Agios Pharmaceuticals Inc (AGIO) 2024 Q4 法說會逐字稿

Good morning, and welcome to Agios' fourth quarter 2024 conference call.(Operator Instructions) Please be advised that this call is being recorded at Agios' request. I would now like to turn the call over to Chris Taylor, VP Investor Relations and Corporate Communications for Agios.

早上好，歡迎參加 Agios 2024 年第四季電話會議。 （操作員指示）請注意，應 Agios 的要求，本次通話正在錄音。現在，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 fourth quarter and full year 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.

謝謝您，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 年第四季和全年財務業績以及近期業務亮點。您可以造訪我們網站 agios.com 的投資者部分來存取今天電話會議的幻燈片。

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, Chief Commercial Officer; and Cecilia Jones, Chief Financial Officer. 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.

在今天的電話會議上，我們與我們的首席執行官 Brian Goff 一起出席；首席醫療官兼研發主管 Sarah Gheuens 博士； Tsveta Milanova，首席商務官；以及首席財務官塞西莉亞·瓊斯（Cecilia Jones）。在我們開始之前，我想提醒大家，我們在本次電話會議上發表的一些聲明將包括前瞻性陳述。

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.

由於各種風險、不確定性和其他因素，包括我們最近向美國證券交易委員會提交的文件以及我們可能向美國證券交易委員會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所表達或暗示的事件和結果存在重大差異。

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

現在，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. We are especially focused on rare diseases that result in the dysfunction and disruption of red blood cells, including pyruvate kinase deficiency, thalassemia, sickle cell disease, and lower-risk myelodydylastic syndromes, or MDS.

謝謝，克里斯。大家早安，感謝大家的收看。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、地中海貧血、鐮狀細胞疾病和低風險骨髓增生異常綜合症（MDS）。

Our lead product, PYRUKYND, a pyruvate 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. Today, we are pleased to share with you our results from the fourth quarter as well as reflect on accomplishments throughout 2024 and our expectations for the exciting new year ahead. Our rare blueprint for success uniquely positions us to drive significant growth in shareholder value creation over both the near and the long term.

我們的主要產品 PYRUKYND 是一種丙酮酸激酶活化劑，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。今天，我們很高興與您分享我們第四季度的業績，並回顧 2024 年全年的成就以及對未來激動人心的新年的期望。我們罕見的成功藍圖使我們能夠在短期和長期內推動股東價值創造的顯著成長。

First, we have the exciting prospect of two additional commercial launches to support what we consider to be a multibillion-dollar growth opportunity for our lead product, PYRUKYND. We are planning for a potential approval and launch in thalassemia in September of this year, followed by sickle cell disease in 2026. Second, our early and mid-stage pipeline is robust and poised for clinical advancement offering a strong foundation for innovation and growth. And finally, supporting it all is our highly experienced team with a proven track record of executional excellence and our strong balance sheet, which puts us in the enviable position of being able to independently grow the company and execute on these exciting opportunities.

首先，我們有一個令人興奮的前景，即另外兩次商業發布，以支持我們認為的主導產品 PYRUKYND 的數十億美元的成長機會。我們計劃在今年 9 月獲得地中海貧血症治療藥物的批准並上市，隨後在 2026 年獲得鐮狀細胞疾病治療藥物的批准並上市。其次，我們早期和中期的產品線十分強大，可以為臨床進展做好準備，為創新和成長奠定堅實的基礎。最後，支持這一切的是我們經驗豐富的團隊，他們在執行方面擁有卓越的記錄，並且擁有強大的資產負債表，這使我們處於令人羨慕的地位，能夠獨立發展公司並抓住這些激動人心的機會。

2024 was an exceptional year of executional and scientific excellence at Agios, as shown on this slide, with checkmarks for each of the key milestones we projected one year ago. We meaningfully advanced each of our key programs, including filing for regulatory approval in thalassemia across four markets and completing enrollment in our Phase III RISE up study for sickle cell disease. And we continue to progress our early pipeline, building the foundation for sustainable long-term growth.

正如這張投影片所示，2024 年是 Agios 在執行和科學方面取得卓越成就的一年，我們一年前預測的每個關鍵里程碑都已實現。我們每個關鍵項目都取得了顯著進展，包括在四個市場申請地中海貧血的監管批准，以及完成鐮狀細胞疾病 III 期 RISE 研究的招募。我們將繼續推進早期產品線，為長期永續成長奠定基礎。

After a transformative 2024, we believe 2025 is a breakout year for Agios. Over the next 12 months, we will focus on three key priorities. Number 1, maximizing the potential of the PYRUKYND franchise. Number 2, advancing and diversifying our key pipeline programs. And number 3, strategically focusing our capital deployment to sustain and drive our growth. And building on all that was accomplished in 2024, we have another year ahead with compelling commercial, regulatory and clinical milestones.

在經歷了變革性的 2024 年之後，我們相信 2025 年將是 Agios 突破的一年。未來 12 個月，我們將重點放在三個關鍵優先事項上。第一，最大限度地發揮 PYRUKYND 特許經營的潛力。第二，推進並多樣化我們的關鍵管道項目。第三，策略性地集中我們的資本部署來維持和推動我們的成長。基於 2024 年所取得的所有成就，我們將迎來令人矚目的商業、監管和臨床里程碑之年。

Today, we announced top line results from the ACTIVATE KIDS Phase III trial with mitapivat in pediatric patients with PK deficiency who are not regularly transfused. This is Agios' first pediatric clinical program for mitapivat in a rare hemolytic anemia, and we are excited for Sarah to share with you the positive top line data from this study in just a moment.

今天，我們發表了 ACTIVATE KIDS 第三階段試驗的首要結果，該試驗針對未定期輸血的 PK 缺乏症兒科患者，使用了 mitapivat 進行治療。這是 Agios 首次針對罕見溶血性貧血進行 mitapivat 的兒科臨床項目，我們很高興 Sarah 很快就能與大家分享這項研究的積極頂線數據。

We also anticipate some exciting developments for our mid- and early-stage pipeline programs. For TevaPIVac, our novel PK activator formerly known as AG-946. We expect to complete enrollment in the ongoing Phase IIb study in lower-risk MDS by year-end and initiate a Phase II study in sickle cell disease by mid-2025. Additionally, we expect to file an investigational new drug application for AG-236, or siRNA targeting 106 inhibition intended for the treatment of polycythemia vera in mid-2025.

我們也預計我們的中期和早期管道項目將取得一些令人興奮的進展。對於 TevaPIVac，我們的新型 PK 活化劑以前稱為 AG-946。我們預計在年底前完成正在進行的低風險 MDS IIb 期研究的招募，並在 2025 年中期啟動鐮狀細胞疾病 II 期研究。此外，我們預計將在 2025 年中期提交 AG-236 或針對 106 抑制的 siRNA 的新藥試驗申請，用於治療真性紅血球增多症。

And the most significant expected events for 2025 include the September 7 PDUFA goal date for our sNDA filing of PYRUKYND in thalassemia and the Phase III readout of the RISE study of mitapivat in sickle cell disease by year-end. As you can see, this year promises to be exciting with multiple catalysts across our pipeline that hold significant value for shareholders and have transformative potential for patients.

2025 年預計最重要的事件包括我們針對地中海貧血的 PYRUKYND 的 sNDA 申請的 PDUFA 目標日期為 9 月 7 日，以及針對鐮狀細胞病的 mitapivat 的 RISE 研究的 III 期讀數將於年底前完成。如您所見，今年將是令人興奮的一年，我們整個產品線中都有多種催化劑，它們對股東具有重要價值，對患者俱有變革潛力。

With those introductory comments, let me now hand it off to Sarah to review our exciting progress in R&D.

有了這些介紹性的評論，現在請容許我交給莎拉回顧我們在研發方面令人興奮的進展。

Thanks, Brian. Our pipeline includes a well-rounded mix of late-stage programs nearing market entry and promising mid- and early-stage opportunities that showcase our therapeutic depth and breadth. We prioritize opportunities where our expertise and resources can make a measurable impact and create significant value.

謝謝，布萊恩。我們的產品線包括即將進入市場的後期項目和有前景的中早期項目，這些項目展示了我們治療的深度和廣度。我們優先考慮那些我們的專業知識和資源能夠產生可衡量的影響並創造重大價值的機會。

As you may have seen, this morning, we announced top line results from our second Phase III pediatric study, ACTIVATE-Kids, which evaluated mitapivat in pediatric patients with PK deficiency who are not regularly transfused. This complements the Phase III activated T study of mitapivat in children with PK deficiency who are regularly transfused, which read out top line data in August of last year.

正如您可能已經看到的，今天上午，我們公佈了第二階段 III 期兒科研究 ACTIVATE-Kids 的頂線結果，該研究評估了 mitapivat 對未定期輸血的 PK 缺乏症兒科患者的作用。這是 mitapivat 對患有 PK 缺乏症並定期輸血的兒童進行的 III 期活化 T 細胞研究的補充，該研究於去年 8 月讀出了頂線數據。

Turning to the results of the Activate-Kids study. A total of 30 patients age 1 to less than 18 years old were enrolled with 19 randomized to mitapivat twice daily and 11 randomized to match placebo. All patients in both arms completed 20-week double-blind period.

談談 Activate-Kids 研究的結果。總共有 30 名年齡在 1 歲至 18 歲以下的患者參與其中，其中 19 名隨機接受每日兩次 mitapivat 治療，另外 11 名隨機接受配對安慰劑治療。雙組所有患者均完成20週的雙盲期。

The primary endpoint of the study was hemoglobin response, defined as a greater than or equal to 1.5 grams per deciliter increase in hemoglobin concentration from baseline that is sustained at two or more scheduled assessments at weeks 12, 16 and 20 during the double-blind period.

