Ironwood Pharmaceuticals Inc (IRWD) 2024 Q4 法說會逐字稿

My name is Kathleen and I will be your conference operator today. At this time I would like to welcome everyone to the Ironwood Pharmaceuticals fourth quarter 2024 investor update conference call.

我叫凱瑟琳，今天我將擔任您的會議主持人。現在，我歡迎大家參加 Ironwood Pharmaceuticals 2024 年第四季投資者更新電話會議。

(Operator Instructions) Thank you. I would like to turn the call over to Greg Martini, Chief Financial Officer. Please go ahead.

（操作員指示）謝謝。我想將電話轉給財務長格雷格·馬蒂尼 (Greg Martini)。請繼續。

Good morning, and thanks for joining us for our fourth quarter and full year 2024 investor update. Our press release issued this morning can be found on our website.

早安，感謝您參加我們的 2024 年第四季和全年投資者更新會議。我們今天早上發布的新聞稿可以在我們的網站上找到。

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

今天的電話會議和隨附的幻燈片包括 1995 年《私人證券訴訟改革法案》所定義的前瞻性陳述。此類聲明涉及風險和不確定性，可能導致實際結果大不相同。

A discussion of these statements and risk factors is available on the current Safe Harbor statement slide, as well as under the heading risk factors in our annual report on Form 10-K for the year ended December 30, 2023 and in our subsequent SEC filings.

有關這些聲明和風險因素的討論可在當前安全港聲明幻燈片中找到，也可在我們截至 2023 年 12 月 30 日的 10-K 表年度報告中的風險因素標題下找到，以及在我們隨後的 SEC 文件中找到。

All forward-looking statements speak as of the date of this presentation, and we undertake no obligation to update such statements. Also included are non-GAAP financial measures which should be considered only as a supplement to and not a substitute for or superior to GAAP measures.

所有前瞻性陳述均截至本簡報發布之日有效，我們不承擔更新此類陳述的義務。其中也包括非 GAAP 財務指標，這些指標僅應被視為 GAAP 指標的補充，而不能替代或優於 GAAP 指標。

To the extent applicable, please refer to the tables at the end of our press release for reconciliation of these measures to the most directly comparable GAAP measures. During today's call, Tom McCourt, our Chief Executive Officer, will begin with a brief overview. Mike Shetzline, our Chief Medical Officer, will discuss our pipeline, and I will provide a commercial update and review of our financial results and guidance.

在適用範圍內，請參閱我們新聞稿末尾的表格，以了解這些指標與最直接可比較的 GAAP 指標的對帳情況。在今天的電話會議中，我們的執行長湯姆·麥考特 (Tom McCourt) 將首先進行簡要概述。我們的首席醫療官 Mike Shetzline 將討論我們的產品線，我將提供商業更新以及對我們的財務結果和指導的審查。

Today's webcast includes slides, so for those of you dialing in, please go to the events section of our website to access the accompanying slides separately. With that, I'll turn the call over to Tom.

今天的網路廣播包含幻燈片，因此撥入的各位請前往我們網站的活動部分單獨存取隨附的幻燈片。說完這些，我會把電話轉給湯姆。

Good morning, everyone, and thanks for joining us today to review the fourth quarter and full year 2024 financial results and business updates. We're entering 2025 with a streamlined focus on advancing apraglutide and realizing its potential to significantly expand the market in GLP-2 treated patients with short bowel syndrome who are dependent on parental support.

大家早安，感謝您今天加入我們，回顧 2024 年第四季和全年財務表現和業務更新。我們將在 2025 年集中精力推進阿普拉魯肽並發揮其在依賴父母支持的 GLP-2 治療短腸症候群患者中大幅擴大市場的潛力。

Recent data from our open label extension study, which is called Stars extend, further reinforce and strengthen our confidence and apraglutide potential to become Ironwood's next blockbuster therapy. Last month, we shared an analysis showing that 27 total patients achieved enteral autonomy. Or in other words, achieved independence from parental support while on apraglutide.

我們開放標籤擴展研究（稱為 Stars extension）的最新數據進一步增強了我們的信心以及阿普拉魯肽成為 Ironwood 下一個重磅療法的潛力。上個月，我們分享了一項分析，顯示共有 27 名患者實現了腸內自主控制。或者換句話說，在服用阿普拉魯肽期間不再需要父母的支持。

These data are important when thinking about the impact apraglutide can have in this patient population and demonstrate apraglutide's potential to provide patients with either longer periods away from or complete freedom from parental support.

在考慮阿普拉魯肽對該患者群體的影響時，這些數據非常重要，並證明了阿普拉魯肽有可能讓患者更長時間地擺脫父母的支持或完全擺脫父母的支持。

Building on these promising results, we're planning to include additional analysis based on exposure time from the long-term extension study into our NDA submission package to support an even more robust, clinically differentiated, and comprehensive data package to the FDA.

