Global Healthcare Conference. My name is Roanna Ruiz. I'm one of the Senior Biotech Analysts here, and it is my pleasure to introduce the Ardelyx team with me. I've got the full lineup here. We've got Mike Raab, CEO, Eric Foster, CCO, Sue Hohenleitner, CFO, and Laura Williams, Chief Patient Officer. Thanks for joining me.
Thank you.
I'm glad to be here. Thank you.
Thanks for having us.
Yeah. Great. I'll start with a bigger picture question before we drill into more specifics. Basically for investors who are new or coming back to the story, could you give us a recap of where things stand in the commercial business so far in terms of R&D development and your commercial priorities for 2026?
That's a mouthful.
It's a lot, yeah.
Yeah. I mean, Eric, if you could address the commercial, how we're doing now and for the rest of 2026.
Yeah. Really pleased with 2025 coming off for IBSRELA, 73% growth. Really excited about the way that the year ended and gave us a lot of confidence obviously coming into 2026. We also feel really good with XPHOZAH. It was the first year, as you know, that there was the TDAPA period for the binders, and felt like the team did a really nice job. We saw 41% growth in that Non-Medicare business, Non-Medicare payer segment, and also a 9% growth in the total dispenses for XPHOZAH. When you think about our commercial business, really last year was all about execution and the team did an excellent job.
We're able to, you know, beat and raise a couple times on the guidance for IBSRELA, and then felt like we really got a good understanding of the market as it relates to XPHOZAH, and we're able to guide to that in 2026, which we think has been well-received. You know, Sue will be able to talk about our guidance here in a bit. Feel really good about last year, where we ended the year, have clear priorities this year, gonna continue to accelerate momentum with IBSRELA. Then on the XPHOZAH side, just really continue to make sure that we're focusing on those Non-Medicare payer segments, and we know that we had good growth last year and feel confident we can get some growth there this year too.
Yep. Sounds great. Digging in a bit on IBSRELA, so pretty solid growth in 2025 and leading into 2026. You know, you sound very optimistic and excited about the opportunity here. So to help frame for investors, what are some of the strongest growth drivers behind IBSRELA that you are really watching for and that people should look out for?
Yeah. Last year was our third full year on the market. At this point, feel like we have a really good understanding of what are the key drivers across the IBSRELA business. You know, we expanded about five quarters ago, our sales force. We ended up doubling it. This year we're really going to try to optimize the sizing around our sales force so that we can get the right reach and frequency with our 14,000 HCPs that we are currently calling on. Last year we expanded our field access or reimbursement team, and we're gonna continue to invest in them this year, and we'll see that team go up in size as well.
They're a really important part of our strategy, because once a patient is identified from the physician, the field reimbursement team can work with the HCPs, work with the patients to pull that script through. Another kind of relatively new driver, if you will, is really focusing on the distribution network. We talked a little bit about this in our earnings call, the IBSRELA Pharmacy Network, and really making sure that the script goes to the right place. Working with the limited distribution network, we see that when prescriptions go there versus retail, we get a higher fulfillment rate and on average more refills throughout the year. Then really the last one is around patient engagement. It's a very motivated and engaged patient population.
As we work on driving more patients to the top of the funnel, pulling them through, getting them to the right place for fulfillment, we'll make sure that we continue to engage with them because when they become aware of IBSRELA, they go in and talk to their doctor, and we know that the doctor will write the prescription for IBSRELA. It's really those four key drivers that we're focused on in 2026, and we know that the investments that we've worked with Sue and her team on, they're gonna continue to pay that forward even after 2026.
Yep. Makes sense. I know you've previously guided $1 billion for IBSRELA in 2029. Could you elaborate a bit on your expectations for IBSRELA getting to that point and then going beyond that point?
Yeah. Again, getting to that point, the investments that we're making in 2026 are not just for 2026, and I think that's really important that everyone understands. These are investments that get us to that guidance that we talked about in 2029 of greater than $1 billion. Laura will be able to talk about our CIC program, which we're very excited about and confident in. Post 2029, there will really be a new inflection. If you think about CIC and IBS-C, they're really a condition, two conditions that are on a continuum or a spectrum. We really feel like this is gonna be able to provide greater value to HCPs and to patients, and we know that we'll continue to grow post that 2029 timeframe.