研究的主要終點是血紅蛋白反應，定義為在雙盲期間的第 12、16 和 20 週兩次或兩次以上預定的評估中，血紅蛋白濃度從基線增加大於或等於每分升 1.5 克。

The primary endpoint of the study was met. There were 31.6% or 6 of 19 patients in the mitapivat arm achieving a hemoglobin response compared to 0% or 0 of 11 patients in the placebo arm. In addition, improvements in changes from baseline for markers of hemolysis were observed in the mitapivat arm compared to the placebo arm.

研究的主要終點已經達到。mitapivat 組有 31.6% 或 19 名患者中有 6 名達到血紅素反應，而安慰劑組為 0% 或 11 名患者中沒有達到血紅素反應。此外，與安慰劑組相比，mitapivat 組的溶血標記物基線變化有所改善。

In the 20-week double by period, a similar proportion of patients have adverse events in the mitapivat and placebo arms, and there are no discontinuations of study treatment due to adverse events for any reason. The safety results were consistent with the safety profile for mitapivat previously observed for adult patients with PK deficiency who are not regularly transfused.

在 20 週的雙倍期內，mitapivat 組和安慰劑組出現不良事件的患者比例相似，且沒有因任何原因的不良事件而停止研究治療。安全性結果與先前觀察到的針對不定期輸血的 PK 缺乏症成年患者的 mitapivat 安全性情況一致。

With data now available from the randomized placebo-controlled double-blind period of both Phase III pediatric PK deficiency studies, we look forward to sharing more detailed findings with the community and interacting with regulators.

目前我們已經獲得了兩項 III 期兒科 PK 缺乏症研究的隨機安慰劑對照雙盲期數據，我們期待與社區分享更詳細的研究結果並與監管機構互動。

The ACTIVATE-KIDS and ACTIVATE-KIDS Phase III studies marked Agios' first pediatric clinical program for a rare hemolytic anemia, providing valuable insights that will help shape the company's future clinical programs evaluating mitapivat in pediatric patients with thalassemia in sickle cell disease.

ACTIVATE-KIDS 和 ACTIVATE-KIDS III 期研究標誌著 Agios 首次針對一種罕見溶血性貧血的兒科臨床項目，該研究提供了寶貴的見解，將有助於塑造該公司未來的臨床項目，評估 mitapivat 對鐮狀細胞疾病地中海貧血兒科患者的療效。

Now turning to thalassemia. This is a rare lifelong inherited blood disorder that causes chronic anemia and patients with thalassemia often experience a range of debilitating complications such as organ damage, stroke and other serious health issues.

現在來談談地中海貧血。這是一種罕見的終生遺傳性血液疾病，會導致慢性貧血，地中海貧血患者通常會經歷一系列使人衰弱的併發症，如器官損傷、中風和其他嚴重的健康問題。

Government management strategy for thalassemia, such as blood transfusions and iron chelation therapy can also lead to significant secondary effects compounding the health challenges patients face. Today, patients have limited or no effective treatment options with 67% of diagnosed patients in the US have no approved therapies.

政府針對地中海貧血的管理策略，例如輸血和鐵螯合療法，也可能導致嚴重的副作用，加劇患者面臨的健康挑戰。目前，患者的治療選擇有限或根本沒有有效的治療選擇，美國 67% 的確診患者沒有核准的治療方法。

In 2024, we announced positive results from the energized and energized Phase III trial evaluating mitapivat versus placebo in adults with non-transfusion-dependent and transfusion attendant alpha or beta thalassemia, respectively. A top line summary of the results across these two studies is shown on the left-hand side of this slide. Based on the favorable benefit risk profile observed in both the ENERGIZE and ENERGIZE-T Phase III studies, we believe mitapivat has the potential to become a foundational and convenient oral medication for thalassemia patients regardless of their genotype or transfusion needs.

2024 年，我們宣布了活力十足和活力十足的 III 期試驗的積極結果，該試驗分別評估了 mitapivat 與安慰劑對非輸血依賴型和輸血伴隨型 α 或 β 地中海貧血成人患者的療效。本投影片左側顯示了這兩項研究結果的頂行摘要。根據 ENERGIZE 和 ENERGIZE-T 第三階段研究中觀察到的良好效益風險狀況，我們相信 mitapivat 有可能成為地中海貧血患者的基礎和便捷口服藥物，無論他們的基因型或輸血需求如何。

In December, we announced a simultaneous filing for regulatory approval of PYRUKYND for this indication in the US, the European Union, Kingdom of Saudi Arabia and the United Arab Emirates. And last month, we announced that the FDA accepted our supplemental new drug application with a PDUFA goal date of September 7, 2025.

12 月，我們宣布同時向美國、歐盟、沙烏地阿拉伯王國和阿拉伯聯合大公國提交 PYRUKYND 用於此適應症的監管批准。上個月，我們宣布 FDA 接受了我們的補充新藥申請，PDUFA 目標日期為 2025 年 9 月 7 日。

Moving on to sickle cell disease. This inherited lifelong blood disorder is estimated to affect approximately 120,000 to 135,000 individuals across the US and EU5 with a global prevalence exceeding 3 million. Clinical features of sickle cell disease are chronic hemolytic anemia and vaso-occlusion, which can lead to pain for quality of life, organ damage and early mortality. There is an urgent need for novel therapeutic options to elevate the standard of care for patients suffering from this debilitating and life-threatening disease.

繼續討論鐮狀細胞疾病。據估計，這種遺傳性終身血液疾病影響美國和歐盟5 約 12 萬至 13.5 萬人，全球患病人數超過 300 萬人。鐮狀細胞疾病的臨床特徵是慢性溶血性貧血和血管阻塞，會導致生活品質下降、器官受損和早期死亡。迫切需要新的治療方案來提高患有這種使人衰弱並危及生命的疾病的患者的護理標準。

Based on the positive results from our Phase II RISE Up study, along with encouraging data from other hemolytic anemias with a shared pathophysiology, we see significant potential with mitapivat in sickle cell disease as well. The Phase III RISE Up study completed enrollment in October 2024 with over 200 patients enrolled globally, achieving this milestone just over a year after improvement began.

根據我們第二階段 RISE Up 研究的積極成果，以及具有相同病理生理學的其他溶血性貧血的令人鼓舞的數據，我們看到 mitapivat 在鐮狀細胞疾病方面也具有巨大的潛力。第三階段 RISE Up 研究於 2024 年 10 月完成招募，全球招募了 200 多名患者，在病情開始改善僅一年多後就實現了這一里程碑。

In this study, we have two independent primary endpoints, hemoglobin response and annualized rate of sickle cell pain crises. Obtaining inter-primary endpoints allows us to apply alpha to the trial secondary endpoints. With our secondary endpoints, we are using a variety of measures to assess mitapivat's potential in improving our patients feel and function. We expect to report top line results from the Phase III study in late 2025, with a regulatory filing and potential US approval in 2026.

在這項研究中，我們有兩個獨立的主要終點，即血紅蛋白反應和鐮狀細胞疼痛危機的年發生率。獲得主要終點間試驗使我們能夠將 alpha 應用於試驗次要終點。透過我們的次要終點，我們正在使用各種措施來評估 mitapivat 在改善患者感覺和功能方面的潛力。我們預計將在 2025 年底報告第三階段研究的頂線結果，並於 2026 年提交監管備案並可能獲得美國批准。

We believe mitapivat has the potential to emerge as a best-in-class therapy aimed at addressing the high unmet need in this disease by improving anemia, reducing sickle cell pain crises and making patients feel better. Next, I'd like to give a brief update on DevatIVA, which is currently being explored as a potential treatment option for low-risk MDS in sickle cell disease.

我們相信，mitapivat 有潛力成為一流的治療方法，透過改善貧血、減少鐮狀細胞疼痛危機和讓患者感覺更好，解決這種疾病中未滿足的高度需求。接下來，我想簡單介紹 DevatIVA，目前正在探索它作為鐮狀細胞疾病低風險 MDS 的潛在治療選擇。

With lower-risk MDS, we aim to deliver the first oral therapy that addresses anemia due to ineffective erythropoiesis in the disease. This disease affects approximately 75,000 to 80,000 patients in the US and EU5 with lower-risk MDS accounting for approximately 70% of all MDS cases. Last year, we initiated a Phase IIb study of tevapipat Viva in MDS featuring three cohorts at dosages of 10, 15 and 20 milligrams, all of which are higher than the 5-milligram dose in the Phase IIa study.

對於低風險 MDS，我們的目標是提供首個口服療法，治療因該疾病中紅血球生成無效而導致的貧血。該疾病影響了美國和歐盟5國約75,000至80,000名患者，其中低風險MDS約佔所有MDS病例的70%。去年，我們啟動了 tevapipat Viva 治療 MDS 的 IIb 期研究，研究對象分為三組，劑量分別為 10、15 和 20 毫克，均高於 IIa 期研究中的 5 毫克劑量。

Enrollment is proceeding well, and we are on track to complete enrollment later this year. Additionally, last September, the FDA granted orphan drug designation to tevapipat in this indication, underscoring the importance of bringing an oral treatment option to patients suffering from this rare disease.

招生工作進展順利，我們預計在今年稍後完成招生。此外，去年 9 月，FDA 授予 tevapipat 用於治療這種罕見疾病的孤兒藥物資格，強調了為患有這種罕見疾病的患者提供口服治療選擇的重要性。

In sickle cell disease, given the significant medical need in the heterogenety of the disease, treating physicians emphasize the importance of having multiple treatment options available. In 2024, we presented Phase I results of tevapipat in sickle cell disease at the ASH annual meeting. Based on these findings, we will advance this clinical program to Phase II development with patient enrollment expected to begin in mid-2025.

