VectivBio Holding AG (VECT) 2022 Q4 法說會逐字稿

Welcome to the VectivBio's fiscal year 2022 results call. At this time, all participants are in a listen-only mode. After the speakers' presentation there will be a question-and-answer session. (Operator Instructions) Please be advised that today's conference is being recorded.

歡迎來到 VectivBio 的 2022 財年業績電話會議。此時，所有參與者都處於只聽模式。演講者演講結束後，將進行問答環節。 （操作員說明）請注意，今天的會議正在錄製中。

I would now like to hand the conference over to your speakers today, Patrick Malloy, Senior Vice President, Investor Relations. Please go ahead.

我現在想把會議交給今天的演講者，投資者關係高級副總裁帕特里克馬洛伊。請繼續。

Thank you, and good morning, everyone. Welcome to today's call during which we will provide an update on the company and review our financial results for the full year ended December 31, 2022. Earlier this morning, we issued a press release summarizing our financial results and progress across the company, which is available on our website.

謝謝大家，早上好。歡迎來到今天的電話會議，在此期間我們將提供公司的最新情況並審查我們截至 2022 年 12 月 31 日的全年財務業績。今天上午早些時候，我們發布了一份新聞稿，總結了我們的財務業績和整個公司的進展，這是在我們的網站上可用。

I'd like to remind everyone that during today's discussion we will make statements about our future expectations, plans and prospects that constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including the risk factors discussed in our SEC filings, and we are not under any obligation to update these forward-looking statements.

我想提醒大家，在今天的討論中，我們將就 1995 年《私人證券訴訟改革法案》下的安全港條款作出構成前瞻性陳述的未來預期、計劃和前景的陳述。實際結果可能由於各種重要因素，包括我們在 SEC 文件中討論的風險因素，與這些前瞻性陳述所表明的內容存在重大差異，我們沒有義務更新這些前瞻性陳述。

Joining me on today's call are Luca Santarelli, our Chief Executive Officer; Claudia D'Augusta, our Chief Financial Officer; along with Chief Medical Officer, Omar Khwaja; and Kevin Harris, our Chief Commercial Officer. Following the prepared remarks, we'll open up the call to a question-and-answer session.

和我一起參加今天電話會議的還有我們的首席執行官 Luca Santarelli； Claudia D'Augusta，我們的首席財務官；與首席醫療官 Omar Khwaja 一起；以及我們的首席商務官 Kevin Harris。在準備好的評論之後，我們將開始電話問答環節。

Now, I'd like to turn the call over to Luca Santarelli.

現在，我想把電話轉給 Luca Santarelli。

Thank you, Pat, and thanks to everyone for joining us today. Ffor those hearing our story for the first time, VectivBio is a growing late-stage biopharmaceutical company that is focused on developing potentially life-transforming therapies for people living with serious rare disease.

謝謝你，帕特，感謝大家今天加入我們。對於那些第一次聽到我們故事的人來說，VectivBio 是一家成長中的後期生物製藥公司，專注於為患有嚴重罕見疾病的人開發可能改變生命的療法。

We are a team of individuals with deep scientific expertise driven by a relentless passion to make a meaningful difference in the lives of people living [with] rare diseases by developing treatments that are both transformational and tailored to the needs of individual patients.

我們是一個擁有深厚科學專業知識的團隊，他們在不懈的熱情的驅使下，通過開發既具有變革性又適合個體患者需求的治療方法，對罕見病患者的生活產生有意義的影響。

In 2022, we have made tremendous progress in developing our lead molecule, Apraglutide, a next generation GLP-2 analog that bears the promise of unlocking the full potential of the GLP-2 class, thanks to its unique pharmacology and also our patient tailored development strategy. We believe that apraglutide could transform the lives of people suffering from a broad range of severe rare gastrointestinal diseases, including short bowel syndrome and intestinal failure, or SBS-IF, and acute graft versus host disease or GvHD.

2022 年，我們在開發我們的先導分子 Apraglutide 方面取得了巨大進展，這是一種下一代 GLP-2 類似物，由於其獨特的藥理學和我們為患者量身定制的開發，有望釋放 GLP-2 類的全部潛力戰略。我們相信阿普拉魯肽可以改變患有廣泛的嚴重罕見胃腸道疾病（包括短腸綜合徵和腸衰竭或 SBS-IF，以及急性移植物抗宿主病或 GvHD）的人們的生活。

In 2022, we focused on execution, both towards our R&D and corporate goals. And we also positioned ourselves for our next phase of growth. We were able to achieve several key strategic and program milestones despite the challenges that '22 created in the biotech environment. In Q1 2022, we signed a Japan licensing deal with Asahi Kasei Pharmaceutical designed to develop and commercialize apraglutide in Japan.

2022 年，我們專注於執行，以實現我們的研發和企業目標。我們還為下一階段的增長做好了準備。儘管 '22 在生物技術環境中創造了挑戰，但我們還是能夠實現幾個關鍵的戰略和計劃里程碑。 2022 年第一季度，我們與 Asahi Kasei Pharmaceutical 簽署了日本許可協議，旨在在日本開發和商業化 apraglutide。

In Q2, we announced the dosing of the first two patients in STARGAZE, our proof-of-concept study in acute GvHD currently recruiting across US and Europe. In Q3, we announced promising interim six-month data from the STARS Nutrition study, a first-of-its-kind study in patients with colon-in-continuity anatomy or CIC, which represents an underserved majority of SBS-IF. patients. In November, we announced the completion of enrollment for the colon-in-continuity stratum of the Phase 3 STARS pivotal study.

在第二季度，我們宣布了 STARGAZE 中前兩名患者的劑量，這是我們目前在美國和歐洲招募的急性 GvHD 的概念驗證研究。在第三季度，我們公佈了 STARS Nutrition 研究的有前途的六個月中期數據，這是一項針對結腸連續解剖或 CIC 患者的首創研究，這代表了 SBS-IF 中服務不足的大多數。患者。 11 月，我們宣布完成 3 期 STARS 關鍵研究的結腸連續性層的招募。

And finally, we strengthened our cash position by raising a total of $284 million to be above non-dilutive and equity transactions. The current cash position provides VectivBio with a financial runway into 2025, which is over 12-months after the Phase 3 results. We believe that 2023 will be a transformational year for VectivBio with clinical readouts from STARS Nutrition, STARGAZE, and the Phase 3 STARS all over the next several months.

最後，我們通過籌集總計 2.84 億美元的非稀釋和股權交易來加強我們的現金狀況。目前的現金狀況為 VectivBio 提供了一條到 2025 年的財務跑道，這比第 3 階段的結果晚了 12 個多月。我們相信 2023 年將是 VectivBio 轉型的一年，在接下來的幾個月裡，STARS Nutrition、STARGAZE 和 3 期 STARS 的臨床讀數。

More specifically, in early May, six-month data from STARS Nutrition will be presented at an upcoming scientific conference. This study aims to demonstrate that apraglutide can improve intestinal absorption and reduce the need of parenteral support in SBS-IF patients with colon-in-continuity in anatomical subtype of SBS, where there is limited data supporting the use of Gattex.

更具體地說，5 月初，STARS Nutrition 的六個月數據將在即將舉行的科學會議上公佈。本研究旨在證明 apraglutide 可以改善腸道吸收並減少 SBS-IF 結腸連續性 SBS 解剖亞型患者的腸外支持需求，其中支持使用 Gattex 的數據有限。

Alongside the progress of the STARS Nutrition study, the enrollment completion in our Phase 3 program of apraglutide in SBS-IF is anticipated by the end of this quarter. At this point, we have closed screening of new patients, as those currently under assessment will enable us to reach the enrollment target based on our current screen failure rates. We plan to issue a press release following the randomization of the last patient.

