Q4 2025 Ardelyx Inc Earnings Call

February 19, 2026

Caitlin Lowie: Welcome to the Ardelyx Q4 2025 Earnings Conference. All participants will be in a listen-only mode. I would now like to turn the conference over to Caitlin Lowie, Vice President of Corporate Communications and Investor Relations. Caitlin, you may begin.

Operator: Welcome to the Ardelyx Q4 2025 Earnings Conference. All participants will be in a listen-only mode. I would now like to turn the conference over to Caitlin Lowie, Vice President of Corporate Communications and Investor Relations. Caitlin, you may begin.

Speaker #4: Caitlin, you may begin.

Speaker #2: Thank you. Good afternoon and welcome to our fourth-quarter and full-year 2025 financial results call. During this call, we will refer to the press release issued earlier today, which is available on the investor section of the company's website at ardelyx.com.

Caitlin Lowie: Thank you. Good afternoon, and welcome to our fourth quarter and full year 2025 financial results call. During this call, we will refer to the press release issued earlier today, which is available on the investor section of the company's website at ardelyx.com. Please note that we are also including a slide presentation to accompany today's remarks. You can view the material by accessing the webcast version of today's call on the investor section of ardelyx.com. During this call, we will be making forward-looking statements that are subject to risks and uncertainties. Our actual results may differ significantly from those described. We encourage you to review the risk factors in our most recent annual report on Form 10-K that will be filed today and can be found on our website at ardelyx.com.

Speaker #2: Please note that we are also including a slide presentation to accompany today's remarks. You can view the material by accessing the webcast version of today's call on the investor section of ardelyx.com.

Speaker #2: During this call, we will be making forward-looking statements that are subject to risks and uncertainties. Our actual results may differ significantly from those described.

Speaker #2: We encourage you to review the risk factors and our most recent annual report on Form 10-K that will be filed today and can be found on our website at ardelyx.com.

Speaker #2: While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change.

Caitlin Lowie: While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change. Our President and CEO, Mike Raab, will begin today's call with opening remarks followed by Eric Foster, Chief Commercial Officer, who will provide an update on the performance of IBSRELA and XPHOZAH. Dr. Laura Williams, our Chief Patient Officer and Interim Chief Medical Officer, will share an update on our recently announced development program before our Chief Financial Officer, Sue Hohenleitner, reviews the company's financial performance. We will then open the call to questions. With that, let me pass the call over to Mike.

Speaker #2: Our President and CEO, Mike Raab, will begin today's call with opening remarks, followed by Eric Foster, Chief Commercial Officer, who will provide an update on the performance of his drill and exposé.

Speaker #2: Dr. Laura Williams, our Chief Patient Officer and Interim Chief Medical Officer, will share an update on our recently announced development programs before our Chief Financial Officer, Sue Hohenleitner, reviews the company's financial performance.

Speaker #2: We will then open the call to questions. With that, let me pass the call over to Mike.

Speaker #3: Thank you, Caitlin, and good afternoon, everyone. It's great to be with all of you here today. 2025 was an extraordinary year for the company, and as a team, we delivered on every single one of our strategic priorities.

Mike Raab: Thank you, Caitlin, and good afternoon, everyone. It's great to be with all of you here today. 2025 was an extraordinary year for the company as the team delivered on every single one of our strategic priorities. That performance establishes a strong foundation for what we will accomplish in 2026. We will continue growing IBSRELA and XPHOZAH and execute on our growth initiatives. What was accomplished over these past 12 months is remarkable. We delivered on all four of our key strategic priorities, accelerating IBSRELA growth momentum, executing our XPHOZAH strategy, building a pipeline focused on addressing areas of unmet patient need, and delivering strong financial performance. First, IBSRELA has proven to be a critical growth engine for the company and is a powerful example of our disciplined execution and our conviction in the benefit that a first-in-class medicine can offer IBS-C patients.

Speaker #3: That performance establishes a strong foundation for what we will accomplish in 2026. We will continue growing Exposé and Umbrella and execute on our growth initiatives.

Speaker #3: What was accomplished over these past 12 months is remarkable. We delivered on all four of our key strategic priorities: accelerating umbrella growth momentum, executing on our exposé strategy, building a pipeline focused on addressing areas of unmet patient need, and delivering strong financial performance.

Speaker #3: First, umbrella has proven to be a critical growth engine for the company and is a powerful example of our disciplined execution and our conviction in the benefit that our first-in-class medicine can offer IBSC patients.

Speaker #3: Umbrella is now helping tens of thousands of patients evidenced by the incredible revenue growth of 73% compared to 2024 and 61% year-over-year growth in the fourth quarter.

Mike Raab: IBSRELA is now helping tens of thousands of patients, evidenced by the incredible revenue growth of 73% compared to 2024, and 61% year-over-year growth in Q4. Second, eighteen months ago, we made the decision to preserve access to XPHOZAH for all appropriate patients, as we recognized at a core foundational level that staying true to our principles and doing what's best for patients will result in doing what's best for the company. Today, I can tell you that our patient-first strategy is working. More patients now have access to XPHOZAH than ever before, and we're confident in our growth expectations. An additional development from just a few weeks ago was the issuance of a new patent for the commercial formulations of IBSRELA and XPHOZAH. That expires in 2042 and is now listed in the Orange Book at the FDA.

Speaker #3: Second, 18 months ago, we made the decision to preserve access to exposé for all appropriate patients as we recognize at a core foundational level the staying true to our principles and doing what was best for patients will result in doing what's best for the company.

Speaker #3: Today, I can tell you that our patient-first strategy is working. More patients now have access to exposé than ever before. And we're confident in our growth expectations.

Speaker #3: An additional development from just a few weeks ago was the issuance of a new patent for the commercial formulations of umbrella and exposé that expires in 2042 and is now listed in the Orange Book at the FDA.

Speaker #3: This patent is an important component of our strategy to create additional, valuable intellectual property to support umbrella and exposé. Our job is to maximize the value of these franchises by building a comprehensive IP portfolio and this patent is an important step in just doing that.

Mike Raab: This patent is an important component of our strategy to create additional valuable intellectual property to support IBSRELA and XPHOZAH. Our job is to maximize the value of these franchises by building a comprehensive IP portfolio, and this patent is an important step in just doing that. Third, we launched two development programs, which, along with our IBSRELA pediatric program, exemplify how we plan to build out our portfolio, develop and commercialize innovative medicines for patients with unmet needs that align with our long-term strategy.... leverage our internal core competencies that reflect thoughtful use of our financial resources to create durable, long-term shareholder value. In the fourth quarter, we announced that our Phase III programs expand the IBSRELA label to include chronic idiopathic constipation, or CIC.

Speaker #3: Third, we launched two development programs which, along with our umbrella pediatric program, exemplify how we plan to build out our portfolio. Develop and commercialize innovative medicine for patients with unmet needs that align with our long-term strategy, leverage our internal core competencies that reflect thoughtful use of our financial resources to create durable, long-term shareholder value.

Speaker #3: In the fourth quarter, we announced that our phase three program to expand the umbrella label to include chronic idiopathic constipation, or CIC. Assuming addition of this indication, umbrella would be better aligned with real-world prescribing habits.

Mike Raab: Assuming addition of this indication, IBSRELA would be better aligned with real-world prescribing habits, allowing us to be more comprehensive in our messaging, serve more patients, and increase the scale and the opportunity for IBSRELA. As well, we announced the commencement of a development program for our next-generation NHE3 inhibitor, RDX10531, which we refer to as 531. Building on our foundational expertise in NHE3 inhibition, 531 presents us with the opportunity to potentially extend our reach into new therapeutic areas. Finally, coupled with this extraordinary performance, is continued disciplined cash management and execution, resulting with ending 2025 in a stronger financial position than was the case at the end of 2024. We made bold, patient-centric decisions in complex market environments. We strengthened our leadership team to pursue our growth aspirations, and we've positioned Ardelyx for long-term growth and value creation.

Speaker #3: Allowing us to be more comprehensive in our messaging, serve more patients, and increase the scale and the opportunity for umbrella. As well, we announced the commencement of a development program for our next-generation NAT3 inhibitor, RDX-10531, which we refer to as 531.

Speaker #3: Building on our foundational expertise in NAT3 inhibition, 531 presents us with the opportunity to potentially extend our reach into new therapeutic areas. Finally, coupled with this extraordinary performance, is continued disciplined cash management and execution, resulting in ending 2025 in a stronger financial position than was the case at the end of 2024.

Speaker #3: We made bold, patient-centric decisions in complex market environments. We strengthened our leadership team to pursue our growth aspirations, and we've positioned Ardelyx for long-term growth and value creation.

Speaker #3: We are in a great position. I'm excited about where we're going and our ability to identify and capitalize on the opportunities ahead. In 2026, we will elevate our organization to even higher levels.

Mike Raab: We are in a great position. I'm excited about where we're going and our ability to identify and capitalize on the opportunities ahead. In 2026, we will elevate our organization to even higher levels. Our priorities haven't changed, but our expectations for them have. We're delivering on our vision for what the future of Ardelyx is becoming: a consequential, patient-centric enterprise built on a broad, thoughtful portfolio of best-in-class medicines. We are focused on significantly growing IBSRELA and maintaining XPHOZAH's momentum. With the guidance we shared in January, IBSRELA is clearly demonstrating its blockbuster potential and is on track to deliver $1 billion in revenue in 2029, with significant growth thereafter. IBSRELA is a powerful engine for the company. We are determined and extremely excited about our future and the many opportunities ahead.

Speaker #3: Our priorities haven't changed, but our expectations for them have. We're delivering on our vision for what the future of our deluxe is becoming: a consequential, patient-centric enterprise built on a broad, thoughtful portfolio of best-in-class medicines.

Speaker #3: We are focused on significantly growing Umbrella and maintaining Exposé momentum. With the guidance we shared in January, Umbrella is clearly demonstrating its blockbuster potential and is on track to deliver $1 billion in revenue in 2029, with significant growth thereafter.

Speaker #3: Umbrella is a powerful engine for the company. We are determined and extremely excited about our future and the many opportunities ahead. Our confidence is high and we have the leadership, the team, the strategy, and the urgency to execute and achieve these goals.

Mike Raab: Our confidence is high, and we have the leadership, the team, the strategy, and the urgency to execute and achieve these goals. With that, I'm turning the call to Eric, Laura, and Sue to walk you through specific drivers and our outlook in more detail. Eric?

Speaker #3: With that, I'm turning the call to Eric, Laura, and Sue to walk you through specific drivers and our outlook in more detail. Eric?

Speaker #4: Thank you, Mike. It's great to be with you all again. 2025 was an outstanding year. It was marked with incredible commercial execution and performance.

Eric Foster: Thank you, Mike. It's great to be with you all again. 2025 was an outstanding year. It was marked with incredible commercial execution and performance. We grew IBSRELA by more than 70% versus the prior year, with record highs across all key performance metrics. For XPHOZAH, we ensured patient access continued, and we increased total dispenses year over year. Our teams drove clinical conviction among ACPs, created greater brand awareness for patients, and ensured the prescriptions that were written were filled. We thoughtfully invested across the commercial organization to improve the patient and HCP journey and accelerate access to our medicines. Those investments turned into consistent quarter-over-quarter growth for both IBSRELA and XPHOZAH and set the stage for what will be an important growth year in 2026. Let me start with IBSRELA.

Speaker #4: We grew umbrella by more than 70% versus the prior year, with record highs across all key performance metrics. For exposé, we ensured patient access continued and we increased total dispenses year over year.

Speaker #4: Our teams drove clinical conviction among ACPs, created greater brand awareness for patients, and ensured the prescriptions that were written were filled. We thoughtfully invested across the commercial organization to improve the patient and ACP journey and accelerate access to our medicines.

Speaker #4: Those investments turned into consistent quarter-over-quarter growth for both Umbrella and Exposé and set the stage for what will be an important growth year in 2026.

Speaker #4: Let me start with umbrella. We reported an incredibly strong year in 2025, generating 73% growth over 2024. In Q4, we delivered our highest net revenue and strongest demand quarter since launch.

