Akebia (AKBA) Q4 2025 Earnings Call Transcript

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DATE

Thursday, February 26, 2026 at 8 a.m. ET

CALL PARTICIPANTS

• Chief Executive Officer — John P. Butler
• Chief Commercial Officer — Nick Grund
• Chief Financial and Chief Business Officer — Erik Ostrowski
• Chief Medical Officer and Head of Research and Development — Steven K. Burke

TAKEAWAYS

• Net Product Revenue -- $227 million for 2025, reflecting revenues from both Vafseo and Auryxia.
• Total Revenue -- $236.2 million in calendar year 2025, compared to $160.2 million in 2024, driven by Vafseo's U.S. launch and higher Auryxia sales.
• Vafseo Net Product Revenue -- $45.8 million for 2025 and $6.2 million in Q4, with Q4 revenue reduced by a $4.8 million inventory drawdown at USRC.
• Auryxia Net Product Revenue -- $181.5 million in 2025 and $48.1 million in Q4, up from $152.2 million and $44.4 million in 2024, respectively.
• Vafseo Prescribing Access -- 290,000 patients have access in dialysis clinics via protocol implementation, with over 1,000 prescribers at 24 organizations having written Vafseo prescriptions.
• Adherence Improvement -- First refill adherence among Vafseo observed dosing patients rose to approximately 91% in Q4, with January data showing around 87% for a larger observed dosing group.
• Commercial Demand -- Vafseo demand was flat at $12 million in both Q2 and Q3, and $11 million in Q4 2025.
• Clinical Outcomes (INNO2VATE Data) -- Vafseo-treated patients exhibited a 7.7% lower annual hospitalization rate, 16% reduction in hospitalization days, and approximately 15% lower Medicare hospitalization costs versus Darbepoetin, translating to roughly $3,700 per patient per year in savings.
• Expense Management -- Total cost of goods sold (COGS) decreased to $39.5 million in 2025 from $63.2 million in 2024, largely due to the elimination of a quarterly $9 million non-cash amortization charge.
• R&D Expense -- Increased to $62.4 million in 2025 from $37.7 million in 2024, mainly due to clinical trial activity, headcount growth, and a $12.8 million AKB-097 acquisition charge in Q4.
• Net Loss -- Decreased to $5.3 million for 2025 from $69.4 million in 2024, with Q4 net loss at $12.2 million, down from $22.8 million in Q4 2024.
• Cash Position -- Cash and cash equivalents were $184.8 million as of December 31, 2025, up from $51.9 million at the end of 2024, with management stating current resources will fund operations for at least two years.
• Generic Competition -- Management expects expanded generic competition for Auryxia in 2026 and forecasts a decline in Auryxia revenue compared to 2025.
• Pipeline Progress -- Phase 2 enrollment ongoing for praliciguat (up to 60 patients in FSGS), phase 2 open-label basket trial for AKB-097 to initiate in H2 2026, and phase 1 study for AKB-9090 in healthy volunteers set to begin in H1 2026.
• Upcoming Data Catalysts -- VOCAL study results on Vafseo three-times-weekly dosing expected in Q4; VOICE study results targeted for early 2027.

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RISKS

• Chief Financial and Chief Business Officer Ostrowski stated, "we anticipate generic competition for Auryxia to expand this year beyond the current authorized generic competition and therefore expect Auryxia revenues to decrease in 2026 as compared to 2025."
• Vafseo demand in Q4 2025 was "slightly down versus Q3" due to dialysis organizations' transition to in-center dosing protocols, causing delayed patient starts and a related $4.8 million one-time inventory drawdown.
• Butler said, "demand basically has been flat. We had $12 million in the third quarter, $11 million in the fourth quarter, and it was actually $12 million in the second quarter as well, right? You know, we absolutely expect and are seeing growth from that level," indicating recent sluggish demand prior to anticipated growth.

SUMMARY

Akebia Therapeutics (NASDAQ:AKBA) delivered a marked year-over-year increase in total revenues accomplished by the commercial launch of Vafseo and rising Auryxia sales. Management highlighted significant expansion in Vafseo prescribing access and adoption by major dialysis organizations, while reporting improvements in patient adherence linked to observed dosing protocols. Newer clinical data reinforce Vafseo's competitive positioning, demonstrating reduced hospitalization rates and Medicare costs compared to Darbepoetin in dialysis patients, with further pivotal trial readouts anticipated. The pipeline advanced across multiple programs, including targeted trials for praliciguat, AKB-097, and AKB-9090, with clear milestones set for the coming year. Capital resources increased considerably, supporting continued R&D and commercial investments.

