Agios Pharmaceuticals Inc (AGIO) 2024 Q3 法說會逐字稿

Good morning and welcome to Agios third quarter, 2024 conference call. (Operator Instruction). Please be advised that today's call is being recorded at Agios requests. And I'd like to turn the call over to Chris Taylor, Vice President, Investor Relations and corporate communications for Agios.

早上好，歡迎參加 Agios 2024 年第三季電話會議。（操作員說明）。請注意，今天的通話是應 Agios 的要求進行錄音的。我想將電話轉給 Agios 投資者關係和企業傳播副總裁 Chris Taylor。

Thank you, operator. Good morning, everyone and welcome to Agios conference call and webcast to discuss our third quarter, 2024 financial results and recent business highlights. You can access the slides for today's call by going to the investors section of our website Agios.com, on today's call. I'm joined by our Chief Executive Officer, Brian Goff, Doctor Sarah Gheuens, Chief Medical Officer, and head of R&D, Tsveta Milanova, Chief Commercial Officer and Cecilia Jones, Chief Financial Officer.

謝謝你，接線生。大家早安，歡迎參加 Agios 電話會議和網路廣播，討論我們的 2024 年第三季財務業績和近期業務亮點。您可以在今天的電話會議上造訪我們網站 Agios.com 的投資者部分，查看今天電話會議的幻燈片。與我一同出席的還有我們的執行長 Brian Goff、首席醫療官 Sarah Gheuens 醫生和研發主管、首席商務官 Tsveta Milanova 和首席財務官 Cecilia Jones。

Before we get started, I would like to remind everyone that some of the statements we make on this call will include forward-looking statements, actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those we set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC, with that please turn the call over to Brian.

在我們開始之前，我想提醒大家，我們在本次電話會議中所做的一些陳述將包括前瞻性陳述，實際事件和結果可能與任何前瞻性陳述中明示或暗示的內容存在重大差異，因為各各種風險、不確定性和其他因素，包括我們在最近向SEC 提交的文件以及我們未來可能向SEC 提交的任何其他文件中列出的風險、不確定性和其他因素，請將電話轉給Brian。

Thanks Chris, good morning, everyone and thank you for joining us. Our mission at Agios is to develop and deliver transformative medicines that elevate and extend the lives of patients living with rare diseases.

謝謝克里斯，大家早安，謝謝您加入我們。我們 Agios 的使命是開發和提供變革性藥物，以提高和延長罕見疾病患者的生命。

We are especially focused on rare diseases that result in the disfunction and destruction of red blood cells including Pyruvate Kinase Deficiency or PKD, Thalassemia, Sickle Cell Disease and low-risk Myelodysplastic Syndrome or MDS.

我們特別關注導致紅血球功能障礙和破壞的罕見疾病，包括丙酮酸激酶缺乏症或 PKD、地中海貧血、鐮狀細胞疾病和低風險骨髓增生異常綜合症或 MDS。

As red blood cells comprise over 80% of all cells in the human body. Optimizing red cell health represents an important path to improved individual health.

因為紅血球佔人體所有細胞的80%以上。優化紅血球健康是改善個人健康的重要途徑。

Our lead product Mitapivat a kinase activator has a novel mechanism of action that improves red blood cell metabolism and increases the amount of energy or ATP available to support red blood cell health.

我們的主導產品 Mitapivat 是一種激酶激活劑，具有新穎的作用機制，可改善紅血球代謝並增加可用於支持紅血球健康的能量或 ATP 量。

We are proud to have delivered positive data in Phase 3 programs in PKD and Thalassemia and we are excited about the prospects of Mitapivat for Sickle cell disease, complementing those data readouts and the continued progress across our current pipeline. I am delighted to confirm today that Agios has received $1.1 billion in milestone payments following FDA approval in August of vorasidenib which originated at Agios.

我們很自豪能夠在 PKD 和地中海貧血的 3 期項目中提供積極的數據，我們對 Mitapivat 治療鐮狀細胞病的前景感到興奮，補充了這些數據讀數以及我們當前管道的持續進展。我今天很高興地確認，繼 8 月 FDA 批准源自 Agios 的 vorasidenib 後，Agios 已收到 11 億美元的里程碑付款。

These payments include a $905 million payment from Royalty Pharma in connection with the vorasidenib royalty purchase agreement Agios announced in May 2024 and a $200 million payment from Servier in connection with Agios' divestiture of its oncology business in 2021.

這些付款包括 Royal Pharma 與 Agios 於 2024 年 5 月宣布的 vorasidenib 特許權使用費購買協議相關的 9.05 億美元付款，以及 Servier 與 Agios 於 2021 年剝離其腫瘤業務相關的 2 億美元付款。

Given the positive Phase 3data readouts of Mitapivat in Thalassemia accomplished this year and the recently announced achievement of full enrollment of the Phase 3 rise up sickle cell disease study. We aim to deploy this strong cash base to prepare for the potential launches of Mitapivat and thalassemia in 2025 and in sickle cell disease in 2026. Beyond this significant infusion of capital, we also made important progress across our advancing clinical pipeline.

鑑於今年完成的 Mitapivat 治療地中海貧血的第 3 期數據，以及最近宣布的第 3 期上升鐮狀細胞病研究的全面入組成果。我們的目標是利用這強大的現金基礎，為 2025 年可能推出的 Mitapivat 和地中海貧血藥物以及 2026 年的鐮狀細胞疾病藥物做好準備。除了大量資本注入之外，我們還在推動臨床管線方面取得了重要進展。

First, we announced top line data from the Phase 3 activate study of Mitapivat in Children with PK deficiency who are regularly transfused. Our first pediatric study of Mitapivat and second, we achieved two milestones in our clinical development program for lower risk MDS.

首先，我們公佈了 Mitapivat 在定期輸血的 PK 缺陷兒童中進行的 3 期活化研究的主要數據。我們的第一項 Mitapivat 兒科研究和第二項研究，我們在低風險 MDS 臨床開發計劃中實現了兩個里程碑。

We announced that the FDA A granted orphan drug designation to our potent PK activator Tebapivat, formerly known as AG 946 for the treatment of myelodysplastic syndromes or MDS.

我們宣布 FDA A 授予我們強效 PK 活化劑 Tebapivat（原名 AG 946）孤兒藥稱號，用於治療骨髓增生異常症候群或 MDS。

And we have initiated enrollment and begun patient dosing in the Phase 2B study of Tebapivat in lower risk MDS, an area with profound unmet need and significant market growth.

我們已經啟動了 Tebapivat 治療低風險 MDS 的 2B 期研究的入組並開始患者給藥，該領域的需求嚴重未得到滿足，且市場增長顯著。

Importantly, as we round out a very productive and successful 2024 we are on track to achieve our key remaining milestone for this year submission of an SNDA for Mitapivat in thalassemia by the end of the year, seeking a broad label that includes adults living with all subtypes of thalassemia.

重要的是，隨著我們度過一個非常富有成效和成功的2024 年，我們有望實現今年剩下的關鍵里程碑，即在今年年底前提交治療地中海貧血的Mitapivat SNDA，尋求一個廣泛的標籤，包括患有所有疾病的成年人地中海貧血的亞型。

Sarah will provide a detailed update on our progress and upcoming milestones across R&D in just a few minutes. Leveraging the positive data observed in the energize and energize T Phase 3 studies of Mitapivat.

莎拉將在短短幾分鐘內提供有關我們的進展和即將到來的研發里程碑的詳細更新。利用 Mitapivat 的 energize 和 energize T 3 期研究中觀察到的正向數據。

Our expanding commercial organization is actively preparing for a potential US launch of Mitapivat in Thalassemia in 2025.

我們不斷擴大的商業組織正在積極準備 2025 年在美國推出地中海貧血的 Mitapivat。

Sarah will provide greater detail on the market opportunity in Thalassemia and the team's robust preparation as well as an update on our current launch in PKD in just a bit.

Sarah 將提供有關地中海貧血市場機會和團隊的強有力準備的更多詳細信息，以及我們目前在 PKD 中推出的最新信息。

Finally, as you'll hear from Cecilia, we ended the third quarter with a very strong cash position with approximately $1.7 billion in cash and investments on the balance sheet, which includes the $1.1 billion in milestone payments we received following FDA approval of war side.

最後，正如您將從塞西莉亞那裡聽到的那樣，我們在第三季度結束時擁有非常強勁的現金狀況，資產負債表上有大約17 億美元的現金和投資，其中包括我們在FDA 批准戰方後收到的11 億美元的里程碑付款。

And before handing off to Sarah, I want to emphasize how incredibly proud we are for all that's been achieved thus far in 2024 how intensely focused we remain on finishing the year strongly and our enthusiasm for continued progress in 2025 and beyond. With that, I'll now turn the call over to Sarah.

在交給 Sarah 之前，我想強調，我們對 2024 年迄今為止所取得的一切感到無比自豪，我們仍然高度專注於強勁地完成這一年，並對 2025 年及以後繼續取得進展充滿熱情。這樣，我現在就把電話轉給莎拉。

Thanks Brian. Just recently, we were able to attend two significant meetings where we continued engaging with the community at both the Academy for Sickle Cell and thalassemia conference and the SECIA annual convention, we were reminded once again about the difficult journey for sickle cell patients. And it reinforces our conviction for what we are aiming to bring to patients, turning to sickle cell disease. We are saddened by the recent events impacting this community and continue to be steadfast in our commitment to deliver a novel oral therapy that potentially improves anemia and how patients feel and function particularly with respect to fatigue.

