Q4 2023 Ironwood Pharmaceuticals Inc Earnings Call

Good day, and welcome to the Ironwood Pharmaceuticals fourth quarter and full year 2023 investor update call.

Operator: Good day, and welcome to the Ironwood Pharmaceuticals fourth quarter and full year 2023 investor update call. All lines have been placed on mute to prevent any background noise.

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: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press the star followed by the number 1 on your telephone keypad. If you would like to withdraw your question, please press star 1 again. For operator assistance throughout the call, please press star zero, and finally, I would like to advise all participants that this call is being recorded. Thank you. I'd now like to welcome Matt Roche, Director of Investor Relations, to begin the conference. Matt, it's over to you.

If you would like to ask a question. During this time simply press star followed by the number one on your telephone keypad.

If you would like to withdraw your question. Please press star one again.

For operator assistance throughout the call. Please press star Zero, and finally, I would like to advise all participants that this call is being recorded thank you.

I'd now like to welcome Matt Roche director of Investor Relations to begin the conference.

Matt Roche: Thank you Kevin.

Matt Roche: Thank you, Gavin. Good morning, and thanks for joining us for our fourth quarter and full year 2023 investor update. Our press release issued this morning can be found on our website. Today's call and accompanying slides include forward-looking statements. Such statements involve risks and uncertainties that may cause actual results to differ materially.

Matt Roche: And thanks for joining us for our fourth quarter and full year 2023 investor update.

Matt Roche: Our press release issued this morning can be found on our website.

Matt Roche: Today's call and accompanying slides include forward looking statements.

Matt Roche: Such statements involve risks and uncertainties that may cause actual results to differ materially.

Matt Roche: A discussion of these statements and risk factors is available on the current Safe Harbor Statements slide, as well as under the heading Risk Factors, in our annual report on Form 10-K for the year ended December 31st, 2022, and our quarterly report on Form 10-Q for the quarters ended June 30th, 2023, and September 30th, 2023, and in our subsequent SEC filings. All four forward-looking statements speak as of the date of this We undertake no obligation to update such statements. Also included are non-GAAP credential measures that should be considered only as a supplement to and not a substitute for or superior to GAAP measures.

Matt Roche: A discussion of these statements and risk factors is available on the current safe Harbor statement slide.

Matt Roche: As well as under the heading risk factors.

Matt Roche: Annual report on Form 10-K for the year.

Ended December 31, 2022, and our quarterly report on Form 10-Q for the quarters ended June 32023 at September 32023, and in our subsequent SEC filings.

Matt Roche: Looking statements speak as of the date of this presentation.

Matt Roche: Take no obligation to update such statements.

Matt Roche: Also included a non-GAAP financial measures.

Matt Roche: Which should be considered only as a supplement to and not a substitute for or superior to GAAP measures.

Matt Roche: 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 gap measures. During today's call, Tom McCourt, our Chief Executive Officer, will begin with a brief overview. Mike Schetzlein, our Chief Medical Officer, will discuss our pipeline, and Shrevan Imani, our Chief Financial Officer, will provide a commercial update and review our financial results and guidance. Today's webcast will include 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. Morning, everyone, and thanks for joining us today.

Matt Roche: And 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.

Matt Roche: During today's call Tom Mccourt, our Chief Executive Officer will begin with a brief overview.

Matt Roche: Mike <unk>, our Chief Medical Officer.

Matt Roche: Discuss our pipeline and <unk> <unk>, our chief financial Officer to provide a commercial update review our financial results and guidance.

Tom Mccourt: 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 slide separately with that I will turn the call over to Tom Thanks, Matt.

Tom Mccourt: Good morning, everyone and thanks for joining us today.

Tom Mccourt: I'm absolutely delighted to share with you the progress we made in 2023 and why we believe our future is bright. We made important progress in 2023 toward realizing our vision of becoming the leading GI healthcare company in the industry. I am very proud of the Ironwood team and the significant headway we made in 2023 across our three strategic priorities, which are maximize LINZUS, advance our GI pipeline, and deliver sustained profits and cash flow. As we turn our attention to 2024, I'm confident in our strategy and look forward to what we expect to be an exciting and transformational year for our company. Let's begin on slide six with a brief overview of some of our key achievements against our strategic priorities in 2023. First, maximizing LINZS.

Tom Mccourt: Absolutely delighted to share with you the progress we've made in 2023 and why we believe our future is bright.

Tom Mccourt: We made important progress in 2023 toward realizing our vision of becoming the leading GI health care company in the industry.

Tom Mccourt: I'm very proud of the Ironwood team and the significant headway, we made in 2023 across our three strategic priorities, which are.

Tom Mccourt: Maximize linzess advance, our Gi pipeline and deliver sustained profits and cash flows as.

Tom Mccourt: As we turn our attention to 2024 I'm confident in our strategy and look forward to what we expect to be an exciting and transformational year for our company.

Tom Mccourt: Let's begin on slide six with a brief overview, but some of our key achievements against our strategic priorities in 2023.

Tom Mccourt: First maximizing linzess.

Tom Mccourt: In its 11th year on the market, Linzess had another terrific year as the leading prescription treatment for adults with IBSD and chronic idiopathic constipation. In 2023, prescription demand increased by a robust 10% year over year. New-to-brand prescriptions ramped up significantly, increasing 15% compared to 2022, which we believe is a key indicator for future growth potential. In addition, Linzess reached an all-time high of 46% in TRX share in the combined branded and generic IBSC and chronic adipathic constipation market, strengthening its market leadership. And in June of 2023, Linzess received FDA approval for functional constipation in pediatric patients ages 6 to 17, becoming the first and only approved prescription therapy for this patient population, and we're incredibly proud of it.

Tom Mccourt: In its 11th year on the market Linzess had another terrific year and the leading prescription treatment for adults with Ibs C in chronic idiopathic constipation.

Tom Mccourt: 23 prescription demand increased a robust 10% year over year.

Tom Mccourt: New to brand prescriptions ramped up significantly increasing 15% compared to 2022, which we believe is a key indicator for future growth potential.

Tom Mccourt: In addition, Linzess reached an all time high of 46% in T Rx share and the combined branded and generic Ibs C in chronic idiopathic constipation market.

Tom Mccourt: Strengthening its market leadership.

Tom Mccourt: And in June of 2023, Linzess received FDA approval for the functional constipation in pediatric patients aged six to 17, becoming the first and only approved prescription therapy for this patient population.

Tom Mccourt: The achievement, we're incredibly proud of.

Tom Mccourt: Moving forward, our focus remains on continuing to grow linzess prescription demand and delivering strong brand profits and cash flow.

Tom Mccourt: Moving forward, our focus remains on continuing to grow Linzess Prescription Demand and delivering strong brand profits and cash flow to advance our GI pipeline in areas of high unmet demand. Last year, we strengthened our GI pipeline with the acquisition of Effective Bio, including its lead asset, Apraglutide. As the next generation, long-acting GLP-2 analog, we believe a pragmatide, if successful, has the potential to become the standard of care in treating patients with short bowel syndrome dependent on parenteral support based on its clinical profile and the potential convenient once-weekly dosing. If approved, we believe a pragmatide could achieve a billion dollars in peak sales.

Tom Mccourt: Next advance our Gi pipeline in areas of high unmet need.

Tom Mccourt: Last year, we strengthened our Gi pipeline with the acquisition effective bio, including its lead asset privately tight.

Tom Mccourt: As the next generation long acting G. L. P. Two analog we believe a pregnant died if successful has the potential to become the standard of care in treating patients with short bowel syndrome dependent on parental support based on its clinical profile and the potential convenient once weekly dosing.

Tom Mccourt: If approved we believe a prioritized could achieve a $1 billion in peak net sales.

Tom Mccourt: Our unique pharmacological properties and strong clinical data to date, including positive data from the STARS Nutrition Study, gives us confidence in the STARS Phase 3 study, which we'll let on track to read out in March. In addition to aparaglutide, we're also excited about the progress of CMP 104, a potential disease-modifying therapy for the treatment of primary biliary cholangitis, or PBC. Late last year, we completed an early analysis that showed evidence of favorable T cell responses in patients treated with CMP104, supporting the mechanistic rationale for the asset, which we believe could positively impact disease progression in PBC.