基於這些有希望的結果，我們計劃將基於長期擴展研究的暴露時間的額外分析納入我們的 NDA 提交包中，以支持向 FDA 提供更強大、臨床差異化和全面的數據包。

As we recently announced, we have initiated the rolling submission of our NDA and expect a complete submission in the third quarter of 2025. If approved, apraglutide will become the first long acting GLP-2 to market for short-bowel syndrome patients who are dependent on parental support, providing a new treatment option with the convenience of once weekly dosing.

正如我們最近宣布的那樣，我們已經啟動了 NDA 的滾動提交，預計將於 2025 年第三季完成提交。如果獲得批准，阿普拉魯肽將成為第一個針對依賴父母支持的短腸症候群患者上市的長效 GLP-2，為患者提供每週一次給藥的便捷新治療選擇。

Aligned with this next phase of growth, we have restructured our business to focus on bringing apraglutide to market, strengthening our commitment to the advancing care for patients with short-bowel syndrome. We believe these changes we've made position us for future growth, long term value creation. And ultimately, reinforce our commitment to bringing new medicines to patients with rare disease.

為了適應下一階段的成長，我們重組了業務，專注於將阿普拉魯肽推向市場，加強我們對短腸症候群患者先進護理的承諾。我們相信，我們所做的這些改變將為我們未來的成長和長期價值創造奠定基礎。最終，加強我們為罕見疾病患者提供新藥的承諾。

We have a strong team in place to drive the success of apraglutide approved. Our commercial efforts led by Tammi Gaskins, our newly-appointed Chief Commercial Officer. And she is supported by an experienced team with expertise in key functional areas of commercialization in both GI and rare disease, and we're actively preparing for a potential commercial launch.

我們擁有一支強大的團隊來推動阿普拉魯肽的成功批准。我們的商業工作由新任命的首席商務官 Tammi Gaskins 領導。她得到了一支經驗豐富的團隊的支持，該團隊在胃腸道疾病和罕見疾病商業化的關鍵功能領域擁有專業知識，我們正在積極為潛在的商業發布做準備。

Unlike LINZESS, launching a treatment for rare disease like short-bowel syndrome requires a targeted approach. And through our extensive market assessment, we now know that this is a much smaller rare disease focused prescriber base primarily located in short bowel syndrome centers of excellence, where the majority of patients are managed.

與 LINZESS 不同，推出針對短腸症候群等罕見疾病的治療方法需要採取有針對性的方法。透過我們廣泛的市場評估，我們現在知道，這是一個規模小得多的針對罕見疾病的處方者群體，主要位於短腸綜合徵卓越中心，大多數患者都在那裡接受治療。

With these insights in mind, we plan to implement a robust patient-support service model, one that ensures seamless care from the point of prescription to treatment authorization, delivery, initiation, and ongoing utilization of apraglutide.

考慮到這些見解，我們計劃實施一個強大的患者支援服務模式，確保從處方到治療授權、交付、啟動和持續使用阿普拉魯肽的無縫護理。

While apraglutide is our focus for the future, LINZESS remains a critical part of our portfolio, helping millions of adults with IBS-C and chronic constipation. Even after 12 years, demand continues to grow, further solidifying LINZESS as the prescription market leader.

雖然阿普拉魯肽是我們未來的重點，但 LINZESS 仍然是我們產品組合的重要組成部分，幫助數百萬患有 IBS-C 和慢性便秘的成年人。即使 12 年後，需求仍在不斷增長，進一步鞏固了 LINZESS 處方藥市場領導者的地位。

In the fourth quarter of 2024, we saw a 12% increase in prescription demand growth compared to the fourth quarter in 2023 for IQBA, and 11% prescription demand growth for 2024 year over year. Due to brand volume growth was 11% for the fourth quarter of 2024 and 14% for the full year. This marks the eighth consecutive quarter for double digit new to brand volume growth, demonstrating that patients and providers continue to choose LINZESS.

2024 年第四季，IQBA 的處方需求成長率與 2023 年第四季相比成長了 12%，2024 年的處方需求成長率與去年同期相比成長了 11%。由於品牌銷量成長，2024 年第四季成長 11%，全年成長 14%。這標誌著新品牌銷售連續第八個季度實現兩位數成長，顯示患者和供應商繼續選擇 LINZESS。

For the full year of 2024, we achieved our latest 2024 financial guidance, delivering $916 million in net sales. And based on IQ via script data, we are starting to see Medicare utilization, a headwind in 2024, stabilize as a percent of our book of business in the second half of 2024.

2024 年全年，我們實現了最新的 2024 年財務指引，淨銷售額達到 9.16 億美元。根據 IQ 透過腳本資料得出的結果，我們開始看到醫療保險利用率（2024 年的一個阻力）在 2024 年下半年占我們業務帳簿的百分比將趨於穩定。

As we look ahead to 2025, we expect to continue to see continued strong demand growth with LINZESS while also anticipating pricing headwinds and therefore have a focused investment to continue to drive profits.

