Ironwood Pharmaceuticals Inc (IRWD) 2024 Q3 法說會逐字稿

Thank you for standing by. My name is Louella, and I will be your conference operator today. At this time, I would like to welcome everyone to the Ironwood Pharmaceuticals Q3 2024 investor update conference call. (Operator Instructions)

謝謝你的支持。我叫盧埃拉，今天我將擔任你們的會議操作員。此時此刻，我歡迎大家參加 Ironwood Pharmaceuticals 2024 年第三季投資者更新電話會議。（操作員說明）

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

我現在想將電話轉給投資者關係總監 Matt Roache。請繼續。

Thank you, Louella. Good morning, and thanks for joining us for our third-quarter 2024 investor update. Our press release issued this morning can be found on our website.

謝謝你，盧埃拉。早安，感謝您接受我們的 2024 年第三季投資者更新。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. A discussion of these statements and risk factors is available on the current safe harbor statement slide as well as under the heading Risk Factors in our annual report on Form 10-K for the year ended December 31, 2023, and in our subsequent SEC filings. All forward-looking statements speak as of the date of this presentation, and we undertake no obligation to update such statements.

今天的電話會議和隨附的幻燈片包含 1995 年《私人證券訴訟改革法案》含義內的前瞻性陳述。此類陳述涉及風險和不確定性，可能導致實際結果有重大差異。有關這些聲明和風險因素的討論可在當前的安全港聲明幻燈片以及我們截至 2023 年 12 月 31 日的 10-K 表格年度報告以及我們隨後向 SEC 提交的文件中的風險因素標題下找到。所有前瞻性陳述均截至本簡報發布之日，我們不承擔更新此類陳述的義務。

Also included are non-GAAP financial measures, which should be considered only as a supplement to and not a substitute for or superior to GAAP measures. To the extent applicable, please refer to the tables at the end of our press release for reconciliations of these measures to the most directly comparable GAAP measures.

還包括非 GAAP 財務指標，這些指標僅應被視為 GAAP 指標的補充，而不是替代或優於 GAAP 指標。在適用的範圍內，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公認會計準則指標的對帳情況。

During today's call, Tom McCourt, our Chief Executive Officer, will begin with a brief overview and discuss the commercial performance of LINZESS. Mike Shetzline, our Chief Medical Officer, will discuss our pipeline. And Sravan Emany, our Chief Operating Officer and the Chief Financial Officer, will review our financial results and guidance.

在今天的電話會議中，我們的執行長 Tom McCourt 將首先簡要概述並討論 LINZESS 的商業表現。我們的首席醫療官 Mike Shetzline 將討論我們的產品線。我們的營運長和財務長 Sravan Emany 將審查我們的財務表現和指導。

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.

今天的網路廣播包括幻燈片。因此，對於撥打電話的人，請前往我們網站的「活動」部分，並單獨訪問隨附的幻燈片。

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

這樣，我就把電話轉給湯姆。

Thanks, Matt. Good morning, everyone, and thanks for joining us today to review our third-quarter 2024 financial results and business updates.

謝謝，馬特。大家早安，感謝您今天加入我們回顧我們的 2024 年第三季財務業績和業務更新。

Starting with LINZESS. LINZESS continues to deliver robust year-over-year prescription demand growth. In the third quarter, prescription demand increased by 13%, driven in part by new-to-brand prescriptions, which also grew by 13%. This marks the seventh consecutive quarter of double-digit new-to-brand volume growth as LINZESS remains the preferred treatment option for both patients and providers.

從林澤開始。LINZESS 處方藥需求持續實現強勁的年成長。第三季度，處方藥需求增加了 13%，部分原因是新品牌處方藥也增加了 13%。這標誌著新品牌銷售連續第七個季度實現兩位數成長，因為 LINZESS 仍然是患者和醫療服務提供者的首選治療選擇。

While prescription volumes remain very strong, LINZESS is continuing to experience pricing headwinds primarily due to the increase in Medicaid prescriptions as a percent of the overall LINZESS business, as we highlighted on last quarter's call.

儘管處方量仍然非常強勁，但林澤繼續面臨定價阻力，這主要是由於醫療補助處方佔林澤整體業務的百分比增加，正如我們在上季度的電話會議中所強調的那樣。

Moving to our pipeline. Over the past several months, we've been working towards an apraglutide NDA submission with a label focused on adult patients with short bowel syndrome who are dependent on parenteral support and remain on track to complete our filing in the first quarter of 2025.

轉向我們的管道。在過去的幾個月裡，我們一直在努力提交阿普拉魯肽 NDA，其標籤重點關注依賴腸外支持的成年短腸症候群患者，並預計在 2025 年第一季完成我們的申請。

We continue to see significant unmet need and market opportunity in short bowel syndrome, and we're excited about apraglutide's potential to support short bowel syndrome patients. Feedback from our Phase III data from the experts in short bowel syndrome support our belief that, if approved, apraglutide will be the drug of choice among physicians to treat adult patients with short bowel syndrome who are dependent on parenteral support.

