Agios Pharmaceuticals Inc (AGIO) 2024 Q2 法說會逐字稿

Good morning and welcome to Agios' second quarter 2024 conference call. At this time, all participants are in a listen only mode. There will be a question and answer session at the end. Please be advised that this call is being recorded at Agios' request.

早上好，歡迎參加 Agios 2024 年第二季電話會議。此時，所有參與者都處於只聽模式。最後將會有一個問答環節。請注意，本次通話是應 Agios 的要求進行錄音的。

I would now like to turn the call over to Chris Taylor, VP, Investor Relations and Corporate Communications for Agios.

我現在想將電話轉給 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 second quarter 2024 financial results and recent business highlights. You can access 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; Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development; Tsveta Milanova, our Chief Commercial Officer; and Cecilia Jones, our Chief Financial Officer.

謝謝你，接線生。大家早安，歡迎參加 Agios 的電話會議和網路廣播，討論 2024 年第二季財務業績和近期業務亮點。您可以造訪我們網站 agios.com 的投資者部分，查看今天電話會議的幻燈片。我們的執行長布萊恩·戈夫 (Brian Goff) 也參加了今天的電話會議。 Sarah Gheuens 博士，首席醫療官兼研發主管； Tsveta Milanova，我們的商務長；和我們的財務長塞西莉亞瓊斯。

Before we get started, I'd 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 set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC.

在我們開始之前，我想提醒大家，我們在這次電話會議中所做的一些陳述將包括前瞻性陳述。由於各種風險、不確定性和其他因素，包括我們最近向SEC 提交的文件以及我們可能未來提交的任何其他文件中所述的因素，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。

And with that, I'm pleased to turn the call over to Brian.

至此，我很高興將電話轉給布萊恩。

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. Our foundation leverages mitapivat novel mechanism of action, which improves overall red blood cell health and has been a key driver of our positive clinical data readouts in recent years.

謝謝，克里斯。大家早安，感謝您加入我們。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。我們的基金會利用 mitapivat 的新穎作用機制，改善紅血球的整體健康狀況，並且是近年來我們積極的臨床數據讀出的關鍵驅動力。

I'm delighted to report that we continued our positive momentum in Q2 with multiple key milestones announced this quarter. First, we announced that the Phase 3 ENERGIZE-T study of mitapivat met both the primary endpoint and all key secondary endpoints, in adults with transfusion dependent alpha or beta-thalassemia.

我很高興地向大家報告，我們在第二季度繼續保持積極勢頭，本季宣布了多個關鍵里程碑。首先，我們宣布 mitapivat 的 3 期 ENERGIZE-T 研究在患有輸血依賴性 α 或 β 地中海貧血的成年人中達到了主要終點和所有關鍵次要終點。

Importantly, ENERGIZE-T is the first Phase 3 study to demonstrate efficacy of an oral disease-modifying treatment for transfusion dependent alpha and beta-thalassemia. Second, data from the positive Phase 3 energized study of mitapivat in adults with alpha or beta-thalassemia who were not regularly transfused, were presented by leading KOLs in two presentations at the recent European Hematology Association Congress in Madrid, including a plenary session.

重要的是，ENERGIZE-T 是第一個證明口服疾病緩解療法對輸血依賴性 α 和 β 地中海型貧血療效的 3 期研究。其次，在最近於馬德里舉行的歐洲血液學協會大會（包括一次全體會議）上，主要KOL 在兩次演講中介紹了mitapivat 在未定期輸血的成人α 或β 地中海貧血患者中進行的3 期積極研究的數據。

Taken together with the positive data from ENERGIZE-T, we plan to submit an sNDA for mitapivat in thalassemia based on all available data from both ENERGIZE and ENERGIZE-T by the end of 2024, seeking a label that covers people living with all subtypes of thalassemia.

結合 ENERGIZE-T 的所有可用數據提交 mitapivat 治療地中海型貧血的 sNDA，尋求一個涵蓋所有亞型地中海貧血患者的標籤地中海貧血。

Third, we announced that Agios has agreed to sell its rights to a 15% royalty on potential US net sales of Servier's Vorasidenib to Royalty Pharma. Under the terms of the agreement at Agios will receive an upfront payment of $905 million upon approval of vorasidenib by the FDA. Cecilia, we'll revisit the details in a moment, and I would like to thank her for directing the process and structuring a tremendous agreement for Agios, our shareholders and a win-win for both Agios and Royalty Pharma.

第三，我們宣布 Agios 已同意將施維雅 Vorasidenib 在美國潛在淨銷售額的 15% 特許權使用費出售給rotyty Pharma。根據協議條款，一旦 FDA 批准 vorasidenib，Agios 將獲得 9.05 億美元的預付款。Cecilia，我們稍後會重新討論細節，我要感謝她指導整個流程並為 Agios、我們的股東制定了一份巨大的協議，並為 Agios 和Royalty Pharma 帶來了雙贏。

This transaction will provide us with the financial independence to prepare for potential launches in thalassemia and sickle cell disease as we build a multi-billion dollar PK activation franchise as well as the ability to opportunistically expand our pipeline. And fourth, just this morning, we announced top line data from the Phase 3 ACTIVATE-kids T study of mitapivat in children with PK deficiency who are regularly transfused.

這項交易將為我們提供財務獨立性，為地中海貧血和鐮狀細胞病的潛在上市做好準備，因為我們建立了數十億美元的PK 激活特許經營權，並有能力機會主義地擴大我們的產品線。第四，就在今天早上，我們公佈了 mitapivat 在定期輸血的 PK 缺陷兒童中進行的 3 期 ACTIVATE-kids T 研究的主要數據。

This is truly a pioneering study for Agios of first pediatric study of mitapivat and representative of our commitment to pursue the potential of mitapivat as a treatment for children with rare diseases. We are also pleased to report that we have completed enrollment in the ACTIVATE-kids study, and we look forward to the top line readout in 2025.

這確實是 Agios 首次對 mitapivat 進行兒科研究的開創性研究，代表了我們致力於探索 mitapivat 作為治療罕見疾病兒童的潛力的承諾。我們也很高興地報告，我們已經完成了 ACTIVATE-kids 研究的註冊，我們期待 2025 年的頂線讀數。

Building on this progress, we look forward to several additional upcoming milestones including completing enrollment in the Phase 3 portion of the rise up study of mitapivat in sickle cell disease by the end of this year and reporting data next year.

在此進展的基礎上，我們期待即將到來的幾個里程碑，包括在今年年底前完成 mitapivat 治療鐮狀細胞疾病的上升研究的第 3 期部分的入組，並於明年報告數據。

Sarah will provide a detailed update on our progress and upcoming milestones across R&D in just a few minutes. Given the consistent and compelling data we've generated across the mitapivat development program and the high unmet need in each of our target disease areas. We believe mitapivat has the potential to transform the course of multiple hemolytic anemias by improving red blood cell health and to become a multi-billion dollar franchise.

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。鑑於我們在 mitapivat 開發計劃中產生的一致且令人信服的數據以及我們每個目標疾病領域的高度未滿足的需求。我們相信 mitapivat 有潛力透過改善紅血球健康來改變多種溶血性貧血的病程，並成為價值數十億美元的特許經營產品。

Leveraging the positive data observed in the ENERGIZE and ENERGIZE-T studies of mitapivat, which together encompass all thalassemia subtypes, our expanding commercial organization is actively preparing for a potential US launch of mitapivat in thalassemia in 2025, as well as a potential launch in sickle cell disease in 2026.

利用mitapivat 的ENERGIZE 和ENERGIZE-T 研究（涵蓋所有地中海貧血亞型）中觀察到的積極數據，我們不斷擴大的商業組織正在積極準備於2025 年在美國推出mitapivat 治療地中海貧血，以及可能在鐮狀細胞病中上市2026年發生細胞疾病。

Tsveta will provide greater detail on the market opportunity in thalassemia and the team's robust preparation for launch as well as an update on our current launch in PK deficiency and just a bit. As part of our news release this morning, we were delighted to announce two updates related to the commercialization of PYRUKYND outside the US. First, we've entered into a distribution agreement with Newbridge Pharmaceuticals, a leading player in the Gulf region. And second, mitapivat has received breakthrough medicine designation from the Saudi FDA.

Tsveta 將更詳細地介紹地中海貧血的市場機會、團隊為上市所做的強有力的準備工作，以及我們目前在 PK 缺陷方面的上市情況的最新情況。作為今天早上新聞發布的一部分，我們很高興地宣布與 PYRUKYND 在美國以外商業化相關的兩項更新。首先，我們與海灣地區的領導企業新橋製藥公司簽訂了分銷協議。其次，mitapivat 已獲得沙烏地阿拉伯 FDA 的突破性藥物認定。

Finally, as you'll hear from Cecilia, we ended the second quarter with a strong cash position with approximately $645 million in cash and investments on the balance sheet. And we have the potential to further bolster our cash position by an additional $1.1 billion upon the potential FDA approval of vorasidenib.

最後，正如您將從塞西莉亞那裡聽到的那樣，我們在第二季度末擁有強勁的現金頭寸，資產負債表上的現金和投資約為 6.45 億美元。在 FDA 可能批准 vorasidenib 後，我們有可能進一步增加 11 億美元的現金狀況。

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

這樣，我就把電話轉給莎拉。

Thanks, Brian. This morning, we were very pleased to announce top-line data from the Phase 3 ACTIVATE-kidsT study of mitapivat in children with PK deficiency who are regularly transfused, which is the first Phase 3 study to report data in this population. And importantly, the first completed pediatric study of mitapivat for Agios.

謝謝，布萊恩。今天早上，我們非常高興地宣布 mitapivat 在定期輸血的 PK 缺陷兒童中進行的 3 期 ACTIVATE-kidsT 研究的主要數據，這是第一個報告該族群數據的 3 期研究。重要的是，首次完成了針對 Agios 的 mitapivat 兒科研究。

We are also pleased to report that we have completed enrollment in a complementary ACTIVATE-kids study of mitapivat in children with PK deficiency who are not regularly transfused. Next year we aim to report top line data from the second study and will review all available data from both the ACTIVATE-kidsT and ACTIVATE-kids studies.

