Ironwood Pharmaceuticals Q1 2024 Earnings Call Transcript

Quartr
Provided by Quartr
May 9, 2024

There are 10 speakers on the call.

Operator

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. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session.

Operator

I would now like to turn the call over to Matt Roche, Director of Investor Relations. Please go ahead.

Speaker 1

Thank you, Kath. Good morning and thanks for joining us for our Q1 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 and may cause actual results to differ materially.

Speaker 1

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 ks 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. 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

Speaker 2

the tables at the end

Speaker 1

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, begin with a brief overview. Mike Schutzlein, our Chief Medical Officer, will discuss our pipeline and Shrevan Imani, 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.

Speaker 1

With that, I'll turn the call over to Tom. Thanks, Matt.

Speaker 3

Good morning,

Speaker 4

everyone, and thanks for joining us. We are pleased to be here to discuss our 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 3 strategic priorities, which are maximize LINZESS, advance our GI pipeline and deliver sustained profits and cash flow. In the Q1 of 2024, LINZESS maintained its strong demand momentum with prescription volume increasing 10% year over year, supported by robust new to brand prescription growth of 18% versus the prior year, marking the 5th consecutive quarter of double digit new to brand growth. As you may have seen in our press release this morning, based on information provided by AbbVie, we recorded an adjustment to the Q1 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.

Speaker 4

Trevor will provide more detail on the impact of this one time adjustment later on 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 the positive top line results in February from the Phase 3 STARS trial, evaluating the efficacy and safety of opraglutide in patients with short bowel syndrome with intestinal failure. These positive Phase 3 results demonstrate the potential of praglutide as the first and only weekly GLP-two therapy for the treatment of adults with short bowel syndrome who are dependent on parenteral support if approved.

Speaker 4

Following the top line results shared in late February, we have continued to analyze the robust data set of the STARS Phase 3. And new data was 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 fraglutide, 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 pryglutide has a high probability of approval. We believe these 3 distinguishing factors will drive uptake, compliance and improvement in quality of life for patients, reinforcing our belief that apraglutide has the potential to achieve $1,000,000,000 in peak net sales.

Speaker 4

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's 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 a pragmatic guide successfully. We are well on our way with the launch planning and believe we are equipped to commercialize opraglutide if approved with a strong sales presence already established in the offices of GI Specialists across the United States.

Speaker 4

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 potential for opraglutide 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. 1st, 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. 2nd, we believe we have transformed our company with the positive Phase III results from the STARS trial, which reinforce our conviction in a preglotized high probability of approval in long term revenue and profit growth potential.

Speaker 4

Finally, we're excited to see the Phase 2 top line results from CMP-one hundred and four later this year. We believe CMP-one hundred and four 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 opraglutide and our pipeline in more detail. Mike?

Speaker 2

Thanks, Tom, and good morning, everyone. We're pleased with the progress we made across our pipeline programs in the Q1. I'll begin with epiglutide for short bowel syndrome in patients dependent on parenteral support. We're very proud of the positive results from the pivotal global Phase 3 STAR study, which is the largest ever GLP-two trial in short bowel syndrome with intestinal failure, generating a robust data set across 68 sites and 18 countries. An important aspect of STARZ Phase 3 study design was the rigorous optimization of parenteral support volumes prior to treatment.

Speaker 2

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 parenteralsport volume at week 24 with a 2 times treatment effect relative to placebo, driven by both stoma and colon incontinuity populations. As a clinician myself, I'm thrilled about apragutide 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 and 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.

Speaker 2

The fact that some patients in both stoma and colon and continuity populations reached enteral autonomy or a complete weaning off of parenteral sport and the low prevalence of reported injection site reactions and abdominal distension which are in line with placebo. Overall, we believe apraglutide differentiated profile including its demonstrated efficacy and tolerability and convenience of once weekly dosing support our belief in apraglutide's high probability of approval and potential to improve the standard of care for patients with 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 data set from the largest ever GLP-two 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 3 results from apraglutide in short bowel syndrome with intestinal failure, we also announced positive results from our exploratory STAR GAZE trial of apralutide in patients with steroid refractory gastrointestinal acute graft versus host disease.