Yep.
Just to remind everybody of what the guidance was. In 2025, we grew 73% for IBSRELA, and we guided for 2026 to be between $410 million and $430 million. At the low end, that's about a 50% growth rate. When you think about growing 73%, then growing 50%, and really what you need to get to $1 billion in 2029 is about a 38% CAGR. Very achievable, and then obviously continuing to grow beyond that.
Roanna, I think it's important to note as you look at the IBS-C market, really over the last three years, it's been growing double digits.
Mm-hmm.
Right? If you look at the position that we hold when GC-C agonists and secretagogues no longer providing the benefit that patients want, that growth's gonna continue for us at the same time, right? I think one of the important things that we try to ground people on, certainly today, but during earnings, is for us to get to the $1 billion, it's between 200 and 250 thousand patients of a patient population of roughly 5 million-7 million today, right? It is a relatively approachable size of a population to get to the $1 billion with substantive opportunity to grow thereafter.
Yep. Makes sense. I think in the past you've talked about refills making up a larger share of IBSRELA scripts. How should investors think about that shift in prescription composition over time? Like, is it gonna continue to lean into that? You know, any other leading indicators that we should think about?
Yeah. Obviously, refills are important. As I mentioned earlier, we know when they go through the IBSRELA pharmacy network, on average, we see one additional refill on an annual basis. Refills will continue to play an important role, but in order to make sure that we're driving our business forward, we need to make sure that we're getting the new prescriptions to come through. That's why we've decided to add on to our field sales team to continue to drive kind of top of the funnel on those new prescriptions. Again, just thinking about how it all comes together, you've got the field sales team that's driving top of the funnel, identifying patients, the field reimbursement team pulling them through. You've got a very specialized distribution network that can ensure that that script gets filled.
When it all works together, it's a great thing. Like I said, we've got a lot of confidence in that. It's really the refills and the new prescription, a combination of both, that's really gonna drive the business forward.
Yep. Got it. It's really interesting. I got this question from investors in the past. Thinking about the prescribing split between primary care and gastroenterologists and that evolving over time for IBSRELA, at what point does primary care become a more meaningful contributor to IBSRELA growth or already seeing some of it today?
Yeah. We actually are seeing some of it today. Take you back about five quarters when I said we expanded our sales force. The reason why we did that was we wanted to be able to reach 50% of the total prescription market, and that is made up of high prescribing primary care physicians, the high prescribing Gastroenterologists, and then the APPs, which are like the nurse practitioners and the PAs. Actually when we think about those three segments, they are currently driving our business today. We feel really good about that 14,000 or so HCPs that make up 50% of the market, and that we need to just continue to drive depth with those existing prescribers, identify more new prescribers, and that's across all three of those segments.
Yep. Got it. That makes sense. I'm gonna shift over to CIC, one of your newer initiatives for IBSRELA. Maybe just to start off thinking about with the first patient dosed in the EXCEL trial in January, I believe. Can you talk us through just what are the key design elements that we should think about for that study? You know, what's important for investors to think about in terms of what would be an exciting result from that trial when it reads out?
Yeah, no, that's a great question. I think, you know, first and foremost, the optionality of having both indications is huge, right? I think, you know, one of the things that we did is we learned obviously from our IBS-C studies, our T3MPO studies, and that gives us a great level of confidence for the ongoing EXCEL trial. When we looked at the IBS-C data with tenapanor and separating out the constipation component versus the abdominal pain component, we saw significant, you know, improvement with tenapanor versus placebo. That allowed us to actually look at the CIC trial, the EXCEL trial, and figure out how we wanted to power it.
We powered the trial at about 95% so that we could see a 14% difference between tenapanor and placebo, and so we have a high level of confidence about it. I mean, the trial itself is a single Phase III trial. It's a double-blind, placebo-controlled trial, about 700 patients. As you noted, we had our investigative meeting in January and subsequently enrolled our first patient. The goal there now is to complete enrollment by the end of the year, and then we would have data that we would analyze in the second half of next year for an NDA submission.
I think a measure of the enthusiasm for the community of this trial is 110 sites that we had our investigator meeting on January ninth. How many of those sites are already up and running?