對於鐮狀細胞疾病，鑑於疾病的異質性具有巨大的醫療需求，治療醫生強調了提供多種治療方案的重要性。2024 年，我們在 ASH 年會上展示了 tevapipat 治療鐮狀細胞疾病的 I 期結果。根據這些發現，我們將推進該臨床計畫進入 II 期開發，預計患者招募將於 2025 年中期開始。

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

說完這些，我現在將電話轉給莎拉。

Thanks, Sarah. By 2026, we have the potential to expand Biocon indications to include thalassemia and sickle cell disease, addressing the needs of these two very underserved patient populations. With our anticipated launch in thalassemia later this year, we are aiming to deliver the first therapy indicated to treat all subtypes of the disease.

謝謝，莎拉。到 2026 年，我們有可能擴大 Biocon 的適應症，包括地中海貧血和鐮狀細胞疾病，滿足這兩類極度缺乏醫療服務的患者群體的需求。我們預計今年稍後推出針對地中海貧血的治療藥物，我們的目標是提供首個用於治療該疾病所有亞型的療法。

And with sickle cell lease, are going to deliver a novel oral therapy that includes anemia, reducing vaso-occlusive crises for VOCs and improved fatigue. By expanding biokine into these two larger patient populations, we aim to transform the treatment landscape for patients living with these diseases, thereby, creating a multibillion-dollar opportunity for our company and our shareholders.

並且透過鐮狀細胞租賃，將提供一種新型口服療法，包括治療貧血、減少 VOC 的血管閉塞危機和改善疲勞。透過將 biokine 擴展到這兩個更大的患者群體，我們旨在改變患有這些疾病的患者的治療前景，從而為我們的公司和股東創造數十億美元的機會。

And our team is working diligently to prepare for a potential near-term launch in thalassemia with three key areas of focus. First, we are executing a robust disease state education campaign that highlights the disease pathology the long-term complications of the disease and current standards of care and the importance of frequent monitoring and management.

我們的團隊正在勤奮努力為近期在地中海貧血領域開展研究做好準備，並專注於三個關鍵領域。首先，我們正在進行強有力的疾病狀況教育活動，強調疾病的病理、疾病的長期併發症、目前的護理標準以及頻繁監測和管理的重要性。

Second, we are rightsizing our cross-functional field team to ensure a successful launch in this larger yet still rare market. For example, for PK deficiency, our sales team was tasked at 18 to 20 professionals. For thalassemia, we have strategically grown the sales organization to approximately twice that size. And third, we are actively engaging and educating payers on thalassemia to facilitate disease understanding and support patient access.

其次，我們正在調整跨職能現場團隊的規模，以確保在這個規模更大但仍然稀有的市場中成功推出產品。例如，針對PK缺陷，我們的銷售團隊配備了18到20名專業人員。對於地中海貧血，我們策略性地將銷售組織規模擴大到大約兩倍。第三，我們積極吸引並教育付款人有關地中海貧血的知識，以促進對疾病的了解並支持患者獲得治療。

There are approximately 6,000 adults diagnosed with thalassemia in the US with most patients diagnosed before adult food. With the availability of claims data, we can identify where these patients are managed within the health care system offering valuable clarity for our launch preparations. Within that population, we estimate that PYRUKYND initial launch problems will address approximately 65% of the adult thalassemia patient population.

美國約有 6,000 名成年人被診斷出患有地中海貧血，大多數患者在成年之前就被診斷出來。有了索賠數據，我們可以確定這些患者在醫療保健系統中的管理位置，為我們的啟動準備提供寶貴的清晰度。在該族群中，我們估計 PYRUKYND 的初始啟動問題將解決約 65% 的成年地中海貧血患者群體。

We expect patients with more frequent contact with the health care system due to their disease symptoms to be considered for therapy first. These patients include those who are transfusion dependent as well as those that are nontransfusion dependent already experiencing complications or debilitating fatigue. Our team is actively engaged in the field, continuously deepening our understanding of this diverse patient segment and the multicultural dimensions of the disease.

我們希望那些由於疾病症狀而更頻繁地與醫療保健系統聯繫的患者能夠首先考慮接受治療。這些患者包括依賴輸血的患者以及已經出現併發症或嚴重疲勞的非依賴輸血的患者。我們的團隊積極參與該領域，並不斷加深對這個多樣化患者群體以及該疾病的多元文化維度的了解。

As we move towards increasingly larger launch opportunities, we are anchoring on the transformative profile of PYRUKYND in thalassemia, characterized by a number of firsts. This is potentially the first therapy for both alpha and beta thalassemia patients, the first oral therapy for the disease, the first treatment to demonstrate quality of life improvement for non-transfusion-dependent patients and the first treatment to demonstrate 36-week durability of effect in reducing transfusion burden. This is what motivates us to deliver PYRUKYND to people suffering from thalassemia as quickly as possible.

隨著我們面臨越來越大的發布機會，我們將重點放在 PYRUKYND 在治療地中海貧血方面的變革性特徵，其特點包括多項首創。這可能是首個同時針對 α 和 β 地中海貧血患者的治療方法、首個針對該疾病的口服治療方法、首個證明能夠改善非輸血依賴患者生活品質的治療方法以及首個證明能夠減輕輸血負擔的效果持續 36 週的治療方法。這就是我們盡快向患有地中海貧血症的人們提供 PYRUKYND 的動力。

Finally, let me provide a brief update on the current launch of PYRUKYND in PK deficiency. In the fourth quarter of 2024, we generated $10.7 million in net PYRUKYND revenue compared to $9 million in the third quarter of 2024. In the US, a total of 223 patients have completed a prescription enrollment form, including 12 in the fourth quarter of 2024, a 6% increase versus the prior quarter. This has translated into 130 net patients on therapy for this ultra-rare disease.

最後，讓我簡單介紹一下目前推出的 PYRUKYND 在 PK 缺乏症治療的進展。2024 年第四季度，我們創造了 1,070 萬美元的 PYRUKYND 淨收入，而 2024 年第三季為 900 萬美元。在美國，共有 223 名患者完成了處方登記表，其中 2024 年第四季有 12 名患者，比上一季增加了 6%。這意味著接受這種極為罕見疾病治療的患者淨增加130人。

We believe the capabilities we continue to strengthen through the current launch will provide a firm foundation from which to maximize potential future US launches of PYRUKYND in thalassemia in 2025 and in sickle cell disease in 2026.

我們相信，透過此次發表會我們不斷加強的能力將為美國在 2025 年和 2026 年分別推出 PYRUKYND 治療地中海貧血和鐮狀細胞疾病的藥物奠定堅實的基礎。

Looking at the months ahead, our team will continue to sharpen its focus on the preparation for launch with thalassemia as our main priority. We are excited about the commercial potential of thalassemia. This is driven by the following three factors -- patients are diagnosed and known to the health care system.

展望未來幾個月，我們的團隊將繼續集中精力做好發射準備工作，並將地中海貧血作為我們的首要任務。我們對地中海貧血的商業潛力感到非常興奮。這是由以下三個因素推動的——患者得到診斷並被醫療保健系統了解。

The burden of disease is well characterized, and they are well-established KOLs and patient advocacy groups. We are confident that all these elements, together with our robust preparation will pave the way for a successful launch. In closing, we are inspired and energized by the potential to bring a new therapy to this underserved patient populations around the world.

疾病負擔已被很好地描述，他們是成熟的 KOL 和患者權益團體。我們相信，所有這些因素加上我們的充分準備將為成功發射鋪平道路。最後，我們為能夠為世界各地這些醫療資源不足的患者群體帶來新的治療方法而感到鼓舞和振奮。

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

說完這些，我將把電話轉給塞西莉亞。

Thanks, Sarah. Our fourth quarter 2024 financial results can be found in the press release we issued this morning, and more detail will be included in our 10-K, which will be filed later today. Let me now take a moment to provide some context and highlight a few key points. Fourth quarter 2024 net PYRUKYND revenue was $10.7 million, an increase of 51% compared to $7.1 million in the fourth quarter of 2023.

謝謝，莎拉。我們的 2024 年第四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我們今天稍後提交的 10-K 中。現在，請允許我花點時間來提供一些背景資訊並強調幾個關鍵點。2024 年第四季 PYRUKYND 淨收入為 1,070 萬美元，較 2023 年第四季的 710 萬美元成長 51%。

We note that revenue in Q4 of 2024 were higher, primarily driven by year-end stocking and adjustments to certain revenue reserves. These account for approximately $1.6 million in Q4, and we do not expect these items to repeat in the first quarter of 2025. While lower in the fourth quarter of 2024, gross to net has generally been and is expected to be in the 10% to 20% range on an annual basis, consistent with other rare disease launches and will experience quarter-to-quarter variability.

我們注意到，2024 年第四季的收入有所增加，這主要得益於年終備貨和某些收入儲備的調整。這些在第四季度的價值約為 160 萬美元，我們預計這些項目不會在 2025 年第一季重複出現。儘管 2024 年第四季的毛利與淨利之比較低，但總體而言預計每年將在 10% 至 20% 的範圍內，與其他罕見疾病藥物的上市情況一致，並且將出現季度間差異。

Cost of sales for the quarter was $1.3 million. R&D expenses were $82.8 million for the fourth quarter, an increase of $5.3 million compared to the fourth quarter of 2023. This was primarily driven by workforce-related expenses. SG&A expenses were $51.7 million for the fourth quarter, an increase of $16.4 million compared to the prior year quarter. This was primarily driven by an increase in commercial-related activities as we prepare for the potential approval of PYRUKYND in thalassemia in 2025.