Speaker 2

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 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.

Speaker 2

The STARGRACE study will continue through its 2 year endpoint where when apraglutide will be evaluated for safety and efficacy. Moving to CMP-one hundred and four on Slide 10, in the Q1, CORE completed patient enrollment for the Phase 2 proof of concept study in patients with PBC and are on track to report top line results in the Q3 of this year. The CMP-one hundred and four Phase 2 study is a 42 patient placebo controlled study evaluating the safety, tolerability, pharmacodynamics and efficacy of CMP-one hundred and four in patients with PBC who are unresponsive to UDCA and dorocalva. Top prime results we based on data through day 120 of treatment. The strong immunology underpinning the CNP program is focused on targeting the specific PDCE2 antigen responsible for the T cell driven pathology of PBC.

Speaker 2

Last year, we saw early data showing favorable PBCE2 specific T cell responses in patients treated with CMP-one hundred and four. In the top line results anticipated in the Q3, 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 would further support the potential for CMP-one hundred and four. We believe CMP-one hundred and four has the potential to be the 1st disease modifying therapy for patients suffering with 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.

Speaker 3

Thanks, Mike, and good morning, everyone. I'll begin on Slide 12. As Tom mentioned earlier, LINZESS carried deposit demand momentum into the Q1. This is now the 12th year on market for LINZESS. And as you can see, prescription demand remains markedly strong.

Speaker 3

LINZESS volume rose 10% year over year in the Q1, while new to brand prescriptions increased 18% compared to the with the Q1 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 pediatrics 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 Q1 of 2024 on Slide 13. In the Q1, AbbVie reported U.

Speaker 3

S. Net sales of $257,000,000 an increase of 3% year over year. Based on information subsequently provided by AbbVie, Ironwood estimates a $60,000,000 adjustment to LINZESS U. S. Net sales representing the difference between AbbVie's gross to net estimates made in 2023 3 and actual subsequent payments made.

Speaker 3

As a result of this change in estimate, Ironwood recorded a $30,000,000 reduction to collaborative arrangements revenue. With this adjustment, total Ironwood revenue in the Q1 was approximately $75,000,000 down 28% year over year. Turning to our Q1 financial performance slide on performance on Slide 14. Q1 LINZESS U. S.

Speaker 3

Net sales as reported by AbbVie were $257,000,000 increase of 3% year over year. LINZESS commercial margin excluding the gross to net change in estimate was 71% in the Q1 of 2024 compared to 73% in the Q1 of 2023. As I noted a few moments ago, Ironwood revenue was $75,000,000 driven primarily by U. S. LINZESS collaboration revenue of $72,000,000 Revenues in Q1 were lower year over year, primarily due to the $30,000,000 change in estimate recorded to collaborative arrangements revenue.

Speaker 3

As a result, GAAP net loss was $4,000,000 and adjusted EBITDA was $13,000,000 In the Q1, Ironwood generated approximately $45,000,000 in cash flow from operations and ended the quarter with $122,000,000 in cash and cash equivalents after repaying $25,000,000 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 $275,000,000 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 from 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 Afroglutide 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 and estimate in the Q1, for full year 2024, we now expect LINZESS U.

Speaker 3

S. Net sales decline in the mid single digits percent. Ironwood revenue of between $405,000,000 $425,000,000 and adjusted EBITDA of greater than $120,000,000 To wrap up, we've made significant advancements across our portfolio in the Q1. We look forward to sharing additional detail from the apraglutide STARS Phase 3 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.

Speaker 3

Looking ahead, we are focused on moving quickly to get apraglutide approved and to patients with SBS who are dependent on parental 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.

