Thanks so much, everyone, again, for joining us for the second day of our Guggenheim Emerging Outlook Biotech Summit. I'm Vamil Divan, one of the Biopharm Analyst here at Guggenheim. Next up in this room, we have the Akebia Therapeutics team. Next to me, we have John Butler, the CEO; Steve Burke, the CMO; and then Erik Ostrowski, the CFO and CBO at the end of the stage. So thanks so much for making the trip and joining us at our conference. Maybe just to kick things off, John, for those less familiar with the Akebia story, as actually stories have evolved a little bit, too, over the last couple of years. For sure. Maybe just an overview on how, where things stand with the company, and then we'll dive into the programs. Sounds good. First of all, Vamil, thanks so much for the invitation to be here. It really is a pleasure. So Akebia is a purpose-driven company, and our purpose is to better the lives of people impacted by kidney disease. We have two commercial products, AURYXIA, which is a phosphate binder, which we have been enjoying the revenue stream from AURYXIA, as it nears the end of its life. We're obviously most excited, and I think we'll spend a lot of time talking about VAFSEO, which is our HIF-PHI, to treat anemia in chronic kidney disease patients on dialysis. And we are about a year into launch, going through the challenges of the dialysis market, but clearly, we feel on track to make this product standard of care to treat anemia in these patients. We're really excited, now that more attention is being paid to our, our pipeline as well, and, and just in December, we announced kind of the initiation, if you will, of our rare kidney disease pipeline, which has two products, initially four indications, possibly many more, to come. But, praliciguat, which we just started a phase II study in FSGS, and in December, we in-licensed, AKB-097 from Q32 Bio, and in the second half of this year, we'll be starting a basket study in, three different rare kidney disease indications. And, you know, then we have early-stage pipeline as well. So, very clear strategic focus and, and a lot of exciting things in the near term. Okay. No, that's great. Obviously, a lot going on now. So yeah, let's talk about VAFSEO and the initial sort of- Sure ... uptake you've been seeing. Maybe you can just talk about kind of the dynamics, as you know, the last few quarters, and kinda how we should expect the, you know, 2026 to go. Sure. So, we launched last January and had very, very strong initial uptake of the product. You know, we were really quite excited about what we were seeing. You know, we knew that dialysis has such a unique, it's a unique market, right? 'Cause it's not just getting the physician to prescribe the product, and they go to the retail pharmacy, and they get it, right? It's very protocolized. It's very controlled by the dialysis providers themselves. So the physicians can really only use what's available through the dialysis provider, and so some, like U.S. Renal, where, you know, we had the initial uptake, clear clinical advocacy, and, you know, understood the business side of the reimbursement, this TDAPA, this transitional drug reimbursement that we have for VAFSEO for last year and this. And others, like, DaVita moves more slowly, as they tend to do. The challenge that we had last year beyond the, you know, moving slowly, was that... Remember, VAFSEO was a once-a-day oral product. For 30+ years, they've been managing anemia by giving people a shot in the chair, and you know, what we saw was what is normal when you give VAFSEO, because it's one starting dose, is that many patients will see a dip in their hemoglobin. Initially, you titrate them up, and the drug works beautifully. Get patients in the range, you keep them in the range. People who are committed to that, you know, really love the outcomes that they're seeing. But you know, it was so new for particularly for the nurses, the anemia managers, sending patients home with a bottle of drug to take. They would see that initial dip, and they would immediately take people off the drug. So we saw a much higher discontinuation rate than we expected to see. Mm-hmm. So, you know, you're putting all these new patients on, but they're coming out the bottom of the funnel. So we put a number of things in place to work on that. It really did start to have an impact. You know, Steve and the clinical team had done work looking at three times weekly dosing for the drug also. Though it's not in our label, we do expect to have a conversation with the FDA about it. But at U.S. Renal first and a number of the others, they've made the decision to go to this TIW dosing, so they can basically, what that means is, they give the drug to the patient while they're in the chair. So