Gossamer Bio Inc (GOSS) 2025 Q1 法說會逐字稿

Good afternoon, ladies and gentlemen. Welcome to the Gossamer Bio Q1 2025 earnings call.

女士們、先生們，午安。歡迎參加 Gossamer Bio 2025 年第一季財報電話會議。

I will now turn the program over to Brian Giraudo, Chief Financial Officer and Chief Operating Officer.

現在我將該計劃移交給財務長兼營運長 Brian Giraudo。

Thank you, operator. Thank you, all, for joining us this afternoon.

謝謝您，接線生。感謝大家今天下午加入我們。

I'm joined on today's call by Faheem Hasnain, Gossamer's Founder, Chairman, and Chief Executive Officer; Dr. Richard Aranda, Chief Medical Officer; Caryn Peterson, Executive Vice President - Regulatory Affairs; and Bob Smith, Chief Commercial Officer.

參加今天電話會議的還有 Gossamer 的創始人、董事長兼首席執行官 Faheem Hasnain；首席醫療官 Richard Aranda 博士； Caryn Peterson，監管事務執行副總裁；以及首席商務官鮑勃·史密斯 (Bob Smith)。

Earlier this afternoon, Gossamer Bio issued a press release announcing its first-quarter 2025 financial results and provided a corporate update.

今天下午早些時候，Gossamer Bio 發布了一份新聞稿，宣布了 2025 年第一季的財務業績並提供了公司最新消息。

Please note that certain information discussed on the call, today, is covered under the Safe Harbor provision of the Private Securities Litigation Reform Act. We caution listeners that, during the call, Gossamer management will be making forward-looking statements. Actual results may differ, materially, from those stated or implied by these forward-looking statements, due to risks and uncertainties associated with the company's business.

請注意，今天電話會議上討論的某些資訊屬於《私人證券訴訟改革法案》安全港條款的涵蓋範圍。我們提醒聽眾，在通話期間，Gossamer 管理層將發表前瞻性陳述。由於公司業務相關的風險和不確定性，實際結果可能與這些前瞻性陳述明示或暗示的結果有重大差異。

These forward-looking statements are qualified by statements contained in Gossamer's news releases, SEC filings, including the annual report on Form 10-K and subsequent filings.

這些前瞻性陳述受到 Gossamer 新聞稿、SEC 文件（包括 10-K 表格年度報告和後續文件）中的陳述的限制。

This conference call also contains time-sensitive information that may be accurate only for a limited period of time. Gossamer Bio undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call.

本次電話會議還包含時間敏感訊息，這些資訊可能僅在有限的時間內準確。Gossamer Bio 不承擔修改或更新任何前瞻性陳述以反映本次電話會議日期之後的事件或情況的義務。

Now, I'd like to turn over to Faheem.

現在，我想把麥克風交給 Faheem。

Thank you, Brian. Good afternoon, everyone. Welcome to our first-quarter 2025 earnings call.

謝謝你，布萊恩。大家下午好。歡迎參加我們的 2025 年第一季財報電話會議。

We're very excited to provide an update on the significant progress and momentum with seralutinib, which is an investigational treatment for pulmonary hypertension, including Pulmonary Arterial Hypertension, or PAH, and Pulmonary Hypertension associated with Interstitial Lung Disease or PH-ILD.

我們非常高興地提供關於色拉替尼重大進展和發展勢頭的最新消息，色拉替尼是一種治療肺動脈高壓的在研藥物，包括肺動脈高壓（PAH）和間質性肺病相關肺動脈高壓（PH-ILD）。

Over the past year and a half, we, at Gossamer, have dedicated immense time, effort, and hard work to enroll our pivotal PAH study: the Phase 3 PROSERA study. In particular, I want to recognize the efforts of our global clinical operations, development, and field medical team, who, quite literally, have been working across the globe, around the clock, to get us to this point.

在過去的一年半里，我們 Gossamer 投入了大量的時間、精力和辛勤工作來開展我們的關鍵 PAH 研究：第 3 階段 PROSERA 研究。我特別要讚揚我們全球臨床營運、開發和現場醫療團隊的努力，他們確實一直在全球各地日以繼夜地工作，才使我們達到這一點。

Today, I'm incredibly proud to announce that we have achieved a significant milestone in the PROSERA study, with a closure of new patient screening.

今天，我非常自豪地宣布，我們在 PROSERA 研究中取得了重要的里程碑，新患者篩檢已經結束。

And while nearing completion of enrollment is a significant achievement in and of itself, what really matters is enrolling the correct patient population to best position PROSERA for a successful outcome. In this case, that successful outcome is a demonstration of a significant treatment effect in 6-Minute Walk Distance at 24 weeks.

雖然接近完成招募本身就是一項重大成就，但真正重要的是招募正確的患者群體，以使 PROSERA 獲得最佳成功結果。在這種情況下，成功的結果是證明了24週時6分鐘步行距離的顯著治療效果。

Now, with this context in mind, we're thrilled to report that the baseline characteristics of the patients enrolled, thus far, are precisely what we have targeted. And we are more optimistic than ever about the likelihood of achieving positive results.

現在，考慮到這一背景，我們很高興地報告，迄今為止，入組患者的基線特徵正是我們所針對的。我們對於取得正面成果的可能性比以往任何時候都更加樂觀。

But I'll dive, more deeply, into that, in a moment.

但我稍後會更深入地探討這個問題。

Now, this year, we've experienced great momentum in rolling the study, as growing appreciation of the 72-week TORREY open-label extension data from patients and physicians sparked strong interest in the PROSERA study.

今年，我們在進行這項研究方面取得了巨大的進展，因為患者和醫生對 72 週 TORREY 開放標籤擴展數據的日益讚賞激發了人們對 PROSERA 研究的濃厚興趣。

Given this late additional surge of interest, the PROSERA study has a substantial number of patients currently in screen. And when those potential patients are added to the 343 patients already enrolled or scheduled to randomize, there are more patients to complete full enrollment by early June.

鑑於最近人們對此興趣的激增，PROSERA 研究目前已對大量患者進行了篩檢。當這些潛在患者加入到已經入組或計劃隨機分組的 343 名患者中時，到 6 月初將有更多的患者完成全部入組。

We owe the PAH community a great deal of gratitude for entrusting us. And we will honor that trust by allowing every patient, in screening, the opportunity to enroll in the PROSERA study, if they qualify.

我們非常感謝 PAH 社群對我們的信任。我們將不辜負這份信任，為每位符合資格的患者提供參與 PROSERA 研究的機會。

While we expect to complete the blinded portion of the study, including the 24-week 6-Minute Walk Distance primary endpoint, by the fourth quarter of this year, we anticipate announcing top-line results in February 2026.

雖然我們預計將在今年第四季完成研究的盲法部分，包括 24 週的 6 分鐘步行距離主要終點，但我們預計將在 2026 年 2 月公佈頂線結果。

This timeline ensures that we can lock the database and thoroughly clean, analyze, and adjudicate the substantial data collected in this robust 48-week double-blind study, without sacrificing data quality or operational excellence.

這個時間表確保我們可以鎖定資料庫並徹底清理、分析和裁決這項為期 48 週的雙盲研究中收集的大量數據，而不會犧牲數據品質或卓越運作。

Let's, now, review, in detail, the baseline characteristics of those enrolled in PROSERA and how this patient population helps set up seralutinib for success.

現在，讓我們詳細回顧 PROSERA 試驗入組患者的基線特徵，以及該患者群體如何幫助色拉替尼獲得成功。

Now, the learnings from the Phase 2 TORREY study helped us to identify specific patient characteristics that would likely respond favorably to seralutinib by carefully selecting patients with impaired 6-Minute Walk Distance and elevated risk at baseline.

現在，透過仔細選擇 6 分鐘步行距離受損和基線風險升高的患者，第二階段 TORREY 研究的經驗幫助我們確定可能對色氨酸替尼產生良好反應的特定患者特徵。

Through use of the REVEAL Lite 2 Risk Score and other criteria, we aim to enroll a population where a greater magnitude of effect could be seen on the 6-Minute Walk Distance at 24 weeks, which is the primary endpoint; thereby, increasing the likelihood of success of PROSERA.

透過使用 REVEAL Lite 2 風險評分和其他標準，我們的目標是招募一個可以在 24 週時看到對 6 分鐘步行距離產生更大影響的人群，這是主要終點；從而增加了PROSERA成功的可能性。

I am happy to say that given the baseline characteristics that we've seen, thus far, the eligibility criteria was successful in enrolling the exact, intended patient population.

我很高興地說，根據我們迄今為止看到的基線特徵，資格標準成功地招募了準確的、預期的患者群體。

Let's take a closer look at the baseline characteristics: those that are currently available to us of the first 324 patients enrolled in the PROSERA study, as of May 12. '25.

讓我們仔細看看基線特徵：截至 5 月 12 日，這是我們目前掌握的 PROSERA 研究的前 324 名患者的基線特徵。'25。

It's important to remember that this 324 patient number is distinct from the previously mentioned 343 patients, which includes additional patients that randomized after the May 12 date and patients that are scheduled to be randomized.

重要的是要記住，這個 324 名患者的數量與前面提到的 343 名患者不同，後者包括在 5 月 12 日之後隨機分組的其他患者和計劃隨機分組的患者。

To start, we find that the average 6-Minute Walk Distance is approximately 376 meters, much lower than the TORREY baseline, where 6-Minute Walk Distance averaged 408 meters. For comparison, the Phase 3 STELLAR study of sotatercepts had a baseline 6-Minute Walk of 401 meters.

首先，我們發現平均 6 分鐘步行距離約為 376 米，遠低於 TORREY 基線，其中 6 分鐘步行距離平均為 408 米。相較之下，Sotatercepts 的 3 期 STELLAR 研究的基線 6 分鐘步行距離為 401 公尺。

Second, our mean NT-pro BNP, which is an important biomarker of heart failure, is 906 nanograms per liter in PROSERA, which denotes a materially more severe population than the TORREY study where the mean NT-pro BNP levels were only 628 nanograms per liter.

其次，我們在 PROSERA 研究中的平均 NT-pro BNP（心臟衰竭的重要生物標記）為每公升 906 納克，這表明該研究的人群狀況比 TORREY 研究的嚴重得多，TORREY 研究的平均 NT-pro BNP 水平僅為每公升 628 納克。

For additional reference, sotatercepts' STELLAR Phase 3 had a baseline mean NT-pro BNP of 1,121 nanograms per liter, nearly double what we enrolled in TORREY and much more similar to what we are seeing in the baseline characteristics of PROSERA.

作為額外參考，sotatercepts 的 STELLAR 第 3 階段的基線平均 NT-pro BNP 為每公升 1,121 納克，幾乎是我們在 TORREY 中登記的兩倍，並且與我們在 PROSERA 的基線特徵中看到的更加相似。

Third, let's address the functional class. Consistent with other precedent positive PAH trials, in our Phase 2 TORREY study, seralutinib demonstrated a larger magnitude of effect in the Functional Class III patients. But a functional class imbalance in the treatment arm versus the placebo arm created, what we believe, was a major limiting factor in the magnitude of effects seen on the 6-Minute Walk Distance in that study.

