Ironwood Pharmaceuticals Inc (IRWD) 2025 Q4 法說會逐字稿

Thank you for standing by. My name is Liz, and I'll be your conference operator today. At this time, I'd like to welcome everyone to the Ironwood Pharmaceuticals Q4 and full year 2025 Investor Update conference call. All lines have been placed on mute to prevent any background noise (Operator Instructions). Thank you. I would now like to turn the call over to Greg Martini, Chief Financial Officer. Please go ahead.

Good morning and thank you for joining us for our fourth quarter and full year 2025 Investor Update. A press release issued this morning can be found on our website.

Today's call and accompanying slides include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements involve risks and uncertainties that may cause actual results to differ materially.

A discussion of these statements and risk factors is available on the current Safe Harbor statement slide, as well as under the heading Risk Factors in our annual report on Form 10-K for the year ended December 31, 2024, and in our subsequent SEC filings.

All forward-looking statements speak as of the date of this presentation, and we undertake no obligation to update such statements.

Also included are non-GAAP financial measures, which should be considered only as a supplement to and not a substitute for superior to GAAP measures.

To the extent applicable, please refer to the tables at the end of our press release for reconciliations of these measures to the most directly comparable GAAP measures.

During today's call, Tom McCourt, our Chief Executive Officer, will begin with an overview of our 2025 progress on our strategic priorities and will provide an update on how we are maximizing Linzess. Mike Shetzline, our Chief Medical Officer, will discuss how we're advancing apraglutide, and I will review our financial results and 2026 guidance.

Tammy Gaskins, our Chief Commercial Officer, will also be available for Q&A at the end of the call. Today's webcast includes slides, so for those of you dialing in, please go to the events section of our website to access the accompanying slides separately. With that, I'll turn the call over to Tom.

Good morning, everyone and thanks for joining us today to review the fourth quarter and full year 2025 financial results and business updates. In 2025, we took several important steps to maximize LINZESS, advance apraglutide, and deliver sustained profits and cash flows to strengthen our financial position and position the company for long-term success.

Preludes us we delivered on the full year 2025 guidance with $865 million in LINZESS US net sales, supported by an impressive 11% demand growth and 8% new to brand volume growth year over year.

We also further strengthened the clinical utility of LINZESS with FDA approval in November of 2025, for the treatment of irritable bowel syndrome with constipation in patients seven years of age and older.

This new indication establishes LINZESS as the first and only prescription drug approved for the treatment of IBSC in patients 7 to 17 years of age. Which is great for patients in need.

In addition to expanding the clinical profile of LINZESS, we also took steps to lower the LINZESS list price effective January 1, 2026, in response to the evolving healthcare dynamics and to support ongoing patient access. For advancing apraglutide, we met with the FDA in the fourth quarter of 2025 and aligned on key elements of a confirmatory phase 3 clinical trial design, which we will be referring to as STARS-2.

We're on track to begin site activation. In the second quarter of this year and continue to believe that the data generated in the prior STARS phase 3 trial will support an eventual NDA submission.

Mike will discuss the phase 2 trial design in more detail later in the call. Lastly, for 2025, we finished the year strong, delivering $138 million in adjusted EBITDA and ended ending the year with $250 million of cash and cash equivalents on the balance sheet.

Positioning us well for 2026. Now looking ahead to 2026, on January 2, we announced a strong outlook for 2026 with our full year financial guidance highlighted by our expectation that Linds us will return to blockbuster status.

With greater than $1.1 billion in US net sales in 2026 driven by improved net price and low single-digit prescription demand growth.

We expect increased lends US net sales and our continued disciplined expense management to drive greater than $300 million in adjusted EBITDA in 2026, which will enable us to continue to advance apraglutide and reduce our debt to further strengthen our financial position.

As such, our priorities in 2026 are clear. We'll continue to maximize LINZESS. We'll advance apraglutide by initiating STARS-2 for short bowel for short bowel syndrome patients with intestinal failure, and we'll continue to emphasize discipline, supply expense management to deliver profits and meaningful cash flows, which will enable us to reduce our debt and further strengthen our financial position.

With clear 2026 priorities and our improved financial position, we now have a clear path to execute our strategy, and we'll continue to evaluate all options to maximize shareholder value.

