Ironwood Pharmaceuticals Inc Q1 FY2024 Earnings Call

Thank you for standing by. My name is Kath, and I will be your conference operator today. At this time, I would like to welcome everyone to the Ironwood Pharmaceuticals First Quarter 2024 Investor Update Call. I would now like to turn the call over to Matt Roache, Director of Investor Relations. Please go ahead.

Thank you, Kath. Good morning, and thanks for joining us for our first quarter 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, 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 Sravan Emany, our Chief Financial Officer, will provide a commercial update to review 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.

Thanks, Matt. Good morning, everyone, and thanks for joining us. We are pleased to be here to discuss the significant advancements that we’ve made across our portfolio so far this year and our mission to become the leading GI healthcare company. I always like to start with the three strategic priorities, which are: maximize LINZESS; advance our GI pipeline; and deliver sustained profits and cash flow. In the first quarter of 2024, LINZESS maintained its strong demand momentum with prescription volume increasing 10% year-over-year, supported by a robust new-to-brand prescription growth of 18% compared with the prior year, marking the fifth consecutive quarter of double-digit new-to-brand growth. Based on information provided by AbbVie, we recorded an adjustment to the first quarter collaborative arrangement revenue as a result of a gross-to-net change in estimate for LINZESS related to the year ended December 31, 2023, which led to our revised full year 2024 outlook. Sravan will provide more detail on the impact of this one-time adjustment later in the call. Moving to our pipeline, we made important progress across our development programs in the quarter. Most notably, we believe we have transformed our company with positive topline results in February from the Phase III STARS trial, evaluating the efficacy and safety of apraglutide in patients with short bowel syndrome with intestinal failure. These positive Phase III results demonstrate the potential of apraglutide as the first and only weekly GLP-2 therapy for the treatment of adults with short bowel syndrome who are dependent on parenteral support, if approved. Following the topline results shared in late February, we have continued to analyze a robust dataset of the STARS Phase III, and new data were submitted as a late-breaking abstract and selected for an oral presentation at the upcoming Digestive Disease Meeting. These data further strengthen the clinical profile of apraglutide, which we’re eager to share with the broader GI medical and scientific community. Based on the combination of demonstrated efficacy, tolerability, and once-weekly dosing, we are confident that apraglutide has a high probability of approval. We believe these three distinguishing factors will drive uptake, compliance, and improvement in quality of life for patients, reinforcing our belief that apraglutide has the potential to achieve $1 billion in peak net sales. We are now focused on ensuring a successful path forward to commercialization, an area where we have significant expertise and a track record of success. We are working swiftly and plan to file the NDA as soon as possible with a label focused on adult SBS patients who are dependent on parenteral support and continue to expect a commercial launch in 2025. We estimate that there are approximately 17,000 adult patients across the United States and Europe who suffer from short bowel syndrome with intestinal failure, with a significant portion of these patients still untreated by GLP-2s. We have the commercial infrastructure already in place and expect only incremental investments needed to launch apraglutide successfully. We are well on our way with the launch planning and believe we are equipped to commercialize apraglutide, if approved, with a strong sales presence already established in the offices of GI specialists across the United States. We are confident the positive results from the STARS trial coupled with our proven track record of effective commercial execution position us uniquely in the market. We’re excited to leverage our expertise to maximize the potential for apraglutide and drive meaningful impactful outcomes for patients with short bowel syndrome who are dependent on parenteral support. So to wrap up, we are poised for future growth for the following reasons: first, LINZESS continues to deliver robust demand growth and is driving meaningful cash flows for Ironwood, which we expect to continue until generic entry in 2029; second, we believe we have transformed our company with positive Phase III results from the STARS trial, which reinforce our conviction in apraglutide's high probability of approval and long-term revenue and profit growth potential; finally, we're excited to see the Phase II topline results from CMP-104 later this year. We believe CMP-104 has the potential to be a disease-modifying therapy for the treatment of primary biliary cholangitis. With that, I'll hand it over to Mike to discuss apraglutide and our pipeline in more detail. Mike?