我們繼續看到短腸症候群的巨大未滿足需求和市場機會，我們對阿普拉魯肽支持短腸症候群患者的潛力感到興奮。短腸症候群專家的 III 期數據回饋支持我們的信念，即如果獲得批准，阿普拉魯肽將成為醫生治療依賴腸外支持的成年短腸症候群患者的首選藥物。

Last week, we had the privilege of presenting new STARS Phase III findings at the American College of Gastroenterology Annual Scientific Meeting, where our STARS safety abstract was the recipient of ACG's Presidential Poster Award. And our subgroup analysis was shared as an oral presentation, which we're very proud of and speaks to the interest in and the quality of the data.

上週，我們很榮幸在美國胃腸病學會年度科學會議上展示了新的 STARS III 期研究結果，我們的 STARS 安全摘要獲得了 ACG 總統海報獎。我們的亞組分析以口頭演示的形式分享，我們對此感到非常自豪，並說明了人們對數據的興趣和品質。

These findings, which Mike will discuss in more detail, build on our previously announced positive data from the Phase III pivotal STARS trial and reinforce apraglutide's strong clinical profile, including its demonstrated efficacy, tolerability, and once-weekly dosing convenience. Our team is focused on getting apraglutide to market as soon as possible, and we look forward to providing more updates to our progress in the months ahead.

Mike 將更詳細地討論這些發現，這些發現建立在我們先前發表的III 期關鍵STARS 試驗的積極數據的基礎上，並強化了阿普拉魯肽強大的臨床特徵，包括其已證實的療效、耐受性和每週一次給藥的便利性。我們的團隊致力於盡快將阿普拉魯肽推向市場，我們期待在未來幾個月提供更多有關我們進展的最新資訊。

Moving to our pipeline programs. We routinely evaluate the risk and reward of our investments and seek to prioritize those which we believe drive most value long term. To this end, we made the decision not to exercise our option to acquire an exclusive license to CNP-104.

轉向我們的管道計劃。我們定期評估投資的風險和回報，並尋求優先考慮那些我們認為能帶來最大長期價值的投資。為此，我們決定不行使 CNP-104 獨家許可的選擇權。

And we also made the decision to end further recruitment in the IW-3300 Phase II proof-of-concept study in interstitial cystitis and bladder pain syndrome. And we'll follow the current study population for a full 12-week efficacy assessment, which will inform next steps on the program. These business decisions allow us to focus our efforts on where we believe we can deliver the most value, including the anticipated launch of apraglutide expected in 2026 and on maximizing LINZESS profits and cash flow.

我們也決定終止 IW-3300 II 期間質性膀胱炎和膀胱疼痛症候群概念驗證研究的進一步招募。我們將追蹤目前的研究人群進行為期 12 週的完整療效評估，這將為該計劃的後續步驟提供資訊。這些業務決策使我們能夠將精力集中在我們認為能夠提供最大價值的領域，包括預計在 2026 年推出阿普拉魯肽以及最大化 LINZESS 利潤和現金流。

Moving to our third strategic priority: delivering sustained profits and cash flow. In the third quarter, we generated $10 million of operating cash flow and delivered $26 million in adjusted EBITDA. Based on the third-quarter performance, we are reiterating our full-year 2024 financial guidance. In addition, we amended our credit facility to strengthen our balance sheet, and we repaid $25 million of the outstanding principal balance on our revolving credit facility.

轉向我們的第三個策略重點：提供持續的利潤和現金流。第三季度，我們產生了 1,000 萬美元的營運現金流，並實現了 2,600 萬美元的調整後 EBITDA。基於第三季的業績，我們重申 2024 年全年財務指引。此外，我們也修改了信貸安排以加強我們的資產負債表，並償還了循環信貸安排中 2,500 萬美元的未償本金餘額。

From a financial perspective, even with continued LINZESS pricing pressure, we believe we are in a good position with meaningful cash flow generation for LINZESS and a capital structure to support continued execution of our strategic priorities over the coming years. Looking ahead, we are intently focused on managing LINZESS pricing pressures to maximize profits and cash flow while simultaneously advancing apraglutide toward an NDA submission and commercial launch.

從財務角度來看，即使林澤持續面臨定價壓力，我們相信我們仍處於有利地位，能夠為林澤創造有意義的現金流，並擁有支持未來幾年繼續執行我們戰略重點的資本結構。展望未來，我們將專注於管理 LINZESS 的定價壓力，以最大限度地提高利潤和現金流，同時推進阿普拉魯肽的 NDA 提交和商業上市。

Now let's take a moment to look at some additional details on the commercial performance of LINZESS on slide 7. In the third quarter, LINZESS US net sales were $226 million. As I mentioned earlier, LINZESS extended units and new-to-brand prescription each rose by 13% in the third quarter, respectively, compared to the third quarter of 2023, reinforcing that patients and health care providers continue to choose LINZESS in a growing market.