Yeah. We have more than 90% of the sites up and running. Again, to your point, Mike, it represents the enthusiasm that both prescribers and patients have for this study.
Yep. Sounds great. I know, I think earlier I mentioned, the continuum between IBS-C and-
Yeah.
CIC, could you help frame for investors, like how they should size the CIC opportunity? Like, how many patients are out there and thinking about how that starts to uplift IBSRELA's reach across different patient populations?
Yeah. Eric, why don't you take this?
Yeah, sure. The CIC patient population is about two or three times that of the IBS-C market. We know that a large percentage of that is really over the counter. I think about like MiraLAX, you see commercials there, or fiber supplements. When you think about the prescription market as it exists today for LINZESS, they already have a CIC indication. A lot of that total market that we see today, we know that some of that is CIC. As we're thinking about the opportunity ahead, what this really does, it makes it much easier for the physician, removes some of the friction points. You can talk about a patient that presents that has constipation plus or minus pain, which would be IBS-C.
With that, feel really confident that we'll be able to get greater penetration, not just on the CIC side, but also on the IBS-C side.
Yep. Thinking ahead, let's say if all works well and you're entering into CIC, what sort of infrastructure or investment are you thinking about in for that indication? I know you mentioned like patient services is really important earlier in our discussion, like what should we be thinking about?
Yeah. We've done a really good job over the past 12 months building out that commercial infrastructure that we think is going to sustain growth over time. One of the things though that I'll tell you that I do think that we'll have to do is we will have to expand the sales force a bit more, probably more so into that primary care market, as you said. I don't think it will be a doubling, but we know, you know, 50% of the IBS-C market is around 14,000 physicians. The other 50% is around 180,000 physicians. When you think about CIC and it being a much larger market, we do realize we may have to go farther from a reach standpoint with HCPs.
We'll just bring on additional resource from the sales side of things. The investment does overlap, so it really won't be a one for one. There will be some synergies there between the CIC and the IBS-C.
Yep. In terms of messaging CIC to physicians, like what sort of data do you hope to leverage in terms of building excitement and awareness about IBSRELA in CIC?
Yeah. Do you want to talk about?
Yeah, I mean, I think the strongest piece obviously is just showing.
Mm-hmm
you know, significant efficacy, obviously on the constipation endpoint, and that's what we're trying to do. I think the study is designed really to show a durable response. When you look at what does that mean, right? I mean, the study itself has a 26-week treatment period, but the primary endpoint is at week 12. Basically, patients have to have shown improvement in their bowel movement functions at nine out of the 12 weeks. That's a durable response. Again, looking at, you know, the data that we have from our IBS-C program, we feel very comfortable that we can do that. When we looked at that data, again, statistically significant efficacy on that front.
I think the other piece is that, you know, because this is a minimally systemically absorbed compound, we obviously, you know, can anticipate the safety profile, which has been, you know, nicely characterized again in the T3MPO studies. I think combining, you know, the data that we have in the T3MPO studies will have a nice safety package. We know what we are looking for from the efficacy standpoint and, we're confident, you know, that the study is powered sufficiently to actually show that.
Yep. That sounds good. So I'll shift gears a little bit to XPHOZAH, another commercial product in your portfolio. I know last year one of the key debates around this product was thinking about like, have scripts bottomed out following the Medicare transition and thinking about that going ahead. I mean, what evidence can you point to just to help investors understand, like where are XPHOZAH revenues now?
Sure.
Are they stabilizing? How should we think about this going forward?
I mean, the bottoming out resoundingly, yes, without question, it did early in the year. We grew that Non-Medicare business, the revenue generating business, by 41%. And that excludes those temporary Medicare transition scripts that we saw in the first quarter. The overall dispenses, including the patient assistance program, grew by 9%. The whole idea here of what we did was try to ensure that patients would be able to retain access, not only short term, but longer term, right? The fact that we are demonstrating the ability to build that business in Non-Medicare segment is really important. I've begun reflecting on, you know, light years ago in terms of when we built the Renagel business at Genzyme. There was no Medicare Part D. That didn't happen until 2007.
There was a significant amount of revenue that was generated in the Non-Medicare segment before Medicare Part D came in. We have evidence of how clear it is and how much you can accomplish with just that segment as part of your TAM. We have the benefit of providing non-revenue drug to all the patients on Medicare who actually deserve it as well.