Thanks, Tom, and good morning, everyone. We're pleased with the progress we made across our pipeline programs in the first quarter. I'll begin with apraglutide for short bowel syndrome in patients dependent on parenteral support. We're very proud of the positive results from the pivotal global Phase III STARS study, which is the largest-ever GLP-2 trial in short bowel syndrome with intestinal failure, generating a robust dataset across 68 sites and 18 countries. An important aspect of the STARS Phase III study design was the rigorous optimization of parenteral support volumes prior to treatment. That resulted in a low placebo rate, which in turn generated a robust treatment effect for apraglutide in this patient population. Apraglutide is the only once-weekly GLP-2 to meet its primary endpoint of relative change from baseline in actual weekly parenteral support volume at week 24 with a 2x treatment effect relative to placebo driven by both stoma and colon-in-continuity populations. As a clinician myself, I'm thrilled about apraglutide's strong profile, including the convenience of once-weekly administration and its potential to benefit a patient community in need of new treatment options. Summarized on Slide 9, I'm excited by the demonstrated efficacy in the primary endpoint in both stoma and colon-in-continuity patient populations at 24 weeks. With further analysis of the data, we're also excited by the rapid onset of treatment effect observed at week 8 and onward throughout the study. The fact that some patients in both stoma and colon-in-continuity populations reached enteral autonomy or a complete weaning off of parenteral support and the low prevalence of reported injection site reactions and abdominal distension, which are in line with placebo. Overall, we believe apraglutide's differentiated profile, including its demonstrated efficacy and tolerability and convenience of once-weekly dosing supports our belief in apraglutide's high probability of approval and potential to improve the standard of care for patients who suffer from short bowel syndrome who are dependent on parenteral support. We're very much looking forward to the upcoming DDW meeting and presenting data, which we believe further supports and enhances the clinical profile of apraglutide. We also look forward to continuing to evaluate the robust dataset from the largest-ever GLP-2 study in short bowel syndrome with intestinal failure, and plan to disclose further findings at additional meetings later this year. In addition to the positive Phase III results from apraglutide in short bowel syndrome with intestinal failure, we also announced positive results from our exploratory STARGAZE trial of apraglutide in patients with steroid-refractory gastrointestinal acute graft versus host disease. The primary objective of the trial was to evaluate the safety and tolerability of once-weekly apraglutide in steroid-refractory acute GVHD patients treated with standard of care. Results up to day 91 showed that apraglutide in acute GVHD was well tolerated with an acceptable safety profile, the study's primary objective. In addition to evaluating safety, secondary endpoints assessed efficacy via lower GI and all organ responses. The majority of patients responded to treatment by day 28 and day 56, all lower GI responders at day 28 maintained their response through day 56 and 91. We're encouraged by the data on safety, tolerability, and maintenance of response and expect to present additional data at a future medical congress. The STARGAZE study will continue through its 2-year endpoint when apraglutide will be evaluated for safety and efficacy. Moving to CNP-104, in the first quarter, COUR completed patient enrollment for the Phase II proof-of-concept study in patients with PBC and are on track to report topline results in the third quarter of this year. The CNP-104 Phase II study is of a 42 patient placebo-controlled study evaluating the safety, tolerability, pharmacodynamics, and efficacy of CNP-104 in patients with PBC who are unresponsive to UDCA and/or Ocaliva. Topline results will be based on data through day 120 of treatment. The strong immunology underpinning the CNP program is focused on targeting the specific PDC-E2 antigen responsible for the T cell-driven pathology of PBC. Last year, we saw early data showing favorable PDC-E2 specific T cell responses in patients treated with CNP-104. In the topline results anticipated in the third quarter, we're looking for a demonstrated T cell response, which we believe is a leading indicator of clinical benefit. The study will also evaluate several markers of liver function. A positive signal on liver function markers in addition to the T cell response could further support the potential for CNP-104. We believe CNP-104 has the potential to be the first disease-modifying therapy for patients suffering from PBC as there are no therapies on the market today that address the root cause of the T cell-driven immune destruction of the liver bile ducts. With that, I'll turn it over to Sravan.