我們也很高興地報告，我們已經完成了一項補充性 ACTIVATE-kids 研究，對象為 PK 缺乏且不定期輸血的兒童。明年，我們的目標是報告第二項研究的主要數據，並將審查 ACTIVATE-kidsT 和 ACTIVATE-kids 研究的所有可用數據。

So turning now to the data from ACTIVATE-kidsT reported to date. As this first slide depicts, our pediatric PK deficiency program includes two Phase 3 studies evaluating regularly transfused and not regularly transfused pediatric patients with Pyruvate Kinase deficiency in ACTIVATE-kidsT and ACTIVATE-kids, respectively. Children represent approximately 20% of the total patient population in PK deficiency, and there are no therapies approved for pediatric PK deficiency.

現在轉向 ACTIVATE-kidsT 迄今為止報告的數據。如第一張幻燈片所示，我們的兒科 PK 缺乏計劃包括兩項 3 期研究，分別評估 ACTIVATE-kidsT 和 ACTIVATE-kids 中定期輸血和不定期輸血的丙酮酸激酶缺乏兒童患者。兒童約佔 PK 缺陷患者總數的 20%，目前尚無核准用於兒童 PK 缺陷的治療方法。

Turning to the top line results announced this morning for ACTIVATE-kidsT trial. A total of 49 patients were enrolled in the study with patients randomized two to one to either mitapivat five daily or placebo. The study consists of a 32 week double-blind period, followed by an open-label extension period. 30 of the 32 patients in the mitapivat arm and 16 of the 17 in the placebo arm completed double-blind period of the study.

轉向今天早上公佈的 ACTIVATE-kidsT 試驗的主要結果。共有 49 名患者參加了研究，其中患者隨機分為 2 對 1 組，分別接受每天 5 次的 mitapivat 或安慰劑。該研究包括 32 週的雙盲期和隨後的開放標籤延長期。米塔皮瓦組 32 名患者中的 30 名和安慰劑組 17 名患者中的 16 名完成了研究的雙盲期。

As we noted in our news release this morning using Bayesian methodology, the prespecified statistical criterion for the primary endpoint in ACTIVATE-kidsT was not met using low or moderate borrowing of data from the ACTIVATE-T study in adults. The results were clinically meaningful as transfusion free response and normal hemoglobin response to key secondary endpoints in this study were only observed in patients in the mitapivat arm.

正如我們在今天早上的新聞稿中指出的那樣，使用貝葉斯方法，使用低度或中度借用成人 ACTIVATE-T 研究的數據，無法滿足 ACTIVATE-kidsT 主要終點的預先設定的統計標準。結果具有臨床意義，因為本研究中僅在 mitapivat 組患者中觀察到對關鍵次要終點的無輸血反應和正常血紅蛋白反應。

Transfusion reduction response was defined as an equal or more than 33% reduction in the total red blood cell transfusion volume from week 9 to week 32 of the double-blind period normalized by weight and actual study drug duration compared with the historical transfusion volume standardized by weight into 24 weeks. 28.1% of patients in the mitapivat arm achieved a transfusion reduction response compared to 11.8% of patients in the placebo arm.

輸血減少反應定義為雙盲期第9 週至第32 週期間按體重和實際研究藥物持續時間歸一化的總紅血球輸血量與按體重和實際研究藥物持續時間歸一化的歷史輸血量相比減少等於或超過33%。米塔皮伐組中 28.1% 的患者實現了輸血減少反應，而安慰劑組中這一比例為 11.8%。

In addition, a higher proportion of patients in the mitapivat arm compared to the placebo arm achieved the secondary endpoints of transfusion free response and normal hemoglobin response, which were measured from weeks 9 through week 32 of the double-blind period. Six patients, nearly 20% in the mitapivat arm compared to zero in the placebo arm had a transfusion free response with no red blood cell transfusions and four patients in the mitapivat arm compared to zero in the placebo arm achieved a normal hemoglobin response.

此外，與安慰劑組相比，米塔皮瓦組中有更高比例的患者達到了無輸血反應和正常血紅蛋白反應的次要終點，這是在雙盲期第9 週至第32 週期間測量的。6 名患者（米塔皮瓦組中近20% 的患者）實現了無輸血反應，沒有進行紅血球輸注，而安慰劑組則為0%；米塔皮瓦組中4 名患者（安慰劑組的零名患者）達到了正常的血紅素反應。

Defined as hemoglobin concentrations within normal limits, at least once eight weeks or more after a transfusion. Safety results for mitapivat were consistent with the safety profile from adaptive up previously observed in adults with PK deficiency who are regularly transfused. During the double-blind treatment period of the study of similar proportion of patients had adverse events in the mitapivat and placebo arms, and there were no discontinuations of study treatment due to AEs.

定義為輸血後至少一次八週或更長時間的血紅素濃度在正常範圍內。mitapivat 的安全性結果與先前在定期輸血的 PK 缺陷成人中觀察到的適應性向上的安全性一致。在研究的雙盲治療期間，類似比例的患者在 mitapivat 組和安慰劑組中出現不良事件，且沒有因 AE 而中斷研究治療。

We plan to present a more detailed analysis of the Phase 3 ACTIVATE-kidsT data at an upcoming medical meeting. We hope that this study will be the first of several pediatric studies to make a positive impact in the lives of children facing rare hemolytic anemia, including thalassemia and sickle cell disease.

我們計劃在即將舉行的醫學會議上對第 3 階段 ACTIVATE-kidsT 數據進行更詳細的分析。我們希望這項研究將成為幾項兒科研究中的第一項，對面臨罕見溶血性貧血（包括地中海貧血和鐮狀細胞疾病）的兒童的生活產生積極影響。

Turning to our progress in thalassemia, an overview of the data from the Phase 3 ENERGIZE study were presented in a plenary session at the EHA meeting in June by Dr. Ali Taher from the American University of Beirut Medical Center, and in a poster detailing health-related quality of life and patient reported outcome measures were presented by Dr. Kevin Kuo from the University of Toronto and in an investor webcast. Greater detail was provided on efficacy and safety.

談到我們在地中海貧血方面的進展，貝魯特美國大學醫學中心的Ali Taher 博士在6 月份EHA 會議的全體會議上概述了3 期ENERGIZE 研究的數據，並在一張詳細介紹健康狀況的海報中介紹了研究的數據。提供了有關功效和安全性的更多細節。

Importantly, patients treated with mitapivat experienced improvements on multiple health-related quality-of-life measures, including fatigue and walking capacity. In addition, last month, we were very pleased to announce positive top line data from the Phase 3 ENERGIZE-T study of mitapivat in transfusion dependent thalassemia, which positions mitapivat as the first oral disease-modifying therapy to demonstrate efficacy in transfusion dependent alpha and beta-thalassemia.

重要的是，接受 mitapivat 治療的患者在多項與健康相關的生活品質指標上都有改善，包括疲勞和步行能力。此外，上個月，我們非常高興地宣布mitapivat 治療輸血依賴性地中海貧血的3 期ENERGIZE-T 研究的積極頂線數據，該研究將mitapivat 定位為第一個口服疾病緩解療法，以證明對輸血依賴性α 和地中海貧血的療效。

Let me now take a moment to review the design and the results of that study. There was a 48 week double-blind period, followed by an open-label extension period. A total of 268 patients were enrolled with patients randomized two to one to either 100 milligrams mitapivat twice daily or placebo. The study met its primary endpoint of transfusion reduction response, defined as an equal or more than 50% reduction in transfused red blood cell units with a reduction of equal or more than two units of transfused red blood cells in any consecutive 12-week period through week 48 compared with baseline.

現在讓我花點時間回顧一下該研究的設計和結果。有 48 週的雙盲期，隨後是開放標籤延長期。共有 268 名患者入組，患者隨機分為 2 組，分別接受每日兩次 100 毫克的 mitapivat 或安慰劑。該研究達到了輸血減少反應的主要終點，即輸注紅血球單位減少等於或超過 50%，並且在任何連續 12 週期間減少輸注紅血球單位等於或超過 2 個單位。

30.4% of patients achieved the primary endpoint compared to 12.6% of patients in the placebo arm. The difference was highly statistically significant with a p-value of 0.0003. Treatment with mitapivat also demonstrated statistically significant reductions in additional measures of transfusion reduction response compared to placebo as assessed by the three key secondary endpoints.

30.4% 的患者達到了主要終點，而安慰劑組的比例為 12.6%。差異具有高度統計顯著性，p 值為 0.0003。根據三個關鍵次要終點的評估，與安慰劑相比，米塔皮瓦治療還顯示輸血減少反應的其他措施有統計學顯著性降低。

An equal or more than 50% reduction in transfused red blood cell units in any consecutive 24 week period through week 48 compared with baseline. An equal or more than 33% reduction in transfused red blood cell units from week 13 to week 48 compared with baseline and an equal or more than 50% reduction in transfused red blood cell units from week 13 to week 48 compared with baseline.

與基線相比，在第 48 週的任何連續 24 週期間，輸注的紅血球單位減少等於或超過 50%。與基線相比，從第 13 週到第 48 週，輸注的紅血球單位減少等於或超過 33%，從第 13 週到第 48 週，輸注的紅血球單位與基線相比，減少等於或超過 50%。

Moreover, 9.9% of patients in the mitapivat arm achieved a secondary endpoint of transfusion independence, defined as remaining transfusion-free for equal or more than eight consecutive weeks through week 48 compared to 1.1% in the placebo arm.

此外，mitapivat 組中有 9.9% 的患者達到了輸血獨立性的次要終點，即在第 48 週之前連續 8 週或以上保持不輸血，而安慰劑組中這一比例為 1.1%。

Finally, during the 48 week double-blind period, incidence of adverse events was similar between mitapivat and placebo arm with 5.8% of the patients in the mitapivat arm experiencing an AE that led to discontinuation compared to 1.2% of patients in the placebo arm. We look forward to presenting a more detailed analysis of these data at an upcoming medical meeting.

最後，在 48 週雙盲期內，mitapivat 組和安慰劑組的不良事件發生率相似，mitapivat 組中有 5.8% 的患者出現 AE，導致停藥，而安慰劑組中這一比例為 1.2%。我們期待在即將召開的醫學會議上對這些數據進行更詳細的分析。

Taken together, the data from ENERGIZE and ENERGIZE-T strongly underscored mitapivat's potential to become a foundational convenient oral treatment option for all subtypes of thalassemia, alpha and beta-thalassemia and transfusion dependent and non-transfusion dependent thalassemia. We are on track to file an sNDA that incorporates all data from both studies by the end of this year, seeking a label that covers people living with all subtypes of thalassemia.