本季銷售成本為 130 萬美元。研發第四季的支出為 8,280 萬美元，比 2023 年第四季增加 530 萬美元。這主要是受勞動力相關費用的影響。第四季銷售、一般及行政開支為 5,170 萬美元，較去年同期增加 1,640 萬美元。這主要是由於我們為 2025 年 PYRUKYND 用於治療地中海貧血的潛在批准做準備，商業相關活動的增加。

It is worth noting that we received a total of $1.1 billion in milestone payments following the FDA approval of vorasidenib, which were recorded in the third quarter. These payments included a $905 million payment from Royalty Pharma in connection with the vorasidenib royalty purchase agreement Agios announced in May 2024 as well as a $200 million payment from Servier in connection with Agios divestiture of its oncology business in 2021.

值得注意的是，在FDA批准vorasidenib之後，我們總共收到了11億美元的里程碑付款，這些付款是在第三季記錄的。這些付款包括 Royalty 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。

As a reminder, Agios will retain a 3% royalty on annual US net sales of vorasidenib greater than $1 billion. Taking all this into account, we ended the fourth quarter with cash, cash equivalents and marketable securities of approximately $1.5 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.

提醒一下，Agios 將保留沃拉西尼佈在美國每年淨銷售額超過 10 億美元時的 3% 的特許權使用費。考慮到所有這些因素，我們在第四季結束時的現金、現金等價物和有價證券約為 15 億美元。我們預計，這項平衡加上預期的產品收入和利息收入將提供財務獨立性，為在地中海貧血和鐮狀細胞疾病領域推出潛在的 PYRUKYND 做好準備，推進現有項目，並透過內部和外部發現的資產趁機擴大我們的產品線。

Going forward and with our PDUFA date in sight, we are shifting our focus to preparing for the potential launch in thalassemia, and we expect 2025 revenues for PK deficiency to be relatively flat compared to 2024. Regarding thalassemia, it is worth reminding everyone that it can be several weeks, particularly at launch between prescription enrollment form and a patient initiating therapy. Combined with the expected time to set up payer access, we're looking at a more of a partial quarter, in Q4, which should be factored into modeling revenue expectations for 2025. Obviously, we are eager for the September 7 PDUFA date to arrive and the team is well prepared for it.

展望未來，隨著 PDUFA 日期臨近，我們將把重點轉向為地中海貧血的潛在上市做準備，我們預計 2025 年 PK 缺乏症的收入將與 2024 年相比相對持平。關於地中海貧血，值得提醒大家的是，這可能需要數週時間，特別是在處方登記表和患者開始治療之間。結合設定付款人存取權限的預期時間，我們預計第四季度會出現更多部分的情況，這應該被考慮到 2025 年的收入預期模型中。顯然，我們迫切希望 9 月 7 日的 PDUFA 日期到來，團隊也為此做好了充分的準備。

Looking into 2026 and beyond, we're optimistic about the team's ability to translate the favorable market dynamics that I described earlier into a significant revenue trajectory for thalassemia. In closing, 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.

展望 2026 年及以後，我們對團隊將我先前描述的有利市場動態轉化為地中海貧血顯著收入軌跡的能力充滿信心。最後，我們仍然專注於創造股東價值，包括積極管理我們的成本基礎和部署嚴謹的現金分配方法，為支持 PYRUKYND 未來的潛在推出做好準備。隨著我們在短期內朝著更多潛在的價值創造里程碑邁進，我相信我們的資產負債表將繼續使我們能夠保持強勢地位。

I will now turn the call back over to Brian.

我現在將電話轉回給布萊恩。

Thanks, Cecilia. Before we conclude, I'd like to highlight one more piece of news from our press release this morning. Dr. David Schenkein has informed us that he will step down from our Board of Directors effective February 28, 2025, to devote more time to his other commitments. He will continue to serve as a strategic adviser to Agios' leadership team, concentrating on advancing the company's clinical development programs.

謝謝，塞西莉亞。在結束之前，我想強調一下我們今天上午新聞稿中的另一個新聞。David Schenkein 博士已通知我們，他將於 2025 年 2 月 28 日起辭去董事會職務，以便將更多時間投入其他事務中。他將繼續擔任 Agios 領導團隊的策略顧問，專注於推進公司的臨床開發計劃。

David has been with Agios for 15 years, serving as the company's CEO for 10 years and throughout as a member of the Board of Directors. On a personal level, I'd like to thank David for his friendship, mentorship and guidance throughout my years leading Agios. He has played an instrumental role in shaping our company into what it is today. On behalf of the entire organization, I also want to express our deep appreciation for his invaluable contributions. We are truly grateful and look forward to continuing our collaboration with him in his new advisory role.

David 在 Agios 工作了 15 年，其中 10 年擔任公司首席執行官，並一直擔任董事會成員。從個人角度來說，我要感謝 David 在我領導 Agios 的這些年裡給予我的友誼、指導和指導。他在我們公司發展到今天這個樣子的過程中發揮了至關重要的作用。我還要代表整個組織對他的寶貴貢獻表示深切的謝意。我們由衷感激並期待與他在新的顧問職位上繼續合作。

2024 was marked by exceptional progress at Agios. And as you've heard, we have exciting regulatory and clinical milestones ahead in 2025. We believe 2025 will be a breakout year for the company based on anticipated approval and launch of PYRUKYND in thalassemia, a critical Phase III readout in sickle cell disease and important anticipated progress across our mid- and early-stage pipeline.

2024 年，Agios 取得了非凡的進步。正如您所聽到的，我們在 2025 年將實現令人興奮的監管和臨床里程碑。我們相信，2025 年將是公司突破的一年，基於 PYRUKYND 預計獲得批准和上市，用於治療地中海貧血，鐮狀細胞病的關鍵 III 期讀數以及我們中期和早期管道的重要預期進展。

In closing, I'd like to briefly reinforce Cecilia's comments. We have a very strong balance sheet, which provides us with the ability to independently execute across our key priorities, which include maximizing the potential PYRUKYND launches in thalassemia and sickle cell disease, advancing our existing early and mid-stage clinical programs and expanding our pipeline with both internal and external opportunities.

最後，我想簡要地重申一下塞西莉亞的評論。我們擁有非常強大的資產負債表，這使我們能夠獨立執行我們的關鍵優先事項，包括最大限度地發揮 PYRUKYND 在治療地中海貧血和鐮狀細胞病方面的潛力，推進我們現有的早期和中期臨床項目，並利用內部和外部機會擴大我們的產品線。

We remain committed to disciplined cash allocation, ensuring our strong balance sheet supports the achievement of key milestones and positions us for continued value creation. We look forward to the future as we strive to change the trajectory of these rare diseases.

我們將繼續致力於嚴格的現金分配，確保強勁的資產負債表支持關鍵里程碑的實現，並使我們能夠持續創造價值。我們期待未來，並努力改變這些罕見疾病的發展軌跡。

With that, I'd like to open the call for questions. Operator, please open the line.

現在，我想開始回答問題。接線員，請接通線路。

(Operator Instructions)

（操作員指令）

Eric Schmidt, Cantor.

埃里克·施密特，康托爾。

Congrats on all the progress looking forward to another remarkable year in 2025. Maybe first for Sarah, what's the company's plan or strategy for updating the investment community on the safety profile of mitapivat should there be any further cases of hepatocellular injury or any signals whatsoever there?

恭喜您所取得的所有進步，期待 2025 年又是一個非凡的一年。首先對 Sarah 來說，如果出現更多肝細胞損傷病例或任何訊號，公司有什麼計畫或策略來向投資界更新 mitapivat 的安全性概況？

And then for Brian, now for probably the past year or so, I think you've been talking about the multibillion-dollar potential of mitapivat in these additional indications. How do you think about peak sales potential in either thalassemia or sickle cell disease as you construct that multibillion-dollar estimate?

然後對於 Brian 來說，大概在過去一年左右的時間裡，我想您一直在談論 mitapivat 在這些額外適應症中的數十億美元的潛力。當您建立數十億美元的估值時，您如何看待地中海貧血或鐮狀細胞疾病的最高銷售潛力？

Sure. Thanks, Eric. Sarah, you want to start on the first question?

當然。謝謝，埃里克。莎拉，你想開始第一個問題嗎？

Sure. So thanks, Eric, for the question. So as we have done when we were aware of this new safety information for thalassemia, we have updated the investor community at the time that we were able to make that call that there was a change in the safety profile of the drug. So if anything would change to the safety profile of the drug as we currently understand it, and we make that call, then we would update you guys as well.

當然。感謝 Eric 提出這個問題。因此，當我們了解到地中海貧血的新安全資訊時，我們已經向投資者社區通報了該藥物的安全性發生了變化。因此，如果我們目前所了解的藥物安全性狀況發生任何變化，並且我們做出了這個決定，那麼我們也會向你們通報最新情況。

And on the second question, Eric, on the multibillion-dollar potential that we see for PYRUKYND, I'll say that we're very excited for the position that we have right now with all the momentum, the backdrop of the clinical data as well as now the PDUFA date for thalassemia that we talked about. And just to characterize why we have such conviction in the long-term potential in thalassemia, as we said on multiple calls, two-third of the patient population in the US have no approved therapy option, which presents a profound opportunity in terms of unmet need for those patients.