第三，我們來討論一下功能類別。與其他先前的陽性 PAH 試驗一致，在我們的 2 期 TORREY 研究中，seralutinib 在功能 III 級患者中表現出了更顯著的效果。但我們認為，治療組與安慰劑組之間的功能類別不平衡是研究中 6 分鐘步行距離效果大小的主要限制因素。

While the placebo arm was 52% Functional Class III, the seralutinib arm only had 32% of its patients classified as Functional Class III, at baseline, in the TORREY study. In contrast, 74% of the patients currently enrolled in our PROSERA study are categorized as Functional Class III at baseline, a significantly larger portion than in TORREY.

在 TORREY 研究中，安慰劑組的功能 III 級患者比例為 52%，而色氨酸組僅有 32% 的患者在基線時被歸類為功能 III 級。相較之下，目前參與我們 PROSERA 研究的患者中有 74% 在基線時被歸類為功能 III 級，這一比例明顯高於 TORREY。

We will also have a higher proportion than the STELLAR study, which mandated that at least 50% of its patients be Functional Class III and ended up enrolling 51% of these of these Class III patients.

我們的比例也將高於 STELLAR 研究，該研究要求至少 50% 的患者為功能 III 級，而最終我們招募了 51% 的 III 級患者。

To prevent an imbalance, we have incorporated a stratification factor for functional class to ensure a balanced population between the arms.

為了防止不平衡，我們加入了功能類別的分層因素，以確保各組之間的人口平衡。

Now, why are we spending so much time walking through these baseline characteristics? Well, in short, study after study, in, PAH has shown us that patients who are sicker (inaudible) baseline; those with more room to improve tend to have better outcomes, particularly on the 6-Minute Walk Distance in the 24-week study.

那麼，為什麼我們要花這麼多時間來了解這些基線特徵呢？嗯，簡而言之，研究表明，PAH 向我們表明，病情較重的患者 (聽不清楚) 基線；那些有更多改進空間的人往往會取得更好的結果，特別是在為期 24 週的研究中，在 6 分鐘步行距離方面。

We saw (inaudible) Centauri, where patients with higher baseline Reveal Risk Score and those with Functional Class III disease had a much more dramatic improvement in their 6-Minute Walk and their PVR.

我們看到（聽不清楚）Centauri，其中具有較高基線顯示風險評分的患者和患有功能性 III 級疾病的患者在 6 分鐘步行和 PVR 方面有更為顯著的改善。

It was also seen in both the Phase 2 and Phase 3 studies of sotatercepts were Functional Class III patients had better outcomes than the Functional Class II patients. Even going back to the pivotal studies of Tyvaso and oral imatinib in PAH, the pattern holds the same.

在 Sotatercepts 的 2 期和 3 期研究中也發現，功能 III 級患者的預後優於功能 II 級患者。即使回顧泰瓦索和口服伊馬替尼在 PAH 治療中的關鍵研究，模式仍然是一樣的。

PROSERA was designed to enroll more of these patients to increase the study's probability of success. Our team has executed against this goal, while maintaining the commercial applicability of the study's findings to a broader population of PAH patients.

PROSERA 旨在招募更多此類患者，以增加研究成功的機率。我們的團隊已經實現了這一目標，同時保持了研究結果對更廣泛的 PAH 患者群體的商業適用性。

We believe that the baseline characteristics in PROSERA represent a population of both Functional Class II and III that is consistent with contemporary studies in PAH, evaluating 6-Minute Walk at 24 weeks.

我們認為，PROSERA 中的基線特徵代表了功能 II 級和 III 級的人群，這與 PAH 中的當代研究一致，評估了 24 週時的 6 分鐘步行。

Because of all this, we believe that we are closer, than ever, to potentially providing patients with a first-in-class new treatment for PAH that addresses the underlying disease.

正因為如此，我們相信，我們比以往任何時候都更接近為患者提供針對潛在疾病的首創 PAH 新型治療方法。

And with that progress in mind, let's now shift our focus to the exciting prospects ahead for seralutinib.

考慮到這一進展，現在讓我們將注意力轉向色拉替尼未來令人興奮的前景。

But before I hand it over to Richard to discuss PH-ILD, I want to take a quick moment to thank our partner the Chiesi Group. Their partnership has enabled seralutinib to immediately enter a global registration on Phase 3 study in PH-ILD. This is one of the key rationale for our joint development and commercialization agreement.

但在交給理查德討論 PH-ILD 之前，我想花一點時間感謝我們的合作夥伴 Chiesi 集團。他們的合作使得 seralutinib 能夠立即進入 PH-ILD 階段 3 研究的全球註冊。這是我們聯合開發和商業化協議的關鍵理由之一。

They are a world leader in relevant disease areas such as respiratory, cardio metabolic, and rare disease. And we feel proud and highly validated that Chiesi sees the same vision for seralutinib as we do. And more than that, they are a committed partner and proponents of this trailblazing clinical development plan in PH-ILD.

他們在呼吸系統、心臟代謝和罕見疾病等相關疾病領域處於世界領先地位。我們感到自豪，並且非常認同 Chiesi 對 seralutinib 有著與我們相同的願景。更重要的是，他們也是 PH-ILD 這項開創性臨床開發計畫的忠實合作夥伴和支持者。

With that, I'll hand it over to Richard for discussion of PH-ILD and the Phase 3 SERANATA study. Richard?

說完這些，我會把主題交給理查德，討論 PH-ILD 和第三階段 SERANATA 研究。理查德？

Thank you, Faheem.

謝謝你，法希姆。

In addition to what Faheem mentioned, I am thrilled to spotlight our planned Phase 3 SERANATA study in patients with Pulmonary Hypertension associated with Interstitial Lung Disease or PH-ILD.

除了 Faheem 提到的內容之外，我很高興重點介紹我們計劃針對間質性肺病或 PH-ILD 相關肺動脈高壓患者進行的 3 期 SERANATA 研究。

To remind you: PH-ILD is a progressive disorder, characterized by the development of pulmonary hypertension in the setting of chronic and progressive lung diseases.

提醒您：PH-ILD 是一種進行性疾病，其特徵是在慢性和進行性肺部疾病的情況下出現肺動脈高壓。

PH-ILD poses a severe burden on patients' quality-of-life diagnosis. The three-year survival rate has been reported to be 40%, which is quite dismal. With only one approved treatment available for PH-ILD in the US and limited availability outside of the US, there remains a substantial unmet need for effective therapies.

PH-ILD為患者的生活品質診斷帶來了嚴重的負擔。據報道，三年存活率為 40%，相當慘淡。由於美國僅有一種核准的 PH-ILD 治療方法，且在美國以外地區的可用性有限，因此對有效治療方法的需求仍然存在很大未得到滿足。

The SERANATA study aims to fill this critical gap, offering a potentially transformative treatment option to a patient population that has long-awaited effective treatment options.

SERANATA 研究旨在填補這一關鍵空白，為期待已久的有效治療方案的患者群體提供具有變革意義的治療方案。

To this end, our development program at PH-ILD underscores our unwavering commitment to innovation, excellence, and our focus on enhancing the lives of patients.

為此，PH-ILD 的發展計畫強調了我們對創新、卓越和改善患者生活的堅定承諾。

Developed, jointly, with Chiesi, the SERANATA study will be a global, double-blind, placebo-controlled registrational Phase 3 trial.

SERANATA 研究由我們與 Chiesi 共同開發，將是一項全球性的、雙盲的、安慰劑對照的註冊 3 期試驗。

Approximately 480 patients will be randomized, evenly, to receive either 90-milligram seralutinib -- twice, daily; 120 milligram seralutinib -- twice, daily; or placebo. The primary endpoint is the change in 6-Minute Walk Distance from baseline, as compared to placebo at week-24.

大約 480 名患者將隨機平均分配接受 90 毫克色拉替尼治療，每日兩次；120 毫克塞拉魯替尼——每天兩次；或安慰劑。主要終點是與第 24 週的安慰劑相比，6 分鐘步行距離相對於基線的變化。

Key secondary endpoints included time to clinical worsening and change from baseline and force vital capacity. A successful outcome on this latter key measure would provide differentiated results, as compared to the currently-approved treatment.

關鍵次要終點包括臨床惡化的時間和相對於基線的變化以及肺活量。與目前批准的治療方法相比，後一項關鍵措施的成功將帶來不同的結果。

We believe that, in addition to targeting the pulmonary hypertension of PH-ILD patients, the PAH, so to say, seralutinib could also target the underlying interstitial lung disease. With pre-clinical data demonstrating seralutinib anti-fibrotic and anti-inflammatory attributes, treatment with seralutinib could also improve lung function, separately, from its effect on pulmonary hypertension by targeting the underlying lung fibrosis, which is characteristic of bile (inaudible).

我們相信，除了針對 PH-ILD 患者的肺動脈高壓（PAH），塞拉替尼還可以針對潛在的間質性肺部疾病。臨床前數據顯示，沙拉替尼具有抗纖維化和抗發炎特性，沙拉替尼治療還可以透過靶向潛在的肺纖維化（膽汁性肺纖維化的特徵）來改善肺功能，同時還能對肺動脈高壓產生作用。（聽不清楚）。

Recent pre-clinical modeling has led us to believe that there is value in testing a higher dose because increasing lung exposure may provide a greater improvement to the lung component of PH-ILD. This potential for a dual mechanistic benefit has led us to incorporate a 120 milligram, twice, daily dose-level of seralutinib, in addition to the 90 milligram, twice, daily dose level in SERANATA study.

最近的臨床前建模使我們相信，測試更高劑量是有價值的，因為增加肺部暴露可能會對 PH-ILD 的肺部成分產生更大的改善。這種雙重機制益處的潛力使得我們在 SERANATA 研究中除了每日兩次、每次 90 毫克的劑量水平外，還加入了每日兩次、每次 120 毫克的沙拉替尼劑量水平。

With the same painstaking detail with which we planned and enrolled the PROSERA study, we are diligently collaborating with our partners to identify the most suitable sites, globally, for this Phase 3 trial.

我們以與規劃和招募 PROSERA 研究時同樣的細緻態度，與我們的合作夥伴緊密合作，在全球範圍內尋找最適合進行此項 3 期試驗的地點。

Considering our unique non-vacillatory mechanism, there is high investor and patient demand. But, given the complexity and significance of this program, we are proceeding with thoughtful consideration.

考慮到我們獨特的非動搖機制，投資者和患者的需求很高。但是，考慮到該計劃的複雜性和重要性，我們正在深思熟慮地進行。

Further, there are no successful registrational, global PH-ILD clinical trial precedents to follow. Therefore, we hope the SERANATA study will be the first. We expect to begin first-site activations in the fourth quarter of this year.

此外，目前還沒有成功的註冊全球 PH-ILD 臨床試驗先例可供效法。因此，我們希望 SERANATA 研究將是第一個。我們預計將於今年第四季開始首批站點的啟動。

With this, we are extremely excited about the possibilities that this trial holds and the profound impact it could have on the lives of so many.