Eric Foster: We reported an incredibly strong year in 2025, generating 73% growth over 2024. In Q4, we delivered our highest net revenue and strongest demand quarter since launch. Our strategy is sound and led to record growth in 2025. IBSRELA is a first-in-class medicine with a winning and sustainable position among patients who continue to experience symptoms despite treatment with a secretagogue. There are many patients who continue to experience symptoms and need a different option. The IBS-C market is robust and continues to grow double digits, with nearly 7 million prescriptions written in 2025, an increase of 11% compared to 2024. As much as 77% of patients on a secretagogue report that they continue to experience symptoms despite treatment.

Speaker #4: Our strategy is sound and led to record growth in 2025. Umbrella is a first-in-class medicine with a winning and sustainable position among patients who continue to experience symptoms despite treatment with a secretagogue.

Speaker #4: And there are many patients who continue to experience symptoms and need a different option. The IBSC market is robust and continues to grow double digits with nearly 7 million prescriptions written in 2025, an increase of 11% compared to 2024.

Speaker #4: As much as 77% of patients on a secretagogue report that they continue to experience symptoms despite treatment. Our strategy, increasing depth and breadth of writing, strengthening our engagement with patients, and supporting prescription pull-through drove notable increases in new and total writers as well as new and refilled prescriptions.

Eric Foster: Our strategy, increasing depth and breadth of writing, strengthening our engagement with patients, and supporting prescription pull-through, drove notable increases in new and total writers, as well as new and refilled prescriptions. In Q4, we finished the year with a record high number of total writers and new and refilled prescriptions. We are confident we have the right levers to drive significant demand. To allow us to capture more of the IBS-C market in 2026 and well into the future, we are investing in three key areas. First, the prescriber continues to be a key focus. We continually optimize our field sales team to drive greater reach and frequency to with our target, high-writing healthcare providers who represent approximately 50% of the IBS-C total prescription market. That optimization allows us to continue to grow the prescriber base and expand the depth of prescribing.

Speaker #4: In the fourth quarter, we finished the year with a record high number of total writers and new and refilled prescriptions. We are confident we have the right levers to drive significant demand.

Speaker #4: To allow us to capture more of the IBSC market in 2026 and well into the future, we are investing in three key areas. First, the prescriber continues to be a key focus.

Speaker #4: We continually optimize our field sales team to drive greater reach and frequency with our target, high-writing healthcare providers who represent approximately 50% of the IBSC total prescription market.

Speaker #4: That optimization allows us to continue to grow the prescriber base and expand the depth of prescribing. Our in-market messaging remains focused on umbrella's differentiated mechanism of action and its strong clinical profile.

Eric Foster: Our end-market messaging remains focused on IBSRELA's differentiating mechanism of action and its strong clinical profile. Our message is resonating and driving HCPs to prescribe IBSRELA. Second, we're planning to double down on the high-impact investments we made last year to improve our prescription pull-through. We are increasing the presence of our field reimbursement managers, who support patient access and brought significant value to our performance last year. We will also be encouraging HCPs to send prescriptions to the IBSRELA Pharmacy Network, a limited group of specialty pharmacies that offer a patient-centric, high-touch experience, who are more equipped to handle prior authorizations and the payer hurdles that restrict patient access. When prescriptions go through a specialty pharmacy, fulfillment rates are higher, and we see, on average, an additional prescription per year for patients. This is a high-value opportunity that we will continue to invest in.

Speaker #4: Our message is resonating and driving HCPs to prescribe Umbrella. Second, we're planning to double down on the high-impact investments we made last year to improve our prescription pull-through.

Speaker #4: We are increasing the presence of our field reimbursement managers who support patient access and brought significant value to our performance last year. We will also be encouraging HCPs to send prescriptions to the Umbrella Pharmacy Network, a limited group of specialty pharmacies that offer a patient-centric, high-touch experience and are more equipped to handle prior authorizations and the payer hurdles that restrict patient access.

Speaker #4: When prescriptions go through a specialty pharmacy, fulfillment rates are higher, and we see, on average, an additional prescription per year for patients. This is a high-value opportunity that we will continue to invest in.

Speaker #4: And third, the patient. Patients with IBSC are highly active in their health, well-being, and condition. Our research has demonstrated that when patients are introduced to umbrella, our messaging of a different option to address their IBSC symptoms resonates and they are likely to ask their physician for umbrella.

Eric Foster: And third, the patient. Patients with IBS-C are highly active in their health, well-being, and condition. Our research has demonstrated that when patients are introduced to IBSRELA, our messaging of a different option to address their IBS-C symptoms resonates, and they are likely to ask their physician for IBSRELA. Taking that one step further, we also know that when a patient requests IBSRELA, the majority of the time, the healthcare provider is willing to write the prescription. This year, we are increasing our opportunities to engage directly with patients. Our plans are to educate, empower, and mobilize patients to take control of their IBS-C by seeking new information and talking to their doctor about the symptoms and the treatment options that are available. We continue to drive significant volume at a rapid pace by activating patients, deepening and broadening writing among target healthcare prescribers, and continually improving our prescription pull-through.

Speaker #4: Taking that one step further, we also know that when a patient requests umbrella, the majority of the time, the healthcare provider is willing to write the prescription.

Speaker #4: This year, we are increasing our opportunities to engage directly with patients. Our plans are to educate, empower, and mobilize patients to take control of their IBSC by seeking new information and talking to their doctor about the symptoms and the treatment options that are available.

Speaker #4: We continue to drive significant volume at a rapid pace by activating patients, deepening and broadening writing among target healthcare prescribers, and continually improving our prescription pull-through.

Speaker #4: We have the opportunity to further strengthen the value of the umbrella franchise with the addition of the investigational CIC indication. This label expansion, if approved, is expected to have a meaningful impact on our business and further strengthen HCP and patient confidence in umbrella.

Eric Foster: We have the opportunity to further strengthen the value of the IBSRELA franchise with the addition of the investigational CIC indication. This label expansion, if approved, is expected to have a meaningful impact on our business and further strengthen HCP and patient confidence in IBSRELA. Not only can it unlock the opportunity to help patients with CIC, but it would also allow us to further grow adoption among patients with IBS-C. These two conditions are closely associated, and the addition of CIC would allow HCPs to consider IBSRELA more closely aligned with how they typically manage patients. These efforts, along with the lack of novel competition currently in development, present a desirable market and an opportunity that can afford IBSRELA the ability to grow volume until we are faced with a generic entrant. I'm excited about the opportunities in front of us.

Speaker #4: Not only can it unlock the opportunity to help patients with CIC, but it would also allow us to further grow adoption among patients with IBSC.

Speaker #4: These two conditions are closely associated, and the addition of CIC would allow HCPs to consider 'umbrella' more closely aligned with how they typically manage patients.

Speaker #4: These efforts, along with the lack of novel competition currently in development, present a desirable market and an opportunity that can afford umbrella the ability to grow volume until we are faced with a generic entrant.

Speaker #4: I'm excited about the opportunities in front of us. We are united with a common purpose to help those impacted by IBSC, and we are committed to act with urgency to reach our true potential.

Eric Foster: We are united with a common purpose to help those impacted by IBS-C, and we are committed to act with urgency to reach our true potential. Moving on to XPHOZAH. In 2025, we had consistent growth quarter-over-quarter through the year. I'm proud of our team's ability to navigate the market while also improving patient access to its highest point since launch and increasing total dispenses by 9%, and paid dispenses by 41% when excluding Medicare compared to 2024. We are pleased with the performance in 2025 and confident in achieving the growth we expect in 2026. XPHOZAH will continue to be a contributor for Ardelyx, and our primary focus remains on supporting and ensuring access for all patients, regardless of insurance coverage.

Speaker #4: Moving on to exposé. In 2025, we had consistent growth quarter over quarter through the year. I'm proud of our team's ability to navigate the market while also improving patient access to its highest point since launch and increasing total dispenses by 9% and paid dispenses by 41% when excluding Medicare compared to 2024.

Speaker #4: We are pleased with the performance in 2025 and confident in achieving the growth we expect in 2026. Exposé will continue to be a contributor for our deluxe, and our primary focus remains on supporting and ensuring access for all patients, regardless of insurance coverage.

Speaker #4: We will continue to drive clinical conviction among healthcare providers for earlier utilization while also growing the prescriber base and expanding depth of prescribing. With the majority of patients treated with binders, not having fully controlled phosphorus, the high unmet need remains.

Eric Foster: We will continue to drive clinical conviction among healthcare providers for earlier utilization, while also growing the prescriber base and expanding depth of prescribing. With the majority of patients treated with binders not having fully controlled phosphorus, the high unmet need remains. We have an agile, high-performing, patient-focused team who is committed to unlocking the full potential of XPHOZAH and bringing this important medicine to patients in need. We are focused on broadening reach by continuing to expand access, employing targeted sales initiatives, and a cross-channel strategy to increase patient engagement. I have a tremendous amount of confidence in our ability to deliver on our priorities for this year. Everyone in the organization is executing at a high level and delivering our shared goals, from our commercial team to our clinical development, medical, manufacturing, and corporate teams.

Speaker #4: We have an agile, high-performing, patient-focused team who is committed to unlocking the full potential of Xphozah and bringing this important medicine to patients in need.

Speaker #4: We are focused on broadening reach by continuing to expand access, employing targeted sales initiatives, and a cross-channel strategy to increase patient engagement. I have a tremendous amount of confidence in our ability to deliver on our priorities for this year.

Speaker #4: Everyone in the organization is executing at a high level and delivering our shared goals. From our commercial team to our clinical development, medical, manufacturing, and corporate teams.

Speaker #4: We are investing across the commercial organization to strengthen our position in the market, support patients along their journey, and accelerate our growth momentum in the years ahead.

Eric Foster: We are investing across the commercial organization to strengthen our position in the market, support patients along their journey, and accelerate our growth momentum in the years ahead. I will now turn it over to Laura. Laura?

Speaker #4: I will now turn it over to Laura. Laura? Thank you, Eric. I'm really pleased to join you today. In addition to all the great work Eric shared with you in support of umbrella and exposé, I'm excited to talk about the progress we've made to advance our pipeline of new medicines to help patients.

Laura Williams: Thank you, Eric. I'm really pleased to join you today. In addition to all the great work Eric shared with you in support of IBSRELA and XPHOZAH, I'm excited to talk about the progress we've made to advance our pipeline of new medicines to help patients. While we've been conducting studies with tenapanor in pediatric patients with IBS-C as part of our post-approval commitments for IBSRELA since late 2022, our research and development teams have also been advancing two new programs, which signal an important inflection point for our company as part of our corporate growth strategy. As you know, IBSRELA and XPHOZAH were discovered and developed by scientists at Ardelyx. Their initial discovery efforts were aimed at treatments for IBS-C and began with evaluating potent, minimally systemically absorbed, selective NHE3 inhibitors that block sodium absorption in the gastrointestinal tract.

Speaker #4: While we've been conducting studies with Tinapinor and pediatric patients with IBSC as part of our post-approval commitments for umbrella since late 2022, our research and development teams have also been advancing two new programs which signal an important inflection point for our company as part of our corporate growth strategy.

Speaker #4: As you know, umbrella and exposé were discovered and developed by scientists at ARDELYX. Their initial discovery efforts were aimed at treatments for IBSC and began with evaluating potent, minimally systemically absorbed, selective NAG3 inhibitors that block sodium absorption in the gastrointestinal tract.

Speaker #4: Inhibition of NAG3 produced an increase in intestinal luminal water content and improved intestinal transit time. These efforts culminated in the discovery of Tinapinor, which was also shown to maintain intestinal barrier function and decrease visceral hypersensitivity in animal studies.