隨著 STARS Nutrition 研究的進展，我們預計將在本季度末完成 SBS-IF 中 apraglutide 3 期項目的註冊。在這一點上，我們已經結束了對新患者的篩查，因為目前正在接受評估的患者將使我們能夠根據目前的篩查失敗率達到入組目標。我們計劃在最後一名患者隨機分組後發布新聞稿。

Moving on to acute GvHD, I'm happy to announce that we have enrolled all patients necessary to perform the preplanned interim analysis of our STARGAZE Phase 2 program by the end of Q3. This analysis will help us inform the development and filing strategy in acute GvHD, where apraglutide has the potential to become the first non-immunosuppressive treatment to address GI damage, which is one of the most critical complications of this disease leading to mortality.

轉到急性 GvHD，我很高興地宣布，我們已經招募了所有必要的患者，以便在第三季度末對我們的 STARGAZE 2 期計劃進行預先計劃的中期分析。該分析將幫助我們為急性 GvHD 的開發和歸檔策略提供信息，其中 apraglutide 有可能成為第一個解決 GI 損傷的非免疫抑制治療，這是該疾病導致死亡的最嚴重並發症之一。

A positive STARGAZE outcome would also establish the rationale to explore the GI healing and regenerative properties in apraglutide in other inflammatory GI conditions, where the immunological therapy is currently the main therapeutic approach.

積極的 STARGAZE 結果也將為探索 apraglutide 在其他炎症性胃腸道疾病中的胃腸道癒合和再生特性奠定基礎，目前免疫療法是主要的治療方法。

Now, I would like to turn the call over to our Chief Medical Officer, Dr. Omar Khwaja, who will share additional details on our pipeline progress. Omar, over to you.

現在，我想將電話轉給我們的首席醫療官 Omar Khwaja 博士，他將分享有關我們管道進展的更多詳細信息。奧馬爾，交給你了。

Thanks, Luca, and good morning, everyone. I will provide more detail on some of the major studies of apraglutide that will read out this year. At Digestive Disorders Week in Chicago on May 9, we will present important six months data on all nine patients enrolled in our STARS Nutrition study.

謝謝，盧卡，大家早上好。我將提供有關今年將宣讀的阿普拉魯肽的一些主要研究的更多詳細信息。在 5 月 9 日於芝加哥舉行的消化系統疾病週上，我們將展示參加我們的 STARS 營養研究的所有九名患者的六個月重要數據。

STARS Nutrition is the first ever dedicated study in patients with SBS-IF with colon-in-continuity or CIC. These are patients where the remnant small intestine remains connected to a functional colon and represent the majority of SBS-IF patients. The study participants were treated with the same dose used in our Phase 3 study and to whom the same CIC specific parenteral support leading algorithm was applied.

STARS Nutrition 是有史以來第一項針對伴有結腸連續性或 CIC 的 SBS-IF 患者的專門研究。這些患者的殘余小腸仍與功能性結腸相連，代表了大多數 SBS-IF 患者。研究參與者接受的治療劑量與我們的 3 期研究中使用的劑量相同，並且應用了相同的 CIC 特定腸胃外支持領先算法。

The study has two components, the main component is an assessment of PS reduction at six months after the first metabolic balanced period. We released interim data on five patients in October 2022, which demonstrated a very robust effect of a 50% reduction in PS volume at six months. We will present data from all patients at this time point.

該研究有兩個部分，主要部分是評估第一個代謝平衡期後六個月的 PS 降低。我們在 2022 年 10 月發布了五名患者的中期數據，這些數據表明在六個月時 PS 量減少了 50%，效果非常好。我們將在這個時間點提供所有患者的數據。

The study also has an exploratory component, which is the metabolic balance analysis to quantitatively assess apraglutide effect on intestinal absorption at an early time point of four weeks and a late time point of 48 weeks as a baseline. We will report data from four-week time point at DDW, where we aim to show data that supports the early positive effects of apraglutide on measures of malabsorption.

該研究還有一個探索性組成部分，即代謝平衡分析，以定量評估阿普魯肽在 4 週的早期時間點和 48 週的晚期時間點作為基線對腸道吸收的影響。我們將在 DDW 報告 4 週時間點的數據，我們的目標是展示支持阿普魯肽對吸收不良措施的早期積極影響的數據。

Midyear, we will have data from the first interim analysis of patients in our STARGAZE Phase 2 proof-of-concept study of apraglutide in patients with steroid-refractory acute GI Graft-versus-Disease. This disorder as a consequence of attack by donor T cells on the GI tract, even with best available therapy, steroid-refractory acute GvHD has a 50% mortality at six months and represents a very high unmet medical need.

年中，我們將在我們的 STARGAZE 2 期概念驗證研究中獲得對類固醇難治性急性 GI 移植物抗病患者的 apraglutide 患者的首次中期分析數據。這種疾病是供體 T 細胞攻擊胃腸道的結果，即使採用最佳可用療法，類固醇難治性急性 GvHD 在 6 個月時的死亡率為 50%，代表著非常高的未滿足醫療需求。

We're recruiting up to 34 patients who are treated with a high or low dose level of apraglutide on top of corticosteroids and ruxolitinib. The interim analysis will include safety, tolerability, response rate, and durability of response in the first 17 patients in the study treated for at least 56 days. All patients to support this interim analysis have been randomized.

我們正在招募多達 34 名患者，他們在皮質類固醇和 ruxolitinib 的基礎上接受高劑量或低劑量水平的 apraglutide 治療。中期分析將包括接受至少 56 天治療的前 17 名患者的安全性、耐受性、反應率和反應持久性。支持該中期分析的所有患者均已隨機分組。

Posted data from the STARGAZE can support the pivotal program in acute GvHD. In addition, we see this data in an immune disease of the GI tract as proof of principle that may unlock the potential for apraglutide in other immune and inflammatory GI conditions such as ulcerative colitis or Crohn's disease.

來自 STARGAZE 的發布數據可以支持急性 GvHD 中的關鍵程序。此外，我們將胃腸道免疫疾病中的這一數據視為原理證明，可能會釋放 apraglutide 在其他免疫和炎症性胃腸道疾病（如潰瘍性結腸炎或克羅恩病）中的潛力。

Finally, by Q4, we will have data from our Phase 3 STARS study in patients with SBS-IF. Positive data will form the basis of our application for approval of apraglutide for use in patients with SBS who are dependent on parenteral support. STARS is the largest clinical study ever conducted in SBS-IF patients and is recruiting 144 patients with prospective stratification to include 50% CIC and 50% stoma.

最後，到第四季度，我們將獲得來自 SBS-IF 患者的 3 期 STARS 研究的數據。陽性數據將構成我們申請批准 apraglutide 用於依賴腸胃外支持的 SBS 患者的基礎。 STARS 是有史以來在 SBS-IF 患者中進行的最大規模的臨床研究，正在招募 144 名具有前瞻性分層的患者，包括 50% CIC 和 50% 造口。

Study participants are randomized in a single 5 milligram dose of apraglutide, 2.5 milligrams for patients with a body weight below 50 kilos, also placebo, in a 2-to-1 ratio. In the placebo-controlled Phase, stoma patients are treated for 24 weeks, while CIC patients who are thought to accrue benefit after six months are treated for 48 weeks.