• Quarterly Vafseo demand remained flat at $11-$12 million across the last three quarters, with management expressing confidence in sequential growth but providing no formal revenue guidance.
• The VOCAL study, currently enrolling 350 patients in DaVita units, aims to establish non-inferiority to erythropoiesis-stimulating agents (ESAs) for hemoglobin control; Burke noted potential for Vafseo superiority in certain hemoglobin safety endpoints, though these are not primary endpoints.
• Butler described the AKB-097 phase 2 basket trial protocol as simplified relative to predecessor Q32 Bio, with FDA alignment maintained and IND reactivation pending protocol revision.
• Cash and cash equivalents more than tripled during 2025, from $51.9 million to $184.8 million, providing the company with at least two years of operational funding under its current burn rate.
• Observed dosing regimens not only improved first refill adherence but showed high 80%-90% continuation rates into subsequent prescriptions, despite a 2%-4% monthly discontinuation background in this population.

INDUSTRY GLOSSARY

• TDAPA: Transitional Drug Add-on Payment Adjustment, a Medicare reimbursement mechanism for new renal drugs, important for Vafseo commercial uptake.
• ESA: Erythropoiesis-Stimulating Agent, standard treatment for anemia in chronic kidney disease.
• HIF-PHI: Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, the drug class of Vafseo and AKB-9090, used for anemia management in CKD.
• FSGS: Focal Segmental Glomerulosclerosis, a rare kidney disorder targeted in Akebia's praliciguat phase 2 program.
• USRC: U.S. Renal Care, a major U.S. dialysis provider where Vafseo is being adopted and protocols are being implemented.
• UPCR: Urine Protein to Creatinine Ratio; primary efficacy endpoint in praliciguat's phase 2 trial.

Full Conference Call Transcript

Mercedes Carrasco: Thank you, welcome to Akebia Therapeutics, Inc.'s fourth quarter and full year 2025 financial results and business updates conference call. Please note that a press release was issued earlier today, Thursday, February 26th, detailing our fourth quarter and full year 2025 financial results, and that release is available on the investor section of our website. For your convenience, a replay of today's call will be available on our website after we conclude. Joining me for today's call, we have John Butler, Chief Executive Officer, Nick Grund, Chief Commercial Officer, and Erik Ostrowski, Chief Financial and Chief Business Officer. Dr. Steven K.

Burke, our Chief Medical Officer and Head of Research and Development, is available for Q&A, dialing in from the Annual Dialysis Conference in Kansas City today, where Akebia Therapeutics, Inc. will present data on Vafseo this weekend. I'd like to remind everyone that this call includes forward-looking statements. Each forward-looking statement on this call is subject to risks and uncertainties that could cause actual results to differ materially from those described in these statements. Additional information describing these risks is included in the financial results press release that we issued on February 26th, as well in the Risk Factors and Management Discussion and Analysis section of our most recent annual report filed with the SEC.

With that, I'd like to introduce our CEO, John Butler.

John Butler: Thanks, Mercedes, and thanks to all of you for joining us this morning. 2025 was an important year for Akebia Therapeutics, Inc., marked by the commercial launch of Vafseo, vadadustat, our oral HIF-PH inhibitor for the treatment of anemia due to chronic kidney disease for patients on dialysis. Vafseo, along with our phosphate binder, Auryxia, generated $227 million in net product revenue in 2025, during which time we also progressed multiple post-marketing clinical trials and advanced and enhanced our growing pipeline. Let's start with Vafseo. 2025 got off to a very fast start before a number of challenges flattened demand in the second half of the year.

We addressed those challenges head-on, we believe today we're starting to see the demand growth that we've expected. Most importantly, the body of evidence is growing that supports the potential for Vafseo to become standard of care in what is a $1 billion U.S. market opportunity after the TDAPA period ends, when we expect Vafseo will be priced roughly in parity with ESA pricing. While we didn't see the growth we expected in the second half of 2025, we built real excitement for Vafseo.

Today, just over a year into the launch, more than 1,000 prescribers at 24 different dialysis organizations have written a prescription for Vafseo, and 290,000 patients have access to Vafseo in dialysis clinics with a protocol in place. I'm particularly encouraged by the shifting dynamics we began to see in Q4 that are continuing in Q1 that suggest greater breadth of prescribers as well as improving adherence rates. Nick will provide more detail on these very encouraging trends in his remarks. A key element of our strategy to have Vafseo become standard of care includes continuing to generate data, supporting the benefits of managing anemia with a more physiologic approach compared to ESAs.

