Agios Pharmaceuticals Inc (AGIO) 2025 Q1 法說會逐字稿

Good morning and welcome to Agios' first quarter 2025 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, Vice President of Investor Relations and Corporate Communications for Agios.

早上好，歡迎參加 Agios 2025 年第一季電話會議。（操作員指示）請注意，此通話是應 Agios 的要求錄製的。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 first quarter 2025 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 的電話會議和網路廣播，討論我們 2025 年第一季度的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。

On today's call, we'll hear from 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.

在今天的電話會議上，我們將聽取執行長 Brian Goff、首席醫療官兼研發主管 Sarah Gheuens 博士、首席商務官 Tsveta Milanova 和首席財務長 Cecilia Jones 的發言。

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

在我們開始之前，我想提醒大家，我們在本次電話會議上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。說完這些，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.

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，以改善和延長罕見疾病患者的生命。

Today, we are fortunate to have multiple late-stage programs nearing critical readouts or potential commercialization and have a very strong balance sheet. We are maintaining our focus on executing against the objectives we've laid out, including the ongoing regulatory reviews of our thalassemia program for which we have seen continued and consistent FDA engagement. And with approximately $1.4 billion of cash on hand and a disciplined approach to capital allocation, we believe we will have financial independence to fund the company through new approvals and product launches while advancing our pipeline, all of which is especially notable in today's market environment.

今天，我們很幸運，有多個後期項目接近關鍵讀數或潛在商業化，並且擁有非常強勁的資產負債表。我們將繼續專注於實現我們制定的目標，包括對我們的地中海貧血計畫進行的持續監管審查，我們已經看到 FDA 持續且持續的參與。憑藉約 14 億美元的現金和嚴謹的資本配置方法，我們相信我們將擁有財務獨立性，透過新的批准和產品發佈為公司提供資金，同時推進我們的產品線，所有這些在當今的市場環境中都特別引人注目。

Our lead product, PYRUKYND or mitapivat, 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. We have the exciting prospect of two additional commercial launches to support our potential multibillion-dollar opportunity for PYRUKYND. We are planning for a potential approval and launch in thalassemia in the US in September of this year, followed by sickle cell disease in 2026.

我們的主要產品 PYRUKYND 或 mitapivat 是一種丙酮酸激酶激活劑，具有新穎的作用機制，可改善紅血球代謝並增加可用於支持紅血球健康的能量或 ATP 量。我們非常期待另外兩次商業發射，以支持 PYRUKYND 潛在的數十億美元機會。我們計劃於今年 9 月在美國批准並推出用於治療地中海貧血的藥物，隨後於 2026 年批准並推出用於治療鐮狀細胞疾病的藥物。

Beyond PYRUKYND, our early and mid-stage pipeline is robust and poised for clinical advancement, offering a strong foundation for innovation and long-term growth. And finally, supporting it all is our highly experienced team and the strong balance sheet I noted earlier.

除了 PYRUKYND，我們的早期和中期產品線也很強大，可以為臨床進展做好準備，為創新和長期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和我之前提到的強勁的資產負債表。

We look at 2025 as a breakout year for Agios as we focus on three key priorities: first, maximizing the potential of the PYRUKYND franchise, including the pursuit of new indications; second, advancing and diversifying our key pipeline programs; and third, strategically focusing our capital deployment to sustain and drive our growth.

我們將 2025 年視為 Agios 的突破之年，因為我們將重點放在三個關鍵優先事項：首先，最大限度地發揮 PYRUKYND 特許經營的潛力，包括尋求新的適應症；其次，推進和多樣化我們的主要管道計劃；第三，戰略性地集中我們的資本部署以維持和推動我們的增長。

We have begun the year with a strong start, executing toward important milestones. Earlier this year, we announced positive top-line results from the ACTIVATE-Kids Phase 3 trial of mitapivat in pediatric patients with PK deficiency who are not regularly transfused. We also anticipate some exciting developments for our mid- and early-stage pipeline programs.

我們以強勁的開局開啟了新的一年，並朝著重要的里程碑邁進。今年早些時候，我們宣布了針對患有 PK 缺乏症且未定期輸血的兒科患者的 ACTIVATE-Kids 第 3 階段試驗的積極頂線結果。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。

For tebapivat, our novel PK activator, we expect to complete enrollment in the ongoing Phase 2b study in lower-risk MDS by year-end and to initiate enrollment in a Phase 2 study in sickle cell disease by mid-2025. Additionally, we expect to file an investigational new drug application for AG-236, our siRNA targeting TMPRSS6 inhibition intended for the treatment of polycythemia vera in mid-2025.

