IRWD - NASDAQ

My name is Kathleen, and I will be your conference operator today. At this time, I would like to welcome everyone to the Ironwood Pharmaceuticals Fourth Quarter 2024 Investor Update Conference Call. All lines have been placed on mute to prevent any background noise. After the speakers remarks, there will be a question-and-answer session. Thank you. I would now like to turn the call over to Greg Martini, Chief Financial Officer. Please go ahead.

Good morning, and thanks for joining us for our fourth quarter and full year 2024 investor update. Our 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, 2023, 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 or 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 a brief overview. Mike Shetzline, our Chief Medical Officer, will discuss our pipeline, and I will provide a commercial update and review of our financial results and guidance. 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 2024 financial results and business updates. We're entering 2025 with a streamlined focus on advancing apraglutide and realizing its potential to significantly expand the market in GLP-2 treated patients with short bowel syndrome who are dependent on parenteral support. Recent data from our open-label extension study, which is called STARS Extend, further reinforce and strengthen our confidence in apraglutide's potential to become Ironwood's next blockbuster therapy. Last month, we shared an analysis showing that 27 total patients achieved enteral autonomy or in other words, achieved independence from parenteral support while on apraglutide. These data are important when thinking about the impact apraglutide can have in this patient population and demonstrate apraglutide's potential to provide patients with either longer periods away from or complete freedom from parenteral support. Building on these promising results, we're planning to include additional analysis based on exposure time from the long-term extension study into our NDA submission package to support an even more robust, clinically differentiated and comprehensive data package to the FDA. As we recently announced, we have initiated the rolling submission of our NDA and expect to complete submission in the third quarter of 2025. If approved, apraglutide will become the first long-acting GLP-2 to market for short bowel syndrome patients who are dependent on parenteral support, providing a new treatment option with the convenience of once-weekly dosing. Aligned with this next phase of growth, we have restructured our business to focus on bringing apraglutide to market, strengthening our commitment to advancing care for patients with short bowel syndrome. We believe these changes we've made position us for future growth, long-term value creation and ultimately reinforce our commitment to bringing new medicines to patients with rare disease. We have a strong team in place to drive the success of apraglutide if approved. Our commercial efforts led by Tammi Gaskins, our newly appointed Chief Commercial Officer, and she is supported by an experienced team with expertise in key functional areas of commercialization in both GI and rare disease. And we're actively preparing for a potential commercial launch. Unlike LIN

Thanks, Tom, and good morning, everyone. We're pleased to have initiated our rolling NDA submission earlier this year, which we expect to be completed in the third quarter of 2025. I want to dive a bit deeper into the opportunity around apraglutide and the compelling data generated from the STARS Phase III clinical trial, including additional data from the open-label extension study, STARS Extend. Short bowel syndrome with intestinal failure results from severe organ failure due to a reduction in intestinal function below the minimum necessary for adequate nutrition and fluid absorption, leading to a dependence on parenteral support or the IV administration of fluid and nutrients to maintain health, growth and survival. Approximately 18,000 adult patients are impacted by this disorder across the U.S., Europe and Japan. This condition is associated with increased mortality, significant morbidity, high economic burden and reduced quality of life. Intervention with parenteral support comes with its own challenges affecting quality of life. Parenteral support can be required for 10 hours a day and 6 days a week on average. Due to the significant patient burden, reducing the number of days and/or the hours a day per week on parenteral support is extremely important to patients and their health care providers. Apraglutide is uniquely designed to accelerate intestinal growth for improved gut function and intestinal absorption. Apraglutide is the only GLP-2 analog to achieve a statistically significant reduction in weekly parenteral support volume with once-weekly dosing. In the STARS Phase III study, patients also achieved clinically meaningful parenteral support volume reductions as early as week 8. Additionally, as previously presented, some patients achieved 2 and 3 days off of parenteral support per week and a portion of patients achieved enteral autonomy in the STARS Phase III study. Enteral autonomy is when individuals no longer require parenteral support, a significant life-changing milestone for patients and their families in their treatment journey. We're now seeing even more patients achieving enteral autonomy in our extension study, further reinforcing apraglutide's clinical profile. As Tom mentioned, based on an analysis we shared in January, 27 total patients treated with apraglutide achieved enteral autonomy. Beyond that, we continue to see encouraging trends in parenteral support volume reduction more broadly with longer exposure to apraglutide. We're excited by this growing body of clinical evidence that we believe supports apraglutide's potential, if approved, to become the first long-acting once-weekly GLP-2 therapy for the treatment of short bowel syndrome. With that, I'll turn it over to Greg to review our financials. Greg?