現在讓我們花點時間看一下投影片 7 上有關 LINZESS 商業表現的一些其他細節。第三季度，LINZESS US 淨銷售額為 2.26 億美元。正如我之前提到的，與 2023 年第三季度相比，第三季度 LINZESS 擴展單位和新品牌處方分別增長了 13%，這表明患者和醫療保健提供者在不斷增長的市場中繼續選擇 LINZESS 。

The strong volume growth was more than offset by continued pricing headwinds primarily due to the increase in Medicaid as a percent of our business, driven by a combination of legislative and market factors such as the AMP cap repeal, Medicaid redetermination, and state-by-state changes. That said, since the first quarter of this year, we have seen Medicare as a percent of our business remain relatively stable at the current levels. We continue to closely monitor Medicaid utilization and additional legislative changes such as the 2025 Medicare Part D redesign and its potential impact on LINZESS.

銷售的強勁成長被持續的定價逆風所抵消，這主要是由於醫療補助占我們業務的百分比增加，這是由立法和市場因素（例如AMP 上限廢除、醫療補助重新確定和各州的情況）共同推動的。也就是說，自今年第一季以來，我們認為醫療保險占我們業務的百分比在當前水準上保持相對穩定。我們將繼續密切關注醫療補助的利用和其他立法變化，例如 2025 年醫療保險 D 部分的重新設計及其對 LINZESS 的潛在影響。

We remain focused on maximizing LINZESS brand profits and cash flow and optimizing the investments as we seek to mitigate the increased pricing pressures. We look forward to providing additional guidance on 2025 LINZESS demand and pricing expectation at the beginning of the year.

我們仍然專注於最大化 LINZESS 品牌利潤和現金流，並優化投資，以減輕不斷增加的定價壓力。我們期待在年初提供有關 2025 年 LINZESS 需求和定價預期的額外指導。

With that, I'll hand it over to Mike to discuss our pipeline. Mike?

有了這個，我將把它交給麥克來討論我們的管道。麥克風？

Thanks, Tom, and good morning, everyone. I'll start with apraglutide for patients with short bowel syndrome who are dependent on parenteral support. As Tom mentioned, last week, we presented new findings from a subgroup analysis of the primary endpoint of the STARS Phase III study at the ACG meeting.

謝謝，湯姆，大家早安。我將從阿普拉魯肽開始治療依賴腸外支持的短腸症候群患者。正如 Tom 所提到的，上週我們在 ACG 會議上介紹了 STARS III 期研究主要終點亞組分析的新結果。

The additional data presented showed the positive treatment effects of apraglutide were consistent across baseline demographics, including gender, age, body weight, region, race, ethnicity, and SBS characteristics such as length of remnant bowel anatomy. These are important results for patients given the established heterogeneity of adults with SBS who are dependent on parenteral support.

提供的額外數據顯示，阿普拉魯肽的積極治療效果在基線人口統計中是一致的，包括性別、年齡、體重、地區、種族、民族和 SBS 特徵，例如殘餘腸解剖結構的長度。鑑於依賴腸外支持的 SBS 成人患者存在異質性，這些結果對患者來說非常重要。

In addition, moving to slide 9. A poster highlighting an in-depth analysis of the STARS Phase III program safety and tolerability data was presented at the meeting, which notably received the Presidential Poster Award from the ACG. The analysis focused on any treatment-emergent adverse event or TEAE and those of special interest in SBS.

此外，轉到投影片 9。會議上展示了一張海報，強調對 STARS III 期專案安全性和耐受性數據的深入分析，該海報特別獲得了 ACG 頒發的總統海報獎。分析的重點是任何治療引起的不良事件或 TEAE 以及 SBS 中特別感興趣的不良事件。

Importantly, no new safety signals were detected for apraglutide in this analysis. Of particular note were the TEAEs of special interest which have been seen with other GLP-2s in SBS such as injection site reactions and GI hepatobiliary neoplasms, which were similar in the apraglutide and placebo arms. These data further characterize the safety profile of apraglutide in this population of patients with short bowel syndrome who are dependent on parenteral support. This type of profile can be meaningful for patients to start and stay on therapy if approved.

重要的是，在該分析中沒有檢測到阿普拉魯肽新的安全訊號。特別值得注意的是在SBS 中與其他GLP-2 一起觀察到的特別令人感興趣的TEAE，例如注射部位反應和胃腸道肝膽腫瘤，這在阿普拉魯肽組和安慰劑組中是相似的。這些數據進一步描述了阿普拉魯肽在依賴腸外支持的短腸症候群患者群體中的安全性。如果獲得批准，這種類型的資料對於患者開始和繼續治療可能有意義。

In regard to our NDA submission, we remain on track with our previous guidance and expect to fully complete the submission in the first quarter of 2025. We continue to be excited about the safety, efficacy, and tolerability demonstrated by apraglutide in the clinical trial and its once-weekly dosing convenience. Assuming approval, we believe these distinguishing factors have the potential to drive uptake and adherence and help improve the quality of life for patients with short bowel syndrome who are dependent on parenteral support.