研究參與者以 2 比 1 的比例隨機分配單次 5 毫克劑量的阿普拉魯肽，體重低於 50 公斤的患者服用 2.5 毫克，也服用安慰劑。在安慰劑對照階段，造口患者接受了 24 週的治療，而被認為在六個月後獲益的 CIC 患者接受了 48 週的治療。

The primary endpoint is parenteral support volume reduction at 24 weeks in the whole study population with colon and anatomy-specific alpha control key secondary endpoints assessed at 24 weeks and 48 weeks. In addition to important clinically meaningful secondary endpoints such as days of parenteral support and enteral autonomy, the study also includes an extensive suite of patient reported outcomes to further establish the clinical benefits of apraglutide.

主要終點是整個研究人群在 24 週時的腸胃外支持量減少，以及在 24 周和 48 週時評估的結腸和解剖學特異性 α 控制關鍵次要終點。除了具有重要臨床意義的次要終點（例如腸外支持天數和腸內自主性）外，該研究還包括大量患者報告的結果，以進一步確定阿普魯肽的臨床益處。

All patients from STARS are eligible to roll over into the STARS Extend full year open-label extension study. Recruitment has remained well on track. We completed recruitment into the CIC arm with a 48-week treatment period in October 2022. We are close to completing recruitment into the stoma arm, which requires a 24-week treatment period.

來自 STARS 的所有患者都有資格轉入 STARS Extend 全年開放標籤擴展研究。招聘工作進展順利。我們於 2022 年 10 月完成了 CIC 臂的招募，治療期為 48 週。我們即將完成造口臂的招募，這需要 24 週的治療期。

As Luca mentioned, we had closed screening of new patients as those currently in screening will enable us to reach our enrollment target. Study retention has been extremely good, and we look forward to our top line results in Q4. We have made strong progress in the clinical development of apraglutide in SBS as well as acute GvHD and are actively exploring additional indications. We look forward to providing updates from the key readouts in 2023.

正如 Luca 提到的，我們已經結束了對新患者的篩查，因為目前正在篩查的患者將使我們能夠達到我們的入組目標。研究保留率非常好，我們期待著第四季度的頂級結果。我們在阿普魯肽治療 SBS 和急性 GvHD 的臨床開發方面取得了重大進展，並正在積極探索其他適應症。我們期待在 2023 年提供關鍵讀數的更新。

Now, I'll turn the call over to our Chief Commercial Officer, Kevin Harris.

現在，我將把電話轉給我們的首席商務官凱文哈里斯。

Thanks, Omar. In 2022, we've made great progress advancing our launch strategy and plans for a apraglutide and have been laying a strong foundation for commercialization over the past three years.

謝謝，奧馬爾。 2022 年，我們在推進 apraglutide 的上市戰略和計劃方面取得了重大進展，並在過去三年中為商業化奠定了堅實的基礎。

We have been focused on four key areas; the first area is market development. We have a good understanding of the unmet need and lessons learned from first-generation GLP-2 treatment and the challenges of living with chronic parenteral support, which will provide an important foundation for our market development messaging and plan.

我們一直專注於四個關鍵領域；第一個領域是市場開發。我們對未滿足的需求和從第一代 GLP-2 治療中吸取的教訓以及長期接受腸外支持的挑戰有很好的了解，這將為我們的市場開發信息和計劃提供重要的基礎。

The second key area is building our product strategy and branding for apraglutide, where we have completed key long lead time activities in advance of Phase 3 results. The third key area is market access. We have had significant engagement with US and European payers, which has informed our value strategy and our market access and data generation plan.

第二個關鍵領域是為 apraglutide 建立我們的產品戰略和品牌，我們已經在第三階段結果之前完成了關鍵的長期準備活動。第三個重點領域是市場准入。我們與美國和歐洲的付款人進行了大量接觸，這為我們的價值戰略以及我們的市場准入和數據生成計劃提供了信息。

The fourth key area is building our patient centric infrastructure to support the successful launch of apraglutide. We have completed the design work for a high-touch distribution and patient services model to enable a positive experience with apraglutide from day one. We have also designed our compliance roadmap and IT infrastructure plans for launch.

第四個關鍵領域是建立以患者為中心的基礎設施，以支持 apraglutide 的成功上市。我們已經完成了高接觸分銷和患者服務模型的設計工作，從第一天起就可以為阿普拉魯肽帶來積極的體驗。我們還設計了合規路線圖和 IT 基礎設施計劃以供發布。

To ensure strong execution, we established a cross-functional launch team which has been building an integrated and an aligned launch plan. And all of our activities have been significantly informed by listening to healthcare professionals, payers, patients, and the advocacy community.

為確保強有力的執行力，我們成立了一個跨職能的發布團隊，該團隊一直在製定一個綜合且一致的發布計劃。通過聽取醫療保健專業人士、付款人、患者和倡導社區的意見，我們的所有活動都得到了重要信息。

As we look ahead, 2023 is a year of launch readiness as we continue to finalize and execute our plans in advance of Phase 3 results. We are already off to a strong start this year. We recently completed a large and robust US insurance claims project with input from experts.

展望未來，2023 年是啟動準備的一年，因為我們將繼續在第三階段結果之前完成和執行我們的計劃。今年我們已經有了一個良好的開端。我們最近在專家的幫助下完成了一個龐大而穩健的美國保險索賠項目。

This project had two goals, the first goal was to further refine US projected prevalence of the SBS-IF population and improve our knowledge of patient demographics and treatment characteristics. We now estimate the number of adult patients living with SBS-IF in the US to be 9,000 and growing. These are patients who have had surgical resections and are on chronic and continuous parenteral support for at least six months.

該項目有兩個目標，第一個目標是進一步完善美國預測的 SBS-IF 人群患病率，並提高我們對患者人口統計和治療特徵的了解。我們現在估計美國患有 SBS-IF 的成年患者人數為 9,000 人，並且還在不斷增加。這些患者接受過手術切除，並接受至少六個月的慢性和連續胃腸外支持。

We also estimate an additional 3,000 to 4,000 pediatric patients living with SBS-IF in the US. The second goal of the project was to generate more accurate and actionable targeting information for our commercial deployment strategy. We now have a very good understanding of who is treating SBS-IF patients and where they are being treated and have established a prioritized targeting list at the physician and account level.

我們還估計在美國還有 3,000 至 4,000 名患有 SBS-IF 的兒科患者。該項目的第二個目標是為我們的商業部署策略生成更準確和可操作的目標信息。我們現在非常了解誰在治療 SBS-IF 患者以及他們在哪裡接受治療，並在醫生和客戶級別建立了優先目標列表。

Account level targeting will be our primary go-to-market approach as we seek to support the multidisciplinary team that takes care of the patients. We will use this information as the basis for our field force size and structure work, which will begin later this year. We continue to be on track for all prelaunch planning activities and look forward to continuing to update you on the progress of our plans.

在我們尋求支持照顧患者的多學科團隊時，帳戶級別定位將是我們進入市場的主要方法。我們將使用這些信息作為我們現場部隊規模和結構工作的基礎，該工作將於今年晚些時候開始。我們將繼續按計劃進行所有啟動前計劃活動，並期待繼續向您通報我們計劃的最新進展。

With that, I will now turn the call over to our CFO, Claudia D'Augusta, to discuss our 2022 financial results. Claudia?

有了這個，我現在將把電話轉給我們的首席財務官 Claudia D'Augusta，討論我們 2022 年的財務業績。克勞迪婭？

Thank you, Kevin. I will briefly comment now on the key financials for the year 2022. We recognized revenue from contracts with customers of $27.3 million over the year ended December 31, 2022, related to the partnering agreement with AKP.