Tom Mccourt: Ah prioritize unique pharmacologic properties and strong clinical data to date, including the positive data from the stars Nutrition study gives us confidence in the <unk> Phase III study, which was on track to read out in March.

Tom Mccourt: In addition to appraise. The guide we're also excited about the progress of CMP <unk> and puts a potential disease modifying therapy for the treatment of primary biliary cholangitis or PBC.

Tom Mccourt: Late last year, we completed an early analysis that showed evidence of favorable T cell responses in patients treated with <unk> for supporting the mechanistic rationale for the asset, which we believe could positively impact disease progression and PVC.

Tom Mccourt: We're looking forward to the top line phase two data in the third quarter. We believe both Apragatide and CMP-104 have the potential to improve the standard of care and the quality of life for patients suffering from these serious GI diseases, with key data expected this year. Our third priority is to deliver sustained profits and cash flow.

We're looking forward to the top line phase III data in the third quarter.

Tom Mccourt: We believe both are prioritized in CMP <unk> four has the potential to improve standard of care and the quality of life for patients suffering from the serious Gi diseases with key data expected this year.

Tom Mccourt: Our third priority is delivered sustained profits and cash flow, we are committed to being thoughtful and disciplined in our capital allocation as we strive to grow the business achieve our vision and deliver value to patients and shareholders.

Tom Mccourt: We are committed to being thoughtful and disciplined in our capital allocation as we strive to grow the business, achieve our vision, and deliver value to patients and shareholders. Looking ahead to 2024, we expect to deliver greater than $150 million in adjusted EBITDA while continuing to progress multiple clinical programs with the potential to deliver long-term growth. We believe the positive momentum across the pipeline programs, combined with the continued strong performance of Linzess, uniquely positions us for success in our mission to be the leader in GI. We're excited about the near-term data catalyst, which we believe will present the opportunity to propel Ironwood's growth and create value for patients and shareholders for years to come. At the end of this month, we will be celebrating Rare Disease Day.

Tom Mccourt: Looking ahead to 2024, we expect to deliver greater than $150 million and adjusted EBITDA, while continuing to progress multiple clinical programs with the potential with the potential to deliver long term growth.

Tom Mccourt: We believe the positive momentum across the pipeline programs combined with the continued strong performance of Linzess uniquely positions us for success of our mission to be the leader in Gi.

Tom Mccourt: We're excited about the key near term debt data catalysts, which we believe will present, the opportunity to propel ironwood's growth and create value for patients and shareholders for years to come.

Tom Mccourt: At the end of this month, we will be celebrating rare disease day I'd.

Tom Mccourt: I'd like to take this opportunity to say a special thank you to all the employees, patients, caregivers, and advocates in the rare disease community for their shared dedication to advancing and supporting new therapies for diseases with significant unmet medical needs. I would now like to turn that call over to Mike to review our pipeline. Mike?

Tom Mccourt: I'd like to take this opportunity to say a special thank you to all the employees patients caregivers and advocates in the rare disease community for their shared dedication to advancing and supporting new therapies for diseases with significant unmet medical need.

Tom Mccourt: I would now like to.

Tom Mccourt: Turn that call over to Mike to review our pipeline Mike.

Mike Schetzlein: Thanks, Tom, and good morning, everyone. Over the past few years, we've made significant strides to expand our footprint in GI. Today, we have a portfolio of innovative GI development programs with upcoming data that could be transformational for our company, as shown on slide 8. In March, we expect top-line data from the STARS Phase III clinical program of apiglutidine short bowel syndrome with intestinal failure, which was our primary focus and the value driver of the VECTIV bioacquisition. We believe epiglutide, if successful and approved, has best-in-class potential as the only once-weekly GLP-2 analog for the whole spectrum of patients with short bowel syndrome dependent on parenteral support, also known as SBSIF, a disease for which there is considerable unmet need. The novel STARS 3 trial is designed to show efficacy across both patient subtypes, stoma and colon incontinuity.

Mike: Thanks, Tom and good morning, everyone over the past few years, we've made significant strides to expand our footprint in Gi.

Mike: We have a portfolio of innovative Gi development programs with upcoming data that could be transformational for our company as shown on slide eight.

Mike: March we expect top line data from the stars Phase III clinical program that preclude tightened short bowel syndrome with intestinal failure, which was our primary focus and the value driver of effective bio acquisition.

Mike: We believe <unk> tight if successful unapproved has best in class potential as the only once weekly G. L. P to analog for the whole spectrum of patients with short bowel syndrome dependent on parental support also known as <unk> a disease for which there is considerable unmet need.

Mike: <unk> III trial is designed to show efficacy across both patient subtypes settlement and colon and continuity.

Mike Schetzlein: As you may recall, the primary endpoint is the relative change from baseline in weekly parenteral score volume at 24 weeks. We view success as achieving the primary endpoint as the only once-weekly GLP-2 therapy for SBSIF and look forward to seeing the pivotal data in March. In addition to evaluating applegotype for short bowel syndrome with intestinal failure, we're also looking at the asset as a potential treatment for patients with graft versus host disease, or GVHD.

Mike: As you May recall, the primary endpoint is relative change from baseline in weekly parental support volume at 24 weeks, we view success as achieving the primary endpoint is the only once weekly <unk> therapy for Spss and look forward to seeing the pivotal data in March.

Mike: In addition to evaluating Applegate type for short bowel syndrome with intestinal failure. We're also looking at the asset as a potential treatment for patients with graft versus host disease or Gvhd data is expected from this exploratory phase II study later this quarter, which will inform a decision on further investment in the program.

Mike Schetzlein: Data is expected from this exploratory phase 2 study later this quarter, which will inform a decision on further investment in the program. Next, CMP104 for PBC. We're encouraged by the favorable T-cell responses in patients treated with CMP104 that we saw last year and look forward to seeing how this may impact liver function in the top-line results expected in the third quarter of 2024. We're excited about CMP-104 because it has the potential to be the first disease-modifying therapy for patients suffering with PBC, as there are no therapies on the market today that address the root cause of the autoimmune destruction of the liver

Mike: Next CMP <unk> for PBC.

Mike: Encouraged by the favorable T cell responses in patients treated with <unk> four that we saw last year and look forward to seeing how this may impact liver function and the top line results expected in the third quarter of 2024, we're.

Mike: We're excited about CMT, one of Florida, because it has the potential to be the first disease modifying therapy for patients suffering with PBC as there are no therapies on the market today that address the root cause of the autoimmune destruction of deliver bio docs and finally, IW 300 wholly owned ironwood asset for <unk>.

Mike Schetzlein: And finally, IW3300, a wholly owned Ironwood asset for visceral pain conditions, including interstitial cystitis and bladder pain syndrome. The phase two study is ongoing and progressing well. The near-term catalysts I just highlighted reinforce our confidence in the tremendous opportunity we have in front of us, with multiple programs that we believe have the potential to improve the standard of care and the quality of life for patients suffering with GI disease. With that, I'll turn it over to Shreven. Thanks, Mike. And good morning, everyone.

Mike: Pain conditions, including interstitial cystitis bladder pain syndrome, the phase II studies ongoing and progressing well.

Mike: The near term catalysts I, just highlighted reinforce our confidence in the tremendous opportunity we have in front of us with multiple programs that we believe have the potential to improve the standard of care and the quality of life for patients suffering with Gi diseases with that I'll turn it over to Travis.

Travis: Thanks, Mike and good morning, everyone I'll begin on slide 10, as Tom mentioned earlier Linzess had another very strong year in 2023 as you can see demand growth has been remarkable over time, reinforcing that patients and healthcare professionals continue to choose linzess and a growing market.

Shrevan Imani: I'll begin on slide 10. As Tom mentioned earlier, Linzess had another very strong year in 2020. As you can see, demand growth has been remarkable over time, reinforcing that patients and healthcare professionals continue to choose Linzess in a growing market. 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 clinical utility from the new pediatrics. Class Leading Formulary Access and Guidelines Recommendation

Travis: 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 clinical utility.

Travis: The new pediatric syndication class, leading formulary access guideline recommendations focused commercial execution.