謝謝布萊恩。就在最近，我們參加了兩次重要的會議，在鐮狀細胞和地中海貧血學會會議以及 SECIA 年會上繼續與社區進行接觸，再次提醒我們鐮狀細胞患者的艱難歷程。它增強了我們的信念，即我們的目標是為患者帶來鐮狀細胞疾病的治療。我們對最近影響該社區的事件感到悲傷，並繼續堅定地致力於提供一種新型口服療法，該療法可能改善貧血以及患者的感覺和功能，特別是在疲勞方面。

Given the positive data we generated in the Phase 2 portion of the rise of study, as well as the positive data we have generated in other hemolytic anemias that share a common pathophysiology. We are excited about the potential for Mitapivat to become a convenient first in class and best in class treatment option that improves red blood cell health for patients living with sickle cell disease.

鑑於我們在研究興起的第二階段部分中產生的積極數據，以及我們在具有共同病理生理學的其他溶血性貧血中產生的積極數據。我們很高興 Mitapivat 有潛力成為一種方便的一流和一流的治療選擇，可改善鐮狀細胞疾病患者的紅血球健康。

As announced last week, we are very pleased that we met our goal of completing enrollment in the Phase 3 rise up study by the end of the year, just over a year after we began recruiting this cohort, as a reminder the Phase 3 study has a planned sample size of 198 subjects randomized 2 to 1 to meet Mitapivat versus placebo across approximately 112 sites globally.

正如上周宣布的那樣，我們非常高興我們實現了在今年年底前完成第 3 階段上升研究入組的目標，就在我們開始招募該隊列一年多後，提醒我們第 3 階段研究已經完成計劃樣本量為198 名受試者，在全球約112 個地點進行隨機2 比1 的隨機分組，以接受Mitapivat 與安慰劑的比較。

There are two primary endpoints hemoglobin response defined as an increase of at least 1gram per deciliter in average hemoglobin concentrations over weeks, 24 to 52. Compared with baseline and analyzed rate of sickle cell pain crises driven by a differentiated mechanism of action. We believe that Mitapivat has the potential to address a high unmet need in this disease by improving anemia, reducing sickle cell pain crises and making patients feel better. We look forward to reporting top line data from the Phase 3 next year. For thalassemia we aim to deliver the first therapy approved for all thalassemia subtypes based on the positive data generated in both the Phase 3 energized study of Mitapivat in adults with nontransfusion dependent alpha or beta thalassemia. And the Phase 3 energized t study of mitapivat in adults with transfusion dependent alpha or beta thalassemia. We believe mitapivat has the potential to become a foundational and convenient oral treatment option for all subtypes of thalassemia including all genotypes and all levels of transfusion burden.

血紅素反應有兩個主要終點，定義為平均血紅素濃度在 24 至 52 週內增加至少 1 克/分升。與基線相比，分析了不同的作用機制驅動的鐮狀細胞疼痛危機的發生率。我們相信，Mitapivat 有潛力透過改善貧血、減少鐮狀細胞疼痛危機和讓患者感覺更好來解決這種疾病中未滿足的高度需求。我們期待明年報告第三階段的頂線數據。對於地中海貧血，我們的目標是根據 Mitapivat 在非輸血依賴性 α 或 β 地中海貧血成人患者的 3 期強化研究中產生的積極數據，提供第一種批准用於所有地中海貧血亞型的療法。mitapivat 在患有輸血依賴性 α 或 β 地中海貧血的成人患者中進行的 3 期 t 研究啟動了 t 研究。我們相信 mitapivat 有潛力成為所有亞型地中海貧血（包括所有基因型和所有輸血負擔水平）的基礎且方便的口服治療選擇。

We are working diligently to progress the filing and continue to expect to file an SNDA by the end of this year, seeking a label that includes adults living with all subtypes of thalassemia. In pediatric PK deficiency, we were pleased to announce top line data from the Phase 3 activate case study of Mitapivat in Children with PK deficiency who are regularly transfused. We are proud of this trial because first, this is the first phase three study to report data in this population. And importantly, it's the first completed pediatric study of mitapivat for Agios while the prespecified statistical criterion for the primary endpoint was not met. We believe these results were clinically meaningful given the percentage of patients that achieved a transfusion reduction response, including those who had a transfusion free response with no red blood cell transfusions. And those who achieved a normal hemoglobin response defined that hemoglobin concentrations within normal limits at least once in 8 weeks or more after in transfusions.

我們正在努力推進申請，並繼續期望在今年年底之前提交 SNDA，尋求一個包含患有所有亞型地中海貧血的成年人的標籤。在兒科 PK 缺乏症方面，我們很高興地宣布來自定期輸血的 PK 缺乏症兒童的 Mitapivat 3 期激活案例研究的主要數據。我們為這項試驗感到自豪，因為首先，這是第一個報告該族群數據的第三期研究。重要的是，這是第一個完成的 mitapivat for Agios 兒科研究，但未達到主要終點的預先設定的統計標準。我們認為，考慮到達到輸血減少反應的患者百分比，包括那些沒有輸注紅血球而達到無輸血反應的患者的百分比，這些結果具有臨床意義。那些達到正常血紅素反應的患者定義，在輸血後 8 週或更長時間內至少有一次血紅素濃度處於正常範圍內。

And second safety results from Mitapivat were consistent with the safety profile for Mitapivat previously observed in adults with PK deficiency who are regularly transfused with enrollment completed in the Phase 3 activated kits trial. We look forward to an anticipated data readout next year.

Mitapivat 的第二個安全性結果與先前在 PK 缺陷成人中觀察到的 Mitapivat 安全性一致，這些成年人在 3 期活化試劑盒試驗中完成入組後定期輸血。我們期待明年的預期數據讀出。

In parallel with the progress we continue to make across the mitapivat development program. This quarter, we also made important advancements in our tap program. First, we initiated the phase 2 study of Tebapivat in lower risk MDS.

同時，我們繼續在 mitapivat 開發計劃中取得進展。本季度，我們的 Tap 計劃也取得了重要進展。首先，我們啟動了 Tebapivat 治療低風險 MDS 的 2 期研究。

This open label study will enroll a total of 60 individuals for transfusion dependent lower risk MDS across three dose levels. 10mg, 15mg and 20mg. Each of which is greater than the 5mg dose that was evaluated in the previous Phase 2A study.

這項開放標籤研究將總共招募 60 名個體，研究三個劑量等級的輸血依賴性低風險 MDS。 10毫克、15毫克和20毫克。每一項都大於先前 2A 期研究中評估的 5mg 劑量。

Each dose level cohort will be opened for enrollment sequentially without pauses between the cohorts. Meaning that we will first enroll 20 patients in the 10mg dose cohort and once those slots are filled, we will begin enrolling 20 patients in the 15mg dose cohort and then we will do the same for the third cohort of 20 patients at the 20mg dose. There is a 24-week court period for each cohort followed by a 156-week extension period.

每個劑量水平隊列將按順序開放招募，隊列之間不會有暫停。這意味著我們將首先在10mg 劑量組中招募20 名患者，一旦這些位置被填滿，我們將開始在15mg 劑量組中招募20 名患者，然後我們將對第三組20 名20mg 劑量組患者進行同樣的操作。每個群體有 24 週的法庭期，然後是 156 週的延長期。

The primary endpoint of this study will be transfusion independence defined as remaining transfusion free for at least eight consecutive weeks during the co period.

本研究的主要終點是輸血獨立性，定義為在治療期間至少連續八週保持不輸血。

Secondary endpoints will include safety change in hemoglobin and additional measures of anemia similar to thalassemia with this program, we aim to deliver the first oral therapy that addresses anemia due to ineffective opposite in lower risk MDS which affects approximately 75,000 patients to 80,000 patients in the US and EU five and accounts for approximately 70% of all MDS cases.

次要終點將包括血紅蛋白的安全性變化以及與地中海貧血類似的貧血的其他措施，我們的目標是提供第一種口服療法，解決低風險MDS 中因相反無效而導致的貧血問題，該療法影響了美國約75,000 至80,000 名患者和歐盟五國，約佔所有 MDS 病例的 70%。

Also this quarter, we were delighted to receive FDA Orphan drug designation for Tebapivot for the treatment of MDS.

同樣在本季度，我們很高興獲得 FDA 授予 Tebapivot 用於治療 MDS 的孤兒藥資格。

This underscores the importance of bringing new oral treatment options to patients suffering from this rare disease. And we expect to provide additional milestone timelines. Once enrollment is further along, looking forward, we are excited to be attending the upcoming annual meeting of the American Society of Hematology Ash and look forward to the publication of accepted abstracts on November 5th. With that, I will now turn the call over to Seta.

這強調了為患有這種罕見疾病的患者提供新的口腔治療選擇的重要性。我們希望提供額外的里程碑時間表。一旦註冊工作進一步推進，我們很高興能夠參加即將舉行的美國血液學會 Ash 年度會議，並期待 11 月 5 日發布已接受的摘要。現在，我將把電話轉給 Seta。

Thanks Sarah as we prepare for a potential launch in thalassemia , we are reminded of the significant and met need in this disease. And also the value Pyrukyndng to thalassemia patients across all subtypes, we continue to validate this through the powerful patient connections. We experience at conferences like APCAP and in local community meetings at selected patient centers.

感謝莎拉，當我們為地中海貧血症的潛在推出做準備時，我們想起了這種疾病的重要且已滿足的需求。此外，Pyrukyndng 對所有亞型地中海貧血患者的價值，我們繼續透過強大的患者聯繫來驗證這一點。我們在 APCAP 等會議以及選定患者中心的當地社區會議上擁有豐富的經驗。

Thalassemia is much more prevalent than PK deficiency with approximately 6,000 adults diagnosed in the US.