謝謝你，凱文。我現在將簡要評論 2022 年的主要財務數據。在截至 2022 年 12 月 31 日的一年中，我們確認了與 AKP 的合作協議相關的客戶合同收入 2730 萬美元。

Research and development expenses were $74 million for the year ended December 31, 2022, as compared to $50.2 million for the year ended December 31, 2021. The increase of $23.8 million year over year was primarily due to an increase of clinical manufacturing expenses of $16.1 million related to the progress made on our Phase 3 STARS study; the Phase 2 STARS Nutrition study of apraglutide in SBS-IF patients and the STARGAZE proof-of-concept study in acute Graft-versus-Disease and the dual-chamber syringe activities; an increase of $0.9 million of employee expenses, primarily caused by the increase in the payroll expenses of $2.2 million driven by an increase in employee headcount, partially offset with a decrease of a non-cash share-based compensation of $1.3 million; and the impact of $6.9 million related to a revaluation gain of contingent liabilities recognized in 2021.

截至 2022 年 12 月 31 日止年度的研發費用為 7,400 萬美元，而截至 2021 年 12 月 31 日止年度的研發費用為 5,020 萬美元。同比增加 2,380 萬美元，主要原因是臨床製造費用增加 16.1 美元萬與我們的第三階段 STARS 研究取得的進展有關； apraglutide 在 SBS-IF 患者中的 2 期 STARS 營養研究和急性移植物抗病和雙腔注射器活動的 STARGAZE 概念驗證研究；員工支出增加 90 萬美元，主要是由於員工人數增加導致工資支出增加 220 萬美元，部分被非現金股份薪酬減少 130 萬美元所抵消； 690 萬美元的影響與 2021 年確認的或有負債的重估收益有關。

General and administrative expenses were $33.9 million for the year ended December 31, 2022, compared to $36.5 million for the year ended December 31, 2021. The decrease of $2.6 million year over year was mainly attributable to a decrease in employee expenses of $5.4 million, primarily caused by a decrease of the non-cash share-based compensation of $6.8 million, partially offset with an increase in the payroll expenses of $1.4 million driven by an increase in employee headcount and an increase in professional services expenses of $2.1 million, mainly due to corporate activities.

截至 2022 年 12 月 31 日止年度的一般及行政費用為 3390 萬美元，而截至 2021 年 12 月 31 日止年度為 3650 萬美元。同比減少 260 萬美元，主要原因是員工費用減少 540 萬美元，主要是由於非現金股份薪酬減少 680 萬美元，部分被員工人數增加導致的工資支出增加 140 萬美元和專業服務費用增加 210 萬美元所抵消，主要是由於到企業活動。

Cash and cash equivalents were $221.4 million as of December 31, 2022, compared to $102.7 million as of December 31, 2021. Based upon our current operating plan, we estimate that our existing cash and cash equivalents will enable us to fund our operating expenses and capital expenditure requirements into 2025.

截至 2022 年 12 月 31 日，現金和現金等價物為 2.214 億美元，而截至 2021 年 12 月 31 日為 1.027 億美元。根據我們目前的運營計劃，我們估計現有的現金和現金等價物將使我們能夠為運營費用和到 2025 年的資本支出要求。

Now, I'd like to hand the call back to Luca.

現在，我想把電話轉回給盧卡。

Thank you, Claudia. We covered a lot of ground during today's call and to close, I'd like to underscore the following three points. First, 2023 promises to be a transformational year for VectivBio as we will readout important datasets, including the six-month Nutrition data in just a couple of weeks, followed by the interim analysis of the Phase 2 STARGAZE study. And then perhaps, most importantly, top line results of our Phase 3 STAR study.

謝謝你，克勞迪婭。在今天的電話會議和結束時，我們討論了很多內容，我想強調以下三點。首先，2023 年有望成為 VectivBio 轉型的一年，因為我們將在短短幾週內讀出重要的數據集，包括六個月的營養數據，然後是 2 期 STARGAZE 研究的中期分析。然後也許，最重要的是，我們的第 3 階段 STAR 研究的頂級結果。

Second, we are executing a comprehensive launch preparation plan with the aim of achieving a blockbuster launch of apraglutide in SBS-Intestinal Failure. And finally, we are operating from a position of financial strength with a cash runway that takes us more than 12 months past the top line readout of the Phase 3 STAR study. And with that, we would like to open the call for questions.

其次，我們正在執行全面的上市準備計劃，旨在實現 apraglutide 在 SBS-Intestinal Failure 中的重磅上市。最後，我們在財務實力和現金跑道的基礎上運營，這使我們比第 3 階段 STAR 研究的頂線讀數多了 12 個月。有了這個，我們想打開問題的電話。

Operator?

操作員？

(Operator Instructions) Allison Bratzel, Piper Sandler.

（操作員說明）Allison Bratzel、Piper Sandler。

Hey, good morning, guys, and thanks for taking the questions. So just first on the STARS Nutrition update at DDW. Could you just frame for us the scope of the data that's going to be available next month and just what measures, body weight, what weight absorption, or other metrics in addition to parenteral support reduction are going to be most important to illustrating the benefits of [Apra] in the CIC population? And then I do have a follow-up question after that.

嘿，早上好，伙計們，謝謝你提出問題。所以首先是在 DDW 的 STARS Nutrition 更新。您能否為我們描述一下下個月將可用的數據范圍，以及除了減少腸外支持之外，哪些措施、體重、體重吸收或其他指標對於說明[apra]中投人口？然後我確實有一個後續問題。

Hey, Alex, thanks for your questions. Thanks for jumping on today. How about we have Omar handle that first question.

嘿，亞歷克斯，謝謝你的提問。感謝您今天繼續前進。我們讓 Omar 處理第一個問題怎麼樣？

Yeah. Thanks, [Allie]. So at DDW as well as the PS volume reduction we'll also show the energy content of the PS over a number of the mass calories in the PS and how that's changed over the six month period. And then also what happen to the patient's body weight over that timeframe.

是的。謝謝，[艾莉]。因此，在 DDW 以及 PS 體積減少中，我們還將顯示 PS 的能量含量與 PS 中大量卡路里的比值，以及它在六個月內的變化情況。然後還有在那個時間段內患者的體重發生了什麼。

Great. And then just on the STARGAZE readout this quarter, can you just kind of frame for us what you need to see to feel like you've established proof-of-concept in GvHD? And also, do you feel like you've established proof of principle in inflammatory GI diseases more broadly? And I'm just hoping you could also describe your thinking on the opportunity or the role of Apra in larger indications like Crohn's and UC and just how the STARGAZE interim data informs on your strategy there?

偉大的。然後就本季度的 STARGAZE 讀數而言，您能否為我們提供您需要看到的框架，讓我們感覺您已經在 GvHD 中建立了概念驗證？而且，您是否覺得您已經更廣泛地建立了炎症性胃腸道疾病的原理證據？我只是希望你也能描述你對 Apra 在克羅恩病和 UC 等更大適應症中的機會或作用的看法，以及 STARGAZE 中期數據如何為你的戰略提供信息？

Great. I think we'll have Luca take that question.