Thanks, Mike, and good morning, everyone. I'll begin on Slide 12. As Tom mentioned earlier, LINZESS carried the positive demand momentum into the first quarter. This is now the 12th year on the market for LINZESS, and as you can see, prescription demand remains remarkably strong. LINZESS volume rose 10% year-over-year in the first quarter, while new-to-brand prescriptions increased 18% compared with the first quarter of 2023, reinforcing that patients and healthcare professionals continue to choose LINZESS. We believe the strong demand momentum and success of LINZESS will continue as a result of high treatment satisfaction with both patients and healthcare professionals, combined with increased utility from the pediatric indication, class-leading formulary access, guideline recommendations, focused commercial execution, and new patient start acceleration. I'd like to take a moment to provide additional details on the LINZESS gross-to-net change in estimate that was reflected in the first quarter of 2024 on Slide 13. In the first quarter, AbbVie reported U.S. net sales of $257 million, an increase of 3% year-over-year. Based on information subsequently provided by AbbVie, Ironwood estimates a $60 million adjustment to LINZESS U.S. net sales, representing the difference between AbbVie's gross-to-net estimates made in 2023 and actual subsequent payments made. As a result of this change in estimate, Ironwood recorded a $30 million reduction to collaborative arrangements revenue. With this adjustment, total Ironwood revenue in the first quarter was approximately $75 million, down 28% year-over-year. Turning to our first quarter financial performance slide on Slide 14. Q1 LINZESS U.S. net sales, as reported by AbbVie, were $257 million, an increase of 3% year-over-year. LINZESS' commercial margin, excluding the gross-to-net change in estimate, was 71% in the first quarter of 2024 compared to 73% in the first quarter of 2023. As I noted a few moments ago, Ironwood revenue was $75 million, driven primarily by U.S. LINZESS collaboration revenue of $72 million. Revenues in Q1 were lower year-over-year primarily due to the $30 million change in estimate recorded to collaborative arrangements revenue. As a result, GAAP net loss was $4 million, and adjusted EBITDA was $13 million. In the first quarter, Ironwood generated approximately $45 million in cash flow from operations, and ended the quarter with $122 million in cash and cash equivalents after repaying $25 million of the outstanding principal balance on our revolving credit facility in cash. As of the end of March, the outstanding drawn balance on the revolver was $275 million. In the near term, we continue to expect to settle our 2024 convertible notes that mature on June 15 through a combination of cash on hand and undrawn revolver capacity. Regarding capital allocation, we are in a fortunate position with meaningful cash flow generation for LINZESS, which we believe will be sufficient to fund all ongoing operations, and we do not anticipate the need to access the capital markets for incremental funding to support the potential apraglutide launch and further progress our development programs. Next, I'll review our updated 2024 guidance on Slide 15. As a result of LINZESS' gross-to-net change in estimate in the first quarter, for the full year 2024, we now expect LINZESS U.S. net sales to decline in the mid-single digits percent. Ironwood revenue is expected to be between $405 million and $425 million, and adjusted EBITDA is expected to be greater than $120 million. To wrap up, we made significant advancements across our portfolio in the first quarter. We look forward to sharing additional detail from the apraglutide STARS Phase III study at Digestive Disease Week later this month, which we believe will further enhance the clinical profile of apraglutide. With the positive STARS data readout, we believe we are well on our way to diversifying our portfolio and extending our growth horizon beyond LINZESS. Looking ahead, we are focused on moving quickly to get apraglutide approved and to patients with SBS who are dependent on parenteral support as soon as possible and executing across our strategic priorities by advancing our other GI pipeline assets, driving robust LINZESS demand growth, and delivering sustained profits and cash flow. I want to close by thanking all of our employees, patients, caregivers, and advocates for their shared dedication to advancing and supporting therapies for GI diseases. Operator, you may now open up the line for questions.