Moving to slide 6. We're particularly excited about the opportunity we have with apraglutide, which has demonstrated strong efficacy and tolerability to date, becoming the first and only GLP-2 to achieve a statistically significant reduction in weekly parental support volume with once weekly administration.

Patients in our open label extension study, STARS extend, continue to reduce parental support volumes with longer-term exposure to apraglutide. Data presented at the American College of Gastroenterology meeting in October reported 34 patients have achieved and maintained mental autonomy or complete weaning of parental support for at least three months.

Our conviction for the commercial opportunity for apraglutide remains high because of the strength of these data and the fact that many GLP-2 eligible patients with high parental support burden go untreated or discontinue therapy.

We believe that the clinical profile with demonstrated efficacy, tolerability, and once weekly administration of apraglutide. Can redefine standard of care for short bowel syndrome with the potential to improve adherence and increase the number of GLP-2 treated patients.

To generate greater than $700 million in US peak net sales. The addition of potential approvals in geographies abroad would further increase the opportunity.

I'd also like to take a moment to acknowledge that February 1, was Intestinal failure Awareness Day, and February is Rare Disease Month. As we work towards our goal of developing and commercializing life changing therapies for patients suffering from GI and rare diseases.

We also seek to increase awareness for people we serve who are at the center of our work year-round. Short bowel syndrome is a devastating condition, and we thank you for your trust as we work with urgency to deliver this important new medicine to short bowel syndrome patients who are dependent on parental support. With that, I'll now hand it over, I will now move to our commercial performance update on page 7.

Throughout 2025, Lins continued to maintain its prescription market leadership. For the treatment of IBSC and chronic constipation in the US, recently surpassing 5.7 million unique patients treated since launch and ending the year with roughly 45% market share.

With over 40 million addressable patients in the US, we believe LINZESS still has a significant potential to grow prescription demand over the over the coming years due to the significant unmet need and the dissatisfaction with OTC therapies.

Once again, LINZESS delivered strong double-digit demand growth, increasing 13% year over year for the fourth quarter and 11% for the full year in 2025, the second consecutive year delivering 11% prescription demand growth.

LINZESS demand growth consistently outpaced the market and was supported by all-time highs in new to brand patient volumes.

Turning to 2026. After two consecutive years of declining LINZESS net sales driven by price headwinds associated with legislative changes, we expect to return lends US net sales growth in 2026.

Effective January 1, LINZESS's list price was lowered in response to the evolving healthcare dynamics and to support ongoing patient access.

As a result of this change, we expect more than a 30% increase in 2026 LINZESS US net sales year over year. Specifically driven by the elimination of the inflationary component of statutory required rebates across the channels, including Medicaid, due to this decrease in list price.

We've maintained our class leading payer access in 2026, and expect low single-digit prescription demand growth over the course of the year. With this improved pricing and net sales growth, we expect LINZESS will continue to drive meaningful cash flows to fund the next stage of growth with the commercialization of apraglutide if approof. With that, I'll turn the call over to Mike to share more details on the continued development of apraglutide. Mike.

Thanks, Tom, and good morning, everyone. 2026 is shaping up to be a critical year for advancing the apraglutide development program with the launch of our phase 3 confirmatory trial, STARS-2, expected in the second quarter of 2026.

In April 2025, we announced that the FDA requested a confirmatory phase 3 trial to seek approval for apraglutide, given the pharmacokinetic analysis of our prior STARS phase 3 data indicated that the exposure and dose delivered in the trial were lower than planned due to dose preparation and administration.

As a reminder, STARS was the largest ever phase 3 trial conducted of the treatment for short bowel syndrome with intestinal failure, and we continue to anticipate this data set, along with the data from STARS-2 will support a future NDA submission. As Tom mentioned, we met with the FDA in the fourth quarter of 2025 and aligned on key elements for the STARS-2 trial, and we're pleased to share some initial details with you today.

For STARS-2, we plan to enroll 124 patients with short bowel syndrome with intestinal failure in a one-to-one randomization. Enrollment will include patients with both stoma and colon in continuity anatomy to be representative of the heterogeneity of the overall population of patients with this condition.

Our primary endpoint for the study will be the same as our prior STAR phase 3 clinical trial evaluating the relative change from baseline in actual weekly parenteral support volume at week 24 in the overall patient population.