總而言之，來自 ENERGIZE 和 ENERGIZE-T 的數據強烈強調了 mitapivat 有潛力成為所有亞型地中海貧血、α 和 β 地中海貧血以及輸血依賴性和非輸血依賴性地中海貧血的基本便捷口服治療選擇。我們預計在今年年底前提交一份 sNDA，其中包含兩項研究的所有數據，尋求一個涵蓋所有地中海貧血亞型患者的標籤。

As Brian mentioned, we are quite pleased to note that mitapivat has received a breakthrough medicine designation by the SFDA or the Saudi FDA. The breakthrough medicine program aims to facilitate and accelerate development and review of new drugs that address unmet medical need in the treatment of serious or life-threatening conditions. Mitapivat becomes one of the first products to receive the breakthrough medicine designation, and we look forward to working with the regulators together with our new partners NewBridge.

正如 Brian 所提到的，我們非常高興地註意到 mitapivat 已獲得 SFDA 或沙烏地阿拉伯 FDA 的突破性藥物認定。該突破性醫學計劃旨在促進和加速新藥的開發和審查，以滿足治療嚴重或危及生命的疾病時未滿足的醫療需求。Mitapivat 成為首批獲得突破性藥物認定的產品之一，我們期待與新合作夥伴 NewBridge 一起與監管機構合作。

Turning to sickle cell disease, enrollment in the Phase 3 portion of the rise of mitapivat continues to progress, and we continue to be on track to complete enrollment by the end of this year. Given the positive data we generated in the Phase 2 portion of the RISE UP study as well as the positive data we have generated in other hemolytic anemias, we are confident in 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.

談到鐮狀細胞疾病，mitapivat 崛起的第 3 期部分的入組工作繼續取得進展，我們繼續預計在今年年底前完成入組工作。鑑於我們在 RISE UP 研究的第 2 期部分中產生的積極數據以及我們在其他溶血性貧血中產生的積極數據，我們對 mitapivat 成為一種方便、一流和最好的藥物的潛力充滿信心一流的治療選擇，可改善鐮狀細胞疾病患者的紅血球健康。

We look forward to reporting top-line data from the Phase 3 portion of the RISE UP study next year and to the potential for mitapivat to address the high unmet need in this disease by improving anemia, reducing sickle cell pain crises and making patients feel better by reducing their fatigue.

我們期待明年報告 RISE UP 研究第 3 期部分的主要數據，並期待 mitapivat 通過改善貧血、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的潛力通過減少他們的疲勞。

Finally, we remain on track to deliver on all milestones across the rest of our advancing pipeline, including beginning enrollment of the Phase 2b study evaluating higher doses of our Novel PK activator AG-946, now named tebapivat in lower risk MDS. We are eager to share more details as the trial gets underway soon.

最後，我們仍有望在我們其餘的推進管道中實現所有里程碑，包括開始招募 2b 期研究，評估更高劑量的新型 PK 活化劑 AG-946，現在在低風險 MDS 中被命名為 tebapivat。隨著審判即將開始，我們渴望分享更多細節。

With that, I will now turn the call over to Tsveta.

現在，我將把電話轉給茨維塔。

Thanks, Sarah. Today, a diagnosis of thalassemia can be done thing for patients and their families. Having just returned from the Cooley's Anemia Foundation Patient and Family Conference in Atlanta, we've heard many powerful stories emphasizing the debilitating impact thalassemia may have on patients and their families.

謝謝，莎拉。如今，地中海貧血的診斷可以為患者及其家人完成。剛從亞特蘭大的庫利貧血基金會患者和家庭會議回來，我們聽到了許多強大的故事，強調地中海貧血可能對患者及其家人造成的衰弱影響。

All forms of thalassemia bring higher rates of serious morbidities, reduced quality of life and a heightened risk of premature death. It is challenging for patients to navigate the disease because treatment options are limited and the burden of disease as well as the associated cost of care is significant.

所有形式的地中海貧血都會帶來更高的嚴重發病率、生活品質下降和過早死亡的風險增加。對於患者來說，應對這種疾病具有挑戰性，因為治療選擇有限，而且疾病負擔以及相關的護理費用很高。

Based on the positive data we have generated into ENERGIZE and ENERGIZE-T studies, we aim to transform the treatment of this disease and bring to market the first therapy approved for all the thalassemia subtypes. There are approximately 6,000 adults diagnosed with the thalassemia in the US, approximately 4,000 of whom are non-transfusion dependent.

基於我們在 ENERGIZE 和 ENERGIZE-T 研究中獲得的積極數據，我們的目標是改變疾病的治療方法，並將第一個批准用於所有地中海貧血亞型的療法推向市場。在美國，大約有 6,000 名成年人被診斷出患有地中海貧血，其中約 4,000 人不依賴輸血。

In the US there are no oral therapies approved for patients living with the thalassemia. And for those with non-transfusion dependent disease, there are no approved therapies at all. Our commercial organization is actively preparing to address this high unmet need with a potential US launch of PYRUKYND in thalassemia next year.

在美國，尚無核准用於地中海貧血患者的口服療法。對於那些患有非輸血依賴性疾病的人來說，根本沒有批准的治療方法。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，明年可能在美國推出 PYRUKYND 治療地中海貧血。

In addition to the consistent and compelling data we have generated in the mitapivat development program, we believe there are three key factors that have the potential to support adoption of cytokines in thalassemia in the US. First, driven by the availability of newborn screening and well-established ICD-10 codes, the diagnosis rate in thalassemia is high with many patients diagnosed before adulthood.

除了我們在 mitapivat 開發計劃中產生的一致且令人信服的數據外，我們相信還有三個關鍵因素有可能支持在美國採用細胞激素治療地中海貧血。首先，在新生兒篩檢和完善的 ICD-10 代碼的推動下，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。

Second, both patients and providers are concentrated in a limited number of centers with approximately 50% of all diagnosed patients treated at a fewer than 150 affiliated practices, providing a clear focus for our initial launch. And third, since some of the centers of excellence were included in our clinical trials sounds treating physicians already have firsthand experience with mitapivat. Taken together, we believe we are well positioned to provide a potential foundational treatment option for patients with thalassemia regardless of subtype.

其次，患者和提供者都集中在數量有限的中心，大約 50% 的確診患者在不到 150 個附屬診所接受治療，這為我們最初的推出提供了明確的重點。第三，由於一些卓越中心被納入我們的臨床試驗，聽起來治療醫生已經擁有米塔皮瓦的第一手經驗。總而言之，我們相信我們有能力為地中海貧血患者提供潛在的基礎治療選擇，無論其亞型如何。

As we continue to progress toward a potential launch in the US, our team is focused on four key areas of launch preparations. First, we continue to conduct extensive market research and claims data analyses to further refine our market insights and our physician targeting. Second, we commenced an education campaign in May, designed for both patients and clinicians. Highlighting the long-term complications and burden of disease across all the leukemia subtypes. I'll share a little more about this campaign in a moment.

隨著我們繼續推進在美國的潛在發布，我們的團隊專注於發布準備的四個關鍵領域。首先，我們繼續進行廣泛的市場研究和理賠數據分析，以進一步完善我們的市場洞察和醫生定位。其次，我們在五月啟動了一項針對患者和臨床醫生的教育活動。強調所有白血病亞型的長期併發症和疾病負擔。稍後我將分享有關此活動的更多資訊。

Third, we are executing a disciplined expansion of our commercial and medical teams to right-size the organization for a successful launch in this larger, but still rare market. 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 PYRUKYND in PK deficiency, and we look forward to the same strong outcome in thalassemia.

第三，我們正在對我們的商業和醫療團隊進行嚴格的擴張，以調整組織規模，以便在這個更大但仍然罕見的市場中成功推出產品。第四，我們的市場准入團隊已經與付款人就疾病狀態教育進行了接觸。我為我們的團隊在 PYRUKYND 治療 PK 缺乏症方面取得的廣泛應用感到自豪，我們期待在地中海貧血方面取得同樣強勁的成果。

On slide 24, we have provided some of the messaging that our team is using in our new disease state education campaigns for both patients and health care providers. With the objective of highlighting the disease burden of the thalassemia and encouraging disease monitoring and management. Our team is reinforcing the messages listed, especially working to reset the perception that non-transfusion dependent patients are at less risk.

在投影片 24 上，我們提供了我們的團隊在針對患者和醫療保健提供者的新疾病狀態教育活動中使用的一些資訊。目的是強調地中海貧血的疾病負擔並鼓勵疾病監測和管理。我們的團隊正在強化所列出的訊息，特別是努力重新建立非輸血依賴患者風險較低的觀念。

Next is a graphic from our campaign. It highlights how we are communicating to physicians that the serious risk of morbidities can exist regardless of the thalassemia patients transfusion history. The response has been very positive with the images and messaging resonating with both patients and health care providers.

接下來是我們活動的圖片。它強調了我們如何與醫生溝通，無論地中海貧血患者的輸血史如何，都可能存在嚴重的發病風險。這些圖像和資訊得到了非常積極的反響，引起了患者和醫療保健提供者的共鳴。

I mentioned that our team continues to deepen our market understanding. On this slide, you can see that insight from our recent market research that helps elucidate the top clinical characteristics healthcare providers will consider when prescribing PYRUKYND, hemoglobin levels, transfusion burden, fatigue and iron overload.

我提到我們的團隊不斷加深對市場的了解。在這張投影片上，您可以看到我們最近的市場研究的見解，有助於闡明醫療保健提供者在開立 PYRUKYND 處方時會考慮的主要臨床特徵、血紅蛋白水平、輸血負擔、疲勞和鐵過載。

Outside of 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. Today, we are pleased to announce that we have entered into a distribution agreement with NewBridge Pharmaceuticals to prepare for potential commercialization of PYRUKYND in the GCC region.

在美國以外，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，該地區的一些領先治療中心是我們臨床試驗的一部分。今天，我們很高興地宣布，我們已與 NewBridge Pharmaceuticals 簽訂分銷協議，為 PYRUKYND 在海灣合作委員會地區的潛在商業化做準備。

NewBridge, a leading specialty company headquartered in Dubai will commercialize PYRUKYND in Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates. We are excited to join forces with NewBridge as we drive toward potential commercialization in the region.