Shrevan Imani: Focused Commercial Execution, and New Patients Start Acceleration. Next, I'll provide a brief update on the Vectiv biotransact. The integration of Ironwood and effective biobusiness operations is ongoing and progressing very well. In December, we successfully completed the Squeeze Out merger under Swiss law. At that time, Ironwood purchased all remaining outstanding ordinary shares of Vector Bio for $17 per share in cash.

Travis: And new patient start acceleration.

Speaker Change: Next I'll provide a brief update on the vector bio transaction the.

Speaker Change: The integration of Iron Wouldnt that give bio business operations is ongoing and progressing very well in December we successfully completed the squeeze out merger under Swiss law.

Speaker Change: That time I would purchase all remaining outstanding ordinary shares affected by over $17 per share in cash.

Speaker Change: Next I will provide additional details on our fourth quarter and full year 2023 slide financial performance.

Shrevan Imani: Next, I will provide additional details on our fourth quarter, full year 2023 slot financials. I'm pleased that we were able to meet or exceed all three of our guidance metrics in 2020. I'll begin with some sacks.

Speaker Change: I am pleased that we were able to meet or exceed all three of our guidance metrics in 2023.

Speaker Change: I'll begin with Linzess.

Shrevan Imani: Linzess U.S. net sales were $274 million in the fourth quarter of 2023, an increase of 5% compared to the fourth quarter of 2022. This was driven by prescription demand growth of 10%, partially offset by price and inventory channel flux. For full year 2023, as shown on slide 11, Linzess U.S. net sales were $1,073,000,000, an increase of 7% year over year driven by continued strong Linzess prescription demand. Commercial margins were 77% in the fourth quarter, compared to 74% in the fourth quarter of 2022. For the full year 2023, commercial margins were 73%, in line with full year 2020.

Speaker Change: Linzess U S. Net sales were $274 million in the fourth quarter of 2023, an increase of 5% compared to the 2022.

Speaker Change: The fourth quarter of 2022.

Speaker Change: Driven by prescription demand growth 10%.

Speaker Change: Actually offset by price and inventory channel fluctuations.

Speaker Change: Full year 2023 as shown on slide 11, late Linzess U S net sales or $1.073 billion an.

Speaker Change: An increase 7% year over year, driven by continued strong linzess prescription demand growth of 10%.

Speaker Change: Commercial margins were 77% in the fourth quarter compared to 74% in the fourth quarter of 2022.

Speaker Change: For the full year 2023 commercial margins were 73% in line with full year 2022.

Shrevan Imani: Moving to Ironwood Revenue. Thank you for Ironwood's $118 million revenue, driven primarily by U.S.-Linz-esque collaboration revenues of $114 million. For the full year, Ironwood revenues were $443 million. Siblings S, U.S. Collaboration revenues of $430 million. In the fourth quarter, and for the full year, Ironwood recorded $32 million and $83 million income tax, respectively, the majority of which was non

Speaker Change: Moving to Ironwood revenues.

Speaker Change: In Q4, Ironwood revenues $118 million, driven primarily by U S. Linzess collaboration revenues of $114 million.

Speaker Change: For the full year Ironwood revenues were $443 million with Linzess U S collaboration revenues of $430 million.

In the fourth quarter and for the full year, Ironwood recorded $32 million and $83 million income tax expense.

Speaker Change: <unk>, the majority of which was noncash.

Shrevan Imani: In addition, Ironwood recorded interest expense of $8 million and $22 million in the fourth quarter and for the full year, respectively, and recorded $1 million and $19 million in interest and investment income, respectively, in the fourth quarter and for the full year. GAAP's net loss was $2 million in the fourth quarter, driven by a one-time, non-cash tax expense tied to a change in Massachusetts state laws and approximately $1 billion for the full year in 2023. As a reminder, for the full year, GAAP net loss includes a one-time charge of approximately $1.1 billion from the acquisition of Vectiv Bio. Adjusted EBITDA was $40 million in Q4 and a loss of $885 million for the full year. Full year adjusted EBITDA also includes a one-time charge of approximately $1.1 billion from the acquisition of Vectiv Bio.

Speaker Change: In addition, ironwood recorded interest expense of $8 million and $22 million in the fourth quarter and for the full year, respectively, and recorded $1 million and $19 million in interest and investment income respectively. In the fourth quarter for the full and for the full year.

Speaker Change: GAAP net loss was $2 million in the fourth quarter.

Speaker Change: Driven by one time noncash tax expense tied to a change.

Speaker Change: Massachusetts State laws and approximately $1 billion for.

Speaker Change: For the full year in 2023 as a reminder for the full year GAAP net loss includes a onetime charge of approximately $1 $1 billion from the acquisition of active buyer.

Speaker Change: Adjusted EBITDA was $40 million in Q4, and a loss of $885 million for the full year full.

Speaker Change: Full year adjusted EBITDA loss also includes the one time charge of approximately $1 1 billion.

Speaker Change: On the acquisition of active buyer.

Shrevan Imani: In the fourth quarter and for the full year 2023, Ironwood generated approximately $36 million and $183 million, respectively, in cash flow from operations and ended the year with $92 million in cash and cash equivalents after repaying $100 million of the outstanding principal balance on our revolving credit facility in cash. As of the end of December, the outstanding drawn balance on the revolver was $300 million.

Speaker Change: In the fourth quarter and for the full year 2023, ironwood generated approximately $36 million and $183 million, respectively, and cash flow from operations and ended the year with $92 million in cash and cash equivalents after paying $100 million of the outstanding principal balance on our revolving credit.

Speaker Change: Facility and cash.

Speaker Change: As at the end of December the outstanding drawn balance on our revolver was $300 million.

Speaker Change: Next I'll review, our 2024 guidance on slide 12.

Shrevan Imani: Next, I'll review our 2024 guidance on slide 12. As previously stated in January, we expect Linzess U.S. net sales growth in the low single digits percent driven by continued high single digit prescription demand. However, offset by a mid to high single-digit price arrow, primarily driven by the Medicaid AMP CAP removal legislation, which went into effect on January 1st of this year. We expect Ironwood revenue of between $435 and $455 million.

Speaker Change: As previously stated in January we expect Linzess U S. Net sales growth in the low single digits percent driven by continued high single digit prescription demand growth.

Offsetting by mid to high single digit price erosion.

Speaker Change: Primarily driven by the Medicaid.

Speaker Change: Amp cap removal legislation, which went into effect on January one of this year.

Speaker Change: We expect ironwood revenue of between 435 and $455 million.

Shrevan Imani: And, we expect adjusted EBITDA of greater than $150 million, which is in line with our previously stated expectations on the announcement of the Vector Bio acquisition of greater than $175 million of operating cash flows in 2020. To wrap up, we are very pleased with the progress we've made. Ironwood is a much different company than we were just a few years ago, and we believe we have positioned 2024 as a potential transformational year for our company.

Speaker Change: And we expect adjusted EBITDA of greater than $150 million, which is in line with our previously stated expectation on announcement.

Speaker Change: <unk> bio acquisition of greater than $175 million of operating cash flows in 2020.

Speaker Change: To wrap up we are very pleased with the progress. We made in 2023 Ironwood is a much different company than we were just a few years ago and we believe we are positioned 2024 as potential transformational year for our company.

Shrevan Imani: Looking ahead, we remain focused on maximizing Linzess, advancing our GI pipeline, and delivering sustained profits in cash. We are excited about the continued strong ones that are and the key pipeline catalysts ahead of us, which we believe can propel Ironwood's next phase of growth. We look forward to sharing the STARS Phase 3 top-line results with you in March. 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 disease. Operator, you may now open up the line for questions at www.ironwood.com. If you wish to ask a question, please press star followed by 1 on your telephone and wait for your name to be announced.

Speaker Change: Looking ahead, we remain focused on maximizing linzess advancing our Gi pipeline and delivering sustained profits and cash flows.

Speaker Change: We are excited about the continued strong linzess performance and the key pipeline catalysts ahead of us.

Speaker Change: We believe can propel ironwood's next phase of growth.

Speaker Change: We look forward to sharing the star's phase III top line results with you in March.

Speaker Change: 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.