展望 2025 年，我們預計 LINZESS 的需求將繼續強勁成長，同時也預期會出現價格阻力，因此我們將集中投資以繼續推動利潤成長。

We expect the cash flows from LINZESS will continue to sustain future capital needs to fund the next stage of growth for Ironwood. Namely, the commercial approval and launch of apraglutide for short-bowel syndrome patients who are dependent on parental support.

我們預計 LINZESS 的現金流將繼續維持未來的資本需求，為 Ironwood 的下一階段成長提供資金。即阿普拉魯肽的商業批准和上市，用於治療依賴父母支持的短腸症候群患者。

Before I turn the call over to Mike to talk about apraglutide and short-bowel syndrome in more detail, I want to take a moment to express our gratitude to our colleagues and partners in the physician, healthcare provider, and patient community.

在我將電話轉給麥克更詳細地討論阿普拉魯肽和短腸症候群之前，我想花點時間向我們的醫生、醫療保健提供者和患者社區的同事和合作夥伴表示感謝。

February is rare disease month, and as we work towards our goal of developing and commercializing life changing therapies for patients with GI and rare diseases, we also seek to increase awareness for the people we serve who are at the center of our work year round.

二月是罕見疾病月，在我們努力實現為胃腸道疾病和罕見疾病患者開發和商業化改變生活的療法的目標的同時，我們也尋求提高我們所服務人群的意識，他們是我們的全年工作的中心。

Without their commitment and your commitment and engagement, we would not have been able to run the largest ever short-bowel syndrome intestinal failure trial with apraglutide. Short-bowel syndrome is a devastating condition that we thank you for your trust in us as we work urgently to deliver this important medicine to short bowel syndrome patients who are dependent on parental support. With that, I'll turn it over to Mike. Mike?

如果沒有他們的承諾以及您的承諾和參與，我們就不可能使用阿普拉魯肽進行迄今為止最大規模的短腸症候群腸衰竭試驗。短腸症候群是一種毀滅性的疾病，我們感謝您對我們的信任，我們正在緊急努力為依賴父母支持的短腸症候群患者提供這種重要藥物。說完這些，我就把麥克風交給麥克。麥克風？

Thanks, good morning, everyone. We're pleased to have initiated our rolling NDA submission earlier this year, which we expect to be completed in the third quarter of 2025. I want to dive a bit deeper into the opportunity around apraglutide and the compelling data generated from the STARS phase three clinical trial, including additional data from the Open label extension study STARS Extend.

謝謝，大家早安。我們很高興在今年早些時候啟動了滾動 NDA 提交，預計將於 2025 年第三季完成。我想更深入地探討阿普拉魯肽的機會以及 STARS 第三階段臨床試驗產生的令人信服的數據，包括來自開放標籤擴展研究 STARS Extend 的附加數據。

Short bowel syndrome with intestinal failure results from severe organ failure due to a reduction in intestinal function below the minimum necessary for adequate nutrition and fluid absorption, leading to a dependence on parenteral support or the IV administration of fluid and nutrients to maintain health, growth, and survival.

伴隨腸衰竭的短腸症候群是由於腸道功能下降到無法滿足足夠營養和液體吸收所需的最低水平而導致的嚴重器官衰竭，從而依賴腸外支持或靜脈注射液體和營養物質來維持健康、生長和生存。

Approximately 18,000 adult patients are impacted by this disorder across the US, Europe, and Japan. This condition is associated with increased mortality, significant morbidity, high economic burden, and reduced quality of life. Intervention with parental support comes with its own challenges affecting quality of life.

美國、歐洲和日本約有 18,000 名成年患者患有這種疾病。這種情況與死亡率增加、發病率升高、經濟負擔加重和生活品質下降有關。在父母支持下介入會帶來影響生活品質的挑戰。

Parental support can be required for 10 hours a day and six days a week on average.

平均每天需要父母照顧 10 小時，每週需要照顧 6 天。

Due to the significant patient burden, reducing the number of days and or the hours a day per week on parental support is extremely important to patients and their healthcare providers. Apraglutide is uniquely designed to accelerate intestinal growth for improved gut function and intestinal absorption.

由於患者負擔沉重，減少每週撫養父母的天數或小時數對於患者及其醫療保健提供者來說極為重要。阿普拉魯肽的獨特設計可以加速腸道生長，進而改善腸道功能和腸道吸收。

Apraglutide is the only GLP-2 analog to achieve a statistically significant reduction in weekly parental sport volume with once weekly dosing.

阿普拉魯肽是唯一每週服用一次就能顯著減少父母每週運動量的 GLP-2 類似物。

In the STARS Phase 3 study, patients also achieved clinically meaningful parental support volume reductions as early as week eight. Additionally, as previously presented, some patients achieved two and three days off of parental sport per week, and the portion of patients achieved enteral autonomy in the STARS Phase 3 study.