NewBridge 是一家總部位於杜拜的領先專業公司，將在巴林、科威特、阿曼、卡達、沙烏地阿拉伯和阿拉伯聯合大公國將 PYRUKYND 商業化。我們很高興與 NewBridge 聯手，推動該地區潛在的商業化。

As noted on slide 27, Saudi Arabia accounts for the largest patient population in the GCC. We are quite proud of the team's effort to successfully secure a breakthrough medicine designation for mitapivat in thalassemia, which was granted by the SFDA, Saudi FDA.

如投影片 27 所示，沙烏地阿拉伯擁有海灣合作委員會 (GCC) 地區最大的患者群體。我們為該團隊的努力感到非常自豪，該藥物成功獲得了米塔皮伐治療地中海貧血的突破性藥物資格，該資格獲得了 SFDA 和沙烏地阿拉伯 FDA 的批准。

As noted in the last bullet, the actual response in individual GCC countries usually begins with a price set at the regulatory level, followed by access with health authorities, local institutions, the private sector and national standards. These are key elements in the process, which we look forward to navigating over time with our partner NewBridge.

正如最後一個要點所述，海灣合作委員會各個國家的實際應對措施通常從監管層面設定價格開始，然後是衛生當局、地方機構、私營部門和國家標準。這些是這個過程中的關鍵要素，我們期待與我們的合作夥伴 NewBridge 一起逐步解決這些問題。

Let me now provide an update on the current launch of PYRUKYND in PK deficiency. In the second quarter of 2024, we generated $8.6 million in net PYRUKYND revenue compared to $8.2 million in the first quarter of 2024. In the US, a total of 201 patients have completed a prescription enrollment form, including 13 in the second quarter of 2024, a 7% increase versus the prior quarter.

現在讓我提供有關 PYRUKYND 目前推出的 PK 缺陷的最新情況。2024 年第二季度，我們的 PYRUKYND 淨收入為 860 萬美元，而 2024 年第一季為 820 萬美元。在美國，共有 201 名患者填寫了處方登記表，其中 2024 年第二季有 13 名患者，比上一季增加了 7%。

This has translated into 128 net patients on therapy, a 7% increase versus the prior quarter. Patients on therapy continues to span from a growing and diverse prescriber base of 173 physicians, and we present a broad demographic and disease manifestation range that is consistent with the adult PK deficiency population in the US.

這意味著有 128 名淨患者接受治療，比上一季增加了 7%。接受治療的患者由 173 名醫生組成，處方者群體不斷擴大且多樣化，我們提供了廣泛的人口統計和疾病表現範圍，與美國成人 PK 缺乏人群一致。

We continue to be encouraged by the persistency of patients on treatment and remain focused on efficiently identifying providers likely to treat patients with PK deficiency. We believe that the capabilities we continue to strengthen through the current launch in PKD, including efficient targeting analytics, patient and physician awareness and education, and patient access will provide a firm foundation from which to maximize potential future US launches of mitapivat, including thalassemia in 2025 and in sickle cell disease in 2026. Above all, we are inspired and energized by the potential to bring a new therapy to these underserved patient populations.

我們繼續對患者堅持治療的態度感到鼓舞，並繼續專注於有效地識別可能治療 PK 缺乏患者的提供者。我們相信，透過目前PKD 的推出，我們繼續加強的能力，包括有效的目標分析、患者和醫生的意識和教育以及患者的獲取，將為最大限度地提高未來在美國推出mitapivat 的潛力（包括地中海貧血）奠定堅實的基礎。最重要的是，我們對為這些服務不足的患者群體帶來新療法的潛力感到鼓舞和充滿活力。

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

這樣，我就把電話轉給塞西莉亞。

Thanks, Tsveta. Our second 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. Second Quarter 2024 net PYRUKYND revenue was $8.6 million, an increase of $1.9 million compared to the second quarter of 2023.

謝謝，茨維塔。我們的 2024 年第二季財務業績可以在我們今天早上發布的新聞稿中找到，更多詳細資訊將包含在我們將於今天晚些時候提交的 10-Q 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 年第二季 PYRUKYND 淨收入為 860 萬美元，較 2023 年第二季增加 190 萬美元。

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. As we pivot our organization focus to the thalassemia launch preparedness, we expect to see more muted growth going forward and quarter-over-quarter variability in PKD revenues. Cost of sales for the quarter was $1.5 million. R&D expenses were $77.4 million for the second quarter, an increase of $8.5 million compared to the second quarter of 2023.

與其他罕見疾病產品的上市情況一致，每年的毛淨值佔比一直在 10% 至 20% 之間。當我們將組織重點轉向地中海貧血症上市準備時，我們預計未來的成長將更為溫和，並且 PKD 收入將出現季度環比變化。該季度的銷售成本為 150 萬美元。研發第二季支出為 7,740 萬美元，比 2023 年第二季增加 850 萬美元。

The year-over-year increase was primarily attributable to an increase in costs associated with the siRNA TMPRSS6 program in licensed from Alnylam last year. SG&A expenses were $35.5 million from the second quarter, an increase of $5.1 million compared to same quarter in 2023. This was primarily attributable to an increase in commercial related activities as we prepare for the potential approval of PYRUKYND and thalassemia.

同比增長主要歸因於去年從 Alnylam 獲得許可的 siRNA TMPRSS6 項目相關成本的增加。第二季的 SG&A 費用為 3,550 萬美元，與 2023 年同季相比增加了 510 萬美元。這主要歸因於我們為 PYRUKYND 和地中海貧血的潛在批准做準備時商業相關活動的增加。

As a reminder, this quarter, we announced that the company has agreed to sell the rights to its 15% royalty on potential US net sales of Servier's vorasidenib to Royalty Pharma. Under the terms of the agreement, Agios will receive an upfront payment of $905 million upon approval of vorasidenib by the FDA. And Royalty Pharma will receive the entirety of the 15% royalty on annual US net sales of vorasidenib up to $1 billion and 12% royalty on annual US net sales greater than $1 billion. Agios will retain a 3% royalty on annual US net sales greater than $1 billion.

提醒一下，本季度，我們宣布該公司已同意將施維雅 vorasidenib 在美國潛在淨銷售額的 15% 特許權使用費出售給Royalty Pharma。根據協議條款，在 FDA 批准 vorasidenib 後，Agios 將獲得 9.05 億美元的預付款。對於vorasidenib 在美國年淨銷售額不超過10 億美元的情況，Royalty Pharma 將收取全部15% 的特許權使用費；對於美國年淨銷售額超過10 億美元的情況，Royalty Pharma 將收取12% 的特許權使用費。Agios 將針對美國年淨銷售額超過 10 億美元保留 3% 的特許權使用費。

In addition, we still retain the rights to a potential $200 million milestone from Servier upon FDA approval of vorasidenib from the divesture of our oncology business. So all together, Agios will receive a total of $1.1 billion in payments upon the potential FDA approval for vorasidenib.

此外，在 FDA 批准 vorasidenib 從我們的腫瘤業務剝離後，我們仍然保留從施維雅獲得潛在 2 億美元里程碑的權利。因此，一旦 FDA 批准 vorasidenib，Agios 將總共獲得 11 億美元的付款。

As a reminder, the PDUFA action date has been set for August 20, 2024. We ended the quarter with cash, cash equivalents and marketable securities of $645.3 million. We expect that this balance, together with anticipated product revenues, interest income and payments upon FDA approval of vorasidenib, will provide a financial independence to prepare for potential biodefense launches in thalassemia and sickle cell disease. And to opportunistically expand our pipeline through both internally and externally discovered assets.

謹此提醒，PDUFA 行動日期已定為 2024 年 8 月 20 日。本季結束時，我們的現金、現金等價物和有價證券為 6.453 億美元。我們預計，這種平衡，加上 FDA 批准 vorasidenib 後的預期產品收入、利息收入和付款，將提供財務獨立性，為地中海貧血和鐮狀細胞疾病的潛在生物防禦產品的推出做好準備。並透過內部和外部發現的資產來機會主義地擴大我們的管道。

We remain focused on creating shareholder value, including by proactively managing our cost base and deploying a disciplined capital 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 strong balance sheet will continue to enable us to execute from a position of strength.

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資本分配方法。隨著我們在短期內朝著更多潛在的價值創造里程碑邁進，我相信我們強大的資產負債表將繼續使我們能夠以強大的實力執行任務。

I will now turn the call back over to Brian, for his closing remarks.

現在我將把電話轉回給布萊恩，讓他發表結束語。

Thanks, Cecilia. Driven by a novel and differentiated mechanism of action that improved red blood cell health, mitapivat has continued to deliver positive late-stage data readouts spanning three hemolytic anemias, and we're pleased to have now completed our first Phase 3 trial in a pediatric patient population. Based on this consistent and compelling data package and the demonstrated strength of the Agios team, we continue to believe that mitapivat is poised to become a first-in-class and best-in-class treatment option for multiple indications and to become a multi-billion dollar franchise.

謝謝，塞西莉亞。在改善紅血球健康的新型差異化作用機制的推動下，mitapivat 持續提供涵蓋三種溶血性貧血的積極後期數據讀數，我們很高興現在完成了針對兒科患者的第一個 3 期試驗人口。基於這個一致且令人信服的數據包以及 Agios 團隊所展示的實力，我們仍然相信 mitapivat 有望成為多種適應症的一流和一流的治療選擇，並成為多適應症的治療選擇。的特許經營權。

Our focus is squarely on thalassemia, where we aim to file an sNDA by the end of this year and seek a label that covers people living with all subtypes of the disease. As we continue to take steps towards realizing our vision of becoming a leading rare disease company will continue to strive to be responsible stewards of our balance sheet and evaluate meaningful opportunities for value creation.

我們的重點是地中海貧血，我們的目標是在今年年底之前提交 sNDA，並尋求一個涵蓋患有該疾病所有亞型的人的標籤。隨著我們繼續採取措施實現成為領先的罕見疾病公司的願景，我們將繼續努力成為我們資產負債表的負責任的管理者，並評估有意義的價值創造機會。

Finally, I'd like to thank all of our employees for their hard work and dedication to our mission of developing and delivering transformative medicines that elevate and extend the lives of patients living with rare diseases and all of our partners, including the patients, physicians, caregivers and participants in our clinical development programs.