關於 NDA 提交，我們仍按照先前的指導進行，並預計在 2025 年第一季完全完成提交。我們仍然對阿普拉魯肽在臨床試驗中所證明的安全性、有效性和耐受性及其每週一次給藥的便利性感到興奮。如果獲得批准，我們相信這些獨特的因素有可能推動接受和依從性，並有助於改善依賴腸外支持的短腸症候群患者的生活品質。

Moving to IW-3300, our wholly owned asset for the potential treatment of interstitial cystitis/bladder pain syndrome, we believe we have enrolled an adequate sample of patients to inform us of next steps and have decided to end further recruitment to complete an analysis of the data set for the patients currently enrolled. Based on this assessment, we expect to provide an update on the program in the first half of 2025.

轉向IW-3300，我們的全資資產，用於潛在治療間質性膀胱炎/膀胱疼痛綜合徵，我們相信我們已經招募了足夠的患者樣本來告知我們下一步的行動，並決定結束進一步招募以完成分析目前登記的患者的資料集。根據這項評估，我們預計將在 2025 年上半年提供該計劃的最新資訊。

With that, I'll turn the call over to Sravan.

這樣，我會將電話轉給 Sravan。

Thanks, Mike. I will begin with collaborative arrangements revenue on slide 11. LINZESS US net sales as reported by AbbVie were $226 million in the third quarter. In the third quarter, Ironwood recorded $5.8 million positive adjustment to collaborative arrangements revenue to reflect Ironwood's estimate of LINZESS gross-to-net reserves as of September 30, 2024. With this adjustment, Ironwood's US collaboration revenue was $89 million in the third quarter. As Tom noted, we continue to closely monitor Medicaid utilization trends and other legislative changes and remain focused on maximizing LINZESS profits and cash flows.

謝謝，麥克。我將從投影片 11 上的協作安排收入開始。根據艾伯維 (AbbVie) 報告，LINZESS 美國第三季淨銷售額為 2.26 億美元。第三季度，Ironwood 對合作安排收入進行了 580 萬美元的積極調整，以反映 Ironwood 對截至 2024 年 9 月 30 日的 LINZESS 總儲備與淨儲備的估計。經過此次調整，Ironwood 第三季美國合作收入為 8,900 萬美元。正如 Tom 指出的那樣，我們將繼續密切關注醫療補助利用趨勢和其他立法變化，並繼續專注於最大化 LINZESS 利潤和現金流。

Moving to slide 12. LINZESS US net sales were down 19% year over year in the third quarter. On a year-to-date basis, US net sales were down 13% compared with the third quarter of 2023 year-to-date. Ironwood's revenue in the third quarter was $92 million, a decrease of 19% year-over-year. GAAP net income was $4 million, and adjusted EBITDA was $26 million.

轉到投影片 12。LINZESS 美國第三季淨銷售額年減 19%。年初至今，美國淨銷售額較 2023 年第三季下降 13%。Ironwood第三季營收為9,200萬美元，較去年同期下降19%。GAAP 淨利潤為 400 萬美元，調整後 EBITDA 為 2,600 萬美元。

In September, we amended our credit facility, providing us with $50 million of additional liquidity and extending the maturity to December 2028, allowing for greater flexibility as we continue to evolve our capital structure and operate our business.

9 月，我們修改了信貸安排，為我們提供了 5000 萬美元的額外流動性，並將期限延長至 2028 年 12 月，從而在我們繼續發展資本結構和運營業務時提供更大的靈活性。

In the third quarter, we also repaid $25 million of the outstanding principal balance on our revolving credit facility, ending the third quarter with $400 million drawn on the facility. We ended the quarter with $88 million of cash and cash equivalents. And we continue to believe LINZESS cash flows will support our existing portfolio, including the potential apraglutide launch, further progress our development programs, and repay our debt.

第三季度，我們也償還了循環信貸額度中 2,500 萬美元的未償本金餘額，截至第三季末，該額度提取了 4 億美元。本季結束時，我們擁有 8,800 萬美元的現金和現金等價物。我們仍然相信 LINZESS 現金流將支持我們現有的投資組合，包括潛在的阿普拉魯肽的推出，進一步推進我們的開發計劃，並償還我們的債務。

Moving to slide 13. Based on our third-quarter performance, including continued stabilization in Medicaid utilization trends, we are maintaining our full-year 2024 guidance that we had issued in the second quarter. We continue to expect LINZESS US net sales between $900 million and $950 million, Ironwood revenue of between $350 million and $375 million, and adjusted EBITDA of greater than $75 million. Disciplined expense management remains a priority as we seek to offset top-line revenue headwinds to optimize profits and cash flow.