關於第二個問題，埃里克，關於我們看到的 PYRUKYND 的數十億美元的潛力，我想說，我們對目前的地位感到非常興奮，因為我們有所有的勢頭、臨床數據的背景以及現在我們談到的地中海貧血的 PDUFA 日期。為了說明為什麼我們對地中海貧血的長期潛力如此有信心，正如我們在多次電話會議上所說的那樣，美國三分之二的患者沒有獲批的治療選擇，這為這些患者尚未滿足的需求提供了巨大的機會。

And we look at the combined opportunity of both the ENERGIZE and ENERGIZE-T data, and it's a really compelling profile. So that will be obviously the first step on that multibillion-dollar pathway. The second, with sickle cell disease, I think it's been really obvious to the whole community that the unmet need in sickle cell disease has always been very high, and it has actually increased in the past few months, given some of the challenges and limitations in available therapeutic options.

我們研究了 ENERGIZE 和 ENERGIZE-T 數據的綜合機會，這是一個非常引人注目的概況。因此，這顯然將是這條耗資數十億美元的道路上的第一步。第二，關於鐮狀細胞疾病，我認為整個社會都非常清楚，鐮狀細胞疾病的未滿足需求一直很高，而且由於現有治療方案的一些挑戰和局限性，過去幾個月這一需求實際上有所增加。

So that's an important step for us, too. And of course, we'll be in a position to give more guidance as we move through these approval pathways, the launch phases. And in the case of sickle cell disease, it's getting to the point of the data readout at the end of this year for the RISE UP Phase III study.

所以這對我們來說也是重要的一步。當然，隨著我們進入這些審批程序和啟動階段，我們將能夠提供更多指導。就鐮狀細胞疾病而言，RISE UP 第三階段研究將在今年底公佈數據。

So a lot of conviction. That's all with PYRUKYND. And of course, we're building out a PK activation franchise beyond that with the benefit of tevapivat. As we've noted, we're pursuing a Phase II study in sickle cell disease as well as we're already enrolling in our Phase IIb for low-risk MDS. So a lot of opportunity ahead.

因此很有信心。這就是 PYRUKYND 的全部內容。當然，我們正在藉助 tevapivat 打造 PK 啟動特許經營權。正如我們所指出的，我們正在進行鐮狀細胞疾病的 II 期研究，並且我們已經開始招募低風險 MDS 的 IIb 期研究。因此未來還有很多機會。

Divya Rao, TD Cowen.

Divya Rao，TD Cowen。

This is Divya on for Mark. Congrats on all the progress. Just two, one on sickle cell. So after the liver tox disclosure in Dow last year, can you provide any details on changes to the sickle cell trial protocol? Is it mostly in the OLE portion? Or were there any changes to the core portion of the trial? And then I have a follow-up.

這是 Divya 為 Mark 表演的。恭喜你所取得的所有進步。只有兩個，一個是鐮狀細胞疾病。那麼，在去年陶氏披露肝毒性事件後，您能否提供有關鐮狀細胞試驗方案變化的任何細節？它主要在 OLE 部分嗎？或者試驗的核心部分有什麼改變嗎？然後我有一個後續問題。

Thanks, Divya, for the question. So we -- in the core period, so after we had made that call, we took a look at the monitoring across all of the trials. And we were already monitoring in our core period for liver test and signs along the way in each of our trials in the blinded period, which is very in line with how people start therapies in the real world and monitor drugs in the beginning when they start patients on drug.

謝謝 Divya 提出這個問題。因此，在核心時期，也就是我們做出決定之後，我們檢視了所有試驗的監控情況。我們在核心期就已經在盲法期的每次試驗中監測了肝功能檢查和體徵，這與人們在現實世界中開始治療以及在開始給患者用藥時監測藥物的方式非常一致。

In the open label, we have to make a tweak to align the monitoring frequency, so once a month to what we were doing into the core period of the sickle cell disease trial. So now everybody is being monitored across all of our programs once a month for the first six months of exposure.

在開放標籤中，我們必須做出調整以調整監測頻率，因此每月一次與我們在鐮狀細胞疾病試驗的核心時期所做的事情一致。因此，現在，每個人在接觸後的前六個月內都會接受所有項目的每月一次監控。

That's helpful. And then with tebapivat being explored in sickle cell, how should we think about the development path there? Is this more of like a proof of concept before moving into other diseases? Or if the trial is successful, do you actually plan to move forward into pivotal development in sickle cell with this program?

這很有幫助。那麼，隨著 tebapivat 在鐮狀細胞中的探索，我們該如何思考那裡的發展路徑？這是否更像是在研究其他疾病之前的概念驗證？或者如果試驗成功，您是否實際上計劃利用該計劃推進鐮狀細胞的關鍵開發？

Yes. Thanks, Divya. I think I'm going to have Cecilia comment on that from a longer-term commercial perspective because, again, it's a real benefit to have not one, but two opportunities in this very complex, very high unmet disease.

是的。謝謝，Divya。我想我會讓塞西莉亞從更長遠的商業角度對此發表評論，因為對於這種非常複雜、未充分治療的疾病來說，擁有不止一個機會，而是兩個機會，確實有益。

Absolutely. So Divya, when we think about sickle cell disease, Brian mentioned it, there is such a high unmet need in that patient community. And we hear it loud and clear from clinicians that there is a need for more than one treatment options with the need for more than one PK activators -- so as we currently stand with tebapivat, we are looking for an opportunity to build a sickle cell disease franchise across both PYRUKYND and tebapapivat.

絕對地。所以 Divya，當我們考慮鐮狀細胞疾病時，Brian 提到了這一點，該患者群體中存在著很高的未滿足需求。我們從臨床醫生那裡清楚地聽到，需要多種治療方案，需要多種 PK 激活劑——因此，正如我們目前對 tebapivat 的立場一樣，我們正在尋找機會在 PYRUKYND 和 tebapapivat 上建立鐮狀細胞病特許經營權。

In terms of specific co-positioning of the two products and how we're going to develop tebapapivat, well, we will be guided by the data as always, we'll need to see the RISE UP data. We'll need to see the tebapapavat Phase II data. We'll be looking at the competitive environment at that point in time. And Sarah and I work very closely together to develop a clinical development plan, which will not only meet the needs of regulators, but will be commercially viable for us as well.

至於兩種產品的具體共同定位以及我們將如何開發 tebapapivat，我們將一如既往地以數據為指導，我們需要看到 RISE UP 數據。我們需要查看 tebapapavat 第二階段的數據。我們將關注當時的競爭環境。我和莎拉密切合作，制定了一項臨床開發計劃，該計劃不僅能滿足監管機構的需求，而且對我們來說也具有商業可行性。

And as we get closer to the midyear start, we'll, of course, get more clarity on the trial design and exactly what that looks like.

隨著年中開始的臨近，我們當然會對試驗設計以及其具體情況有更清晰的了解。

Gregory Renza, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Gregory Renza。

Great. Brian and team, congrats on the progress in the year. Brian, maybe just dipping into the pipeline and as you get your hand on the PK activation portfolio, I just wanted to ask about just your enthusiasm on how you're characterizing your level of enthusiasm with respect to AG-181 that the PAH stabilizer. Maybe just remind us of that specific mechanism, how it stabilizes PAH and perhaps why it should work well with patients who don't respond to that co-factor treatment?

偉大的。Brian 和團隊，恭喜你們今年的進步。Brian，也許您只是涉足管道，當您開始接觸 PK 激活產品組合時，我只想問一下您的熱情，您如何描述對 AG-181 PAH 穩定劑的熱情程度。也許只是提醒我們那個特定的機制，它如何穩定 PAH，以及為什麼它對那些對輔助因子治療沒有反應的病人有效？

Sure. The first thing I'll just say, Greg, is I'm not -- I do not pick favorites among children within our pipeline. We're really proud of all of the across the pipeline is my first comment. The second is we're in a really good position of strength from a diversification within the pipeline in both type of asset, disease as well as stage of development. With respect to AG-181, which is a phenylalanine hydroxylase stabilizer, in a way, it's similar to pyruvate kinase activation where it stabilizes the enzyme that's needed for the conversion of phenylalanine to tyrosine.

當然。格雷格，我首先要說的是，我不會──我不會在我們的孩子隊伍中挑三揀四。我的第一條評論是，我們真的為整個管道感到自豪。第二，我們在資產類型、疾病以及發展階段的多元化發展中處於非常有利的地位。AG-181 是一種苯丙胺酸羥化酶穩定劑，在某種程度上，它類似於丙酮酸激酶活化，可以穩定苯丙胺酸轉化為酪胺酸所需的酵素。

We're in Phase I now. And of course, we look forward to giving continued updates as we make progress on the development opportunity. But this is a very high unmet need population. We're talking about 35,000 to 40,000 patients and a very small subset of those who are actually actively treated, and they have, frankly, very limited treatment options.

我們現在處於第一階段。當然，我們期待在發展機會取得進展的同時繼續提供更新資訊。但這是一個未滿足需求的族群。我們談論的是 35,000 到 40,000 名患者，其中只有一小部分患者真正接受了積極治療，坦白說，他們的治療選擇非常有限。

So it's another mark of excellence that this came out of the Agios development, discovery and development. And again, it's right in the sweet spot of what we do best at Agios, which is address high unmet need in rare diseases, and we definitely look forward to giving you more updates.

所以這是 Agios 開發、發現和發展的另一個卓越標誌。再次強調，這正是 Agios 最擅長的領域，即解決罕見疾病領域未滿足的巨大需求，我們非常期待為您提供更多更新資訊。

That's helpful. And maybe just a broader question, taking a step back. As you look at your potential cash deployment internally and of course, externally, how are you seeing the market for external assets, especially in light of what is a rather active market, not just domestically, but also globally.