由此，我們對這次試驗帶來的可能性以及它可能對許多人的生活產生的深遠影響感到非常興奮。

Now, I will hand it over to our CFO and COO, Bryan Giraudo, for a financial update. Bryan?

現在，我將把財務更新交給我們的財務長兼營運長 Bryan Giraudo。布萊恩？

Thank you, Richard.

謝謝你，理查。

We'll now review the end-of-quarter financial results for the first quarter of 2025.

我們現在來回顧 2025 年第一季的季末財務表現。

We ended the quarter with $257.9 million in cash and cash equivalents and marketable securities.

本季末，我們的現金、現金等價物和有價證券為 2.579 億美元。

We continue to maintain a robust balance sheet and anticipate that our financial resources will provide sufficient capital for the first half of 2027.

我們繼續保持穩健的資產負債表，並預計我們的財務資源將為2027年上半年提供充足的資本。

For the quarter ended March 31, 2025, recognized revenue was $9.9 million. Our revenues associated with our collab with Chiesi includes $6.6 million in cost reimbursements for the quarter.

截至 2025 年 3 月 31 日的季度，確認收入為 990 萬美元。我們與 Chiesi 合作的收入包括本季 660 萬美元的成本補償。

R&D expenses were $38 million, compared to $32.4 million for the same period in 2024. G&A expenses for the first quarter of 2025 were $8.7 million, compared to $9.6 million for the same period in 2024.

研發費用為 3,800 萬美元，而 2024 年同期為 3,240 萬美元。2025 年第一季的 G&A 費用為 870 萬美元，而 2024 年同期為 960 萬美元。

The net loss for the three months ended March 31, 2025, was $36.6 billion or $0.16 per share, compared to a net loss of $41.9 billion or $0.19 per share for the same period in 2024.

截至 2025 年 3 月 31 日的三個月的淨虧損為 366 億美元或每股 0.16 美元，而 2024 年同期的淨虧損為 419 億美元或每股 0.19 美元。

Now, I'll turn the call back over to Faheem for closing remarks.

現在，我將把電話轉回給法希姆，請他作最後發言。

Yeah. Thanks, Bryan.

是的。謝謝，布萊恩。

Before we take questions, I just want to remind everyone of the substantial unmet need in PAH and PH-ILD. These are progressive diseases, with high mortality, that need new, safe, and effective therapies.

在我們回答問題之前，我只想提醒大家，肺動脈高壓 (PAH) 和肺動脈高壓-間質性肺部疾病 (PH-ILD) 方面存在大量未滿足的需求。這些都是死亡率很高的漸進性疾病，需要新的、安全的、有效的治療方法。

Due to this dire need and historical lack of innovation, even approved therapies with limited efficacy or poor tolerability have achieved commercial success. Patients and physicians are eagerly awaiting new therapies, particularly those with differentiated mechanisms and improved outcomes.

由於這種迫切的需求和歷史上缺乏創新，即使是療效有限或耐受性差的核准療法也取得了商業上的成功。患者和醫生都熱切期待新的治療方法，特別是那些具有差異化機制和改善結果的治療方法。

With its potential first-in-class mechanism and growing body of evidence of the potential for reverse remodeling in this disease -- paired with the safety profile observed, to date -- we can envision a future where seralutinib becomes a backbone therapy and PAH and a multi-billion dollar franchise.

憑藉其潛在的首創機制和越來越多的證據表明這種疾病具有逆轉重塑的潛力——再加上迄今為止觀察到的安全性——我們可以預見未來沙拉替尼將成為 PAH 的骨幹療法和價值數十億美元的特許經營權。

This [opportunity] is not confined to the United States. It extends to international markets, as well.

這[機會]並不僅限於美國。它也延伸到國際市場。

Japan -- which is the second largest PAH market, globally, after the US -- has a number of clinical sites participating in the PROSERA study.

日本是全球第二大 PAH 市場，僅次於美國，擁有多個參與 PROSERA 研究的臨床站點。

Considering seralutinib recent Orphan Drug Designation and the participation of Japanese patients in PROSERA, we believe that, with positive result, this could support a [PMDA] and a subsequent approval in Japan.

考慮到 seralutinib 最近獲得孤兒藥資格認定以及日本患者參與 PROSERA 的情況，我們相信，如果取得積極成果，這將支持 [PMDA] 並隨後獲得日本的批准。

So if there's one takeaway from today's discussion, let it be that Gossamer is doing everything that we can to increase the chances of long-term clinical and commercial success for seralutinib. And we're committed to maintaining the highest standards to accomplish this mission.

因此，如果今天的討論有一個要點，那就是 Gossamer 正在盡一切努力來增加 seralutinib 取得長期臨床和商業成功的機會。我們致力於保持最高標準來完成這項使命。

Our focus is not to just achieve a provable results, that's the bare minimum. Our focus is on generating comprehensive, definitive, and differentiated outcomes in both of our Phase 3 trials that will set seralutinib apart from other therapies on the market, helping lay the groundwork for a seralutinib franchise.

我們的重點不僅僅是實現可證明的結果，這是最低限度。我們的重點是在我們的兩個 3 期試驗中產生全面、明確和差異化的結果，這將使 seralutinib 有別於市場上的其他療法，並為 seralutinib 特許經營奠定基礎。

Operator, you may now open the line to questions.

接線員，您現在可以開始回答問題了。

(Operator Instructions)

（操作員指示）

Joe Schwartz, Leerink Partners.

Leerink Partners 的 Joe Schwartz。

Great. Thanks so much for taking my questions. I have two.

偉大的。非常感謝您回答我的問題。我有兩個。

First. With 343 patients enrolled in PROSERA, to date, have you considered stopping enrollment there, in order to be able to still report data this year? Could you give us some insight into your (inaudible) here? And why you've decided to enroll these last patients and push the data into '26?

第一的。到目前為止，PROSERA 已有 343 名患者入組，您是否考慮停止入組，以便今年仍能報告數據？您能否向我們介紹一下您的（聽不清楚）？為什麼您決定招募最後這些患者並將數據推遲到 26 年？

And then, I have a follow-up.

然後，我有一個後續問題。

Yeah. Thanks, Joe. Thanks for your question.

是的。謝謝，喬。謝謝你的提問。

It really relates to the fact that there's been such incredible demand to study, Joe. Obviously, as we started to signal that we were nearing the end of enrollment, that demand got even bigger.

喬，這確實與研究需求如此巨大有關。顯然，當我們開始發出信號表明招生即將結束的時候，需求就會變得更大。

And it's really important that we honor the commitment we have to patients and to their physicians to ensure that we have worked alongside of all of these physicians and continue to do so into the future; not only with seralutinib but, also, with the PH-ILD Phase 3, which many of these physicians will also be investigators in.

我們必須履行對患者及其醫生的承諾，確保我們與所有這些醫生一起工作，並在未來繼續這樣做，這一點非常重要；不僅有 seralutinib，還有 PH-ILD 第 3 階段，其中許多醫生也將成為該階段的研究者。

And so, we wanted to honor that commitment and decided to honor -- and we closed off screening. So we will no longer be screening patients.

因此，我們想要履行這項承諾並決定履行——我們結束了放映。因此我們將不再對患者進行篩檢。

But there is a bolus -- a large bolus -- of patients that are in the screening funnel, now. And our commitment was to follow through: determine which of those patients would qualify for the study. And then, if they qualify, enroll them. So that should take us into somewhere around the June timeframe.

但是現在，有大量患者正在接受篩檢。我們的承諾是堅持到底：確定哪些患者有資格參與研究。然後，如果他們符合資格，就讓他們入學。因此這應該會將我們帶入六月左右的時間範圍。

And just as we think about the timing for that: first and foremost, we care about the quality of the study; first and foremost, we care about bringing the right patients into the study; and timelines (inaudible) course (inaudible).

正如我們考慮時機一樣：首先，我們關心研究的品質；首先，我們關心的是讓合適的患者參與研究；和時間表（聽不清楚）課程（聽不清楚）。

So we will conclude the study. Last-patient-out will certainly be in the fourth quarter, near the end of the fourth quarter. But by the time we scrub, analyze, or collect the data -- scrub the data, analyze the data, and get it ready for a top presentation, that will take a little bit of time. That's the February date.

因此我們將結束這項研究。最後一位病人出院肯定會在第四季度，接近第四季末的時候。但是，當我們清理、分析或收集資料時——清理資料、分析資料並準備好進行頂級演示時，這將花費一點時間。那是二月的日期。

Very helpful. Thanks.

非常有幫助。謝謝。

And then, could we delve more into baseline characteristics in PROSERA? Since the TORREY trial enrolled patients primarily from North America, whereas PROSERA will be more global, I was wondering if we could get your thoughts on how this factor could influence the results.

那麼，我們能否更深入地研究 PROSERA 中的基線特徵？由於 TORREY 試驗招募的患者主要來自北美，而 PROSERA 的招募對象則更加全球化，我想知道您是否可以聽聽您對這個因素如何影響結果的看法。

Yeah. In TORREY, we had sites, also, globally; but not as extensively as we have with PROSERA. So PROSERA has a much broader global footprint, in the context of the sites that we've rolled.

是的。在 TORREY，我們在全球也有站點；但不如 PROSERA 那麼廣泛。因此，從我們推出的網站來看，PROSERA 的全球影響力更為廣泛。

As an example, there is a significant portion of patients that will come out of places like Latin America, South America, Eastern European countries, and Asia-Pacific. And the reason I highlight that is it's really interesting because what we find in those jurisdictions are really excellent patients for us to enroll in this study.

例如，相當一部分患者來自拉丁美洲、南美洲、東歐國家和亞太地區。我強調這一點的原因是，這真的很有趣，因為我們在這些司法管轄區內找到了非常優秀的患者，可以讓我們參與這項研究。

And, by that, I mean, low morbidities and patients that, in historical trials from those regions, have shown a much larger magnitude of effect on their 6-Minute Walk.

我的意思是，這些地區的發病率較低，而且在歷史試驗中，患者的 6 分鐘步行活動表現出了更大的效果。

So, as an example, the STELLARs study for sotatercepts, the patients that they enrolled in South America saw somewhere in the neighborhood of mid-70-meter improvement in walk versus the US patients in that study, who were around 26 meters. That, largely, we believe because these patients are just more pure PAH patients, with less comorbidity and an easier opportunity to show that magnitude of effect.

舉個例子，在 STELLARs 針對 sotatercepts 的研究中，他們在南美招募的患者的步行成績提高了大約 70 米，而該研究中的美國患者的步行成績提高了大約 26 米。我們認為，這主要是因為這些患者只是較純粹的 PAH 患者，合併症較少，也較容易顯示出這種程度的療效。

Richard, I don't know if you have anything else you want to add to that?

理查德，我不知道您是否還有什麼要補充的？

No. Faheem, I think that's exactly right.

不。法希姆，我認為這完全正確。

The younger patients, the different treatment regimens, also, contribute to those patients that you've outlined.

對於較年輕的患者，不同的治療方案也對您概述的那些患者有所貢獻。

Bryan?

布萊恩？

Joe, I'd also just remind you that part of the reason why we had a disproportionately large number of patients from North America and the United States in TORREY was because many of our US sites were closed because of the COVID-19 pandemic and those physicians were not actively doing clinical research.