Speaker Change: Operator, you May now open up the line for questions.

Speaker Change: Okay.

Speaker Change: If you wish to ask a question. Please press star followed by one on your telephone and wait for your name to be announced that is star. One if you wish to ask a question.

Operator: That is Star 1 if you wish to ask a question. And your first question comes from the line of Amy Lees from Jefferies. Your line is open, www.ironwood.com. Hey. Thanks so much for taking our questions. Just two from us.

Speaker Change: And your first question comes from the line of Amy <unk> from Jefferies. Your line is open.

Amy: Hey, Thanks, so much for taking our question just two from us on CIC. It looks like <unk> had twice daily wholesaling higher improvement on P. S reduction compared to GATX and CIC patients. Despite a relatively similar meaning protocols do you view this as a sign that improved PK will translate.

Amy Lees: On CIC, it looks like glepiglutide twice daily is showing higher improvement on PS reduction compared to GADx in CIC patients despite a relatively similar weaning protocol. Do you view this as a sign that improved PK will translate to efficacy? Additionally, can you walk us through the order of the hierarchical testing that you'll be looking at for the secondary endpoints and where CIC falls relative to this? And then, finally, can you give us any color on how much additional sales force you may need to add to launch apriclutide in SBS and how we should model SGNA? Thanks so much.

Amy: Jesse.

Amy: Can you walk us through the order of the hierarchy, all testing that youll be looking at for the secondary endpoints and we're CIC pumps valid to today and then finally can you give us any color on how much additional sales force that you may need to add to launch epically tied in SBS and how we should model SG&A. Thanks, so much.

Amy: Okay. Thanks, Amy I guess I'll start by handing it over to Mike can answer the first two questions and I'll answer the third on the sales force, yes. Thanks, Amy good good questions.

Tom Mccourt: Okay. Well, thanks, Amy. I guess I'll start by handing it over to Mike who can answer the first two questions, and I'll answer the third on the sales force. Yeah, thanks, Amy. Good questions. So, the first question you asked is related to PK and exposure around the Glycoglutide program and sort of some of the findings they had, which did sort of portend a better, you know, from a parenteral support reduction perspective outcome in the CIC population. The root of your question is obviously what gives you the best pharmacodynamic response from a PK perspective, and we've actually modeled and looked into this quite extensively because the question is whether it's C-max or whether it's AUC, right, whether you need to cover the receptor for multiple times or consistently throughout time, and that's sort of where you're getting at with the Glycoglutide twice weekly, that by doing it twice weekly or giving the drug twice weekly, they maintain sort of a higher trough throughout the week, and is that the reason why they might see better parenteral support reductions?

Mike: First question is related to PK and exposure around the clinically type program and sort of some of the findings they had which did sort of portend.

Speaker Change: <unk> from parental support reduction perspective, our covenant CIC population.

Mike: The root of your question is obviously what gives you the best Pharmacodynamic response from a PK perspective, and we've actually modeled and looked into this quite extensively because the question is whether it's <unk> or whether it's AUC right, whether you need to cover the receptor for multiple times are consistently throughout time, and thats sort of where you're getting at with the classic blue tie.

Mike: Weis weekly that by doing it twice weekly or giving the drug twice weekly they maintain sort of a higher trough throughout the week and is that the reason why they might see better parental support reductions.

Mike Schetzlein: We certainly think that there is an exposure-related benefit to having, you know, the drug chronically or at least persistently available to the receptors, and that's one of the reasons why we think the once weekly... has the potential opportunity to be best in class. So we certainly consider that. We're gonna learn a lot from the study in terms of how to model that pharmacodynamic response, but it certainly is part of the PK PD profile that we think is very positive and aspirational for apiglutide. The second question you asked was about the key secondaries.

We certainly think that there is an exposure related benefit to having drug chronically or at least persistently available to the receptors.

Mike: And that's one of the reasons why we think the once weekly.

Mike: It has the potential opportunity to be best in class. So we certainly consider that we're going to learn a lot from the study in terms of how to model that that Pharmacodynamic response, but it certainly is part of that the PK PD profile that we think is very positive and aspirational for our glass Appro Glu tide.

Mike: The second question you asked was about the key secondaries. So we have taken into account statistically the secondary endpoints, obviously to have future discussions with the agency on potential label language. Those key secondaries are that the first one is really the reduction of at least one day off parental support for the total population at week 24. So.

Mike Schetzlein: So we have taken into account statistically the secondary endpoints, obviously to have future discussions with the agency on potential label language. Those key secondary endpoints are, the first one is really the reduction of at least one day off parenteral support for the total population at week 24. So it's not a subtype endpoint; it's the total population.

Mike: It's not a subtype.

Mike: And points to the total population the second one really looks at the parental support volume reductions in stoma, the subpopulation at week 24.

Mike Schetzlein: The second one really looks at the parenteral support volume reductions in stoma, the subpopulation at week 24. And then the third one looks at the parental support volume reductions for CIC, specifically at week 48. Because, as we've mentioned many times, we think the CIC population takes a little longer to respond. They start with lower parental support volume needs and those kind of things.

And then the third one looks at the parental support volume reductions for CIC, specifically at week 48, because as we've mentioned many times, we think the CIC population takes a little longer to respond they start with lower plasma parental support volume needs and those kind of things.

Mike: The fourth one is what is the enteral autonomy.

Tom Mccourt: The fourth one is the enteral autonomy end point, and that's at week 48. And then, with respect to the sales force question, at launch, we will have the largest sales force ever arrayed against this disease state with over 90, our existing 90 reps, 90 plus reps here at Ironwood. From an incremental investment standpoint, I think we'll see as we get closer to launch how much that needs to evolve. We don't think it's very much.

Mike: <unk> Nenets at week 48.

Mike: And then with respect to the sales force question.

Mike: At launch we will have the largest sales force ever rate against this disease States, where it's over 90% are existing 90 reps 90, plus reps here at Ironwood.

Mike: From an incremental investment standpoint, I think we'll we'll see as we.

Mike: As we get closer to launch how much that needs to evolve we don't think it's very much we.

Tom Mccourt: We do think there will be additional investments, though, tied to selling a therapy that is a rare disease, and so that includes hub services, patient services, and there is, this becomes much more of a service model where we have to follow the patient through their patient journey and help support them. So, we'll build out some of those additional ancillary components of our sales force and our team. We don't think it's significant in terms of incremental spending and would not affect the guidance we've already given in terms of where we're going. I mean, I think that this is Tom, I think the big thing to understand with the Salesforce deployment is that we're already in the offices today that, you know, a lot of these physicians who really kind of specialize in managing these patients reside.

Mike: We do think there will be additional investment stout tied.

Mike: Tied to selling a therapy that is a rare disease.

Mike: And so that includes hub services patient services. There is this becomes much more of a service model, where we have to follow the patient through and.

Mike: There their patient journey and help support them.

Mike: So we will build out some of those additional or ancillary components of our our sales force.

Mike: And our team at that now.

Mike: We don't think is significant in terms of incremental spend and would not affect the guidance. We've already given in terms of where b in 2025, Jimmy I think this is Tom I think the big thing to understand with the sales force deployment as.

Mike: Because we're already in the offices today.

Mike: A lot of these physicians, who really kind of specialized.

Mike: Managing these patients.

Tom Mccourt: So that's the reason why we feel very confident that we have an adequate sales force. There may be some additional roles, you know, that will be specific to certain large GI practices that we're taking a look at that I think could very creatively and effectively accelerate the uptake of the drug. But we're not looking at certainly a significant incremental spend in sales. Great, that's super helpful. Thanks so much, www.ironwoodpharmaceutical.com. Your next question comes from the line of David Amsellem from Piper Sandler. Your line is open. Hey, thanks. This is Tim on behalf of David.

Mike: Reside so that's the reason why we feel very confident that we have an adequate salesforce there may be some additional roles.

Mike: That will be specific.

Mike: For certain large Gi practices that we're taking a look at that I think could very creatively and effectively accelerate the uptake of the drug but we're not looking at certainly a significant incremental spend in salesforce.

Speaker Change: Great that's super helpful. Thanks, so much.

Your next question comes from the line of David Anderson from Piper Sandler Your line is open.