這很有幫助。退一步來說，這也許只是一個更廣泛的問題。當您考慮內部和外部的潛在現金部署時，您如何看待外部資產市場，尤其是考慮到不僅在國內而且在全球都相當活躍的市場。

Yes, great question. First of all, to reinforce what you just said, we're clearly as one of our key ingredients as a compelling rare disease company with a very bright future ahead. We're pleased with the, I'll call it, enviable strength of our balance sheet. And that enables us to, as a first priority, as I noted in my comments, to make sure that we maximize these launch opportunities.

是的，很好的問題。首先，為了強調您剛才所說的話，我們顯然是我們成為一家引人注目的罕見疾病公司的關鍵因素之一，未來前景非常光明。我們對我們的資產負債表令人羨慕的實力感到非常滿意。正如我在評論中提到的那樣，這使我們能夠將首要任務確保最大限度地利用這些發布機會。

We have thalassemia with a PDUFA date this year. We have sickle cell disease potentially next year following the RIS UP readout. So that's job one. Job two is, as you just asked me, we have other mid- and early-stage products in our pipeline. We want to make sure that we continue to deliver on those value-creating inflection points. And then to your question, we have actually scaled up our business development capabilities, particularly from a search and evaluation standpoint.

我們今年發現了地中海貧血，其 PDUFA 日期為今年。根據 RIS UP 讀數，明年我們可能會患上鐮狀細胞疾病。這是第一項工作。第二項工作是，正如您剛才問我的那樣，我們還有其他中期和早期產品正在研發中。我們希望確保繼續實現這些創造價值的轉折點。然後回答您的問題，我們實際上已經擴大了我們的業務發展能力，特別是從搜尋和評估的角度。

I think it's important as any healthy company will do is to be very disciplined in that approach. But we're very clear on what would match well with the Agios rare disease capabilities, which continue to increase, particularly on the commercial side. And we look in domestically, and we also have global line of sight as well. But we'll be very thoughtful and disciplined in where we believe we can add significant value creation.

我認為，任何一家健康的公司都應嚴格遵守這種方法，這一點很重要。但我們非常清楚什麼才能與 Agios 罕見疾病能力相匹配，而 Agios 的能力仍在不斷增強，特別是在商業方面。我們的眼光不僅限於國內，同時也放眼全球。但我們會非常謹慎和嚴謹地考慮我們可以創造重大價值的領域。

Greg Harrison, Scotiabank.

加拿大豐業銀行的格雷格·哈里森。

Congrats on the progress. Thinking about how you think investors should be modeling the launch trajectory in mitapivat in thalassemia in maybe in 2026, understanding there will be some time to get access and lag time before initiating therapy in 4Q. But would you expect there to be pent-up demand or an initial bolus in some of these patient groups that you discussed as the initial launch focus?

祝賀你取得進展。想想您認為投資者應該如何模擬 2026 年左右地中海貧血症 mitapativat 的推出軌跡，了解在第四季度開始治療之前需要一些時間才能獲得治療機會和滯後時間。但是，您是否預計，在您討論的最初推出重點的患者群體中，會出現被壓抑的需求或初始劑量？

Yes. Thanks, Greg. I'm going to start by just saying I'm really proud of Seta and her entire commercial organization that has been so dedicated to particularly disease state education for thalassemia, which is very much needed in this arena. And we're really well positioned and prepared for now the PDUFA date in September. And Stea, do you want to comment on what those dynamics look like towards the end of the year?

是的。謝謝，格雷格。首先我想說，我為塞塔和她的整個商業組織感到非常自豪，他們一直致力於地中海貧血的疾病狀態教育，這在該領域是非常需要的。現在，我們已經為 9 月的 PDUFA 做好了充分的準備。斯蒂亞，您想評論一下今年年底的動態嗎？

Absolutely. So thanks for the question. The team is working very diligently to prepare for launch, and we are super excited by the opportunity to provide these treatment options to patients in the US. As you mentioned, we've given guidance on our initial launch focus, which cover about 65% of all of the thalassemia -- adult thalassemia patients in the US, which is 4,000 -- which is 6,000 in total. From a launch perspective, we are definitely educating to increase the urgency to act to monitor and treat these patients.

絕對地。感謝您的提問。團隊正在非常努力地為產品發布做準備，我們非常高興有機會為美國患者提供這些治療選擇。正如您所說，我們已經對最初的發布重點給出了指導，涵蓋了美國所有地中海貧血患者（成人地中海貧血患者）的約 65%，即 4,000 人，總共 6,000 人。從啟動的角度來看，我們肯定在進行教育，以增強採取行動監測和治療這些患者的緊迫性。

Having said that, we don't expect to have an initial bolus in patients. Patients come to their doctors on a frequent visit depending on their transfusion-dependent or nontransfusion-dependent status and complications. So we expect to capture these patients as they come. And of course, we'll continue with the disease education to ensure that the right conversations are happening for them to make the appropriate choice for the best treatment for patients moving forward.

話雖如此，我們並不期望患者會接受初始推注。患者是否頻繁就診取決於其輸血依賴或不輸血依賴的狀態和併發症。因此我們希望在患者到來時就能捕捉他們。當然，我們將繼續進行疾病教育，以確保正確的對話，以便他們做出適當的選擇，為患者提供最佳的治療方案。

Yes. And I'll -- I mean, this is smart, triaging, too. When we say 65% targeting, it doesn't, of course, mean we don't eventually target the other 35%, but we're making thoughtful choices to make sure that we get off to a solid start in terms of that launch ramp. And the team, as Sta had noted earlier, has already been so-called rightsized for this opportunity. And now the intensive focus between now and the launch is disease state education. And then once we get clarity on the label and we have that launch opportunity, we're going to be in a great position.

是的。而且我會—我的意思是，這也是一種智慧的分類。當我們說 65% 的目標時，當然並不意味著我們最終不會瞄準另外 35%，但我們正在做出深思熟慮的選擇，以確保我們在發射坡道方面有一個良好的開端。正如 Sta 之前所指出的，該團隊已經為這一機會進行了所謂的適當規模調整。從現在到發表會開始，重點關注的是疾病狀況教育。一旦我們明確了標籤，並且有了發布機會，我們就會處於非常有利的位置。

That's helpful. I also wanted to ask about the Gulf region and the launch there. Are you getting a better handle on the commercial potential in the region? And how should investors be thinking about that opportunity?

這很有幫助。我還想問一下海灣地區和那裡的發布會的情況。您是否更掌握了該地區的商業潛力？那麼投資人該如何看待這個機會呢？

Yes. We're seeing the Gulf region. Obviously, the US is our number 1 commercial priority as an organization. Then when we look ex-US, the Gulf is the second commercial opportunity for us. Within the Gulf, Saudi Arabia is the biggest market. As we've noted, we have a breakthrough designation in that region, and we're working very closely with the new bridge team to go through the regulatory process in Saudi Arabia.

是的。我們正在觀察海灣地區。顯然，作為一個組織，美國是我們首要的商業重點。當我們將目光投向美國以外時，海灣地區是我們的第二個商業機會。在海灣地區，沙烏地阿拉伯是最大的市場。正如我們所指出的，我們在該地區取得了突破性的進展，並且我們正在與新的橋樑團隊密切合作，以完成沙烏地阿拉伯的監管流程。

When we think about launch ramp in that region, the way I'll think about it is more closely related and similar to the European market dynamics. It's a national health care system when there is a national decision on approval and price.

當我們考慮該地區的發布管道時，我的想法與歐洲市場動態更加密切相關且相似。當國家決定批准和價格時，它就是一個國家醫療保健系統。

However, within the different segments within Saudi Arabia in the health care system, for example, the private sector, the Ministry of Health as well as academic institutions, we will need to work with those segments in the health care system to ensure that there is a formulary access, which can take time to ramp up over time. But there is a big commercial opportunity from patient numbers, and we will navigate that with NewBridge accordingly.

然而，在沙烏地阿拉伯醫療保健系統的不同部門內，例如私營部門、衛生部以及學術機構，我們需要與醫療保健系統中的這些部門合作，以確保能夠獲得處方藥，而這可能需要一段時間才能逐漸改善。但患者數量蘊含著巨大的商業機會，我們將與 NewBridge 一起把握這個機會。

Chris Raymond, Piper Sandler.

克里斯雷蒙德、派珀桑德勒。

Two questions. First, I guess, on the PD studies in PKD, I think you've characterized ACTIVATE Kids and ACTIVATE Kids T as giving insights into future pediatric work in thal and sickle cell. Can you maybe elaborate a little bit on this benefit? Would you expect some perhaps short circuiting. I guess, of a pediatric program there? Or would there potentially be labeling benefits sort of out of the gate? -- just from this work?

兩個問題。首先，我想，關於 PKD 中的 PD 研究，我認為您已經將 ACTIVATE Kids 和 ACTIVATE Kids T 描述為對未來兒科 T 和鐮狀細胞工作提供了見解。您能否詳細說明一下這項好處？您是否預料到可能會發生短路？我想，那裡有一個兒科計畫吧？或者說，是否會有潛在的標籤優勢呢？ ——僅從這項工作來看？

And then the second question, I know you've had this question a number of times, but just on the PDUFA and a potential panel. Just with all this focus on liver injury, are you -- companies rarely hope for a panel, but it would seem that with all this attention that's on this, this actually might be beneficial just to sort of put some light on this. Any thoughts there on your desire there on a panel or not?