Operator

Thank you. We will now begin the question and answer session. Your first question comes from the line of David Amsellem with Piper Sandler. Your line is open.

Speaker 5

Hey, thanks. So 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 there statistical separation, say, at earlier time points, say, 24 weeks or 12 weeks?

Speaker 5

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? I'll leave it there.

Speaker 5

Thanks.

Speaker 2

Okay. Thanks for the question, David. So we're very excited about the data from eparolutide and a lot has been discussed around CIC versus stoma. It's just critical to remember that the primary endpoint included both stoma and colon and continuity patients. So we clearly think we have a high probability of approval for the whole population stoma and C on C based on the fact that colon and continuity patients contributed to the primary endpoint.

Speaker 2

That was quite distinct from what happened with the regulatory precedent that Gattex set where they really didn't see a meaningful contribution for the colon and continuity patients. So, we continue to believe that the potency of the asset is well established now with this Phase 3 data and that that's given us the opportunity for once weekly therapy and what you'll see at DDW is further rollout of the colon and continuity specific data which certainly gives us even more confidence in the efficacy in colon and continuity patients. And 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 and continuity and stoma patients. In addition, there'll be a fair amount of tolerability data, which will further support the differentiation of epiglutide from other GLP-two therapies in the class. We've really learned a lot from the pivotal trial data in terms of the safety and tolerability and you'll see details on events and numbers at PDW, which really support a very safe and well tolerated profile.

Speaker 2

And 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 CMP, okay. What we plan what we hope to see in CMP as we discussed the real strength of the CNC program is the science behind the immunology and what we know about the pathology of PBC. It's a pdce2 driven disease and we can test the t cells that destroy the bile ducts with PDCE 2 to determine if treatment with CMT 104 modulates or reprograms those T cells.

Speaker 2

So we're really looking for a demonstrated T cell effect that shows that those T cells are no longer pathologic, no longer prone to destroying bile ducts. And 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. And this 120 day assessment, it gives the opportunity to look at that demonstrated T cell response and the potential opportunity to improve a liver function assessment.

Speaker 6

Okay. Thank you.

Operator

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

Speaker 7

Good morning, guys. Thanks for taking the questions. 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 $60,000,000 adjustment was that was not accounted for by AbbVie?

Speaker 2

Yes. So first of

Speaker 3

all, Chase, thank you for your question. Good morning. I'd say that, I'm taking zooming out first. I would say that fluctuations in gross to net relating to shift in channel mix are common and they're normal occurrence within this industry as you know. It's something that happens on a periodic basis for us, Rarely is it this material.

Speaker 3

I think the change in estimate for us was based on information that AbbVie provided subsequent to their reporting. And it was the difference between the gross announcements during the year and the actual invoices they got. And it was primarily associated with government and contractual rebates. I think that's the color I probably can give you in terms of where

Speaker 4

we were.

Speaker 7

That's helpful. And 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?

Speaker 2

Yes, sure. That's a good question. And clearly, that's our key priority. Our number 1, 2, and 3 priorities is the APRA submission. So it's all hands on deck for that.

Speaker 2

We clearly 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 obviously 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 to get the submission in and on track. So we're currently now planning the pre NDA meeting, which we will will do as well.

Speaker 2

And we're really looking forward to moving that submission forward as expeditiously as possible. We're still targeting a potential launch in 2025 and as we get more granular on the submission timelines, we'll certainly make that available.

Speaker 7

Okay. And then, just last for me on CNP 104. Just to confirm for investors, when we get that data in 3Q, that will be both T cell response and we will also be able to see that liver function data. Is that right, Mike?

Speaker 2

Yeah. We plan to talk about the T cell, the demonstrated T cell effects to obviously prove the point of the program which is the reprogramming and the immunology around the pdce2 specific antigens. So we plan to share that as well as liver function, outcomes as well. Remember, it's a 120 day study. It's a phase 2 study.

