, we're not contracting with the MA plans, so we won't know exactly how many of those patients have access to an innovation payment, but I guarantee it's more than just the 40% of fee-for-service patients today. Over the course of TDAPA, that will continue to grow. If you want to be the most conservative today, you say 40% of the 500,000 have access. I guarantee you it's larger than that today. By the time we get outside of TDAPA, remember what we've said is we have our TDAPA pricing, but part of the rationale for providers signing these contracts and providing access to patients today is that they have price predictability post TDAPA. That's where you have to provide them the pricing that they have for ESAs today. That's a decrease in price for sure once TDAPA ends. How much that decreases depends on how much penetration we get during TDAPA, right? Because you're giving people volume-based discounts during TDAPA. The more patients they put on, the higher the discount we're giving them. Post TDAPA, you'll have the average price today is about $2,500 a year per patient. But now instead of just having the TDAPA population, you've got the entire dialysis population. We'll be kind of fishing in a bigger pond post TDAPA. As physicians have gotten comfortable using the drug, look at the advantages of the drug based on the mechanism, and we generate data like the VOICE trial that we're doing with Jeff Block. This is where the third leg of the stool is. You've got to continue to generate evidence. We have positive outcome there. That's how you become standard of care in the dialysis population. Excellent. Then maybe just one last one on the launch. You mentioned phosphate binders going into the bundle. January 1st, is there any sense on your side that the distribution change from wholesalers to dialysis organizations, is that going to create headwinds or speed bumps for Vafseo, at least maybe those first couple of weeks of launch, first month or so? Yeah. Well, I think importantly, having Auryxia and having a phosphate binder going into the bundle on January 1st brought all the dialysis providers to the table, right? So it has been a tailwind from a contracting perspective, unquestionably. Folks who, hey, we've got to have a contract for our phosphate binders. Well, all of our contracts are portfolio contracts. They're for Auryxia and for Vafseo. So that's been phenomenally helpful. I can't even describe much more so than I thought. Now, once you get to January 1st, I would say they will be getting used to putting kind of managing the phosphate binders differently than they were. So might they be more focused on that and kind of create some slowness in moving Vafseo? It's possible. This is why the reps are so focused on identifying the patients who start immediately upon product availability. So we can kind of help cut through that and not have that distraction be a part of it. But it's certainly something for us to keep looking at. As you sort of referenced, I think the very short-term thing, because they're putting all those plans in place. Again, it's been more helpful than not, I think. Excellent. Okay, now shifting to the VOICE trial. I know it's come up a couple of times. You know where you're looking at 3x weekly, Vafseo, your power for superiority on hospitalization. Just discuss for us the rationale, some of the nuances there, why this is important to run. And also, I think in terms of timing, I think you've talked about this trial completing around the time period when TDAPA ends. So just kind of what gives you confidence there and where do you stand with that? Great. So we just put out a press release this morning that Jeff Block and U.S. Renal started enrolling patients in the study. We've worked with Jeff a number of times. I've worked with him a number of different trials, and he's a phenomenal trialist, and he gets things done incredibly efficiently from a cost perspective, but incredibly quickly as well. So we're really, really pleased that we're working with him. He's the best. The rationale for doing VOICE, again, the idea is you need to continue to generate data, right? And why VOICE? Why are we going to do this outcome study? Well, when you looked at INNOVATE, the FDA had asked us to start with a lower dose of Vafseo. So we started at a 300 mg dose every day. And what we saw was when patients were on a higher dose of ESA, you had a drop in hemoglobin level. Titratable drug easily achieved the primary efficacy endpoint, but you had patients when their hemoglobins dropped who had to have an ESA rescue event. And when you looked at ESA rescue, it was the same in the darbepoetin group as it was in the Vafseo group. But when you looked at the MACE data, what you found was two of the things most closely associated with MACE risk was excursions above a hemoglobin of 12, where we always had fewer, and ESA rescue, where we were the same as darbepoetin. In