At the ASN meeting in November, we presented a post hoc hierarchical composite endpoint analysis of prospectively collected outcomes of death and hospitalization from our phase 3 INNO2VATE program in dialysis. This analysis demonstrated that patients treated with Vafseo experienced a lower risk of dying or being hospitalized than patients treated with the ESA comparator. This coming weekend, at the ADC in Kansas City, we're presenting a cost comparison of Vafseo versus Darbepoetin based on INNO2VATE data. In this analysis, Vafseo showed a 7.7% lower annual hospitalization rate, 16% reduction in hospitalization days, and based on Medicare cost data, approximately 15% lower Medicare hospitalization costs for patients treated with Vafseo versus Darbepoetin.

Reduced hospitalization translated into a cost savings of about $3,700 per patient per year, meaning a savings of almost $2 billion per year if all eligible patients were treated with Vafseo. Late this year, we'll have the results from the VOCAL study that we're conducting at DaVita Clinics that's evaluating Vafseo dosed three times weekly. The trial also contains a sub-study of red blood cell characteristics, which we believe could make a compelling argument for Vafseo. Fundamentally, when you manage hemoglobin levels with a more physiologic approach, you get a more physiologic and potentially better functioning red blood cell.

The VOCAL data will be followed by results from the VOICE trial being run by USRC, evaluating Vafseo versus standard of care on a hierarchical composite of all-cause mortality and hospitalization rates. Data expected in early 2027. In my experience, in order to make a drug standard of care, particularly with nephrologists, you have to continue to deliver data that demonstrates the benefit of the product for their patients versus current treatment. In addition to the launch of Vafseo in 2025, we introduced our rare kidney disease pipeline, which we believe will be an additional and important value driver for the company going forward.

Strategically, this initiative is a natural extension for us as it leverages our expertise in kidney disease drug development, broadens our presence within the kidney disease community, and fits squarely within our corporate mission. We will host an R&D day for investors on April 2nd to discuss our mid-stage assets in detail, namely praliciguat and AKB-097, as well as introduce our early HIF-PHI, AKB-9090. praliciguat is an oral, once-daily, soluble guanylate cyclase stimulator being evaluated in a Phase 2 clinical trial of focal segmental glomerulosclerosis, or FSGS. We expect to enroll up to approximately 60 patients in this trial, which will evaluate change from baseline in urine protein to creatinine ratio, or UPCR, at 24 weeks as the primary endpoint.

Both the extensive preclinical work in FSGS disease models, as well as previous clinical results for praliciguat in diabetic kidney disease, give us confidence in the potential for the therapy to impact FSGS. AKB-097 is our tissue-targeted complement inhibitor that we acquired late last year. We believe this product candidate could have comparable efficacy to the most efficacious, currently approved products in a well-characterized pathway. The tissue targeting allows for the potential to, first, avoid the box warning for infection risk, and second, to deliver the drug in a more convenient dosing regimen. We believe this has best-in-class potential. We plan to initiate a phase 2 open label basket trial in the 2nd half of this year.

We will be looking at initial indications of IgA nephropathy, lupus nephritis, and C3 glomerulopathy. These diseases represent a multibillion-dollar market opportunity in areas of high unmet need. As part of the basket study, we'll be evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, and effects on disease-relevant biomarkers such as proteinuria and kidney function. As this is an open label basket study, we expect to begin to report initial data in 2027. Lastly, we plan to initiate a phase I study in healthy volunteers of AKB-9090 in the first half of 2026, with top-line results later this year. Our initial target disease area for 9090 is acute kidney injury associated with cardiac surgery.

Our research and development team is working hard to deliver these important catalysts as quickly as possible. Of course, all of this work will be built on the success of Vafseo. Let me turn it over to Nick, give more granularity on the launch.

Nick Grund: Thanks, John. Good morning, folks. Like John, I am encouraged by the growth potential for Vafseo in 2026, which is supported by early Q1 data. First, let me recap Q4 2025. During the quarter, approximately 800 prescribers wrote a prescription for Vafseo, and each prescriber, on average, wrote approximately 10.3 prescriptions. Of note, 128 of those were new prescribers. During Q4, we were pleased to see our customer base expand and the number of new starts at dialysis organizations outside of USRC, specifically at DaVita and IRC, increased over Q3. Approximately 25% of new patients came from dialysis organizations other than USRC during the fourth quarter.

