Ardelyx, Inc.

Welcome to the Ardelix First Quarter 2026 Earnings Call. All participants will be in a listen-only mode. I would now like to turn the conference over to Lisa Capparelli, Senior Vice President of Corporate Communications and Investor Relations. Lisa, you may begin.

Thank you, Ross. Good afternoon, everyone, and welcome to our First Quarter 2026 Financial Results and Business Update Call. Earlier today, we issued our earnings release, which can be found on the investor section of our website at ardellix.com. Slides that accompany today's call can also be found on our website. On today's call, I'm joined by Mike Robb, President and CEO of Ardellix, who will share our Q1 progress towards our 2026 priorities. Eric Foster, Chief Commercial Officer, will provide an update on the performance of Ibsrella and Exposa. And Sue Hohenleitner, our Chief Financial Officer, will provide some key highlights from our financial results. Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements. which are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our annual report on Form 10-K, our quarterly report on Form 10-Q, which was filed today, and from time to time in our other documents filed with the SEC. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligations to do so, even if our views change. I will now pass the call over to Mike. Mike?

Thank you, Lisa. Good afternoon, everyone. It's great to be with all of you today. Before we dive in, I want to take a moment to welcome Lisa to the team. We're excited to have her on board, leading our IR efforts as our new head of investor relations. 2026 is poised to be another significant year of growth for our company, and we're already off to a great start. At Ardellix, we're building an innovative pipeline of medicines for patients with unmet medical needs. Our first quarter's performance reinforces our confidence in the strategy we've laid out and in our ability to capture the opportunities ahead to create long-term value. As we build on this momentum, our focus is on executing on our four key priorities. Accelerating the growth of the umbrella, maintaining the exposure momentum, building and expanding our pipeline, and delivering strong financial results. Starting with Ibsrella, in the first quarter, our disciplined commercial execution drove 58% year-over-year revenue growth. With more than 7 million prescriptions written for IVSE-indicated medicines last year, Ibsrella is well-positioned as a differentiated mechanism for patients who continue to experience symptoms despite treatment with a secretagogue. Our strategy continues to positively impact demand drivers, and today, Israel is helping tens of thousands of patients with IBSC, and we remain on track to deliver at least a billion dollars in annual revenue in 2029. With Exposa, our patient-first strategy continues to guide our execution with demand growing. Today, more patients have access to Exposa than ever before, and we remain committed to supporting patients irrespective of payer coverage. Next, our pipeline. As a result of our performance and execution, we are at a stage where we have the financial flexibility to further invest in our pipeline, positioning our company for durable long-term growth. Earlier this year, we initiated Excel Trial, a phase three clinical trial about evaluating mozzarella for chronic idiopathic constipation, or CIC, as part of our efforts to expand our label and to reach more patients. This trial has rapidly gained attention from clinicians and patients alike. And all pre-identified sites have been initiated in under four months and are engaged in patient recruitment activities. We remain on track to complete enrollment by year end and to announce top line data in the second half of 2027. If Excel reads positive, IBSRELA will expand treatment options for more patients. In addition, we have a strategy to expand the use of IBSRELA, which may help pediatric patients with IBSC and has potential to extend Tenapenor's patent life for an additional six months. Our ongoing pediatric program consists of several studies evaluating Azrel and patients with IBSC and functional constipation, pediatric equivalent to the adult CIC. This effort is an example of our ongoing strategy to extend Synapenor, which includes our recently announced orange booklet listed 2099 patent covering the commercial formulations of Azrel and Exfosa, building additional value for these franchises. Also included in our pipeline is our development program for our next generation NHG3 inhibitor, 531, which continues to progress through IND-enabling studies, building on our foundational experience in NHG3 inhibition. And 531 may extend our reach into other therapeutic areas, which would be driving additional value for shareholders. We're excited for this next phase of Ardelix's evolution as we execute on our pipeline and explore various external opportunities that align with our mission and core capabilities and meet our disciplined capital allocation approach. We've been growing our team at Ardelix and now have a deep bench of talent at the executive level. I'm excited with the two newest additions who have joined the executive team. Felicia Attenberg, our chief legal officer, and Dr. Rajani Dhanabahi, our chief medical officer. Felicia's broad legal training and experience as a business partner, as well as Rajani's experience in advancing innovative therapies from development to patients will be beneficial to our deluxe as we build upon our commercial foundation, invest in our pipeline, and focus on delivering meaningful outcomes for patients. I'd also like to take a moment to thank Dr. Laura Williams, our Chief Patient Officer, who's been serving the dual role of CMO and CPO while helping to guide us on this journey and has done an outstanding job advancing our clinical programs. Thank you, Laura. Finally, we remain in a position of financial strength. Our Q1 revenue performance position is to reiterate our previously communicated full year 2026 revenue guidance for Absrolla and Exfosa. We have the flexibility to allocate capital to both near-term commercial execution and investments that will expand our pipeline to drive long-term growth value for the company, our patients, and our shareholders. I'm confident in our strategy and our team's ability to deliver on our key priorities. Together, we are advancing a growing, differentiated, innovative pipeline of medicines that address unmet patient needs. And with that, I'm pleased to turn the call over to Eric to walk you through our commercial success. Eric?