轉到投影片 13。根據我們第三季的業績，包括醫療補助利用趨勢的持續穩定，我們維持第二季發布的 2024 年全年指引。我們仍預期 LINZESS 美國的淨銷售額將在 9 億美元至 9.5 億美元之間，Ironwood 營收將在 3.5 億美元至 3.75 億美元之間，調整後的 EBITDA 將超過 7,500 萬美元。在我們尋求抵銷營收逆風以優化利潤和現金流的過程中，嚴格的費用管理仍然是首要任務。

To summarize, LINZESS demand growth is robust, and the brand's market leadership position continues to strengthen. Our goal now and for the future is to focus demand growth to maximize LINZESS profits and cash flow. In addition, we're making smart decisions in clinical development to focus on therapies with a clear path to market such as apraglutide to fulfill unmet patient needs. As such, we remain focused on advancing towards approval and commercialization of apraglutide as soon as possible.

總而言之，LINZESS 的需求成長強勁，該品牌的市場領導地位不斷加強。我們現在和未來的目標是專注於需求成長，以最大限度地提高 LINZESS 的利潤和現金流。此外，我們在臨床開發中做出了明智的決定，專注於具有明確市場路徑的療法，例如阿普拉魯肽，以滿足未滿足的患者需求。因此，我們仍然致力於盡快推進阿普拉魯肽的批准和商業化。

The new data presented at ACG are further evidence of apraglutide's strong clinical profile, not only for the potential treatment of adult SBS patients who are dependent on parenteral support, but also for the significant life cycle management opportunities that lie ahead.

ACG 上公佈的新數據進一步證明了阿普拉魯肽強大的臨床特徵，不僅可以用於依賴腸外支持的成年 SBS 患者的潛在治療，而且還可以用於未來重要的生命週期管理機會。

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.

最後，我要感謝我們所有的員工、病人、照護人員和倡議者，感謝他們共同致力於推動和支持胃腸道疾病的治療。

Operator, you may now open up the line for questions.

接線員，現在可以撥打電話提問。

(Operator Instructions) Amy Li, Jefferies.

（操作員說明）Amy Li，Jefferies。

Just two. We noticed that the commercial margin for LINZESS is slightly up quarter over quarter. Could we see this continue to expand going forward and help offset some of the pricing headwinds? And then finally, wanted to get your latest thoughts on the impact to LINZESS from Part D redesign in 2025. How much do you actually expect LINZESS to eat into the catastrophic phase, given the annual WAC is around 6,500?

只有兩個。我們注意到 LINZESS 的商業利潤率逐季度略有上升。我們能否看到這種情況繼續擴大並幫助抵消一些定價阻力？最後，想了解您對 2025 年 D 部分重新設計對 LINZESS 影響的最新想法。鑑於年度 WAC 約為 6,500，您實際上預計 LINZESS 在災難階段會吃掉多少？

Yes. Thanks, Amy. So let me just start by saying we do believe there's going to be a pricing headwind in 2025. We haven't given specific guidance on 2025 at this point. We'll provide guidance full year next year, earlier in the year as we normally do. Just given how this year has kind of gone from a guidance perspective, we want to make sure we give the best possible guidance we can. And I think we'll be in a good position earlier next year.

是的。謝謝，艾米。首先我要說的是，我們確實相信 2025 年將會出現定價逆風。目前我們還沒有給出 2025 年的具體指引。我們將像往常一樣在今年早些時候提供明年全年的指導。考慮到今年從指導角度來看的情況，我們希望確保提供盡可能最好的指導。我認為明年初我們將處於有利位置。

With respect to commercial margins, look, I think the -- we're pleased with where the margins came out in the quarter. And we'll continue to manage, track expenses to draw as much profits out of the brand as we can. But right now, I think what you're seeing is a good predictor of where the brand will be for the year.

就商業利潤率而言，我認為我們對本季的利潤率感到滿意。我們將繼續管理、追蹤費用，以盡可能從品牌中獲取利潤。但現在，我認為你所看到的可以很好地預測該品牌今年的表現。

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆，派珀·桑德勒。

Just a couple. Maybe taking a step back on LINZESS and just looking at contracting in general. Is there the potential for taking a fundamentally different look at contracting with payers as the product moves into -- towards the end of its commercial life? In other words, is there the potential for renegotiations such that you try to get better net economics? Just trying to better understand what you can do to improve the gross to net thinking beyond this year. So that's number one.