Thanks, Mike. We ended 2024 in a strong financial position, achieving our 2024 full year guidance. Our business continues to be supported by strong LIN

Thank you. We will now begin the question-and-answer session. [Operator Instructions] And your first question comes from the line of Chase Knickerbocker of Craig-Hallum. Your line is now open.

Good morning. Thanks for taking our questions. Just first for me, I get it's kind of early after kind of just taking these kind of headcount changes. But can you kind of just speak to the confidence you have in any kind of initial kind of learnings now that you kind of went to more virtual-based marketing, at least personally with yourselves, around kind of the confidence you have on high single-digit volume growth this year without that in-person promotion from the Ironwood side? Thanks.

Tom, do you want to take that?

Yeah, sure. Thanks, Chase. As you know, we still have a very solid marketing mix supporting and driving the growth of LIN

That's great, Tom. Thanks. And Greg, maybe just a couple on the model. First, if we think about kind of the cadence of cost savings, should we be kind of assuming that Q1 has a fairly full kind of recognition, at least on a run rate basis of kind of those cost savings? And then just second, on the R&D line, as these kind of trial activities start to roll off, I mean, when should we be kind of modeling a decrease in R&D? Is it back half of '25? Is it in '26? Just help us think about expenses.

Yeah. Thanks, Chase. In terms of the cost savings actions that were taken last month, first quarter, we won't see the full impact because these actions were taken at the end of January. So you'll really start seeing that full run rate in Q2 for the rest of the year. And then as you think about R&D, really R&D for 2025 would not expect to see a decline really year-over-year, specifically with apraglutide in the ongoing extension study and also some of the CMC activities that we're continuing to complete as we move forward and prepare for a commercial launch. The 2026 is where we would start to see some of that inflection in terms of overall R&D spend. We'll provide more details on that as we get closer to '26.

I think it's important to mention, Chase, too, on the long-term extension. As Mike mentioned earlier, I mean, as we continue to actively follow these patients, we're seeing ongoing reduction in parenteral support and even enteral autonomy. So I think this is a really solid investment for us to really further understand the potential benefit that these patients can occur over time. And certainly, that obviously strengthens the overall profile of the drug.

Got it. And then just last thing for me, Greg, and I'll hop back in queue. But can you just kind of speak to the confidence around maintaining compliance on the covenants around the revolver. And it gets a little bit complex. I think it would be kind of helpful to kind of walk through a little bit of the kind of detailed math on kind of some of those add-backs, if you'd oblige us. Thank you.

Yeah, absolutely. Thanks, Chase. I think just broadly speaking, we have a high degree of confidence in our outlook of 2025. With our financial guidance, we will be able to continue to maintain covenant compliance throughout the year and have a very high degree of confidence there. We did adjust the adjusted EBITDA definition, as I noted in the prepared remarks, to give a little bit more clarity about some of the key adjustments we have with those debt covenants, specifically with stock-based compensation. But there are other add-backs, and I can't necessarily go through all of them in detail. But there are other add-backs that do give us additional room and comfort with being able to achieve those covenant amounts for our debt throughout '25. And it's something we're very much focused on and very focused on disciplined expense management to continue to drive profits and cash flows with those covenants in mind.

Thanks, guys. Operator Your next question comes from the line of Jason Butler of Citizens JMP. Please go ahead.

Hi. Thanks for taking the question. Just had one on the long-term data for apraglutide. Can you maybe speak to the patient characteristics of those patients reaching or achieving enteral autonomy? I guess were you seeing this from both CIC and stoma patients? And then how does this compare to the double-blind period of the study where you - I think it was about 7 patients achieved enteral autonomy. Have any of those patients maintained enteral autonomy for the entire period? Thank you.