Laura Williams: Inhibition of NHE3 produced an increase in intestinal luminal water content and improved intestinal transit time. These efforts culminated in the discovery of tenapanor, which was also shown to maintain intestinal barrier function and decrease visceral hypersensitivity in animal studies. The clinical effect of this NHE3 inhibition was improvement in constipation and abdominal pain, as demonstrated in our clinical trials in patients with IBS-C, and that led to the approval of IBSRELA. Notably, it was also through these early studies with tenapanor that we uncovered the primary pathway for phosphorus absorption, the paracellular pathway, and tenapanor's ability to block phosphorus absorption via that pathway eventually led to the approval of XPHOZAH. And our recent pipeline programs resulted from our knowledge and expertise around NHE3 inhibition with tenapanor. First, let's start with the planned CIC labeled expansion.

Speaker #4: The clinical effect of this NAG3 inhibition was improvement in constipation and abdominal pain, as demonstrated in our clinical trials in patients with IBS-C, and that led to the approval of Ibsrela.

Speaker #4: Notably, it was also through these early studies with Tinapinor that we uncovered the primary pathway for phosphorus absorption, the paracellular pathway, and Tinapinor's ability to block phosphorus absorption via that pathway eventually led to the approval of exposé.

Speaker #4: And our recent pipeline programs resulted from our knowledge and expertise around NAG3 inhibition with Tinapinor. First, let's start with the planned CIC label expansion. As Eric mentioned, the addition of a CIC indication would better align umbrella with the standard treatment patterns that physicians use when diagnosing and treating patients with CIC and IBSC, which represent a continuum of functional gut disorders, whereby patients present with overlapping symptoms of constipation and abdominal pain, with the primary issue of having infrequent and difficult bowel movements.

Laura Williams: As Eric mentioned, the addition of a CIC indication would better align IBSRELA with the standard treatment patterns that physicians use when diagnosing and treating patients with CIC and IBS-C, which represent a continuum of functional gut disorders whereby patients present with overlapping symptoms of constipation and abdominal pain, with the primary issue of having infrequent and difficult bowel movement. The main distinction between the two conditions is that in addition to constipation, IBS-C is also characterized by abdominal pain, often accompanied by other abdominal symptoms like bloating, cramping, and discomfort. However, the reality for many patients is that they often alternate between the two conditions and therefore might be diagnosed with either one over time. The need for treatments with different mechanisms of action has proven essential for the management of IBS-C, and we believe this holds true for CIC as well.

Speaker #4: The main distinction between the two conditions is that in addition to constipation, IBSC is also characterized by abdominal pain, often accompanied by other abdominal symptoms like bloating, cramping, and discomfort.

Speaker #4: However, the reality for many patients is that they often alternate between the two conditions, and therefore might be diagnosed with either one over time.

Speaker #4: The need for treatments with different mechanisms of action has proven essential for the management of IBSC, and we believe this holds true for CIC as well.

Speaker #4: We're confident in Tinapinor's ability to manage patients with CIC, and we have designed a robust clinical trial to support this hypothesis.

Laura Williams: We're confident in tenapanor's ability to manage patients with CIC, and we have designed a robust clinical trial to support this hypothesis. Why are we confident? First, in our clinical development program for IBS-C, the TEMPO studies, we demonstrated tenapanor's ability to safely and effectively treat adults with IBS-C, which is typically considered the more challenging condition. Secondly, in a post-hoc analysis of that TEMPO data, looking at just the constipation component, tenapanor showed a significantly better durable, complete spontaneous bowel movement, or CSBM, responder rate compared to placebo. And finally, we've had very productive discussions with the FDA and are encouraged that the strong safety package from our IBS clinical studies, when combined with the safety and efficacy results we expect to establish from a single Phase III clinical trial, will be sufficient to support a supplemental new drug application, or sNDA.

Speaker #4: Why are we confident? First, in our clinical development program for IBSC, the TIMPO studies, we demonstrated Tinapinor's ability to safely and effectively treat adults with IBSC, which is typically considered the more challenging condition.

Speaker #4: Secondly, in a post-hoc analysis of that TIMPO data, looking at just the constipation component, Tenapanor showed a significantly better durable, complete, spontaneous bowel movement, or CSBM, responder rate compared to placebo.

Speaker #4: And finally, we've had very productive discussions with the FDA and are encouraged that the strong safety package from our IBS clinical studies, when combined with the safety and efficacy results we expect to establish from a single Phase 3 clinical trial, will be sufficient to support a supplemental new drug application, or sNDA.

Speaker #4: Last month, we enrolled, randomized, and dosed our first patient in a cell. The Phase 3 clinical trial evaluates the safety and efficacy of Tinapinor in adults with CIC.

Laura Williams: Last month, we enrolled, randomized, and dosed our first patient in ACCEL, the phase III clinical trial that evaluates the safety and efficacy of tenapanor in adults with CIC. ACCEL is a randomized, double-blind, placebo-controlled clinical trial with a planned enrollment of approximately 700 patients across 110 sites in the US, of which more than half are already up and running. Patients will be randomized into one of four treatment groups, which include three different tenapanor doses, and the placebo group, with each active dose group randomized in a 3-to-1 manner versus placebo. The study is comprised of a 2-week screening period, a 26-week randomized treatment period, and a 4-week follow-up safety period.

Speaker #4: A Cell is a randomized, double-blind, placebo-controlled clinical trial with a planned enrollment of approximately 700 patients across 110 sites in the US, of which more than half are already up and running.

Speaker #4: Patients will be randomized into one of four treatment groups, which include three different Tinapinor doses and the placebo group, with each active dose group randomized in a three-to-one manner versus placebo.

Speaker #4: The study is comprised of a two-week screening period, a 26-week randomized treatment period, and a four-week follow-up safety period. Our primary endpoint is measured at week 12 and will be the proportion of patients who achieve a durable CSBM response, defined as an increase from baseline of at least one in average weekly CSBM frequency and at least three CSBMs, both occurring during the same week.

Laura Williams: Our primary endpoint is measured at week 12 and will be the proportion of patients who achieve a durable CSBM response, defined as an increase from baseline of at least one in average weekly CSBM frequency and at least three CSBMs, both occurring during the same week. Additional information about ACCEL, including key secondary endpoints and evaluation of safety, can be found on clinicaltrials.gov. We have a thoughtful, comprehensive recruitment plan and expect to have the study fully enrolled by the end of this year. That timeline allows us to complete data analysis and report top-line results in the second half of next year, with subsequent sNDA filing shortly thereafter. This is a well-designed clinical trial with a strategic regulatory path that will hopefully allow us to ultimately bring this therapeutic option to patients. Now, moving on to our next-generation NHE3 inhibitor, 531.

Speaker #4: Additional information about a cell including key secondary endpoints and evaluation of safety can be found on clinicaltrials.gov. We have a thoughtful, comprehensive recruitment plan and expect to have the study fully enrolled by the end of this year.

Speaker #4: That timeline allows us to complete data analysis and report top-line results in the second half of next year, with subsequent SNDA filing shortly thereafter.

Speaker #4: This is a well-designed clinical trial with a strategic regulatory path that will hopefully allow us to ultimately bring this therapeutic option to patients. Now, moving on to our next-generation NAG3 inhibitor, 531.

Speaker #4: As leaders and entrepreneurs in this space, we're excited about NAG3 inhibition, and I'd like to first provide some scientific background. Sodium hydrogen exchangers, or NHEs, are transport proteins called antiporters that reside on the membrane of cells, and there are nine distinct isoforms or subgroups.

Laura Williams: As leaders and entrepreneurs in this space, we're excited about NHE3 inhibition, and I'd like to first provide some scientific background. Sodium hydrogen exchangers, or NHEs, are transport proteins called antiporters that reside on the membrane of cells, and there are nine distinct isoforms or subgroups. Their fundamental role is to maintain normal sodium, water, and pH balance in our cells. NHE3 is an antiporter that is found in the gut, primarily the small and large intestine, as well as the kidney. It transports sodium into the cell and hydrogen out of the cell, thereby regulating sodium absorption, maintaining body salt and fluid balance, and blood pressure homeostasis. In preclinical studies, 531 was approximately 10 times more potent and 30 times more soluble than tenapanor. Those improvements alone not only support the potential for once-daily dosing, but may also provide more opportunities across different therapeutic areas.

Speaker #4: They're fundamental role is to maintain normal sodium, water, and pH balance in our cells. NHE3 is an antiporter that is found in the gut, primarily the small and large intestine, as well as the kidney.

Speaker #4: It transports sodium into the cell and hydrogen out of the cell, thereby regulating sodium absorption, maintaining body salt and fluid balance, and blood pressure homeostasis.

Speaker #4: In preclinical studies, 531 was approximately 10 times more potent and 30 times more soluble than Tinapinor. Those improvements alone not only support the potential for once-daily dosing, but may also provide more opportunities across different therapeutic areas.

Speaker #4: So where does that take us? Right now, we're focused on finalizing our preclinical studies to support an IND submission in the second half of this year, with plans for a Phase 1 first-in-human safety trial to begin shortly thereafter.

Laura Williams: So where does that take us? Right now, we're focused on finalizing our preclinical studies to support an IND submission in the second half of this year, with plans for a phase I first-in-human safety trial to begin shortly thereafter. Additionally, we will continue to conduct preclinical research to further inform strategies for our clinical development programs, and we will continue to follow where the science and data lead. I am very excited about the potential for tenapanor as a treatment option for adult patients with CIC and the opportunities that 531 may offer across several therapeutic areas. These clinical development activities not only bolster the growth of our company, but equally and perhaps more importantly, they continue to expand our efforts to make a positive impact in the lives of patients, families, and caregivers, and the healthcare providers who help manage their care.

Speaker #4: Additionally, we will continue to conduct preclinical research to further inform strategies for our clinical development programs, and we will continue to follow where the science and data lead.

Speaker #4: I am very excited about the potential for Tinapinor as a treatment option for adult patients with CIC and the opportunities that 531 may offer across several therapeutic areas.

Speaker #4: These clinical development activities not only bolster the growth of our company, but equally and perhaps more importantly, they continue to expand our efforts to make a positive impact in the lives of patients, families, and caregivers, and the healthcare providers who help manage their care.

Speaker #4: I look forward to sharing additional updates in the months ahead. With that, I will now pass it to Sue.

Laura Williams: I look forward to sharing additional updates in the months ahead. With that, I will now pass it to Sue.

Speaker #2: Thank you, Laura. Four months ago, I joined Ardelyx as it was clear to me that I had a unique and incredible opportunity to become part of building a great company, helping patients, and creating real value for shareholders.

Sue Hohenleitner: Thank you, Laura. Four months ago, I joined Ardelyx as it was clear to me that I had a unique and incredible opportunity to become part of building a great company, helping patients, and creating real value for shareholders. On one of my first days at Ardelyx, I heard Dr. Laura deliver a powerful message that resonated deeply with me: the patients are waiting. To me, that phrase reflects urgency, purpose, and accountability. When we deliver with excellence for patients, shareholder value creation follows. Since October, my conviction has only gotten stronger that we are at a turning point for our company's future. We are turning our commercial momentum into a multibillion-dollar opportunity, a once sparse pipeline into a robust development portfolio, and a strong organization into an extraordinary one by elevating our game and building the capabilities required to compete and win.

Speaker #2: On one of my first days at ARDELYX, I heard Dr. Laura deliver a powerful message that resonated deeply with me. The patients are waiting.

Speaker #2: To me, that phrase reflects urgency, purpose, and accountability. When we deliver with excellence for patients, shareholder value creation follows. Since October, my conviction has only gotten stronger that we're at a turning point for our company's future.

Speaker #2: We are turning our commercial momentum into a multibillion-dollar opportunity—a once-sparse pipeline into a robust development portfolio—and a strong organization into an extraordinary one by elevating our game and building the capabilities required to compete and win.

Speaker #2: Furthermore, we're turning disciplined capital allocation into a clear strategic advantage and investing with purpose. This is more than progress. We are turning a critical corner as we drive towards profitability and meaningful cash flow generation, allowing us to strengthen our balance sheet, fund our ambitions, and build long-term shareholder value.