Key secondary endpoints also to be measured at week 24 for the overall population include clinical response defined as less than 20% reduction of defined at least 20% reduction in parental support volume, number of days off parental support per week, and enteral autonomy.

Patients will receive a 3.5 milligram once weekly dose of apraglutide to align with what was delivered in the prior phase 3 trial. In designing this STARS-2 trial, we have leveraged learnings from a prior STARS phase 3 to refine the instructions for use to optimize dose administration.

We expect to begin initiation of trial sites in the second quarter of 2026 and anticipate the study timeline to support an NDA submission before the end of 2029.

We are encouraged by the efficacy and tolerability data of apraglutide to date through the STARS trial and the long-term extension study, which give us confidence in the potential outcome of this confirmatory trial and in apraglutide's potential to be a best-in-class treatment for short bowel syndrome with intestinal failure as we pursue an eventual regulatory approval.

We look forward to initiating the STARS-2 trial as we continue to grow our body of clinical evidence supporting apraglutide's potential to become the first long acting once weekly GLP-2 therapy for the treatment of short bowel syndrome if approved. With that, I'll turn it over to Greg to review our financial performance in 2025. Greg.

Thanks, Mike. We ended 2025 in a strong financial position, achieving our latest full year 2025 guidance. Turning to slide 14 to review full year 2025 financial highlights.

LINZESS US net sales were $163 million in the fourth quarter and $865 million for the full year. Fourth quarter, LINZESS US net sales decreased 27% year over year, with net price erosion being partially offset by 13% prescription demand growth.

Fourth quarter net price was impacted by unfavorable quarterly phasing of gross to net rebate reserves due to units dispensed for the quarter exceeding units sold to wholesalers.

As a reminder, in the fourth quarter of 2025, in the first quarter of 2025, we noted a change in ABV's estimate of gross to net rebate reserves for 2025, based on expected rebates owed for units dispensed by channel in each quarter, which was expected to impact the quarterly phasing of LINZESS US net sales but not impact full year results.

Accordingly, full year LINZESS US net sales decreased 6% year over year, with net price erosion primarily associated with the Medicare Part D redesign, partially offset by 11% prescription demand growth.

Total Ironwood revenue was $296 million. GAAP net income was $24 million and adjusted EBITDA was $138 million.

Now moving to our balance sheet. We significantly improved our financial position by the end of 2025. Disciplined expense management, including a $61 million reduction in operating expenses year over year, resulted in $127 million in cash flows from operations and $215 million of cash in cash equivalents at year end.

We expect our strong cash position and 2026, outlook will support delivering of our balance sheet while simultaneously funding investment to drive long-term growth. We plan to use our cash on hand and cash flows generated to reduce our total debt balance in 2026, including repayment of our 2026, convertible notes at maturity in June, and expect to end the year with approximately $300 million of debt on the balance sheet, less than one-time 2026 adjusted EBITDA by year end.

Moving to our financial guidance on slide 16, we are reiterating our 2026 guidance. This includes US LINZESS net sales between $1.125 billion and $1.175 billion a greater than 30% increase year over year driven by improved net price and low single-digit prescription demand growth.

We expect Ironwood revenue between $450 million and $475 million and we expect adjusted EBITDA of greater than $300 million.

In summary, we are entering 2026 in a position of renewed financial strength and have a clear set of priorities as we strive to deliver long-term value by maximizing LINZESS, advancing apraglutide, and delivering sustained profits and cash flows.

We look forward to beginning site initiation for STARS-2, a confirmatory phase 3 trial for apraglutide in the second quarter, and we believe we have the opportunity to redefine the standard of care for patients living with short bowel syndrome with intestinal failure.

I want to close by thanking all of our employees, patients, caregivers, and advocates for their shared dedication to advancing life-changing therapies for patients with GI and rare diseases. Operator, you may now open up the line for questions.

(Operator Instructions).

Jason Butler, Citizens.

Hey, thanks for taking the question. Just a couple on STARS-2. You, can you give us any more details on the learnings and, from STARS and the refined options for use that you're now including in the STARS-2? Can you also just give us an overview of where you and FDA aligned on using the same primary and key secondary endpoints? What gives you the confidence in repeating the data from STARS-1.