偉大的。我想我們會讓盧卡回答這個問題。

Thanks, Allie. So in terms of what we will report in that analysis, we likely will report the effects of the drug on overall response rate, both at one month and two months and durability of response, which obviously have a precedent as endpoints from previous trials assessing, for example, ruxolitinib in this indication. And the exact bar is being set by the data that was generated in the past, both with Incyte and Novartis in their REACH1 and REACH2 trial as well as other datasets that we have been able to access in Germany and in the US. And we will create that comparator group from those combined datasets.

謝謝，艾莉。因此，就我們將在該分析中報告的內容而言，我們可能會報告藥物對一個月和兩個月的總體反應率以及反應持久性的影響，這顯然有先例作為先前試驗評估的終點，例如，ruxolitinib 在這個適應症中。確切的標準是由過去生成的數據設置的，包括 Incyte 和 Novartis 在他們的 REACH1 和 REACH2 試驗中以及我們能夠在德國和美國訪問的其他數據集。我們將從這些組合數據集中創建比較組。

The importance of those data as such because we -- all of those have a standard of care ruxolitinib and of course, steroids. And we are able to extract all the patients that had GI symptoms among -- which represents about 80% of the patients in steroid-refractory GvHD. So it's a very appropriate dataset. In terms of where the bar is, we'll communicate that as soon as we have those datasets finalized.

這些數據本身的重要性是因為我們——所有這些人都有一個標準的護理 ruxolitinib，當然還有類固醇。我們能夠提取所有有胃腸道症狀的患者——這代表了大約 80% 的類固醇難治性 GvHD 患者。所以這是一個非常合適的數據集。就標準的位置而言，我們會在最終確定這些數據集後立即進行溝通。

In terms of new indications, well, first, I would say, I'd like to start by saying that clearly the novelty of this approach is that we're combining regeneration of the intestine and healing of the intestine with immunosuppression. So immunosuppression in these patients is crucial to dampen the alloimmune response from the engrafted tissue and is achieved by steroids and other immunosuppressants such as JAK inhibitors.

就新適應症而言，首先，我想說的是，這種方法的新穎之處在於我們將腸道再生和腸道癒合與免疫抑制相結合。因此，這些患者的免疫抑制對於抑制移植組織的同種免疫反應至關重要，可通過類固醇和其他免疫抑製劑（如 JAK 抑製劑）實現。

And then you combine with those standard of care, you combine the GLP-2 mechanism, which adds [guttery] growth as well as increased barrier function, healing, improvement in absorption, all of those features that are known to be part of the GLP-2 mechanism.

然後你結合那些護理標準，你結合 GLP-2 機制，它增加 [排水溝] 增長以及增加屏障功能，癒合，吸收改善，所有這些已知的特徵是 GLP 的一部分-2 機制。

But the importance of this proof-of-concept is that this can be extended to additional immunological conditions of the intestine, and we think IBD is next place to looking for opportunity when it comes to apraglutie. And of course, there the notion and the cost will be similar, we'll be combining our drug with existing immunosuppressant therapies, for example, anti-TNFs or anti-integrins that are currently the standard of care for biologics in this indication or at least second line in this indication.

但這種概念驗證的重要性在於，它可以擴展到腸道的其他免疫學狀況，我們認為 IBD 是下一個尋找 apraglutie 機會的地方。當然，概念和成本將是相似的，我們將把我們的藥物與現有的免疫抑制療法相結合，例如，抗腫瘤壞死因子或抗整合素，它們目前是該適應症或此指示中的至少第二行。

Great. And maybe just one last one. I think we talked about developing a pre-filled syringe or a dual-chamber syringe. Could you just remind us kind of what's the status of that? And just if you have a sense of what kind of data you need to generate to get of a pre-filled syringe for Apra approved? Thanks.

偉大的。也許只是最後一個。我想我們討論過開發預充式註射器或雙室注射器。你能提醒我們一下它的狀態嗎？如果您知道需要生成什麼樣的數據才能獲得 Apra 批准的預填充注射器？謝謝。

Yes. So we're developing with the timelines that is compatible with launching in 2025 with the -- with such a device, drug-device combination. So our main case is to launch -- our base case is to launch with the dual chamber pre-filled syringe.

是的。因此，我們正在製定與 2025 年推出兼容的時間表 - 使用這樣的設備，藥物設備組合。所以我們的主要案例是發射——我們的基本案例是用雙室預填充注射器發射。

We're going through a series of planned programs in the development of the syringe, including human factor studies, including relative [BA] studies, and -- or bioavailability studies, and validation studies that are purely on the CMC side. And all of that is work -- is progressing in parallel with the conduct of the Phase 3. We have completed the GMP manufacturing that will be required for the relative bioavailability study, which is due to start imminently. So we're basically on time for a launch with the dual-chamber syringe.

我們正在註射器的開發中進行一系列計劃的項目，包括人為因素研究，包括相對 [BA] 研究，以及 - 或生物利用度研究，以及純粹在 CMC 方面的驗證研究。所有這些都是工作——與第三階段的進行同時進行。我們已經完成了相對生物利用度研究所需的 GMP 製造，該研究即將開始。所以我們基本上準時推出雙腔注射器。

Excellent. Thank you.

出色的。謝謝。

Tazeen Ahmad, Bank of America.

Tazeen Ahmad，美國銀行。

Hi, guys. Thanks so much for taking my questions. I have a couple. So maybe just conceptually, Luca, can you explain to us like, we've been getting a lot of inbounds with interest specifically in the CIC population that is enrolled into the STARS study. Obviously, the competitive landscape is wide open for CIC, but I think it would help if you could frame for us why you think apraglutide in particular has a better chance of showing higher success rate in CIC patients mechanistically relative to what's already on the market and from competitors? And then I have a follow-up. Thank you.

嗨，大家好。非常感謝你回答我的問題。我有一對。所以也許只是概念上，盧卡，你能向我們解釋一下嗎？顯然，競爭格局對 CIC 來說是開放的，但我認為如果你能為我們解釋為什麼你認為阿普拉魯肽在機械上相對於市場上已有的藥物更有可能在 CIC 患者中顯示出更高的成功率，並且來自競爭對手？然後我有一個後續行動。謝謝。

Well, there's two reasons. One is that -- one is small molecule specific, and the other reason is design -- trial design specific. So when it comes to the molecule, we believe our molecule has one of the greatest features, pharmacologically speaking, both in terms of half-life and pharmacology like affinity to the receptor that make it more potent as shown in published preclinical head-to-head studies.

嗯，有兩個原因。一個是 - 一個是特定於小分子的，另一個原因是設計 - 特定於試驗設計。因此，當談到分子時，我們相信我們的分子具有藥理學上最偉大的特徵之一，無論是在半衰期還是藥理學方面，如對受體的親和力，使其更有效，如已發表的臨床前頭對-頭研究。

And then when it comes to design, I think this point is actually perhaps just as important, if not more important. CIC patients are physiologically different from stoma patients. They display a response to drug in a way that is distinct from stoma operations. The old methodology for detecting response and adjusting parenteral support in clinical trials was perfected for stoma patient but not for CIC patients. And we have evolved that methodology as shown in our Nutrition trial, where that methodology was deployed for the first time to basically be -- increase the sensitivity of detecting the response in CIC patients.

然後在設計方面，我認為這一點實際上可能同樣重要，甚至更重要。 CIC 患者在生理上不同於造口患者。它們以不同於造口手術的方式顯示對藥物的反應。臨床試驗中用於檢測反應和調整胃腸外支持的舊方法適用於造口患者，但不適用於 CIC 患者。我們已經改進了該方法，如我們的營養試驗所示，該方法首次部署基本上是——提高檢測 CIC 患者反應的靈敏度。

So essentially, we are enhancing both the chance of seeing a response because of the molecular nature of apraglutide as well as for the methodology used in the trial. And of course, to be more specific, in CIC patients, their focus in terms of tracking their response is more on changes to their metabolism, changes to their body weight, their stool, consistency, or frequency, and less so on the fluid balance changes. In other words, diuresis and absorption of fluids, which are more critical for stoma. Those are the key differentiation aspects of the trial design.