That said, Vafseo demand in Q4 was slightly down versus Q3, as we reported $6.2 million in Vafseo net product revenue on about $11 million in demand. We believe the slight decrease in demand, specifically in Q4, was primarily a result of a lower number of patient starts at dialysis organizations deciding to transition to an observed in-center dosing protocol and thereby waiting until the observed dosing protocol was available. USRC, for example, began to transition in November in approximately 25% of clinics. By the end of Q1, we expect the vast majority of USRC in-center patients to be receiving Vafseo three times a week while receiving dialysis, utilizing USRC's observed dosing protocol.

Of note, USRC's decision to transition to an in-center observed dosing protocol did result in a reduction in their inventory as they shifted from shipping a bottle to a patient's home to stocking bottles at their centers. The distribution change resulted in a one-time inventory drawdown impact of about $4.8 million in the fourth quarter of 2025. Now, let's turn to 2026. We begin the year on an optimistic note as we are already building momentum. At present, 290,000 patients have prescribing access, as DCI has implemented a Vafseo protocol.

With the almost fivefold increase in prescriber access since the end of Q3 2025 and our field teams actively calling on physicians with expanded access, we are seeing an expansion of brand awareness and a comfort prescribing Vafseo within the nephrology community. Additional commercial trends give us confidence in Q1 and the year ahead. First, we saw improved adherence from the beginning of 2025 through the end of the year and continuing into 2026. More importantly, the percentage of patients who got an initial refill rose from approximately 75% for all daily dosing patients in the first 9 months of 2025 to approximately 91% among the small subset of patients who were on observed dosing regimen.

Looking at early patient data from January, we've continued to see an improvement in first refill adherence, with approximately 87% among the now larger subset of patients on an observed dosing regimen. We're encouraged by this improvement and will continue to monitor adherence rates in 2026 as centers implement their observed dosing protocols. We're also seeing a nice pickup in utilization and broader adoption from IRC, the fourth largest dialysis center, after IRC made Vafseo available in late August and implemented an observed dosing protocol late in Q4. DCI has started to put patients on therapy. We also see the number of prescribers within DaVita starting to increase, with some physicians trialing Vafseo in their patients.

This has led to a higher % of new patients being from non-USRC clinics than in 2025. The investment dialysis organizations continue to make in Vafseo, taking the time and effort to integrate the therapy into protocols and care plans, make me believe that providers and prescribers understand the clinical benefit Vafseo can deliver and are committed to using it long term. As prescribers continue to gain real-world experience as they transition patients onto Vafseo, I expect the momentum to continue to build. Our dedicated sales team is focused on increasing the breadth and depth of prescribing, a critical step to becoming standard of care for patients on dialysis. Let me now turn it over to Erik.

Erik Ostrowski: Thanks, Nick. As John mentioned, we saw a strong top-line performance in calendar year 2025, as net product revenues increased nearly 50% over calendar year 2024, driven by the U.S. introduction of Vafseo and increased sales of Auryxia. Our continued careful expense management in 2025 allowed us to both invest in R&D initiatives we believe can generate significant shareholder value and maintain our solid financial position. We are excited for a strong 2026 and executing on our plans to grow Vafseo revenues and advance our pipeline, including our mid-stage rare kidney disease programs. I'll now provide an overview of our Q4 2025 and calendar year 2025 financial results as compared to the prior year.

Total revenues were $57.6 million in Q4 2025, compared to $46.5 million in Q4 2024, and $236.2 million in calendar year 2025, compared to $160.2 million in calendar year 2024. These increases were driven by sales of Vafseo and an increase in Auryxia sales. Vafseo net product revenues were $6.2 million in Q4 2025 and $45.8 million in calendar year 2025. As Nick mentioned, Q4 Vafseo sales were negatively impacted by the inventory drawdown at USRC. Auryxia net product revenues were $48.1 million in Q4 2025, compared to $44.4 million in Q4 2024, and $181.5 million in calendar year 2025, compared to $152.2 million in calendar year 2024.

We note that we anticipate generic competition for Auryxia to expand this year beyond the current authorized generic competition and therefore expect Auryxia revenues to decrease in 2026 as compared to 2025 Auryxia. Turning to expenses, cost of goods sold was $12.5 million in Q4 2025, compared to $20.4 million in Q4 2024, and $39.5 million in calendar year 2025, compared to $63.2 million in calendar year 2024. COGS in both periods was driven by higher Auryxia sales volumes in 2025 and was impacted by the elimination in 2025 of a quarterly $9 million non-cash intangible amortization charge we incurred through Q4 of 2024.