Speaker 2

It's the first, in human study for CMP 104, and so that that is a sort of early time frame, you may know that things like obeticholic acid and Cinibay and those products went out to a year, but we clearly think based on the science and the technology and why we did the deal that we have an opportunity to see a real early clinical endpoint in those liver function assessments.

Speaker 7

Great. And then just last, Ravin, to come back to you. Just on guidance, I mean, looking at it, it certainly seems that really the only material changes to your guys' expectations was this $30,000,000 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.

Speaker 3

So I would say that our guidance now is reflective of the one time adjustment. As you can see, had the based on AbbVie's reporting, that I think we would have been relative to 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 having of high single digit price erosion and low single digit revenue growth were kind of there, outside of the one time out of period adjustment.

Speaker 4

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, year 12 for the brand, which we obviously want to continue to nurture. And what we do know is there's really kind of 3 things that are driving that. Certainly the high treatment satisfaction, no question. But I think the other piece is payer access, which is part of the marketing mix. Now what we'll 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.

Speaker 4

So we have been doing this from day 1 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.

Speaker 2

Great. Thanks guys.

Operator

Your next question comes from the line of Amy Lee with Jefferies. Your line is open.

Speaker 8

Hey, good morning guys. Thanks so much for taking my question. On apraglutide, what is your current internal estimate on durability treatment? And will we get any data at CDW to support potential differentiation on disc of organics? Additionally, can you give us any updates on how you're thinking about the addressable market for APRA post the ICD-ten codes being put in place late last year?

Speaker 8

And how many of these patients do you have access to with your current sales

Speaker 3

force? Well, Mike, why don't you start with the first one and I'll answer the second.

Speaker 2

So thanks, Amy. So in terms of durability, I suspect you mean the more longer term. I mean, clearly, as the only once weekly available, therapy, we we certainly think that phase 3 data supports the weekly administration and sort of the pharmacokinetics and pharmacodynamics really lend itself to that once weekly dosing. So the data speaks for itself in that regard. It's a once weekly therapy.

Speaker 2

I think in terms of longer term, right, 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-two therapy to maintain that intestinal growth. Then from that going forward, it will be up to them obviously and their physician caretaker 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-two because as we've seen with other GLP-two therapies when you come off it is we often revert back to a need for parenteral support.

Speaker 3

And then on the question about the ICD-ten 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, the ICD-ten codes, we're really excited about this development, honestly, Emily. Amy, I think the big thing for us is that these ICD-ten codes are starting to shed real light on how many patients there actually are. I think you've heard a little bit in some of the things you've posted yourself about differences in what the estimates are.

Speaker 3

I think there have been 7,000 or so patients that have been identified already to date through the ICD-ten codes in just a few months. It just reinforces our estimates as more data comes to light about how many patients there are. And then I think given our presence across the United States, I think our ability to capture share with our best in class product, with our, as an overall profile with apoblutide having once weekly administration, demonstrated real efficacy across the both stoma and CIC patient populations. And then now, as you'll see in a few weeks, the safety and tolerability data being equivalent placebo, I think that is, I think our ability to penetrate that and capture share to be a $1,000,000,000 brand is in sight. We feel confident about it.

Speaker 8

Great. Thank you so much.

Operator

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

Speaker 6

Hey, thanks for taking the questions. First one is for Afra. Can you maybe talk about the work you're doing pre commercial to build awareness in the brand? And beyond just obviously presentation of data, what work you're going to get 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?

Speaker 6

Thanks.

Speaker 2

Yes. So, Tom, why

Speaker 3

don't you handle the first one and then maybe I'll take the second part of the question if that works. I mean, remind me the first question was? The brand awareness, the activity. Sure.

Speaker 4

So as far as the pre launch 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. So this is really about increasing the awareness of who these patients are, how debilitating this disease is and the need for more effective therapy. And 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've been very, 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, privatide in the clinical trials. And they're all looking forward to working in a very collaborative way, not just as far as educating people, but also how do we really work with the patients to help them through the process to get better care.