只是一對。也許可以退一步考慮 LINZESS，只專注於一般的合約。當產品進入其商業生命週期時，是否有可能對與付款人簽訂合約採取根本不同的看法？換句話說，是否有可能進行重新談判，以便您嘗試獲得更好的淨經濟效益？只是想更了解今年之後您可以採取哪些措施來提高整體思維到淨思維的水平。所以這是第一。

And then number two, regarding the commercial margins, I mean, is this a case where as the product nears the end of its commercial life, there's going to be less spend associated with LINZESS such that you're just sort of managing the brand for profitability? Maybe help us better understand how you're thinking about that, not really a 2025 question, but just sort of longer term through the LOE.

第二，關於商業利潤，我的意思是，當產品接近其商業生命週期時，與 LINZESS 相關的支出將會減少，這樣您就可以管理該品牌盈利能力？也許可以幫助我們更好地理解您的想法，這並不是一個真正的 2025 年問題，而只是透過 LOE 的長期問題。

Yes. So I think as I think about where we are, where we're going, I mean, we're at a point right now where the product is in a very, very strong place in the marketplace, the dominant player. It continued to gain share even in spite of some emerging competition. And I think we're at a point now where, as we've mentioned earlier, we need to really look critically at how we continue to increase profits and cash flow.

是的。所以我認為，當我思考我們現在的處境、我們要去的地方時，我的意思是，我們現在正處於產品在市場上處於非常非常強大的地位、佔據主導地位的時刻。儘管出現了一些競爭，但它的市場份額仍在繼續增長。我認為，正如我們之前提到的，我們現在需要真正批判性地審視如何繼續增加利潤和現金流。

So as I look at the overall investment in the brand and I look at market access and contracting as part of that, the question is how do we balance ongoing growth, investment in promotion, and contracting, and we're critically looking at all those. There's no question at this point in time, the objective is to increase the margins and the profitability. So right now, we're looking at everything from what we spend in media to our selling effort and how we contract to really maximize what we can push to the bottom line.

因此，當我審視品牌的整體投資、市場准入和簽約作為其中的一部分時，問題是我們如何平衡持續成長、促銷投資和簽約，我們正在批判性地審視所有這些。毫無疑問，目前的目標是增加利潤和獲利能力。因此，現在，我們正在考慮一切，從我們在媒體上的支出到我們的銷售努力，以及我們如何簽訂合約以真正最大限度地提高我們的利潤。

And there's no question, we continue to look and we'll -- other contracting strategies to really maximize that, including things like copay assistance. So I think all of those things right now are on the table, and we're working very closely with AbbVie, who is absolutely aligned with us to say it's time to really start looking at increasing profits and cash flow.

毫無疑問，我們將繼續尋找其他合約策略，以真正最大限度地發揮這一作用，包括共付額援助等。因此，我認為所有這些事情現在都已擺在桌面上，我們正​​在與艾伯維（AbbVie）密切合作，艾伯維（AbbVie）絕對同意我們的觀點，認為是時候真正開始考慮增加利潤和現金流了。

Jason Butler, Citizens JMP.

Jason Butler，公民 JMP。

Just another on LINZESS. When you look forward through to LOE, how do you think about the drivers of demand growth? And obviously, promotions being one of them, but I guess I'm thinking more in terms of things like breadth and depths of prescriber base and not just market share but the patient profile that's receiving the drug.

林澤 (LINZESS) 上的又一個。當您展望 LOE 時，您如何看待需求成長的驅動因素？顯然，促銷是其中之一，但我想我更多地考慮處方者基礎的廣度和深度等問題，而不僅僅是市場份額，還有接受藥物的患者概況。

Yes. I'll take that. It's Tom. I think there's probably three pieces to that. When you're the market leader, this is all about growing the market and capturing disproportionate share, and we've been doing that for the last several years. But we're at a point right now where the momentum is extremely strong, both with regard to the market dynamics, but also the presence of the brand. So what we have seen over the past couple of years is there's significantly more people seeking care.

是的。我會接受的。是湯姆。我認為這可能分為三個部分。當你是市場領導者時，一切都是為了擴大市場並佔領不成比例的份額，過去幾年我們一直在這樣做。但我們現在正處於一個勢頭極其強勁的時刻，無論是市場動態還是品牌的存在。因此，我們在過去幾年中看到，尋求護理的人顯著增加。

Obviously, in part that's due to the increased awareness of the disease that has been driven with -- by years of DTC campaigns and also physicians' view of who the appropriate patient is, which is also something that we spent a great deal of time educating physicians on as far as who is the right patient, and is the patient appropriate for the drug. And of course, adding the pediatric indications expanded that significantly.

顯然，部分原因是人們對這種疾病的認識不斷提高，多年來的 DTC 活動以及醫生對合適患者的看法，這也是我們花費大量時間進行教育的內容醫生會確定誰是合適的患者以及適合該藥物的患者。當然，添加兒科適應症顯著擴大了這個範圍。

And as we move forward, certainly, we want to continue to drive demand, but we want to do that in a very -- a far more efficient way, which we're looking at, and also other life cycle management plays such as OTC, which clearly is on the horizon and something that we are working with AbbVie on to really understand kind of when that happens and how it happens because as you know, it's a very large market, and these tend to be very durable brands over time over the counter.