最後，我要感謝我們所有員工的辛勤工作和對我們開發和提供變革性藥物的使命的奉獻，這些藥物可以提高和延長罕見疾病患者的生命，以及我們所有的合作夥伴，包括患者、醫生、我們臨床開發計畫的護理人員和參與者。

With that, I will now open the call for questions.

現在，我將開始提問。

(Operator Instructions)

（操作員說明）

Eric Schmidt, Cantor Fitzgerald.

埃里克·施密特，康托·菲茨傑拉德。

Thanks for taking my question and congrats on all the continued progress. Maybe I'll ask about the new development today, the NewBridge transaction. Can you give us a little bit more color on some of the economics there and what you hope to receive? And maybe also talk about the timing now that you have breakthrough designation in Saudi Arabia. Thanks.

感謝您提出我的問題，並祝賀所有的持續進展。也許我會問一下今天的新進展，NewBridge 交易。您能為我們介紹一下那裡的一些經濟狀況以及您希望收到的結果嗎？也許還可以談談現在在沙烏地阿拉伯獲得突破性指定的時機。謝謝。

Thanks, Eric. Tsveta worked really hard with quite a large team on this new arrangement with Newbridge and GCC, you know that's our second most important market for thalassemia and the first most important outside the US. So I'm going to let Tsveta to comment on that.

謝謝，埃里克。Tsveta 與一個相當大的團隊一起努力與 Newbridge 和 GCC 達成這項新安排，你知道這是我們的地中海貧血症第二大市場，也是美國以外的第一大市場。所以我將讓茨維塔對此發表評論。

That's wonderful and we are really, really happy to announce the agreement with NewBridge because we've been working hard to select a partner with a very thorough and good experience in the region to represent us as Agios. We are also very proud to announce that we actually received the breakthrough medicines designation from the Saudi FDA with Saudi Arabia being the biggest market in the region and we look forward to work with NewBridge actually to utilize the breakthrough designation and submit for regulatory approval for thalassemia as soon as possible and we'll be providing more information on that, as we enter into the process.

這太棒了，我們真的非常高興宣布與 NewBridge 達成協議，因為我們一直在努力選擇一個在該地區擁有非常全面和良好經驗的合作夥伴來代表我們 Agios。我們也非常自豪地宣布，我們實際上已獲得沙烏地阿拉伯 FDA 的突破性藥物指定，沙烏地阿拉伯是該地區最大的市場，我們期待與 NewBridge 實際合作，利用突破性指定並提交地中海貧血的監管批准盡快，當我們進入該流程時，我們將提供更多相關資訊。

When you think about the new operations agreement that we have with them, they are full service distributor. They will represent Agios across the board from regulatory approval and commercialization activities across the whole region. It's a very typical kind of agreement for this type of relationships, which is basically a revenue split deal. There'll be no upfront payments for us as Agios. And as we continue to basically progress this commercialization, there'll be a revenue split as part of it.

當您考慮我們與他們簽訂的新營運協議時，他們是全方位服務經銷商。他們將代表 Agios 全面參與整個地區的監管審批和商業化活動。對於這類關係來說，這是一個非常典型的協議，基本上就是一個收入分成協議。我們作為 Agios 無需預付款。隨著我們繼續基本推動這種商業化，收入分成將作為其中的一部分。

When we look at the region, we are really, really excited about the potential of our product, because not only that there is a high unmet medical need in the region, but we have conducted clinical studies in the region. There is already a firsthand experience with some of the key centers and care wealthy in the region and we look forward to provide access to patients.

當我們審視該地區時，我們對我們產品的潛力感到非常非常興奮，因為不僅該地區存在大量未滿足的醫療需求，而且我們已經在該地區進行了臨床研究。我們已經在該地區的一些主要中心和護理中心獲得了第一手經驗，我們期待為患者提供服務。

And then, Eric, to follow-up on the question around timing of regulatory engagement, we are of course very excited to keep on moving forward with the development of our program. And so in part, we will be working as soon as we can with the regulators across the board.

然後，埃里克，為了跟進有關監管參與時間的問題，我們當然非常高興能夠繼續推進我們計劃的開發。因此，我們將盡快與監管機構全面合作。

I'll just close by saying that breakthrough medicines designation in Saudi is pretty unusual. And so we've been pleased to have that as a recognition of -- as Sarah noted, just a profound unmet need in that region. So it's an important part of the puzzle for us, as we get ready to expand our presence outside the US and particularly focus on these high unmet need regions.

最後我要說的是，在沙烏地阿拉伯獲得突破性藥物認定是非常不尋常的。因此，正如莎拉指出的那樣，我們很高興將此視為對該地區未滿足的巨大需求的認識。因此，這對我們來說是難題的重要組成部分，因為我們準備擴大我們在美國以外的業務，特別關注這些未滿足的需求較高的地區。

Great. Thanks a lot.

偉大的。多謝。

Thank you.

謝謝。

Christopher Raymond, Piper Sandler.

克里斯多福·雷蒙德，派珀·桑德勒。

Hey, thanks. Just a couple from me. Just with, vorasidenib's upcoming PDUFA, you guys, as you noted in your press release, you're in line for pretty meaningful cash infusion. Brian, I know you've talked about M&A and I'd say, your language has been relatively cautious, I guess in the past. But this is a $1 billion-plus infusion sort of changes things I would guess. In terms of the size and scope of what you could do. Can you maybe talk about how you're viewing M&A now as a lever after the August 20 PDUFA? And then, I have a follow-up question.

嘿，謝謝。只是我的一對。正如你們在新聞稿中指出的那樣，vorasidenib 即將推出的 PDUFA，你們將獲得相當有意義的現金注入。布萊恩，我知道你談論過併購，我想說，你的語言一直相對謹慎，我想過去是這樣。但我猜這是一筆超過 10 億美元的注資，會改變一些事情。就您可以做的事情的規模和範圍而言。您能否談談在 8 月 20 日 PDUFA 之後，您現在如何看待併購作為槓桿？然後，我有一個後續問題。

Yeah, sure. And thanks a lot. Obviously, I just want to reiterate again. I'm very proud of the work that Cecilia did with the royalty monetization of vorasidenib, that's an important step. As a side note, vorasidenib itself is a mark of excellence for Agios science. It's very important for patients and of course it adds to our potential balance sheet enhancement.

是的，當然。非常感謝。顯然，我只是想再次重申。我對塞西莉亞在沃拉西尼布的版稅貨幣化方面所做的工作感到非常自豪，這是重要的一步。順便說一句，vorasidenib 本身就是 Agios 科學卓越的標誌。這對患者來說非常重要，當然它還可以增強我們潛在的資產負債表。

So I think, you mentioned M&A, I'll just maybe take it up a step and just talk about capital allocation for us. The focus is efficient use of capital no matter what. This certainly puts us in a position of strength. Our top priority above all else is preparing for -- and delivering upon these really important launches that we have near-term.

所以我想，你提到併購，我可能會更進一步，談談我們的資本配置。無論如何，重點是有效利用資本。這無疑使我們處於有利地位。我們的首要任務是做好準備並交付我們近期推出的這些非常重要的產品。

And we're quite excited about the fact that, with success this could be back-to-back launches for thalassemia, Tsveta and the team are preparing for next year. And as we noted in our comments with sickle cell disease, the RISE UP trial is on track for complete enrollment by year end that points towards data readout next year and then again, the possibility for a back-to-back launch. That's the number one priority.

我們非常興奮的是，如果取得成功，這可能會連續推出針對地中海貧血的藥物，Tsveta 和團隊正在為明年做準備。正如我們在鐮狀細胞疾病評論中指出的那樣，RISE UP 試驗預計將在年底前完成註冊，這表明明年將有數據讀出，並且有可能連續啟動。這是第一要務。

Secondly, we continue to make great progress on advancing our own internal pipeline and of course that will use some of the capital. A great example is MDS and we're looking forward to commencing on the Phase 2b study for low risk MDS. That's a market that is growing beautifully and we're very excited about that potential. And that's by the way with tebapivat, which we were pleased to announce today as our INN for what was formerly known as AG-946.

其次，我們在推進我們自己的內部管道方面繼續取得巨大進展，當然這將使用一些資本。MDS 就是一個很好的例子，我們期待著開始針對低風險 MDS 的 2b 期研究。這是一個正在蓬勃發展的市場，我們對這種潛力感到非常興奮。順便說一下 tebapivat，我們今天很高興地宣布將其作為我們以前稱為 AG-946 的 INN。

And then to your point, Chris, about business development more broadly, it's always a focus. That said, we're very disciplined because we have no shortage of internal organic opportunities as well. Cecilia and the team do a great job of making sure that our analysis of what creates the most value-enhancing opportunity goes through a rigorous and very competitive process. And BD, all of that is certainly in our sites, but again great organic opportunities as well.

克里斯，關於更廣泛的業務發展，它始終是一個焦點。也就是說，我們非常自律，因為我們也不缺乏內部有機機會。塞西莉亞和團隊做得很好，確保我們對創造最具價值機會的因素的分析經過嚴格且極具競爭力的過程。BD，所有這些當然都在我們的網站上，但同樣也有巨大的有機機會。

Okay, great. And then maybe just a quick follow-up. On sickle cell and the opportunity -- we've had some feedback from KOLs that not all, sickle cell patients experience VOCs. Maybe just talk about your view around VOCs as an endpoint and the applicability for a broad population?

好的，太好了。然後也許只是快速跟進。關於鐮狀細胞疾病和機會——我們從 KOL 那裡得到了一些回饋，表明並非所有鐮狀細胞疾病患者都會經歷 VOC。也許只是談談您對揮發性有機化合物作為終點的看法以及對廣泛人群的適用性？

Yes, that's a great one for Sarah.

是的，這對莎拉來說是一件好事。

Yes, thank you. You're right. Not all patients experience VOCs. And as you know our intent is to deliver a product that can treat all aspects of sickle cell disease, so hemolytic anemia and sickle cell pain crises. We do as a principle across our different programs, we believe based on the mechanism of action of our drug, the drug can work across the whole spectrum of disease. A range of hemoglobin levels and a range of sickle cell pain crises.