And then just lastly, when you think about the enrollment timeline and enrollment criteria, how should we think about, a, the ability to enroll the trial on the timeline you gave, and B, the similarities of the patient populations between one and two. Thank you.

Thanks Jason. Mike.

Yeah, thanks Jason. So in terms of the learnings, as the original STARS trial was a very successful outcome in terms of the primary endpoint and the benefit for patients as well as the GI and other systemic tolerability.

As we mentioned, what we learned most was about the dose and administration and what was involved in discussion with the agency was along those lines. So we really made a great effort in the revised approach to STARS-2 to ensure very accurate dosing and administration with better kit components and also instructions for use. I mean, that's the main difference, so to speak, in the two trials.

In terms of your next question was about the alignment on the endpoints. The agency clearly appreciated the endpoint in the primary STARS trial, the trial we completed successfully, and that's why the STARS-2 trial has the same primary endpoint as well as the.

In the key secondary endpoints as well, so those remain pretty much the same, and we obviously have a high degree of confidence in the outcome of the STARS-2 trial because of that similarity, and we do think we've drastically improved the instructions for use and the dose and administration for patients.

So expect that to be a positive contribution for the study as well. In terms of timelines, we learned a lot with the STARS original program. We certainly have taken those learnings to better inform us to start the STARS-2 trial. We already have a lot of sites in the STARS Extend program which we're going to continue to use as well, so we're thinking we're in a good position.

To successfully enroll the program in a timely fashion, that's why we put the timelines on the table in this call, but we're certainly going to do everything we can. It's a lot of work and the team puts a lot of effort into it. We're going to have to push to make it successful, but we absolutely believe we can do that and achieve it in the timelines we propose.

That that's great. I appreciate all the details.

Chase Knickerbocker, Craig Holland.

Good morning. Thanks for taking the questions. Maybe just to start on the strategic alternatives process in a respect, we're not getting, a kind of a formal update, but can you maybe just update us on your thinking as far as kind of now that you can, at least in our model, clearly continue on as a standalone company, you retire the debt, kind of how you're thinking about the strategic alternatives process, as we kind of go forward in the '26.

Thanks Chase. This is Tom, and you know we're obviously in a very different financial position today than we were nine months ago when we were looking at, what were, what are our strategic alternatives, and I think because of that, we clearly have a path forward to certainly, leverage the revenue that is coming, the increased revenue that's coming off lends us.

As well as reduce our debt and mobilize the trial. That being said, we're obviously always open to alternatives that would increase shareholder value, there was a lot of interest, in Ironwood and in our assets, but we wanted to make sure that we were really smart with regard to the choices we made to make sure that we could protect the shareholders.

So I think as we move forward. We'll focus on executing as quickly as we can and as strongly as we can and always consider, are there ways in which we can increase your holder value.

Understood. Thanks. Maybe just, another one for Mike on the, on STARS-2. It seems like timelines, expectations for full enrollment are somewhat similar to STARS-1, maybe a little bit shorter, maybe just talk about kind of some of the assumptions you're making.

As far as kind of that time timeline to full enrollment, I know there's another, large study in the same patient population, at least relative to overall, kind of market size. Can you just kind of talk about some of the assumptions that you're making on total enrollment as it compares to STARS-1?

I think that's a good question, Chase. Thanks for the question. I think it's you're correct in a lot of ways. We've aligned with how we saw STARS-1 play out. We thought we did a fair job executing that study as well. So that's where a lot of the assumptions are based. We certainly I think we can achieve that in the STARS-2 program, and that's what the team is pushing and positioning to do and deliver, the trial as we project here for an eventual NDA submission, but it really is grounded in what we did in STARS-1, which, as we said, was a very successful study.

The other thing, to consider here, Chase, is, this is a very attractive study if you're a patient. You think about how strong the drug performed in the first trial, so there's a very high probability of success, it's an extremely well tolerated once weekly dosing administration and it's a 24 week trial.

So I think when you combine the fact that you have a very high probability of success, you have a, highly effective, extremely well tolerated once weekly therapy, and a 24 week trial, I think we're delighted with what Mike has been able to do with the FDA as far as, not only get the trial up and running with the design we have, but also, the length of the trial as well, which obviously. Is a big driver, with regard to the time to get to market.