Yeah. You know, with the guidance that we did provide, I think in a good way it made us give some certainty, where I think last year investors and people were just like, "Well, what is it gonna be?" I think that really helped. That's about a 5%-10% growth in 2026 versus 2025. The other thing we're doing is being very judicious about how we're spending our OpEx, both, you know, with IBSRELA as well as XPHOZAH. XPHOZAH still continues to be a contributor for us. Yep. Yep. Digging in a little bit more, another top question I get is. What level of investment are you thinking about for XPHOZAH going forward, and how do you track ROI on this investment to drive the right level of demand and growth, et cetera? Yep, that's a great question.
We are tracking ROI on all of our programs for both IBSRELA as well as XPHOZAH, and it's really just all about what it's gonna take to keep that top line going, you know, while we're in this period and then beyond. It's just, we're gonna continue to look at that as we always do with all of our products, I'd say. I don't know, anything you can add.
No, I agree. I mean, we certainly track our investments. I mean, in my experience, field sales team always has kind of the highest return. You know, I will go back to some of the things that Mike said. If you look at 2025 and you say, "Did you grow total dispenses versus 2024 when there was 60% coverage?" The answer to that is yes, it grew by 9%.
Mm-hmm.
Did you grow your patient or your revenue business versus the prior year? The answer to that is yes, we grew that by 41%. Then our strategy around access.
Mm-hmm
Regardless of who the payer is, whether it's Medicare, Medicaid, commercial, did access improve? Actually it did. Access is higher now than it was in 2024 when we had coverage. For me, really those three metrics give me confidence that it was the right strategy, the right thing to do, and we can actually grow the business moving forward.
Yep. Interesting. Are there any legislative or regulatory pathways that you're thinking about to possibly restore broader Medicare access for XPHOZAH? If not, any other strategies that you're thinking about or that investors should keep an eye out for?
The baseline in my mind should be status quo, right? 220,000 patients is our TAM for revenue generation. In that is what we say, you know, we generate $750 million at peak, and that of the 220 is only 60,000 patients. So there is a significant business to build from a revenue perspective in that 40% of the market. Are there other things? We'll always keep our eyes open for this, right? I mean, we clearly have worked hard over the last better part of a decade trying to fix some of the broken part of the system for patients on dialysis. And the biggest problem with it is there's little to no new innovation for dialysis patients.
Right.
Clearly evolving innovation for the chronic kidney disease population. For those patients that ultimately end up on dialysis, very little innovation is occurring there. That's the shame of the structure that we currently operate in, which is one of the reasons we made the decision that we did. I do believe if we can demonstrate success with that base case, then that may open up some other avenues for innovation. That to me is the biggest challenge that we face as an industry, and patients do too.
Yep, I hear you. Switching gears to another topic, thinking about the pipeline a little bit more and IP. I know you recently disclosed you have a new tenapanor formulation patent, that's extending protection in terms of IP. Could you just explain for the audience, how do we think about the IP estate and its evolving over time?
Sure.
You know, what's your conviction level with the new IP coming on board and thinking about protecting the product?
Well, conviction's very high, right?
Okay.
I mean, if you look at our strongest IP is the composition of matter in 2033. We have method of use for exposure to 2034. The 299 patent, as you note, is a formulation patent. It's Orange Book listed, and it is but one of, we expect others that allow us to have a debate, discussion, negotiation with the eventuality of generics coming in. How many additional years or plenty of predicates out there that one can model and look at, but each incremental year beyond that LOE is massively valuable. So folks can either look at it a 1-year, 2-year, 3-year, whatever they choose, or further, but there's plenty of evidence out there in terms of what kinds of agreements ultimately are struck with the generic competition that does afford us additional years of support and protection.
Yep. Got it. Got it. I have more of a science question for you guys. Thinking about the next gen NHE3 inhibitor, what are some of the implications, and I think you mentioned greater solubility and potency versus tenapanor. How does that expand the potential for the next gen program in terms of future indications?