In addition, costs for calendar year 2024 included a $12.3 million benefit due to our ability to sell inventory previously written down as excess inventory. Of note, Vafseo-related COGS in both periods of 2025 was derived from pre-launch inventory, which does not include the full cost of manufacturing, as a portion of those inventory-related expenses were reported as R&D expenses in the period incurred prior to Vafseo's approval in the U.S. R&D expenses were $26.6 million in Q4 2025, compared to $11.8 million in Q4 2024, and $62.4 million in calendar year 2025, compared to $37.7 million in calendar year 2024.

The increase in expenses in both periods was driven by increased clinical trial-related activities for Vafseo and our other product candidates, higher headcount-related costs, as well as by a $12.8 million charge incurred during Q4 2025 related to acquired in-process R&D costs associated with the acquisition of AKB-097. SG&A expenses were $26.1 million in Q4 2025, compared to $27.7 million in Q4 2024, and $107.5 million in calendar year 2025, compared to $106.5 million in calendar year 2024. Net loss in Q4 2025 decreased to $12.2 million, as compared to a net loss of $22.8 million in Q4 2024.

Net loss for the year also decreased to $5.3 million in calendar year 2025, as compared to a net loss of $69.4 million in calendar year 2024. The decrease in net loss in both periods was driven by the increase in net product revenues, which was partially offset by higher expenses. Turning to the balance sheet, cash and cash equivalents as of December 31, 2025, were $184.8 million, as compared to $51.9 million as of December 31, 2024. We believe our existing cash resources and cash from operations will be sufficient to fund our current operating plan for at least the next two years. With that, we welcome questions.

Operator: Thank you. At this time, we'll conduct a question-and-answer session. As a reminder, to ask a question, you will need to press star one on your telephone and wait for your name to be announced. To withdraw your question, please press star one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Julian Harrison of BTIG. Your line is now open.

Julian Harrison: Hi, good morning. Thank you for taking the questions. I have a few, and I'll just go one by one here. First, can you talk more about your expectations for sequential Vafseo growth in 2026? Wondering also how we should be thinking about that in relation to your inventory-adjusted demand in the Q4 of 2025. Second, to what extent do you expect data from the VOICE study to potentially accelerate uptake next year across dialysis providers? Finally, I'm curious how operationalized the Vafseo access at DaVita currently is. Are the VOCAL data a big gaining step there, or do you expect broad commercial uptake at DaVita before the VOCAL data are reported?

John Butler: Great. That's a great list, Julian. Thanks. Expectations for growth first in Vafseo. We're not guiding for revenue. I'll start with that. I mean, I think it's, you know, again, when you're in a launch, particularly in this dialysis market, if you saw last year, you know, we certainly, I certainly expected that dialysis providers would latch on to the opportunities around TDAPA more quickly, and, you know, we certainly didn't anticipate the issues we had with adherence. You know, we're certainly dealing with those, as I said, you know, very much head-on. I think the way to think about it is, kind of forget the inventory fluctuations.

You know, we give you the demand number, you know, and really think about that, right? I mean, demand basically has been flat. We had $12 million in the third quarter, $11 million in the fourth quarter, and it was actually $12 million in the second quarter as well, right? You know, we absolutely expect and are seeing growth from that level. You know, exactly how quickly that will increase, I think, you know, some people are kind of looking for this sort of magical hockey stick.

You know, when I think about launches that I've been a part of in this market, that didn't have the complexity of the dialysis provider in between, I mean, I go way back in time to Sevelimer, you know, Renagel launch. We did $20 million in the first year, $55 million in the second year, $130 million or something in the third year. Ultimately, it was a $1.3 billion product, right? Nephrologists don't adopt products like oncologists, right? You know, you definitely have a more measured growth.

I think that's what we're seeing here as well, particularly, I think, as you look at DaVita, where, you know, DaVita's made the product available, but aren't, you know, sending out lists to physicians of patients that have reimbursement. They're leaving it to the physician to make the decision. That's fine. That's on our field teams to sell and educate physicians about the benefits. You know, it's things like the data from VOICE. You look at the data from the ASN meeting last year, it's super important data, right? Will make a huge impact, it's not published yet, right? It's been submitted for publication. It's just been presented at ASN.

Our medical affairs folks can't educate physicians with that data until there's a reprint, you know, in publication, peer-reviewed, which we expect is gonna happen this year. You know, the same thing will be the case with the with the cost analysis that's being presented this weekend. You have to get those things published. I think you'll see the same with VOICE and VOCAL as well. As these things are published, available, and our sales and medical affairs folks can use them, these are the things that influence utilization and physicians.