Yeah. Thanks, Jason. Thanks for the question. So in terms of the patients achieving enteral autonomy, we really benefit from the fact that we have completed the largest ever done Phase III program in SBS-IF. So it's SBS-IF, as you know, is a very heterogeneous syndrome patient disease. So having that large patient population really gives us an opportunity to look at a broad spectrum of patients and their outcomes. And if you - to direct your question to the enteral autonomy, we certainly are seeing patients achieve enteral autonomy on both stoma and CIC. We'll actually roll out the details on the whole population. That's one of the things we're putting together for the submission because we know that's an important question for all of us in terms of understanding the critical benefit to this patient population. And it's fair to say that it is in all of the secondaries, we presented some of this data last year, too. In all the secondaries that look at subpopulations across SBS-IF, we really do always see a numerical benefit with apraglutide. So we really do think this - the patient population that we're targeting is the right one, meaning the broad patient population with short bowel syndrome and intestinal failure. In terms of the double-blind data, you probably recall that initially, we saw enteral autonomy achieved at 24 weeks, and that actually included stoma patients as well. And then by the end of 48 weeks, we had roughly 10 patients achieve enteral autonomy. The 27 comes from adding in the STARS Extend data, which is the 012 study, which is the extension study. And that brought that number up, obviously, to a very meaningful number of 27, which really in aggregate is a pretty robust outcome if you look at other comparator products in terms of how many patients are achieving enteral autonomy. And the patients who achieved enteral autonomy in the double-blind period carry on into the extension program. So we're really seeing good fidelity. And once patients achieve enteral autonomy, they maintain it.

Great. Thank you for taking the question.

Your next question comes from the line of Amy Li of Jefferies. Please go ahead.

Hi. This is Kathy on for Amy. Congrats on the quarter. So I guess I was wondering, as we think about the timing of the Medicare Part D redesign impact, is it fair to assume that the impact to LIN

Yeah. Thanks, Kathy, for the question. I think the key for us is our full year guidance obviously takes into account our expectations for this redesign for the full year. I think there is an element of timing here where we will have to see how prescription demand trends and ultimately the tiering within Medicare Part D plays out over the course of the year. So I do think each quarter we move forward, we'll have better insights into what the potential price exposure is, but we feel very confident that our guidance range appropriately accounts for the trends and the expectations we have for the year.

Okay, great. Thank you.

Your next question comes from the line of Faisal Khurshid of Leerink Partners. Please go ahead.

Hi, guys. This is Matt Cowper on for Faisal. Thanks for taking my questions. Just a couple for me. How should we be thinking about the launch expenses for apraglutide, both in terms of magnitude and timing? And what levels are contemplated in the 2025 adjusted EBITDA guide? And then second question, just what options exist around the 2026 convert? And how is the company thinking about managing that? Thank you.

Thanks, Matt. I can take both of those. In terms of the commercial launch expenses, we have been working on commercial planning activities from 2024, and we'll continue that into 2025. I would say at this point, they are not significant expenses within the overall P&L, and we would expect to see a bit of a ramp-up as we get closer to launch in 2026. And we'll provide additional details on exactly what that spend looks like as we get closer to that timing. And then in terms of the 2026 convertible notes, this is something that we continually evaluate our capital structure in the context of our overall forecast and outlook, and we are very much focused throughout 2025 on strengthening our balance sheet with the intent on driving profits and cash flows to repay our existing debt. And so we'll provide additional details as we make decisions on any further actions on our balance sheet. But at this point, I really want to focus on driving cash flows to repay our outstanding debt.

Got it. Thank you.

Your next question comes from the line of David Amsellem of Piper Sandler. Please go ahead.

Hey, thanks. I joined late, so maybe you already addressed this. But can you just talk more broadly about the cost structure? It's not so much about your ability to launch apraglutide, but the extent to which you can extract more savings. I know you had the recent restructuring. But maybe talk more about how you're thinking about further streamlining just given the state of the capital structure. Thanks.

Yeah. Thanks, David. In terms of cost structure, I think we feel very good about our outlook, as I mentioned, in terms of 2025 and the actions we've taken to really focus on profits and cash flows in '25. As we move forward, we'll continue to evaluate other alternatives to really prioritize investments focused on those investments we think will drive the best long-term value. And that includes the Ironwood P&L, as well as the overall LIN

Okay. Thank you.