Speaker Change: Hey, Jay this is Tim on for David as we get closer to the absolute that data what are your latest thoughts on pricing of absolutely tied to the extent that generic <unk> materializes.

David A. Amsellem: As we get closer to apiglutide data, what are your latest thoughts on pricing for apiglutide to the extent that a generic GATX materializes? And what's your latest thinking on your strategy for apiglutide XUS, particularly in Europe? Yeah, so thanks, Tim.

Tim: And what's your latest thinking on the strategy, where applicable tied ex U S, particularly in Europe.

Jay: Yeah. So thanks, Tim first on pricing I think we're still.

Shrevan Imani: First on pricing, I think we're still working on some of that in terms of where those, where we'll price them. I don't think we've communicated our strategy yet. I think we still have some time before we feel like we're ready to do that.

Jay: Working on on some of that in terms of where those.

Tim: Where we'll price it I don't think we've communicated yet our strategy.

Tim: And I think we still have some time before we feel like we're ready to do that I think a lot of it will tie to what our clinical profile actually it looks like and how differentiated it actually is.

Shrevan Imani: I think a lot of that will tie to what our clinical profile actually looks like and how differentiated it actually is. And so we'll wait until we have the data in March before we start working on that. With respect to the second component of your question, which is APRA-US, I think we understand that our current field in Salesforce is heavily US-based.

Tim: And so we'll wait till we have the data in March before we start working on that with respect to the second part of your question, which is out of our U S. I think we understand them our current field and sales forces heavily U S.

Shrevan Imani: And we're open, I think, to some flexibility about how we'll think about ex-US in a very strategic manner. I mean, you can imagine, having a best-in-class product like this or potentially a best-in-class product like this, you know, we are certainly getting a fair bit of inbound interest. You know, but, you know, it's obviously something we're going to certainly take advantage of as we move forward. Thanks guys, www.ironwood.com. Your next question comes from the line of Mahita Branfell from Wells Fargo. Your line is open.

And we're open I think.

Tim: Some flexibility about how we will think about.

Ex U S and are in a very strategic manner for for our company.

Tim: I mean, you can imagine I mean, having a best in class product like this or potentially best in class product.

Tim: We are certainly getting a fair bit of inbound interest.

Tim: But.

Tim: Obviously, it's something we could certainly take advantage of as we move forward.

Speaker Change: Awesome. Thanks, guys.

Speaker Change: Okay.

Speaker Change: Your next question comes from the line of Mohit Bansal from Wells Fargo. Your line is open.

Mohit Bansal: Great. Thank you for taking my question.

Mohit Bansal: I have two so one is like how much how much information about the secondary endpoints that you just mentioned you could expect to see with the top line release in March. So that's the first question and the second one is you do have a differentiated leaning mechanism from the parental support.

Mahita Branfell: Great, thank you for taking my question. I have two, so one is, how much information about the secondary endpoints that you just mentioned can we expect to see with the top line release in March? That's the first question.

Mike Schetzlein: And the second one is, you do have a differentiated weaning mechanism from the parenteral support. Could you talk a little bit more about that and how it could impact placebo as well as we look forward to the data? Thank you. Yeah, sure. I can give you the key secondaries as described in the prior question.

Mohit Bansal: Could you talk a little bit more about that and.

Mohit Bansal: Could it impact placebo as well as the ER.

Mohit Bansal: As we look forward because of the data. Thank you.

Mohit Bansal: Yeah sure. So as I mentioned, I mean, I can't give you. The key secondaries are described as I put them forward in the prior question I mean, the main one is the days off the one at least one day off parental support you may recall that as kind of a standard endpoint, it's been around since the GATX days, because GATX use a responder definition and the responder was at 20%.

Mike Schetzlein: I mean, the main one is the days off, at least one day off parental support. You may recall that's kind of a standard end point. It's been around since the GATX days because GATX is a responder definition, and the responder was a 20% reduction. That translated roughly to like one day out of the week and stuff like that.

Mohit Bansal: Reduction that translated roughly like one day out of the week and stuff like that but that's sort of been one thats been compare to crust agents and agents in the class.

Mike Schetzlein: But that's sort of been one that's been compared across agents in the class. And then the other two, we're really just trying to get granular on the subpopulations between STOMA and CIC. The STOMA population is that 24 weeks, as we mentioned, because oftentimes the STOMA populations have a higher parental support volume need, and they tend to respond more quickly.

Mohit Bansal: The other two were really just trying to get granular on the subpopulations between film NCIC. The stoma is at 24 weeks as we mentioned because oftentimes sistema populations have a higher purchase volume need and they tend to respond more quickly. That's why the 24 week is also at that point for that reason.

Mike Schetzlein: That's why the 24 week is also at that point for that reason. The third one is the CIC specific subpopulation, but that's a parental support volume reduction at week 48 because they often take longer to respond. And then finally, enteral autonomy, which is the complete weaning off of parental support, which we think is of value to patients. And then we'll certainly share the data in March with the top line results. And the second question you talked about, the weaning algorithm, you know, the weaning, the aspect of weaning, obviously weaning is a part of the study, right? But the aspect of the difference between STOMA and CIC has been around since the GAT-Tex days and really became clearer sort of in the post-marketing approach to GAT-Tex with patients.

Mohit Bansal: The third one is the CIC specific subpopulation, but that's a parental support volume reduction at week 48, because they often take longer to respond and then finally enter autonomy, which is the complete weaning off of French Eurosport, which we think is value value to patients.

Mohit Bansal: And then we'll certainly share the data in March with the top line results.

Mohit Bansal: And then second question you talked about the weaning algorithms.

Mohit Bansal: Waning.

Mohit Bansal: The aspect of waning, obviously leanings are part of the study right, but the aspect of the difference between stoma NCIC has been around since the GATX days and really became clear sort of in the post marketing.

Mohit Bansal: Approach to GATX with patients because even though the CIC subpopulation did not participate in the primary endpoint in the GATX program or even go up a program.

Mike Schetzlein: Because even though the CIC subpopulation did not participate in the primary endpoint in the GAT-Tex program or even the GLAPA program, really highlighting the differences between CIC and STOMA, the real data, looking closer at that data, it really became clear that the reason for that is that CIC patients start with a lower parenteral spore volume at baseline and therefore make smaller incremental reductions. And that calls into question this 10% threshold for urine output to define who gets to wean. And so that got to a lot of external discussions, which have been happening for the last decade, honestly. Could CIC patients participate in the primary endpoint if they could wean off the drug without hitting the 10% endpoint? And that's what the weaning algorithm is all about.

Mohit Bansal: Really highlighting the differences between CIC.

Mohit Bansal: And stone that the real data.

Mohit Bansal: Looking closer at that data it really became clear that the reason for that is the CIC patients start with a lower parental support volume at baseline and therefore make smaller incremental reductions in that called into question. This 10% threshold for urine output to define who gets to wean.

Mohit Bansal: And so that got to a lot of external discussions which are happening for the last decade honestly could CIC patients participated in the primary endpoint, if they could wean without hitting the 10% endpoint and thats what the waning algorithm is all about it saying if patients in their waning have greater than 10% reduction or increase.

Mike Schetzlein: It's saying if patients during weaning have a greater than 10% increase in urine output, they can wean all patients. But if they have less than 10% and they're a CIC patient, then they go through a bunch of other parameters, like their diet, like their stool input, their nutritional status, or their stool output, their nutritional status, their body weight, and all those parameters. And if they're all in line and the subject is doing nutritionally very well, then even if they don't hit the 10%, they could still participate in weaning. The weaning algorithm we used in a STARS nutrition study, and you saw that data presented at UAGW, and the patients did very well.

Mohit Bansal: And you announced but they can win all patients, but if they have less than 10% and there a CIC patient then they go through a bunch of other parameters like their diet like theres still input their nutritional status or stool output their nutritional status their body weight and all of those parameters and if theyre all in line and the subjects doing nutritionally.

Mohit Bansal: Well and even if they don't hit the 10% they could still participate in weaning the.

Mohit Bansal: The weaning algorithms, we used an historic nutrition and study.

Mohit Bansal: You saw that data presented at <unk>.