the INNOVATE study, we saw about a 6% decrease in hospitalization. Fast forward to the FO2CUS study, the three times weekly study, where we kind of managed that initial dosing by dosing based on their baseline ESA level, and you saw you didn't see that drop. You saw a very smooth hemoglobin level. And what else did you see? You saw about 50% reduction in ESA rescue. So the thought behind VOICE is managing that ESA or sorry, that hemoglobin response, dropping that ESA rescue, if you can move that hospitalization number from 6%-10%, we're powered to show a statistically significant advantage in all-cause hospitalization. That's the kind of data that's phenomenal for dialysis providers because it's a cost savings and it keeps people in the chair, and obviously it's great for patients as well. And that's the kind of data that we think gets you to standard of care. Again, I mean, as of yesterday, I think he was about 20 patients. I mean, he's moving very quickly. It's all about getting the data. It's all about when we get the patients in. So he's got over 100 centers that will be part of the study. He's moving quickly, and again, the hope is to have data by TDAPA and probably more likely shortly after that, having that data available as they now can fish in that larger pond will be incredibly important to growing in dialysis beyond the TDAPA period. Excellent. We're kind of running out on time, so I want to shift to non-dialysis. I have plenty of time on it. Yeah, yeah. But I think when you talk to docs, kind of the other big thing that comes through is they're excited to use Vafseo in non-dialysis patients. So I know you've talked about engagement with FDA this year about a path forward there. And we should get a communication on the outcomes on that engagement before the end of the year. So just kind of talk to that. What does that communication look like and kind of what kind of additional clinical data generation is on the table? Yeah. So you're right. Physicians really want to use the drug in non-dialysis. Every single time you talk to a doc, "Oh, home patients, high dose ESA, but I really want to use it in CKD." I'm sure you've heard that too. So we have a responsibility to patients to do this. And from a market opportunity, it is, I think, 5x the size from a dollar perspective. So we are in that discussion with the FDA. We clearly will have to do clinical work. If you remember, our overall MACE PROTECT trial missed the primary safety endpoint. But from a pre-specified analysis, we looked at U.S. versus the rest of the world. And in the U.S., we clearly didn't show an increase in MACE risk. And everyone in the U.S. is treated the same. We treated to a 10-11 hemoglobin level. Even the FDA agrees that that is interesting data, but we're going to have to show outcomes data. So the question is, what does that study look like? How quickly can we execute it? FDA agrees that there is a high unmet need for an effective oral product. So my hope is that we can kind of find a path that allows us to get started quickly and, more importantly, get finished quickly and get it in the label. We've said we do expect that we'll have some feedback before the end of the year. Given kind of where we are, maybe that ends up being a press release around the January conference that we all go to. But we're excited about the opportunity to move into that patient population. And we feel patients want it. The patient groups are all behind us and looking for that as well. It just needs to be a path that's reasonable that we can execute quickly. Great. And I think you discussed when you disclosed your Vafseo pricing decision that you made that decision factoring in the potential non-dialysis approval. Can you just expand on that? Walk through factors that could make a non-dialysis patient significantly more valuable than a dialysis patient. I mean, the reality is, so the WAC price for a year based on the starting dose is about $15,500, right? So if you look at the average dose in the non-dialysis study, that would be about $20,000 per patient per year. What you have in non-dialysis is a much more traditional distribution and reimbursement, right? About half the patients are commercial, about half are Part D Medicare. So you take your $20,000, you put a rational kind of gross to net on that and take a WAC for compliance, and you're still talking about comparing to the $2,500 per patient per year in dialysis, a number that's probably four or more times higher than that. And the market size is about the same, right? It's about 550,000 stage 4 and stage 5 non-dialysis patients who are anemic. And three out of four of them today aren't being treated. When I joined Akebia, we were modeling this opportunity. We were modeling that Vafseo would be one of three products available. And today, we are one of one product is available, and there's no one else who's going to be looking into that