Your first question comes from the line of David Amsellem with Piper Sandler.

So a couple of questions here. I know you've got the data coming at DDW. But I just wanted to get some additional color on what you mean about efficacy across both stoma and colon-in-continuity patients. And I guess what I'm getting at is just within the CIC subgroup, is there statistical separation? I know what you had shown at 48 weeks, but is the statistical separation, say, at earlier time points, say, 24 weeks or 12 weeks? So just help us understand that. And if you can't answer it, that's fine, but I thought I'd ask the question anyway. And then secondly, on 104, what do you have to see in order to move forward? Help us understand how you're thinking about the bar for continued advancement.

David. So we're very excited about the data from apraglutide. A lot has been discussed around CIC versus stoma. It's just critical to remember that the primary endpoint included both stoma and colon-in-continuity patients. So we clearly think we have a high probability of approval for the whole population, stoma and CIC based on the fact that colon-in-continuity patients contributed to the primary endpoint. That was quite distinct from what happened with the regulatory precedent that GATTEX set, where they really didn't see a meaningful contribution from the colon-in-continuity patients. We continue to believe that the potency of the asset is well established now with this Phase III data, and that’s given us the opportunity for once-weekly therapy. What you'll see at DDW is a further rollout of the colon-in-continuity specific data, which certainly gives us even more confidence in the efficacy in colon-in-continuity patients. We certainly fully support the submission we're going to do for the whole population and have a high probability of success for approval in colon-in-continuity and stoma patients. In addition, there will be a fair amount of tolerability data, which will further support the differentiation of apraglutide from other GLP-2 therapies in the class. We've really learned a lot from the pivotal trial data in terms of safety and tolerability. And you'll see details on events and numbers at DDW, which really support a very safe and well-tolerated profile. In principle, most all events were actually in line with placebo. So we think it's a very good profile for commercial success. And the next question you asked was on CNP. What we plan to see in CNP as we discussed, the real strength of the CNP program is the science behind the immunology and what we know about the pathology of PBC. It's a PDC-E2-driven disease. And we can test the T cells that destroy the bile ducts with PDC-E2 to determine if treatment with CNP-104 modulates or reprograms those T cells. So we're really looking for a demonstrated T cell effect that shows that those T cells are no longer pathological, no longer prone to destroying bile ducts. In combination with that, we're looking for a meaningful clinical outcome, and that's why we have a number of liver function assessments in the trial as well. This 120-day assessment gives us the opportunity to look for that demonstrated T cell response and the potential opportunity to improve liver function assessment.

Your next question comes from the line of Chase Knickerbocker with Craig-Hallum.

Maybe just digging in a little bit on the gross-to-net adjustment from last year. Can you just talk to us about kind of what that was specifically as far as probably by payer channel? Or just however you think it's best to break that down just a little bit more detail around exactly what that $60 million adjustment was that was not accounted for by AbbVie?

Thank you for your question, Chase. To provide some context, the fluctuations in gross-to-net due to changes in channel mix are typical and occur regularly in this industry. This is something we experience periodically and it’s not material for us. The change in estimate was based on information provided by AbbVie after their reporting, highlighting the difference between the gross-to-net for the year and the actual invoices they received, primarily linked to government and contractual rebates. That's the information I can share regarding our position.

That's helpful. Maybe one for Mike. Can you just talk around kind of next steps with the APRA NDA? Certainly looking forward to the data, just maybe specifically on the filing. Have you had your Type B meeting or is that scheduled for soon? And then kind of talk a little about what's left to be done with all the data work that you've been doing in the background to prepare the submission.

Yes, sure. That's a good question. Clearly, that's our key priority. Our number one, two, and three priorities are the APRA submission. So it's all hands on deck for that. We continue to look at the data. That's what resulted in the DDW oral abstract acceptance, so we're very excited about that. That's going to support getting the data out. But also all that data is part and parcel to the submission and aligns with everything we're trying to do to get the submission in and on track. Currently, we're not planning the pre-NDA meeting, which we'll do as well. We're really looking forward to moving that submission forward as expeditiously as possible. We're still targeting a potential launch in 2025. As we get more granular on the submission timelines, we'll certainly make that available.