Yeah, no, it's a great question. We're obviously excited about that program. I mean, we've been entrepreneurs in this space for a long time here. I think, you know, again, the increased solubility lends itself to increased potency. What do we mean? I mean, the fact that, you know, the compound remains soluble throughout the entire intestine, right? Not just in one particular area. That lends itself potentially to increased, you know, efficacy. It also might mean QD dosing in the areas that we already play in, but it also opens up the opportunity, right, for other therapeutic areas. When you think about, you know, GLP-1s, SGLT2s, and you think about colocation of NHE3 receptors in similar areas, that also makes you think about other potential opportunities.
What we're planning with the five three one program, right, we're conducting our IND enabling studies now. The plan is to submit the IND by the end of the year, and then follow on shortly after with, you know, your typical phase one safety, first in human safety program. In conjunction with that, we're doing other, you know, preclinical studies to actually see where the data leads us in terms of other potential opportunities.
Yeah.
Roanna, that's the path we took with tenapanor, right? It was a CIC program that we started in 2008. We then saw with preclinical models that visceral hypersensitivity pain had a benefit, so that said IBS-C was a potential. We then saw in a 5/6 nephrectomized rat study, oh my gosh, we're blocking phosphorus absorption. So that opened up that potential. So the solubility and potency beyond what allows for our current indications to maybe do better for patients, other indications that we could potentially expand into. As we have the example in tenapanor, more than one IND in a molecule is completely possible.
That's super interesting. Just wanna double click on that. In terms of potential future indications, like would you think about staying within your wheelhouse in terms of renal or GI, or would you be considering other options beyond that?
I mean, I'll answer that and ask Eric to weigh in. I knew nothing about GI until we started this program when we founded the company. You can learn lots of things with capable, smart people. You can get there. Opportunism is really important, and it's ultimately about good science, good medicine matters first and foremost for patients, and then strong commercial organization to execute. You will then make money in that order. If you change that order, then you're gonna get in trouble.
Yeah. I mean, we clearly have deep insights in GI and in nephrology, so there's obviously a benefit there to look there or in the adjacent areas. But those are two very different therapeutic areas, and we know that we are successful in both. So we also have a competitive advantage in the commercial capabilities that we've built. So that allows us to be opportunistic as we look at different things.
Yep. Zooming out a bit, thinking about the pipeline and everything you're working on, like how are you thinking about possible future BD or possible partnerships? Can you just refresh us on your current thoughts?
Well, it's funny, people have asked the question today, why did we wait so long for CIC? Well, I'm cheap. Also wanna make sure that we have the capital to support our aspirations. You know, if you look at the corporate development team that we have at Ardelyx, we're looking at a lot of stuff, and we will look at things that we can afford at the right time or have complete conviction around that are the appropriate thing for this company to do. You know, by your model alone, if you look at the cash that we will generate between now and the end of 2030, the cumulative cash is significant. Our job is to appropriately invest that and build this company to what I and we believe we can do.
We have the good fortune of potentially doing the vast majority of that, if not all of it, with the cash that we generate.
Got it. Moving to a bit of a financial question too. You recently guided the 25% step up in OpEx.
Mm-hmm.
Could you just walk us through, you know, what exactly, you know, went into that thinking and how should we break it up in terms of thinking about R&D?
Right
SG&A changes and, like, any sort of tailwinds that could come through with that level of investment?
Yeah. Just to remind everybody, we did guide up to $520 million for 2026. The one thing I do wanna point out is that we also said on the earnings call, it's gonna be a pretty steady clip on that, so it's not something that's gonna kinda rise as the year goes through. It's gonna be pretty steady as we go. With that, you know, we obviously have both sales and marketing, commercial expenses as well as R&D there. With CIC and with 531, there's two new pieces to the puzzle that we're actually having to invest in a good way. You know, they're gonna be a piece of it. We didn't break that out necessarily.
You know, you can look at last year's you know, the 10-K that we filed and everything, and you can see that R&D as a percentage of the total OpEx was, at the time, I think about 18%-20%. My assumption is that's gotta be higher, especially with everything we've got going on in the space, which is exciting. Sorry.
Roanna, I think probably the most important thing, as Sue Hohenleitner said when we gave that guidance.
Mm-hmm
Top line is growing faster than expenses.
Yes.
That seemed to have gotten lost because at the lower end of our guidance for IBSRELA, it's 50% growth, right?
Good point.