Mohit Bansal: The patients did very well granted a small nine patient open label study, but there. They all did respond and then we're able to win.

Mike Schetzlein: Granted, it was a small nine-patient open-label study, but they all did respond and were able to wean. And so the point you asked about the placebo response is a good question. That's an open-label study. So we certainly got the treatment effect from that study. We had a 40% reduction in parenteral sport volume at week 24, that increased to 52% in week 52.

Mohit Bansal: And so the point to the question you asked about the placebo response is a good question.

Mohit Bansal: That's an open label study. So we certainly got the treatment effect from that study we had a 40% reduction in <unk> at week 24 that increased to 52% by week 50, and week 52, and so we certainly think there's an opportunity for therapeutic gain to your point about placebo, we roughly look at that placebo response at an agnostic.

Mike Schetzlein: So we certainly think there's an opportunity for therapeutic gain. To your point about placebo, we roughly look at the placebo response and are agnostic about that aspect across the patient population. So even including what we've seen in other studies with the placebo response around 20%, we think there's certainly room there for therapeutic gain with the weaning algorithm in CIC patients. Thank you very much. Your next question comes from the line of Chase Knickerbocker from Craig Hallam Capital Group. Your line is open.

Mohit Bansal: That aspect across the patient population, so even including what we've seen in other studies with the placebos pattern placebo response around the 20%. We think there's certainly room there for therapeutic gain with the weaning algorithms and CIC patients.

Speaker Change: Helpful. Thank you very much.

Speaker Change: Alright.

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

Chase Knickerbocker: Good morning, guys. Thanks for taking the question I actually wanted to start with Linzess question believe it or not.

Chase Knickerbocker: So a longer one to start I just wanted to dig in a little bit deeper on 2024 net revenue guidance, maybe talk about the different moving pieces that could drive outperformance or underperformance in that guide from a standpoint of of the net pricing decline assumptions. So you guys like pretty confident in those assumptions.

Chase Knickerbocker: Good morning, guys. Thanks for taking the questions. I actually wanted to start with Alonzo's question, believe it or not, so a longer one to start. I just want to dig in a little bit deeper on 2024 net revenue guidance, maybe talk about the different moving pieces that could drive health performance or underperformance on that guide from a standpoint of the net pricing decline assumptions. So you guys are pretty confident in those assumptions. But is the assumed pediatric growth driving some increased Medicaid exposure that actually makes that erosion a little bit worse? And what does additional pediatric exposure or a differing patient mix kind of do to that erosion kind of assumption? Morning, Chase.

Chase Knickerbocker: The assumed pediatric growth driving some increased Medicaid exposure that actually makes that erosion, a little bit worse, and you know what does additional pediatric exposure or differing patient mix kind of do.

Chase Knickerbocker: To that erosion kind of assumption.

Speaker Change: Good morning Chase. So thanks for your question I would say our guidance is pretty straightforward and consistent with how we've done it in past years, which is at this point in time, we're still anticipating high single digit.

Chase Knickerbocker: Volume growth year over a very strong 2023, the fact that we're going to still grow another year from a volume perspective.

Shrevan Imani: So, thanks for your question. I would say our guidance is pretty straightforward and consistent with how we've done it in previous years, which is, at this point in time, we're still anticipating high single-digit volume growth over a very strong 2023. The fact that we're going to still grow another year from a volume perspective, that's going to be high small digits again. It's pretty impressive in my mind.

Speaker Change: That.

Speaker Change: That's going to be high single digits again, this is pretty impressive in my mind.

Speaker Change: We also gave guidance at the Jpmorgan Health care conference that we think in today that we think the price erosion and.

Speaker Change: Any other fluctuations will essentially be.

Speaker Change: Mid to high single digit headwind to have low single digit growth.

Tom Mccourt: We also gave guidance at the Chief Morgan Healthcare Conference that we think in today that we think the price erosion and any other fluctuations will essentially be mid to high single-digit headwinds to have low single-digit growth for the full year. Now, if some of those headwinds do not materialize, we could have a year that resembles last year. But at this point in time, we feel that given the change in the AMCAP rules from Medicaid that we anticipate, just given our volume and where our book of business has been over the last few years, that that's going to affect us this year. But it won't affect us from a 2025 perspective over 2024 perspective because it's a year-over-year measure. But for this year, we do think that there will be a meaningful headwind from a price perspective, just given our volume and volume. I think the one thing that we are seeing is that we're seeing growth across the entire population. I think that's important to note. Across all doses, we're seeing very strong growth, both in new-to-brand new prescriptions as well as overall total Rxs. So, I mean, that's very healthy.

Speaker Change: And for the full year now.

Speaker Change: If some of those headwinds do not materialize, we could have a year that resembles last year, but at this point in time, we feel.

Speaker Change: That given the change in the end cap.

Speaker Change: For Medicaid that we anticipate given our volume and where our book of business has been over the last few years.

Speaker Change: That's going to affect us this year and won't affect us on a 2025 over 2020 for perspective since a year over year measure.

Speaker Change: But for this year, we do think that there will be a meaningful headwind from a price perspective.

Speaker Change: And just given our volume and volumes in Medicaid.

Speaker Change: I think the one thing that we are seeing is we're seeing growth across the entire population and I think that's important to note.

Speaker Change: Look across all doses, we're seeing very strong growth both in new to brand new prescriptions as well as overall total Rx So that's very healthy.

Speaker Change: We are seeing some very promising promising movement in the pediatric population, but at this point, it's a relatively small percent of our business, but it's growing rapidly and there is probably some additional exposure on the Medicaid side in the pediatric population, but I think as far as the overall health of growth where.

Tom Mccourt: We are seeing some very promising movement in the pediatric population, but at this point, it's a relatively small percent of our business. But it's growing rapidly, and there is probably some additional exposure on the Medicaid side in the pediatric population. But I think as far as overall health growth is concerned, we're seeing it across all patient populations and all payer segments. So I think it's all heading in the right direction. You know, the FCAP cap change is kind of a one-time hit this year.

Speaker Change: <unk> seen it across all patient populations all payer segments.

Speaker Change: So I think it's all heading in the right direction and to <unk> point, we see this.

Speaker Change: Cap change as kind of a onetime hit this year, but the most important thing that we have to continue to do is drive demand growth. It's the one thing that's within our control and what we do know about this brand. It continues to be extremely promotional responsive. So we're going to continue.

Chase Knickerbocker: But the most important thing that we have to continue to do is drive demand. It's the one thing that's within our control, and what we do know about this brand, it continues to be extremely promotionally responsive, so we're going to continue to invest appropriately in the brand. Yeah, thanks, Tom. And maybe kind of piggybacking off of that, if we dig in a little bit more to the volume growth assumptions, what percentage, I guess, or what portion of that growth kind of comes from the pediatric population in your guys' assumptions? You know, what portion of that kind of growth assumption? And then also, just to ask another question before I hop back in the queue. On 104, I mean, a pretty high price tag acquisition recently, obviously, in PPE.

To invest appropriately in the brand.

Speaker Change: Yeah, Thanks, Tom and maybe kind of piggybacking off of that if we dig in a little bit more to the.

Speaker Change: To the volume growth assumptions, what percentage I guess or what portion of that growth kind of comes from the pediatric population in your guys' assumptions what.

Speaker Change: <unk> of that kind of growth assumption and then also just ask another.

Speaker Change: Another question before.

Speaker Change: Ill hop back into queue on one off or I mean pretty high price Tag acquisition recently, obviously in PBC.

Speaker Change: And maybe speak to how this kind of validates your kind of attempts at the space and way too early of a question, but if your thesis plays out here. One O floor is an approvable medicine, and how do you see it kind of fitting into the treatment paradigm.

Speaker Change: Oh, great, yes, so I changed we haven't given guidance on on the size of the pediatric indication I think we're still evaluating it.

Chase Knickerbocker: Um, you know, maybe speak to how this kind of validates your kind of attempts in the space. And, way too early of a question, but if your thesis plays out here, 104 is an approvable medicine. And, you know, how do you see it kind of fitting into the treatment paradigm? So, Chase, we haven't given guidance on the size of the pediatric indication.

Speaker Change: It's small and we're still but it's growing we're still evaluating it through some of the pilots that were running we extended them into this year I think we mentioned that earlier this year.