Okay. And then just last for me on CNP-104. Just to confirm for investors, when we get that data in Q3, that will include both T cell response, and we will also be able to see that liver function data. Is that right, Mike?

We plan to discuss the T cell effects, which will support the program’s focus on reprogramming and the immunology related to the PDC-E2 specific antigens. We intend to share this information along with liver function outcomes. Keep in mind that it's a 120-day Phase II study, which is the first in-human study for CNP-104. This is an early timeframe for analysis. Unlike other products which were studied for a year, we believe that our scientific approach offers a chance to observe early clinical endpoints in liver function assessments.

Great. And then just last Sravan, I'll come back to you. Just on guidance. I mean, looking at it, it certainly seems like the only material changes to your expectations were this $30 million adjustment. Is that fair to say as far as the Medicaid changes on the rebate cap this year, everything else is the same as far as your expectation goes on your revenue expectations in 2024 from LINZESS?

Yes. So I would say that our guidance now is reflective of the one-time adjustment. As you can see, had this been based on AbbVie's reporting, that I think we would have been relatively aligned, considering our performance of the brand continues to be really strong with double-digit demand growth. The pricing headwinds that we would have faced, or we anticipated, would include high single-digit price erosion and low single-digit revenue growth. So we're kind of there outside of the one-time out-of-period adjustment.

I think the only other comment that I would make on this is, as you can see, the demand is really remarkable with regard to what kind of growth we're seeing in year 11 and year 12 for the brand, which we obviously want to continue to nurture. What we do know is there are three things driving that. Certainly, the high treatment satisfaction is no question. But I think the other piece is payer access, which is part of the marketing mix. Now what we will be doing moving forward is really working with our partner to continue to evolve that marketing mix so we can really optimize the value that LINZESS can create. We have been doing this from day one as we've evolved the marketing mix; we've reduced the investment and increased the profit of the brand. As we move forward, I think we're seeing very durable growth in brand demand, and what we really want to focus on now is what is the right appropriate marketing mix and investment to continue to drive profits to the bottom line.

Your next question comes from the line of Amy Li with Jefferies.

On apraglutide, what is your current internal estimate on durability of treatment? And will we get any data at DDW to support potential differentiation on this? Additionally, can you give us any updates on how you're thinking about the addressable market for APRA post the ICD-10 codes being put in place late last year? And how many of these patients do you have access to with your current sales force?

So thanks, Amy. So in terms of durability, I suspect you mean more longer term. I mean, clearly, as the only once-weekly available therapy, we certainly think that Phase III data supports the weekly administration and sort of the pharmacokinetics and pharmacodynamics really lend itself to that once-weekly dosing. The data speaks for itself in that regard. In terms of longer term, the actual ideal goal for most patients is enteral autonomy, where they could come off all parenteral support. In that setting, they often would need continued GLP-2 therapy to maintain that intestinal growth. From that going forward, it will be up to them, obviously, and their position to caretake to understand how that long-term plays out. But the reality is in patients with short bowel who have limited bowel epithelium, they benefit from continued therapy from the GLP-2 because as we've seen with other GLP-2 therapies, when you come off it, you often revert back to a need for parenteral support.

And then on the question about the ICD-10 codes and our overall sales force, just taking a step back again, our level of access to the major GI practices across the United States is probably unparalleled from our perspective. We've got over 90 sales reps calling on these practices and leading clinicians. Specifically with the ICD-10 codes, we're really excited about this development, honestly, Amy Li. I think the big thing for us is that these ICD-10 codes are starting to shed real light on how many patients there actually are. I think there have been about 7,000 patients that have been identified already to date through the ICD-10 codes in just a few months. It just reinforces our estimates as more data comes to light about how many patients there are. Our presence across the United States gives us confidence in our ability to capture share with our best-in-class product and the overall profile of apraglutide having once-weekly administration, demonstrated real efficacy across both stoma and CIC patient populations, and then now, as you'll see in a few weeks, the safety and tolerability data being equivalent to placebo. I think that our ability to penetrate that and capture share to be a billion dollar brand is insightful. We feel confident about it.