在 STARS 第 3 階段研究中，患者早在第八週就實現了具有臨床意義的父母支持減少。此外，如前所述，在 STARS 第 3 階段研究中，有些患者每周可以有兩到三天不參與父母體育運動，並且部分患者實現了腸內自主。

Enteral autonomy is when individuals no longer require parental support, a significant life changing milestone for patients and their families in their treatment journey. We're now seeing even more patients achieving enteral autonomy in our extension study, fairly further reinforcing Aroglutide's clinical profile.

腸內自主是指患者不再需要父母的支持，這是患者及其家人在治療過程中的重要的人生轉捩點。現在，我們在擴展研究中看到更多的患者實現了腸內自主，這進一步強化了阿羅魯肽的臨床特性。

As Tom mentioned, based on an analysis we shared in January, 27 total patients treated with apraglutide achieved enteral autonomy. Beyond that, we continue to see encouraging trends in parental sport volume reduction more broadly with longer exposure to apraglutide. We're excited by this growing body of clinical evidence that we believe supports apraglutide's potential if approved to become the first long acting once weekly GLP-2 therapy for the treatment of short bowel syndrome.

正如湯姆所提到的，根據我們在一月份分享的分析，共有 27 名接受阿普拉魯肽治療的患者實現了腸內自主治療。除此之外，隨著阿普拉魯肽使用時間的延長，我們繼續看到父母運動量減少的令人鼓舞的趨勢。我們對不斷增長的臨床證據感到興奮，我們相信，如果阿普拉魯肽獲批成為第一個用於治療短腸綜合徵的長效每週一次 GLP-2 療法，它將具有巨大的潛力。

With that, I'll turn it over to Greg to review our financials. Greg?

說完這些，我將把任務交給格雷格來審查我們的財務狀況。格雷格？

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

謝謝，麥克。2024 年結束時，我們的財務狀況良好，實現了 2024 年全年預期。我們的業務持續受到強勁的 LINZESS 處方需求的支持。

We saw 11% full-year 2024 prescription demand growth and recognized $223 million in LINZESS US net sales in the fourth quarter and $916 million for the full year.

我們看到 2024 年全年處方需求成長 11%，第四季 LINZESS 美國淨銷售額為 2.23 億美元，全年淨銷售額為 9.16 億美元。

Ironwood recorded $88.4 million in collaborative arrangements revenue in the fourth quarter of 2024 and $340.4 million for the full year.

Ironwood 在 2024 年第四季的合作安排收入為 8,840 萬美元，全年營收為 3.404 億美元。

As you can see on slide 11 in 2024, LINZESS continued to deliver strong double digit extended unit and new to brand prescription demand growth. The continued strong prescription demand growth bolsters our confidence in the strength of LINZESS over time. And the expectation that LINZESS will drive meaningful cash flows moving forward to fund the next stage of growth through the advancement of apraglutide.

正如您在 2024 年第 11 張投影片上看到的，LINZESS 繼續實現強勁的兩位數擴展單位和新品牌處方需求成長。處方需求的持續強勁成長增強了我們對 LINZESS 長期實力的信心。並且預計 LINZESS 將透過阿普拉魯肽的進步推動有意義的現金流，為下一階段的成長提供資金。

Turning to slide 12 to review full year 2024 financial highlights.

翻到第 12 張投影片來回顧 2024 年全年財務亮點。

Total revenue was $351.4 million GAAP net income was $1.8 million and adjusted EBITDA was $100.6 million which includes stock-based compensation. As a reminder, we have provided 2025 financial guidance for adjusted EBITDA excluding stock-based compensation expense. And we'll be moving to this new definition beginning in the first quarter of 2025.

總收入為 3.514 億美元，GAAP 淨收入為 180 萬美元，調整後 EBITDA 為 1.006 億美元（其中包括股票薪酬）。提醒一下，我們已提供 2025 年調整後 EBITDA（不包括股票薪酬費用）的財務指導。我們將從 2025 年第一季開始採用這個新定義。

We ended the full year 2024 with $88.6 million of cash and cash equivalents on the balance sheet. In the fourth quarter, Ironwood repaid $15 million of debt, ending the year with $385 million drawn on our credit facility.

截至 2024 年全年，我們的資產負債表上有 8,860 萬美元的現金和現金等價物。第四季度，Ironwood 償還了 1,500 萬美元的債務，年底我們的信貸額度已達 3.85 億美元。

Over the past 12 months, in the midst of pricing headwinds in 2024, Ironwood reduced its total debt balance outstanding by roughly $115 million. As of December 31, 2024, Ironwood had access to roughly $254 million in liquidity between the $88.6 million of cash on hand and $165 million undrawn revolver capacity.

在過去 12 個月中，在 2024 年定價逆風的情況下，Ironwood 將其未償還債務總額減少了約 1.15 億美元。截至 2024 年 12 月 31 日，Ironwood 擁有約 2.54 億美元的流動資金，包括 8,860 萬美元的現金和 1.65 億美元的未提取循環信貸額度。

In 2025, we remain focused on delivering sustained profits and cash flows to fund the advancement of apraglutide, and repay debt to strengthen our balance sheet.