喬，我還要提醒你，TORREY 醫院之所以接收大量來自北美和美國的患者，部分原因是由於 COVID-19 疫情，我們在美國的許多醫療點都關閉了，而那些醫生也沒有積極開展臨床研究。

So we do believe the combination of operating in a normal time and in a broader global reach is going to give us (inaudible) that much more patient population.

因此，我們確實相信，在正常時期和更廣泛的全球範圍內開展業務相結合將為我們帶來（聽不清楚）更多的患者群體。

Thanks for the color.

謝謝你的顏色。

Thanks, Joe.

謝謝，喬。

Andreas Argyrides, Oppenheimer.

安德烈亞斯·阿吉里德斯，奧本海默。

Great. Thanks for taking our questions. Congrats on all the progress on your completion of enrollment. And, also, thanks for the comparisons, the various baseline characteristics for STELLAR. You pre-empted one of my questions -- (inaudible) very helpful.

偉大的。感謝您回答我們的問題。恭喜您完成入學並取得所有進展。另外，也感謝您對 STELLAR 的各種基準特徵的比較。您搶先回答了我的一個問題——（聽不清楚）非常有幫助。

So we only have a couple here. We'll keep it as short as we can.

所以我們這裡只有幾個。我們會盡量簡短。

With baseline in PROSERA now in hand, have power and assumptions changed, at all?

現在有了 PROSERA 中的基線，功率和假設是否有所改變？

And then, was stringent enrollment criteria the reason that the enrollment took a little longer than previously expected?

那麼，入學標準嚴格是否是導致入學時間比預期要長的原因呢？

And then, last, when it comes to safety, seralutinib has a clean profile, to date. How do you think these upcoming results can address the generalized concern that (inaudible) have off-target effects and seralutinib doesn't?

最後，就安全性而言，迄今為止，沙拉替尼的狀況良好。您認為這些即將得出的結果如何能夠解決普遍存在的擔憂，即（聽不清楚）具有脫靶效應，而沙拉替尼沒有？

Thanks.

謝謝。

Yeah. I'll take a portion of that question and have Richard, as well, jump in -- anybody else on the team.

是的。我將回答該問題的一部分，並讓理查德也參與其中——團隊中的其他人也可以參與其中。

Certainly, as it relates to the baseline characteristics that you've seen, I think your question, Andreas, was, really, does that lend to the focus on those baseline characteristics; and the stringent entry criteria lend to the time that it took to enroll the study? I would say, unequivocally, yes.

當然，由於它與您所看到的基線特徵有關，我認為您的問題，安德烈亞斯，是，這是否真的有助於關注這些基線特徵？而嚴格的入學標準是否增加了參與研究所需的時間？我會毫不含糊地說，是的。

As an example and to just further highlight that point, Andreas: we screened somewhere in the neighborhood of 750 patients to this day, which is a significant number of patients. And the fact that that's about double what we'll actually will end up enrolling, that should tell you two things:

舉個例子，為了進一步強調這一點，安德烈亞斯：到目前為止，我們已經篩檢了大約 750 名患者，這是一個相當大數量的患者。事實上，這個數字大約是我們實際招生人數的兩倍，這應該說明兩件事：

One. That we've been incredibly stringent to our entry criteria into this study for all the reasons that we've talked about. We think we've given this criteria that we put into place and, now, have been able to achieve. We think that really enhances our probability of success.

一。基於我們討論過的所有原因，我們對這項研究的准入標準非常嚴格。我們認為我們已經制定了這些標準，並且現在已經能夠實現。我們認為這確實提高了我們成功的可能性。

And I think the second thing that that says, in terms of the number of screening opportunities that we've had, is the significant demand for this study. That's a significant number of patients. And there was a tremendous amount of demand from physicians -- the treaters -- to be able to have their patients evaluated for their entry into the study.

我認為，就我們擁有的篩檢機會數量而言，第二件事就是對這項研究的巨大需求。這是一個相當數量的患者。醫生（治療者）對能夠對患者進行評估以確定其是否參與研究有著極大的需求。

And I think that's a vote of confidence, if you will, from the physician community about the promise of seralutinib.

如果你願意的話，我認為這是醫生團體對沙拉替尼前景的信任投票。

Richard?

理查德？

I think one of your first questions around the baseline characteristics impact the power of the study -- the answer is no.

我認為，您首先要問的有關基線特徵是否會影響研究的效果的問題之一是——答案是否定的。

Directly, from a technical standpoint, we have over 90% power, given the sample size. In fact -- just to reiterate what Faheem mentioned -- the study, intentionally, was designed to enroll this population.

直接從技術角度來看，考慮到樣本量，我們的效力超過 90%。事實上——只是重申一下 Faheem 提到的——這項研究的目的是招募這個群體。

So in anticipation of the treatment effect that we would observe -- which is complementary to the sample size and the expected power, based on that treatment effect and standard deviation -- we're basically right on target.

因此，對於我們將觀察到的治療效果的預期——這是對樣本量和預期功效的補充，基於治療效果和標準差——我們基本上達到了目標。

I think, Andreas, your last question was around safety. Certainly, to date, we remain very pleased with the safety profile we have seen -- again, that it's a function of both design of the molecule, the route of administration, as well as the fact that we've designed everything to be on target, which we think, again, as Bob has spoken many times about, long term, in addition to what (inaudible) robust efficacy, our safety profile and ease of use will be a competitive advantage.

安德烈亞斯，我認為你的最後一個問題是關於安全的。當然，到目前為止，我們對所看到的安全性感到非常滿意——再次強調，這是分子設計和給藥途徑的功能，也是我們設計一切以實現目標的事實，我們認為，正如鮑勃多次談到的那樣，從長遠來看，除了（聽不清）強大的功效之外，我們的安全性和易用性也將成為我們的競爭優勢。

Yeah. Andreas, if I could just add just to what Brian said -- just for one last comment here.

是的。安德烈亞斯，如果我可以補充布萊恩所說的內容——這裡只是最後一條評論。

That safety profile, combined with the efficacy that we expect to see -- certainly, the efficacy that we saw in the Functional Class III; and higher-risk patients in TORREY; and the open-label extension experience that showed that we continue to see improvement, over time -- possibly, related to the reverse remodeling effect that that we hypothesized is going on -- really positions us well, commercially, to be used across not only a broad swath of PAH patients but, also, to suggest that there's an opportunity for positioning this drug as the backbone of therapy for earlier use to prevent longer-term progression.

該安全性，加上我們期望看到的功效——當然，是我們在功能 III 類中看到的功效；以及 TORREY 中的高風險患者；開放標籤擴展經驗表明，隨著時間的推移，我們繼續看到病情改善 — — 這可能與我們假設的逆向重塑效應有關 — — 這確實為我們在商業上奠定了良好的基礎，不僅用於廣泛的 PAH 患者可用於廣泛定位的支柱治療。

As we all know, this is a progressive disease, where every patient progresses. And if we can delay, halt, that progression, that's an incredibly meaningful outcome for patients.

眾所周知，這是一種進行性疾病，每位患者的病情都會惡化。如果我們能夠延緩或阻止病情進展，這對患者來說將是一個非常有意義的結果。

Fantastic. I appreciate the color. Congrats on all the progress.

極好的。我很欣賞這個顏色。祝賀你取得的所有進展。

Yeah. Thank you.

是的。謝謝。

Yasmeen Rahimi, Piper Sandler.

亞斯明·拉希米、派珀·桑德勒。

Good afternoon, team. Really excited for you. Congrats on so many milestones, right, enrollment completion, unveiling the baseline, and the PH-ILD is kicking that all off -- really incredible progress; and updates, today.

大家下午好。真的為你感到興奮。恭喜你們取得瞭如此多的里程碑，對吧，招生完成，公佈基線，以及 PH-ILD 開啟這一切——真是令人難以置信的進步；以及今天的更新。

Few questions through for you.

我為您解答幾個問題。

The first question, team, is for the baseline measures. Did you look at baseline PVR in the PROSERA study? Question 1.

團隊，第一個問題是關於基線措施。您是否查看過 PROSERA 研究中基線 PVR？問題 1.

Question 2. Once the study finishes, fully, enrollment, are you planning to give us another cut of the baseline and, maybe, a little bit additional information? I don't know if there's going to be another disclosure around it, before we get the data in February.

問題2.一旦研究完成，全面招生，您是否計劃為我們提供另一份基線，或一些額外的資訊？我不知道在我們二月份獲得數據之前是否會有其他相關披露。

And then, the third one is: given that the end points for both of these -- between the PH-ILD and the PAH study are the 6-Minute Walk Test, is there anything we can infer from read-through from PROSERA to SERANATA, now that we have the study design?

然後，第三個問題是：鑑於 PH-ILD 和 PAH 研究這兩個研究的終點都是 6 分鐘步行測試，現在我們有了研究設計，我們可以從 PROSERA 到 SERANATA 的通讀中推斷出什麼嗎？

Appreciate if you could take three questions.

如果您能回答三個問題我將非常感激。

Thanks for your question, Yasmeen.

謝謝你的提問，Yasmeen。

As it relates to the question around further updates: I think, as it relates to the baseline, we've given you baseline data on 323 patients. We don't expect that to materially change, given just the number of patients that we've been able to evaluate baselines on.

關於進一步更新的問題：我認為，就基線而言，我們已經為您提供了 323 名患者的基線數據。考慮到我們能夠評估基線的患者數量，我們預計這種情況不會發生實質變化。

And I think we can be pretty clear with you that we will, complete enrollment by, latest, mid-Junne. And so, there won't be any mystery there. Just we know that, now, with great certainty; given that we know exactly how many patients are in the funnel.

我想我們可以很清楚地告訴你們，我們將最晚在六月中旬完成招生。所以，那裡不會有任何神秘。我們現在非常肯定地知道這一點；假設我們確切知道漏斗中有多少名患者。

So I think there should be no uncertainty as to when our last-patient-in will be. As I said, it'll be by mid-June. And I think it's fair to conclude that the baseline that we've given you will be very close to the baseline that we'll end up within this study.

所以我認為我們最後一位病人入院的時間應該毫無疑問。正如我所說，將在六月中旬完成。我認為可以公平地得出這樣的結論：我們給您的基線將非常接近我們在本研究中最終確定的基線。

Richard?

理查德？

Yasmeen, to answer your question about the PVR: we did have a PVR-entry criteria of 400 or greater. We did not mandate to have a PVR as an endpoint so we won't have that in this particular study.

Yasmeen，回答您關於 PVR 的問題：我們的 PVR 准入標準確實為 400 或更高。我們沒有要求將 PVR 作為終點，因此在本次特定研究中我們不會採用 PVR。

But, yes, we did have minimal criteria for a PVR. And that could have been based on some historic data, at the time of screening. It's in line to what you would expect, given the requirement that that we had.

但是，是的，我們確實對 PVR 有最低標準。這可能是基於篩選時的一些歷史數據。考慮到我們的要求，這符合您的預期。

In terms of your question around read through: of course, assuming that PROSERA is positive, that portends the possibility that the PH-ILD would also be positive. Having said that, we also know that PH-ILD patients are going to have lower 6-Minute Walks than in group 1 patients. They're actually sicker, overall.