Speaker 4

So we're, 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.

Speaker 6

Can I take the LINZESS question?

Speaker 3

Yes, I'll happily do that. So Jason, good morning. So I think on your question about the pediatric launch and its progress, I think we are, really, I think overall, I think, since the launch has started, feel really positive about, 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. I think, Tom mentioned earlier on the call that 18% new to brand growth, that's specifically a large portion of that growth in 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.

Speaker 3

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.

Operator

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

Speaker 9

Great. Thank you very much for taking my question.

Speaker 3

I have

Speaker 9

a couple of questions. So one on the guidance again. So thanks for clarification. But one thing I wanted to ask was that typically this happens because you had a particular mix in the mind for government versus commercial and that mix change subsequently because you don't know it until you get the receipts and all. Are you expecting similar mix, which like the updated mix for 2024 as well?

Speaker 9

I'm asking because by our math, the impact that you are modeling is little bit more than $60,000,000 So that's the first question. And the second question is on ALP with CNP-one hundred and four. So if I look at drugs like seldelpar, 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 day enough to see benefit? I appreciate the mechanisms are different.

Speaker 9

So how should we think about benefit on endpoints like ALB there? Thank you.

Speaker 3

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

Speaker 2

Yes, thanks, Rene. It's a good question because, as you know, the regulatory, like, precedent is around ALK fast. That's clearly what how obeticholic acid got approved and what semibase gone through right now. So it it clearly is an approved path for accelerated approval, which is which is not full approval. You may know some base actually added pruritus and that sort of help balance that that need.

Speaker 2

ALCOS is a very non specific sort of effect on on liver function in a lot of ways because it really speaks to how the bile is moving through the liver. So it's very important to understand that if you give something like obeticholic acid which is a bile acid mimetic it actually increases bile flow. One of the early benefits you'll get from that is improved alk phos. It's also not necessarily part and parcel that that's aligning with liver function improvement and that's why obeticholic acid had to have a post marketing commitment to show a benefit in liver function brought more broadly with histology which incidentally did not meet needs at the time. So it is important to understand what ALKFOX is there for and as you highlighted our mechanism is completely different.

Speaker 2

We're actually targeting the root cause of PBC, which is the T cell driven bile duct destruction. So we clearly believe that we can affect the T cells and then reprogram those T cells so they no longer attack the bile ducts, we'll see clinical improvement. And then to your point, the timeline for that clinical improvement, we're gonna learn. We clearly think we have an opportunity to see it early given the specificity of PDCE 2 and the specificity of this therapy. That's why we have a 120 day, look, but we're certainly gonna learn from that.

Speaker 2

And that's why we have this combination of of need, meaning to demonstrate a T cell response and deliver function improvement. So certainly the different mechanism is important to understand and also it's very important to realize that we're actually going for a very disease modifying approach not just moving bile flow through the liver better which is a biomarker for potential benefit for liver disease.

Speaker 3

Great. Got it. And so on your guidance question, look, I think I'll high level, I'd say again, 1, I think from our perspective and it's the guidance we gave for 2024 accounts for the mix we anticipate in 2024. It's our 2024 guidance. We expect to still see high single digit prescription demand growth.

Speaker 3

And I think the decline is as stated based on our, our overall annual guidance. This is a one time adjustment. We've been pretty good as a brand over the last several years and, in anticipating or with our estimates as with respect to what the mix is in a channel. Channel mix is pretty fluid and predicting LINZESS net sales can move in a positive or negative direction. This has always been true, but we've been pretty good about it over the years.

Speaker 3

And I think at this point, we're still expecting to deliver, a mid single digit decline, as I said before, and that's predominantly driven by, the one time out of period adjustment. Outside of that, I think we would have been in line with guidance for the full year.

Speaker 1

Got it. Helpful. Thank you.