地中海貧血比 PK 缺乏症更為普遍，在美國約有 6,000 名成年人被診斷出患有地中海貧血。

Approximately 4,000 of whom are Non transfusion dependent. The diagnosis rate in thalassemia is high with many patients diagnosed before adulthood.

其中約 4,000 人不依賴輸血。地中海貧血的診斷率很高，許多患者在成年之前就被診斷出來。

Given the availability of claims data and ICD 10 codes. These patients are known to the health care system which provides important clarity for our launch preparation.

鑑於索賠數據和 ICD 10 代碼的可用性。這些患者為醫療保健系統所熟知，這為我們的啟動準備工作提供了重要的清晰度。

Treatment options are limited, especially for patients with Non transfusion dependent disease with most patients relying on supportive therapy, all forms of thalassemia bring high rates of serious morbidities, reduced quality of life and a heightened risk of premature death.

治療選擇有限，特別是對於患有非輸血依賴性疾病的患者，大多數患者依賴支持性治療，所有形式的地中海貧血都會帶來很高的嚴重發病率、生活品質下降和過早死亡的風險增加。

The burden of disease is high and the associated cost of care is significant galvanized by the positive data from the energize and energize T studies. Our commercial organization is actively preparing to address this high unmet need with a potential us launch of Pyrukynd in thalassemia next year, we're especially enthusiastic about the potential for pyrokind to become the first therapy approved for all thalassemia subtypes.

Energize 和 energize T 研究的正面數據刺激了疾病負擔很高，相關的照護費用也很高。我們的商業組織正在積極準備解決這一未滿足的高度需求，明年我們可能會推出 Pyrukynd 治療地中海貧血，我們對 Pyrokind 成為第一個被批准用於所有地中海貧血亞型的療法的潛力感到特別興奮。

Our team continues to make progress across four areas of launch preparation.

我們的團隊繼續在啟動準備的四個領域取得進展。

First, we continue to conduct extensive market research and claims data based analysis to further refine our market insights and inform our launch, targeting and execution based on the work we've done. We estimate that pyrokind initial launch focus will address approximately 65% of the adult thalassemia patient population.

首先，我們繼續進行廣泛的市場研究和基於索賠數據的分析，以進一步完善我們的市場洞察，並根據我們所做的工作為我們的發布、定位和執行提供資訊。我們估計，pyrokind 最初的推出重點將解決約 65% 的成人地中海貧血患者群體。

We expect patients who already have regular contact with the health care system due to symptoms of their disease to be considered for therapy. First, these patient segments include transfusion dependent patients as well as Non transfusion dependent patients who are already experiencing complications or are living with debilitating fatigue.

我們希望那些因疾病症狀而定期接觸醫療保健系統的患者會被考慮接受治療。首先，這些患者群體包括依賴輸血的患者以及已經出現併發症或生活在虛弱疲勞中的非輸血依賴患者。

Our team is actively engaged in the field deepening our insights across the different patient segments and the diverse multicultural aspects of thalassemia.

我們的團隊積極參與該領域，加深我們對地中海貧血不同患者群體和多元文化方面的見解。

Second, our ongoing disease state education campaign has been focused on three areas. First, we are highlighting the pathophysiology of the disease, including ineffective erythropoiesis and hemolysis. Second, we believe it's important for patients and physicians to understand the long-term complications and burden of disease across all thalassemia subtypes particularly for patients with non-transfusion dependent disease who suffer from the misconception that they are at less risk. and third, as we continue to engage with both patients and physicians, we highlight the importance of frequent disease monitoring and management. So treatment plans can be tailored to the individual patient's needs to bring all of this together. We are pleased to share another example of the powerful rethink thalassemia campaign which we have rolled out in the recent months.

其次，我們正在進行的疾病狀態教育活動重點在於三個領域。首先，我們強調該疾病的病理生理學，包括無效的紅血球生成和溶血。其次，我們認為，患者和醫生了解所有地中海貧血亞型的長期併發症和疾病負擔非常重要，特別是對於患有非輸血依賴性疾病的患者，他們錯誤地認為自己的風險較低。第三，隨著我們繼續與患者和醫生接觸，我們強調頻繁的疾病監測和管理的重要性。因此，可以根據患者個體的需求量身定制治療計劃，將所有這些結合在一起。我們很高興與大家分享我們近幾個月推出的強有力的反思地中海貧血運動的另一個例子。

The striking images and headlines invite closer inspection of the words depicting the hidden risks of thalassemia. The feedback from this campaign has been very positive from both patients and physicians. They highlight how relevant and valuable they find the disease education content, not only when it comes to understanding the disease pathophysiology and complications, but also to connect that to the importance of ongoing monitoring and management.

引人注目的圖片和標題讓人仔細審視描述地中海貧血隱藏風險的文字。患者和醫生對此活動的回饋都非常正面。他們強調了他們認為疾病教育內容的相關性和價值，不僅在了解疾病病理生理學和併發症方面，而且還將其與持續監測和管理的重要性聯繫起來。

Our third area of focus in launch preparation is the discipline expansion of our commercial and medical teams to right size. The organization for a successful launch in this larger but still rare market.

我們在啟動準備工作的第三個重點領域是將我們的商業和醫療團隊的學科擴展至適當的規模。該組織在這個更大但仍然稀有的市場中成功推出。

We're steadily building the team and adding additional capabilities as we approach a potential launch with a keen focus on being as capital efficient as possible.

隨著我們接近潛在的發布，我們正在穩步建立團隊並增加額外的能力，並專注於盡可能的資本效率。

And fourth, our market access team is already engaging with payers on disease, state education. I'm proud of the broad access our team has achieved for Pyrukyndin PK deficiency and we are aiming for the same strong outcome in thalassemia.

第四，我們的市場准入團隊已經在疾病和國家教育方面與付款人接觸。我為我們的團隊在 Pyrukyndin PK 缺乏症方面取得的廣泛進展感到自豪，我們的目標是在地中海貧血方面取得同樣強勁的成果。

Outside the US. The Gulf Cooperation Council or GCC region is home to approximately 70,000 patients with thalassemia and some of the leading treatment centers in the region were part of our clinical trials.

美國境外。海灣合作委員會或海灣合作委員會地區擁有約 70,000 名地中海貧血患者，該地區一些領先的治療中心是我們臨床試驗的一部分。

As we announced last quarter, we're pleased to have entered into a distribution agreement with New British Pharmaceuticals to prepare for a potential commercialization of Pyrukynd in the GCC region.

正如我們在上季度宣布的那樣，我們很高興與 New Britain Pharmaceuticals 簽訂了分銷協議，為 Pyrukynd 在海灣合作委員會地區的潛在商業化做準備。

Complementing this partnership, we are delighted to have secured breakthrough medicine designation for Pyrukynd thalassemia granted by the Saudi FDA or S FDA. We're actively collaborating with Newbridge to develop an optimal regulatory and commercial strategy for the GCC region.

作為對這項合作關係的補充，我們很高興獲得沙烏地阿拉伯 FDA 或 S FDA 授予的 Pyrukynd 地中海貧血突破性藥物資格。我們正在與 Newbridge 積極合作，為海灣合作委員會地區制定最佳的監管和商業策略。

As a reminder, the access but in individual GCC countries usually begins with a price set at the regulatory level followed by access negotiations with health authorities, local institutions and the private sector.

需要提醒的是，在個別海灣合作委員會國家，取得通常從監管層級設定價格開始，然後與衛生當局、當地機構和私營部門進行取得談判。

We look forward to navigating each of these elements in collaboration with Newbridge.

我們期待與 Newbridge 合作探索這些元素。

Next, let me provide a brief update on the current launch of pins in PK deficiency. In the third quarter of 2024 we generated $9 million in net pruin revenue compared to $8.6 million in the second quarter of 2024.

接下來，讓我簡單介紹一下目前PK不足的腳位推出情況。2024 年第三季度，我們的淨淨收入為 900 萬美元，而 2024 年第二季為 860 萬美元。

In the USA total of 211 patients have completed a prescription enrollment form including 10 in the third quarter of 2024 a 5% increase versus the prior quarter.

在美國，共有 211 名患者填寫了處方登記表，其中 2024 年第三季有 10 名患者，比上一季增加了 5%。

This has translated into 127 net patients on therapy.

這意味著 127 名淨患者正在接受治療。

We believe the capabilities we continue to strengthen through the current launch will provide a current foundation from which to maximize potential future us launches of Pyrukynd and thalassemia in 2025 and in sickle cell disease in 2026. In closing, we are inspired and energized by the potential to bring a new therapy to this underserved patient populations around the world. With that, I will turn the call over to Cecilia.

我們相信，我們透過目前的推出繼續加強的能力將為我們未來在 2025 年最大程度地推出 Pyrukynd 和地中海貧血以及 2026 年鐮狀細胞疾病的潛在潛力奠定基礎。最後，我們對為世界各地得不到充分服務的患者群體帶來新療法的潛力感到鼓舞和充滿活力。這樣，我就把電話轉給塞西莉亞。

Thanks Tsveta. Our third quarter, 2024 financial results can be found in the press release we issued this morning, and more detail will be included in our 10-Q which will be filed later today. Let me now take a moment to provide some context and highlight a few key points. Third quarter, 2024 net Rican revenue was $9 million. An increase of 22% compared to the third quarter of 2023.