關於您關於通讀的問題：當然，假設 PROSERA 為陽性，則預示著 PH-ILD 也有可能為陽性。話雖如此，我們也知道 PH-ILD 患者的 6 分鐘步行次數會比第 1 組患者少。總體而言，他們的病情實際上更加嚴重。

And so, under the thesis that, in PROSERA, we have an enriched population of greater severity -- I think, just implicit in studying the group 3 population, those patients are sicker, so if the drug is effective in that population, we should also see a very good treatment effect on 6-Minute Walk, as well as other parameters such as NT-proBNP, et cetera.

因此，基於這一論點，在 PROSERA 中，我們擁有一個病情更為嚴重的豐富人群 - 我認為，在研究第 3 組人群時就隱含著這些患者的病情更為嚴重，因此，如果該藥物對該人群有效，我們也應該看到對 6 分鐘步行以及 NT-proBNP 等其他參數有非常好的治療效果。

Yeah. And so, I think that definitely does increase the probability of success and there would be a read-through.

是的。所以，我認為這確實會增加成功的可能性，而且會進行通讀。

But I think the other dimension, here, that's exciting about the PH-ILD population and the opportunity for seralutinib is that, certainly, pre-clinically, we've been able to determine that seralutinib also has some anti-fibrotic properties infecting really important markers of fibrosis.

但我認為，PH-ILD 族群的另一個令人興奮的方面以及沙拉替尼的機會是，當然，在臨床前階段，我們已經能夠確定色拉替尼也具有一些抗纖維化特性，可以感染真正重要的纖維化標記。

And as you think about this next patient population, those with interstitial lung disease, that could be a significant added benefit to the treatment of those patients.

當您考慮下一組患者，即患有間質性肺病的患者時，這可能會對這些患者的治療帶來顯著的額外益處。

Excellent. Thank you so much, team. I'm really excited for you. I'll jump back in the queue.

出色的。非常感謝，團隊。我真為你感到興奮。我會重新回到隊列中。

Thank you, Yasmeen.

謝謝你，Yasmeen。

Paul Choi, Goldman Sachs.

高盛的保羅·崔（Paul Choi）。

Hi, everyone. Good afternoon. Thank you for taking our questions. Congratulations on all the progress.

大家好。午安.感謝您回答我們的問題。祝賀你取得的所有進展。

I want to return to baseline characteristics, for a moment. Can you share or do you plan to share, with the final baseline, just what baseline sotatercepts usage is, given that it's been available both in the US and ex-US for a few quarters now?

我想暫時回到基準特徵。鑑於 sotatercepts 已在美國和美國以外地區上市數個季度，您能否分享或計劃分享最終基線，即 sotatercepts 的基線使用情況？

And then, in terms of a clinical impact from that, can you maybe just comment on how you're thinking of what is considered clinically meaningful now ,in in terms of 6-Minute Walk, given that it has been available commercially -- if there have been any evolution and change of thought among the KOL community on 6-Minute walk here, given (inaudible) stuff has been on the market for a few quarters.

然後，就臨床影響而言，您能否評論一下，就 6 分鐘步行而言，考慮到它已經實現商業化，您如何看待現在什麼才具有臨床意義？考慮到（聽不清楚）該產品已經上市幾個季度了，KOL 社群對 6 分鐘步行的想法是否有任何演變和變化。

And then, one for Bryan. Can you just remind us what key related milestones are baked into your cash runway guidance? Is there anything else that we should be factoring in what the pushes and pulls are that could potentially extend your cash runway?

然後，再給布萊恩一個。您能否提醒我們您的現金流指引中包含了哪些關鍵的相關里程碑？在考慮可能延長現金流量的推拉因素時，我們還需要考慮其他什麼因素嗎？

Thank you for taking our questions.

感謝您回答我們的問題。

Sure, Paul. I'll start with the first one, around backgrounds sotatercepts. As you'll recall, we had expectations that we would probably have about 10% of the study or roughly 35 patients on backgrounds sotatercepts.

當然，保羅。我將從第一個開始，圍繞背景 sotatercepts。您可能還記得，我們​​預計大約有 10% 的研究對像或大約 35 名患者會接受 Sotatercepts 治療。

Recall: if you were on background sotatercepts, there were two important components to that. You had to meet our entry criteria, which would suggest that sotatercepts wasn't working for you; or/and you would have to have been on stable sotatercepts dosing for six months.

回想一下：如果您使用的是背景 sotatercepts，那麼其中有兩個重要組成部分。您必須符合我們的入選標準，這表明 Sotatercepts 對您不起作用；或者/並且您必須已經穩定服用 Sotatercepts 劑量六個月。

I think we were very surprised on how few patients were on stable backgrounds sotatercepts dosing. So of the a couple of dozen inquiries we had about patients coming in, to date, I think we've enrolled three or four patients on background sotatercepts, which we think, again, speaks to the real-world experience of sotatercepts being not as linear as we were expecting.

我認為我們對如此少的患者在穩定的 Sotatercepts 劑量背景下感到非常驚訝。因此，到目前為止，我們收到了幾十個關於患者的問詢，其中有三到四名患者接受了 Sotatercepts 背景治療，我們認為這再次說明了 Sotatercepts 在現實世界中的應用並不像我們預期的那樣線性。

In regards to clinical effect, I'll it turn over to Faheem.

關於臨床效果，我會把它交給 Faheem。

Yeah. Paul, it's a really interesting question that that you've asked and one that I think is really important: the clinically meaningful effect for 6-Minute Walk.

是的。保羅，你問了一個非常有趣的問題，我認為這個問題很重要：六分鐘步行的臨床意義效果。

I'll start off by saying seralutinib appears to be differentiated from any other PAH treatment, thus far, that we've seen. In that, we see continued improvement over time, as evidenced by our open-label extension data, where patients -- even the less sick patients in TORREY that didn't have as profound a result -- saw improvement out to week 72.

首先我想說的是，到目前為止，沙拉替尼似乎與我們所見過的任何其他 PAH 治療方法有所不同。在這方面，我們看到病情隨著時間的推移不斷改善，正如我們的開放標籤擴展數據所證明的那樣，患者——即使是 TORREY 中病情較輕、沒有明顯改善的患者——在第 72 週也看到了改善。

(inaudible), even those patients with a more profound improvement, the more sick patients, also saw an improvement.

（聽不清楚），甚至那些病情改善較明顯的患者，病情較重的患者，也看到了好轉。

And that is a fairly unprecedented result. Assuming that we continue to see that trend in the open-label extension portion of the PROSERA study, what I believe that the treating community is thinking about is that the week-24 data will just be a point in time to which, then, they can expect patients to improve beyond that.

這是一個相當前所未有的結果。假設我們繼續在 PROSERA 研究的開放標籤擴展部分看到這種趨勢，我相信治療界正在考慮的是，第 24 週的數據只是一個時間點，然後他們可以預期患者的病情會在此之後得到改善。

And so, that really starts to then, ask and play into the question that you've asked -- is what is a clinically meaningful effect for PROSERA? Certainly, in the dialogue that we've had with our experts, our Key Opinion Leaders, our steering committee, I would say that anything in the in the 20-meter-plus improvement in 6-minute Walk becomes a very clinically meaningful effect, given the safety profile of the drug, the opportunity to use it earlier in line of therapy to try to prevent longer -term progression, and the promise of improvement over time.

那麼，這實際上開始詢問並探討您所提出的問題——PROSERA 的臨床意義是什麼？當然，在我們與專家、關鍵意見領袖和指導委員會的對話中，我想說，考慮到該藥物的安全性、在治療早期使用它來嘗試阻止長期進展的機會以及隨著時間的推移而改善的前景，6 分鐘步行 20 米以上的任何改善都具有非常有意義的臨床效果。

Again, that's unprecedented, had not been seen in this environment. So I think it's erroneous to actually just say sotatercepts was at X and, therefore, you need to be at X or Y. Because the basic point is this: every one of these patients will progress.

再說一次，這是史無前例的，在這種環境下從未見過。所以我認為，僅僅說 sotatercepts 在 X，因此你需要在 X 或 Y，這是錯的。因為基本要點是：這些病人中的每一個都會出現病情進展。

Sotatercepts will see really profound effects in a subset of patients somewhere in the neighborhood of 30% -- it's what we've seen from the trials -- which leaves a large swath of patients with significant unmet need.

Sotatercepts 將在大約 30% 的患者群體中看到真正顯著的效果——這是我們從試驗中看到的——這意味著很大一部分患者的巨大需求尚未得到滿足。

Certainly, there will still be patients who experience intolerable side effects with sotatercepts. We're seeing that continuing to build in the real-world database. And we will see patients who wane in their effect with sotatercepts and are, also, left with a need.

當然，仍會有患者因服用索他西普而出現無法忍受的副作用。我們看到現實世界的資料庫正在不斷建構。我們會看到患者對索他西普的療效逐漸減弱，但仍有需要。

So by the time we get to the market, there is going to be a large portion of patients that really need something. And the promise of a drug like this -- that has the potential to show reverse remodeling effects -- can be pretty profound.

因此，當我們的產品進入市場時，將有很大一部分患者確實需要某種產品。而像這樣的藥物——有可能表現出逆轉重塑的效果——的前景是相當深遠的。

Richard?

理查德？

Just to add: I think it's also important that the treatment effect needs to be interpreted without the context of the influence of hemoglobin that, probably, influenced the response that was observed with sotatercepts, for example; plus, the population that we've been talking about is a much more sicker population, overall.

補充一點：我認為同樣重要的是，治療效果需要在沒有血紅蛋白影響的背景下進行解釋，例如，血紅蛋白可能影響了使用 sotatercepts 觀察到的反應；另外，我們談論的人口總體上是患病率更高的人群。

So I think those are some additional considerations.

所以我認為這些是一些額外的考慮。

Bryan , do you want --

布萊恩，你想--

I think, Paul, your question on (inaudible) milestones -- our cash runway does not have any of the big milestones that we would expect on (inaudible) milestones.

保羅，我認為你關於（聽不清楚）里程碑的問題——我們的現金跑道沒有我們期望的任何重大里程碑（聽不清楚）里程碑。

I think the biggest influence on our financials, with the Chiesi relationship, is the cost sharing. And we expect that cost sharing to meaningfully increase, as we bring the cost in, from the PROSERA study; and kick off the SERANATA study, where we'll be cost sharing on a fifty-fifty basis.

我認為，與 Chiesi 的關係對我們的財務狀況影響最大的是成本分攤。我們預計，隨著我們從 PROSERA 研究中引入成本，成本分攤將顯著增加；並啟動 SERANATA 研究，我們將以五五分成的方式分攤費用。

Great. Thank you very much.

偉大的。非常感謝。

Olivia Brayer, Cantor.

奧莉薇亞·布雷爾，領唱。

Hi. Good afternoon, guys. Thank you for the question. Congrats on all the progress you've been making this year.

你好。大家下午好。謝謝你的提問。恭喜你今年的所有進步。

Can you disclose what treatment effect you're targeting, as it relates to your powering assumptions?