Speaker Change: And so as we know more we'll come back and give more granular guidance potentially over the course of the year, but at this time it is baked into our guidance I want to reiterate what Tom said is.

Speaker Change: We continue to see.

Shrevan Imani: I think we're still evaluating. It's small, but it's growing. We're still evaluating through some of the pilots that we're running. We extended them into this year. I think we mentioned that earlier this year. And so, as we know more, we'll come back and give more granular guidance, potentially over the course of the year. But at this time, it's baked into our guidance. I want to reiterate what Tom said. We continue to see more patients seeking care in this space, and the good news is that as the market leader, we're seeing more patients, we get a disproportionate share, and more patients end up coming on Linzess based on the clinical profile, patient satisfaction, and formulary access, which is class-leading, and, you know, just the duration on the market and effectiveness. So we do get a disproportionate share of that, but a lot Um, with respect to CMP 104, you know, it's, you know, congratulations to the Simon Bay team. Obviously, that's a great outcome for them.

Speaker Change: <unk> more patients seeking care in this space.

And the good news is that as the market leader.

Speaker Change: We're seeing it.

Speaker Change: More patients will get a disproportionate share of more patients end up.

Speaker Change: Coming on Linzess based on the clinical profile of patient satisfaction and at formulary access which is class leading.

Speaker Change: And just a just you know the duration on the market and effectiveness.

Speaker Change: We do get a disproportion of that a lot of it is also just.

Speaker Change: Broader demand also is patiency care.

Speaker Change: With respect to <unk> 104.

Speaker Change: Relations to the Sima Bay team obviously.

Speaker Change: Great outcome for them.

Speaker Change: We think this space is a is the reason we entered the spaces. We found an asset from a science perspective, and a profile perspective, we think that actually one.

Speaker Change: As an extension of our Gi continuity continuum.

Speaker Change: And in terms of where we can we as an organization.

Shrevan Imani: You know, we think this space is, the reason we entered the space is we found an asset from a science perspective and a profile perspective. We think that actually, one, is an extension of our GI, continuity, continuum, and in terms of where, you know, we can, we as an organization, treat GI diseases, so it's core within our strategy. Two, I think we found the science behind this asset and the potential to be disease-modifying exceptionally interesting. As Mike had mentioned earlier, all the other therapies on the market essentially treat the underlying symptoms of PVC; very few actually get to the root of the problem.

Speaker Change: Continuing to treat Gi diseases, so it's core within our strategy too.

Speaker Change: We found the science behind this asset and have tended to chose to be disease modifying exceptionally interesting.

Speaker Change: Mike had mentioned earlier all of the other therapies on market essentially treat the underlying symptoms of PVC or if you actually get to the autoimmune.

Speaker Change: Destruction.

Speaker Change: Whereas we think and again, we will with the hypothesis, which we will have more data for you in the third quarter. This year.

Speaker Change: And hopefully it's validated and that we think that CMT one of four actually will stop and arrest that autoimmune destruction.

Shrevan Imani: Hi, www.ironwoodpharmaceuticals.com Again, with the hypothesis, which we will have more data for you in the third quarter this year, and hopefully it's validated, that we think that CMP 104 actually will stop and arrest that destruction. And so, which we think will be a differentiated asset. And so that's our perspective. But again, congratulations to the summit team. Yeah, I think this is all great news. I mean, this really puts a focus on it. It's a serious, highly problematic disease that needs better care.

Speaker Change: And so which we think will be a differentiated asset in this market.

Speaker Change: And so that's our perspective, but again congratulations to the <unk>.

Speaker Change: This is all great news I mean this is it really puts a focus on it is at the high highly problematic disease that needs better care. So I think it increases the intention and the momentum in this marketplace and hopefully if we're right. We can really take advantage of them.

Speaker Change: Great. Thanks, guys.

Speaker Change: Your next question comes from the line of Jason Butler from JMP Securities. Your line is open.

Jason Butler: Hi, Thanks for taking the questions just two for me for African side could you just walk us through the gating items are following positive results from our stars and a potential regulatory submission and then just on Linzess. How are you thinking about further investment in the pediatric <unk>.

Tom Mccourt: So I think it increases the attention and the momentum in this marketplace, which hopefully, if we're right, you know, we can really take advantage of. Great. Thanks, guys.

Jason Butler: Your next question comes from the line of Jason Butler from J&P Securities. Your line is open. Hi, thanks for taking the questions. Just two for me.

Jason Butler: Herschel opportunity. It's still early like you said, but are you seeing signals of it.

Speaker Change: Thank you to justify it.

Shrevan Imani: For Apoglypse, could you just walk us through the gain items following positive results? And then, just on that, how are you thinking about further investment in the pediatric, you know, commercial opportunity? It's still early, like you said, but are you seeing signals that continue to justify investing in that business? Yeah, I'll start with the second one.

Investing in that in that business. Thanks.

Speaker Change: Yes, I'll start with the second one Jason on Linzess just for point of continuity and then Mike will answer the first question regarding regulatory pathway.

Speaker Change: Yeah look at early signs are very positive on pediatrics.

Speaker Change: And.

Speaker Change: Just from a new to brand specific dose sized debt.

Shrevan Imani: Jason Unlins asks just for a point of continuity, and then Mike will answer the first question regarding the regulatory pathway. Yeah, look, early signs are very positive in pediatrics. And, you know, just from a new-to-brand specific dose size, that is, a 92-microgram dose, we feel really positive about it. We think it's an opportunity worth pursuing between now and 2029 and worthy of the investment. But again, it's still too early to provide granular guidance as to what we think it will be this year. And so we're just, as we know more, we'll share that. We just don't want to, given the growth profile and given how small it is right now, it's something that we just want to... be more cautious about as a guide. But we are pleased with the uptake and pleased with the return on investment. But we're not seeing a dramatic increase in our investment.

Speaker Change: And 92, microgram or something you see microgram dose.

Speaker Change: We feel really.

Speaker Change: Yeah, we feel positive about it and we think it's an opportunity worth pursuing between now and 2029 and worthy of the investment, but again, it's still too early to provide granular guidance as to what we think it will be.

Speaker Change: In this year and so we're just as we know more we'll share that we just don't want to given the growth profile and given how small it is right now.

Speaker Change: It's something that we just want to.

Speaker Change: Be more cautious about from a guidance perspective.

Speaker Change: But we are pleased with the uptake and I'm pleased with the return on investment but.

Speaker Change: But we're not seeing a dramatic increase in our investment I think yes isn't it maybe a refinement of our marketing mix.

Speaker Change: I mean, there's no question, we're running a number of pilots digital pilots right now certainly sales pilots right now and you know we're taking a critical look too on the whole <unk>.

Speaker Change: Medicaid exposure piece, which has to be part of the equation with regard to where we're going to focus our activity on investment. So I think we're very we're very pleased with what we're seeing is as Robin said, but.

Tom Mccourt: I think this is maybe a refinement of our marketing mix. I mean, there's no question, you know, we're running a number of pilots, digital pilots right now, certainly sales pilots right now. And, you know, we're taking a critical look, too, on the whole Medicaid exposure piece, which has to be part of the equation with regard to where we're going to focus our activity and invest. So I think we're very pleased with what we're seeing, as Shrevan said, but we certainly are going to be very, very disappointed with how we invest their money at this point in the life cycle. Yeah, so yeah, for the upper group type for phase three, I mean, honestly, we're clearly 110% focused on the March top line results, and we're very committed to that and delivering that. So we all can understand where we are.

Speaker Change: But we certainly are going to be very very disciplined.

Speaker Change: With regard to how we invest our money is.

Speaker Change: And at this point in the lifecycle.

Speaker Change: Yeah, so yeah for upper grid tied for the phase III I mean honestly, we're clearly 110% focused on the March at top line results and very much committed to that and delivering that so that we all can understand where we are and then of course, we still have a launch opportunity for 2025, which we're focused on and they've been in between that that will all fall in as we see the data in March.

Speaker Change: <unk>.

Speaker Change: As a reminder, if you wish to ask a question. Please press star followed by one on your telephone.