I've never been more confident that the data that we're generating supports that managing anemia with a HIF-PHI, and the only one that's available is Vafseo, is going to be standard of care for this patient population. It really is just a question of how quickly that happens. You know, we're seeing growth now, we're confident in that growth, but, you know, we're not in a place where we want to guide around that. We want to see it continue to move in the direction that it's moving now. Maybe, Nick, you can talk more about operationalizing at DaVita?

Nick Grund: Certainly DaVita made the product widely available throughout their "Village" in late Q4. As they've started to focus on educating their physicians, they're really starting with the home dialysis population. That population within DaVita is greater than 30,000 patients, so just about the size of USRC. So that's a great step. It really fits with USRC in total. It really fits well within the profile of Vafseo. Super excited about that. Second, they're also, you know, really contemplating an observed dosing protocol, which will certainly hopefully handle some of the adherence challenges that we've seen in the past. You know, DaVita is not going to, as John suggested, send out lists and compel physicians to try it.

It's our field teams, whether that be medical, educating them about Vafseo or sales, selling Vafseo, that are really going to help physicians try and then increase usage and then ultimately adopt Vafseo as a standard of care. When we think about that process, you know, DaVita is a fairly big organization, you know, getting them to try it, and we're very encouraged. You know, we, in Q4, we saw a number of DaVita physicians starting to utilize Vafseo, and that's continued into Q1. As John suggested, we're not gonna see this hockey stick inflection. It is gonna be steady growth month-over-month, quarter-over-quarter, as we start to penetrate deeper in terms of breadth and depth.

John Butler: I mean, it definitely depends on how you define a hockey stick, right? Three quarters of flat sales, you will have growth. you know, that's.

Nick Grund: You can call that a hockey stick. We do expect that to continue to grow. It really is about what's the slope of that curve, right? You know, again, I think as I said, one of the things that surprised me most was that it didn't happen faster because of the economic benefits of using the drug during TDAPA. At the end of the day, it was always about the clinical benefit, and that's, you know, what we're showing now. You know, Nick talked about the observed dosing protocols that are being put in place.

You know, we really do think by the end of the year, most patients who are being treated in center are going to be treated with that observed dosing, and that observed dosing means they get it three times a week when they're sitting in the chair. That helps greatly with compliance. You know, the anecdotes that we're hearing from physicians that have begun utilizing three times weekly dosing are. More importantly, maybe the anemia managers that are managing those patients on a daily basis, they're really very, very positive. You know, we're really excited that DaVita's moving forward with that as well.

If they focus on the first part of the year on their home population, that will be fantastic for us from a growth perspective. Hopefully, that helps, Julian.

Julian Harrison: Excellent. This is very helpful all around. Thank you very much.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Roger Song of Jefferies. Your line is now open.

Nabil (for Roger Song): Hey, good morning, team. Congrats on the progress, and thanks for taking our question. This is Nabil on for Roger. It's encouraging to hear about the improvement in the first refill adherence. I was curious if you'd comment on how second and third refill rates are trending, and then any other comments just on the anemia manager education. I have a second one.

John Butler: Nick, do you wanna take that one?

Nick Grund: Yeah, you know, super, let's kinda repeat the first refill because I think it is significant. Historically, we've seen roughly a 75% adherence on the first refill. A patient receives an initial prescription, that first refill is the next prescription. That moving from 75% to 91% in the fourth quarter in that small subset of patients was really an important, I'll call it, bellwether for what we're gonna see moving on. We were waiting for the bigger subset in quarter one, and specifically in January, to say, "Okay, now is it, is it really coming to fruition in a larger patient population?" It is. We're seeing, you know, this 87% first refill rate.

As they moved into the second prescription, I think your question is a really good one. We've seen, you know, significant continuation of that adherence rate. You know, you have to remember, these patients have significant comorbidities, comortality, they receive transplants. There's an always an underlying, let's call it, 2%-4% discontinuation rate in that population, every single month. We've seen this continuation of this high 80%-90% adherence rate, even through the 2nd prescription, is starting to lead towards some positive trends for annual adherence rates.

John Butler: You know, the other thing you're going to see, as the clinical data continues to build, you know, even if a patient, you know, one of the main reasons that a patient would go off is if they feel like they have some GI tolerability issues. We know those are transient, right? What we've seen from physicians who really believe in the clinical benefit, they talk to the patient and say, "I understand you're dealing with this, but we put you on this medicine for a reason. You know, we really believe this is going to benefit you. I want you to try to work through it, and, you know, it will go away." It does.