it's observed dosing. They know they're getting compliance. They see the dip. They know it's not because the patient's not taking the drug. And, you know, early days, they just started this process late last year, but in the first centers that made that change, where before you had upwards of 30% of the patients never got a second prescription, in patients who were given this observed dosing regimen, that in the first month was less than 10% who didn't get that second. So we're really encouraged by what we're seeing there. And, you know, at the end of the day, we left 2025 with access to about 275,000 patients. So, you know, over the course of 2025, we broadened the access. Now, they're figuring out how to use it. Still a lot of wood to chop, but we're really happy with what we're seeing, and then we have more data coming to support the long-term growth of the product to make this a standard of care for these patients. And then one quick follow-up on that, just in terms of the dosing. Is that something you would look to get in the actual label, or is it more just communicating? Most definitely. I mean, you know, that's a conversation we have to have with the FDA. We have two studies ongoing now, one that we're the sponsor of, and one that we're, that's a collaborative study with U.S. Renal, VOCAL and VOICE. Both of those studies use TIW dosing. So VOCAL, particularly, where we're the sponsor, we think that's an important data set. We already have two studies, MODIFY and FOCUS, that use TIW dosing to support a label, but, you know, the assumption is now that VOCAL will be done by the end of this year. You know, you go to talk to the FDA about it, they'll say, "Well, we want to see the results of that study. Yeah. So why not wait until you see the results of that study?" So, and then VOICE, which is over 2,000 patients, you know, we certainly will be able to share those results. We're not the sponsor of the study, so it'd be a little bit different, but FDA would want to see that as well, and that study will read out, early next year. So, you know, I think it will be... it will really be at that point that, that we have that conversation again in the label. And, and again, I mean, these physicians, and dialysis providers are making the decision, to do that TIW dosing, because they can control, you know, the patients and, and guarantee that compliance. So, so they're doing it without it being in the label. Then maybe just following up on VOICE and VOCAL, so obviously, data coming in the next year or so here, how—just your level of confidence and what... maybe you talk about the design and kind of what you expect to see out of those? Sure. Maybe Steve, you can talk about VOCAL and VOICE. Yeah, the VOCAL study, which we're doing with DaVita, where we're the sponsor, we should get that data by the end of the year. I expect to see excellent hemoglobin control. We're comparing ourselves to Mircera, which is a long-acting ESA, so we expect to see, just like we saw in the FOCUS trial, you know, excellent hemoglobin, great stability, less need for rescue therapies, less hemoglobin variability. There's an important sub-study associated with VOCAL, where we're taking patients who are looking at their red blood cell phenotypes. We've seen previously that red blood cells made under the influence of VAFSEO are larger, they have more hemoglobin and have a less, you know, wide distribution of widths, which is a good thing. We're doing a study looking at proteomics, metabolomics, lipidomics, membrane fluidity, resistance to oxidative stress, the kind of things that, you know, matter in terms of red blood cell phenotypes. This is really demonstrating that this more physiologic approach to managing anemia, that it matters, right? You're not just getting, you know, you're not just getting hemoglobin, right? You're getting a better red blood cell, and that matters. You know, Steve and I just came back from a sales meeting in Arizona. We were talking to the folks there. You know, Steve and I worked together at Genzyme on Renagel and Renvela, and the playbook is kind of the same, you know? I mean, this was... you know, you bring this new product in, you had to continue to generate data to demonstrate to physicians why this is different. You know, we have that now, and we presented data just at the ASN meeting, an analysis from our big phase III study, looking at, you know, using a new statistical technique, this win odds technique, and we showed that there was a statistically significantly lower risk of dying or being hospitalized using VAFSEO versus darbepoetin, you know, a long-acting ESA. So, you know, it is. That's the kind of data that gets physicians excited about using it. We have to get that published, then you get it in the hands