Got it. Maybe just less for me on, actually going to ask a question on 2027, but just on LINZESS, as we kind of approach that negotiated price, can you maybe just talk to us about kind of what you've seen in the market, from prior negotiated drugs as far as, actually kind of some volume acceleration as we kind of go into that negotiated price here, and kind of how you think, we should be thinking about 2027, for LINZESS, when that negotiated price goes into place.

Yeah, thanks, Chase. This is Greg. So for 2026, we're clearly excited about the improved outlook that we have with our guidance that we provided back in January, reiterated today. We have a significant growth we're expecting in LINZESS net sales for 2026. We haven't provided any guidance for 2027, and beyond, but I would say that we continue to be very optimistic about the future of the brand and its ability to continue to drive strong net sales, which will continue to deliver profits and cash flows for Ironwood.

Understood, thanks.

Amy Li, Jefferies.

Hey, thanks so much for taking my question. So, for STARS-2, how much of your existing clinical data is the FDA allowing you to reference or bridge to a future NDA? And I think, people have said that your planned enrollment size seems slightly higher than your competitors, which is enrolling 90 patients.

So just curious if the trial size was by FDA request or is it more conservative decision on your end to have a more robustly powered trial. And then finally, given the competitive pressure in SBS-IF and potential for [adherence], could you potentially add a higher dose arm to maximize efficacy differentiation?

Yeah, thanks, Amy. So yeah, so in terms of the STARS-2 data, we were hoping to leverage the STARS data as much as possible, honestly, as we said, we're bridging based on the similar dose. The dose is aligned in the STARS-2 trial with what we put in the STARS original trial, so we're anticipating that we'll have to, we'll be able to use.

The original STARS data in the NDA submission. Now, obviously that's going to be a review decision because obviously we'll have to see the data and progress the trial as planned, but given that PK bridging, we think that the STARS original STARS data will be applicable for our future NDA.

In terms of the size of the STARS trial, we certainly did align with the agency on the key elements of the program to take forward, and we believe this current sample size that we've put on the table here with 124 patients gives us adequate and robust power along the primary endpoint and secondary endpoints as well.

And so that's what really drove the decision on the sample. Was to make sure we had a very robust clinical trial and confidence in the outcome. That's what we wanted to achieve. We recognize there may be differences with some other trials being performed, but this is where we settled based on the confidence we have in the program. We also had a significant amount of data from 07 to put strong numbers behind that selection.

And your last comment was about the higher doses. I think again we certainly have considered, continue to consider the opportunity with high doses. We're actually in, I think, an excellent position given the fact that SARS already has very robust efficacy data with a potential best in class profile and outstanding GI tolerability and weekly dosing.

So we certainly want to leverage that going forward, but we do continue to evaluate the opportunity to introduce a higher dose. As not everybody responds in a clinical trial, so there's certainly opportunity to potentially increase the breadth of response. But right now we're focused on getting fastest to market, and the best way to do that is to bridge with the 07 or the original STARS data set and complete this trial and confirm that evidence for an eventual submission.

Got it. Thank you so much.

Mohit Bansal, Wells Fargo.

Good. Thank you very much for taking my question and congrats on all the progress here. So a couple of questions from my side. So one is, did you ever see data from the STARS trial to look at patients who could achieve the optimum dose? Did they benefit more than the other patients who couldn't get to the optimum dose? That's the first question.

And the second question, I would love to understand how you are thinking about market opportunity for APRA in the case, you have [Gat-X] generic potentially reaching the market around the same time that is the latest on the Gat-X generic at this point?

Thank you.

How about I start with your question. Thanks, good question on the optimum dose. I think it's a really great question because obviously you raised the point of optimum dose. I think what has been amazing in the original STARS data set is the robust efficacy in the presence of basically placebo-like tolerability.

So that's a pretty amazing outcome in our industry where you really don't see any really negative consequences and it was. Pretty robust large trial, so that is quite a big learning. So we really think we had a way to get into sort of optimum dose with the STARS trial, and as I mentioned, that came out to be 3.5 milligram, which is what we're taking forward in the STARS-2 I think in the background of your question is kind of what we alluded to earlier is there an opportunity for greater efficacy?