non-dialysis population. So that really does change the picture dramatically. I mean, I think you're not looking at you haven't modeled non-dialysis opportunity, and I understand that based on the outcome of PROTECT. But once we have that path forward, and you think about it, the clinical risk is not going to be high based on the 1,300+ patients we have in the U.S. part of PROTECT. That opportunity is huge for us. Excellent. You mentioned kind of being one of one hits on the market, referencing GSK is removing Dapro from the U.S. market, I think in a couple of weeks. Does that affect the Vafseo launch at all? Or as you talk to docs, does that influence how they think about HIFS? Not really at all. I mean, look, you try to learn lessons from those who go before. And I mean, one of the things that I really think is a competitive advantage for Akebia is our depth of knowledge and expertise in the dialysis space. Not competing with a larger company doesn't always mean you're at a disadvantage, particularly in a very specialized market. And we think we learned some things from how they approached contracting that we've done differently. And of course, the Dapro label had some complexity to it around potential increased risk of hospitalization for heart failure that we don't have. So there were business issues and maybe clinical issues that impacted the drug. We think we're well positioned to be successful there. And again, it's pretty exciting to be now kind of bringing this product. Physicians wanted to use the product, but it just wasn't available to them. So that excitement from physicians is still there. We just get to take advantage of it now. Excellent. We got maybe a minute and a half left. Want to sneak a couple or one in on the pipeline. Sure. There is stuff going on in the pipeline. You've got the focus on AKI and retinopathy of prematurity. So just discuss that and kind of your plans to leverage your expertise in renal just to grow the company. Right. So as you said, we have the first product from our own internal discovery from the HIFs platform, AKB-9090, which we expect to enter the clinic next year in a phase one. Our target first indication is AKI. We also think this is kind of our acute care drug. I mean, also we saw the data from vadadustat ARDS in COVID-related ARDS that was really interesting. We are doing another ARDS study with UT in a more serious ARDS population. That should initiate soon. That will help us decide what is our first indication for 9090. But those are both incredibly high unmet medical needs. Look forward to spending more time talking about that. And then building that pipeline outside of renal, ROP retinopathy of prematurity is all about oxygen. The opportunity to bring a HIFs product to that population to prevent the potential for ROP, we think, could be a massive opportunity. Hopefully, it's just shortly behind 9090 and getting into the clinic. We look forward to getting through the launch and spending more time talking about the pipeline because we think there's some exciting things to come. Excellent. Well, yeah, very exciting time for Akebia on the precipice of launching Vafseo. A long time coming. Yeah, a very long time coming. So exciting 2025 ahead. So thanks for stopping by and walking us through it. Thanks for having me. Appreciate it. Okay. Let's go ahead and get started. My name is Ally Bratzel. I'm a biotech analyst here at Piper. Thanks for joining us at our healthcare conference. And it's my pleasure to introduce Codexis. So joining us today for the fireside, we have Chairman, President, and CEO Stephen Dilly. So this is meant to be an informal format. So if anyone in the audience has a question, just go ahead, raise your hand. We'll get to your questions. So first, just to get going, maybe Stephen, a lot of things have changed since you came to Codexis: strategic refocusing, meaningful extension of the cash runway, tangible progress on ECO synthesis. So just high level, walk us through some of that and kind of what is the value proposition for Codexis now and your vision for the company. Thanks, Eileen. It's great to be here. So Codexis has a long history in building an expertise around enzyme engineering and applying enzymes to the manufacture of drug product. And my job when I came into the CEO role just over two years ago now was to work out what the sort of most valuable go-forward strategy was. And part of that was looking at the base business, which is making biocatalysts for small molecule API production and seeing that as a very attractive but finite proposition in terms of just how much value you can capture from that sector of the market. But then saying, so where else is there an unmet need that we can address? And really looking at all the things we could do with the emergence of oligonucleotides as therapeutics that was quite compelling, and particularly RNA, where to make current siRNA drugs require.