Your next question comes from the line of Jason Butler with Citizens JMP.

First one is for APRA. Can you maybe talk about the work you're doing pre-commercial to build awareness of the brand, and beyond just obviously the presentation of data? What work you're going to do this year to prepare the market for the drug? And then just secondly, on LINZESS, can you maybe speak to the contribution of the pediatric market to growth this quarter and looking forward into 2024?

I mean, remind me, the first question was...

As far as the prelaunch activities, we are just in the midst of launching a disease education program targeted primarily on the GI community which will probably stretch into a digital platform for patients and for patients to seek better understanding and options. This is really about increasing the awareness of who these patients are, how debilitating this disease is, and the need for more effective therapy. Through that exercise, a big objective here as far as overall impact on performance is identifying available patients within these large GI practices as well as the academic centers of excellence. We’re very encouraged by the feedback that we’re getting from the key opinion leaders in the center of excellence as far as the response rate and the acceptance of apraglutide in the clinical trials, and they are all looking forward to working in a very collaborative way, not just as far as educating people, but also how we can help patients through the process to get better care. I think we’re very well positioned to prepare our go-to-market strategy. And of course, that work has been ongoing, and we're just in the early stages of implementing the disease awareness program. Do you want to take the LINZESS question? So Jason, on your question about the pediatric launch and its progress, I think we are clearly, overall, very positive about the pediatric indication. We're still early in the launch, frankly. But to date, we're really encouraged by the strong new-to-brand prescription volume growth. A large portion of that growth on a year-over-year basis is in the 72-microgram dose, which is the approved dose for the 6- to 17-year-old patient group. So it's embedded in those numbers, and I think it's part of what's sustaining our long-term growth here for LINZESS as we're in year 12.

Your next question comes from the line of Mohit Bansal with Wells Fargo.

I have a couple of questions. So one on the guidance again, thanks for the clarification. But one thing I wanted to ask was that typically, this happens because you had a particular mix in the, Mike, for government versus commercial, and that mix changed subsequently because you don't know it until you get the receipts and all. Are you expecting a similar mix, like the updated mix for 2024 as well? I'm asking because by our math, the impact that you are modeling is a little bit more than $60 million. So that's the first question. And the second question is on ALP with CNP-104. If I look at drugs like Seladelpar, there was an impact on ALP by month 1, and then at month 3, it was more like stabilized; after that, it was not an incremental impact. So isn't 120 days enough to see benefits? I appreciate the mechanisms are different. So how should we think about benefits on endpoints like ALP there?

Mike, why don't you go first and then I'll answer the guidance question.

Yes, thank you for the question. It's significant to note that the regulatory precedent focuses on ALP, which is how obeticholic acid received approval and what CymaBay is currently experiencing. This establishes an approved route for accelerated approval, albeit not full approval. CymaBay has also included pruritus to address that requirement. ALP provides a broad reflection of liver function, as it relates to bile movement through the liver. When administering something like obeticholic acid, a bile acid mimetic, bile flow increases, resulting in improved ALP as an early benefit. However, this improvement doesn't inherently correlate with the overall enhancement of liver function. This is why obeticholic acid necessitated a post-marketing commitment to demonstrate a broader benefit in liver function through histology, which didn't fulfill expectations at the time. It's crucial to understand ALP's role, and as you noted, our approach is fundamentally different. We are targeting the root cause of PBC, specifically the T cell-driven destruction of bile ducts. We firmly believe we can influence and reprogram T cells to prevent them from causing further damage. We anticipate clinical improvement, and while the timeline for this improvement is yet to be determined, we are optimistic about seeing early results due to the specificity of PDC-E2 and our therapy. That’s why we have set a 120-day assessment period, and we will be monitoring this closely. We need to demonstrate both a T cell response and improvements in liver function.