謝謝茨維塔。我們的 2024 年第三季財務業績可在我們今天上午發布的新聞稿中找到，更多詳細資訊將包含在今天稍後提交的 10-Q 報告中。現在讓我花點時間提供一些背景資訊並強調幾個關鍵點。2024 年第三季 Rican 淨收入為 900 萬美元。與 2023 年第三季相比成長 22%。

Consistent with other rare disease launches gross to net has been and is expected to be in the 10% to 20% range on an annual basis going forward. Aligned with our strategic shift towards preparing for the potential launch in thalassemia for PKD revenues. We expect to see new growth and quarter over quarter variability in line with what we have seen in recent quarters, cost of sales for the quarter was $0.8 million. R&D expenses were $72.5 million for the third quarter. A decrease of $9.4 million compared to the third quarter of 2023. This decrease was primarily driven by the $17.5 million upfront payment associated with the license agreement with an Islam which was recorded in the prior year.

與其他罕見疾病產品的推出一致，每年毛淨比預計將在 10% 至 20% 的範圍內。與我們的策略轉變一致，即為 PKD 收入在地中海貧血領域的潛在推出做準備。我們預計將看到新的成長和季度環比變化，與最近幾季的情況一致，本季的銷售成本為 80 萬美元。研發第三季費用為 7,250 萬美元。與 2023 年第三季相比減少 940 萬美元。這一下降主要是由於上一年記錄的與伊斯蘭教許可協議相關的 1,750 萬美元預付款所致。

SDNA expenses were $38.5 million for the third quarter, an increase of $12.7 million compared to the prior year quarter.

SDNA 第三季支出為 3,850 萬美元，比去年同期增加 1,270 萬美元。

This was primarily driven by an increase in commercial related activities as we prepare for the potential approval of Pyrukynd in Thalassemia in 2025.

這主要是由於商業相關活動的增加，因為我們正在為 2025 年 Pyrukynd 治療地中海貧血的潛在批准做準備。

Importantly, this quarter, we received a total of $1.1 billion in milestone payments. Following the FDA approval of vorasidenib.

重要的是，本季我們總共收到了 11 億美元的里程碑付款。FDA 批准 vorasidenib 後。

These payments include a $905 million payment from royalty farmer in connection with the vorasidenib royalty purchase agreement. A just announced in May 2024 as well as a $200 million payment from Servier in connection with a just dive of the oncology business in 2021 both of which were recorded under other income in the P&L as a reminder, agent will retain a 3% royalty on annual US net sales of work side and greater than $1 billion including this milestone payments we ended the quarter with cash, cash equivalents and marketable securities of approximately $1.7 billion. We expect that this balance together with anticipated product revenue and interest income will provide the financial independence to prepare for potential Pyrukynd launches in thalassemia and sickle cell disease, advance existing programs and opportunistically expand our pipeline through both internally and externally discovered assets.

這些付款包括與 vorasidenib 特許權使用費購買協議相關的特許權使用費農民支付的 9.05 億美元。2024 年5 月剛宣布的一項以及Servier 因2021 年腫瘤業務剛剛投入使用而支付的2 億美元款項均記錄在損益表的其他收入項下，作為提醒，代理商將保留3% 的特許權使用費美國年度工作淨銷售額超過 10 億美元，包括這一里程碑付款，本季末我們的現金、現金等價物和有價證券約為 17 億美元。我們預計，這種平衡連同預期的產品收入和利息收入將提供財務獨立性，為可能的Pyrukynd 在地中海貧血和鐮狀細胞病領域的推出做好準備，推進現有項目，並透過內部和外部發現的資產機會性地擴大我們的管道。

We remain focused on creating shareholder value including by proactively managing our cost base and deploying a disciplined cash allocation approach as we prepare to support potential future launches of Pyrukynd. As we move toward additional potential value creating milestones in the near term. I am confident that our balance sheet will continue to enable us to execute from a position of strength. I will now turn the call back over to Brian.

我們仍然專注於創造股東價值，包括在我們準備好支援未來可能推出的 Pyrukynd 時，積極管理我們的成本基礎並部署嚴格的現金分配方法。隨著我們朝著更多潛在價值邁進，在短期內創造里程碑。我相信，我們的資產負債表將繼續使我們能夠以強大的實力執行任務。我現在將把電話轉回給布萊恩。

Thanks Cecilia. Before we open the line for questions, I want to conclude with a few words, 2024 has been marked by exceptional progress at Agios. We continue to deliver on our key priorities and have a very strong financial position allowing us to maintain this great momentum in the final months of the year and beyond.

謝謝塞西莉亞。在我們開始提問之前，我想用幾句話來總結：2024 年 Agios 取得了非凡的進展。我們繼續實現我們的關鍵優先事項，並擁有非常強大的財務狀況，使我們能夠在今年最後幾個月及以後保持這一巨大勢頭。

In addition to its approved indication in PKD Mitapivat represents a significant opportunity to meaningfully elevate the standard of care for patients with thalassemia and sickle cell disease. We consistently hear firsthand from these communities that there is an immediate critical need for new regimens to treat these diseases.

除了在 PKD 中獲得批准的適應症外，Mitapivat 還為有意義地提高地中海貧血和鐮狀細胞疾病患者的護理標準提供了重要機會。我們不斷從這些社區直接聽到，迫切需要新的治療方案來治療這些疾病。

With this. We believe Mitapivat is poised to become a first and best in class treatment option for multiple indications translating into a franchise with multibillion dollar potential.

有了這個。我們相信，Mitapivat 有望成為多種適應症的首個也是同類最佳的治療選擇，並轉化為具有數十億美元潛力的特許經營權。

In addition to Mitapivat, we continue to drive our other promising clinical programs forward, focusing on areas where there is a high patient need and providing us with additional opportunities to create significant long-term value and impact for all stakeholders. We look forward to the future as we strive to change the trajectory of these rare diseases. With that, I'd like to open the call for questions, operator. Please open the line.

除了 Mitapivat 之外，我們還繼續推動其他有前途的臨床項目，重點關注患者需求量大的領域，並為我們提供額外的機會，為所有利益相關者創造重大的長期價值和影響。我們展望未來，努力改變這些罕見疾病的發展軌跡。接線員，我想開始提問。請打開線路。

Thank you. (Operator Instruction) our first question off line of Greg Harrison from Scotia Bank. Your line is open.

謝謝。 （操作員說明）我們的第一個問題來自豐業銀行的格雷格·哈里森（Greg Harrison）。您的線路已開通。

Hey, good morning. Thanks for taking the question and great to see all the progress. Two for me. First, how are you thinking about capital allocation and appetite for business development? Now that for side has been largely monetized, maybe there's a particular area you guys find attractive or complementary and then on sickle cell, maybe you can speak to expectations for the Phase 3 portion of the trial. And if you can comment on powering with respect to VLC.

嘿，早安。感謝您提出問題，很高興看到所有的進展。給我兩個。首先，您如何看待資金配置和業務發展意願？現在 for side 已經很大程度上貨幣化了，也許有一個特定領域你們覺得有吸引力或互補，然後在鐮狀細胞上，也許你們可以談談對試驗第三階段部分的期望。您是否可以評論一下 VLC 的供電情況。

Sure and Greg, welcome back. Great to hear you again. two parts. Well, Cecilia can handle the capital allocation question, then Sarah can take over for rise up phase three expectations.

當然，格雷格，歡迎回來。很高興再次聽到你的聲音。兩部分。那麼，Cecilia 可以處理資本分配問題，然後 Sarah 可以接手提高第三階段的期望。

Great. Thanks Greg. So in terms of capital allocation, we're of course, very proud of the strong balance sheet we have now. And in terms of how we think about that, our priorities, of course will be the potential launches for that. And then hopefully Sickle us and continuing to advance our pipeline, which you'll hear a little bit more about MDS today as well and then expanding that pipeline both internally and or externally, we're pretty disciplined and the amount of cash we have in the balance sheet doesn't change that. We look at things, you know, with our same criteria, we have in the past, in terms of being rare, transformative, have a clear regulatory path and obviously create value for, for a shareholder. So that hasn't changed. We, we continue to look at that and different areas we've said we are agnostic in terms of modality and we will keep looking to how we want to expand that.

偉大的。謝謝格雷格。因此，就資本配置而言，我們當然對現在擁有的強勁資產負債表感到非常自豪。就我們如何看待這一點而言，我們的首要任務當然是潛在的發布。然後希望 Sickle 我們並繼續推進我們的管道，今天您也會聽到更多有關 MDS 的信息，然後在內部和外部擴展該管道，我們非常有紀律，並且我們擁有大量現金資產負債表並沒有改變這一點。你知道，我們以我們過去相同的標準來看待事物，在稀有性、變革性方面，有明確的監管路徑，並且顯然為股東創造價值。所以這並沒有改變。我們，我們繼續關注這一點以及我們所說的我們在模式方面不可知的不同領域，我們將繼續尋找我們想要如何擴展它。

And then I'll turn it over to Sarah, but I do want to just lead in by saying how proud I am of Sarah and the team for this incredible consistent executional excellence. We are really pleased with the fact that even before today's call, we were able to announce complete enrollment of the Phase 3 study for rise up. And if you're keeping track, it's been about 12 months. And I think that says a lot about the profile, the trust the community has in us and again, very importantly, the executional excellence from the team. So with that, Sarah, how about that as a set up?