Speaker Change: And your next question comes from the line of Tim Chiang of <unk>. Your line is open.

Tim Chiang: Alright. Thanks.

Tim Chiang: Mike I wanted to ask you a couple of questions just on <unk>, obviously, there's not going to be any head to head data.

Mike Schetzlein: And then, of course, we still have a launch opportunity for 2025, which we're focused on. And then, in between that, that'll all fall in as we see the date in March. www.ironwood.com. As a reminder, if you wish to ask a question, please press star followed by 1 on your telephone. And your next question comes from the line of Tim Chiang of Capital One. Your line is open.

Tim Chiang: With Apple glued tied in type and GATX, but just looking at the <unk> label, obviously that drug was approved a long long time ago.

Tim Chiang: Their primary efficacy endpoint with there's really a clinical response measurement and I.

Tim Chiang: I wanted to get your comments on it because obviously.

Tim Chiang: Let's assume you have good data in March, but how would you sort of I mean will you provide.

Tim Chiang: Hi, Mike. I wanted to ask you a couple questions just on, like, obviously there's not going to be any head-to-head data with apraglutide and GADX, but, you know, just looking at the GADX label, obviously that drug was approved a long, long time ago. You know, their primary efficacy endpoint was really a clinical response measurement, and, you know, I wanted to get your comments on that because, obviously, let's assume you have good data in March, but how would you sort of, I mean, will you provide data on the secondary outcome measure of at least a 20% reduction in Parental Support Volume from Baseline at Weeks 20 and 24, just sort of as a relative comparator to GADAC. Yeah So, you're exactly right, and I kind of alluded to this in my other comments, but the GATX program had a responder definition. The responder definition required a 20% reduction in print support volume to be a responder.

Tim Chiang: Data on the.

Tim Chiang: The secondary outcome measure of at least a 20% reduction of parental support volume from.

Tim Chiang: From baseline at week, 20, and 24, just sort of the relative comparator to GATX.

Speaker Change: Yeah, Thanks, Tim So yeah.

Speaker Change: Exactly right and I kind of alluded this tend to my other comments, but the GATX program had a responder definition responder definition required a 20% reduction in printed for volume to be responder.

Tim Chiang: And that actually translates quite well to the endpoint is a reduction in at least one day off per week. In fact, you may recall I don't know if you're aware, but at the at GATX Advisory Committee. It all came down to that fraud from the agency is one day, a week meaningful and does this sort of 20% relate to that meaning the responder definition.

Tim Chiang: And it was a key discussion point unclear that the advisors agreed and it ultimately got NPS has approval for GATX ensure best syndrome, requiring parental support.

Mike Schetzlein: And that actually translates quite well to the endpoint of the reduction in at least one day off per week. In fact, you may recall, I don't know if you're aware, but at the GATX Advisory Committee, it all came down to that from the agency: is one day off a week meaningful, and does this sort of 20% relate to that, meaning the responder definition? And it was a key discussion point, and clearly the advisors agreed, and it ultimately got NPS's approval for GATX and short bowel syndrome requiring parenteral support. So, for us, it translates to that one day off.

Tim Chiang: So for us it translates into that one day off to your point, we have a 20% reduction endpoint, but it's not one of the key secondaries.

Tim Chiang: Statistically accounted for because it's also in the regulatory discussions taken a second seat to the parental support readout volume reduction at 24 weeks as well as the one day off and that's what the discussions have gone with the agency, but they do very much correlate whether you take the relative change from baseline a percent change.

Mike Schetzlein: To your point, we have a 20% reduction endpoint, but it's not one of the key secondaries that's statistically accounted for, because it's also in the regulatory discussions taking a second seat to the parenteral support volume reduction at 24 weeks, as well as the one day off endpoint. And that's how the discussions have gone with the agency. But they do very much correlate; whether you take the relative change from baseline or percent change, those volumes do translate pretty well. And if you look, you know, GLEP's primary was a little nuanced, too, in the percent change. They didn't use the responder definition GATX did, but if you look at the data, it actually translates pretty well across the two studies, even 10 years apart, which I think is quite interesting, given the nature of a short bowel syndrome with intestinal failure.

Tim Chiang: Yeah.

Tim Chiang: Those those volumes do.

Tim Chiang: Translate pretty well and if you look you know Glenn is a primary was a little nuance to is the percent change they didn't used to responder definition GATX it but if you look at the data it actually translates pretty well across the two studies, even 10 years, apart, which I felt quite quite interesting given the nature of his short bowel syndrome, but with intestinal.

Tim Chiang: Earlier.

Speaker Change: Okay. That's helpful, Mike and I guess just the.

Speaker Change: The common ground between the data that we have with GATX and gloves.

Mike: Is that.

Speaker Change: Have obviously shown a bay.

Speaker Change: About 2.2 liter reduction.

Speaker Change: Per week in parental support.

Mike Schetzlein: Okay, that's helpful, Mike. And I guess just the common ground between the data that we have with GADx and GLEPPA is that, you know, they have obviously shown basically about a two point or a two liter reduction per week in parenteral support needs, right? I mean, and that's sort of, that's like the absolute delta over placebo.

Speaker Change: Needs right and that's sort of that's like the absolute delta over over placebo.

Speaker Change: I just wanted to make sure that.

Speaker Change: That's sort of I mean, if you can get that similar type of efficacy that would be considered a win Mike.

Mike: Yeah, well I think right now I mean, you're getting into the granular volumes, but honestly right now for US the win is gonna be.

Mike Schetzlein: So I just wanted to make sure, you know, that sort of, I mean, if you can get that similar type of efficacy, that would be considered a win, Mike. Yeah, well, I think right now, I mean, you're getting to the granular volumes, but honestly, right now, for us, the win is going to be the statistics around the primary endpoint. I mean, because that's how it's going to play out with the agency perspective, and that's what we're committed to delivering. But we certainly will have all that data, Tim, as things roll forward, you know, just like it happened with the GATX and the GLEPA programs. A lot of those more nuanced volume data points do come out later because the primary top-line data usually sticks to the statistically relevant endpoints from a first-run perspective.

Mike: Statistics around the primary endpoint I mean, because that's how it is going to play forward with the agency perspective, and that's what we're committed to delivering but we certainly will have all that data to them as things roll forward.

Mike: Just like it happened with the gap at GATX and neglect the programs a lot of those more nuanced volume data is do come out later, because the primary topline data usually sticks at a statistically relevant endpoints from a first run perspective, and then we'll have multiple scientific sessions, which will continue to roll out data to inform us of that study.

Mike: The study outcomes.

Speaker Change: I mean is it possible that some of this more specific data might be able to be released at an upcoming medical conference like CDW or do you think you'll you won't make the cut off.

Speaker Change: Well the abstract deadline for this cdw's plus last December so, it's that's kind of a.

Mike Schetzlein: And then we'll have multiple scientific sessions, which will continue to roll out data to inform us of the study outcomes. I mean, is it possible that some of this more specific data might be able to be released at an upcoming medical conference like DDW, or do you think you won't make the cutoff? Well, the abstract deadline for this DDW is for us last December, so it's that's kind of a there's obviously, you know, the fast track point. But the point is that for the top line, we really stick to the statistically relevant endpoints.

Speaker Change: Theres obviously.

Speaker Change: The fast track point, but the point is for the top line, we really stick to the statistically relevant endpoints, so they're going to they're going to there'll be a lot of data coming later.

Speaker Change: Got it okay. Thanks, thanks, so much Mike.

Speaker Change: Hmm.

Speaker Change: Okay.

As there are no further questions I would like to thank all speakers for today's presentation and thank you all for joining US. This now concludes today's conference you may now disconnect.

Mike Schetzlein: So they're going to, they're going to, there'll be a lot of data coming later. Got it. Okay. Thanks. Thanks much, Mike. Hmm.

Speaker Change: Please wait the conference will begin shortly.

Operator: As there are no further questions, I would like to thank our speakers for today's presentation and thank you all for joining us. This now concludes today's conference. You may now disconnect.

Speaker Change: Okay.

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Operator: Please wait; the conference will begin shortly. Please stand by for the conference to begin. Please stand by for the conference to begin.

Speaker Change: [music].

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Speaker Change: Okay.