2025年，我們將繼續致力於實現持續的利潤和現金流，以資助阿普拉魯肽的進步，並償還債務以加強我們的資產負債表。

Moving to financial guidance on slide 13. We are reiterating our 2025 guidance at this time. This includes US Linnet sales between $800 million and $850 million. We expect LINZESS prescription demand to remain strong with high single digit prescription demand growth.

轉到第 13 張投影片上的財務指引。我們此時重申我們的 2025 年指導方針。其中包括價值 8 億至 8.5 億美元的美國紅雀銷售額。我們預計 LINZESS 處方需求將保持強勁，處方需求將實現高個位數成長。

This strong demand growth is expected to be more than offset by pricing headwinds associated with the Medicare Part B redesign that went into effect earlier this year. We expect Ironwood revenue between $260 million and $290 million.

預計強勁的需求成長將被今年稍早生效的醫療保險 B 部分重新設計所帶來的價格阻力所抵消。我們預計 Ironwood 的營收將在 2.6 億至 2.9 億美元之間。

As a reminder, Ironwood recognizes collaborative arrangement revenues from LINZESS as a portion of commercial profits, which includes an ad back for Ironwood selling and marketing expenses. And we expect adjusted EBITDA excluding stock-based compensation of greater than $85 million, which reflects a roughly $55 million decrease from 2024 operating expenses, primarily within SG&A driven by the reorganization actions announced last month.

提醒一下，Ironwood 將 LINZESS 的合作安排收入確認為商業利潤的一部分，其中包括 Ironwood 銷售和行銷費用的廣告回報。我們預計，不包括股票薪酬的調整後 EBITDA 將超過 8,500 萬美元，這反映出 2024 年營運費用減少約 5,500 萬美元，主要是由於上個月宣布的重組行動推動的銷售、一般及行政費用減少。

In summary, we have taken actions to continue to generate profits and cash flows, pay down debt, strengthen our balance sheet, and support the advancement of apraglutide in 2025, and to position the company for long-term growth.

總而言之，我們已採取行動繼續創造利潤和現金流，償還債務，加強資產負債表，支持阿普拉魯肽在 2025 年的進步，並為公司的長期成長做好準備。

We are increasingly encouraged by the positive body of clinical evidence that we believe supports apraglutide 's potential to meaningfully change the treatment paradigm for short-bowel syndrome and become our second blockbuster therapy.

我們越來越受到積極的臨床證據的鼓舞，我們相信這些證據支持阿普拉魯肽有可能徹底改變短腸症候群的治療模式，並成為我們的第二個重磅療法。

We are working diligently to complete our NDA submission by the third quarter of 2025, and pre-launch planning is well under way to support the commercialization of apraglutide upon approval by the FDA.

我們正在努力在 2025 年第三季之前完成 NDA 提交，並且上市前規劃正在順利進行，以支持阿普拉魯肽在獲得 FDA 批准後實現商業化。

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

最後，我要感謝我們所有的員工、患者、照護者和倡導者，感謝他們共同致力於為胃腸道疾病和罕見疾病患者提供改變生活的治療方法。接線員，您現在可以打開熱線來回答問題了。

Thank you. We will now begin the question and answer session.(Operator Instructions)

謝謝。我們現在開始問答環節。 （操作員指示）

Chase Knickerbocker, [Quay Callum].

蔡斯·尼克博克，[奎卡勒姆]。

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

噢，早安。感謝您回答我們的問題。對我來說只是第一次。我明白，在進行這些人員變動之後，現在說這個還為時過早，但是您能否談談您對任何初步學習的信心，因為您現在已經更多地進行虛擬營銷，至少就您個人而言，您對今年在沒有 Ironwood 方面進行面對面推廣的情況下實現高個位數銷量增長的信心。謝謝。

Yeah. Sure, thanks, Chase. As we still have a very solid marketing mix supporting and driving the growth of LINZESS. We still have a number of AI sales personnel in the really the key offices. And at this point, it's a lot of the consumer advertising that's probably driving the ongoing growth. Certainly, when we look at ROIs, it tends to look very positive. And this is something that we've continued to refine over time. You think about where we were three or five years ago, we basically cut our selling effort more than by half. And we've also pulled back on, the media buy to increase the bottom line profit of the drug, and we have not seen any evidence that demand is slowing down and we're seeing that so far out of the gate. It's early. The numbers, as don't always line up year over year.

是的。當然，謝謝，蔡斯。因為我們仍然擁有非常穩固的行銷組合來支持和推動 LINZESS 的成長。我們在關鍵的辦公室仍然擁有一些人工智慧銷售人員。目前，大量的消費者廣告可能是推動持續成長的動力。當然，當我們看投資回報率時，它往往看起來非常積極。這是我們隨著時間的推移而不斷改進的事情。想想我們三、五年前的情況，我們的銷售力道基本上減少了一半以上。我們還減少了媒體購買，以增加藥品的底線利潤，我們還沒有看到任何需求正在放緩的跡象，而且我們目前已經看到了這一點。現在還早。這些數字並不總是逐年保持一致。

But we're still seeing very strong momentum on the brand. And I think as long as we can maintain broad payer access, I don't see that slowing down, when you have a brand in a market that has almost 50% market share. It's really hard for an emerging competitor to really, capture share around you and away from you, and we're actually continuing to see either maintaining or increasing our market share even in the face of multiple competitors over the last four or five years. So I think we feel very confident in the single digit demand growth.