Sue Hohenleitner: Furthermore, we're turning a disciplined capital allocation into a clear strategic advantage and investing with purpose. This is more than progress. We are turning a critical corner as we drive towards profitability and meaningful cash flow generation, allowing us to strengthen our balance sheet, fund our ambitions, and build long-term shareholder value. Now let me walk you through the financials... For 2025 results, I'll be focusing my commentary on the full year performance. However, you can see the fourth quarter results on the slide and in the press release we issued earlier this afternoon. We had significant year-over-year total revenue growth of 22%, with full year 2025 revenues of $407.3 million, compared to $333.6 million in 2024.

Speaker #2: Now let me walk you through the financials. For 2025 results, I'll be focusing my commentary on the full-year performance, however, you can see the fourth-quarter results on the slide and in the press release we issued earlier this afternoon.

Speaker #2: We had significant year-over-year total revenue growth of 22%, with full-year 2025 revenues of $407.3 million compared to $333.6 million in 2024. That growth was driven by a significant increase in its relative demand, which grew revenues to $274.2 million and increased of 73% compared to the full year of 2024, and finishing 2025 at the upper end of our most recent guidance range.

Sue Hohenleitner: That growth was driven by a significant increase in XPHOZAH demand, which grew revenues to $274.2 million, an increase of 73% compared to the full year of 2024, and finishing 2025 at the upper end of our most recent guidance range. As Eric outlined, that growth was driven by increases in total prescription volume. We also recorded $103.6 million of XPHOZAH revenue in 2025, compared to $160.9 million in 2024, a decrease of 36%. As you know, as of 1 January 2025, we no longer receive Part D reimbursement for Medicare patients, who represent roughly 60% of the total XPHOZAH patient base.

Speaker #2: As Eric outlined, that growth was driven by increases in total prescription volume. We also recorded $103.6 million of exposure revenue in 2025, compared to $160.9 million in 2024, a decrease of 36%.

Speaker #2: As you know, as of January 1, 2025, we no longer receive Part D reimbursement for Medicare patients, who represent roughly 60% of the total exposure patient base.

Speaker #2: However, our focus on protecting patient access, driving clinical conviction, and supporting prescription pull-through drove year-over-year growth in total dispenses by 9%, and we grew paid dispenses by 41% when excluding Medicare.

Sue Hohenleitner: However, our focus on protecting patient access, driving clinical conviction, and supporting prescription pull-through drove year-over-year growth in total dispenses by 9%, and we grew paid dispenses by 41% when excluding Medicare. We are tremendously proud of the efforts made this year to advance our objective that every patient prescribed XPHOZAH receives XPHOZAH, regardless of their coverage. Now turning to expenses. Research and development expenses for 2025 were $71.5 million, compared to $52.3 million in the prior year. This increase reflects development activities for our ongoing pediatric trials, as well as the ACCEL trial for CIC, preclinical research activities for the 531 program, and increased medical engagement with the scientific community.

Speaker #2: We are tremendously proud of the efforts made this year to advance our objective that every patient prescribed exposure received exposure, regardless of their coverage.

Speaker #2: Now turning to expenses. Research and development expenses for 2025 were $71.5 million, compared to $52.3 million in the prior year. This increase reflects development activities for our ongoing pediatric trials, as well as the Excel trial for CIC, preclinical research activities for the 531 program, and increased medical engagement with the scientific community.

Speaker #2: Selling general and administrative expenses were $337.2 million for the full year 2025 compared to $258.7 million in 2024. The increase was primarily related to continued investments to drive demand and adoption of Entrella.

Sue Hohenleitner: Selling, general, and administrative expenses were $337.2 million for the full year 2025, compared to $258.7 million in 2024. The increase was primarily related to continued investments to drive demand and adoption of XPHOZAH. Our net loss for the full year 2025 was $61.6 million, or $0.26 per share, compared to a net loss of $39.1 million or $0.17 per share for the full year of 2024. The net loss for 2025 includes $49 million for non-cash expenses from share-based compensation, compared to $37.4 million in 2024.

Speaker #2: Our net loss for the full year 2025 was $61.6 million or $26 per share compared to a net loss of $39.1 million or $0.17 per share for the full year of 2024.

Speaker #2: The net loss for 2025 includes $49 million for non-cash expenses from share-based compensation compared to $37.4 million in 2024. We finished 2025 in a strong cash position with $264.7 million in total cash, cash equivalents, and short-term investments, an increase from $250.1 million at the end of 2024.

Sue Hohenleitner: We finished 2025 in a strong cash position, with $264.7 million in total cash, cash equivalents, and short-term investments, an increase from $250.1 million at the end of 2024. We now have had two consecutive quarters that we generated positive cash flow due to growing revenue. Now turning to guidance for 2026. First, looking at our revenue projections for Xarelto, we continue to anticipate 2026 revenues for Xarelto to be between $410 and 430 million. That represents at least 50% year-over-year growth at the low end of the guidance range. Similar to 2025, we expect growth to be driven by quarter-over-quarter increases in demand, along with improved prescription pull-through.

Speaker #2: We now have had two consecutive quarters that we generated positive cash flow due to growing revenue. Now, turning to guidance for 2026. First, looking at our revenue projections for Entrella, we continue to anticipate 2026 revenues for Entrella to be between $410 and $430 million.

Speaker #2: That represents at least 50% year-over-year growth at the low end of the guidance range. Similar to 2025, we expect growth to be driven by quarter-over-quarter increases in demand, along with improved prescription pull-through.

Speaker #2: As for the phasing of revenue, we expect the overall market dynamics in 2026 to be similar to those we saw last year. As we've shared in the past, the IBSC market historically contracts in the first quarter due to copay resets, insurance changes, and prior authorization renewals, among other factors.

Sue Hohenleitner: As for the phasing of revenue, we expect the overall market dynamics in 2026 to be similar to those we saw last year. As we've shared in the past, the IBS-C market historically contracts in the first quarter due to co-pay resets, insurance changes, and prior authorization renewals, among other factors. We expect those factors to similarly impact Q1 of 2026, in addition to the recent winter storm, Fern, that affected a large portion of the country. As in prior years, we expect the market to rebound in the second quarter. Using 2025 as a proxy, we recorded approximately 16% of the full year IBSRELA revenues in the first quarter, and we anticipate that 2026 will likely follow a similar pattern.

Speaker #2: We expect those factors to similarly impact Q1 of 2026 in addition to the recent winter storm fern that affected a large portion of the country.

Speaker #2: As in prior years, we expect the market to rebound in the second quarter. Using 2025 as a proxy, we recorded approximately 16% of the full-year Entrella revenues in the first quarter, and we anticipate that 2026 will likely follow a similar pattern.

Speaker #2: 2026 growth will be supported by thoughtful investments that will also fuel continued growth to $1 billion in 2029, representing a CAGR of 38%.

Sue Hohenleitner: 2026 growth will be supported by thoughtful investments that will also fuel continued growth to $1 billion in 2029, representing a CAGR of 38%. We expect growth to be driven thereafter by continued adoption of IBSRELA among IBS-C patients, as well as growth from patients with CIC, assuming approval and market launch of tenapanor for CIC. And to build on Mike's comments earlier regarding the new formulation patent, we recognize that there's an opportunity to see IBSRELA growth continue even beyond 2033, when our composition of matter patent expires. IBSRELA will have the same winnable position, and we anticipate volume growth to continue until we face generic competition. Now turning to XPHOZAH. We expect revenues to be between $110 million and $120 million in 2026.

Speaker #2: We expect growth to be driven thereafter by continued adoption of Entrella among IBSC patients as well as growth from patients with CIC, assuming approval and market launch up to NAPINOR for CIC.

Speaker #2: And to build on Mike's comments earlier regarding the new formulation patent, we recognize that there's an opportunity to see Entrella growth continue even beyond 2033, when our composition of matter patent expires.

Speaker #2: Entrella will have the same winnable position, and we anticipate volume growth to continue until we face generic competition. Now, turning to exposure. We expect revenues to be between $110 million and $120 million in 2026.

Speaker #2: We're focusing on driving depth and breadth of exposure prescribing and investing at an appropriate level to ensure that exposure remains a financial contributor for our deluxe.

Sue Hohenleitner: We're focusing on driving depth and breadth of XPHOZAH prescribing and investing at an appropriate level to ensure that XPHOZAH remains a financial contributor for Ardelyx. We expect that XPHOZAH will experience similar market dynamics in Q1 as Xarelto. We are reaffirming our expectations of $750 million before the expiration of the XPHOZAH method of use patent in 2034. And as is the case with Xarelto, XPHOZAH growth is expected to continue until we face generic competition. Just a note on our gross to net deduction rates. We expect our future GTNs for Xarelto and XPHOZAH to be similar to the results we saw in 2025, which were in line with our expectations. Two of our key priorities for 2026 are to deliver, to deliver commercial growth and to advance our pipeline, which requires high-impact investments in R&D and SG&A.

Speaker #2: We expect that Exposure will experience similar market dynamics in the first quarter as Entrella. We are reaffirming our expectations of $750 million before the expiration of the Exposure method of use patent in 2034.

Speaker #2: And as is the case with Entrella, exposure growth is expected to continue until we face generic competition. Just a note on our growth to net deduction rates.

Speaker #2: We expect our future GTNs for Entrella and exposure to be similar to the results we saw in 2025, which were in line with our expectations.

Speaker #2: Two of our key priorities for 2026 are to deliver commercial growth and to advance our pipeline, which requires high-impact investments in R&D and SG&A.

Speaker #2: With that said, we expect overall 2026 operating expenses, inclusive of R&D and SG&A, to increase by approximately 25%, for a total OPEX of up to $520 million.

Sue Hohenleitner: With that said, we expect overall 2026 operating expenses, expenses inclusive of R&D and SG&A, to increase by approximately 25% for a total OpEx of up to $520 million. We are continuing to fuel the pipeline, and with that comes increased investments in R&D, reflecting both the ACCEL Phase 3 trial for tenapanor and planning for a Phase 1 trial for five thirty-one, along with other expenses to support our engagement with the scientific community. We also expect SG&A to grow to support a disciplined investment approach to drive IBSRELA growth through commercial execution, improved prescription pull-through, and patient engagement. These high ROI investments reflect areas of growth in 2026 and will generate momentum to deliver on our longer-term IBSRELA guidance expectations, as well as our planned pipeline expansion.

Speaker #2: We are continuing to fuel the pipeline, and with that comes increased investments in R&D, reflecting both the Excel phase three trial for Tinapinor and planning for a phase one trial for 531, along with other expenses to support our engagement with the scientific community.

Speaker #2: We also expect SG&A to grow to support a disciplined investment approach to drive Entrella growth through commercial execution, improved prescription pull-through, and patient engagement.

Speaker #2: These high ROI investments reflect areas of growth in 2026 and will generate momentum to deliver on our longer-term Entrella guidance expectations as well as our planned pipeline expansions.

Speaker #2: Our strong cash position of $265 million supported by the significant revenue growth we expect is sufficient to cover all of our planned operating expenses and allow us to reach consistent, positive cash flow with our current operations.

Sue Hohenleitner: Our strong cash position of $265 million, supported by the significant revenue growth we expect, is sufficient to cover all of our planned operating expenses and allow us to reach consistent, positive cash flow with our current operations. We remain focused on thoughtful capital allocation throughout this year as we prioritize growing the top line and further advancing our pipeline. Before I turn the call back to Mike, I want to say how proud I am to be here representing Ardelyx for my first earnings call as our CFO. I am both excited and optimistic about the future and the tremendous value we will create as a team for patients and for you, our shareholders. With that, I'll hand it back to Mike.

Speaker #2: We remain focused on thoughtful capital allocation throughout this year as we prioritize growing the top line and further advancing our pipeline. Before I turn the call back to Mike, I want to say how proud I am to be here representing our deluxe for my first earnings call as our CFO.

Speaker #2: I am both excited and optimistic about the future and the tremendous value we will create as a team for patients and for you, our shareholders.

Speaker #2: With that, I'll hand it back to Mike.

Speaker #1: Thank you, Sue. And I'm thrilled to welcome you to these calls. Your perspective further strengthens our confidence as we communicate the clear growth trajectory that we're on.