然後我會把它交給莎拉，但我確實想先說一下，我為莎拉和團隊如此令人難以置信的一致卓越執行力感到多麼自豪。我們非常高興的是，甚至在今天的電話會議之前，我們就能夠宣布 3 期研究的完成註冊。如果你仔細觀察的話，已經過了大約 12 個月。我認為這充分說明了我們的形象、社群對我們的信任，以及非常重要的團隊的卓越執行力。那麼莎拉，這樣的安排呢？

Thank you, Brian. Thanks for the question.

謝謝你，布萊恩。謝謝你的提問。

So yes, so we are very proud of the rise up team. We indeed accomplished complete enrollment, which was one of our milestones for this year. So, are very excited about that and are now looking forward to you know, to finish the trial to get it to the end. So the expectations for Phase 3. So it's a one year duration. We have two primary end points, one is hemoglobin response. The other one is sickle cell pain crisis reduction. And that is with the goal to try to deliver a drug that can hit on the totality of sickle cell disease, meeting both hemolytic anemia and vaso occlusion improvements, both endpoints are powered to have 90% or slightly more. So to be able to detect that difference. So we're very excited about this and are looking forward to the end of the trial.

所以，是的，我們為崛起團隊感到非常自豪。我們確實完成了全部註冊，這是我們今年的里程碑之一。因此，我們對此感到非常興奮，現在期待完成試驗以取得最終結果。所以對第三階段的期望。所以它的持續時間是一年。我們有兩個主要終點，一個是血紅素反應。另一種是減少鐮狀細胞疼痛危機。我們的目標是嘗試提供一種可以治療所有鐮狀細胞疾病的藥物，同時滿足溶血性貧血和血管閉塞改善的要求，這兩個終點都有望達到 90% 或稍高。所以能夠偵測到這種差異。因此，我們對此感到非常興奮，並期待試驗的結束。

Great, thanks so much.

太好了，非常感謝。

Our next question line of Danielle Brill from Raymond James. Your line is open.

我們的下一個問題是雷蒙德詹姆斯 (Raymond James) 的丹妮爾布里爾 (Danielle Brill)。您的線路已開通。

Hey guys, this is Alex on for Danielle. Thanks for taking our question. Another one on Rise Up. Can you talk a little bit about your primary endpoints in the Rise Up study? Do you think you need to hit on both end points or will success on just one support a regulatory filing? For example, is it possible that hitting on hemoglobin response and another secondary clinical endpoint like fatigue could support a regulatory filing? Thank you so much.

大家好，我是亞歷克斯為丹妮爾代言。感謝您提出我們的問題。另一張是《崛起》。您能談談 Rise Up 研究中的主要終點嗎？您認為您是否需要同時滿足兩個端點，或僅在一個支援監管備案上就能成功？例如，血紅素反應和疲勞等另一個次要臨床終點是否有可能支持監管備案？太感謝了。

So, thanks for the question. So yes, we have two primary end points. One being hemoglobin, as I just mentioned and then the other one focused on VOCS. We did choose the two primary end points because they can provide relevant information for the totality of the disease. So in a situation in which we would not be able to hit on one end point, but only with it on the other end point, we still have an opportunity to transfer alpha to secondary endpoint testing, which would allow us to further look for a clinical benefit. One of those endpoints is indeed fatigue. We always try to deliver with our drug across the different hemolytic anemias that we have studied the hemoglobin plus story that we improve hemolytic anemia, but then also try to hit on feel and function. And we've been able to deliver to that on PKD and thalassemia highlighting an improvement in fatigue. Our thalassemia data also highlighted that there was an improvement in the six minute walk test. And so our rise up study is set up in a similar way to to provide, multiple ways that we can speak to clinical benefit for sickle cell disease patients in regard to what is needed for regulatory approval. That is the regulators who look at the clinical trial data at the end of the package. Of course, when we submit, we believe that there is a benefit risk profile that supports approval. But it's ultimately the regulators that do the review and decide on approval.

所以，謝謝你的提問。所以是的，我們有兩個主要終點。正如我剛才提到的，其中一個是血紅蛋白，另一個是 VOCS。我們確實選擇了兩個主要終點，因為它們可以提供整個疾病的相關資訊。因此，在我們無法擊中一個端點，而只能擊中另一個端點的情況下，我們仍然有機會將 alpha 轉移到輔助端點測試，這將使我們能夠進一步尋找臨床獲益。這些終點之一確實是疲勞。我們總是嘗試用我們的藥物來治療不同的溶血性貧血，我們研究了血紅蛋白加上我們改善溶血性貧血的故事，但也嘗試著擊中感覺和功能。我們已經能夠在 PKD 和地中海貧血方面實現這一目標，並強調疲勞的改善。我們的地中海貧血數據也強調，六分鐘步行測試有所改善。因此，我們的上升研究以類似的方式進行，以提供多種方式，我們可以透過監管批准所需的內容來談論鐮狀細胞疾病患者的臨床益處。監管機構會查看一攬子計劃末尾的臨床試驗數據。當然，當我們提交時，我們相信存在支持批准的利益風險概況。但最終是由監管機構進行審查並決定是否批准。

I would like to add. And this is again, echoing not just the point of executional excellence, but also the scientific expertise from the team that everything that Sarah just went through was actually outlined in a poster in 2021. In other words, we didn't change the design from day one. It's been set up this way. And I think that's important particularly in the context of the recent evolution in sickle cell disease with other therapeutic options. And we're very proud of the fact that from day one, we had a design that was intended to be a so-called hemoglobin plus design.

我想補充一下。這再次呼應了卓越執行力的觀點，也呼應了團隊的科學專業知識，莎拉剛剛經歷的一切實際上都在 2021 年的海報中概述了。換句話說，我們從第一天起就沒有改變設計。就這樣設定了。我認為這一點尤其重要，尤其是在鐮狀細胞疾病與其他治療方案最近演變的背景下。我們感到非常自豪的是，從第一天起，我們的設計就是所謂的血紅素加設計。

Our next question will come from line of Greg Renza from R BC capital Markets. Your line is open.

我們的下一個問題將來自 R BC 資本市場的 Greg Renza。您的線路已開通。

Great, good morning, Brian and team congrats on the progress and thanks for taking my question. Brian, you, you've commented on just the trust that you've earned with respect to the, the community on the execution and the value that you're providing in the development program for permitted pivot with Sickle cell. Just curious if you can comment on the general feedback, the potential for mistrust from the community just given the brighter withdrawal and the happenings that, that you alluded to there. What is doing to at least track that detect that and sort of incorporate that into your go forward with the trial and also how you are touching patients and just secondarily, have you had any communications or plan to with regulatory, just on the potential risks that have been sort of highlighted about running trials in the Africa site. Thanks so much and congrats.

太好了，早上好，布萊恩和團隊祝賀我們的進展，並感謝您提出我的問題。Brian，你，你剛剛評論了你在執行方面贏得的社區信任，以及你在鐮狀細胞許可樞軸開發計劃中提供的價值。只是好奇您是否可以對一般反饋發表評論，考慮到您提到的更光明的撤回以及您在那裡提到的事件，社區可能會產生不信任。正在做什麼至少追蹤檢測到的情況並將其納入您的試驗進展以及您如何接觸患者，其次，您是否與監管機構進行了任何溝通或計劃，只是關於潛在的風險關於在非洲站點進行試驗的情況已經得到了強調。非常感謝並祝賀。

Yeah, thanks a lot, Greg. I, it's an important question that you ask because the sickle cell disease community, I think not surprisingly to anybody has been through a lot. It's always been limited treatment options that have been available and the community at large has certainly gone through a journey of drugs available and then not available in certain regions. And it's a real challenge.

是的，非常感謝，格雷格。我，這是你問的一個重要問題，因為鐮狀細胞病界，我認為任何人都經歷了很多事情，這並不奇怪。可用的治療選擇始終有限，整個社區肯定經歷了藥物可用但在某些地區無法使用的過程。這是一個真正的挑戰。

And an example of what we do is Sarah and I and others from the team just attended the annual Sickle Cell Disease Association of America meeting in Atlanta. it was a chance for us to listen most importantly and hear what's on their mind, what their concerns are and how they think about treatment options in the future and again, just to echo what I'm very proud of is we have always looked to maintain high touch with the community and an example of that goes all the way back to when we designed the rise up trial we very deliberately involved members of the sickle cell warrior community and the input that we got was not just in the trial design inclusion exclusion criteria, but very importantly how to appropriately recruit for the trial.

我們所做的一個例子是莎拉和我以及團隊的其他人剛剛參加了在亞特蘭大舉行的美國鐮狀細胞疾病協會年度會議。對我們來說，最重要的是，這是一次傾聽他們的想法、他們的擔憂是什麼以及他們如何看待未來治療方案的機會，只是為了呼應我感到非常自豪的一點，那就是我們一直在尋求與社區保持高度接觸，這方面的一個例子可以追溯到我們設計崛起試驗時，我們非常刻意地讓鐮狀細胞戰士社區的成員參與進來，我們得到的意見不僅僅是在試驗設計納入排除中標準，但非常重要的是如何適當地招募試驗人員。

And now you've seen the results of that. It recruited beautifully. and then hopefully, when we get to the point of commercialization, we're leaning on that community to guide us in that regard as well. So I think the main message about trust is we try to be very visible. We listen without bias, and we make sure that the community sees their fingerprint on what we do based on the input that they've provided.