And as we did do some early trials looking at 2.55 milligrams and 10 milligrams from a biomarker perspective. So there clearly is some biomarker evidence that there could be some response out there above 3.5, and as I said, we certainly have been considering that, but for right now, with again giving the optimum outcome we have in the original STARS trial, meaning robust efficacy in a very well tolerated once weekly therapy that people like, maintain, and continue because we still see improved outcomes even a year and two years out in the.

STARS extend trial. We really think the best opportunity is to take that forward in the confirmatory trial and get to market as soon as possible because as we're hearing, patients and investigators really like the drug and really want to maintain patience on it, and we'd like to get it to market as soon as possible. I think for the market question.

Yeah, hi Mohit, this is Tammy. Thanks for the question on the commercial opportunity. Just to echo Mike's comments commercially, we have very strong conviction.

In the overall clinical profile of glutide, right, and its potential to be differentiated in the GLP-2 class, especially because as Mike was just talking about, not only do we have a positive phase 3 trial, but also in the STARS extend long-term extension study, we continue to see increased improvement and PS volume reduction and days off of PS and even internal autonomy achievement, which we know.

Is really critical for patients in this market who are burdened by the everyday demands of being on parental support. And when we look to, as Tom referenced in the presentation, peak US net sales of, greater than $700 million that assumes that there will be a lepid glutide, and at least one generic set of glutide on the marketplace. But even with that, we still believe in the potential to drive apraglutide to market leadership.

Through expanding utilization of GLP-2 therapies and improved adherence, and we don't anticipate that this would be a multi-source generic market because of a lot of the demands required for small patients. Size for rare disease and demands required to support these patients both clinically and from a reimbursement perspective. So full belief in the commercial opportunity and what glutide can do as a different differentiated agent within that market.

(Operator Instructions).

Dominic Rose, [Ian Health].

Hi, and thanks for taking my questions. I've got two. My first question is, can you help us to understand what channel mix effects drove the LINZESS rebate in Q4 and whether we should expect ongoing volatility in pricing, this year.

And my second question is that the LINZESS commercial volume looks to have fallen at the beginning of the year based on the data we can see. So can you tell us what your formerly positioning looks like in this year versus the prior year? Thank you.

Thanks, Dominic. This is Greg. So fourth quarter pricing wasn't necessarily impacted by channel mix. It was really based on timing of recognition of gross to net rebate reserves. And in 2025, gross to net rebate reserves are based on units dispensed in the quarter.

So we had a higher volume of units dispensed in the fourth quarter relative to the units sold to wholesalers. So we saw a disproportionate impact from those gross to net rebates in the fourth quarter.

So it wasn't mixed. It was really timing of when those rebates were recognized. And if you look across the full year, it's really normalized from a timing perspective and you don't see a significant of an impact on the full year results as you did in first quarter and fourth quarter specifically, which were unfavorably impacted by that trend.

Moving forward in '26, we do not expect to have the same degree of volatility quarter over quarter. We do expect '26, will be a bit more consistent sequentially quarter over quarter than what we saw in 2025. And then from an overall, payer access, I'll have Tammy, talk to that in terms of 2026 coverage.

Yeah, so, as we've talked about already, of course, we, issued our full year guidance, which has both, significantly improved year over year due to a combination of improved net price as well as, low single-digit, anticipated low single-digit demand volume growth.

So we have maintained a big part of our decision to lower the back was also to ensure patient access, and we have maintained broad patient access for LINZESS across our biggest books of business, both commercial and Medicare Part D, which was critical in this.

And in terms of the low single-digit, we did expect Some impact on Medicaid as a percentage of business as states may decide to respond to the removal of the inflationary component of the statutory rebates, but we feel that we've taken the right approach for the guidance and continue to give patients branded prescription leading market access for LINZESS.

I think the other question you had was the reduction in volume year over year and you know this this drug has been on a linear growth curve since we launched it and its remarkable what sustained growth we've seen. We do see some seasonality, in the first part of the year because of the high deducting plans that there's a reset.

So we always, we generally always see in effect for the last 10 years we saw a reduction in the first quarter, first the prior fourth quarter, but then it accelerates through the year. So I think we're right on track from where we said we wanted to be, and we feel very good about, what the outlook for 2026, looks like.

Okay, thank you, that that's very helpful.

Ladies and gentlemen, that concludes today's call.

Thank you all for joining. You may now disconnect.