Mike Raab: Thank you, Sue, and I'm thrilled to welcome you to these calls. Your perspective further strengthens our confidence as we communicate the clear growth trajectory that we're on. As you heard from Eric, Laura, and Sue, our priorities are focused and execution-driven, significantly grow IBSRELA, maintain XPHOZAH momentum, further advance our pipeline, and continue delivering strong financial results. We are moving with urgency and discipline against these priorities, and we look forward to demonstrating continued progress as the year unfolds. With that, we'll open the call to questions. Operator?

Speaker #1: As you heard from Eric, Laura, and Sue, our priorities are focused and execution-driven. Significantly grow Entrella, maintain exposure momentum, further advance our pipeline, and continue delivering strong financial results.

Speaker #1: We are moving with urgency and discipline against these priorities, and we look forward to demonstrating continued progress as the year unfolds. With that, we'll open the call to questions.

Speaker #1: Operator?

Speaker #3: Thank you. If you would like to ask a question, please press star one on your telephone keypad now. You'll be placed into the queue in the order received.

Operator: Thank you. If you would like to ask a question, please press star one on your telephone keypad now. You'll be placed into the queue in the order received. Please be prepared to ask your question when prompted. Once again, if you have a question, please press star one on your phone now. Our first question will come from Dennis with Jefferies and Company.

Speaker #3: Please be prepared to ask your question when prompted. Once again, if you have a question, please press star one on your phone now. And our first question will come from Dennis with Jefferies & Company.

[Analyst] (Jefferies): Hi, this is Anthea on for Dennis. Thank you for taking our questions. Could you talk about your level of confidence on the underlying volume growth for IBSRELA to get to your $410 to $430 million IBSRELA guidance? What's really driving that outside of big TAM? And, how much of that guidance assumes improvements on the pull-through and the shift to specialty pharmacies? Thank you.

Speaker #4: Hi, this is Anthea on for Dennis. Thank you for taking our questions. Could you talk about your level of confidence on the underlying volume growth for Entrella to get to your 410 and 430 million Entrella guidance?

Speaker #4: What's really driving that outside of big TAM and how much of that guidance assumes improvements on the pull-through and the shift to specialty pharmacies?

Speaker #4: Thank you.

Speaker #1: Yeah, first let me address it from a top line. We wouldn't give you the guidance if we didn't have great confidence in reaching that number.

Mike Raab: Yeah. First, let me address it from a top line. We wouldn't give you the guidance if we didn't have great confidence in reaching that number. You know, as we've talked over the years, Anthea, and with Dennis, is you look at the size of this market and the number of patients that are needing a new alternative versus what they have with secretagogues. There's a vast patient population out there to, tap to access this. So our confidence is significant and, and hasn't wavered, honestly. Eric, if you can address some of that too.

Speaker #1: As we've talked over the years and with Dennis, you look at the size of this market and the number of patients that are needing a new alternative versus what they have with secretogogues, there's a vast patient population out there to tap to access this.

Speaker #1: So our confidence is significant, and it hasn't wavered, honestly. Eric, if you can address some of that too.

Speaker #5: Yeah, thanks very much for the question. As Mike said, we've got tremendous confidence in the guidance that we've given for 2026. In order to drive volume, we're continuing to optimize our sales force.

Eric Foster: Yeah. Thanks very much for the question. As Mike said, we've got tremendous confidence in the guidance that we've given for 2026. You know, in order to drive volume, we're continuing to optimize our sales force. Last year, the team did an excellent job in execution, was able to drive to 73% growth, and we'll continue to optimize that so they can drive top of the funnel. As Mike said, 77% of the patients out there on a secretagogue are currently continuing to experience symptoms. So we know that the market's there. As it relates to pull-through, we are going to double our field reimbursement manager team.

Speaker #5: Last year, the team did an excellent job in execution, was able to drive to 73% growth, and we'll continue to optimize that so they can drive top of the funnel.

Speaker #5: As Mike said, 77% of the patients out there on a secretogogue are currently continuing to experience symptoms. So we know that the market's there.

Speaker #5: As it relates to pull-through, we are going to double our field reimbursement manager team. We know that they provided significant value to us last year.

Eric Foster: We know that they provided significant value to us last year in IBSRELA, to increase in approvals and resubmission rates, so we know that we can continue to improve there, and we've got a team that's gonna expand and be focused there. With regards to the IBSRELA Pharmacy Network, we're really excited about this opportunity. It's actually something that we started to work on towards the end of last year, and we know that these patients, they need high touch and a more patient-centric option than going to a retail pharmacy. So what we've put in place is the opportunity for them to get the care that they need, to work closely with them and the physicians to make sure that we get a higher rate of fulfillment.

Speaker #5: In relates to increase and improvements and resubmission rates, so we know that we can continue to improve there, and we've got a team that's going to expand and be focused there.

Speaker #5: With regards to the Entrella pharmacy network, we're really excited about this opportunity. It's actually something that we started to work on towards the end of last year, and we know that these patients, they need high-touch and a more patient-centric option than going to a retail pharmacy.

Speaker #5: So, what we've put in place is the opportunity for them to get the care that they need, to work closely with them and the physicians to make sure that we get a higher rate of fulfillment.

Speaker #5: So when you think about all those three things together, we feel really good about 2026 and what we're going to be able to deliver.

Eric Foster: So when you think about all those three things together, we feel really good about 2026 and what we're gonna be able to deliver.

Speaker #4: Great. Thank you.

[Analyst] (Jefferies): Great. Thank you.

Speaker #1: Thanks, Anthea.

Mike Raab: Thanks, Anthea.

Speaker #3: And our next question will come from Allison with Piper Sandler.

Operator: Our next question will come from Allison with Piper Sandler.

Speaker #6: Hey, good afternoon, and thanks for taking the question. First, just for Sue, following up on some of the prepared remarks on expenses, could you provide any more color on the cadence of the R&D and SG&A step-ups for '26? And just with those increases, how should we be thinking about the path forward or the path toward sustained cash flow positivity?

Sue Hohenleitner: Hey, good afternoon, and thanks for taking the question. First, just for Sue, following up on some of the prepared remarks on expenses, just, you know, could you provide any more color on the cadence of the R&D and SG&A step-ups for 2026? And just with those increases, you know, how should we be thinking about the path forward or the path toward sustained cash flow positivity? And then just on, you know, the $410 to $430 million guidance for this year, going to $1 billion for IBSRELA in 2029, do you feel your existing commercial infrastructure is sufficient for hitting that longer-term guidance? Or just how should we be thinking about incremental investments on that front? Thank you. Yeah. Thank you, Allison.

Allison Bratzel: Hey, good afternoon, and thanks for taking the question. First, just for Sue, following up on some of the prepared remarks on expenses, just, you know, could you provide any more color on the cadence of the R&D and SG&A step-ups for 2026? And just with those increases, you know, how should we be thinking about the path forward or the path toward sustained cash flow positivity? And then just on, you know, the $410 to $430 million guidance for this year, going to $1 billion for IBSRELA in 2029, do you feel your existing commercial infrastructure is sufficient for hitting that longer-term guidance? Or just how should we be thinking about incremental investments on that front? Thank you.

Speaker #6: And then just on the 410 to 430 million guidance for this year, going to 1 billion for Entrella in '29, do you feel your existing commercial infrastructure is sufficient for hitting that longer-term guidance or just how should we be thinking about incremental investment on that front?

Speaker #6: Thank you.

Speaker #4: Yeah, thank you, Allison. I'll start out with your questions around OPEX. So yeah, we are going to be increasing our OPEX about 25% year over year based on the guidance, where our top line is going to grow more than 38%.

Sue Hohenleitner: Yeah. Thank you, Allison.

Sue Hohenleitner: I'll start out with your questions around OpEx. So yeah, we are gonna be increasing our OpEx about 25%, year-over-year, based on the guidance, where our top line is gonna grow more than 38%. So, you know, good news is we are growing the OpEx, but not necessarily as much as we are growing the top-line momentum. In terms of what we're doing, these investments that we're making, this is really all about growth. Growth not only in the commercial business, but also within the R&D pipeline that Laura talked all about. A lot of the sales and marketing that we're gonna be investing in, these are not relatively new programs. These are things that are proven, high ROI programs that are really gonna drive that growth.

Speaker #4: So good news is we are growing the OPEX, but not necessarily as much as we are growing the top line momentum. In terms of what we're doing, these investments that we're making—this is really all about growth.

Speaker #4: Growth not only in the commercial business, but also within the R&D pipeline that Laura talked all about. A lot of the sales and marketing that we're going to be investing in, these are not relatively new programs.

Speaker #4: These are things that are proven. High ROI programs that are really going to drive that growth. We are going to be and continue to be significantly disciplined and in all that we do.

Sue Hohenleitner: We are going to be and continue to be significantly disciplined and, you know, in all that we do. The other thing I would like to note, too, is as the year has already started, we have already begun these investments. So the clip that we're on is a pretty good clip to get to do that. In terms of cash flow positivity, we have been cash flow positive. We're very proud of that, the last two quarters. And we'll continue to do what we can to drive that. We're not really guiding to positivity at the moment, but stay tuned. And with that-

Speaker #4: And the other thing I would like to note too is as the year has already started, we have already begun these investments. So the clip that we're on is a pretty good clip.

Speaker #4: To get to do that. In terms of cash flow positivity, we have been cash flow positive. We're very proud of that. The last two quarters, and we'll continue to do what we can to drive that.

Speaker #4: We're not really guiding to positivity at the moment, but stay tuned and with that.

Mike Raab: I guess the other thing I would note is, and I'll have Eric comment on it. As you've seen throughout, you know, when we started the IBSRELA program three years ago, we started with 30 people. We expanded to 60, we expanded to 124. We now see the benefits of the fans and the field-based folks out there. So understand that we always look at how to optimize and invest, and that's something we will continue to do as this program continues to expand. And certainly, you can imagine the future with CIC, that there's other opportunities to continue to expand in, in this organization. Eric?

Speaker #1: And I guess the other thing I would note is—and I'll have Eric comment on it—as you've seen throughout, when we started the Entrella program three years ago, we started with 30 people.

Speaker #1: We expanded to 60. We expanded to 124. We now see the benefits of the FAMS and the field-based folks out there. So understand that we always look at how to optimize and invest.

Speaker #1: And that's something we will continue to do as this program continues to expand. And certainly, you can imagine the future with CIC, that there's other opportunities to continue expanding in this organization.

Speaker #1: Eric?

Speaker #5: Yeah, I would say in terms of really maximizing the return from the investment, we're recognizing that we do have an opportunity to improve on reach and frequency.

Eric Foster: Yeah, I would say, you know, in terms of really maximizing the return from the investment, you know, we're recognizing that we do have an opportunity to improve on reach and frequency. So you may have seen, we posted some positions online for the ABD role, where we're going to be going up around 15 to 20 roles. As I mentioned, we will be doubling the size of the field reimbursement team, and I feel pretty confident over that over the next couple of years. We are starting those investments now, so we can maximize the return that we're gonna be able to get in 2026, as well as into 2027.

Speaker #5: So you may have seen we posted some positions online. For the ABD role, where we're going to be going up around 15 to 20 roles.

Speaker #5: As I mentioned, we will be doubling the size of the field reimbursement team. And I feel pretty confident over that over the next couple of years.

Speaker #5: We are starting those investments now so we can maximize the return that we're going to be able to get in 2026, as well as into 2027.

Speaker #5: And so, I don't anticipate too much changing there, but of course, we are always looking at the market and our performance and seeing ways that we can be better for patients.

Eric Foster: And so I don't anticipate too much changing there, but of course, we are always looking at, always looking at the market and our performance and see ways that we can be better for patients. The other thing that I would just call out from a marketing standpoint, the team has really done a nice job of digital marketing and making sure that we're engaging with physicians, reaching that population that's out there. And so this year, you will see a concerted effort and focus on the patient. As Mike mentioned, we know that it's a sizable patient population out there, and we have an opportunity to reach out, engage with them. We know when they are aware of IBSRELA, they go into the office and the physician will write that prescription.