因此，從本質上講，由於 apraglutide 的分子性質以及試驗中使用的方法，我們正在增加看到反應的機會。當然，更具體地說，在 CIC 患者中，他們在跟踪反應方面的重點更多地放在新陳代謝的變化、體重的變化、大便、稠度或頻率上，而不是體液平衡變化。換句話說，利尿和吸收液體，這對造口來說更為關鍵。這些是試驗設計的關鍵差異化方面。

And lastly, I would add to that, Tazeen, the fact that being able to inform the use of the drug in a bespoke fashion, in a patient tailored fashion in the two subtypes will also increase adherence to treatment and ease of use and compliance and persistency, which are three critical objectives for our drug one sees on the market. So to help make use easier and more appropriate with patients, something that has been left on the table, we think, from the past experience of the -- the pioneering experience of Gattex.

最後，我要補充一點，Tazeen，事實是能夠以定制的方式告知藥物的使用，以兩種亞型的患者量身定制的方式也將增加對治療的依從性以及易用性和依從性和持久性，這是我們在市場上看到的藥物的三個關鍵目標。因此，為了幫助患者更輕鬆、更合適地使用，我們認為，根據過去的經驗——Gattex 的開創性經驗，一些東西已經擺在桌面上。

Okay. That's super helpful. Is there anything that we should be looking for at that top line for the STARS results as it relates to CIC? You talked about some of the observations that might be more important for those patients. But as it relates to those endpoints, are there certain cut-offs that you think are necessary in order for this to be -- consider clinically meaningful data in that subgroup?

好的。這非常有幫助。在與 CIC 相關的 STARS 結果中，我們應該在頂線尋找什麼？你談到了一些對這些患者可能更重要的觀察結果。但是，當它與這些終點相關時，您是否認為有必要進行某些截斷，以便 - 考慮該子組中具有臨床意義的數據？

Well, in the CIC subgroup, we put a lot of emphasis. First of all, there's a couple of different aspects that are relevant. The timeline of the response is it's focused more on metabolic changes and less on fluid changes is a bit longer. So the expectation to add a very quick response should be tempered for this patient. That's why we ran our Phase 3 trial and our Nutrition trial for 48 weeks to double the duration of what we've done for stoma and what has been done in the past.

那麼，在 CIC 子組中，我們非常重視。首先，有幾個相關的不同方面。響應的時間表是它更多地關注代謝變化而不是體液變化，時間更長一些。因此，應該為該患者降低對增加非常快速反應的期望。這就是為什麼我們進行了為期 48 週的 3 期試驗和營養試驗，以將我們為造口所做的工作和過去所做的工作的持續時間加倍。

The other point is we expect the effects not to stop at six months but to accrue beyond six months. So basically, we'll likely -- we hope and we likely able to demonstrate that there is still benefit for patients to be on treatment beyond six months in a 9 month to 12 month timeframe and then we can record maybe a larger effect size beyond the six month's point for this group. And again, that's why we kept the STARS Phase 3 trial blinded for these patients all the way to 48 weeks.

另一點是我們預計影響不會在六個月後停止，而是會在六個月後累積。所以基本上，我們可能 - 我們希望並且我們可能能夠證明，在 9 個月到 12 個月的時間範圍內，患者接受超過 6 個月的治療仍然是有益的，然後我們可以記錄可能更大的效應量超過該組的六個月點。再一次，這就是為什麼我們一直對這些患者進行 STARS 3 期試驗直至 48 週不知情。

In terms of what outcomes are more relevant for these patients, of course, is the -- these are patients that are more likely to being able to shave days off because they don't dehydrate as readily as stoma operations. Dehydration is a key enemy of being able to come off days of infusion because one can be dehydrated very quickly within a 24-hour period.

當然，就與這些患者更相關的結果而言，這些患者更有可能休假幾天，因為他們不像造口手術那樣容易脫水。脫水是能夠在輸液幾天后脫離的主要敵人，因為一個人可以在 24 小時內很快脫水。

And secondly -- so again, days off is a crucial endpoint that we have at the top of our hierarchy. And then another point is obviously, enteral autonomy or complete win-off from parenteral support, which we think is more achievable for CIC than it is for stoma patients. Again, for the same reason, they have less of a propensity to dehydrate, it start from fewer days a week on average of infusion. So achieving a full enteral autonomy, it's a potentially easier for these patients.

其次 - 再一次，休假是我們在層次結構頂部的一個關鍵端點。然後另一點顯然是腸內自主或完全贏得腸外支持，我們認為 CIC 比造口患者更容易實現。同樣，出於同樣的原因，他們脫水的可能性較小，這是從平均每週輸液的天數減少開始的。因此，實現完全的腸道自主，對這些患者來說可能更容易。

Okay, perfect. Thanks, Luca.

好的，完美。謝謝，盧卡。

Thomas Smith, SVB Securities.

SVB 證券公司的 Thomas Smith。

Hey, guys. Good morning. Thanks for taking the questions and congrats on all the progress. Couple of questions on our end. I guess first follow-up question on the STARS pivotal trial and some of the assumptions you're making for the CIC patients. We know, in the Gattex program, there was a 24% reduction in PS volume in the placebo arm for CIC, but that was with a titration algorithm that relied only on changes in fluid balance. How do you expect the CIC patients who received placebo and STARS to respond using your algorithm relative to the Gattex study? And can you remind us of the assumed treatment effect and powering assumptions for the anatomy-specific endpoints?

大家好。早上好。感謝您提出問題並祝賀所有進展。我們這邊有幾個問題。我想第一個跟進問題是關於 STARS 關鍵試驗以及你為 CIC 患者所做的一些假設。我們知道，在 Gattex 計劃中，CIC 安慰劑組的 PS 體積減少了 24%，但這是使用僅依賴於液體平衡變化的滴定算法。您如何看待接受安慰劑和 STARS 的 CIC 患者使用您的算法相對於 Gattex 研究做出反應？您能否提醒我們特定解剖學終點的假設治療效果和動力假設？

Yeah. Thanks for the question. So basically, we're -- we have changed not just the winning algorithm, which should increase the sensitivity of detection and response to CIC, but we also changed significantly the optimization and stability mechanisms that are designed to reduce the placebo responses in this population. Essentially, what was observed in the past was, on average, 20%, 22% placebo response, which was attributable to patients during the -- in the course of the trial, requiring less parenteral support irrespective of the GLP-2 treatment because of a better optimization of that nutrition, oral nutrition or parenteral support nutrition.

是的。謝謝你的問題。所以基本上，我們 - 我們不僅改變了獲勝算法，這應該增加檢測的靈敏度和對 CIC 的響應，而且我們還顯著改變了旨在減少該人群安慰劑反應的優化和穩定性機制.從本質上講，過去觀察到的是平均 20%、22% 的安慰劑反應，這歸因於患者在試驗過程中，無論 GLP-2 治療如何，都需要較少的胃腸外支持，因為更好地優化該營養、口服營養或腸外支持營養。

So we have invested significant amount of effort and time in making these patients very stable and optimized before they start receiving drug. And so again -- so these two factors, the placebo response reduction and the winning algorithm which we tested already in the nutrition trial are predicted to give us a more significant single in the CIC subgroup.