of your medical folks and communicate it. So, you know, long term, you know, and we are taking the long-term view here. This is a billion-dollar market for ESAs today in dialysis. We expect to be standard of care over time, and, you know, that's a standard of care is 50% plus one. Yeah. You know, and that's, so that's a $500+ million opportunity for us. And, and we're very confident, given the data we've seen and the data that's coming, that, that we'll get there. Okay. You know, the VOICE trial, the 2,100+ patients we're studying at U.S. Renal Care, it's a randomized comparison against Epogen, which is a short-acting ESA, and the primary endpoint for that study is this composite endpoint of death and hospitalization rate using the win ratio. And that study completed enrollment last June, and we will lock a database by the end of this year and you know, present results early in 2027. So we're very optimistic. The primary endpoint is non-inferiority for that endpoint, but then it flips to superiority. And, and based on what we've seen from FOCUS and other TIW data that we have, this should be a very, very good chance, you know, we could show some, some real benefits along the lines of all-cause mortality and hospitalization. Okay. Okay, great. Yeah, and those hospitalization rates that we'll be looking at in the VOICE study are very important to the DOs from an economic perspective. I mean, first and foremost, we're looking to show, you know, clinical, you know, benefits to patients, but the DOs do share in a portion of the hospitalization costs for patients. So if we can show obviously a reduction in those costs versus the standard of care, we think that, you know, increases the economic proposition. Yeah, makes sense. Okay, makes sense. So, one quick, more on the VAFSEO side. So you had some updates late last year around the non-dialysis population with the conversation with the FDA. You sort of suggested there might be some specific, Right ... subgroups that you maybe still may all have some potential, and so maybe you can talk about the latest conversations you've had with the FDA, your thoughts around that. Sure. Yeah, I mean, we continued to follow up with the FDA on, on the non-dialysis population. A once a day oral product, it make perfect sense there. Large population, real high need. Physicians want to use it there. They still want to use it there, regardless of our conversations with the FDA. And at the end of the day, in October, we had a Type C meeting, and they... while we had thought we had been having very productive conversations, at the end of the day, they really wanted us to redo the PROTECT trial, which, you know, was 3,000+ patients, you know, in 5 years. And, and, you know, from an economic, timing perspective, it just didn't make sense for us to do that. Now, while we were in that meeting, we did talk about other subpopulations that, you know, that truly have a need, where the benefit would outweigh their perceived risk. And, you know, we're continuing to engage with them on that. We think any opportunity to get this drug to patients, you know, is worth pursuing. Given their approach, you know, we're being very conservative about how we think about that, right? I mean, I- Yeah. We were very disappointed in, you know, their approach to this. But so that's why we're kind of focusing on, look, we have the drug approved in dialysis. It's a huge market opportunity. Physicians want to use it in non-dialysis. Will they decide to do that as they get experience in dialysis? I'm 100% sure they will. They talk about it to me every time I talk to them. It's just a matter of them having to go through the process of getting a medical exception and getting it reimbursed. But we do expect some non-promoted use in the non-dialysis population, and anything we can do to demonstrate, you know, and add those populations to the label, you know, help provide evidence for physicians on that. Okay. All right, so why don't we shift to the pipeline? All right. So you obviously brought in a couple assets here you touched on in the beginning. Maybe just before we get into the details, just the decision to do this and kind of why, you know, why these assets looked interesting to you? Yeah, look, I mean, we, as I said at the beginning, I mean, we're a purpose-driven company that's focused on kidney disease. So, you know, when you think about building out a company, rare kidney is perfect opportunity for a company of Akebia's size, right? So, we in-licensed praliciguat from a company, Cyclerion, back in 2021. You know, they had generated data in diabetic kidney disease. We wanted to be sure it worked. We thought targeting FSGS, and Steve can talk about this, made a ton of sense for us. But we wanted to do some