當然，隨著我們前進，我們希望繼續推動需求，但我們希望以一種非常高效的方式來做到這一點，我們正在考慮這種方式，以及其他生命週期管理遊戲，例如場外交易，這顯然即將到來，我們正在與艾伯維合作，真正了解這種情況何時發生以及如何發生，因為如您所知，這是一個非常大的市場，隨著時間的推移，這些往往是非常耐用的品牌櫃檯。

So I think when I look at that, I think LINZESS is in a very strong position that continue to grow. And I think the momentum itself will continue to carry it in the years to come, and we really need to focus on profits and cash flow.

所以我認為，當我看到這一點時，我認為林澤處於非常有利的地位，並且會繼續增長。我認為這種勢頭本身將在未來幾年繼續保持下去，我們確實需要關注利潤和現金流。

Great. And then I just had one on apraglutide. You're obviously continuing to focus on presenting data at medical meetings. Can you maybe talk about the other aspects of the commercial readiness work that you're doing now and have planned for, for the coming months during the regulatory review?

偉大的。然後我就吃了一粒阿普拉魯肽。顯然，您繼續專注於在醫學會議上展示數據。您能否談談您現在正在做的以及未來幾個月在監管審查期間計劃進行的商業準備工作的其他方面？

Yes. This has been ongoing for the last six to nine months. You just don't turn on a switch and go to market, as you know and everybody on this call knows. There's really focus on how do we prepare the market, how do we prepare the brand, how do we prepare the organization.

是的。這種情況在過去六到九個月裡一直持續著。你只是不打開開關就進入市場，正如你所知，參加這次電話會議的每個人都知道。我們真正關注的是我們如何準備市場、如何準備品牌、如何準備組織。

And we are very diligent in moving all of those things forward, including we're already out there in medical meetings with the disease awareness program about what is short bowel syndrome, and what are the current limitations of therapies. And as we prepare the market, obviously, Mike and his team are working towards pulling together the best possible label we can.

我們非常努力地推動所有這些事情的進展，包括我們已經與疾病意識計劃一起參加醫學會議，討論什麼是短腸綜合症，以及目前治療的局限性是什麼。顯然，當我們準備市場時，麥克和他的團隊正在努力打造盡可能最好的品牌。

And then, of course, we have some significant things we need to create as far as core capabilities in the organization, particularly things like a patient service hub, which really is going to be critical for pulling patients through the system, both with regard to getting them on the drug, but also keeping them on the drug, which is something that I think we'll be sharing in the upcoming months with regard to our go-to-market strategy, but also the potential value of apraglutide, not only its attractiveness as the drug of first choice but also the durability and the likely adherence to therapy, which then increases the overall value of each patient that's treated. And the team is working on those. And as we complete that work and move it forward, we'll be sharing that with you in the months to come.

當然，就組織的核心能力而言，我們需要創造一些重要的東西，特別是像患者服務中心這樣的東西，這對於透過系統吸引患者確實至關重要，無論是在讓他們服用藥物，但也要讓他們繼續服用藥物，我認為我們將在未來幾個月分享我們的上市策略，以及阿普拉魯肽的潛在價值，不僅是它作為首選藥物的吸引力，以及耐久性和對治療的可能依從性，從而增加了每個接受治療的患者的整體價值。該團隊正在努力解決這些問題。當我們完成這項工作並向前推進時，我們將在未來幾個月內與您分享。

Mohit Bansal, Wells Fargo.

莫希特·班薩爾，富國銀行。

I have two, if I may. One is that can you help us understand the -- seems like the $30 million charge you took in the first quarter, it seems like a lot of that is reversing. Can you help us understand the dynamic here, and why it is not impacting the guidance because it seems like a positive impact?

如果可以的話，我有兩個。一個是你能幫助我們理解——看起來你在第一季收取的 3000 萬美元的費用，看起來很多都在逆轉。您能否幫助我們了解這裡的動態，以及為什麼它沒有影響指導，因為它看起來像是正面的影響？

And then the second question is regarding the -- I mean it seems like the fourth quarter, if I do the math, fourth quarter, you are expecting a decent bump in your share of profit, not as much as the top-line number for LINZESS. Can you help us understand the dynamic that would play out here for fourth quarter here?

然後第二個問題是關於——我的意思是，如果我算一下，第四季度，你預計你的利潤份額會出現相當大的增長，而不是像公司的頂線數字那麼大。 。您能幫助我們了解第四季的動態嗎？

Yes. So Mohit, I don't necessarily understand the second question. Could you repeat that?

是的。所以莫希特，我不一定理解第二個問題。你能再說一次嗎？

So like if I look at the guidance for LINZESS, it is $350 million to $375 million for your co-promotion profit. You did about $252 million so far in nine months. So it seems like there is a bump, there's an inflection in fourth quarter. So can you help us understand what is causing the inflection? It doesn't see -- okay.