Thank you, Mike. It's great to be with you all again. In Q1, we continued to build upon the incredible commercial momentum and execution and performance from last year. Ipsrella grew in total riders, new and refilled prescriptions, and total prescriptions year over year. For Exposa, we continued to ensure patient access regardless of payer coverage, which drove an increase in total dispenses and paid prescriptions year over year. Our commercial team remains focused on expanding adoption among HCPs, creating greater brand awareness for patients, and ensuring the fulfillment of written prescriptions. Our investments to improve the HCP and patient journey and expand access to our medicines have turned into consistent year-over-year growth for both Ipsrella and Exposa. Let me start with Ipsrella. Ipsrella continues to be our main revenue driver, and our commercial execution generated 58% product revenue growth year-over-year. During the quarter, we saw robust demand trends, notwithstanding expected first quarter market dynamics and temporary disruption from two severe winter storms. Our growth in demand is a result of our efforts to capture more of the IBSC market in 2026 by driving Ipsrella as the first-line therapy following a secretagon failure. Ipsrella is a first-in-class, innovative medicine with a winning and sustainable position in a growing market with nearly 7 million prescriptions written last year. Through research, we know that as many as 77% of patients on a secretagogue continue to experience symptoms despite treatment, demonstrating a high unmet medical need for additional options. I'll now walk you through our key demand drivers, which include growing both breadth and depth of writing, increasing patient activation, and lastly, improving prescription pull-through and fulfillment. Beginning with growing breadth and depth of writing, we are focusing on high-writing healthcare providers who are responsible for approximately 50% of the IBSC total prescriptions, and our field sales team is driving greater reach across those targets. These efforts resulted in an increase in the number of writers in Q1, underscoring the effectiveness of our commercial activities. We are also seeing deeper prescribing within existing accounts. When an HCP is familiar with the access path and sees positive patient experiences, they are more likely to prescribe Ipsrella more broadly. Our in-market messaging focused on Ipsrella's differentiated mechanism of action and its established safety and efficacy profile is resonating and continuing to drive HCPs to prescribe Ipsrella. With respect to patients, the IBSC population is highly engaged in managing their condition. As awareness of Ipsrella's effectiveness and safety increases, patients are more likely to initiate conversations with their physicians, which in most cases results in a prescription. We continue to focus on identifying and reaching patients through multifaceted marketing efforts. We are currently seeing robust engagement across digital and social channels, while we continue to explore new channels to reach and engage with the sizable IBSC patient population looking for something different. One such initiative is through our partnership with the LPGA, where we will educate, empower, and mobilize patients to take control of their IBSC by seeking new information and talking to their doctor about their symptoms and the treatment options that are available. We chose to partner with the LPGA due to their clear strategic alignment between the LPGA's legacy of empowering women and Ardellix's mission to empower patients to proactively manage their health. Patients deserve open dialogue about their symptoms and their options, and we are excited to partner with the LPGA to accomplish this goal. Lastly, our full commercial organization is focused on driving prescription pull-through to help ensure that all patients prescribed Ipsrella get on treatment. Based on prior success, we are increasing the presence of our field reimbursement managers who support patient access. This team is talking directly to prescribers and supporting them with account education and patient pull-through to improve patient access. To drive further adoption, we are continuing to encourage HCPs to send prescriptions to the Absarola Pharmacy Network, a limited group of specialty pharmacies that offer a patient-centric, high-touch experience and who are best equipped to handle prior authorizations and to pair hurdles that can restrict patient access. As prescriptions go through our specialty pharmacy network, fulfillment rates are higher, and we see, on average, an additional refill per year for patients. This is a high-value opportunity that we will continue to help achieve our projected revenue growth. We are united in our purpose to make a meaningful difference to patients impacted by IBSC, and we are moving with urgency to capture the opportunities ahead and realize our full potential. Moving on to Exposa. Our high-performing, patient-focused Exposa team committed to achieving the full potential of Exposa and bringing this important medicine to patients in need. I continue to be proud of the team's ability to improve patient access and drive growth. As a result, we saw an increase in total dispenses by 32% and paid prescriptions by 19% compared to the same quarter in 2025, which is important as the overall prescription market declined by 10% over the same time period. We are broadening our reach by employing targeted sales initiatives and a cross-channel strategy increase HCP and patient engagement. We saw solid growth across key metrics in Q1, with notable increases in total riders, new and refilled prescriptions, and total prescriptions across the non-Medicare segments compared to the same time period last year. This growth shows progress against our key strategic initiatives, which includes optimized HCP targeting and enhanced access messaging to support pull-through. Exposa continues to be an important contributor for our DELICs, and we remain focused on supporting and ensuring access for all patients, regardless of payer coverage. With the majority of patients treated with binders not having fully controlled phosphorus, the high unmet need is clear. I'm confident in the team's ability to deliver on our priorities for both Ipsrella and Exposa this year. The entire organization is executing incredibly well at a high level in a fast-paced environment, consistently achieving our shared goals as a result. At the same time, we are making prudent investments across the commercial organization to strengthen our position in the market, support patients along their journey, and accelerate long-term growth. I will now turn it over to Sue. Sue?