因此，我們投入了大量的精力和時間來使這些患者在開始接受藥物之前非常穩定和優化。又一次——所以這兩個因素，安慰劑反應減少和我們已經在營養試驗中測試過的獲勝算法預計會給我們一個更重要的 CIC 子組。

Now, in terms of what we have powered towards for the CIC, we powered -- the study was powered for the overall effect size. But I would say specifically, the CIC, we powered it to about a 10% delta between placebo and active. So it's a relatively small delta that we are aiming for here.

現在，就我們為 CIC 提供的動力而言，我們提供了動力——這項研究是為整體效果大小提供動力的。但我要具體說，CIC，我們在安慰劑和活性劑之間提供了大約 10% 的增量。因此，我們的目標是一個相對較小的三角洲。

What we have seen in the Nutrition trial would indicate that the delta could be as big as 30%. But of course, we had to assume that in a placebo-controlled trial, we may not get that large delta between placebo and active arm simply because it's a more -- typically, when you run trials on a large number of sites and large number of countries, the [female] section diminishes. So we think that the -- nutrition which has a reduction of about 50%, if you assume 20% placebo, it's about close to 30% delta there, I think that will be the best case scenario.

我們在營養試驗中看到的結果表明，增量可能高達 30%。但是，當然，我們不得不假設，在安慰劑對照試驗中，我們可能無法在安慰劑組和活性組之間獲得如此大的差異，僅僅是因為它更——通常，當你在大量站點和大量站點上進行試驗時在國家中，[女性]部分減少了。所以我們認為——營養減少了大約 50%，如果你假設 20% 的安慰劑，它大約接近 30% 的三角洲，我認為這將是最好的情況。

Got it. That's super helpful. Great. And then just one on the competitive landscape in SBS. Can you just update us on your latest expectations for competing GLP-2 programs and generic Gattex and how you see the market shaping up over the next three to five years?

知道了。這非常有幫助。偉大的。然後只是關於 SBS 競爭格局的一個問題。您能否向我們介紹一下您對競爭性 GLP-2 計劃和通用 Gattex 的最新期望，以及您如何看待未來三到五年的市場形成？

Yes, I'll start and then I'll have Kevin continue. In terms of the expectations from other sponsors, we're using our [comment] about our programs. We're confident we have a very competitive package here; we are the only company with a weekly drug. We are the only company with an ability to discriminate between different anatomical subtypes, which we think is very crucial for this population.

是的，我先開始，然後讓 Kevin 繼續。就其他贊助商的期望而言，我們正在使用我們對我們計劃的[評論]。我們相信我們在這裡有一個非常有競爭力的套餐；我們是唯一一家每週提供藥物的公司。我們是唯一一家有能力區分不同解剖學亞型的公司，我們認為這對這一人群非常重要。

And we are the only company that has a significant amount of patient reported outcomes that are bespoke that were designed specifically for this population. And so there's plenty -- and if you combine that with what we know about our molecule versus the others, we are very confident we have a very high chance of differentiation. In terms of the generic landscape, I think we now are further advanced into the [genericization] of Gattex.

我們是唯一一家擁有大量專為這一人群設計的定制患者報告結果的公司。所以有很多 - 如果你將其與我們對我們的分子與其他分子的了解結合起來，我們非常有信心我們有很高的差異化機會。就通用景觀而言，我認為我們現在進一步推進了 Gattex 的 [通用化]。

I'll have Kevin comment on that, because he has done a lot of work in this space. Kevin?

我會讓 Kevin 對此發表評論，因為他在這個領域做了很多工作。凱文？

Yeah. Thanks, Luca. As you may know, or may be aware of, there could have been a possibility for a generic of Gattex to launch in the second half of March of this year. And we haven't seen one emerge at this point. We think there's a lot of reasons why, both the SBS-IF market and the profile of Gattex, in particular, has limited attractiveness for generics. There's some challenges one have to overcome in transitioning from the recombinant manufacturing approach for Gattex today to synthetic manufacturing, which would be required under the [ANDA] guidelines, and that clearly would require pretty significant CMC investment.

是的。謝謝，盧卡。您可能知道或可能知道，Gattex 的仿製藥有可能在今年 3 月下半月推出。目前我們還沒有看到一個出現。我們認為 SBS-IF 市場和 Gattex 的形像對仿製藥的吸引力有限的原因有很多。在從今天的 Gattex 重組製造方法過渡到合成製造的過程中，必須克服一些挑戰，這是 [ANDA] 指南所要求的，而且顯然需要相當大的 CMC 投資。

It does take some effort to identify patients and to keep them on treatment. As we've shown, patients on Gattex have significant challenges with persistency and half of them discontinue by month 12 and up to two thirds by month 24. There's REMS and registry requirements for Gattex. And so these are just some of the factors we think why the market isn't particularly attracted for generics. We've only seen one paragraph for filing to date, and that was done back in 2016 and we still have not yet seen an approval.

確實需要一些努力來識別患者並讓他們繼續接受治療。正如我們所展示的，使用 Gattex 的患者在持久性方面面臨重大挑戰，其中一半在第 12 個月前停藥，最多三分之二在第 24 個月前停藥。Gattex 有 REMS 和註冊要求。因此，這些只是我們認為市場對仿製藥沒有特別吸引力的部分因素。到目前為止，我們只看到了一段申請，那是在 2016 年完成的，但我們還沒有看到批准。

So yeah, I think generic remains to be seen whether one will come to market. If one does come to market, we've had significant engagement with payers. And at the end of the day, they view generic Gattex as Gattex without a lot of the support that a corporation would provide. And as Luca mentioned, we believe we'll be able to demonstrate very significant differentiation on efficacy, and obviously, on dosing, being a weekly dose drug. So we don't see a generic as a strategic threat to the opportunity that we think apraglutide have in SBS-IF.

所以是的，我認為仿製藥是否會上市還有待觀察。如果確實有一款產品上市，我們就會與付款人進行大量接觸。歸根結底，他們將通用 Gattex 視為沒有公司提供的大量支持的 Gattex。正如 Luca 所提到的，我們相信我們將能夠展示出非常顯著的療效差異，顯然，在劑量方面，作為一種每週劑量的藥物。因此，我們不認為仿製藥對我們認為阿普拉魯肽在 SBS-IF 中所擁有的機會構成戰略威脅。

Got it. That's super helpful. Thanks, guys, for taking the questions.

知道了。這非常有幫助。謝謝，伙計們，提出問題。

Patrick Dolezal, LifeSci Capital.

LifeSci Capital 的 Patrick Dolezal。

Hi, thanks for taking the questions. It's interesting thinking about the speed of CIC enrollment and now waiting a little bit longer for the stoma cohort. Just curious, what's the relative proportion of CIC versus stoma patients currently receiving Gattex? And how might your marketing strategy and pivotal trial design ultimately shift this ratio over time?

您好，感謝您提出問題。考慮到 CIC 的註冊速度以及現在等待造口隊列的時間稍長，這很有趣。只是好奇，CIC 與目前接受 Gattex 的造口患者的相對比例是多少？隨著時間的推移，您的營銷策略和關鍵試驗設計最終會如何改變這一比例？

Yeah. So hi, Patrick. So basically, the -- we have different sources of information that we can rely on, including our own study experience in 18 countries and feasibility work done leading up to that, including market research we are conducting, both in the US and in Europe.