因此，如果我查看 LINZESS 的指導，您的聯合促銷利潤為 3.5 億至 3.75 億美元。到目前為止，您在 9 個月內的收入約為 2.52 億美元。因此，第四季似乎出現了波動、出現了轉折點。那麼你能幫助我們理解是什麼導致了這種改變嗎？它沒有看到——好吧。

Yes. So first of all, Mohit, it's cyclical, right? And the brand has been historically cyclical that the fourth quarter tends to have more of the profit than other quarters. So that's the answer to the second question.

是的。首先，莫希特，這是週期性的，對吧？而且該品牌歷來具有週期性，第四季的利潤往往高於其他季度。這就是第二個問題的答案。

With the first question, the first question was tied to just the adjustments we've taken. I would say that, look, there's been a small divergence about when and timing for the recording of these gross-to-net adjustments with respect to AbbVie. And they will even out over the course of the full year. But that's all you're seeing is just timing differences at this point in time.

對於第一個問題，第一個問題與我們所做的調整有關。我想說，看，關於艾伯維記錄這些總淨值調整的時間和時機存在著小小的分歧。並且它們將在全年中保持平衡。但此時您所看到的只是時間差異。

Natalya Davies, Intron Health Research.

Natalya Davies，內含健康研究中心。

Just on costs, should we expect a jump in SG&A associated with the prelaunch cost for apra? And how should we think about R&D going into 2025 compared to the current year?

僅就成本而言，我們是否應該預期與 apra 的預發布成本相關的銷售管理費用 (SG&A) 會大幅上漲？與今年相比，我們該如何看待 2025 年的研發？

Yes. So first of all, thanks for the question. And I think, as I mentioned earlier, we'll give guidance on 2025 as we normally do next year, but just know that we have an existing sales force. Part of the rationale for acquiring apraglutide and buying an asset that we think we could take commercial is the fact that we already have a significant commercial infrastructure. But we'll give guidance on where we think we will be next year for spend and launch and profitability when we give guidance.

是的。首先，感謝您提出問題。我認為，正如我之前提到的，我們將像明年通常那樣提供 2025 年的指導，但只知道我們擁有現有的銷售團隊。收購阿普拉魯肽併購買我們認為可以商業化的資產的部分原因是我們已經擁有重要的商業基礎設施。但當我們提供指導時，我們將就明年的支出、發布和盈利能力給予指導。

(Operator Instructions) Leerink Partners.

（操作員說明）Lerink Partners。

This is Matt Cowper on for Faisal Khurshid. Just on apraglutide, how large of a sales force do you need here? And how will this work between the current LINZESS team and apraglutide? Will the LINZESS team start selling apraglutide as well? Or if so, like how overlapping or not is the prescriber base?

我是費薩爾·庫希德 (Faisal Khurshid) 的馬特·考珀 (Matt Cowper)。就阿普拉魯肽而言，您需要多少銷售人員？目前的 LINZESS 團隊和阿普拉魯肽之間將如何合作？LINZESS 團隊也會開始銷售阿普拉魯肽嗎？或者如果是這樣，例如處方者基礎有多少重疊？

Yes. I think this is the real strength that we bring to the table here is we have a very tenured and experienced sales force in gastroenterology. They continue to do a fantastic job with LINZESS, as you well know. And there is a great deal of overlap with regard to where we -- which offices. There may be slightly different prescribers, but it's largely the same offices.

是的。我認為這是我們在這裡帶來的​​真正優勢，因為我們在胃腸病學領域擁有一支非常資深且經驗豐富的銷售團隊。如您所知，他們繼續與 LINZESS 一起出色地完成工作。我們的辦事處地點有許多重疊之處。開處方的人可能略有不同，但辦公室基本上相同。

Now there will be some additions to that such as large academic centers and some other areas that we would focus. But keep in mind, this being a rare disease, this is also far fewer prescribers than we're currently calling on. So I think we feel very strongly that we can easily fold apra into our existing selling effort and be able to get up and running very quickly because of the strong access we have from day one. So I think it is one of the real towering strengths that Ironwood has and brings to the table in this space.

現在將會有一些補充，例如大型學術中心和我們關注的其他一些領域。但請記住，這是一種罕見的疾病，開處方的人也比我們目前呼籲的要少得多。因此，我認為我們非常強烈地認為，我們可以輕鬆地將 apra 納入我們現有的銷售工作中，並且能夠快速啟動並運行，因為我們從第一天起就擁有強大的訪問權限。所以我認為這是 Ironwood 在這個領域擁有並帶來的真正的巨大優勢之一。

We do not have any more questions at this time. Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

目前我們沒有更多問題。女士們、先生們，今天的電話會議到此結束。感謝大家的加入。您現在可以斷開連線。