Thank you, Eric. As you heard from Mike and Eric, we are continuing to advance our commercial momentum to drive significant value creation. We are leveraging disciplined capital allocation into a clear strategic advantage by investing with purpose in commercial growth and building our pipeline. We are driving towards profitability and meaningful cash generation, allowing us to strengthen our balance sheet, invest in growth, and build long-term shareholder value. Now let me walk you through the financials. Our quarter-over-quarter total product revenues were $93.4 million compared to $67.8 million in the same period last year, representing 38% growth. That growth was driven by a significant increase in XRELA demands with Q1 2026 revenues of $70.1 million, an increase of 58% compared to Q1 of 2025. The Q1 2026 demand for XRELA increased despite the expected Q1 seasonal dynamics that were further exacerbated by the winter storm. We continue to expect XRELA revenues to grow quarter over quarter for the remainder of the year. Revenue for Expoza during the first quarter of 2026 was $23.3 million and on an as-reported basis remained consistent with the prior year revenue. However, it's important to understand the underlying business results we're seeing. As you may recall, in Q1 2025, we recorded a $3.8 million favorable adjustment related to product returns. Taking that adjustment into account, our paid prescriptions of Expoza revenue actually grew 19% year over year. Now turning to expenses. R&D expenses for the first quarter of 2026 were $20.2 million compared to $14.9 million for the same period in 2025. This increase primarily reflects development activities for the cell phase three trial for CIC. SG&A expenses were $102.3 million for the first quarter of 2026 compared to $83.2 million for the same period in 2025. This increase was reflective of the ongoing investments to drive commercialization demand and adoption of Insurella. Our net loss for the first quarter of 2026 was $37.6 million, or a loss of 15 cents per share, compared to a net loss of $41.1 million, or 17 cents per share, for the same period in 2025. The net loss for Q1 2026 included $14.2 million for non-cash expenses from share-based compensation compared to $12.1 million for the same period in 2025. We're in a position of financial strength with $238.1 million in total cash, cash equivalents, and short-term investments as of the end of the first quarter. To capitalize on the favorable market conditions, we recently refinanced our existing debt with SLR. You may recall we entered into a loan agreement with SLR in 2022 that provided a total of $300 million of cash which $200 million has been drawn down. The remaining $100 million of cash is available for drawdown this year. We are pleased with the positive outcome of this refinancing with SLR, which extended the maturity and interest-only period of our loan by two years and lowered our overall cost of capital and annual interest expenses throughout the term of the loan. Now turning to guidance for 2026. We are reiterating our 2026 revenue guidance for Exrella between $410 and $430 million. That represents a 50% to 57% year-over-year growth. We expect the growth to be driven by quarter-over-quarter increases in demand, along with improved prescription pull-through. Our long-term growth expectation for Exrella remains to reach at least $1 billion in 2029, representing a 38% CAGR. Now turning to Exfosa. We are reiterating our revenue guidance between 110 on $120 million in 2026. We continue to invest at an appropriate level to ensure that exposure remains a contributor of financial growth for our deli. Our full year product revenues are expected to grow between 38 and 46%, outpacing our operational expenses, which will grow by approximately 25%, consistent with prior guidance. We're at a stage in our development where it's necessary for us to prudently invest in our growth accelerators, our commercial operations, and our pipeline, all of which require high-impact investments in R&D and SG&A. In 2025, we grew our cash balance year over year, even as we increased investment in both commercial execution and pipeline development. As we transition into more steady and measurable cash flow positivity in the near future, I think it's important to begin to share our capital allocation priorities as we head into this new era. Our priorities include, one, accelerating Israel growth, as this is our highest ROI use of capital today. Two, investing in our current pipeline to create additional growth drivers and expand with external business development opportunities. And three, maintain our financial strength. Importantly, we are funding current operations and pipeline from our revenue base, which demonstrates the growing financial maturity of Ardelix. In addition, as I stated previously, we have proactively refinanced our debt and reduced our cost of capital while preserving optionality for BD partnerships or other future opportunities. Ultimately, all of this builds towards sustainable profitability. We hope this view of our capital allocation priorities is helpful as you continue to support the strategic value of Ardelix now and as we evolve into the future. With that, I'll hand it back to Mike.