但我們仍然看到該品牌的發展勢頭非常強勁。我認為，只要我們能夠保持廣泛的付款人訪問權限，當你的品牌在市場上擁有近 50% 的市場份額時，我認為這種增長不會放緩。對於新興競爭對手來說，真正奪取周圍的市場份額並奪走你的市場份額是非常困難的，事實上，在過去的四五年裡，即使面對多個競爭對手，我們仍然能夠保持或增加我們的市場份額。因此我認為我們對個位數的需求成長非常有信心。

And we'll be certainly watching, what's going on with our payer mix to really better understand what kind of exposure we have as the year goes on, but I think, we feel very confident in the guidance we've given that you know it's very achievable and hopefully we'll do everything we can to exceed it.

我們當然會關注我們的付款人組合的狀況，以便更好地了解隨著時間的推移我們會面臨什麼樣的風險，但我認為，我們對我們給出的指導非常有信心，你知道這是非常可實現的，希望我們會盡一切努力超越它。

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

太好了，湯姆，謝謝。格雷格，也許只是模特兒中的一對。首先，如果我們考慮成本節約的節奏，我們是否應該假設人們對這些成本節約有相當充分的認識，至少在運行率基礎上，然後在研發線上，隨著這些試驗活動開始展開。我的意思是我們應該什麼時候模擬研發的減少。它會回到 25 年嗎，會回到 26 年嗎，只是幫助我們考慮開支。

Yeah, thanks, Chase. In terms of the cost savings actions that were taken last month, first quarter, we won't see the full impact because these actions were taken at the end of January. So you'll really start seeing that full run rate in Q2 for the rest of the year.

是的，謝謝，蔡斯。就上個月第一季採取的成本節約措施而言，我們不會看到全部影響，因為這些措施是在一月底採取的。因此，您實際上將在第二季開始看到今年剩餘時間的完整運行率。

And then as you think about R&D, really R&D for 2025 would not expect to see a decline really year over year, specifically with apraglutide in the ongoing extension study. And also some of the CMC activities that we're continuing to complete as we move forward and prepare for a commercial launch.

然後，當您考慮研發時，實際上 2025 年的研發預計不會逐年下降，特別是對於正在進行的擴展研究中的阿普拉魯肽。在我們繼續前進並為商業發布做準備的過程中，我們還在繼續完成一些 CMC 活動。

The 2026 is where we would start to see some of that inflection in terms of overall R&D spend. And we'll provide more details on that as we get closer to two.

到 2026 年，我們將開始看到整體研發支出方面的一些變化。隨著 2 號日期臨近，我們將提供更多詳細資訊。

I think it's important to mention Chase too on the long-term extension, as Mike mentioned earlier, I mean, as we continue to actively follow these patients, we're seeing ongoing reduction in parental support and even enter autonomy.

我認為在長期延長方面也有必要提到 Chase，正如 Mike 之前提到的，我的意思是，隨著我們繼續積極跟踪這些患者，我們看到父母的支持不斷減少，甚至進入自主狀態。

So you know I think this is a really solid investment for us to really further understand the potential benefit that these patients can occur over time. And certainly you know that obviously strengthens the overall profile of the drug.

所以，我認為這對我們來說是一項非常可靠的投資，讓我們進一步了解這些患者隨著時間的推移可能獲得的潛在益處。當然，您知道這顯然增強了藥物的整體形象。

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

知道了。然後我要說的最後一件事是，格雷格，我稍後再說，你能否談談對遵守左輪手槍契約的信心，這有點複雜。我認為，如果您願意的話，稍微介紹一下這些廣告背後的一些詳細數學計算將會很有幫助，對吧？謝謝。

Yeah, thanks. I think just broadly speaking, we have a high degree of confidence in our outlook of 2025 with our financial guidance, we will be able to continue to maintain covenant compliance throughout the year and have a very high degree of confidence there. We did adjust the adjusted EBITDA definition.

是的，謝謝。我認為從廣義上講，我們對 2025 年的前景充滿信心，憑藉我們的財務指導，我們將能夠在全年繼續保持遵守契約，並對此抱有非常高的信心。我們確實調整了調整後的 EBITDA 定義。

As I noted in the prepared remarks, to give a little bit more clarity about some of the key adjustments we have with those debt covenants, specifically with stock-based compensation. But there are other adbacks, and I can't necessarily go through all of them in detail.

正如我在準備好的發言中提到的那樣，為了更清楚地說明我們對這些債務契約的一些關鍵調整，特別是基於股票的薪酬。但還有其他的廣告，我沒辦法一一詳述。

But there are other adbacks that do give us additional room and comfort with being able to achieve those covenant amounts for our debt throughout ’25. And it's something we're very much focused on and very focused on disciplined expense management to continue to drive profits and cash flows with those covenants in mind.