現在你已經看到結果了。它招募得很漂亮。希望當我們達到商業化時，我們也能依靠該社區在這方面指導我們。所以我認為關於信任的主要訊息是我們努力讓自己變得非常引人注目。我們不帶偏見地傾聽，並確保社區根據他們提供的意見了解我們所做的事情。

Yes. And then to add to that in regards to going forward with the trial. So we continue to you know, it's a Phase 3 trial. So obviously, we do monitoring of data as we go along, we do all of our standard procedures to make sure that we continue to execute well on this trial. And we'll continue to watch carefully as this trial evolves. And in regards to potential risk for sickle cell disease, specifically with running clinical trials, you know, it's a tough devastating disease in which patients are suffering from a ton of comorbidities and it's a deadly disease. So there's always challenges when you run a trial like this, but it speaks to the unmet need in this patient population. So while these trials are challenging and difficult, there's such a met need in this patient population that we, that we really hope to be able to deliver a drug that can be meaningful for the patient community and treat the fatality of the disease.

是的。然後補充一下有關審判進展的情況。所以我們繼續告訴您，這是第三階段試驗。顯然，我們在進行過程中會監控數據，我們會執行所有標準程序，以確保我們在這次試驗中繼續良好執行。我們將繼續密切關注該試驗的進展。關於鐮狀細胞疾病的潛在風險，特別是進行臨床試驗時，您知道，這是一種嚴重的破壞性疾病，患者患有大量合併症，並且是一種致命的疾病。因此，當您進行這樣的試驗時總是會遇到挑戰，但這說明了該患者群體的需求未得到滿足。因此，雖然這些試驗充滿挑戰和困難，但我們確實希望能夠提供一種對患者群體有意義的藥物，並治療這種疾病的致命性，從而滿足了該患者群體的需求。

Just maybe one more point on this to drive it home is Sarah and I also had a call with members of the sickle cell disease warrior community, actually part of the advocacy group that I just talked about. And on that call, there were seven members of the community.

也許還有一點可以讓我明白這一點，莎拉，我還與鐮狀細胞病戰士社區的成員通了電話，他們實際上是我剛才談到的倡導小組的一部分。在那次電話會議上，有七名社區成員。

And among that three of them were in crisis or recently had a crisis. And we walked away with a sobering reminder about just how serious this disease is and how desperate the community is for new therapeutic options, and it should be plural form. We always cheer for progress from everybody because this is a disease that needs multiple options.

而這其中，有三人正處於危機之中，或者是最近遭遇了危機。我們帶著一個發人深省的提醒離開，提醒我們這種疾病有多嚴重，以及社區對新的治療選擇有多絕望，而且它應該是複數形式。我們總是為每個人的進步而歡呼，因為這是一種需要多種選擇的疾病。

Our next question line of Eric Schmidt from Cantor Fitzgerald, your line is open.

我們的下一個問題是來自 Cantor Fitzgerald 的 Eric Sc​​hmidt，您的線路已開通。

Well, thanks for all the updates and for taking my question. Just sticking with this topic of the unfortunate withdrawal of VRS about a month ago. What have you learned scientifically or what kind of thoughts do you have scientifically with regard to, you know, the mechanism of that drug and, and how it relates or doesn't relate to the PVAD and how it sort of maybe influences your chances of success in the ongoing study. Thank you.

嗯，感謝您的所有更新並提出我的問題。繼續討論大約一個月前 VRS 不幸退出的話題。您從科學上學到了什麼，或者您對這種藥物的機制有什麼科學的想法，以及它與 PVAD 的關係或無關性，以及它如何影響您的機會正在進行的研究取得成功。謝謝。

So thanks for the question. Well, as you know, right, has a very different mechanism of action and we feel it should start like we really feel sad about what happened and to Brian's earlier point, it's, it's a sad circumstance, right? Because this patient community really has barely any options. So we're sad to see this.

謝謝你的提問。嗯，正如你所知，對，有一個非常不同的作用機制，我們覺得它應該開始，就像我們真的對發生的事情感到悲傷一樣，對於布萊恩之前的觀點，這是一個悲傷的情況，對嗎？因為這個患者群體實際上幾乎沒有任何選擇。所以我們很遺憾看到這一點。

It is a very different mechanism of action of the clinical trials were set up differently as well. So I think that is we don't know what happens beyond what has been publicly declared.

這是一個非常不同的作用機制，臨床試驗的設定也不同。所以我認為我們不知道除了公開宣布的事情之外還會發生什麼。

But then focusing on our trial, our drug works very differently and have that multimodal approach to treating potentially treating sickle cell disease. So we do reduce 23 DPG and increase ATP. And we think both of these components can interplay and be important to avoid sickling and to improve hemolysis and thereby the anemia component. So very different mechanism of action than RISA, which then also of course, translates into the clinical data that we have seen so far with a very, with a Phase 2 clinical trial data set that was very robust, a placebo-controlled trial. And that mechanism of action has translated into us demonstrating an improvement on hemoglobin. And then also observing that positive trend for hemolysis and VOC reduction. So we are excited to continue to progress this the drop forward in this history.

但接下來關注我們的試驗，我們的藥物的作用非常不同，並且採用多模式方法來治療潛在的鐮狀細胞疾病。所以我們確實減少了 23 DPG 並增加了 ATP。我們認為這兩種成分可以相互作用，對於避免鐮狀形成和改善溶血從而改善貧血成分非常重要。與 RISA 的作用機制非常不同，當然，這也轉化為我們迄今為止所看到的非常可靠的 2 期臨床試驗數據集的臨床數據，這是一項安慰劑對照試驗。這種作用機制已轉化為我們展示血紅蛋白的改善。然後也觀察到溶血和 VOC 減少的正面趨勢。因此，我們很高興能夠繼續推動這一歷史性的進步。

Our next question will come from line of Chris Raymond from Piper Sandler, your line is open.

我們的下一個問題將來自 Piper Sandler 的 Chris Raymond 專線，您的專線已開放。

Thanks for taking the question and congrats to you guys. And maybe just another question with regard to the [xray] situation I Know you talked about engaging the sickle cell community but, this is a question that's come up with investors a lot and I'm not sure if there's a real good answer here. But do you have a sense as to how the regulatory perspective has changed on this? there's some debate that perhaps has made it, you know, raise the bar, and then another debate that perhaps it's actually lowered the bar in term of another therapy on the market. Just any sense there for how you regulators might have re be reacting to this.

感謝你們提出問題並祝賀你們。也許只是關於 [X 射線] 情況的另一個問題，我知道您談到了讓鐮狀細胞社區參與進來，但是，這是投資者經常提出的一個問題，我不確定這裡是否有真正好的答案。但您是否知道監管觀點對此有何變化？你知道，有一些爭論可能提高了標準，然後另一場爭論可能實際上降低了市場上另一種療法的標準。監管機構可能對此有何反應？

And I think so thanks for that question because I think Brian actually touched upon it like with the poster that we presented in 2021 which was a trial design or Phase 3 from the get-go, we had a very different clinical development approach plus a regulatory approach than the pathway that Oxbryta followed. So Oxbryta had and accelerated approval and by demonstrating hemoglobin improvement at the time of submission and then had to follow on studies to further demonstrate clinical benefits. Our goal from when we first designed this trial is to deliver a treatment that at the end of the clinical trial can speak to clinical meaningful benefit, meaning hemoglobin and sickle crisis reduction. So, based on what happened, we have not changed our approach to our clinical design or our approach to the regulators, as I mentioned earlier, for any data package you submit, it's always a collaboration with the regulators after they review the first package and then they'll ask us more questions and ultimately, they get to decide on the ultimate benefit risk.

我認為非常感謝這個問題，因為我認為布萊恩實際上談到了這個問題，就像我們在2021 年展示的海報一樣，這是一個試驗設計或從一開始的第3 階段，我們有一個非常不同的臨床開發方法加上監管方法比 Oxbryta 遵循的途徑更重要。因此，Oxbryta 在提交時證明了血紅蛋白的改善，並加速了批准，然後必須進行後續研究以進一步證明臨床益處。從我們最初設計這項試驗開始，我們的目標就是提供一種治療方法，在臨床試驗結束時能夠帶來臨床上有意義的益處，這意味著減少血紅蛋白和鐮刀危象。因此，根據所發生的情況，我們沒有改變我們的臨床設計方法或與監管機構的方法，正如我之前提到的，對於您提交的任何資料包，始終是在監管機構審查第一個資料包後與監管機構合作，然後他們會問我們更多問題，最終他們決定最終的利益風險。

Our next question come from the line of Tessa Romero from JP Morgan. Your line is open.

我們的下一個問題來自摩根大通的泰莎·羅梅羅。您的線路已開通。

Good morning, Brian and team. Thanks so much for taking our question. So switching gears a little bit to thalassemia you outlined this morning, several patient groups in your slide deck that are part of your initial launch focus for Pyrukynd.

早上好，布萊恩和球隊。非常感謝您提出我們的問題。因此，稍微切換一下您今天早上概述的地中海貧血症，幻燈片中的幾個患者組是 Pyrukynd 最初發布重點的一部分。

Are you able to provide a little bit more specific quantitative detail around how the epidemiology breaks out in terms of patient numbers and each of these three key target populations you mentioned. And how often are these patients generally seeing their health care provider across these three key groups? Thanks so much.

您能否提供一些更具體的定量細節，以了解流行病學在患者數量和您提到的這三個關鍵目標人群方面的爆發情況。這些患者通常多久見一次這三個關鍵群體的醫療保健提供者？非常感謝。

Thanks, Tessa. I'm just going to start by saying that you're making Tsveta a smile because we love the questions on sickle cell disease. We're very excited about the potential with a potential launch scenario in 2026 but even closer is thalassemia where we've consistently a message that we're looking forward to this potential launch in 2025. So I'm going to let that take over on your questions.