Speaker #5: The other thing that I would just call out from a marketing standpoint: the team has really done a nice job of digital marketing and making sure that we're engaging with physicians, reaching that population that's out there.

Speaker #5: And so this year, you will see a concerted effort and focus on the patient. As Mike mentioned, we know that it's a sizable patient population.

Speaker #5: Out there, and we have an opportunity to reach out, engage with them. We know when they are aware of Entrella, they go into the office and the physician will write that prescription.

Speaker #5: So, we want to make sure that we're pulling through not just on the sales side, but also on the marketing side, and the team has already started that.

Eric Foster: So we wanna make sure that we're pulling through, not just on the sales side, but also on the marketing side, and the team has already started that. And the investments that we're making in Q1, you'll see those will be fairly consistent throughout this year.

Speaker #5: And the investments that we're making in Q1, you'll see those will be fairly consistent throughout this year.

Sue Hohenleitner: Yep. Thank you.

Allison Bratzel: Yep. Thank you.

Speaker #3: Thank you. And we'll move next to Chris with Raymond James.

Operator: We'll move next to Chris with Raymond James.

Speaker #7: Hey, this is Sam on for Chris. Thanks for taking our questions. Just one on the CIC trial. Can you talk more about the two lower doses you're testing?

Chris Raymond: Hey, this is Sam on for Chris. Thanks for taking our questions. Just one on the CIC trial. Can you talk more about the two lower doses you're testing? If I recall correctly, these dose levels weren't quite as efficacious in IBS-C. So what are your expectations for how these dose levels will perform in this trial? And, is having multiple dose options part of your strategy in CIC, or are you trying to find just one optimal dose? Thanks.

Speaker #7: If I recall correctly, these dose levels weren't quite as efficacious in IVSC, so what are your expectations for how these dose levels were performed in this trial?

Speaker #7: And is having multiple dose options part of your strategy in CIC, or are you trying to find just one optimal dose? Thanks.

Speaker #8: Yeah, I think at the end of the day, we want to obviously make sure that as we evaluate safety and efficacy, that we are able to actually look at a dose that we don't expect to provide as much, right?

Laura Williams: Yeah. I think at the end of the day, we wanna obviously make sure that, you know, as you know, we evaluate safety and efficacy, that we are able to actually look at a dose that we don't expect, you know, to provide as much, right? You typically want to look at the, you know, the least effective dose, and so that is the lowest dose. We don't expect a lot from that. But I think, you know, as I said earlier, CIC seems to be the less difficult condition to treat.

Speaker #8: You typically want to look at the least effective dose. And so that is the lowest dose. We don't expect a lot from that. But I think as I said earlier, CIC seems to be the less difficult condition to treat.

Speaker #8: And so it makes sense for that middle dose of 25 milligrams BID and then the 50 milligram dose is obviously the dose that we used and the data that we used in our temple trials to actually provide us some probability of success for this trial.

Laura Williams: And so it makes sense for that middle dose of 25mg BID, and then the 50mg dose is obviously the dose that we used, and the data that we used, you know, in our TEMPO trial to actually, you know, provide us some probability of success for this trial. So, it's a nice way to look at, you know, dose response in a single phase 3, you know, well-designed, robust study.

Speaker #8: So it's a nice way to look at dose response in a single phase three well-designed, robust study.

Speaker #1: And I'll just highlight that too is we're going to follow the data, right? And what these three different doses tell us will tell us what we move forward with.

Mike Raab: And I'll just highlight that, too, is we're gonna follow the data, right? And what these three different doses tell us, will tell us what we move forward with.

Speaker #7: Got it. Thank you.

Chris Raymond: Got it. Thank you.

Speaker #1: Thank you.

Mike Raab: Thank you.

Operator: Next, we'll hear from Matthew with HC Wainwright.

Speaker #3: And next, we'll hear from Matthew with HC Wingrate.

Operator: Next, we'll hear from Matthew with HC Wainwright.

Speaker #9: Hi guys. Great to see the successful quarter and thanks for taking our question. So with Entrella offering its differentiated NAT3 inhibitor profile, what do you see being the greatest distinctions in the future for the CIC market when we think about the other GCC agonists or serotonin receptor agonist mechanisms, for instance?

Matthew Caulfields: Hi, guys. Great to see the successful quarter, and thanks for taking our question. So with the IBSRELA offering its differentiated NHE3 inhibitor profile, what do you see being the greatest distinctions in the future for the CIC market when we think about the other GCC agonists or serotonin receptor agonist mechanisms, for instance? Really, just any color on the unmet need and the differentiation there. Thanks.

Speaker #9: Really just any color on the unmet need and the differentiation there. Thanks.

Laura Williams: Well, thanks for the question. It's a great question. I think at the end of the day, what we talked about before was the fluidity, right, between these two conditions, IBS-C and CIC. And so you know, just as we've seen with IBS-C, the need for a different mechanism of action, right? Because a number of patients, you know, on other drugs are still symptomatic. And so that is important also with CIC, and I think that really speaks to, you know, the potential utility of tenapanor in that patient population.

Matthew Caulfields: Well, thanks for the question. It's a great question. I think at the end of the day, what we talked about before was the fluidity, right, between these two conditions, IBS-C and CIC. And so you know, just as we've seen with IBS-C, the need for a different mechanism of action, right? Because a number of patients, you know, on other drugs are still symptomatic. And so that is important also with CIC, and I think that really speaks to, you know, the potential utility of tenapanor in that patient population.

Speaker #10: Well, thanks for the question. It's a great question. I think at the end of the day, what we talked about before was the fluidity, right, between these two conditions.

Speaker #10: IBSC and CIC. And so just as we've seen with IBSC, the need for a different mechanism of action, right, because a number of patients on other drugs are still symptomatic.

Speaker #10: And so that is important also with CIC. And I think that really speaks to the potential utility of Tanapinor in that patient population.

Speaker #1: And you look at the evolution of how CIC, functional constipation, IBS-C, are characterized by the Rome Foundation, it is continuing to evolve over time.

Mike Raab: You know, you look at the evolution of how CIC, functional constipation, IBS-C, are characterized by the Rome Foundation; it is continuing to evolve over time. You know, notably, the CIC population is certainly larger, but many of those patients early on are well treated by over-the-counter medications. If you look at the prescriptions that we talk about where there isn't a differentiation in IQVIA or other data in terms of what is for IBS-C or CIC, you're seeing a mix between the two. So that's why the continuum that Eric mentioned of how we can speak to IBSRELA and NHE3 inhibition as a different choice versus all the secretagogues, which is basically it. And the serotonin is a motility drug, completely different mechanism and impact on the patient.

Speaker #1: And notably is the CIC population certainly larger, but many of those patients early on are well treated by over-the-counter medications. And if you look at the differentiation in IQV or other data in terms of what is for IBSC or CIC, you're seeing a mix between the two.

Speaker #1: So that’s why the continuum that Eric mentioned of how we can speak to Entera and NHE3 inhibition as a different choice versus all the SGLT2s, which is basically it.

Speaker #1: And the serotonin is a motility drug completely different mechanism and impact on the patient. So this seems for us, and I think as we hear from the work that we're doing, that it is ripe for this to be going into CIC because there is such a continuum between CIC and IBSC.

Mike Raab: So this seems for us, and I think as we hear from the work that we're doing, that it is right for this to be going into CIC because there is such a continuum between CIC and IBS-C.

Speaker #9: Very helpful. Thank you, guys.

Laura Chico: Very helpful. Thank you, guys.

Matthew Caulfields: Very helpful. Thank you, guys.

Speaker #1: Sure.

Mike Raab: Sure.

Speaker #3: Next, we'll hear from Roanna with Lyrinc.

Operator: Next, we'll hear from Roanna with Leerink.

Speaker #11: Great. Hi, everyone. So I was curious, for CIC, what will prescribers focus on most in terms of the primary and secondary endpoints in the phase three study?

Roanna Ruiz: Great. Hi, everyone. So, I was curious for CIC, what will prescribers focus on most in terms of the primary and secondary endpoints in the Phase 3 study? Is there an efficacy bar that you're thinking about for defining a highly successful trial in CIC?

Speaker #11: And is there an efficacy bar that you're thinking about for defining a highly successful trial in CIC?

Mike Raab: One comment, then I'll probably go too far with it, but I'll ask Eric then to comment what it's like in the field. What's interesting is when you talk to gastroenterologists about this, they know how to make people have bowel movement, right? They know that they can do that. And if they're going to have a hard time succeeding with the different over-the-counter and other things that they do, they move to pharmacologic intervention. So those patients that are not getting relief, and it's a primary endpoint of CSBMs that are ultimately a durable response that Laura described in the endpoints, that's what you want to see in a patient that's having these challenges with bowel movements. You know, that's what you look for.

Speaker #1: One comment then, I'll probably go too far with it, but I'll ask Eric then to comment just like in the field. What's interesting is when you talk to gastroenterologists about this, they know how to make people have bowel movement, right?

Speaker #1: They know that they can do that. And if they're going to have a hard time succeeding with the different over-the-counter and other things that they do, they move to pharmacologic intervention.

Speaker #1: And so those patients that are not getting relief, and it's a primary endpoint of CSDMs that are ultimately and a durable response that Laura described in the endpoints, that's what you want to see in a patient that's having these challenges with bowel movements.

Speaker #1: And that's what you look for. Secondary endpoints, I'm sure there's quality of life benefits, but at the end of the day, someone with chronic idiopathic constipation, you want them to be able to have a bowel movement.

Mike Raab: Secondary endpoints, I'm sure, there's quality of life benefits, but at the end of the day, someone with chronic idiopathic constipation, you want them to be able to have a bowel movement.

Speaker #10: Yeah, I would just add these patients are chronically constipated, as Mike said, and it has a significant impact on their life. So, first and foremost, from a primary endpoint, we want to make sure that it can work in constipation and have a lot of confidence there.

Eric Foster: Yeah, I would, I would just add, you know, these patients are chronically constipated, as Mike said, and it has a significant impact on their life. So first and foremost, from a primary end-endpoint, we want to make sure that it can work in constipation and have a lot of confidence there. From a secondary endpoint, as Mike mentioned, quality of life, patient-reported outcomes, those are areas that we're going to focus on to be able to show that we can treat not just the CIC, but the patient as a whole, and feel really good about being able to do that. And lastly, as Laura mentioned, with a differentiating mechanism of action, these are multifactorial conditions, and patients need options. And so we want to be that option for them, just like we are with IBS-C.

Speaker #10: From a secondary endpoint, as Mike mentioned, quality of life, patient reported outcomes, those are areas that we're going to focus on to be able to show that we can treat not just the CIC, but the patient as a whole.

Speaker #10: And feel really good about being able to do that. And lastly, as Laura mentioned, with a differentiated mechanism of action, these are multifactorial conditions and patients need options.

Speaker #10: And so we want to be that option for them, just like we are with IBSC. We've got a good position there and feel like we would be able to create a similar market and opportunity for CIC.

Eric Foster: We've got a good position there and feel like we'd be able to create a similar market and opportunity, for CIC.

Speaker #11: Got it. Super helpful. Thanks.

Roanna Ruiz: Got it. Super helpful. Thanks.

Speaker #1: Thanks, Rod.

Eric Foster: Thanks, Roanna.

Speaker #3: And next, we'll hear from Yigal with Citigroup.

Operator: Next, we'll hear from Yigal with Citigroup.

Speaker #12: Hi, this is Joohwan Kim on for Yigal. Congrats on the progress. Thanks for taking our question. Maybe just a quick one from us. Any additional color you can provide on additional patents or other layers of protection you could, you're thinking about building up in the future?

Joohwan Kim: Hi, this is Juan Kim on for Yigal. Congrats on the progress, and thanks for taking our question. Maybe just a quick one from us. Any additional color you can provide on additional patents or other layers of protection you could-- you're thinking about building up in the future?

Joohwan Kim: Hi, this is Joohwan Kim on for Yigal. Congrats on the progress, and thanks for taking our question. Maybe just a quick one from us. Any additional color you can provide on additional patents or other layers of protection you could-- you're thinking about building up in the future?