您能否透露一下您所針對的治療效果，因為它與您的動力假設有關？

And then, as you think about the regulatory bar for success, do you know whether FDA is looking for a certain thresholds on 6-Minute Walk improvement, both with respect to key value but, also, meter improvement?

然後，當您考慮成功的監管標準時，您是否知道 FDA 是否正在尋求 6 分鐘步行改進的某些閾值，包括關鍵值和米數改進？

And then, just, maybe, in terms of timing of the disclosure, does that include a safety period? Or was anything else added to that protocol that's maybe, changing the time of those data?

那麼，就揭露時間而言，是否包含安全期？或者該協議中是否添加了其他內容，可能會改變這些數據的時間？

To answer your question about the powering, the initial powering, which is the same, is based on a 30-meter treatment effect on 6-Minute Walk, with a standard deviation of 70 [meters], which gives us greater-than-90% power. But that hasn't changed.

回答您關於功率的問題，初始功率是相同的，是基於 6 分鐘步行 30 公尺的治療效果，標準差為 70 [米]，這使我們的功率大於 90%。但這一點並沒有改變。

And the other question was around -- the time of the data read-out does include that the safety follow-up. And that, also, hasn't changed.

另一個問題是——資料讀取的時間確實包括安全追蹤。這一點也沒有改變。

Did we capture all your questions there?

我們是否記錄了您的所有問題？

(multiple speakers) you regulatory guidance, as well.

（多位發言者）您也應該得到監管指導。

Maybe, just to follow up on that safety close-out period: was anything added to the protocol that's actually, maybe, shifted timing of the data read-out?

也許，只是為了跟進安全關閉期：協議中是否添加了任何內容，實際上可能改變了資料讀取的時間？

No.

不。

Okay. And then, the other question, Faheem, was just on the regulatory bar and how the FDA is thinking about 6-Minute Walk's improvement. Have they said anything, in terms of what key value or an act or improvement that they're looking to see for approval?

好的。然後，Faheem，另一個問題是關於監管標準以及 FDA 如何看待 6 分鐘步行計劃的改進。他們是否就他們希望獲得批准的關鍵價值或行為或改進發表了任何言論？

I'll turn that question over to Caryn Peterson, our Head of Regulator Affairs.

我將把這個問題轉交給我們的監管事務主管 Caryn Peterson。

Yeah. We had this discussion with the FDA, when we designed the protocol, as well as (inaudible). They agreed to both the powering and how it was powered, in terms of the distance and the magnitude of the fact that we were looking.

是的。我們在設計方案時與 FDA 進行了討論，並且（聽不清楚）。他們就供電和供電方式、以及我們所觀察的距離和程度達成了一致。

Okay. Great. Helpful. Thank you, guys.

好的。偉大的。很有幫助。謝謝你們。

Thank you.

謝謝。

Patrick Trucchio, H.C. Wainwright.

帕特里克·特魯基奧，H.C.溫賴特。

Thanks. Good afternoon. I have a few questions on PAH.

謝謝。午安.我對 PAH 有幾個問題。

The first is just on baseline. Do we know the number of patients who discontinued sotatercepts, previously?

第一個只是基線。我們知道之前停止服用 Sotatercepts 的病人人數嗎？

And then, separately, you've presented open-label extension data that shows continued PVR and 6-Minute Walk distance benefit. What read-through from this data do you see to PROSERA, if any? And, separately, what are the commercial implications of that (inaudible) data?

然後，您還單獨展示了開放標籤擴展數據，顯示了持續的 PVR 和 6 分鐘步行距離效益。如果有的話，您認為 PROSERA 可以從這些資料中讀取什麼？另外，這些數據（聽不清楚）的商業意義是什麼？

And then, a few on PH-ILD.

然後，還有一些關於 PH-ILD 的內容。

The first is just the doses -- the rationale behind the doses selected for this study.

首先是劑量－本研究選擇劑量背後的原理。

And then, separately, it was mentioned the data could demonstrate seralutinib as having a beneficial impact on underlying interstitial lung disease: what data -- or if you're able to demonstrate this benefit, what are the implications for the (inaudible) profile? What data should we be looking for to show that potential? And what are the implications, then, for the potential addressable patient population?

然後，另外提到，數據可以證明色拉替尼對潛在的間質性肺病具有有益的影響：什麼數據 - 或者如果您能夠證明這種益處，那麼對（聽不清楚）概況有何影響？我們應該尋找什麼數據來顯示這種潛力？那麼，這對於潛在的可尋址患者群體有何影響？

Thanks, Patrick. I'll take the first one, as far as patients who discontinued sotatercepts.

謝謝，派崔克。就停止使用 Sotatercepts 的病人而言，我會選擇第一個。

Due to the long half-life of sotatercepts, our requirement is that you need to have a five half-life [wash-out] before you can come in. We had very few sotatercepts discontinuations in the study.

由於 Sotatercepts 的半衰期很長，我們的要求是您需要經過 5 個半衰期 [洗脫期] 才能進來。我們在研究中很少停用 Sotatercepts。

If memory serves me correct, I think it was high single digits, to date.

如果我沒記錯的話，我認為到目前為止，這個數字還是個位數。

Rich, I'll turn it over for the other part.

里奇，我來翻看另一部分。

You just remind me what the other question --

你只是提醒我另一個問題--

(multiple speakers) the second part on PAH was just around the open-label extension data, the read-through from that data (inaudible) to PROSERA; and, as well, just commercial implications of that (inaudible) data.

（多位發言者）關於 PAH 的第二部分僅圍繞開放標籤擴展數據，以及從該數據（聽不清楚）到 PROSERA 的解讀；而且，這些數據（聽不清楚）還具有商業意義。

Yeah. I'll have Bob Smith, our Chief Commercial Officer, to touch on that one.

是的。我將請我們的首席商務官鮑勃·史密斯來談談這個問題。

Yeah. I think there's a very positive read-through there. As we have taken the (inaudible) data out into the community, the KOL community, we've just had really impressive feedback.

是的。我認為那裡的解讀非常正面。當我們將（聽不清楚）數據帶入社群、KOL 社群時，我們收到了非常令人印象深刻的回饋。

And we saw, as well, that, being a key lever for the increased enrollment in PROSERA, when they started to realize the benefits, over time, which, as Faheem mentioned, is to seralutinib and --

我們也看到，這是 PROSERA 增加註冊人數的關鍵槓桿，當他們開始意識到隨著時間的推移，正如 Faheem 所提到的，seralutinib 和--

Yeah. I think the open -label extension implications on commercial are what I've already mentioned, Patrick, which is: if that data is replicated as we hope it will be in the context of the PROSERA study, it is -- and we've had this feedback from the community that, as I said, it was largely unprecedented.

是的。我認為開放標籤擴展對商業的影響就是我已經提到的，帕特里克，那就是：如果這些數據能夠像我們希望的那樣在 PROSERA 研究的背景下複製，那麼——我們已經從社區得到了這樣的反饋，正如我所說的，這在很大程度上是前所未有的。

Most studies, you see and would expect to see, just, a plateauing of [effective]. So it really has an impact on positioning of the drug in the marketplace.

大多數研究，你會看到，也期望看到，[有效的]。因此它確實對藥物在市場上的定位有影響。

And that is -- like other progressive diseases, we see the desire and the hope to be able to use these drugs earlier, assuming that they've got the right safety profile. Because if you're using a drug earlier in the line of therapy, quality of life matters because they're going to be on treatment for a long period of time -- longer duration of treatment. And they're being treated in the earlier stage of their disease, which means they're, otherwise, living a reasonably normal life.

就像其他進行性疾病一樣，我們看到了能夠更早使用這些藥物的願望和希望，假設它們具有正確的安全性。因為如果您在治療早期使用藥物，生活品質就很重要，因為他們將接受長期治療 - 更長的治療時間。他們在疾病早期就接受了治療，這意味著他們的生活還算正常。

So safety really matters. And if there's a promise there or potential to actually remodel both lung and heart, as we've seen by our imaging data and our echo data, that's hugely impactful, in terms of the potential to stave off progression for a longer period of time.

所以安全真的很重要。如果確實存在重塑肺部和心臟的希望或潛力，正如我們從影像數據和超音波數據中看到的那樣，那麼就有可能在較長時間內阻止病情進展而言，這將產生巨大的影響。

So that will be an important positioning concept, commercially.

因此從商業角度來看這將是一個重要的定位概念。

Yeah. Cause what we're hearing a lot in the community is the desire to use these "disease-modifying", if you will, therapies, earlier, in the process.

是的。因為我們在社區中經常聽到的是，人們希望在治療過程中儘早使用這些「疾病改良療法」。

And I think if our profile plays out from the (inaudible) through to PROSERA, we'll have a very safe, tolerable, and effective agent that can be used very early along with the (inaudible).

我認為，如果我們的方案從（聽不清楚）一直到PROSERA，我們將擁有一種非常安全、耐受性良好且有效的藥物，可以與（聽不清楚）。

So, yeah, that's one of the rationale for the interest that we're getting for early utilization.

是的，這就是我們對早期利用感興趣的原因之一。

I could further comment on your question around the PH-ILD, around dose and the potential impact.

我可以進一步評論您關於 PH-ILD、劑量和潛在影響的問題。

First, let me start off by saying that we're confident in the 90 milligram dose in PH-ILD, given the results that we have in group 1.

首先，我要說的是，根據我們在第 1 組中取得的結果，我們對 PH-ILD 的 90 毫克劑量充滿信心。

Nonetheless, we believe it's important to acknowledge that, as we mentioned, PH-ILD represents basically two -disease processes. One, a vascular component with a PAH. And then, a lung component, characterized by the lung fibrosis.

儘管如此，我們認為必須承認，正如我們所提到的，PH-ILD 基本上代表兩種疾病過程。一是具有 PAH 的血管成分。然後是肺部成分，其特徵是肺纖維化。

So factoring in some of the pre-clinical work that we had performed and was presented at the (inaudible) Conference in 2024, using fibrotic models, using human lung and fibroblast cells, which (inaudible) showed a favorable effect, the thought process is we wanted to deliver more drug to the lung; factoring in the fact that the lung architecture is already distorted due to the lung fibrosis so we want to ensure that sufficient exposure is occurring in the setting of that differences in the architecture.

因此，考慮到我們已經完成的一些臨床前工作，並在 2024 年的（聽不清）會議上進行了展示，使用了纖維化模型，使用了人類肺和成纖維細胞，（聽不清）顯示出了良好的效果，我們的思維過程是希望向肺部輸送更多的藥物；考慮到肺結構已經由於肺纖維化而變形，因此我們希望確保在肺部暴露的環境中發生足夠的差異。

Recall that we have elevated the functional (inaudible) vital capacity as a secondary endpoint. That was done, intentionally, because we believe that this could be a clear differentiating feature of this molecule in treating both the PAH part and the lung disease part.

回想一下，我們已經將功能性（聽不清楚）肺活量提升為次要終點。我們是故意這樣做的，因為我們相信這可能是該分子在治療 PAH 部分和肺部疾病部分的明顯區別特徵。

And so, assuming that we have positive results, not only would it be differentiating for us but we would obviously have a discussion with regulators about potential mentioning of it or positioning of it in the product label.