是的，謝謝。你說得對。並非所有患者都會遇到揮發性有機化合物。如您所知，我們的目的是提供一種可以治療鐮狀細胞疾病各個方面的產品，例如溶血性貧血和鐮狀細胞疼痛危機。作為我們不同項目的原則，我們相信根據我們藥物的作用機制，該藥物可以在整個疾病譜上發揮作用。一系列血紅蛋白水平和一系列鐮狀細胞疼痛危機。

Now, from a clinical trial perspective, if you want to be able to measure a treatment effect, you need to enroll a patient population that has enough of the event ongoing to be able to measure that reduction. That is why our clinical trial from an endpoint perspective has the inclusion criteria of sickle cell pain crisis two or more. But I mean, just to be able to measure that treatment effect, but our expectation is that it can work for no matter how many sickle cell pain crises you have including just one or zero.

現在，從臨床試驗的角度來看，如果您希望能夠衡量治療效果，您需要招募有足夠的事件正在進行的患者群體，以便能夠衡量這種減少。這就是為什麼我們的臨床試驗從終點角度來看有鐮狀細胞疼痛危機兩個或兩個以上的納入標準。但我的意思是，只是為了能夠衡量治療效果，但我們的期望是，無論您有多少鐮狀細胞疼痛危機，包括一次或零次，它都可以發揮作用。

Unfortunately, that patient population can't enroll into the trial, because we would not be able to measure a treatment effect in that patient population over the course of a year. Again, the drug is meant to address all aspects of sickle cell disease and our intent would therefore be based on the data we have generated across the program, including in all of our clinical trials to go for a label that can treat sickle cell disease after a regulatory review.

不幸的是，該患者群體無法參加試驗，因為我們無法衡量該患者群體在一年內的治療效果。同樣，該藥物旨在解決鐮狀細胞疾病的所有方面，因此我們的意圖將基於我們在整個計劃中產生的數據，包括在我們所有的臨床試驗中尋找可以治療鐮狀細胞疾病的標籤監管審查。

To that point, Sarah, maybe you want to comment too on fatigue, which we try really hard not to oversimplify these diseases, especially sickle cell disease is so complex and sickle cell pain crises, VOCs is one aspect, but fatigue is another very profound need.

在這一點上，莎拉，也許你也想對疲勞發表評論，我們非常努力地不過度簡化這些疾病，特別是鐮狀細胞病是如此複雜，鐮狀細胞疼痛危機，揮發性有機化合物是一個方面，但疲勞是另一個非常深刻的方面需求。

Right. So I just mentioned the primary endpoints, the hemoglobin primary endpoint of hemoglobin and sickle cell pain crisis reduction of the other primary endpoints to be able to measure hemolytic anemia and VOC impact. As you know, that's like supported by a bunch of other secondary endpoints of which one is indeed focused on fatigue because that's what we hear from patients and from physicians that fatigue is a very, very, very impactful and burdensome to the patient population and as typical for all of our designs.

正確的。所以我剛才提到了主要終點，血紅素主要終點是血紅素和鐮狀細胞疼痛危機的減少，其他主要終點能夠衡量溶血性貧血和VOC的影響。如您所知，這就像得到了一系列其他次要終點的支持，其中一個確實關注疲勞，因為我們從患者和醫生那裡聽到，疲勞對患者群體來說是非常、非常、非常有影響和負擔的，並且我們所有設計的典型特徵。

We really try to incorporate patient feedback and therefore have incorporated fatigue as a main secondary endpoint. We've just announced the thalassemia trial data for ENERGIZE in which we did meet our key secondary endpoint for the first time on a patient reported outcome that measures fatigue. So we are very hopeful for the RISE UP study as well.

我們確實嘗試納入患者回饋，因此將疲勞作為主要的次要終點。我們剛剛公佈了 ENERGIZE 的地中海貧血試驗數據，其中我們首次根據患者報告的測量疲勞的結果達到了關鍵的次要終點。所以我們對 RISE UP 研究也充滿希望。

Gregory Renza, RBC Capital Markets.

格雷戈里·倫扎（Gregory Renza），加拿大皇家銀行資本市場部。

Great. Good morning, Brian and team. Congrats as always on the continued progress. Thanks for taking my questions. Maybe, Brian, I'll just start with, ACTIVATE-kidsT perhaps for Sarah. Sarah, could you just help us understand maybe the statistical assumptions? Certainly seems to us that that PYRUKYND effect is clinically meaningful, the results largely consistent with the adult studies.

偉大的。早上好，布萊恩和球隊。一如既往地祝賀您的持續進步。感謝您回答我的問題。也許，布萊恩，我會從「激活孩子」開始，也許是為了莎拉。莎拉，你能幫助我們理解統計假設嗎？當然，在我們看來，PYRUKYND 效應具有臨床意義，其結果與成人研究基本一致。

Was the study underpowered? Was there a placebo behavior that maybe was consistent or inconsistent with historical transfusion rates? Any added color you have would be great. And then I have a follow-up. Thank you.

研究動力不足嗎？是否存在與歷史輸血率一致或不一致的安慰劑行為？任何添加的顏色都會很棒。然後我有一個後續行動。謝謝。

Sure. Thanks for the question. So ACTIVATE-kidsT, we really tried to design a study that is appropriate for an ultrarare disease population and therefore it shows to really leverage the adult data we have generated to get to a sample size that would be appropriate for this stage of development and provide us with adequate data. We have to use pretty complex statistical methodology to look at the primary endpoint of transfusion reduction.

當然。謝謝你的提問。因此，ACTIVATE-kidsT，我們確實嘗試設計一項適合極其罕見疾病人群的研究，因此它表明真正利用我們產生的成人數據來獲得適合這一發展階段的樣本量，並提供我們有足夠的數據。我們必須使用相當複雜的統計方法來研究減少輸血的主要終點。

As mentioned, it's pretty complex because it depends on the amount of data you borrow from the adult study, and that gives them specific weights that you leverage to look at your pediatric data and we can't say that across the board, we see a treatment effect. That's why we were very specific in the press release around our low or moderate weight borrowing of the adult study data because the data, while we see positive odds ratios, the confidence intervals around that do include one. That's why we are very mindful of that.

如前所述，它非常複雜，因為它取決於您從成人研究中藉用的數據量，而這給了您用來查看兒科數據的特定權重，我們不能說一刀切，我們看到了治療效果。這就是為什麼我們在新聞稿中非常具體地介紹了成人研究數據的低或中等權重借用，因為雖然我們看到數據為正比值比，但圍繞該數據的置信區間確實包括一個。這就是為什麼我們非常關注這一點。

To your point, the data that we have observed, the fact that there are six patients, who became transfusion free, remember this is a regularly transfused patient population, meaning, they have a lot of transfusions coming into the trial. Now, these patients become transfusion free. That is a clear demonstration of a treatment effect in that specific patient population. If you're one of those six kids, that is a very meaningful difference for that specific person and their family, because this has also obviously an impact to the family.

就你的觀點而言，我們觀察到的數據，有六名患者不再需要輸血，請記住這是一個定期輸血的患者群體，這意味著他們有大量的輸血進入試驗。現在，這些患者無需輸血。這清楚地證明了該特定患者群體的治療效果。如果您是這六個孩子之一，這對那個特定的人和他們的家庭來說是一個非常有意義的差異，因為這顯然也對家庭產生了影響。

So that's why we are very excited about the results actually, because we do feel like there is a meaningful story to be told out of this study. The main goal, of course, of this study, which we also can't -- which we are very happy about is the safety assessment. This is our first pediatric clinical trial after completing an adult program and get to an indication statement there.

這就是為什麼我們實際上對結果感到非常興奮，因為我們確實覺得這項研究有一個有意義的故事可以講述。當然，這項研究的主要目標是安全評估，但我們也無法實現這一目標，我們對此感到非常高興。這是我們完成成人計畫並獲得適應症聲明後的第一個兒科臨床試驗。

This is our first endeavor to really expand the age range of that patient population. And so From that perspective, we do feel the safety data is very important. The efficacy data that we have generated is very encouraging. And so we're very excited about the next steps in the development.

這是我們真正擴大患者群體年齡範圍的第一次努力。所以從這個角度來看，我們確實覺得安全資料非常重要。我們產生的功效數據非常令人鼓舞。因此，我們對下一步的開發感到非常興奮。

That's helpful. Thank you. And just one other question, just on thalassemia. It's helpful to have sort of walk through some of the messaging as well as some of the characteristics that doctors could value. Just wondering if you had any thoughts on maybe real-world usage patterns assume all goes as planned and the approval comes through.

這很有幫助。謝謝。還有一個問題，關於地中海貧血。了解一些資訊以及醫生可能重視的一些特徵會很有幫助。只是想知道您是否對現實世界的使用模式有任何想法，假設一切按計劃進行並且批准通過。

When it comes to the patients may be staying on the drug longer-term, any expectations or thoughts on patients perhaps with less hemoglobin improvement benefit, but maybe more meaningful quality of life improvements or staying on the drug? And if you have any thoughts on what level of hemoglobin improvement we would anticipate for that patients to stay on the drug longer-term? Thanks again, Brian and team.

當涉及到患者可能會長期服用藥物時，對患者的任何期望或想法可能會帶來較少的血紅蛋白改善益處，但可能更有意義的生活品質改善或繼續服用藥物？如果您對我們預期患者長期服用該藥物的血紅素改善程度有何想法？再次感謝布萊恩和團隊。

There's a lot in there, Greg. And so maybe we'll just focus on the crux of your question that I heard was focused on the unmet need. And I think Tsveta could certainly put some color on that, because we just returned from -- she noted in her prepared comments the Cooley's Anemia Foundation meeting, which is the annual meeting for thalassemia patients in the US.

裡面有很多東西，格雷格。因此，也許我們只會關注您問題的癥結所在，我聽說您的問題主要集中在未滿足的需求上。我認為茨維塔肯定可以對此做出一些說明，因為我們剛從庫利貧血基金會會議回來——她在準備好的評論中指出，這是美國地中海貧血患者的年度會議。

It's a pretty inspiring venue to be in and certainly brings home the range of unmet need that exists. Keeping in mind these are the engaged patients. These are the ones that are actually skewed towards transfusion dependency and attend meetings like that. But Tsveta has a lot of insights that we're continuing to build upon.

這是一個非常鼓舞人心的場所，並且肯定會讓人們認識到一系列存在的未滿足的需求。請記住，這些是參與其中的患者。這些人實際上傾向於輸血依賴並參加這樣的會議。但茨維塔有許多見解，我們將繼續以這些見解為基礎。

Absolutely. I'll start and then maybe I can also transfer to Sarah to talk a little bit kind of the broad applicability of our mechanism of action to across the hemolytic anemia being thalassemia. Absolutely, Brian and I had the opportunity to attend the Cooley's Anemia Foundation Patient and Family Conference. It was truly, truly inspiring.