Thank you, Sue. As you heard, we're focused on executing on our priorities, significantly grow Exrella, maintain Exposa momentum, further advance our pipeline, and continue delivering strong financial results. We are moving with purpose, urgency, and discipline against these priorities, and we look forward to demonstrating continued progress as the year unfolds. To our investors, employees, and especially the patients, thank you for your continued engagement and support. We're encouraged by the progress we've made and excited about the opportunities ahead. We remain focused on discipline execution, long-term value creation, and we appreciate your continued confidence as we move forward. And with that, we'll open the call for questions. Operator?

If you would like to ask a question, please press star one on your telephone keypad now. You will be placed into the queue in the order received. Please be prepared to ask your question when prompted. Once again, if you would like to ask a question, Please press star 1 on your phone now. And our first question comes from Rowana Ruiz from Lear Inc. Partners. Please go ahead, Rowana.

Yep, thanks. A couple from me. First one, I thought it was interesting you mentioned the Ibsrella demand increased despite the storms and seasonality. How should that flow through to the next quarters and in light of your current guidance?

Sure. I'll ask Eric to comment a bit on it. But, you know, for us, seeing what we all went through in the first quarter, which is normal seasonality in those two storms, seeing that continued growth in demand only strengthens our conviction in terms of where we're seeing this business grow. And very, very pleased with those results. Eric, anything to add?

Yeah, thanks, Rona, for the question. Very pleased with what we saw in terms of demand in Q1 and very similar to the patterns that we've seen in the past. We expect to continue to see quarter-over-quarter growth as we move forward. I feel very confident with the team that we have in place and continuing to invest in access and making sure that all patients that are written the prescription can get fulfillment. So I feel very comfortable about the strategy that we have in place and our ability to be able to continue the strong execution, and you should see that continue to grow as we move through the year.

Great. And the other question I had, I was curious about any color you could share about OPEX throughout 2026. How should we think about this with the Phase III CIC study ramping up as well?

Yeah, thanks, Rowana. Yeah, I would say that we've said before we're going to guide and we are up to about 520 in total OPEX, and that would be consistent throughout the quarters. So, you saw in first quarter that we've recorded about $122 million of that OpEx expense. So what I would see is a bit of a ramp up then as we move through. And yeah, as we continue to enroll the patients in the study, you will see more of those expenses come through the rest of the year.

And then to be clear, that was all factored into the guidance that we gave, the expectation of the spend that we would have on CIC.

Understood. Thanks a lot. Thanks, Rhonda.

And our next question comes from Yigal from Citi. Please go ahead, Yigal.

Hi, this is Joel and came on for Yigal. Congrats on the progress and thanks for taking our question. Maybe just a quick one from us. Have you tracked towards your December enrollment completion target for the phase three CIC trial? Can you provide any color on the pace of enrollment relative to internal expectations so far? And are there any learnings from the IVSC Tempo enrollment experience that are helping you optimize recruitment? Thanks.

Oh, interesting question with regards to tempo. You know, as I stated in my comments that we have all the preconceived sites up and running, right? And that pace of enrollment of the sites was wonderful to see. you know, was on par with what we expected out of the TEMPO program. As I also noted, the enthusiasm both by treating physicians and patients is evident, and that enrollment continues at pace. So we're very confident with the timeframe that we have shared where we'd be able to expect both for it to be completed and the data to be shared.

Great. Appreciate it. Thank you.

And our next question comes from Dennis Ding from Jefferies and Company. Please go ahead, Dennis.

Hey, guys. Thanks for taking my questions. I had several questions from Israel. So number one, So Q1 had some seasonality, and on a quarter-over-quarter basis, it was a bigger step down relative to last year, which is, you know, totally fine because it's a bigger base. But in terms of the recovery, should we also expect a bigger recovery than what we saw last year as well? I believe consensus for Q2 assumes about like a 30 million quarter-over-quarter recovery for Q2. Question number two, so specifically around the specialty pharmacy dynamic, can you share if that shift away from retail is working out in terms of better fill in reauthorization relative to last year? The channel's about 30% in the mix, but how much higher can that go? And then I have one more follow-up.