然後是第二個問題，我知道你已經問過這個問題，但只是關於 PDUFA 和潛在的小組。鑑於人們對肝損傷的關注程度如此之高，您是否——公司很少希望有一個小組討論，但看來，鑑於人們對這一問題的關注程度如此之高，這實際上可能有益，只是為了對此進行一些闡述。您是否想參加小組討論？您有什麼想法嗎？

Thanks, Chris. Sarah, you want to start on both (inaudible) pediatric?

謝謝，克里斯。莎拉，你想從（聽不清楚）兒科開始嗎？

Yes, I'll start with the pediatric. So while we're saying that this is really helpful is pediatric development is very hard. And so transfusion trials are also very hard to run. So we have worked through a lot of logistical things that we needed to consider for those pediatric trials and have now experienced implementing these pediatric trials and bringing them to a successful completion. All of those lessons learned along the way will apply to any other future pediatric trial we run.

是的，我將從兒科開始。因此，雖然我們說這確實有幫助，但兒科發展卻非常困難。因此輸血試驗也很難進行。因此，我們已經解決了許多兒科試驗需要考慮的後勤問題，現在已經實施了這些兒科試驗並成功完成了它們。在這過程中獲得的所有經驗教訓都將適用於我們未來進行的任何其他兒科試驗。

So there's a huge benefit from actually having that hands-on experience. And that will impact things like feasibility start-up and clinical trial logistics on any of those programs. So we're very happy with that. And then, of course, because we're following a very similar path across the hemolytic anemias in the adult development. We went from PKD to thalassemia to sickle cell disease had benefit risk in the PKD adults and now in the tau adults.

因此，實際擁有這樣的實務經驗會帶來巨大的好處。這將影響任何項目的可行性啟動和臨床試驗物流等事項。我們對此感到非常高興。當然，因為我們在成人發展過程中遵循了與溶血性貧血非常相似的路徑。我們從 PKD 到地中海貧血再到鐮狀細胞疾病，對 PKD 成人患者有益，現在對 tau 成人患者也有益處。

There is a lot of lessons that can be applied from adults to peds as well. So we're just, in general, very excited about expanding the patient population there. And then that, of course, any label negotiation you go through helps with the next label negotiation as well. So multiple benefits along the way.

有很多經驗教訓可以適用於成人和兒童。因此，總的來說，我們對擴大那裡的患者數量感到非常興奮。當然，您經歷的任何標籤談判也會有助於下一次標籤談判。因此，一路上可獲益良多。

In regards to the PDUFA date and the potential for a panel, so we are very happy that the PDUFA date has been announced. So for September 7, we have not heard that we would be having a panel at this point in time. So indeed, panels are a lot of work, both for us and for the FDA. So I'm not sure if I still fully agree with the assessment that we might be hoping for a panel. I would just -- I don't know. I think either way, we will be ready if it would happen.

關於 PDUFA 日期和專家小組的可能性，我們很高興 PDUFA 日期已經公佈。因此，對於 9 月 7 日，我們目前還沒有聽說我們會在此時召開小組討論會。所以，對於我們和 FDA 來說，小組工作確實非常繁重。所以我不確定我是否仍然完全同意我們可能希望有一個小組的評估。我只是——我不知道。我認為無論如何，如果它發生，我們都會做好準備。

That being said, I do think you already have light on what actually happened because we had the PKD label update with the warning and precaution, which truly highlights what we have observed in the thalassemia patient population. And that assessment has been agreed upon with the FDA for the label update in PKD. So I think we're good with the current data.

話雖如此，我確實認為您已經了解實際發生的情況，因為我們已經更新了 PKD 標籤，並添加了警告和預防措施，這真正突出了我們在地中海貧血患者群體中觀察到的情況。並且該評估已與 FDA 達成一致，以便對 PKD 中的標籤進行更新。所以我認為我們對目前的數據很滿意。

Alec Stranahan, Bank of America.

美國銀行的亞歷克‧斯特拉納漢 (Alec Stranahan)。

On the updates from us as well and look forward to a busy 2025 ahead. Just two from us. Thinking about the process of scaling your sales force for thal, given the ENERGIZE studies have both been presented at major medical meetings, what is your sense of the level of awareness amongst physicians as well as patient advocacy groups? Is this kind of tracking with your hopes? Or is there maybe more work to do there? And has this fed into the number of reps you've hired for commercialization or not really?

我們也收到了最新消息，期待即將到來的忙碌的 2025 年。就我們兩個了。考慮到擴大 Thal 銷售隊伍的過程，鑑於 ENERGIZE 兩項研究均已在主要醫學會議上發表，您認為醫生以及患者權益團體對此的認知程度如何？這樣的追蹤符合你的期望嗎？或者那裡可能還有更多工作要做？這是否真的影響了您為商業化僱用的銷售代表的數量？

Yes, Tsveta, do you want to get started?

是的，茨維塔，你想開始嗎？

Yes, absolutely. So first of all, in a very disciplined way, once we have the data from the ENERGIZE study, we made the decision to actually press the button and start rightsizing the customer-facing organization for launch. The way we approach the launch as any rare disease we launch is a very comprehensive way, focusing on the patients, physicians and payers and ensuring we have the right organization.

是的，絕對是如此。因此，首先，以非常嚴謹的方式，一旦我們獲得了 ENERGIZE 研究的數據，我們決定真正按下按鈕並開始調整面向客戶的組織的規模以供啟動。與推出任何罕見疾病產品一樣，我們推出的產品都採用非常全面的方式，重點關注患者、醫生和付款人，並確保我們擁有正確的組織。

We have already rightsized the sales force, in particular, as we've said, we had about 18 to 20 hemolytic anemia specialists covering PK deficiency for thalassemia. Given the fact that we have very well-established ICD cents, it allowed us to actually rightsize the organization appropriately. So the totality is about double that size.

我們已經對銷售隊伍進行了適當調整，具體來說，正如我們所說，我們有大約 18 至 20 名溶血性貧血專家，負責地中海貧血的 PK 缺乏症。鑑於我們擁有非常完善的 ICD 分部，它使我們能夠適當地調整組織規模。因此總量大約是這個數字的兩倍。

From an awareness perspective, the team has been in the field, in the US, connecting both with the KOL community, but also with the prescriber base, majority of which is community hematologists. And I can tell you, aligned with expectations, there is a high awareness not only of the disease, but of the potential for new therapeutic options for these patients and PYRUKYND profile.

從知名度的角度來看，該團隊一直在美國實地工作，不僅與 KOL 社區建立了聯繫，還與處方者群體建立了聯繫，其中大多數是社區血液學家。我可以告訴你，與預期一致，人們不僅對這種疾病有很高的認識，而且對這些患者和 PYRUKYND 特徵的新治療選擇的潛力也有很高的認識。

We are continuing our efforts on disease state education with both patients and physicians as well as we are very well connected as an organization with the patient communities and the patient advocacy groups. Sarah and I actually had the opportunity to meet with T recently. And I can tell you that the excitement that comes from those groups is very, very high for the potential of PYRUKYND.

我們將繼續致力於對患者和醫生進行疾病狀況教育，並且作為一個組織，我們與患者社區和患者權益團體保持良好的聯繫。事實上，莎拉和我最近有機會與 T 見面。我可以告訴你們這些團體對於 PYRUKYND 的潛力感到非常興奮。

So we are working hard to prepare. I can tell you, we are ready for launch and the team now is actually going deeper and deeper to make sure that we execute very successfully from the beginning on the opportunity ahead of us.

所以我們正在努力做好準備。我可以告訴你們，我們已經做好了發布的準備，現在團隊實際上正在深入研究，以確保我們從一開始就非常成功地抓住眼前的機會。

Yes. And the -- of course, before we got the PDUFA date, we didn't know when the date would be set. And so the team has any great prelaunch team does. We've been prepared for a range of scenarios. The fact that we now know in September, Tsveta and the team are maximizing this opportunity in terms of disease state awareness between now and then. And every month, we've seen continued progress with the KOL community as well as the into-community treating physicians. They're doing a great job.

是的。當然，在我們獲得 PDUFA 日期之前，我們不知道該日期何時確定。因此，該團隊擁有與任何優秀的預發布團隊一樣的能力。我們已經為各種情況做好了準備。事實上，我們現在知道，從現在到 9 月份，Tsveta 和團隊正在最大限度地利用這個機會來了解疾病狀況。每個月我們都能看到 KOL 社區以及社區治療醫生的不斷進步。他們做得很好。

And then just a quick one on pediatric PKD. Curious if you -- just to put a finer point, if you intend to seek approval in both transfusion populations, the regularly and not regularly transfused. And whether you think approval across the patient groups could be warranted, maybe given the totality of the data across the two studies.

然後我們簡單介紹一下兒童 PKD。我很好奇——只是為了更詳細說明，如果您打算尋求兩種輸血人群的批准，即定期輸血和不定期輸血。而且您是否認為有必要在所有患者群體中都予以批准，也許考慮到兩項研究的全部數據。

That's an emphatic, yes.

是的，這是強調的。

That's an emphatic, yes. When you asked the question, I actually nodded yes. So the data across the two trials is really supportive of benefits of the total positive benefit risk profile across the patient population. We -- in the regularly transfused trial, we have patients and we still have patients who are completely transfusion-free.

是的，這是強調的。當你問到這個問題的時候，我的確點頭表示是。因此，兩項試驗的數據確實支持了整個患者群體的整體積極效益風險狀況的益處。在定期輸血試驗中，我們既有接受治療的患者，也有完全不需要輸血的患者。

So that is an enormous clinically meaningful benefit. And then here on this trial, we clearly have positive results across the board, statistically significant across -- using both methodologies, Bayesian methodology and a frequentist approach. So we're very pleased with that as well. And we're looking forward to -- and hopefully obtain that broader label for patients with PKD.