There's other physicians or nurse managers who aren't as, you know, as sold on the drug, maybe it's a way to say it, or don't have the same level of education on the product benefits, and they'll acquiesce and take the patient off, right? Yeah, Nick, you wanna add something?

Nick Grund: Yeah, the only thing I'd probably add is, by people moving from daily dosing to observed therapy, in the clinic, what we've seen is a number of restarts patients coming back in. That means that physicians are saying, "Hey, that patient who may not have been compliant the first time around, by being able to give it to them in the chair, we now can go back to that patient because we believe in the value that Vafseo might bring," and by being able to dose it in the clinic three times a week, has allowed them to offset that compliance challenge and really provide Vafseo for that patient.

John Butler: Nabil, you had a second question. I'm sorry, I didn't write it down. I can't remember what it is.

Nabil (for Roger Song): All good. Yeah. Thank you so much for those updates and that color. Just on the 9090 asset, again, congrats on the progress here. Just curious how that's, if you can comment a little bit more on how that's mechanistically differentiated from prior HIFs, and then, any other thoughts there? Thank you.

Nick Grund: ... On AKB-9090. Steven, are you on? can you-

Steven Burke: Yeah.

Nick Grund: Take that one?

Steven Burke: The, you know, the molecule has a different, you know, pharmacokinetics and a slightly different profile. Vadadustat tends to preferentially target the liver. That's where the erythropoietin is made, whereas ninety, because of its structural differences, has more widespread tissue penetration, so it gets into the lung and the kidney. In our non-clinical models of ischemia-reperfusion injury, nine oh nine oh is clearly the best compound that we had for that indication, whereas vadadustat probably would not work in that indication. It's all about the structure and the PK.

Nabil (for Roger Song): Thank you. Very helpful. That's all for me.

John Butler: Bill, I think your other question was around anemia manager education, I think it may be important to point out, you know, we definitely recognize how significant that is. You know, a lot of that education has to be done through the medical affairs folks, our MSLs. You know, we made the decision earlier this year to expand our medical affairs group so that we have more folks' feet on the ground, if you will, doing that education. You know, so much of this data that's coming out really needs to be delivered, whether it's to a physician, KME or an anemia manager through the medical function rather than the sales function.

You know, we're still finalizing the last couple of positions there, you know, those folks have kind of hit the ground running and, you know, are really ramping up our education. Nick, you want to add something?

Nick Grund: You know, it's great to see that the dialysis organizations are actually participating in that education, right? You know, UCSF, we've had great advocacy from Mary Dittrich and Geoffrey Block all along, and they've been educating proactively. Within DaVita, they have a centralized anemia management model, so those folks aren't necessarily in the clinic, and they've been educating their centralized anemia managers themselves, which also is a great step for getting folks comfortable with Vafseo.

John Butler: Cool.

Nick Grund: Thank you.

Operator: Thank you.

John Butler: Thanks, Nabil.

Operator: Thank you. One moment for our next question. Our next question comes the line of Roanna Ruiz of Leerink Partners. Your line is now open.

Michael (for Roanna Ruiz): Hi, this is Michael, on for Roanna Ruiz at Leerink Partners. Thank you for taking our question. For VOCAL study, can you give us a sense of what success looks like? Is this primarily about demonstrating TIW non-inferiority versus ESAs, or are you powering for superiority on any endpoints? Also, how important is the RBC sub-study in differentiating Vafseo's mechanism? Thank you.

John Butler: Steve, do you want to take that one?

Steven Burke: Sure. You're right about the study. It's 350 patients. DaVita felt it was important for them to do the study in their own units, you know, partly to operationalize it, but also establish that the drug is as safe and effective as the ESAs, Mircera, that they're using today. I suspect we'll see superiority on some of the hemoglobin-related safety endpoints, which we saw in the focus study, so less rapid rises, less high hemoglobins and less need for dose adjustments. It's not, you know, that's all pre-specified, it's not like it's a primary endpoint. The primary endpoint is non-inferiority for hemoglobin control, which makes sense because you're targeting people to a range of hemoglobin between 10.

I do think the red blood cell study will be interesting and important because, I think there may be some... You know, people who aren't really as close to this don't understand how different Vafseo is from ESAs. Where ESAs, you're basically giving a recombinant human EPO. It binds to receptor on cells in the bone marrow and helps them differentiate into red blood cells. Vafseo does so many more things, and we already know that the red blood cells that are made under the influence of Vafseo are different. They're bigger, they have more hemoglobin, they have a more uniform distribution of widths.