是的。嗨，帕特里克。所以基本上，我們擁有可以依賴的不同信息來源，包括我們自己在 18 個國家/地區的研究經驗以及為此所做的可行性工作，包括我們正在美國和歐洲進行的市場研究。

So we estimate the CIC population to have increased since the first launch of Gattex because of the greater appreciation of the importance of keeping at least a portion of the colon intact, provide patients with the ability of absorbing fluids. And so we have seen an increase in proportion. We estimate that the number of CIC could be anywhere between 60% to 70%. We don't obviously know exactly that number, but that's sort of -- I would say, a fair estimate will be around 65% versus 45%, 35% being stoma.

因此，我們估計自 Gattex 首次推出以來 CIC 人口有所增加，因為人們更加認識到保持至少一部分結腸完整的重要性，為患者提供吸收液體的能力。因此，我們看到了比例的增加。我們估計 CIC 的數量可能在 60% 到 70% 之間。我們顯然不知道確切的數字，但這有點——我想說，一個公平的估計是 65% 左右，而不是 45%，35% 是造口。

And what was the other part of the question?

問題的另一部分是什麼？

I think it was how it may impact our marketing approach?

我認為這會如何影響我們的營銷方式？

Okay. So maybe we'll have Kevin --

好的。所以也許我們會有凱文——

Yeah. Kevin, you want to take the second part of the question?

是的。凱文，你想回答問題的第二部分嗎？

Yes. And we've got a couple of data points to suggest that Gattex is used at least 1.5 to 2 times more frequently in stoma than CIC, recognizing that CIC represents the majority of patients. And so we've always believed that these patients have been underserved. We obviously have seen that Gattex in a retrospective analysis didn't demonstrate any effect in that population. We also have a good understanding that that is one of the main drivers of discontinuation for Gattex, which is lack of efficacy, in particular, in the CIC population.

是的。我們有幾個數據點表明，Gattex 在造口中的使用頻率至少是 CIC 的 1.5 到 2 倍，認識到 CIC 代表了大多數患者。因此，我們一直認為這些患者得不到充分的服務。我們顯然已經看到，在回顧性分析中，Gattex 並未證明對該人群有任何影響。我們也很好地理解，這是 Gattex 停藥的主要驅動因素之一，即缺乏療效，特別是在 CIC 人群中。

So much of our strategy beyond, obviously, having a product with better pharmacology is really to address the unmet need by anatomy. There's certainly significant room for growth in the stoma population because our market research indicated that still less than half of patients might be getting Gattex in that population. But really the market growth potential and the long-term potential of apraglutide can be significantly driven by that 60% to 70% of CIC patients of whom only a fraction are getting Gattex today.

很明顯，我們的許多策略超越了具有更好藥理學的產品，實際上是為了通過解剖學解決未滿足的需求。造口人口肯定有很大的增長空間，因為我們的市場研究表明，在該人口中仍然只有不到一半的患者可能會獲得 Gattex。但實際上，60% 至 70% 的 CIC 患者今天只有一小部分獲得 Gattex，這可以顯著推動 apraglutide 的市場增長潛力和長期潛力。

So our design of the Phase 3 trial with anatomy-specific endpoints and our ability to be able to demonstrate in a prospective alpha-controlled manner, days off, and enteral autonomy in the CIC population, I think uniquely position us to be able to proactively promote and educate people not only on the benefits of Apra, but as Luca mentioned earlier, how best to measure Apra's effect into appropriately winning the CIC patient off of PS. So I think there's very tight integration between our development strategy and our commercial and marketing strategy, and I think we're well positioned for success.

因此，我們設計的具有特定解剖學終點的 3 期試驗以及我們能夠以前瞻性 alpha 控制方式、休息日和 CIC 人群的腸道自主性進行展示的能力，我認為我們的獨特定位是能夠主動不僅要宣傳和教育人們了解 Apra 的好處，而且正如 Luca 之前提到的那樣，如何最好地衡量 Apra 的效果，以適當地使 CIC 患者擺脫 PS。所以我認為我們的發展戰略與我們的商業和營銷戰略之間有著非常緊密的結合，我認為我們已經做好了成功的準備。

Got it. And in the STARGAZE trial for GvHD, can you just walk us through how GI involvement in particular affects outcomes? And then just curious how the propensity control arm is kind of handled? Do you guys have patient level data to match disease characteristics and other features?

知道了。在 GvHD 的 STARGAZE 試驗中，您能否向我們介紹一下 GI 的參與對結果有何影響？然後很好奇傾向控制臂是如何處理的？你們有患者級別的數據來匹配疾病特徵和其他特徵嗎？

Yes. Thanks, Patrick. It's Omar. So that's the actual injury to the gut, so patients in preparation for stem cell transplant undergo conditioning, and that itself is toxic to -- particularly to the gut epithelium, which is continuing to providing tissue. And then post-transplant, the donor T cells, which are contained in the graft and attack the host, and the GI tract, the liver, and skin are the primary targets for that. And that basically -- in the gut that leads to profound inflammatory condition which often leads to the mucosa of the gut being denuded and the patients develop a quite -- life-threatening bile salts and osmotic diarrhea.

是的。謝謝，帕特里克。是奧馬爾。所以這是對腸道的實際傷害，所以準備幹細胞移植的患者要接受調理，這本身就是有毒的——特別是對繼續提供組織的腸道上皮細胞。然後在移植後，移植物中包含的供體 T 細胞攻擊宿主，胃腸道、肝臟和皮膚是其主要目標。這基本上 - 在腸道中導致嚴重的炎症狀況，這通常會導致腸道粘膜被剝蝕，並且患者會發展出相當 - 危及生命的膽汁鹽和滲透性腹瀉。

The other problem is that the gut barrier itself becomes -- intestinal barrier becomes impaired as well. And so the transportation of bacteria across from the gut lumen into the bloodstream, and the patients will develop sepsis. So the GI tract (inaudible) probably accounts for significant proportion of the mortality. The skin and liver typically are reasonably well-addressed with immunosuppression, but it's the gut that kind of remains the significant unmet need in the population. In --

另一個問題是腸道屏障本身變得——腸道屏障也會受損。因此，細菌從腸腔進入血液，患者就會患上敗血症。因此，胃腸道（聽不清）可能佔死亡率的很大一部分。皮膚和肝臟通常可以很好地解決免疫抑制問題，但腸道仍然是人群中未滿足的重要需求。在 -

Thanks, Omar. Patrick, does that answer your question?

謝謝，奧馬爾。帕特里克，這能回答你的問題嗎？

Yes. And then I guess the second part was your conduct propensity match control arm and --

是的。然後我猜第二部分是你的行為傾向匹配控制臂——

Yeah, so we do have patient level data and the propensity score matching basically is used to ensure that we've got a well-matched synthetic control to compare our outcomes from STARGAZE.

是的，所以我們確實有患者水平的數據，並且傾向得分匹配基本上用於確保我們有一個匹配良好的綜合控制來比較我們從 STARGAZE 獲得的結果。

Got it. Perfect. Thank you.

知道了。完美的。謝謝。

I show no further questions at this time. I would now like to turn the conference back to Luca Santarelli for closing remarks.

我現在沒有進一步的問題。我現在想把會議轉回 Luca Santarelli 作閉幕詞。

Thanks to everybody for participating, and to all the people that participated in the Q&A for your insightful questions and for helping us continue to become a better company. Thank you.

感謝大家的參與，感謝所有參與問答的人，感謝你們提出的富有洞察力的問題，感謝你們幫助我們繼續成為一家更好的公司。謝謝。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。