因此，假設我們取得了積極的成果，這不僅會為我們帶來差異化，而且我們顯然會與監管機構討論在產品標籤中提及它或定位它的可能性。

And, maybe, Bob would just want to comment on some of the commercial implications of this approach, of the (inaudible).

也許，鮑伯只是想評論一下這種方法的一些商業影響，（聽不清楚）。

Okay. Yeah. Commercially, it'd be a huge differentiator because, right now, Tyvaso looked at (inaudible) as a safety endpoint in the study; whereas, we're looking at it as an efficacy endpoint in the study. So that would be a significant commercial differentiator for seralutinib.

好的。是的。從商業角度來看，這將是一個巨大的區別，因為現在，Tyvaso 將（聽不清楚）視為研究中的安全終點；然而，我們將其視為研究中的療效終點。因此，這將成為 seralutinib 的一個重要的商業差異化因素。

And I also think, Patrick, importantly, in conjunction with our partners at Chiesi, having an (inaudible) signal on (inaudible) would also be a significant barrier-to-entry in the European Union, where no drugs are approved.

派翠克，我還認為，重要的是，與我們在 Chiesi 的合作夥伴一起，在 (聽不清楚) 上發出 (聽不清楚) 信號也將成為進入歐盟的重大障礙，因為歐盟沒有批准任何藥物。

Terrific. Thanks so much.

了不起。非常感謝。

Thank you.

謝謝。

Laura Chico, Wedbush.

勞拉·奇科，韋德布希。

Hey. Good afternoon. Thanks very much for taking the questions. I just have a couple here.

嘿。午安.非常感謝您回答這些問題。我這裡只有幾個。

First -- and I apologize -- I'm just trying to reconcile some of the commentary around the geographic split on recruitment in PROSERA and some of the commercial dialogue you've had there. How do you think about the types of patients that would be more suited for seralutinib, presuming success in PROSERA versus a sotatercepts patient.

首先 —— 我很抱歉 —— 我只是想調和一些有關 PROSERA 招聘地理分佈的評論和您在那裡進行的一些商業對話。假設 PROSERA 與 sotatercepts 患者相比能夠取得成功，您認為哪些類型的患者更適合使用 seralutinib。

I'm just curious: Is there certain characteristics that might skew the market, one or the other?

我只是好奇：是否存在某些可能扭曲市場的特徵？

And then, related to the SERANATA -- I think I missed this -- could you elaborate a little bit further? This is blazing new trails here so trying to understand the powering assumptions around the primary endpoint; specifically on treatment effect and how you derive that.

然後，關於 SERANATA——我想我錯過了這一點——您能進一步詳細說明嗎？這是開闢新道路，因此試圖了解圍繞主要終點的動力假設；特別是治療效果以及如何獲得該效果。

Thanks very much.

非常感謝。

Yeah. On the commercial side, assuming positive PROSERA, we will launch seralutinib at roughly three years after sotatercepts launched in the market.

是的。在商業方面，假設 PROSERA 表現積極，我們將在 Sotatercepts 上市約三年後推出 Seralutinib。

At that point, what you'll see is basically a market reset. So all of the prevalent patients that are currently out there will have tried sotatercepts, probably three-quarters of them. Not all patients are going to be good candidates for sotatercepts. But call it 70%.

到那時，你將看到市場基本上重新開始。因此，目前所有普遍的患者都嘗試過 Sotatercepts，大概佔其中的四分之三。並非所有患者都適合使用 Sotatercepts。但稱之為 70%。

So by the time of the launch, you'll have this mark reset where patients have been on sotatercepts, have come off sotatercepts, that now have advanced in their progression of their disease. And that's the large patient population that Faheem spoke of before.

因此，到產品發佈時，您將會重置這個標記，即患者已經服用過 Sotatercepts，已經停用 Sotatercepts，並且病情已經得到進展。這就是 Faheem 之前提到的龐大患者群。

So we could potentially look at having a 70% to 80% of the market opportunity out there because sotatercepts will probably have a 30% of the market in that three years because of the discontinuations and just the normal progression of the market and the disease.

因此，我們可能會看到 70% 到 80% 的市場機會，因為由於停產以及市場和疾病的正常發展，sotatercepts 在這三年內可能只佔有 30% 的市場份額。

In addition, I think there's a lot of interest, as well, to using both seralutinib and sotatercepts, in combination.

此外，我認為合併使用沙拉替尼和索他西普也會引起人們濃厚的興趣。

As Bryan mentioned, we only have very few patients in the study on that combination. But there are data that are being looked at both pre-clinically -- and then, we'll have a little bit of clinical data to suggest how these therapies could be used in combination.

正如布萊恩所提到的，我們只有極少數患者參與了這個組合的研究。但是，我們正在對臨床前數據進行研究——然後，我們將獲得一些臨床數據來建議如何結合這些療法。

If I take my crystal ball up to say, let's fast forward to the time that we launched, as Bob said, say, early 2027.

如果我拿起水晶球說，讓我們快轉到我們發射的時間，正如鮑勃所說，比如說 2027 年初。

All the points that Bob made is exactly right. What we're going to see is not only the patients that have either tried sotatercepts, failed; the patients that weren't eligible for sotatercepts for one reason or another; and the patients who've been on sotatercepts and overall treatment is weighing those patients.

鮑伯提出的所有觀點都是完全正確的。我們將看到的不僅是那些嘗試過 Sotatercepts 但失敗了的患者；由於某種原因而不符合 Sotatercepts 治療條件的患者；並且對接受過 Sotatercepts 和整體治療的患者進行了權衡。

Those patients that have been on sotatercepts that may still be on sotatercepts -- but we're starting to see a waning of the effect, one can imagine doctors are going to be very encouraged to use combination therapy, especially given the pre-clinical evidence that's been generated, thus far, around the potential synergy between these two agents.

那些曾經服用過 Sotatercepts 的患者可能仍在服用 Sotatercepts - 但我們開始看到其效果減弱，可以想像醫生將非常鼓勵使用聯合療法，特別是考慮到迄今為止圍繞這兩種藥物之間潛在協同作用產生的臨床前證據。

But I think that seralutinib gets positioned as a drug to try first before seralutinib, once we're in the market, as we see newer patients coming in. I think that is the potential just because -- as you see it -- for the reason that I mentioned -- to be able to see the potential to prevent longer-term progression but, also, to be able to put these patients on a product with a safer profile, I think, will be incredibly encouraging for docs.

但我認為，一旦我們進入市場，隨著我們看到新患者的加入，沙拉替尼將被定位為在沙拉替尼之前首先嘗試的藥物。我認為這就是潛力，因為——正如您所看到的——出於我提到的原因——不僅能夠看到預防長期進展的潛力，而且能夠為這些患者提供更安全的產品，我認為這對醫生來說將是極大的鼓舞。

I think it'll an interesting marketing concept and positioning concept, once we get approved.

我認為，一旦我們獲得批准，這將是一個有趣的行銷理念和定位理念。

I could answer your question on some of the powering assumptions around our PH-ILD 6-Minute Walk. I think, as you mentioned and as we stated, there's not a lot of precedent for randomized controlled trials. But we do have the increased trial -- we could get the 6-Minute Walk data from that particular trial. And so, we had to do some extrapolations.

我可以回答您有關我們的 PH-ILD 6 分鐘步行活動的一些主要假設的問題。我認為，正如您所提到的以及我們所說的，隨機對照試驗的先例並不多。但我們確實進行了增加試驗——我們可以從那次特定試驗中獲得 6 分鐘步行數據。因此，我們必須做一些推論。

Just add to, maybe, three points around trying to provide a framework; and then, I'll get into the to the power assumptions that we did:

也許只需添加三點來嘗試提供一個框架；然後，我將介紹我們所做的功率假設：

As I mentioned, this is a very sick population. They're going to have lower 6-Minute Walks in group 1. And, furthermore, over the course of a trial, they're likely going to deteriorate much more in group 1.

正如我所提到的，這是一個病得很嚴重的群體。他們將在第 1 組中進行較低的 6 分鐘步行。此外，在試驗過程中，第一組的情況可能會惡化得更嚴重。

And I want to go back and look at the increased trial. That was a 16-week trial. Our trial is 24 weeks. So the assumption here is that those that are randomized to placebo are likely going to get worse than even in the increased trial. So that that's one factor.

我想回過頭來看看增加的審判。那是一次為期16週的試驗。我們的試用期為 24 週。因此，這裡的假設是，那些隨機服用安慰劑的人的情況可能會比增加劑量的試驗中的情況更糟。這是一個因素。

Related to that, then, as in the active arm, we have assumed at least a 30 meter difference; much like what we did for group 1. But we have some latitude there. If it's slightly -- less likely more, we still have greater than 94%, 95% power, comparing the active arm versus placebo.

與此相關，就像在活動臂中一樣，我們假設至少有 30 公尺的差異；就像我們對第 1 組所做的一樣。但我們在這方面有一定的自由。如果稍微 - 可能性較小，我們仍然有超過 94%、95% 的功效，將活性組與安慰劑組進行比較。

And that's also assuming a standard deviation of about [70].

這也假設標準差約為[70]。

That's super helpful. Thank you, guys.

這非常有幫助。謝謝你們。

Thank you.

謝謝。

Eliana Merle, UBS.

瑞銀的 Eliana Merle。

Hey, this is [Jasmine], on for Eli. Congratulations on all the progress. Thanks so much for taking our question.

嘿，我是 [Jasmine]，為 Eli 發言。祝賀你取得的所有進展。非常感謝您回答我們的問題。

First, a follow-up to an earlier question in your comments. Are you allowing such (inaudible) drop-ins in PROSERA? And then, more generally, how are you thinking about how looking at a combination of fact, here, could impact the opportunity, commercially?

首先，我想回答一下您評論中先前提出的一個問題。您是否允許在 PROSERA 中進行此類（聽不清楚）插入？然後，更一般地說，您如何看待這裡的事實組合會對商業機會產生怎樣的影響？

And, then, secondly, can you just talk about the population you're aiming to enroll in SERANATA for PH-ILD? Do you think that, similarly to PAH, (inaudible) feel greater effects in the more severe range of patients here?

其次，您能否談談您計劃在 SERANATA 中招收的 PH-ILD 人群？您是否認為，與 PAH 類似，（聽不清楚）對這裡更嚴重的患者的影響更大？

Thanks.

謝謝。

Yeah. In terms of the -- allowing sotatercepts patients who are on sotatercepts into the PROSERA study: we actually do allow for patients who are on sotatercepts but, of course, in order for them to get into the study, they need to actually qualify for the study, which means there is a period where they need to be on stable medication.

是的。就允許正在服用 sotatercepts 的患者參加 PROSERA 研究而言：我們確實允許正在服用 sotatercepts 的患者參加研究，但當然，為了讓他們參加研究，他們需要真正符合研究資格，這意味著他們需要在一段時間內服用穩定的藥物。

Richard, you can outline the criteria for sotatercepts -- eligible patients.