This additional information, I think, will build on what we know to be true today, that the red blood cells really are different. I think it gives physicians a reason to believe that Vafseo is different, and then when we have data around things like, you know, death and hospitalization, it makes more sense to them. There's a mechanism by which they can understand these clinical benefits.

Michael (for Roanna Ruiz): Got it. Thank you. Another question, if you, if I may. Have you reactivated the IND for AKB-097 yet? Are there any changes you made to the protocol from Q32 Bio that was previously aligned with FDA?

Steven Burke: That's a great question. We have been reworking the protocol just to make it simpler, but fundamentally, it's the same protocol that FDA agreed to with Q32 Bio. We're just trying to make it less operationally complex so that it's easier to recruit and easier to run. We won't activate that IND until we resubmit the protocol that we're very close to finalizing. I hope that answered your question.

Michael (for Roanna Ruiz): Yep. Thank you.

Operator: Thank you. One moment for our next question. Our next question comes to the line of Allison Bratzel of Piper Sandler. Your line is now open.

Ashley (for Ally Pratzel): Hi, this is Ashley on for Ally Pratzel of Piper Sandler. Just 1 question from us because you guys did a great job of answering our other questions. Just on the R&D day, on April 2, when you're discussing your pipeline, can you help frame some expectations for investors? You know, what should investors look forward to? You know, what level of detail are you planning to provide? Any color there would be super helpful. Thank you.

John Butler: Sure, Ashley. Obviously, we're still bringing together the agenda for that. As I said, I mean, we really will focus, you know, there's so much that we could talk about. That's kind of the exciting thing for the company right now. You know, there's so many areas we can go. I think, you know, we really wanna focus on praliciguat and oh-nine-seven. You know, we think it's important that you hear from other people other than Akebia Therapeutics, Inc. employees. I mean, you'll hear from Akebia Therapeutics, Inc. employees, we really wanna bring in KMEs to talk about...

You know, when we think about the process we went through to make the decision to in-license AKB-097, you know, Steve always, you know, kinda says, "Well, you know, when Erik brought this forward, it was like, oh, another complement inhibitor, do we really need this?" It was really talking to KMEs, you know, one of whom, you know, we expect you'll be able to hear at the R&D Day, that, you know, this concept of a next generation complement inhibitor, really, you know, I think those are the words that were used. Hearing the excitement around that product from people other than Akebia Therapeutics, Inc. employees, I think is important. It'll give us the opportunity.

We haven't had the opportunity to kinda go into depth on, you know, the data that underlies the decisions we made, the data, the preclinical data on praliciguat, for instance, that gave us confidence in moving forward in FSGS. You know, it was exciting to get a question on AKB-9090 on this call. You know, this is, you know, the first product we're putting in the clinic from our own discovery efforts, small but mighty discovery efforts at Akebia Therapeutics, Inc., and kind of introducing that product and answering questions like Nabil asked about, you know, what differentiates it from vadadustat. We think it'll be a very robust day.

I mean, it's the kind of thing you can spend six hours on, but we'll do it in a, in a much more streamlined fashion. I think it will. You know, right now, we just introduced this rare kidney pipeline in December, and I don't think people really have had the opportunity to focus on it, because quite rightly, they're focusing on the Vafseo launch. You know, we're really happy with how the Vafseo launch is going.

We think that will continue to, you know, to deliver for the company and be the financial driver for, you know, continuing to build the pipeline. now people will be able to really understand, you know, what we've got and why we're so excited about, not just the rare kidney pipeline, but our capabilities in expanding that HIF, pipeline as well.

Ashley (for Ally Pratzel): Great, I really appreciate it.

John Butler: Thanks, Ashley. Good to talk to you.

Operator: Thank you. I'm showing no further questions at this time. I'll now turn it back to John Butler for closing remarks.

John Butler: Great. Thank you, Marvin. I do wanna take a moment again to outline the catalyst-rich next 12 months that we have at Akebia Therapeutics, Inc. In addition to watching our progress towards standard of care for Vafseo and the billion-dollar dialysis market, we'll see Vafseo top-line data from VOCAL in Q4 and VOICE in Q1 of 2027. We'll initiate the AKB-097 basket study in the second half and expect to see the first data in 2027. We'll begin and complete the phase 1 study of AKB-9090 during the course of this year, as well as continuing to enroll the praliciguat phase 2 in FSGS. We are very excited about the present and future for Akebia Therapeutics, Inc.

We're eager to share more about our pipeline programs at our R&D Day on April second, and I look forward to speaking to you then. Have a great day.

Operator: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

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