XPHOZAH is contributing at the guidance that we've given. We are growing the top line. We were generating cash for the last two quarters of last year. When you hear me say we're gonna do the things that we can afford, it's because we're generating cash.
Mm-hmm
W ith which we can spend to do our aspirational work. That was probably something that didn't get as much attention as it could've, the top line is growing much faster than is the expense line.
Yep. A lot of the investments in the top line are obviously helping to generate that revenue in 2026 and beyond, particularly as we get into the 2027, 2028, 2029 timeframe.
Yep. Got it. Thanks for clarifying.
Mm-hmm.
I wanted to circle back to CIC 'cause we still have a few minutes. One thing, question that I get is, so let's say everything works out, your Phase III works, you're filing and it gets approved eventually. What types of patients would be the best early candidates in CIC for IBSRELA? Like, what would physicians be looking for in terms of features or, you know, finding these patients as the best suited for this profile that you're targeting?
Yeah, I mean, I think Eric touched on it before. I mean, there's while the CIC population is a larger population, most of those patients are actually taken care of by over-the-counter, you know, treatments. Similar to IBS-C, I think you can envision the fact that, you know, upwards of 70% of folks will come in and say on a GC-C agonist that I still have symptoms, right? I need something else. That's where IBSRELA has made the biggest impact. I think very similar to that is CIC. Again, there are patients who are being treated with CIC with pharmacologic therapy, and there may be some who still aren't getting the benefits that they need.
I think it's that patient population, I mean, very similar to what we saw with IBS-C.
Roanna Ruiz, the way I think about that is right now there are physicians who wanna treat their CIC patients with IBSRELA and they can't. Through prior authorizations.
Right
Everything that happens, they can't, right? What we get rid of is that can't, because suddenly they don't have to worry about it, and they can code for IBS-C or CIC, and it'll get through. That to me, it's not that there's a patient profile that's uniquely suited to what it is that we're gonna have. It's any patient the physician believes deserves a different treatment, especially when you're seeing that with the secretagogues, 70% of them still saying, "I got issues, doc, and I need some help.
Mm-hmm.
Not to flip the question, but I think that's the way to think about it.
Yep
is we're preventing by not having it versus allowing when we do.
Yep. I hear you. Anything to think about, if you're able to elaborate, just how payer coverage could change, like if CIC comes on board as another indication for IBSRELA?
Yes, Eric?
Yeah. From a payer standpoint, you know, we're coming off a year for IBSRELA with significant growth at 73%. You know, payers are always looking for a way to apply utilization management, so, you know, we start to see some friction kind of in the system, if you will. That's one of the reasons why we continue to invest in that pull-through piece. We know that that's critical. The last thing we want to happen is a patient identified and not be able to get the prescription. You know, right now we don't contract with payers, but, you know, we certainly have relationships with them and continue to look at the landscape and see what's there.
As we drive greater value with CIC, we know that IBSRELA will be something that they'll wanna talk about, and we feel really confident in the value proposition that we'll be able to have for any patient that comes in with CIC or IBS-C.
Yep. Makes sense. In our last minute, just a bigger picture question, just what do you think that the market is currently most underappreciating about the Ardelyx story?
All of it. I mean, if you look at what we've gone through, you know, in the last 14 years, is really understanding how to develop a drug on our own, invented in our labs. You know, certainly chronic diseases and bigger population diseases were less popular at the time that we were doing that, right? We have focused on diseases and syndromes that impact millions of people. We've applied from much of our backgrounds the high touch approach that you have with rare disease, because all people who are patients who are waiting for help need that kind of attention. I don't think people really are grasping $1 billion in IBSRELA, basically alone for IBS-C, is very close on the horizon. The cumulative cash that we're gonna generate is significant.
The growth that happens subsequent to 29 is very significant. Any incremental year we get from the 299 patent and others is that much more valuable. It's all of it. We've been patient, we've been thoughtful, I think, in the way that we prosecute this business. I don't think people yet have really spent the time that they should to understand what it is that we do and to see the value that obviously, biased as though I am, we see.
Yep. Got it. Well, with that, we're at time, so thank you so much for joining me and looking forward to more updates from you.
Thanks, Roanna Ruiz.
Great. Thanks, everyone.
Thanks, Roanna. Thank you.