All right, let me just quickly address some of those, and I'll ask Eric to comment. You know, I think the Q2 recovery, I think, rather than recovery, is just a normal course of business. And I think that term is an important one to think about, is what we expect and what we plan for, given the predicted and expected dynamics that everyone sees in Q1. Now, the surprise was the storm, the two storms, both the Mid-Atlantic one and the one in the Northeast. And that clearly had a meaningful impact in that sector of the country. And you think about where many distribution centers are, there was smack dab in the middle of the Ohio River Valley, where much of that was hit. So one can't predict, you know, we're not weather people and they are wrong 50% of the time at least. So we don't try to predict storms, but it is one thing that's notable. I'm very confident with, you know, the data that you show every week that we're on the path to what we expected out of Q2. I mean, I do think, again, just to reemphasize, it's not a recovery, rather just the pattern of the business. Um, I'll ask Eric to comment a little bit more on that in terms of what they saw in the field. Um, but the IPN and pharmacy network is a fundamental important part of our strategy moving forward given Eric's comments and his opening statements. It is better for patients. Um, and I'll let him talk about the dynamics in terms of the shift and. I think at this point it's early for us to say what we think the ultimate potential of percentage of the business that would go through that. It's probably a little bit too much detail. That will become evident through the data that we know is imperfect, but that will become evident over time. Eric?

Yeah, thanks, Mike. And thanks for the question, Dennis. As far as Q1 goes, we had talked about the seasonality. And as Mike said, for us, we've got the experience and the knowledge to know most of that that's coming. What we were not aware of, obviously, were the storms. So we feel like the team planned accordingly. We were able to push through the temporary disruption there. And just like we saw last year, we really started to see the acceleration in the back half of the quarter. And we certainly see that, which gives us great confidence as we moved into Q2. With regards to the Ipsrella Pharmacy Network, we continue to be very excited about that opportunity and really to bring Ipsrella to patients that are prescribed Ipsrella. So if we think about the fulfillment rate and your question around is there better fulfillment, absolutely there is when it goes to the Ipsrella Pharmacy Network. And that's really the driver for us to make sure that patients that are prescribed Ipsrella can get access to the treatment. So we'll continue to work on moving business into the Ipsrella Pharmacy Network. we expect that to continue through the year and also it's important to note when that happens there is an additional on average prescription written or refill written in that year so it's really great for patients you get a higher fulfillment rate you get better refill rate as those prescriptions go through the australia pharmacy network yeah the one thing i would add dennis um you kind of talked about the guidance i think we were pretty um overt about q1 with kind of a soft guy but

You know, that was all factored into our full year, and that's all factored into our full year guidance. But we aren't going to provide, you know, similar color. We felt like that was appropriate for Q1, just given the storms and some of the volatility. But I think as we go forward, as we said, we're going to continue to grow quarter over quarter.

Okay, perfect. And then as my follow-up, so Lilly is running a phase two with its GLIP skipper agonist for IBSC. Data might be in 20 seconds. I'm curious how you're thinking about that study and the durability of the Epsirella franchise. you know, over the long term in the 2030s, and we'll be well north of a billion dollars in revenue. Thanks so much.

Yeah, I mean, I think for us, what we need to do is follow the data. And anything that helps patients is a good thing. I think that is just a fundamental way that we and I look at this business. Anything that's going to help patients is the right thing to do. The realities are, if you look at the potential patients that could, should, or might be taking GLP-1, it's a relatively small percentage who actually are versus those who would benefit from it. So I wouldn't imagine there's going to be a massive degradation of the market, given the positioning that we have for Absrella in that market. I don't see that as a massive threat on the horizon. Is it better for patients if it works? Of course it is, and that's something we should all cheer.

Perfect. Thanks so much.

Thanks, Dennis.

And our next question comes from Chris Raymond from Raymond James. Please go ahead, Chris.

Hey, yeah, thanks. So we've talked to some KOLs who indicate they're already using Ibsrella to some extent in CIC. Mike, I know you're not going to want to give too much color here, but just maybe in broad strokes, can you guys talk maybe about what kind of CIC use you're seeing in the field I mean, Linzess, Trulance, Ameteza, they all have CIC on their labels already. So maybe the second part of that question is, would the competitive dynamic in this indication be maybe similar to what we've seen with IBSC, or are you thinking something different? Thanks.