但還有其他的返還確實為我們提供了額外的空間和舒適度，使我們能夠在整個 25 年內實現債務的契約金額。這是我們非常關注的事情，非常注重嚴格的費用管理，以便在考慮這些契約的情況下繼續推動利潤和現金流。

Jason Butler, Citizens JMP.

傑森‧巴特勒 (Jason Butler)，公民 JMP。

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

感謝您回答這個問題。剛長期服用阿普拉魯肽。您能否談談那些達到或實現腸內自主的患者的特徵，我想您是否從 CIC 和造口患者身上都看到了這一點，然後這與研究的雙盲期相比如何 - 我認為當時大約有七名患者實現了腸內自主。這些患者中是否有人在整個治療期間保持了自主性？謝謝。

Yeah, thanks, Jason. Thanks for your question. So in terms of the patients achieving enteral autonomy, we really benefit from the fact that we have completed the largest ever done Phase 3 program in SBS-IF. So it's SBS-IF as is a very heterogeneous syndrome patient disease.

是的，謝謝，傑森。謝謝你的提問。因此，就患者實現腸內自主而言，我們真正受益於我們已經完成了 SBS-IF 有史以來規模最大的 3 期專案。因此，SBS-IF 是一種非常異質性的綜合徵患者疾病。

So having that large patient population really gives us an opportunity to look at a broad spectrum of patients. And their outcomes and if you to direct your question to this enteral autonomy, we certainly are seeing patients achieve enter autonomy on both stoma and CIC.

因此，擁有如此龐大的患者群體確實使我們有機會觀察廣泛的患者群體。他們的結果以及如果您的問題是關於腸內自主性的，我們肯定會看到患者在造口和 CIC 上都實現了進入自主性。

We'll actually roll out the details on the whole population. That's one of the things we're putting together for this submission because we know that's an important question for all of us in terms of understanding the critical benefit to this patient population. And it's fair to say that it is in all of the secondaries we presented some of this data last year too in all the secondaries that look at subpopulations across the SBS-IF, we really do all we see a numerical benefit with apraglutide.

我們實際上將向全體民眾公佈詳細資訊。這是我們為本次提交的內容之一，因為我們知道，對我們所有人來說，這都是一個重要的問題，有助於我們了解該患者群體的關鍵益處。公平地說，我們在所有的二級研究中都展示了一些數據，去年，我們在所有研究 SBS-IF 亞群的二級研究中也展示了一些數據，我們確實看到了阿普拉魯肽在數值上的優勢。

So we really do think the patient population that we're targeting is the right one, meaning the broad patient population with short bowel syndrome and intestinal failure. In terms of the double blind data, you probably recall that initially we saw enter autonomy achieved at 24 weeks, and that actually included stoma patients as well.

因此，我們確實認為我們所針對的患者群體是正確的，即患有短腸症候群和腸衰竭的廣大患者群體。就雙盲數據而言，您可能還記得，我們​​最初看到在 24 週時實現了進入自主性，並且實際上也包括造口患者。

And then by the end of 48 weeks we had roughly 10 patients achieve enter autonomy. The 27 comes from adding in the STAR's Extend data, which is the o'12 study, which is the extension study. And that brought that number up obviously to a very meaningful number of 27. Which really in aggregate is a pretty robust outcome if you look at other comparative products in terms of how many patients are achieving, enter autonomy, and the patients who achieved enter autonomy in the double blind period carry on into the extension program. So we're really seeing good fidelity and once patients achieve enter autonomy they maintain it.

到 48 週結束時，我們大約有 10 名患者實現了自主進入。27 來自於添加 STAR 的擴展數據，即 o'12 研究，即擴展研究。這顯然使這個數字上升到了 27 這個非常有意義的數字。如果你看一下其他比較產品，看看有多少患者實現了自主治療，並且有多少患者在雙盲期實現了自主治療並繼續進入延長計劃，那麼總體而言，這確實是一個非常強勁的結果。因此，我們確實看到了良好的保真度，一旦患者達到自主，他們就會保持這種狀態。

Great. Thank you for taking the question.

偉大的。感謝您回答這個問題。

Amy Li, Jefferies.

艾米李 (Amy Li)，傑富瑞 (Jefferies)。

Hi, this is Kathy on for Amy. Congrats on the quarter. So I guess I was wondering, as we think about the timing of the Medicare Part D redesign impact, is it fair to assume that the impact to LINZESS revenues won't be until the second half of 2025 since LINZESS is low cost and it takes time for patients to get into catastrophic coverage?