Speaker #1: Yeah, I mean, I think as I said in my opening comments, our job in this business is to continue to strengthen our intellectual property position for products like Expos and Entrella.

Mike Raab: Yeah, I mean, I think as I said in my opening comments, our job in this business is to continue to strengthen our intellectual property position for products like XPHOZAH and IBSRELA, and that's what we're continuing to do. I think this patent on the formulation is really important, the fact that it's listed in the Orange Book, exactly what you would want to see. And needless to say, I think, you know, without any specifics of what we're going to file or have filed, there are other things that we are working on to further strengthen that position.

Speaker #1: And that's what we're continuing to do. I think this patent on the formulation is really important, the fact that it's listed in the orange book exactly what you would want to see.

Speaker #1: And needless to say, I think without any specifics of what we're going to file or have filed, there are other things that we are working on to further strengthen that position.

Joohwan Kim: Got it. Thank you. And maybe just one more, if I could. How are you thinking about long-term XPHOZAH growth post-2026, given potential adjustments in Medicare base rates for phosphate binders? Any additional color you could provide on that?

Speaker #12: Got it. Thank you. And maybe just one more, if I could. How are you thinking about long-term exposure growth post-2026, given potential adjustments in Medicare-based rates for phosphate binders?

Speaker #12: Any additional color you could provide on that?

Speaker #1: Well, to remind you, Medicare-based rate and phosphate binders we do not benefit from that. We made the decision, as I noted in my opening comments, that 18 months ago we made the determination not to participate in that.

Mike Raab: Well, to remind you, Medicare base rate and phosphate binders, we do not benefit from that. We made the decision, as I noted in my opening comments, that 18 months ago, we made a determination not to participate in that. So our business is focused on, in terms of the revenue generating businesses, Medicaid and Medicare, Medicaid and commercial, excuse me. And the Medicare segment is what Sue referenced to as well, is to make sure that any patient that is appropriate and needs XPHOZAH per our label, has access to it. And that's what we're extremely proud of, where you saw both the non-Medicare segment of 41% growth during that first year of the TDAPA period, and an overall growth of dispense of 9% in the face of all that's going on.

Speaker #1: So our business is focused on, in terms of the revenue-generating business, Medicaid and Medicare. Medicaid and commercial, excuse me. And the Medicare segment is what Sue referenced to as well is to make sure that any patient that is appropriate and needs Expos per our label has access to it.

Speaker #1: And that's what we're extremely proud of, where you saw both the non-Medicare segment of 41% growth during that first year, that TADAPA period, and an overall growth of dispenses of 9%.

Speaker #1: In the face of all that's going on. So we're extraordinarily proud of that. And certainly longer answer than I think your question. But the base rate increase is not relevant to this business.

Mike Raab: So we're extraordinarily proud of that, and certainly longer answer than I think your question, but, you know, the base rate increase is not relevant to this business.

Joohwan Kim: Got it. Thank you very much. Appreciate it.

Speaker #1: Thank you.

Mike Raab: Thank you.

Speaker #3: And our next question comes from Laura with Wedbush Securities.

Operator: Our next question comes from Laura with Wedbush Securities.

Speaker #9: Hey, good afternoon. Thanks for taking the question. This is Thomas on for Laura Chico so perhaps one question for Entrella. So historically, you've positioned Entrella for later lines of treatment for IBSC.

Laura Chico: Hey, good afternoon. Thanks for taking the question. This is Thomas on for Laura Chico. So perhaps one question for IBSRELA. So historically, you've positioned IBSRELA for later lines of treatment for IBS-C. But as you're now projecting over $400 million in revenue for this year, just wonder if there might be more leverage to reengage with payers in reexploring how frontline use can fit into the picture. And to that end, wonder if frontline utilization how much, if at all, factors into your 2029 peak revenue target?

Speaker #9: But as you're now projecting over 400 million dollars in revenue, for this year, just wonder if there might be more leverage to re-engage with payers in re-exploring how frontline use can fit into the picture.

Speaker #9: And to that end, wonder if frontline utilization how much if at all factors into your 2029 peak revenue target?

Speaker #1: Sure. No, thanks for the question, Tom. And it's interesting. We've talked about this before is it's 50,000 new patients coming on to IBSC indicated therapies a month.

Mike Raab: Sure. No, thanks for the question, Tom. And it's interesting, we've talked about this before, you know, it's 50,000 new patients coming on to IBS-C indicated therapies a month. There is over 7 million prescriptions written last year for IBS-C therapies. We need a small fraction of that, in order to get to our aspirational numbers. So we're extremely confident in the market opportunity there that's for our indication, without having to go to frontline. Notably, however, our clinical work, our package insert, is a first-line therapeutic. The payer dynamics, which continue to be befuddling to me in this industry, and the challenge is to get good medicines to patients are the challenge that we all face.

Speaker #1: There were over 7 million prescriptions written last year for IBS-C therapies. We need only a small fraction of that in order to get to our aspirational numbers, so we're extremely confident in the market opportunity there—that's for our indication, without having to go to frontline.

Speaker #1: Notably, however, our clinical work, our package insert is a first-line therapeutic. The payer dynamics, which continue to be the fuddling to me in this industry and the challenges to get good medicines to patients, are the challenge that we all face.

Mike Raab: I think the work that Eric and our market access team and the leadership that we have there is having us be very thoughtful about how we ensure appropriate market access and the lessening as many hurdles as possible. Going after frontline is not an objective that we have and is not factored into the numbers. Although, as we've noted in other calls, there is some organic growth in first-line use because I think people have conviction, the benefit this product is providing their patients. Yeah, you know, I would say last year one of our priorities in the commercial side was building out our payer and market access team. We've done a nice job of bringing in the right team, and these individuals are engaged with payers and, you know, they continue to, you know, put hurdles in place.

Speaker #1: I think the work that Eric and our market access team and the leadership that we have there is having us be very thoughtful about how we ensure appropriate market access and the lessening as many hurdles as possible.

Speaker #1: Going after frontline is not an objective that we have and is not factored into the numbers, although as we've noted in other calls, there is some organic growth in first-line use because I think people have conviction in the benefit this product is providing their patients.

Speaker #1: Anything to add, Eric?

Speaker #10: Yeah, I would say last year, one of our priorities in the commercial side was building out our payer and market access team. We've done a nice job of bringing in the right team.

Speaker #10: And these individuals are engaged with payers. And they continue to put hurdles in place and we are working with them to make sure that patients can have access to our product.

Mike Raab: And we, you know, we are working with them to make sure that patients can have access to our products. So, we don't aspire to have first-line therapy at this point in time. And you had mentioned kind of later line utilization, and I would say, you know, when we look at our internal market research, it's typically around second and third line. So our goal is to be the first branded product, post the brand or generic utilization. And so that's the team what they're messaging out there. And, you know, based on the tremendous amount of success that we saw last year in 2025, we continue to feel that that's the right position.

Speaker #10: So we don't aspire to have first-line therapy at this point in time. And you had mentioned kind of later-line utilization. And I would say when we look at our internal market research, it's typically around second and third line.

Speaker #10: So our goal is to be the first branded product post the brand or generic utilization. And so that's the team what their messaging out there.

Speaker #10: And based on the tremendous amount of success that we saw last year in 2025, we continue to feel that that's the right position. But yes, we continue to work with all of the stakeholders that are out there to make sure the patients have access to our products.

Mike Raab: But yes, we continue to work with all of the stakeholders that are out there to make sure that patients have access to our products. And again, we'll continue to invest in those areas and feel good about the direction that we're headed.

Speaker #10: And again, we'll continue to invest in those areas and feel good about the direction that we're headed.

Speaker #9: Understood. Thank you again for the kind of questions.

Eric Foster: Understood. Thank you again for taking our questions.

Speaker #1: Thank you.

Mike Raab: Thank you.

Speaker #3: And we'll move next to Julian with BTIG.

Operator: We'll move next to Julian with BTIG.

Speaker #13: Hi, thank you for taking the questions and congrats on the progress. First, can you talk about how the recently issued 299 patent contributes to your overall IP strategy for TADAPA-NOR?

Julian Harrison: Hi, thank you for taking the questions, and congrats on the progress. First, can you talk about how the recently issued 299 patent contributes to your overall IP strategy for tenapanor? Wondering if the patent covers unexpected effects or any other features that you believe help strengthen the patent. And then I thought I heard in prepared remarks that CIC labeling could potentially bolster your ongoing efforts in IBS-C. Just wondering if you could expand on that some more. What dynamics would you expect to be at play there?

Speaker #13: Wondering if the patent covers unexpected effects or any other features that you believe help strengthen the patent? And then I thought I heard in Prepared Remarks that CIC labeling could potentially bolster your ongoing efforts in IBSC.

Speaker #13: Just wondering if you could expand on that some more. What dynamics would you expect to be at play there?

Speaker #1: Sure. Just brief comment on the intellectual property. This is a formulation patent. Very clear and straightforward. It's now orange book listed. It goes out to 2042.

Mike Raab: Sure. Just a brief comment on the intellectual property. Yeah, this is a formulation patent, very clear and straightforward. It's now Orange Book listed. It goes out to 2042. And that's the important thing to focus on, is building that sort of bulwark of support as we continue to build this business. So feel good about it and ultimately other IP that we will pursue. But this is a strong formulation patent for the commercial formulation of the two products.

Speaker #1: And that's the important thing to focus on is building that sort of bulwark of support as we continue to build this business. So feel good about it.

Speaker #1: And ultimately, other IP that we will pursue. But this is a strong formulation patent for the commercial formulation of the two products.

Speaker #10: Yeah, and I'll take the second part of that question as it relates to CIC and IBSC. So, as Laura mentioned, I mean, these two conditions are closely related.

Eric Foster: Yeah, and I'll take the second part of that question as it relates to CIC and IBS-C. So as Laura mentioned, I mean, these two conditions are closely related, and we know that physicians use the secretagogues in both indications. And so, you know, as we gain experience and if approved, an indication in CIC, we know that it will improve physician confidence across both CIC and IBS-C, that we feel like we can be the product of choice for those physicians. So when we did our research, not only did we see improvement in the CIC, but we also saw increased confidence in the IBS-C side, and that's what continues to feed into our optimism as we think about really the true value that IBSRELA can provide for those patients out there with CIC and IBS-C.

Speaker #10: And we know that physicians use the Scritagox in both indications. And so as we gain experience and if approved in indication in CIC, we know that it will improve physician confidence across both CIC and IBSC.

Speaker #10: That we feel like we can be the product of choice for those physicians. So, when we did our research, not only did we see improvement in the CIC, but we also saw increased confidence on the IBSC side.

Speaker #10: And that's what continues to feed into our optimism as we think about, really, the true value that Entrella can provide for those patients out there with CIC and IBS-C.

Speaker #3: And we'll move to our next question from Aydin with Ladenburg.

Operator: We'll move to our next question from Aiden with Ladenburg.

Operator: We'll move to our next question from Aidan with Ladenburg.

Speaker #11: Hello, good afternoon. Congrats on the great quarter and appreciate you taking our questions. I got a couple. So first, an Entera question. So you guide now $2.9 billion-plus, so you've consistently guided a billion dollars.

[Analyst] (Ladenburg Thalmann): Hello, good afternoon. Congrats on the great quarter, and appreciate you taking our questions. I got a couple. First, a thorough question. You guide now $29 billion plus. You consistently got $1 billion, but we previously assumed to think that would occur in 2033. Do you have any comments, any forecasts, any sort of soft guidance as it comes to 2033? How, what, what should we expect for that year? When do you think that peak year actually may happen for Ixcela? The second question I'll ask is about the CIC trial. As you mentioned, those have always been interrelated indications, and you decided to start the trial.