絕對地。我先開始，然後也許我也可以轉到莎拉那裡，談談我們的作用機制對於溶血性貧血（地中海貧血）的廣泛適用性。當然，布萊恩和我有機會參加庫利貧血基金會患者和家庭會議。這真的非常非常鼓舞人心。

To have the opportunity to connect with many patients and treating physicians as well, listen and learn about the patient journeys and the stories there, and very importantly get the excitement and the enthusiasm of both the patient and the clinical community, about potential new innovative therapies coming to the thalassemia space, including the potential of mitapivat as an approved product for that indication in the US.

有機會與許多患者和主治醫生建立聯繫，傾聽並了解患者的旅程和故事，並且非常重要的是獲得患者和臨床界對潛在的新創新療法的興奮和熱情進入地中海貧血領域，包括mitapivat 作為美國批准用於此適應症的產品的潛力。

Of course, this is the most engaged and educated audience and it was great to get their feedback. Greg, as you mentioned, we've heard it very clearly from -- the physician community and the market research that they'll consider all of the relevant endpoints that we measure in our clinical trials, as patients' characteristics when making a treatment decision being hemoglobin level, being transfusion burden, being iron overload and of course fatigue. Sarah talked about the importance of fatigue both in thalassemia and sickle cell disease.

當然，這是參與度最高、受過教育最多的觀眾，很高興得到他們的回饋。格雷格，正如您所提到的，我們從醫生社區和市場研究中清楚地聽到，他們會在做出治療決定時考慮我們在臨床試驗中測量的所有相關終點，作為患者的特徵血紅蛋白水平、輸血負擔、鐵超負荷，當然還有疲勞。莎拉談到了疲勞對於地中海貧血和鐮狀細胞疾病的重要性。

As commercial preparation, we are actually looking to reach a lot broader audience both from the physician and patient space and we are actively educating on the disease, the importance of actually improving hemoglobin levels and hemolysis, given that hemolysis is truly linked to developing disease complications and leads to increased morbidity and mortality in that patient population.

作為商業準備，我們實際上希望從醫生和患者領域獲得更廣泛的受眾，並且我們正在積極開展有關該疾病的教育，以及實際改善血紅蛋白水平和溶血的重要性，因為溶血確實與疾病並發症有關並導致該患者群體的發病率和死亡率增加。

You asked a little bit about kind of the initial patient segments that probably we'll focus on at launch and how we can expand that over time. When you think about the feedback that we got from the clinicians on the patient's characteristics, they'll look to prescribe and when you think about, which are the patients that are more likely to have regular visits and interactions with the healthcare system, this will be the transfusion-dependent patients, given that they are regularly going and seeing their clinicians when they're being transfused.

您詢問了一些關於我們在發佈時可能會關注的初始患者細分類型以及我們如何隨著時間的推移擴展它。當您考慮我們從臨床醫生那裡得到的關於患者特徵的反饋時，他們會考慮開處方，當您考慮哪些患者更有可能定期就診並與醫療保健系統互動時，這將是依賴輸血的患者，因為他們在輸血時會定期去看臨床醫師。

As well as patients, who are more symptomatic either have comorbidities linked to the disease as well as lower hemoglobin levels and fatigue, we would expect these patients probably to hear and be considered for makeup -- in the initial stages of the launch. As we look to educate product clinical and patient community, we'll look to expand that into a broader patient population.

除了症狀較重、患有與該疾病相關的合併症以及血紅蛋白水平較低和疲勞的患者外，我們預計這些患者可能會在啟動的初始階段聽到並考慮化妝。當我們希望對產品臨床和患者群體進行教育時，我們將尋求將其擴展到更廣泛的患者群體。

And now I'll hand it over to Sarah to talk about the importance of mitapivat's mechanism of action in treating the totality of thalassemia.

現在我將把它交給 Sarah 來談談 mitapivat 的作用機制在治療地中海貧血的重要性。

Thanks, Tsveta. I would like to come back to the hemoglobin cutoffs in the clinical trials. As you know, we have the clinical trial endpoint of 1 gram per deciliter or more that we look at. But to your point, Greg, there are patients who may not reach that bar of becoming a responder in the clinical trial, but still may experience some benefit that we have seen in our PKD patient population. We also see that in the thalassemia patient population.

謝謝，茨維塔。我想回到臨床試驗中的血紅素臨界值。如您所知，我們研究的臨床試驗終點為 1 克/分升或更多。但就你的觀點而言，Greg，有些患者可能無法達到臨床試驗中反應者的標準，但仍然可能會體驗到我們在 PKD 患者群體中看到的一些益處。我們在地中海貧血患者群體中也看到了這一點。

We highlighted at Dr. Taher showed a waterfall plot showing how the hemoglobin distribution in the patient population exposed to mitapivat versus exposed to placebo looks like and you could see a very similar figure in the thalassemia patient population, as what we have shown before in the pyruvate kinase deficiency patient population.

我們在Taher 博士中強調顯示了一個瀑布圖，顯示了暴露於mitapivat 的患者群體與暴露於安慰劑的患者群體中的血紅蛋白分佈情況，您可以在地中海貧血患者群體中看到非常相似的數字，正如我們之前在丙酮酸激酶缺乏症患者族群。

So there is definitely people who are improving some of their hemoglobin values, but they not reach that clinical trial endpoint. Which is also one of the reasons why to set up points, the hemolysis component is important, how patients feel is important. This is why we allow patients and physicians to decide at the end of a clinical trial to still roll over in the open label extension even if they don't meet the clinical trial bar.

因此，肯定有人正在改善一些血紅蛋白值，但他們沒有達到臨床試驗終點。這也是為什麼要設點的原因之一，溶血成分很重要，病人的感受也很重要。這就是為什麼我們允許患者和醫生在臨床試驗結束時決定仍然在開放標籤擴展中滾動，即使他們不符合臨床試驗標準。

Divya Rao, TD Cowen.

迪維亞·拉奧 (Divya Rao)，TD 考恩 (TD Cowen)。

Hi, guys. Congrats on the quarter. I had a question on the ACTIVATE-kidsT. Looking at the AEs in the trial, could you comment on if there are any changes in sex hormone levels, in the mitapivat arm versus the placebo? And then I have a follow-up.

嗨，大家好。恭喜本季。我有一個關於 ACTIVATE-kidsT 的問題。看看試驗中的 AE，您能否評論一下 mitapivat 組與安慰劑組中性激素水平是否有任何變化？然後我有一個後續行動。

Thanks for the question. So we have not gone into deeper detail yet on all of the safety beyond what we've actually put out in our press release. So we look forward to do that at an upcoming medical meeting.

謝謝你的提問。因此，除了我們在新聞稿中實際發布的內容之外，我們還沒有更深入地了解所有安全性。因此，我們期待在即將召開的醫學會議上做到這一點。

Okay. That's helpful. And then, on AG-946, I was curious when we could expect to see the Phase 2a data. And if it would be at a medical meeting or if that's sort of --?

好的。這很有幫助。然後，在 AG-946 上，我很好奇我們什麼時候可以看到 2a 階段的數據。如果是在醫學會議上或如果是這樣的話——？

First Divya, we have to practice saying tebapivat because that's [new] (corrected by company after the call). We're going to try to do the same because 946 is burned into our heads, but Sarah, you're going to comment on that.

首先 Divya，我們必須練習說 tebapivat，因為那是[新]（公司在通話後更正）。我們將嘗試做同樣的事情，因為 946 已經深深烙印在我們的腦海中，但是莎拉，你要對此發表評論。

The numbers are still burning in my head as well, so apologies if I switch. But yes, as mentioned, our current milestone and focus is the Phase 2b. The team is very, very focused on that. So we will declare later when we present the 2a data at an appropriate time, but it will be at an upcoming medical meeting.

這些數字仍然在我的腦海中燃燒，所以如果我換了，我很抱歉。但是，正如前面提到的，我們目前的里程碑和重點是 2b 階段。團隊非常非常專注於此。所以我們稍後會在適當的時候公佈 2a 數據時宣布，但會在即將舉行的醫學會議上宣布。

And I just want to reemphasize really quick that, again for MDS, and we'll learn as we proceed through the clinical trial program here, but this is a very compelling market for us. We certainly took note of the Reblozyl recently reported sales data that shows now a run rate in excess of $1.6 billion annualized. There is very high unmet need in this population.

我只是想再次強調一下，對於 MDS，我們將在進行臨床試驗計劃時了解到這一點，但這對我們來說是一個非常有吸引力的市場。我們當然注意到 Reblozyl 最近報告的銷售數據，該數據顯示目前年化運行率超過 16 億美元。該族群的未滿足需求非常高。

Certainly, as is the case in all the diseases we pursue, there's room for multiple mechanisms of action. And if we're successful, this would be not only novel PK activation, but in a pill form, which would be very significant for patients.

當然，正如我們所研究的所有疾病一樣，存在著多種作用機制的空間。如果我們成功了，這不僅是一種新穎的 PK 激活，而且是一種藥丸形式，這對患者來說非常重要。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Hi. This is Lydia on for Salveen. Thanks so much for taking our question. Just another on thalassemia. Ahead of the full Phase 3 ENERGIZE-T data that's coming at a medical meeting later this year, could you just frame expectations for the data in terms of any additional insights or data points that we could expect to glean from it in terms of the clinical meaningfulness? Thanks so much.

你好。這是薩爾文的莉迪亞。非常感謝您提出我們的問題。又一個關於地中海貧血的問題。在今年稍後的一次醫學會議上公佈完整的 3 期 ENERGIZE-T 數據之前，您能否根據我們期望從臨床方面收集的任何其他見解或數據點來構建對數據的期望？非常感謝。

So yes, we in our press release, we highlighted the primary details around the primary endpoints and one of the secondary endpoints from transfusion independence. So we will have that again because we are very happy with that. As mentioned we also met all three settings very end points and we will be presenting the data on that as well. And then, of and we will be presenting the data on data as well, and then of course safety as well. It's going to be a typical intent to treat analysis presentation in line with how we designed and ran the clinical trial and have done the pre-specified analyses.