So, yes. You know, what's important about what you said is all the others have dual indication. And clearly, we have heard and understand what you've described as well in your KOL clinician discussions. As you know, physicians in the art of what they practice can prescribe things off-label. We cannot promote things off-label, and we won't and don't. That is a fundamental part of this business, as everyone understands. If a physician feels it's appropriate for CIC, they should. And what's really interesting, if you haven't looked at Rome 5, which was just published, The changing definition of CIC, functional constipation, IBSC, which we know, given our experiences on the front lines, is a continuum of care. And understanding how the Rome Foundation has evolved its definitions is one of the fundamental reasons why we moved into the CIC program. It's a natural course. And I think as we've spoken over the years, would we have loved to have had both indications at launch? Of course. But as you know, I'm cheap and we didn't have the money to invest in both indications. And now that we are in a place that we can, we are to provide those benefits and try to eliminate some of the barriers in the way that physicians think about this and the further hurdles that the prior authorizations will put them through if it's an off-label indication. I agree with everything that is the genesis of your question. And I think what we're doing with the CIC program is specifically designed to address that, coupled with what's happened with Rome 5.

Thank you.

Thanks, Chris.

And our next question comes from Allison Abretzo from Piper Sandler and Company. Please go ahead, Allison.

Hi, this is Ashley on for Allie. Congrats on the quarter and all the progress made. So just two questions from us. You talked about it in your prepared remarks, but could you talk a little more about the Absrella pediatric trials and just the workings of the potential six months of additional patent life and how meaningful those additional six months could be for Absrella? And then also just wondering, once the IND is filed, do you have any line of sight into timelines around getting 531 into the clinic and how quickly do you plan to move if the IND studies are positive? Thank you.

We will work at pace if those studies are positive because it's the right thing to do. But fundamental again to what we do is we follow the data and all this pre-IND work is really critical for us to understand. Remember, actually let me remind you that when we created tenafinor back in 2009, It was based upon a huge amount of preclinical work that we had done to understand all aspects of where this molecule engages, starting with animal models and ultimately into man. So we have good experience in this, and there are very tried and true approaches that one takes in order to make the decision to or not to file an IND. And the data tell us what the right thing is to do. With regards to the pediatric indication, this is a tried and true practice that everyone does in the industry. One of the things that the FDA put in place was the Pediatric Act to encourage companies to develop drugs for the pediatric populations. Now, it is pretty hard in IBSC, given different age groups, the inability or challenge to describe pain. It's subjective. So it's a harder population. It's a smaller population. But the mere operational effort to put this in place, primarily to show safety, is one of the fundamental tenants of pediatric development is it allows you flexibility to treat the younger patients if you demonstrate the safety that we expect to demonstrate given our long history of the utility of this molecule. So the benefit of that six months, you look at whatever peak it is that you guys have modeled, just look at each incremental month of value that that will generate, and that will tell you the value in your modeling of what those six months are worth. It's significant.

Got it. Thank you for the call.

And our next question comes from Joseph Comey from TD Cowan. Please go ahead, Joseph.

Hi, there. Good afternoon, and thank you for taking my questions. Maybe a little bit of an extension of a prior question, but can you offer the physician touchpoint differences between CIC and IBS constipation? I guess if you are successful in CIC, would you need to go a little bit more maybe into a primary care segment or anything like that with your sales force? Or by the time they're presenting to the level of getting Ibsorol, they may be in a GI office. Anything around that would be helpful. Yeah, I'll ask Eric Thompson. Sorry, go ahead, Joe. No, and then you mentioned a couple times, obviously, on the call. Can you talk a little bit about the company's willingness to maybe lever up the balance sheet, given what your expectations are for the growth of the Pizzarella, to do something maybe a little bit larger in size?

Sure. Let me address the first one and ask Eric to comment, too, is, you know, I think as we said when we announced the Excel program is the CIC market is significantly larger. than the IBSC market. However, the vast majority of those patients are effectively treated with over-the-counter medication. So I think that's an important distinction as you look at the epi in these populations as to what the differences are and not get over your skis in terms of what that market sizing might be. Because it's an important distinction of those that are not served by OTC meds are the ones that end up going and being referred to other offices. And Eric, do you want to comment a little bit on what we would do in the field, if anything, in differences?

Yeah, thanks, Joe, for the question. So as you know, today, we focus on high-riding GIs, APPs, and high-riding non-GI. So that does put us in more of the primary care setting. I feel really confident about the targeting that we have right now for IBSC, and you can see a lot of the great momentum that we have. With regards to CIC, I do think you're correct. As Mike mentioned, it is a bit of a larger patient population, and we do see and expect more patients to be going to their primary care. So at some point, as we're continuing to look at that patient population and making sure that we have the right reach, we'll make that decision at that time. But certainly, I can see that there is more utilization in the primary care market. And that's something that we definitely will consider as we look at the right sizing of the team as we get closer to product being approved in the market.