Aidan Redmond: Hello, good afternoon. Congrats on the great quarter, and appreciate you taking our questions. I got a couple. First, a thorough question. You guide now $29 billion plus. You consistently got $1 billion, but we previously assumed to think that would occur in 2033. Do you have any comments, any forecasts, any sort of soft guidance as it comes to 2033? How, what, what should we expect for that year? When do you think that peak year actually may happen for Ixcela? The second question I'll ask is about the CIC trial. As you mentioned, those have always been interrelated indications, and you decided to start the trial.

Speaker #11: But we previously assumed to think that would occur in 2033. So do you have any comments, any forecasts, any sort of self-guidance as it comes to 2033?

Speaker #11: What should we expect for that year? And when do you think that peak year actually may happen for Entrella? And the second question I'll ask is about the CIC trial.

Speaker #11: So those, as you mentioned, those are those have always been interrelated indications. And so you decided to start the trial. Just curious to understand, how do you think changed over the past several years?

[Analyst] (Ladenburg Thalmann): Just curious to understand how do things changed over the past several years? So was it previously you didn't start the trial because of financial constraints, or what are other potential reasons that sort of, you know, stimulated you?

Aidan Redmond: Just curious to understand how do things changed over the past several years? So was it previously you didn't start the trial because of financial constraints, or what are other potential reasons that sort of, you know, stimulated you?

Speaker #11: So was it previously you didn't start the trial because of financial constraints or what are other potential reasons that sort of stimulated you?

Mike Raab: Sure. I mean, I, I'll answer the second part first, but then actually ask, Laura to address it as well. I'm cheap, and wanted to make sure that we had enough capital to do the work we need to do. Honestly, that, that's the very simple calculus that got us to where we are today. The fact that we ended last year with more cash than we did the year before, gave me the confidence that we can do this and, and invest appropriately into the pipeline. And then for your first question, you know, the fact that we gave you the numbers, $1.029 billion, you know, I would argue that our, our internal projections might have been close to that, and we were not yet, we decided to not yet provide that. We will continue to grow thereafter.

Speaker #1: Sure. I mean, I'll answer the second part first, but then actually ask Laura to address it as well. I'm cheap. And wanted to make sure that we had enough capital to do the work we need to do.

Speaker #1: Honestly, that's the very simple calculus that got us to where we are today. The fact that we ended last year with more cash than we did the year before gave me the confidence that we can do this and invest appropriately into the pipeline.

Speaker #1: And then for your first question, the fact that we gave you the numbers of billion in '29, I would argue that our internal projections might have been close to that and we were not yet we decided to not yet provide that.

Speaker #1: We will continue to grow thereafter. Linzess continues to grow. Has not peaked. So this business, this patient population, where there's a huge, huge need, continue to come for therapy.

Mike Raab: Linzess continues to grow, has not peaked. So this business, this patient population, where there's a huge, huge need, continue to come for therapy, and the more innovation that comes, the more patients that are going to evolve. So what peak ultimately looks like, we're all going to get there together, and starting where we are now, with the kind of growth of 73% over 2024 and a 38% CAGR to get to a billion, the math's pretty straightforward. So I would urge you to take a look at that and the kind of growth that you've seen in the IBS-C marketplace, where we see the kind of growth with only one mechanism, GCC agonists before us, should give you some perspective as to what the market through LOV would look like before this generic entrant.

Speaker #1: And the more innovation that comes, the more patients that are going to evolve. So what peak ultimately looks like, we're all going to get there together.

Speaker #1: And starting where we are now with the kind of growth of 73% over '24 and a 38% CAGR to get to a billion, the math's pretty straightforward.

Speaker #1: So I would urge you to take a look at that and the kind of growth that you've seen in the IBSC marketplace where we see the kind of growth with only one mechanism of GCC agonist before us should give you some perspective as to what the market through LOE would look like before this generic entrant.

Speaker #11: All right. Thanks so much. Appreciate the comments and congrats on the quarter. And appreciate the guidance for '26.

[Analyst] (Ladenburg Thalmann): All right. Thanks so much. Appreciate the comments and congrats with the quarter, and appreciate the guidance for 2026.

Aidan Redmond: All right. Thanks so much. Appreciate the comments and congrats with the quarter, and appreciate the guidance for 2026.

Speaker #1: Thanks, Aydin.

Mike Raab: Thanks, Aiden.

Speaker #3: And we'll move next to Peyton with TD Cowen.

Operator: We'll move next to Peyton with TD Cowen.

Speaker #13: Hi, guys. This is Peyton on for Joe. Thanks for taking our questions. I guess just a quick one for me. Could you talk about how the CIC trial is powered and then what proportion of patients need to be CBSM responders and that you're targeting?

[Analyst] (TD Cowen): Hi, guys. This is Peyton on for Joe. Thanks for taking our questions. I guess just a quick one for me. Could you talk about how the CIC trial is powered, and then what proportion of patients need to be CSBM responders and that you're targeting? Thank you.

Peyton Bohnsack: Hi, guys. This is Peyton on for Joe. Thanks for taking our questions. I guess just a quick one for me. Could you talk about how the CIC trial is powered, and then what proportion of patients need to be CSBM responders and that you're targeting? Thank you.

Speaker #13: Thank you.

Speaker #10: Yeah. So the powering, it's a pretty robust sort of sample size calculation. We powered it at 95%. So we feel really comfortable there. And when you couple that with the data that we saw in our TEMPO studies, it gives us a lot of confidence in terms of the probability of both technical and regulatory success.

Laura Williams: ... Yeah, so the powering is, it's a you know a pretty robust you know sort of you know sample size calculation. We powered it at 95%, so we feel really comfortable there. And when you couple that with the data that we saw in our TEMPO studies, it gives us a lot of confidence in terms of you know the probability of both technical and regulatory success. So as I said before, the sample size is about 700 patients, and obviously that reflects the four you know sort of treatment arms, right? Three active doses and placebo. And again, it's about 173 patients per arm.

Speaker #10: So, as I said before, the sample size is about 700 patients. And obviously, that reflects the four sort of treatment arms, right? Three active doses and placebo.

Speaker #10: And again, it's about 173 patients per arm.

Speaker #13: And the proportion of patients that need to be CBC responders per arm?

[Analyst] (TD Cowen): The proportion of patients that need to be IBS-C responders per arm?

Peyton Bohnsack: The proportion of patients that need to be IBS-C responders per arm?

Speaker #10: Yeah. Our initial when we looked at the data in terms of our TEMPO studies, we saw about at least a 20% difference between placebo and anaprenor.

Laura Williams: Yeah. Our initial, you know, when we looked at the data in terms of our TEMPO studies, we saw about at least a 20% difference between placebo and active tenapanor. And so, our sample size calculations are such that we're looking really about around the same sort of difference, 18% to 20% difference, you know, between placebo and active drug. And that is for the two, for the 25mg and 50mg dose.

Speaker #10: And so our sample size calculations are such that we're looking really about around the same sort of difference, 18 to 20 percent difference between placebo.

Speaker #10: And active drug. And that is for the two for the 25 milligram and 50 milligram dose.

Speaker #13: Great. Thanks for taking our questions.

[Analyst] (TD Cowen): Great. Thanks for taking our questions.

Peyton Bohnsack: Great. Thanks for taking our questions.

Speaker #3: And our next question comes from Jennifer with Cantor Fitzgerald.

Operator: Our next question comes from Jennifer with Cantor Fitzgerald.

Speaker #12: Hi. This is Jennifer Gia on behalf of Picard Agrol from Cantor. Thanks for taking my questions. I wanted to ask about Entrella. Can you talk about the IBSC market where you're finding the greatest opportunity?

[Analyst] (Cantor Fitzgerald): Hi, this is Jennifer Jia on behalf of Prakar Agrawal from Cantor. Thanks for taking my questions. I wanted to ask about IBSRELA. Can you talk about the IBS-C market, where you're finding the greatest opportunity, and what is driving the market growth of double-digit, and how long do you think this is sustainable? And on XPHOZAH, you shared that the peak opportunity being at $750 million. Can you talk about how you get to that number based on the current trends? Thank you.

Jennifer Kim: Hi, this is Jennifer Jia on behalf of Prakar Agrawal from Cantor. Thanks for taking my questions. I wanted to ask about IBSRELA. Can you talk about the IBS-C market, where you're finding the greatest opportunity, and what is driving the market growth of double-digit, and how long do you think this is sustainable? And on XPHOZAH, you shared that the peak opportunity being at $750 million. Can you talk about how you get to that number based on the current trends? Thank you.

Speaker #12: And what is driving the market growth of double-digit? And how long do you think this is sustainable? And on Exposa, you shared that the peak opportunity being at 750 million.

Speaker #12: Can you talk about how you get to that number based on the current trends? Thank you.

Speaker #1: Sure. With the Entrella market, I'm sorry, if you could repeat the question. I didn't hear you clearly.

Mike Raab: Sure. With the IBSRELA market, I'm sorry, if you could repeat the question. I didn't hear you clearly.

Speaker #12: Oh, so with the Entrella drug on IBSC, I wanted to understand where is the greatest opportunity and what is driving the market growth of double-digit?

[Analyst] (Cantor Fitzgerald): Oh, so with the IBSRELA drug on IBS-C, I wanted to understand where is the greatest opportunity, and what is driving the market growth of double-digit, and how sustainable do you think it's going to be?

Jennifer Kim: Oh, so with the IBSRELA drug on IBS-C, I wanted to understand where is the greatest opportunity, and what is driving the market growth of double-digit, and how sustainable do you think it's going to be?

Speaker #12: And how sustainable do you think it's going to be?

Speaker #1: Well, I think in the previous question that I answered, with 50,000 patients coming in every month from the GCC agonist already, there is a and 7 million patients already on therapy.

Mike Raab: Well, I think as I, in the previous question that I answered, with 50,000 patients coming in every month from the GCC agonist already, there is a and 7 million patients already on therapy, there's a very small percentage of that, that ultimately we need to get to $1 billion. So confidence in there is high, particularly given our clinical differentiation. And with the XPHOZAH, very much the same kind of dynamic, right? I mean, if you look at the Medicare population that we lost, so the original numbers, and I've gone through this before, is 550,000 patients on dialysis. Sixty percent of those are Medicare. You lose those, that's around 330,000, 220,000 patients that are Medicaid and Medicare. Those are the revenue-generating patients for us.

Speaker #1: There's a very small percentage of that that ultimately we need to get to a billion dollars. So confidence in there is high, particularly given our clinical differentiation.

Speaker #1: And with the Exposa, very much the same kind of dynamic, right? I mean, if you look at the Medicare population that we lost, so the original numbers that I've gone through this before is 550,000 patients on dialysis.

Speaker #1: 60% of those are Medicare. You lose those, that's 330. It's 220,000 patients that are Medicaid and Medicare. Those are the revenue-generating patients for us.

Speaker #1: It's less than 100,000 patients, closer to 50,000 that you require in order to get through the guidance that we gave. Thank you.

Mike Raab: It's less than 100,000 patients, closer to 50,000, that you require in order to get to the guidance that we gave.

[Analyst] (Cantor Fitzgerald): Great. Thank you.

Jennifer Kim: Great. Thank you.

Mike Raab: Thank you.

Speaker #3: And this concludes our question-and-answer session. I'd like to turn the conference back to our host for any additional or closing remarks.

Operator: This concludes our question and answer session. I'd like to turn the conference back to our host for any additional or closing remarks.

Speaker #1: Yeah. Thank you, operator. To our investors, our employees, and really especially our patients, thank you for your continued engagement and support. We're encouraged by the progress we've made and excited about the opportunities ahead.

Mike Raab: Yeah, thank you, Operator. To our investors, our employees, and really especially our 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 disciplined execution and long-term value creation, and we appreciate your continued confidence as we move forward. With that, we can now end the call. Thank you, Operator.

Speaker #1: We remain focused on disciplined execution and long-term value creation, and we appreciate your continued confidence as we move forward. With that, we can now end the call.

Speaker #1: Thank you, operator.

Speaker #3: And this does conclude today's conference call. Thank you for attending.

Operator: This does conclude today's conference call. Thank you for attending.

[Analyst] (TD Cowen): The host has ended this call. Goodbye.

Peyton Bohnsack: The host has ended this call. Goodbye.

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