preclinical work to make sure that was the case. You know, we hit a bump in the road when we got the CRL. We kind of had to focus on the dispute resolution and getting VAFSEO approved. Yeah. And then, you know, there were some issues from Cyclerion in getting us API for the product, which kind of worked out fine for us. But, you know, we were very excited about that product and FSGS, and we initiated that phase II in just in December, we dosed the first patients. And then in December also we in-licensed AKB-097 from Q32, and this is a tissue-targeted complement inhibitor, and Steve can talk about that as well. And we'll be starting a basket study in the second half of the year, looking at IgAN, C3G, and lupus nephritis. And we think this can be really an incredibly important product for treating these diseases. Very, very much able to be differentiated from the complement inhibitors that are out there today. Okay. Okay, great. So maybe let's talk about praliciguat and FSGS. Maybe just the mechanistic rationale to pursue this, and maybe just more broadly, FSGS, a lot of activity there around the space. How have you seen the sort of competitive dynamics, kind of the market evolving there? Yeah, sure. Praliciguat's a small molecule. It binds to something called soluble guanylate cyclase, and it stimulates that to make cyclic GMP. That's the second messenger for nitric oxide, and what it's doing is stimulating good things. So it's very beneficial to the podocyte, which is a specialized cell in the glomerulus that's the main barrier to protein getting into your urine. It's also anti-inflammatory and antifibrotic. So when we acquired the product, they had already had a very extensive package of non-clinical studies in kidney disease models and in vitro, in vivo, et cetera. So we were looking for a disease that progressed rapidly to end-stage kidney disease, and we thought about IgAN, and we thought about FSGS. We thought FSGS made the most sense because there's less crowded space, and so we did ourselves models of FSGS, you know, in rodents, in rats, and we saw excellent activity in the models that, you know, would predict benefits in patients. I'd say the biggest benefit was in reducing scarring in the glomerulus, which fundamentally what FSGS is. Mm-hmm. So, yeah, and then we went back and we looked at the diabetic kidney disease data to see were patients getting to what you would consider to be like a complete remission for this condition. And, using urine albumin-creatinine ratio from the diabetes study, we were able to sort of project what we would see for urine protein-creatinine ratios, which is now becoming the standard endpoint for FSGS trials. So it looked very encouraging. So I'm very bullish about that trial. And, yeah, we're gonna do a randomized, double-blind, placebo-controlled trial in about 60 patients. Half will get placebo for six months, half will get praliciguat, and at that six-month period, the placebo patients will be able to cross over to praliciguat. Okay. The primary endpoint is reduction in UPCR. Yep. And when do we expect to see the data? We haven't guided on timing. We really wanted to, you know, kind of see how the enrollment- Uh-huh ... goes before we get over our skis too far. You know, we got the first patients started to enroll last year, so we're, we're happy with how we're going. But as you said, it is a more competitive space, so we wanna see, you know, what the dynamics there just from a patient enrollment perspective will be. You know, it is FSGS is a very heterogeneous disease, right? I mean, it's biopsy diagnosed. So, you know, the idea of kind of multiple products being able to be successful in that space, where, you know, different patients will benefit from different products. Polypharmacy will probably make sense for patients with FSGS. You know, not every FSGS patient will be not everyone, but they'll be unique. Yeah. So, you know, we think even though there are more products in development in that space, praliciguat has a unique profile that really can be quite successful. I mean, you see when the FDA, which they did with IgAN, right? They define a clear regulatory path, which, you know, they've done now, we think, with FSGS as well. It really does encourage more innovation in the space and we think we're kind of at the forefront of that. Yeah -with poly. It seems like they're really highlighting this. Obviously, IgAN's been a great success, but- Yes ... leveraging this, another rare renal- That's right. But- That's right. In terms of just maybe for this trial, you mentioned a very heterogeneous population. Are there certain patient subgroups that you're focused on here, or how are you trying to get a- We're focusing on, you know, primary FSGS and/or FSGS attributable to a