理查德，您可以概述一下 sotatercepts 的合格病患標準。

Yeah. They have to be on background sotatercepts for six months, at a stable dose, without changing due to hemoglobin or platelet changes. And then, they still have to meet our PVR criteria of greater than 400 Reveal Lite 2 Risk Score (inaudible) or a PVR greater than 800.

是的。他們必須連續六個月服用穩定劑量的索他西普，且劑量不能因血紅素或血小板變化而改變。然後，他們仍然必須滿足我們的 PVR 標準，即 Reveal Lite 2 風險評分大於 400（聽不清楚）或 PVR 大於 800。

After 24 weeks.

24週後。

Yeah. 24 weeks.

是的。 24週。

And so, just given the stringent application of the entry criteria, we will probably just get a handful of patients on sotatercepts. There really won't be a substantive number in this study, given the timeframe under which it's been launched and the access to patients who've been on for six months, as Richard just laid out.

因此，鑑於入選標準的嚴格應用，我們可能只會讓少數患者服用 Sotatercepts。正如理查德剛才所說，考慮到研究啟動的時間範圍以及對已經服藥六個月的患者進行調查，這項研究實際上不會得出實質性的數字。

So the short answer is yes. We allow sotatercepts patients in. But they got qualify in the context of the entry criteria, which will equate to a small number.

所以簡短的回答是肯定的。我們允許使用 sotatercepts 的病患進入。但他們符合入學標準，因此人數較少。

And then --

進而--

Yeah. I could comment (inaudible) the target population for SERANATA.

是的。我可以評論（聽不清楚）SERANATA 的目標群。

Probably, the best way to frame this is -- suggest to go back and look at the increased trial and their population. We have some similarities. But, clearly, some difference. And I can just highlight some of those differences.

可能，最好的表達方式是－建議回頭去看看增加的試驗及其人口。我們有一些相似之處。但顯然，還是存在一些差異。我只能強調其中的一些差異。

First of all, our, hemodynamic criteria are (inaudible). We have four (inaudible) units for PVR. They have three (inaudible) units. That's because we do want to leverage the fact that there are more severe patients. And we would anticipate a greater treatment effect in those patients.

首先，我們的血流動力學標準是（聽不清楚）。我們有四個（聽不清楚）PVR單元。他們有三個（聽不清楚）單位。這是因為我們確實想利用重症患者較多這一事實。我們預期這些患者的治療效果會更好。

In addition we are targeting Idiopathic Interstitial Pneumonia, IPF -- systemic autoimmune disease-related PAH, fibrotic interstitial pneumonitis, and occupational interstitial lung disease.

此外，我們也致力於治療特發性間質性肺炎、IPF（系統性自體免疫疾病相關的肺動脈高壓）、纖維化間質性肺炎和職業性間質性肺病。

Unlike increased, however, we're not allowing for a combined pulmonary fibrosis or emphysema. We're not allowing sarcoid in either.

然而，與增加不同的是，我們不允許肺纖維化或肺氣腫。我們也不允許肉瘤進入。

And then we're much more stringent upon criteria around having CT scans reviewed by (inaudible) and other things like that.

然後，我們對 CT 掃描的審查標準（聽不清楚）和其他類似事項更加嚴格。

And, probably, related to your question is do we anticipate the more severe population -- that we would also observe of a greater treatment effect? I think the answer is yes to that question.

而且，可能與您的問題相關的是，我們是否預期更嚴重的族群—我們也會觀察到更大的治療效果？我認為這個問題的答案是肯定的。

Okay. Great. That's helpful.

好的。偉大的。這很有幫助。

Just to clarify: patients are not allowed to drop in or begin sotatercepts during PROSERA?

只是為了澄清一下：患者在 PROSERA 期間不允許來訪或開始使用 sotatercepts 嗎？

As far as dropping in with sotatercepts, no. When you are enrolled, you have to be on (inaudible) therapy.

至於使用 sotatercepts，則沒有。當你入學時，你必須接受（聽不清楚）治療。

Great. Thanks so much for answering my questions.

偉大的。非常感謝您回答我的問題。

Thank you.

謝謝。

Vamil Divan, Guggenheim.

瓦米爾·迪萬 (Vamil Divan)，古根漢美術館。

Hi. This is [Daniel], on for Vamil. Thanks for taking our questions.

你好。我是 [Daniel]，代表 Vamil。感謝您回答我們的問題。

The first one is you described seralutinib a multi-billion dollar PAH franchise, potentially. Can you, maybe, compare the commercial opportunity for this drug in PAH versus PH-ILD?

第一個是，您描述了 seralutinib 可能是一個價值數十億美元的 PAH 特許經營權。您能否比較一下這種藥物在 PAH 和 PH-ILD 中的商業機會？

And then, my second question is just if you'd go into more details around the expected geographic distribution of enrollment for the PH-ILD trial? Do you think it'll be similar to what we saw in PAH, with the majority seen, internationally? Or is there less of a need for this imbalance, without the (inaudible) dynamic at play?

然後，我的第二個問題是，您是否可以更詳細地介紹 PH-ILD 試驗的預期入組地理分佈？您認為它會與我們在 PAH 中看到的情況類似嗎？大多數都是在國際上看到的？或者說，如果沒有（聽不清楚）動態因素的作用，這種不平衡的必要性就沒那麼大了？

Thanks.

謝謝。

Bob?

鮑伯？

Yeah. In terms of the multi-billion dollar opportunity: if you look at PAH, there's about 50,000 patients in the US.

是的。就數十億美元的機會而言：如果你看看 PAH，美國大約有 50,000 名患者。

If you look at the current pricing of the newer therapies, obviously, we haven't presented anything, publicly, but if you look at sotatercepts price, quickly -- sotatercepts, right now, is on about a 1.5 billion downgrade in its second full year. Right now, they're sitting at, I think, 5,800 patients or 5,200 patients have already started to drug. And that continues to grow.

如果你看一下較新療法的當前定價，顯然我們還沒有公開提出任何價格，但如果你看一下 Sotatercepts 的價格，很快你會發現，Sotatercepts 在其第二個完整年度中價格下降了約 15 億美元。目前，我認為已經有 5,800 名或 5,200 名患者開始服藥。而這一數字還在持續成長。

So you can see the opportunity within the PAH marketplace, in terms of the number of patients and the potential price associated with it.

因此，從患者數量和相關潛在價格來看，您可以看到 PAH 市場中的機會。

In terms of, the ILD-PH, that market is probably 3 times to 4 times greater than PAH; call it, roughly, worldwide, 400,000 -- something like 400,000 patients.

就 ILD-PH 而言，該市場規模可能是 PAH 的 3 到 4 倍；全世界範圍內約有 40 萬名患者。

So again -- and if you look at what Tyvaso is doing with their price point and number of patients, despite a very high number of discontinuations on that therapy, their run rate in in PH-ILD is roughly 2 billion.

所以再說一次 — — 如果你看看 Tyvaso 的價格點和患者數量，儘管該療法的停藥次數非常多，但他們在 PH-ILD 中的運行率約為 20 億美元。

To answer your question about geographic mix for SERANATA, I do think it will be similar to PROSERA, anything -- it may be an even larger contribution from the European Union. And that's really a function is -- remember: the dynamics in PROSERA is that, well, sotatercepts was not available in the European Union.

回答您關於 SERANATA 地理分佈的問題，我確實認為它將與 PROSERA 類似，甚至可能是來自歐盟的更大貢獻。這確實是一個功能——記住：PROSERA 中的動態是，嗯，sotatercepts 在歐盟不可用。

There was an expectation that it was coming. So patients were saying, I'll wait for sotatercepts before I go on (inaudible). That dynamic doesn't exist because (inaudible)Tyvaso has not been approved. And there is, at least, what we can tell from looking at regulatory processes, there is not a plan for United's partner,(inaudible), to get the drug registered in the European Union.

人們期待著它的到來。所以病人說，我要等到索他西普斯（Sotatercepts）好了再繼續（聽不清楚）。這種動態並不存在，因為（聽不清楚）Tyvaso 尚未獲得批准。至少，從監管流程來看，我們可以發現，聯合公司的合作夥伴（聽不清楚）沒有計劃在歐盟註冊該藥物。

So there is an even greater unmet medical need in Europe for PH-ILD therapies than there was for PAH therapies.

因此，歐洲對 PH-ILD 治療的未滿足醫療需求比 PAH 治療的未滿足醫療需求更大。

So in summary, you've got a patient population, PH-ILD, that is much larger, significantly underserved, with only one drug approved in the US -- being Tyvaso.

總而言之，PH-ILD 患者群體規模更大，醫療服務嚴重不足，而美國僅批准一種藥物，即泰瓦索 (Tyvaso)。

I think Tyvaso is now available in a couple other smaller jurisdictions; but, for the most part, only available in the US.

我認為 Tyvaso 現在可以在其他幾個較小的司法管轄區使用；但大多數情況下僅在美國有售。

With a sicker patient population than PAH, so the unmet need is substantial. And the opportunity, therefore, is also substantial.

由於患者人數比 PAH 更龐大，因此未滿足的需求相當大。因此，這個機會也是巨大的。

Okay. Great. Yeah. Thank you very much.

好的。偉大的。是的。非常感謝。

Thanks. All right. Any other questions in the queue, operator?

謝謝。好的。接線員，還有其他問題嗎？

At this time, there are no further questions in queue.

目前，隊列中沒有其他問題。

Okay. I would just like to, first off, thank everybody for your participation on this call. We've enjoyed the opportunity to be able to speak with you and be able to outline the progress that we've made on PROSERA.

好的。首先，我要感謝大家參加這次電話會議。我們很高興有機會與您交談並概述我們在 PROSERA 上取得的進展。

We, of course, eagerly await the top -line results from this study.

當然，我們熱切地期待這項研究的最終結果。

And for all the reasons that we've discussed today, we're very excited about the potential of seralutinib making a huge difference for patients.

基於我們今天討論的所有原因，我們對沙拉替尼為患者帶來巨大改變的潛力感到非常興奮。

And I just want to end this call by, first and foremost, thanking those patient who contributed themselves to this study and to their physicians for having the confidence in Gossamer and seralutinib; to entrust us with treating their patients, the ability to treat their patients.

在結束本次電話會議之前，我首先要感謝那些為這項研究做出貢獻的患者，以及他們的醫生對 Gossamer 和 seralutinib 的信任；委託我們治療他們的病人，並賦予我們治療他們病人的能力。

And, lastly, I just want to thank the Gossamer organization for the tireless effort, over the last couple of years, to be able to get us to where we are today.

最後，我只想感謝 Gossamer 組織在過去幾年中所做的不懈努力，使我們達到了今天的水平。

So thank you, all. We look forward to being able to talk to you, again; and, certainly, look forward to the top-line results on PROSERA.

謝謝大家。我們期待再次與您交談；當然，我們也期待 PROSERA 取得最佳成果。

Thanks, everybody.

謝謝大家。

With that, ladies and gentlemen, that does conclude your call.

女士們、先生們，你們的通話到此結束。

You may now disconnect your lines.

現在您可以斷開線路了。

Thank you, again, for joining us today.

再次感謝您今天加入我們。