Operator

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

Speaker 6

Hey, thanks. Mike, I was just looking back at the secondary endpoints from the STAR study. Do you guys plan on showing, 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?

Speaker 2

Yes. Tim, if you're referring to sort of specifically things like enteraltonomir, things we might see at 24 weeks versus the key secondaries at 48, the answer is yes. And we certainly think that that data further, you know, supports our conviction of of good, efficacy in both stoma and CIC patient populations. So, yeah, we plan to to see that have that at DDW as well as sort of the decrease in parenteral support, volume and and the relative change from baseline in that capacity as well. We we the the DDW have planned oral presentation.

Speaker 2

It's obviously still, in development, but we have a lot done on it already and it's it's very data heavy. I think you'll be very impressed with the amount of data. We're certainly clearly very excited by it because it clearly supports our conviction that the drug is approvable and works in both colon and continuity and stoma patients. So, we really are looking forward to sharing that more broadly with the community.

Speaker 6

Mike, just one follow-up. Why is the placebo effect so high in these studies? Because I noticed on your 3rd secondary endpoint, the placebo rate was almost 44%. Can you comment on that?

Speaker 2

Yes. I mean, 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. So I think that's a key thing to keep aware of. The other thing to realize is the 48 week endpoints never had been tested in at GLP 2 therapy before.

Speaker 2

And there can be a tendency for placebo response to change during a clinical trial. And it's also important to realize that what we're actually talking about here, 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 3rd key secondary you alluded to that's 44%. And then in addition, we instituted a new design in this trial which is the weaning algorithm. So that's clearly played forward through the study. We're going to analyze that data real cost carefully to make sure we understand it.

Speaker 2

But there is a potential, opportunity for the weaning 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, because early in the study, it might be more volume driven whereas as people wean, then you may fall under the urine output threshold of 10% and you may get exposed to the weaning out. We're still looking into that, but that's clearly one thing on the list to to figure out if that's what made the 48 week endpoint placebo response so high. And one final point to realize, even though the placebo response was high at the 3rd key endpoint on the CIC population, APRA was still numerically superior. So 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.

Speaker 2

And then given the things we talked about on the primary and the first key secondary being positive in the whole population, we clearly think that bodes well for high probability of success for approval for both populations.

Speaker 6

And 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 and continuity patient population?

Speaker 2

Yeah. 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 is higher now obviously because they didn't meet statistical significance.

Speaker 2

But as I mentioned both are numerically better. So we certainly have a strong confidence for approvability.

Speaker 6

Okay, great. Thanks.

Operator

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

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Key Takeaways

  • LINZESS maintained strong momentum in Q1 with prescription volume up 10% year-over-year and new-to-brand growth of 18%, marking its fifth consecutive quarter of double-digit new-to-brand gains.
  • Ironwood recorded a $60 million adjustment to LINZESS gross-to-net estimates, resulting in a $30 million reduction to collaborative arrangement revenue and updated 2024 guidance of $405–425 million in total revenue and over $120 million in adjusted EBITDA.
  • Positive top-line results from the Phase 3 STARS trial of apraglutide in short bowel syndrome showed a 2× treatment effect versus placebo on the primary endpoint at 24 weeks across stoma and colon-in-continuity patients, supporting an NDA filing and a planned 2025 launch with potential $1 billion peak sales.
  • An exploratory Phase 2 STARGAZE trial in steroid-refractory acute graft-versus-host disease demonstrated apraglutide was well tolerated and produced lower GI responses maintained through day 91, with additional safety and efficacy data to be reported at the 2-year study endpoint.
  • The Phase 2 study of CMP-00104 in primary biliary cholangitis is fully enrolled and on track for Q3 2024 topline results, with expectations of showing PDCE2-specific T-cell responses and liver function improvements, potentially making it the first disease-modifying therapy for PBC.
A.I. generated. May contain errors.
Earnings Conference Call
Ironwood Pharmaceuticals Q1 2024
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