genetic mutation. We're excluding secondary FSGS- Okay ... which, you know, like morbid obesity or people on certain types of medications. Kind of the playbook that other companies have followed in the past. Okay. Okay, no, that's great. So look forward to seeing progress there and, and the data. So maybe on 097, you're taking a basket trial approach, which we've seen other companies- Yeah ... look at. Talk about that, yeah, that mechanism and kinda what, what, you know, what, what indications are you most excited about there? Yeah, I think it's a really unique molecule. It's a fusion protein, so it's a monoclonal antibody that recognizes C3d, which is a breakdown product of C3. And on the back end, there are two tails of Factor H molecules. Factor H is a negative regulatory complement inhibitor, so it binds to the C3 and the C5 convertases of the alternative pathway, and you know, dissociates them and degrades them. So it will be administered either subcutaneously, which is the primary route of administration, or you could give it intravenously. It will go to the sites where complement is being activated, where C3 is being degraded to C3d. So it's taking the complement inhibitor right to the site where the disease is. And so you don't get the systemic complement inhibition you get with other agents that are on the market today. They all have boxed warnings because of this side effect. You're much more likely to get a serious, potentially fatal bacterial infection, and we don't expect to have that with this product. Also use a lower dose, and so we think it ultimately would be amenable to have an auto-injector once a week or once every two weeks. So we think we'll get the best of both worlds. We'll get the great efficacy of a drug like pegcetacoplan, but with a better administration schedule. Yeah. Without the box warning. Without the box warning. Yeah. Okay. In terms of indications, patient population, where are you sort of most focused here? We're focused on the rare kidney diseases, but there are other conditions where a complement activation is localized. You probably wouldn't develop a drug like this for PNH or something that's affecting the entire body, because you'd have to give a much larger dose and sort of undermine the benefits of this product. So- So Q32 had a protocol basically agreed with the FDA on, you know, looking at IgAN- IgAN. C3G and lupus nephritis. We thought the fastest path to get into the clinic was to follow that protocol as closely as possible. So that's what Steve's team is working on now. And the nice thing about a basket trial is, you know, you can look at data kinda as you go. Okay. So, you know, we expect to start the study in the second half of the year, and, you know, with this one, we are kind of saying we'll have data in 2027- Yep ... to start to share. Okay. Okay, great. So maybe then just rounding out the discussion here. The cash position for the company right now, and kinda how you see your runway? Yeah, we have a strong balance sheet. $166 million in cash as of the end of Q3, and we've guided, we have at least two years of cash runway. Okay, and then as we sort of bring it all together, how would you lay out sort of the key catalysts, key events investors should focus on for the next 12 months? Well, I think people are clearly gonna keep looking for, you know, at the VAFSEO launch. I mean, that is thing one, right? I mean, that is the engine that fuels the development pipeline, as well, right? So, people will look at our progress there and get... you know, kind of see that inflection. And then, you know, we initiated the Praliciguat study, getting AKB-097 into the clinic. AKB-9090, which we didn't talk about at all, which is a HIF compound from our own research. We will start a phase I in healthy volunteers. We're targeting AKI associated with cardiac surgery as a first indication, but we'll start that study and have it completed before the end of this year. As I said, AKB-097 data, you'll start to get next year. And then, as we've talked about earlier in the half hour here, the VOCAL study will read out before the end of this year and VOICE, early next. So if you look at the next 12 months from a clinical catalyst perspective, you've got very important readouts that will kinda confirm the ability of Vafseo to become standard of care in this market, and you'll really start to see the fruits of our pipeline as well. It's gonna be a very, very exciting 12 months for the company. Okay. All right, why don't we leave it there? We only got a minute left anyway, so- Great. Thanks again so much for coming. A lot of interesting events coming up. We'll look forward to following the progress. Vamil, thanks for the invitation. Thank you. Great. Thanks so much. Appreciate it. Thanks.