So on your guidance question, on a high level, I’d say again, our guidance for 2024 accounts for the mix we anticipate. We expect to still see high single-digit prescription demand growth, and I think the decline is as stated, based on our overall annual guidance. This is a one-time adjustment. We’ve been pretty good over the last several years in anticipating our estimates with respect to what that mix is in a channel. Channel mix is pretty fluid, and predicting LINZESS net sales can move in a positive or negative directions and has always been true. But we’ve been pretty good about it over the years. We are still expecting to deliver a mid-single-digit decline, as I said before, and that is predominantly driven by the one-time out-of-period adjustment.

Your next question comes from the line of Tim Chiang with Capital One.

Mike, I was just looking back at the secondary endpoints from the STARS study. Do you plan to show, I guess, the earlier week data from the CIC patient population at DDW, especially with the secondary endpoints that you didn't need statistical significance on?

Yes, Tim, if you're referring to specifically things like enteral autonomy or things you might see at 24 weeks versus the key secondaries at 48, the answer is yes. We certainly think that data further supports our conviction of good efficacy in both stoma and CIC patient populations. We plan to share that data at DDW, as well as sort of the decrease in parenteral support volume and the relative change from baseline in that capacity. The DDW have planned oral presentation; it's still in development, but we have a lot done on it already, and it’s very data-heavy. I think you'll be very impressed with the amount of data. We're very excited by it because it clearly supports our conviction that the drug is approvable and works in both colon-in-continuity and stoma patients. We're really looking forward to sharing that more broadly with the community.

Mike, just one follow-up. Why is the placebo effect so high in these studies? Because I noticed on your third secondary endpoint, the placebo rate was almost 44%. Can you comment on that?

Yes. I think the key to realize there is that the primary endpoint placebo response was 12.5%, right? And that’s the key driver for the study's positivity statistically and the path to approval. The other thing to realize is the 48-week endpoints had never been tested in a GLP-2 therapy before. There can be a tendency for placebo response to change during a clinical trial. It’s also important to realize that what we’re actually talking about here, the placebo response is different at 24 weeks on the primary endpoint, meaning it’s the relative change from baseline versus the one day off, which is the third key secondary that you alluded to that's 44%. We instituted a new design in this trial, which is the winning algorithm. That’s clearly played forward through the study. We’re going to analyze that data cost carefully to make sure we understand it. There’s a potential opportunity for the winning algorithm, which would be in place for both placebo and drug-treated patients, could elevate the placebo response with later time points in the study. Early in the study, it might be more volume-driven, whereas as people wean, then you may fall under the year an output threshold of 10% and you make it exposed to weaning out. We’re still looking into that, but that’s clearly one thing on the list to figure out if that’s what made the 48-week endpoint, we’ll see the response so high. One final point to realize, even though the placebo response was high at the third key endpoint on the CIC population, APRA was still numerically superior. When we get to this sort of aspect of approvability, that fact that APRA still did numerically better will be a positive in terms of not looking at it like we’re worse than placebo or things like that; that’s not the case. Given the things we talked about on the primary and first key secondary being positive in the whole population, we clearly think that bodes well for a high probability of success for approval for both populations.

Maybe just one last follow-up, Mike. Are some of these items, do you think that you could get them on the label? Because I think those would be important, especially in the colon-in-continuity patient population.

Yes. I think we’re going to work to get everything in the label we can. We certainly think the drug works very well in both patient populations. One of the reasons we included those additional secondaries was for exactly that reason. However, that challenge is higher now, obviously, because they didn't meet statistical significance. But as I mentioned, both are numerically better. We certainly have strong confidence for approvability.

Ladies and gentlemen, that concludes our Q&A session and today's call. Thank you all for joining. You may now disconnect.