大家好，我是 Kathy，為 Amy 服務。恭喜本季取得佳績。所以我想知道，當我們考慮 Medicare Part D 重新設計的影響時間時，是否可以公平地假設對 LINZESS 收入的影響要到 2025 年下半年才會出現，因為 LINZESS 成本低，而且患者需要時間才能獲得災難性保險？

Yeah, thanks, Cathy, for the question. I think the key for us is our full year guidance obviously takes into account our expectations for this redesign for the full year. I think there is an element of timing here where we will have to see how prescription demand trends and ultimately the tiering within Medicare Part D plays out over the course of the year.

是的，謝謝 Cathy 提出這個問題。我認為對我們來說關鍵的是我們的全年指導顯然考慮到了我們對全年重新設計的期望。我認為這裡有一個時間因素，我們必須觀察處方需求趨勢以及醫療保險 D 部分的分級最終在一年內如何發揮作用。

So I do think each quarter we move forward we'll have better insights into what the potential price exposure is. But we feel very confident that our guidance range appropriately accounts for the trends and the expectations we have for the year.

因此我確實認為，未來每季我們都會對潛在的價格風險有更好的了解。但我們非常有信心，我們的指導範圍能夠適當地反映出今年的趨勢和預期。

Okay, great. Thank you.

好的，太好了。謝謝。

[Pitakar Seat], Leerink Partners.

[Pitakar 座椅]，Leerink Partners。

Hi guys, this is [Matt Calperon] for Pitakar. Thanks for taking my questions. Just a couple for me. How should we be thinking about the launch expenses for apraglutide both in terms of magnitude and timing and what levels are contemplated in the 2025 adjusted eBay guide, and then second question just what options exist around the 2026 convert and how is the company thinking about managing that?

大家好，我是 Pitakar 的 [Matt Calperon]。感謝您回答我的問題。對我來說只有一對。我們應該如何考慮阿普拉魯肽的上市費用（包括規模和時間）以及 2025 年調整後的 eBay 指南中考慮的水平，然後第二個問題是 2026 年轉換存在哪些選擇以及公司如何考慮管理它？

Thank you. Thanks, Matt. I can take both of those. In terms of the commercial launch expenses, we have been working on commercial planning activities from 2024. And we'll continue that into 2025. I would say at this point they are not significant expenses within the overall P&L. And we would expect to see a bit of a ramp up as we get closer to launch in 2026, and we'll provide additional details on exactly what that spend looks like as we get closer to that timing.

謝謝。謝謝，馬特。我可以接受這兩個。在商業發射費用方面，我們從2024年開始就致力於商業規劃活動。我們將在 2025 年繼續這樣做。我想說，目前這些並不是整體損益表中的重大開支。隨著 2026 年發布日期的臨近，我們預計支出會增加，隨著發布日期的臨近，我們將提供有關支出情況的更多詳細資訊。

And then in terms of the 2026 convertible notes, this is something that we continually evaluate our capital structure in the context of our overall forecast and outlook, and we are very much focused throughout 2025 on strengthening our balance sheet with the And on driving profits and cash flows to repay our existing debt and so we'll provide additional details as we make decisions on any further actions on our balance sheet, but at this point I really want to focus on driving cash flows to repay our outstanding debt.

就 2026 年可轉換票據而言，我們會根據整體預測和前景不斷評估我們的資本結構，並且在整個 2025 年，我們都非常注重加強我們的資產負債表，並推動利潤和現金流來償還我們現有的債務，因此，在決定對資產負債表採取任何進一步行動時，我們將提供更多詳細信息，但此時我們想做的

Got it, thank you.

知道了，謝謝。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆、派珀·桑德勒。

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

嘿，謝謝。我加入得比較晚，所以也許你已經解決了這個問題，但是你能更廣泛地談談成本結構嗎？這與您啟動阿普拉魯肽的能力關係不大。而是在多大程度上可以提取更多的儲蓄。我知道你們最近進行了重組。但也許您可以多談談，考慮到目前的資本結構，您是如何考慮進一步精簡的？謝謝。

Yeah, thanks, David. In terms of cost structure, I think we feel very good about our outlook, as I mentioned, in terms of 2025 and the actions we've taken to really focus on profits and cash flows in '25.

是的，謝謝，大衛。就成本結構而言，正如我所提到的，我認為我們對 2025 年的前景以及我們為真正關注 2025 年的利潤和現金流而採取的行動感到非常滿意。

As we move forward, we'll continue to evaluate other alternatives to really prioritize investments focused on those. We think will drive the best long term value and that includes the Ironwood P&L as well as the overall brand investment in conjunction with that. So at this point I think we've communicated everything that we can at this time on what we plan to do for '25 and we'll continue to evolve that as we move forward in '26.

隨著我們不斷前進，我們將繼續評估其他替代方案，以真正優先考慮針對這些方案的投資。我們認為這將帶來最佳的長期價值，其中包括 Ironwood 損益表以及與之相關的整體品牌投資。因此，我認為，目前我們已經盡我們所能地傳達了 25 年的計劃，並且我們將在 26 年繼續推進這一計劃。

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

好的，謝謝。女士們、先生們，我們的問答環節和今天的電話會議到此結束。感謝大家的參與。您現在可以斷開連線。