所以，是的，我們在新聞稿中強調了主要終點的主要細節以及輸血獨立性的次要終點之一。所以我們會再這樣做，因為我們對此感到非常高興。如前所述，我們也滿足了所有三個設定的終點，我們也將提供相關數據。然後，我們也會展示數據上的數據，當然還有安全性。根據我們設計和運行臨床試驗以及完成預先指定的分析的方式來處理分析演示將是一個典型的意圖。

We're very pleased with the results, in the key secondary endpoints. You may see that we actually have a very long interval in which we measure transfusion reduction for the first time. And so we are of course again very happy with the results that that trial generated. The two trials have now completed and have their data read out. We are very eager to move forward in the development and the regulatory engagement and are looking forward to really have the review started.

我們對關鍵次要終點的結果非常滿意。您可能會發現，我們第一次測量輸血減少實際上有很長的時間間隔。因此，我們當然對這次試驗的結果再次感到非常滿意。這兩項試驗現已完成並已讀出數據。我們非常渴望在開發和監管參與方面取得進展，並期待真正開始審查。

Thanks so much.

非常感謝。

Tessa Romero, JPMorgan.

泰莎‧羅梅羅，摩根大通。

Hi, good morning, Brian and team. Thanks for taking our question. On the regulatory side in the US for thalassemia, how should we think about the gating factors at this point for your submission of the sNDA? And is the base case here a standard or priority review? And then our second question is just a follow up on the arrangement with NewBridge. How should we think about the soonest we could start to see revenue here, any patient types, specifically in the Saudi region? Thanks.

嗨，早上好，布萊恩和團隊。感謝您提出我們的問題。在美國對地中海貧血的監管方面，我們現在應該如何考慮你們提交 sNDA 的限制因素？這裡的基本案例是標準審查還是優先審查？然後我們的第二個問題只是與NewBridge 的安排的後續。我們應該如何考慮最快可以在這裡開始看到收入，任何類型的患者，特別是在沙烏地阿拉伯地區？謝謝。

Sarah, you want to start with the regulatory pathway?

莎拉，你想從監管途徑開始嗎？

Yeah. So again, we're very eager to work together with the SBA and submit the package for their review and assessment. We're doing a typical process really. We don't comment on when or how, those are milestones for later. So I think we're just pleased with the progress our team is making and are just very excited to get everything going.

是的。再次強調，我們非常渴望與 SBA 合作並將該方案提交給他們進行審查和評估。我們確實正在做一個典型的過程。我們不會評論何時或如何，這些都是以後的里程碑。因此，我認為我們對團隊的進展感到滿意，並且對一切順利進行感到非常興奮。

And then Cecilia -- sorry, Tsveta, NewBridge and GCC.

然後是塞西莉亞——抱歉，還有茨維塔、NewBridge 和 GCC。

The same thing with GCC. As we've mentioned, we're super excited about having signed agreement with NewBridge to take on the next steps of preparing for submission and potential commercialization given that GCC is the second most important region for us after the US. When it comes to submissions and approval timelines, we'll start working with NewBridge. We haven't provided the specific timelines on that.

海灣合作委員會也是如此。正如我們所提到的，鑑於海灣合作委員會是我們繼美國之後的第二個最重要的地區，我們非常高興與 NewBridge 簽署協議，以採取下一步準備提交和潛在的商業化。當談到提交和批准時間表時，我們將開始與 NewBridge 合作。我們尚未提供具體時間表。

It is -- there are about 70,000 patients with thalassemia in the region. As we start working with the NewBridge to deepen our market understanding, we might be able to provide more information, but not in this stage.

該地區約有 7 萬名地中海貧血患者。當我們開始與 NewBridge 合作以加深我們對市場的了解時，我們也許能夠提供更多信息，但目前還不能。

And clearly, Saudi Arabia is the largest component of that. That part is very clear. And do you want to just make one comment on access pathways in the region?

顯然，沙烏地阿拉伯是其中最大的組成部分。那部分非常清楚。您是否想對該地區的訪問途徑發表一點評論？

Absolutely. When we think about the GCC region, the best way to think about it is probably closer to the European kind of ways assessing pricing and reimbursement submission, getting to a pricing and reimbursement agreement and uptake. The process starts with the submission at the regulatory level where you actually obtain a price at the national level.

絕對地。當我們考慮海灣合作委員會地區時，最好的思考方式可能更接近歐洲評估定價和報銷提交、達成定價和報銷協議以及採用的方式。這個過程從向監管層面提交申請開始，您實際上在國家層面獲得了價格。

And then depending on the market, there are numerous steps out there that you actually get formulary approval and agreements with the health institutions, other local hospitals and other private markets, and over time we are expected to see tenders in the different markets and we look forward to working with NewBridge to navigate all of these key steps to patient access and speed the process as quickly as we can.

然後根據市場的不同，有很多步驟可以讓你實際上獲得與衛生機構、其他當地醫院和其他私人市場的正式批准和協議，隨著時間的推移，我們預計會在不同的市場看到招標，我們會尋找期待與 NewBridge 合作，引導患者就診的所有關鍵步驟，並儘快加快這一過程。

We're excited about that arrangement, but just to come back to by far our number one priority is the US. And again, we're thrilled to have the opportunity and Tsveta is working very assertively with the commercial team to build out our commercial prowess in rare diseases, building on the momentum, we've had in PKD and moving into thalassemia and hopefully beyond sickle cell as well.

我們對這項安排感到興奮，但回到目前為止我們的首要任務是美國。再次，我們很高興能有這個機會，Tsveta 正在與商業團隊非常自信地合作，以增強我們在罕見疾病領域的商業實力，以我們在PKD 領域的勢頭為基礎，進入地中海貧血領域，並希望超越鐮狀細胞病細胞也是如此。

Thanks so much for taking our questions.

非常感謝您回答我們的問題。

You're welcome.

不客氣。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Hey, guys. Thanks for taking our questions. Just a couple from us. First, one follow-up on the sNDA submission and just sort of framing the data that will be going into that. Is the full data we should expect by the end of this year, kind of the complete picture of what the FDA will be reviewing, and anything incremental on efficacy from that update, or more just sort of expanding on the safety and the secondaries?

嘿，夥計們。感謝您回答我們的問題。只有我們幾個人。首先，對 sNDA 提交進行後續跟進，並建立將要納入的數據。我們應該在今年年底之前獲得完整的數據，FDA 將審查的內容的完整情況，以及該更新中功效的任何增量，還是只是安全性和次要方面的擴展？

And then, one question on the PK study in the non-transfusion setting next year. Any read throughs to be made from the data today to that study? Obviously, different primary endpoints and different patient population? Thanks.

然後是關於明年非輸血環境下的 PK 研究的一個問題。是否需要從今天的數據中對這項研究進行通讀？顯然，不同的主要終點和不同的患者群體？謝謝。

Sure. Thanks, Alex. So we'll take those in sequence. And Sarah, maybe the first one, you can just comment on our planned package of data. And secondly, we'll talk about pediatrics.

當然。謝謝，亞歷克斯。所以我們將按順序進行。莎拉，也許是第一個，您可以對我們計劃的數據包發表評論。其次，我們要談談兒科。

So of course, now the program as mentioned the two randomized clinical trials have completed, have been locked and we have the data. So we're very excited to put that together. We are really doing the standard type of work that we would normally be doing for a submission that follows standard cuts, timelines and updates that we need to do and are very eager to work with the regulators and get that process started. There is always questions back and forth.

當然，現在提到的兩個隨機臨床試驗的計劃已經完成，已經鎖定，我們有了數據。所以我們很高興能把它們放在一起。我們實際上正在做標準類型的工作，我們通常會按照我們需要做的標準削減、時間表和更新進行提交，並且非常渴望與監管機構合作並啟動流程。總是有來來回回的問題。

So there -- I mean, we're just going to go through the motion. And in regards to the ACTIVATE-kidsT endpoint, so we are very pleased with the data that was generated in this clinical trial, both from a safety and efficacy.

所以，我的意思是，我們只是要進行一下議案。至於 ACTIVATE-kidsT 終點，我們對這項臨床試驗中產生的數據感到非常滿意，無論是安全性還是有效性。

Yes. And then, thoughts on the link or the read through as it would be called to ACTIVATE-kids non transfusion dependent patients?

是的。然後，對連結或通讀的想法，因為它會被稱為激活兒童非輸血依賴患者？

So again, it's a similar methodology applied for ACTIVATE-kids non-regularly transfused patient population and we're blinded. We are very eager to get to the next point and then we'll get that data package. We in the ACTIVATE-kidsT trial, we are very pleased because the transfusion free response truly highlights that the mechanism of action of mitapivat is applicable to kids as well. And so now we're hoping that that also translates into the other trial.

再次強調，這與適用於 ACTIVATE-kids 不定期輸血患者群體的類似方法相同，但我們是盲目的。我們非常渴望進入下一個點，然後我們將獲得該資料包。我們在 ACTIVATE-kidsT 試驗中感到非常高興，因為無輸血反應真正凸顯了 mitapivat 的作用機制也適用於兒童。所以現在我們希望這也能轉化為其他試驗。

Thank you.

謝謝。

And thank you. And I'm showing no further questions. I would now like to turn the call back over to Brian Goff, CEO, Andreas for closing remarks.

謝謝你。我沒有再提出任何問題。現在我想將電話轉回給 Andreas 執行長 Brian Goff 致閉幕詞。

Thanks, Justin, and so thanks a lot, everybody, for the great questions and for participating in today's call. This is clearly a very exciting time at Agios and just thinking of the year so far to date, it's been a little bit breathless in the best way possible with continued delivery on our milestones and maybe more importantly, a lot still to come that we're very much looking forward to.

謝謝賈斯汀，非常感謝大家提出的好問題並參加今天的電話會議。這顯然是Agios 非常激動人心的時刻，想想迄今為止的這一年，我們以盡可能最好的方式繼續交付我們的里程碑，這有點讓人喘不過氣來，也許更重要的是，我們還有很多事情要做。

So we have strong conviction that we're poised to deliver transformative new therapies for patients and ultimately to also can create significant long-term value to shareholders. So thanks again, and we look forward to speaking with you again soon.

因此，我們堅信，我們準備為患者提供變革性的新療法，並最終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。

This concludes today's conference. Call and thank you for participating. You may now disconnect.

今天的會議到此結束。致電並感謝您的參與。您現在可以斷開連線。