And, Joe, I think a fundamental part of that is, you know, Eric has talked about this in the past, we call in 50% of the HCPs today that write for IBSC and, frankly, CIC-indicated drugs alike, and that's the 14,000 HCPs. The other 50% is 182,000 HCPs, and we're not going to cover them all, right? So it's going to be an optimization of those who might be writing disproportionately amount for CIC, which you can find through the data. But a little bit of a cautionary note not to take this as though we're going to double or treble the size of the organization, but rather an optimization as you've seen us do this year. With regards to levering the balance sheet, you know, we're at such an incredible pivotal time for the evolution of the company where not really reading between the lines, Sue has said explicitly, we're going to generate more top line than expense. So that journey that we're on, that horizon is not that far away with what we're trying to do. So I'll ask Sue to comment. I'm not sure how much leverage is needed versus execution here. in the way we're doing, but certainly we're not afraid of doing the right thing for opportunities that present themselves.

Yes, and as Joe, you heard that we already did do a refinance of our debt. We still have access to an extra $100 million of that loan, so we've got that. We've got plenty of options to do that if and when it's necessary or a great opportunity presents itself.

Great, thank you. Thanks, Joe.

And our next question comes from Laura Chico from Wedbush Securities. Please go ahead, Laura.

Thank you very much for taking the question. Three for me. First, I thought I heard Eric mention an expansion of the field manager level, and I'm just trying to understand if that's more impactful on the depth of prescribing or the breadth of prescribing, and which of those two levers impacts hitting the upper range of guidance or kind of impacts the guidance swing there. I have two quick follow-ups.

Yeah, thanks for the question, Laura. So I hate to say it, but both, actually. You know, it's very hard getting the physician to write that first prescription. And so we want to make sure when they write the prescription that they have confidence that it will be filled. And that's what the field reimbursement manager does. They work with the physician's office to ensure as they navigate the payer dynamics that they're able to pull through and get that prescription filled. With regards to physicians, as they continue to increase their depth of prescribing, that same confidence is important, that not just the first one goes through, but subsequent ones. So that team is really focused on helping prescriptions get pulled through, whether it's the first prescription or subsequent ones. I think you heard me say in my prepared remarks, we saw increase in riders as well as increase in depth of prescribing as well. So we are having impact across both of them. And that's why I kind of go to both of them to say that it's important to make it happen across both.

Laura, when Eric first started talking about hiring the skill set, one of the things that really opened my eyes is really a very simple example. If I'm the salesperson, I worry that that script is going to be filled. That's the way you're going to compensate me. So if I'm spending my time looking at Dr. Foster and whether or not that script is actually getting filled. I'm not calling on Dr. Rob because I'm worried about that. So bringing on the field access managers allows the ABDs to have confidence that they can drive the top of the funnel and that there will be those there to help pull through at the bottom of the funnel, resulting in compensation, ultimately an incentive comp, right? So it is, I don't think I would ever imagine not having both in the launch of a drug going forward.

Okay. And I guess two quick follow-ups and kind of related to that. I think in the prepared remarks, I heard that the EXPOSA paid rate was also up. Just curious if you could quantify that and then With respect to Excel, the site activation on the pre-identified sites has moved really rapidly. How are you monitoring, I guess, any conversation around quality checks that you can do to ensure you're getting sites to adhere to protocols and recruiting the right patients would be helpful, but also monitoring What are your assumptions around discontinuation rates?

Now, once the site is up and running, we don't pay any attention to it. No, you're right. I mean, for the quality of the patients is really, really important, right? And as you get the enthusiasm of startup, you know, there's training and reminding people of, you know, why you started at any clinical trial, you have screen failures that happen. And then the sites get better and better at identifying the patients. So that's just a natural progression of clinical development and recruitment. So Rajani, you know, a couple of weeks now onto the job is into this with both feet and both arms. And we all feel very good about both the quality of the sites as well as those sites learn. and get better at enrollment that we see those failure rates begin to taper, which is something you factor into your projections of how you enroll. So I think we all feel very good about what we've said and ultimately the quality of the patients are going to be there defined by our inclusion exclusion criteria. So feel very good about that quality that Rajni's team is ultimately in our CROs following through with. With regards to your first question, I think what's important is on a gap basis, of course, the year-over-year quarters look similar. It is so important what Sue reminded everyone of is that $3.8 million return reserve reversal that we did in Q1 should be excluded as you look at the base business that we've defined, which is a non-Medicare business, which grew by 19%. And if you look at our sequential growth, even since we started in this effort to not participate in Tdapa because we believe what we are now seeing is ultimately what was going to be true, is proving out. And the growth that we're seeing in that non-Medicare segment, with all the challenges dialysis organizations are facing, further emphasizes the value of this program and the product for patients who need phosphorus management. So it's an opaque and difficult business that we've chosen to partaken in the way that we have, but the numbers are showing that actually we're helping the patients that we anticipated that we would.

Thanks very much. Thanks, Lauren.

And our next question comes from Prakhar Agrawal from Cantor Fitzgerald. Please go ahead, Prakhar.