因此，這是一個具有巨大臨床意義的益處。在這次試驗中，我們顯然取得了全面的正面成果，具有統計意義——使用這兩種方法，即貝葉斯方法和頻率學派方法。因此我們對此也非常高興。我們期待並希望為 PKD 患者獲得更廣泛的標籤。

Yes. I mean I know this is an investor call, but from what fuels us as an organization is the stories that we hear from patients. And these are in PKD, in general, of course, PYRUKYND is the only approved therapy for adult patients. And these pyramids have had kids who some have been splenectomized and others are awaiting that might have that as a potential and to have this promising data clinically relevant in the ACTIVATE-KIDS T trial in transfusion-dependent pediatric patients. And now with today's data this is really compelling, and we will certainly do our best to move that along with the regulators at the right time to make this available for patients.

是的。我的意思是，我知道這是一個投資者呼籲，但作為一個組織，我們動力的來源是我們從病人那裡聽到的故事。這些都是 PKD，一般來說，當然，PYRUKYND 是唯一獲準針對成年患者的治療方法。這些金字塔中的一些孩子已經接受了脾切除術，而其他一些孩子則在等待接受治療，他們可能具有這種潛力，並且這些有希望的數據在輸血依賴兒科患者的 ACTIVATE-KIDS T 試驗中具有臨床意義。現在，根據今天的數據，這確實令人信服，我們一定會盡最大努力在適當的時間與監管機構一起推動這一進程，以便患者能夠使用它。

Salveen Richter, Goldman Sachs.

高盛的薩爾文·里希特（Salveen Richter）。

This is Lydia on for Salveen. Congrats on the progress. Maybe just a follow-up to the previous question on pediatric PKD. Could you just discuss how expanding into the pediatric population could potentially impact the total opportunity in PKD?

這是 Salveen 的 Lydia。祝賀你取得進展。也許只是關於兒童 PKD 的上一個問題的後續。您能否討論擴大到兒科族群可能對 PKD 的整體機會產生什麼影響？

Tsveta?

茨維塔？

Yes, absolutely. So the pediatrics is about 20% of the PKD opportunity. As we know, PKD is ultra-rare disease. When we look at the pediatric trial, as Sarah mentioned, for us, it's a good opportunity to provide a treatment option for patients in need that currently have no treatment options. But very importantly, is a starting point for us to continue the pediatric development across all the other indications and apply all the learnings there to thalassemia and potentially sickle cell disease in the future.

是的，絕對是如此。因此兒科約佔 PKD 機會的 20%。眾所周知，PKD 是一種極為罕見的疾病。正如莎拉所說，當我們研究兒科試驗時，對我們來說，這是一個很好的機會，為有需要但目前沒有治療選擇的患者提供治療選擇。但非常重要的是，這是一個起點，讓我們能夠繼續在所有其他適應症中進行兒科開發，並將所有學習成果應用於地中海貧血和未來潛在的鐮狀細胞疾病。

Yes. And maybe just to reinforce the point that Cecilia made earlier, too, in PKD revenue, this is about 20% of the population, but this is an ultra-rare population. So again, the way we look at PKD this year, particularly in light of the preparation and focus we have for thalassemia, we're expecting flat revenues over 2024. But again, for pediatrics, it's an important addition when we get to that point for treatment optionality for these patients.

是的。也許只是為了強調塞西莉亞之前提出的觀點，在 PKD 收入中，這約佔人口的 20%，但這是一個極其罕見的群體。因此，再次重申，我們今年對 PKD 的看法，特別是考慮到我們對地中海貧血的準備和關注，我們預計 2024 年的收入將持平。但是，對於兒科來說，當我們為這些患者提供治療選擇時，這是一個重要的補充。

Tessa Romero, JPMorgan.

摩根大通的泰莎·羅梅羅 (Tessa Romero)。

So just a brief financial question from us to start. Cecilia, in terms of your OpEx, what is the right way to think about the evolution of your SG&A expenses and the cadence of a ramp-up there over 2025 and into 2026. And on the R&D side, any additional color you can give us there? And then I have one follow-up.

我們首先想問一個簡短的財務問題。塞西莉亞，就您的營運支出而言，如何正確看待銷售、一般和行政費用 (SG&A) 的演變以及 2025 年至 2026 年的成長節奏？在研發方面，您可以提供我們更多資訊嗎？然後我還有一個後續問題。

Sure. Thanks for the question. So as we mentioned, we continue to proactively manage our cost basis as part of our disciplined capital allocation approach. That being said, as Brian described earlier, we have three buckets or three priorities on that. The first one is preparing to maximize the PYRUKYND opportunity with the potential to have back-to-back launches and also advancing the pipeline. So for both SG&A and R&D, we expect to see growth year-over-year in the coming couple of years. You will see some quarter-over-quarter variability, everything obviously straight line, but we do anticipate to see growth on both items.

當然。謝謝你的提問。正如我們所提到的，作為我們嚴謹的資本配置方法的一部分，我們將繼續積極地管理我們的成本基礎。話雖如此，正如 Brian 之前所描述的，我們對此有三個重點或三個優先事項。第一個是準備最大限度地利用 PYRUKYND 的機會​​，有可能進行連續的發射，並推進管道建設。因此，我們預期未來幾年銷售、一般及行政開支和研發開支都會較去年同期成長。您會看到季度間存在一些變化，一切顯然都是直線，但我們確實預計這兩項都會成長。

Okay. And can you quantify what growth means?

好的。您能量化一下成長的意義嗎？

We haven't given specific guidance on growth. But like I said, we're being very disciplined on how we approach this. Like Sarah mentioned, we waited to see the thalassemia data to kick off like the bigger ramp on thalassemia. We're doing a similar approach on sickle cell. We want to try to be prepared, so we don't want to find ourselves in a positive scenario where we didn't prepare for that, but we're doing it in a very disciplined approach.

我們還沒有給出關於成長的具體指導。但就像我說的，我們在處理這個問題時非常嚴謹。正如莎拉所提到的，我們等待著看到地中海貧血的數據開始發揮作用，就像地中海貧血的更大進展一樣。我們正在對鐮狀細胞採取類似的方法。我們希望做好準備，因此我們不希望發現自己處於沒有準備的積極情況下，但我們會以非常自律的方式去做。

Okay. And then within that from a timeline perspective can you lay out for region beyond the US how you are thinking about timing of approval? So I'm thinking about the EU, Saudi Arabia and the UAE?

好的。然後從時間軸的角度來看，您能否為美國以外的地區闡述如何考慮批准時間？所以我考慮的是歐盟、沙烏地阿拉伯和阿聯酋？

Yes. Sarah, do you want to comment there, and Tsveta can touch on commercialization approach.

是的。莎拉，你想對此發表評論嗎？茨維塔可以談談商業化方法。

Yes, the timing of approval. So the PDUFA date for the FDA, that's September 7 that is announced and everything. The others, it's less -- they don't give proactively a date by which they will approve. So it depends on how the process go and the round of -- the amount of questions you get along the way. We -- but we're very excited about the progress that is currently being made and are on track to deliver.

是的，批准的時間。因此，FDA 的 PDUFA 日期是 9 月 7 日，已經公佈了一切。其他的則較少——他們沒有主動給出批准日期。所以這取決於整個過程的進展和你在過程中遇到的問題數量。我們——但我們對目前的進展感到非常興奮，並且正在按計劃實現目標。

Yes. And from a commercialization perspective, as I commented earlier, in the Gulf region with the biggest opportunity Saudi Arabia, after you have an approval, will need to go through the access and formulary discussions with the different parts of the country. So the actual ramp is going to take some time, but not like very similar to how the European health care systems work.

是的。從商業化角度來看，正如我之前所評論的，在海灣地區，機會最大的地方是沙烏地阿拉伯，在獲得批准後，將需要與該國不同地區進行准入和處方討論。因此，實際的提升將需要一些時間，但與歐洲醫療保健系統的運作方式並不十分相似。

For Europe from a commercialization perspective, we are looking for a potential partnership there as well. So as soon as we have EMA approval, we will be able to actually navigate the European health care systems as well. as you know, very well in Europe, it's a country-by-country pricing and reimbursement decisions. So again, there will be a time lag between approval and financial commercialization in Europe, too.

從商業化角度來看，我們也在尋求歐洲的潛在合作關係。因此，一旦我們獲得 EMA 批准，我們將能夠真正進入歐洲醫療保健體系。如您所知，在歐洲，每個國家都自行製定定價和報銷決定。因此，在歐洲，從批准到金融商業化之間也會有一個時間差。

I'm showing no further questions. I'd like to turn the call back over to Brian for closing remarks.

我沒有其他問題。我想將電話轉回給布萊恩，請他作最後發言。

All right. Thanks a lot, Michelle. Well, thank you very much, everybody, for participating in today's call. We are a month and a half into the start of what promises to be a very busy and exciting year. It's an exciting time at Agios. We really believe that we're poised to deliver transformative new therapies for patients and create significant long-term value to shareholders. So thanks again, and we look forward to speaking with you again soon.

好的。非常感謝，米歇爾。好吧，非常感謝大家參加今天的電話會議。已經過去一個半月了，新的一年註定會非常忙碌和令人興奮。這是 Agios 令人興奮的時刻。我們確實相信，我們已準備好為患者提供變革性的新療法，並為股東創造重大的長期價值。再次感謝，我們期待很快再次與您交談。

Thank you for your participation. This does conclude the program, and you may now disconnect. Everyone, have a great day.

感謝您的參與。這確實結束了程序，您現在可以斷開連接了。祝大家有個愉快的一天。