謝謝，泰莎。我首先要說的是，您讓茨維塔微笑了，因為我們喜歡有關鐮狀細胞疾病的問題。我們對 2026 年可能推出的方案感到非常興奮，但更接近的是地中海貧血，我們一直在傳達這樣的訊息：我們期待在 2025 年推出這項可能的方案。所以我將讓它來回答你的問題。

Absolutely. Thanks for the question. We are very excited with the potential of having an approval for thalassemia next year and actively preparing for launch. When we think about thalassemia it's an indication, it's a beautiful area, these indications when it comes to commercialization for three main reasons.

絕對地。謝謝你的提問。我們對明年有望獲得地中海貧血症的批准感到非常興奮，並積極準備上市。當我們想到地中海貧血時，它是一個適應症，這是一個美麗的領域，這些適應症在商業化方面有三個主要原因。

The first thing is that we know that there are 6,000 adults diagnosed with thalassemia in the US. And I'm going to underline diagnose here because these patients are known and engaged to the health care system. And we know that that's the case because there are ICD 10 codes available which allows us to effectively and efficiently deploy our resources when it comes to launch preparation.

首先，我們知道美國有 6,000 名成年人被診斷出患有地中海貧血。我要在這裡強調診斷，因為這些患者是已知的並且參與醫療保健系統。我們知道情況確實如此，因為有可用的 ICD 10 程式碼，這使我們能夠在啟動準備時有效且有效率地部署我們的資源。

We talked a lot about sickle cell disease and the high unmet need there. But that's also very, very true for thalassemia as well. The unmet need is known and and we continue to engage both with patients and physicians in our prelaunch efforts to continue to educate them on the burden of disease. When it comes to which patients will be considered for our initial launch focus first, as you mentioned, we believe that about 65% of the 6,000 patients will be our focus for initial launch.

我們談論了很多關於鐮狀細胞疾病和那裡未滿足的高度需求。但這對地中海貧血來說也是非常非常正確的。未滿足的需求是眾所周知的，我們將繼續在啟動前的工作中與患者和醫生合作，繼續教育他們了解疾病的負擔。當談到我們將首先考慮哪些患者作為我們首次啟動的重點時，正如您所提到的，我們相信 6,000 名患者中約 65% 將成為我們首次啟動的重點。

And these patients are three groups of patients. These are patients that are very actively engaged with the healthcare system. The first one is the transfusion dependent patients who are going frequently for their transfusions and I have an engagement with their hematologist. That depends on their transfusion frequency, but more or less you can say that they are seeing and engage with the health care system is probably on a monthly basis. The second group of patients are the Non transfusion dependent patients who have already developed comorbidities. They require frequent monitoring and management. It depends on the specific patient population and the frequency there. But we know both from claims data and our initial account profiling that these patients are relatively regularly seen and they will be considered for management and and and further monitoring as well.

而這些患者又分為三組患者。這些患者非常積極參與醫療保健系統。第一個是依賴輸血的患者，他們經常接受輸血，我與他們的血液科醫生接觸了。這取決於他們的輸血頻率，但或多或​​少你可以說他們可能每月都會看到並參與醫療保健系統。第二組患者是已經出現合併症的非輸血依賴患者。他們需要頻繁的監控和管理。這取決於特定的患者群體和頻率。但從索賠數據和初步帳戶分析我們知道，這些患者相對經常就診，我們將考慮對他們進行管理和進一步監測。

And the third part of the patient population which comprises the 65% are the Non transfusion dependent patients who are experiencing debilitating fatigue. It's impacting their daily life and they will be seeking for a potential treatment option as well. We haven't provided specific details on this patient population, but as the launch progresses, we'll be providing additional information as well.

患者群體中的第三部分（佔 65%）是非輸血依賴患者，他們正在經歷衰弱性疲勞。這正在影響他們的日常生活，他們也會尋求潛在的治療選擇。我們尚未提供有關該患者群體的具體詳細信息，但隨著發布的進展，我們也將提供更多資訊。

And I'll just add too. I mean, Tsveta with all of her rare disease launch experience is the first to remind us that launch sometimes is a sort of odd term because it's not a point in time, it's a continuum. So even on this guidance with the sequencing, if we could say it that way of segments will continue, that is constantly working on keeping the team ahead of segment one, segment two, etcetera. And we expect to be you know, progressing for the long term in thalassemia and then again, hopefully in sickle cell disease as well.

我也補充一下。我的意思是，茨維塔（Tsveta）憑藉她所有罕見疾病發布經驗，第一個提醒我們，發布有時是一個奇怪的術語，因為它不是一個時間點，而是一個連續體。因此，即使按照這個排序指導，如果我們可以說分段方式將繼續下去，那就是不斷努力保持團隊領先於第一分段、第二分段等。我們希望在地中海貧血症方面取得長期進展，並希望在鐮狀細胞疾病方面也能取得進展。

Okay, great. Thanks so much for taking our question.

好的，太好了。非常感謝您提出我們的問題。

Our next question is Line of Davio Rao from TD. Kend. Your line is open.

我們的下一個問題是來自 TD 的 Davio Rao。肯德。您的線路已開通。

Good morning team. This is Davio for Mark. Thanks for taking our questions. Want to stay on Thia, would you be able to discuss how you're thinking about timing and design of the pediatric trials? Now that we have at least initial data or the top line data from the kids trial and PKD. And then our second question is the initial data at [T pivot] and MDS. It obviously shared a little bit of signal but it was relatively modest for the five-meg dose. Could you talk about what you think the bar for success is for the Phase 2B? Now that you're looking at dose levels that are higher than the initial dose tested? Thank you.

早上好，團隊。這是馬克的達維奧。感謝您回答我們的問題。想留在 Thia，您能談談您對兒科試驗的時間安排和設計的看法嗎？現在我們至少有了兒童試驗和 PKD 的初始數據或頂線數據。然後我們的第二個問題是[T樞紐]和MDS的初始資料。顯然它共享了一點信號，但對於五兆劑量來說相對適中。您能否談談您認為 2B 階段成功的標準是什麼？現在您正在考慮高於初始測試劑量的劑量等級？謝謝。

Thanks Davio. So for thalassemia, the pediatric trials. Yes. So indeed, we are very proud of the first PKD pediatric trial in which we were able to demonstrate that some Children experience transfusion independence. So we're very pleased to see that because that's definitely clinically meaningful for the timing and the design of the trial. So we are now also now have the benefit risk profile in the thalassemia adult patient population. So you can expect a similar approach from us as what we have taken for PKV. We have not gone into further detail on the timing of when we would initiate. So that more to come at a later time point in regards to MDS. Yes, we did meet our pre specified criteria for the phase 2A in which we observed 40% of transfusion independent in the patient population. We had enrolled. And to your point, we did learn there that the, the PK in MDF patients was different than what we had observed in healthy volunteers. So that of course, led to changes for our phase 2B. And as you see, we have moved forward with the phase 2B testing higher doses, three higher doses to be able to hopefully strengthen the observations that we had observed and are focused on transfusion independence in that trial and an eight week or more transfusion independence based on clinical advisory feedback that we received. So, are excited to progress that trial and more to come.

謝謝達維奧。對於地中海貧血，兒科試驗也是如此。是的。事實上，我們對第一個 PKD 兒科試驗感到非常自豪，在該試驗中我們能夠證明一些兒童具有輸血獨立性。所以我們很高興看到這一點，因為這對試驗的時機和設計絕對具有臨床意義。因此，我們現在也了解了地中海貧血成人患者群的獲益風險概況。因此，您可以期待我們採取與 PKV 類似的方法。我們尚未詳細說明啟動時間。因此稍後會提供更多有關 MDS 的資訊。是的，我們確實滿足了 2A 期預先指定的標準，其中我們觀察到患者群體中有 40% 的輸血獨立。我們已經報名了。就您的觀點而言，我們確實了解到 MDF 患者的 PK 與我們在健康志願者中觀察到的不同。當然，這導致了我們 2B 階段的變化。正如你所看到的，我們已經推進了2B 期測試，測試了更高的劑量，三個更高的劑量，希望能夠加強我們觀察到的觀察結果，並重點關注該試驗中的輸血獨立性，以及基於八週或更長時間的輸血獨立性。因此，我們很高興能取得該試驗的進展以及未來的更多試驗。

And we are, we're very excited about the potential in MDS. I know folks pay attention to others who are in this market. And we took note this morning of the continued progress that we see with [rev WASO] and it's a rapidly growing market. There is very high on that need. It's similar in a way to sickle cell disease and that multiple therapeutic options will be the answer. And we're very proud of the fact that we have a very differentiated mechanism. So this is an important step for us to be able to start the phase two B.

我們對 MDS 的潛力感到非常興奮。我知道人們會關注這個市場上的其他人。今天早上我們注意到 [rev WASO] 所取得的持續進展，這是一個快速成長的市場。這種需求非常高。它在某種程度上與鐮狀細胞疾病相似，多種治療選擇將是答案。我們非常自豪我們擁有一個非常差異化的機制。因此，這是我們能夠啟動第二階段 B 的重要一步。

Our next question, the line of Alex Shanahan from Bank of America. Your line is open.

我們的下一個問題是來自美國銀行的亞歷克斯·沙納漢 (Alex Shanahan)。您的線路已開通。

Hey guys, thanks for taking our questions. Two from me. First on the thalassemia launch prep given it is a continuum as Brian said, wonder if you have a sense as to how quickly payer access could come online. And would you say payers are fairly aware of Mitapivat clinical profile and its unmet need or maybe some more work to do there? And then on the upcoming full readout for energize t should we expect any additional efficacy data from the readout beyond what was showed shown in the top line? I guess where would you direct people's attention in the next update? And it seems like Ash is probably the next most likely venue, right? Thank you.