Hi, thank you for taking my questions and congrats on the quarter as well. Maybe firstly on Exposa, maybe I missed this, but I did not hear you reiterate the long-term guide of 750 million. I know the street is a little bit more conservative, but just wanted to check if you are reiterating that. And you talked about investing in high value opportunities as well. So has there been a change in the level of investments for Exposa this year and maybe in the future too? Secondly, maybe if you can talk about the growth to net for both products for 1Q and trends for the rest of the year. And last question, given the investments you are making both on the R&D side and SG&A, how should we think about the cash for profitability? Thank you.

Thanks, Prakash. That's a lot for me. So let's see if I can hit it all. In terms of the high-value opportunities with Exposa, yes, we ensure that Exposa continues to be a contributor. So we don't necessarily tease out separate product P&Ls, but rest assured, we continue to ensure that all of the spending that's done and the investments we make behind those patients and that growth makes them a financial contributor. So that's good. In terms of the GTN, you probably saw in what we filed, we're a little over 36.4% of GTN, and that's a blend. We don't necessarily list that out. And what I'd say is first quarter is going to be really probably your highest quarter in terms of GTN, just given all the dynamics with co-pay assistance, et cetera. So, and what we've always said before is it's about low 30s when you think about a blended total GTN rate for the year. So, but I would say that, you know, so you'll see that high in Q1 and then kind of taper off as we go into further quarters. Before I leave EXPOSA, yes, we will reiterate the 750, and I am reiterating that. So, within the guidance, we've given the billion for Azrella and the 750 for EXPOSA. In terms of R&D and SG&A, it was more around the expenses for the rest of the year. Yeah, so I would say, and with cash flow, it is something that we're continuing to monitor. As you can see with the top line guide, being, you know, 520 to 550 and our OPEX only at 520, you know, there is a possibility we'll get to a cash flow positivity. But certainly, we want to continue to see how the year unfolds and make sure that we're hitting on all cylinders. And then we will likely come back with an update if it's appropriate on cash flow.

And we appreciate the question of wanting trajectory quarter to quarter. But, you know, we're not going to get into the practice of quarter guidance. I think the yearly guidance that Sue just went through is really important.

Thank you so much.

And our next question comes from Matthew Caulfield from HC Wainwright. Please go ahead, Matthew.

Hi, thank you, guys. With the investor focus on sales execution, is there further granularity that you could share on Ipsrella growth between the new patient starts versus refill persistence trends, and then where things may stand presently for the total penetration among target prescribers there? Just, you know, thanks for any color there on execution overall.

Yeah, I think that's getting into detail that we probably wouldn't get into specifics on. You know, you can begin to look through your script data in terms of NRXs versus TRXs and tease that out to some extent with what you do. I recognize that it's going to be imperfect data. But, you know, suffice it to say with Eric's prepared remarks that we're seeing both You know, with the other question that was asked, breadth and depth. So, we're seeing great refills, and we're seeing lots of new prescriptions coming through as well.

Eric, anything to add? Okay. No. Thank you.

And our next question comes from Julian Harrison from BTIG. Please go ahead, Julian.

Hi. This is Andrew Cassin. I'm for Julian. Congratulations on the results this quarter, and thanks for taking our question. On Ibsrella, which of the growth drivers would you say do you believe still has the most room to grow, writers, new prescriptions, refill, or pull through? Thank you.

I think Eric will probably say yes to all of the above. I think what's interesting is, you know, for the 7 million prescriptions for IBSC indicated products that I referenced in my opening remarks, it's a very small percentage in the market that one needs to penetrate in order to get to our guidance.

of peak so there is massive opportunity out there and you know i think eric any granularity around the specifics would be great sure yeah i'm very excited about all of them as you list them so you know as we think about the umbrella opportunity as mike said you know there are seven million prescriptions written for ivsc on an annual basis and we continue to see that market grow we feel very confident in the position that we have winning positions sustainable over time that we've had for the past three years And we continue to see an increase in writers, total writers, new writers, as well as depth of prescribing. And that's really important. So what that tells you is physicians continue to have confidence in Ipsrella and look at it as a viable options for their patients that are in need. So, of those patients, we know that 77% continue to have symptoms despite treatment with the Secretagogue. So, very healthy market, strong position for Ipsrella, continuing to go riders, as well as depth of prescribing, and feel really good about the opportunity we have moving forward. When you think about the Ipsrella Pharmacy Network and being able to improve the fulfillment rate, as well as the number of refills for patients, It really leads to success across the business and those important drivers of the business. And that's really what gives us that confidence to that $1 billion in 2029 and beyond.

Thank you very much.

There are no further questions at this time. This now concludes today's conference call. Thank you for joining. You may now disconnect.