嘿夥計們，感謝您提出我們的問題。我的兩個。首先，考慮到地中海貧血症的推出準備工作是一個連續體，正如布萊恩所說，想知道您是否知道付款人訪問可以多快上線。您是否認為付款人相當了解 Mitapivat 的臨床概況及其未滿足的需求，或者可能還需要做更多的工作？然後，在即將推出的 Energize 完整讀數中，我們是否應該預期讀數中除了頂行顯示的數據之外還有任何其他功效數據？我想在下次更新中你會把人們的注意力引向哪裡？看來艾什可能是下一個最有可能的地點，對吧？謝謝。

Thanks Alex. And so I can start with the question on the payers and the Tsveta you want and then Sarah can take over with energized.

謝謝亞歷克斯。所以我可以從關於付款人和你想要的 Tsveta 的問題開始，然後莎拉可以充滿活力地接手。

Absolutely. Thanks Alex. It's a very good and relevant question. So from a fairer perspective, probably as you've seen from the slides and what we communicate to get to today. The market access is a core fever. In our launch preparation, our market access team is already engaging with payers on disease, state education. When you look at telos and you put a pair lens on it, it's a rare disease, there is a relatively low awareness of the disease. So we are definitely educating on the disease, but on the positive side of it is that it's a rare disease. And and we don't expect that to be high on the the payer radar for management as well. So the team is preparing for launch. I must say we had an excellent outcome in our access efforts from PK deficiency. We have a very strong team and we continue to see the same success and progress moving forward with the lamia.

絕對地。謝謝亞歷克斯。這是一個非常好的且相關的問題。因此，從更公平的角度來看，可能正如您從幻燈片以及我們今天所傳達的內容中看到的那樣。市場准入是核心發熱。在我們的啟動準備過程中，我們的市場准入團隊已經與付款人就疾病和國家教育問題進行了接觸。當你戴上一副鏡片觀察telos時，你會發現這是一種罕見的疾病，人們對這種疾病的認識相對較低。所以我們肯定是在對這種疾病進行教育，但積極的一面是它是一種罕見的疾病。而且我們預計這也不會成為付款人管理階層關注的重點。因此，團隊正在準備發布。我必須說，我們在 PK 缺陷的准入工作中取得了出色的成果。我們擁有一支非常強大的團隊，我們將繼續看到 Lamia 取得同樣的成功和進步。

Great and then Sarah for energize T.

太棒了，然後莎拉為 T 注入了活力。

Yes, for energized T. So we in our press release, you know that we've declared our primary end point plus one of the secondary end points. So you can expect from us typical to how we do all of our phase 3 readouts and intent to treat analysis with the details around key secondary endpoints as well in the safety overview. Indeed, we're hoping to be able to present at an upcoming medical meeting. Ash is currently not, available yet. So, you know, abstract will be released on November 5th. So we are eagerly waiting for that as well.

是的，對於充滿活力的 T。因此，您可以期待我們典型地了解我們如何進行所有第 3 階段的讀數，以及如何利用關鍵次要終點的詳細資訊以及安全性概述來處理分析。事實上，我們希望能夠在即將召開的醫學會議上發表演說。Ash 目前還沒有可用。所以，你知道，摘要將於 11 月 5 日發布。所以我們也熱切地等待著。

Our next question will come from the line of Salveen Richter from Goldman Sachs. Your line is open.

我們的下一個問題將來自高盛的 Salveen Richter。您的線路已開通。

Hi, this is Lydia on for Salveen and thanks so much for taking our question and congrats on all the progress. Just two quick ones from us. So on Sickle Cell. Now that enrollment is complete, are you able to provide any details on the number of baseline VOC's and then just on Tebapivat, can you just discuss when you plan to share data from the phase 2B and just remind us what will be included with this update? Thank you so much.

大家好，我是 Salveen 的 Lydia，非常感謝您提出我們的問題，並祝賀我們取得的所有進展。我們只有兩個快的。所以關於鐮狀細胞。現在註冊已完成，您是否能夠提供有關基線 VOC 數量的任何詳細信息，然後僅在 Tebapivat 上，您能否討論一下您計劃何時共享 2B 階段的數據，並提醒我們此更新中將包含哪些內容？太感謝了。

So for sickle cell disease, we do not present baseline characteristics, we typically tend to present everything when we release the top line results. So nothing to come before we provided the full data read out. And then in regards to Tebapivat and the Mitapivat Phase 2B, we have obviously now met our corporate milestone for this year. So we are looking forward to provide more detail and timing on the rest of the trial next year.

因此，對於鐮狀細胞疾病，我們不提供基線特徵，我們通常傾向於在發布頂線結果時提供所有內容。因此，在我們提供完整的數據讀出之前，沒有什麼可做的。至於 Tebapivat 和 Mitapivat 2B 期，我們現在顯然已經達到了今年的公司里程碑。因此，我們期待在明年提供有關試驗其餘部分的更多細節和時間安排。

Our next question will come. The line of Andrew Barons from Lein partners. Your line is open.

我們的下一個問題就來了。Lein Partners 的 Andrew Barons 系列。您的線路已開通。

I think the two for me. On 946, I think he does some patients in the phase 2A trial higher than the 5 mg.

我認為這兩個對我來說。關於946，我認為他在2A期試驗中對某些患者的劑量高於5毫克。

If that's correct. We see those data presented somewhere. And can you remind me of how much headroom you think you have on dosing before you might hit ADLT? And then I think this was touched on a bit, but we've heard that there was a problem with sepsis and malaria and the African trial sites. And some investors think that this was related to problems and conduct at those sites. I think your trial is at some of those sites. And can you give us some color on what's being done to ensure that a similar problem doesn't occur? Thanks.

如果這是正確的。我們在某處看到這些數據。您能否提醒我一下，您認為在達到 ADLT 之前您還有多少劑量空間？然後我認為這有點被觸及，但我們聽說敗血症和瘧疾以及非洲試驗地點存在問題。一些投資者認為這與這些網站的問題和行為有關。我認為您的試用是在其中一些網站上進行的。您能否告訴我們為確保不會發生類似問題而採取的措施？謝謝。

Thanks, Andrew. I'm going to let Sarah go, but I did want to first say you asked in terms of 946 and we're practicing on our end to say Tebapivat. We're very proud of the new INN that we have for our second more potent PK activator. And Sarah, you want to start with the Phase 2A.

謝謝，安德魯。我要讓莎拉走，但我確實想先說你用 946 來問，我們正在練習說 Tebapivat。我們對第二個更有效的 PK 活化劑的新 INN 感到非常自豪。莎拉，你想從 2A 階段開始。

So the, the phase 2A tested the 5 mg dose and so we did not test higher doses in that phase 2A. So right now, the higher doses that are being tested is in the phase 2B portion of the trial, which is 1mg,15mg and 20 mg in regards to when I expect to hit the DLTII, I don't know because we haven't gathered the data yet. So the data will accrue over time and then we'll see if we observe anything that makes us not want to further explore a certain dose. So, more to come on that in regards to what you asked for Mitapivat and malaria observed in the Oxbryta trials. So, malaria is endemic in certain regions of the world. We have part of our trials and R&D conducted in, in Africa as well. But we have a very good geographical distribution across the board within rise up. So we are excited about that. The observations that have happened on Oxbryta are not observations that have happened on hydroxyurea, for instance, that have been observed in Africa. So I think our data will accrue over time and, and we'll, we'll observe when we have the final trial.

因此，2A 期測試了 5 毫克劑量，因此我們沒有在 2A 期測試更高劑量。所以現在，正在測試的更高劑量處於試驗的 2B 階段，即 1 毫克、15 毫克和 20 毫克，關於我預計何時達到 DLTII，我不知道，因為我們還沒有尚未收集數據。因此，數據會隨著時間的推移而積累，然後我們將看看是否觀察到任何使我們不想進一步探索特定劑量的東西。因此，關於您要求的 Mitapivat 和 Oxbryta 試驗中觀察到的瘧疾，還有更多內容。因此，瘧疾在世界某些地區流行。我們的部分試驗和研發也在非洲進行。但我們在上升過程中擁有非常好的地理分佈。所以我們對此感到興奮。在 Oxbryta 上發生的觀察結果與在非洲觀察到的羥基脲發生的觀察結果不同。因此，我認為我們的數據會隨著時間的推移而積累，並且我們會在進行最終試驗時進行觀察。

Thanks Sandy.

謝謝桑迪。

And this includes our Q&A and I'll turn it over to Brian for any final remarks.

這包括我們的問答，我將把它交給布萊恩，讓他發表最後的評論。

All right. Thanks a lot Victor and thank you very much everyone for participating in today's call. It is clear, this is a very exciting time at Agios. We, we truly believe that we're poised to deliver transformative new therapies for patients and to create significant long-term value for shareholders. So thanks again and we look forward to speaking with you again soon.

好的。非常感謝維克多，也非常感謝大家參加今天的電話會議。顯然，這對 Agios 來說是一個非常令人興奮的時刻。我們堅信，我們有能力為患者提供變革性的新療法，並為股東創造顯著的長期價值。再次感謝，我們期待很快再次與您交談。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect everyone. Have a great day.

感謝您參加今天的會議。這確實結束了該程式。您現在可以斷開所有人的連線。祝你有美好的一天。