對於我們的新型 PK 活化劑 tebapivat，我們預計將在年底前完成正在進行的低風險 MDS 2b 期研究的招募，並在 2025 年中期啟動鐮狀細胞疾病 2 期研究的招募。此外，我們預計將於 2025 年中期提交 AG-236 的新藥研究申請，AG-236 是我們針對 TMPRSS6 抑制的 siRNA，旨在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, now only four months away, and the Phase 3 readout of the RISE UP study of mitapivat in sickle cell disease by year-end.

2025 年預計發生的最重大事件包括：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，現在僅剩四個月的時間，以及年底前對鐮狀細胞病的 mitapivat 進行 RISE UP 研究的 3 期讀數。

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. Before I turn it over to Sarah, I'd like to formally welcome Krishnan Viswanadhan, who joined us in March as Chief Corporate Development and Strategy Officer, having previously served as the President and Chief Operating Officer of Be Biopharma and in various senior roles at both Bristol-Myers Squibb and Celgene. His diverse experience and strategic vision will be instrumental in maximizing the potential of our current assets while also exploring potential expansion opportunities. With that, let me now turn it over to Sarah.

如您所見，今年將是令人興奮的一年，我們的產品線中存在多種催化劑，它們為股東帶來重大價值，並為患者帶來變革潛力。在將時間交給莎拉之前，我想正式歡迎克里希南·維斯瓦納丹 (Krishnan Viswanadhan)，他於 3 月份加入我們，擔任首席企業發展和戰略官，此前曾擔任 Be Biopharma 的總裁兼首席運營官，並在百時美施貴寶和 Celgene 擔任過多個高級職務。他的豐富經驗和策略眼光將有助於最大限度地發揮我們現有資產的潛力，同時探索潛在的擴張機會。現在，讓我把話題交給莎拉。

Thanks, Brian. Our pipeline includes a well-rounded mix of late-stage programs nearing market entry and promising mid- and early-stage opportunities. Thalassemia 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.

謝謝，布萊恩。我們的產品線包括即將進入市場的後期項目以及有前景的中早期機會。地中海貧血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。

One of the most commonly cited patient concerns is chronic fatigue, which is unaddressed by the currently available therapies. Common management strategies 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 having no approved therapies.

患者最常擔心的問題之一是慢性疲勞，而目前的治療方法尚未解決這個問題。地中海貧血的常見治療策略，例如輸血和鐵螯合療法，也會導致嚴重的副作用，加劇患者面臨的健康挑戰。目前，患者的有效治療選擇有限或根本沒有，美國 67% 的確診患者沒有獲得批准的治療方法。

In 2024, we announced positive results from the ENERGIZE and ENERGIZE-T Phase 3 trials evaluating mitapivat versus placebo in adults with non-transfusion-dependent and transfusion-dependent alpha or beta-thalassemia, respectively. Based on the compelling clinical profile observed in both the ENERGIZE and ENERGIZE-T Phase 3 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 ENERGIZE 和 ENERGIZE-T 第 3 階段試驗的正面結果，這兩項試驗分別評估了 mitapivat 與安慰劑對非輸血依賴性和輸血依賴性 α 或 β 地中海貧血成人患者的療效。根據 ENERGIZE 和 ENERGIZE-T 在第 3 階段研究中觀察到的令人信服的臨床特徵，我們相信 mitapivat 有可能成為地中海貧血患者的基礎和便捷的口服藥物，無論他們的基因型或輸血需求如何。

In December, we announced the simultaneous filing for regulatory approval of PYRUKYND for this indication in the US, European Union, Kingdom of Saudi Arabia, and the United Arab Emirates. As Brian mentioned, in the US, we are now just four months away from our PDUFA goal date of September 7, and our interactions with the FDA have continued as expected. The FDA has communicated that at this time, no advisory committee meeting is planned, and the review is ongoing.

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。正如 Brian 所提到的，在美國，我們現在距離 PDUFA 目標日期 9 月 7 日僅有四個月的時間，我們與 FDA 的互動也如預期地繼續進行。FDA 表示，目前沒有計劃召開諮詢委員會會議，審查仍在進行中。

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, poor quality of life, organ damage and early mortality. There is an urgent need for novel therapeutic options, and our data to date indicate that mitapivat may be a transformational therapy for these patients with the ability to address multiple aspects of the 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國約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，可導致疼痛、生活品質不佳、器官損害和早期死亡。迫切需要新的治療方案，我們迄今為止的數據表明，mitapivat 可能成為這些患者的一種轉化療法，能夠解決疾病的多個方面。

The Phase 3 RISE UP study completed enrollment in October 2024 with over 200 patients enrolled globally, achieving this milestone just over a year after recruitment began. In this study, we have two independent primary endpoints, hemoglobin response and analyzed rate of sickle cell pain crises. Attaining either primary endpoint allows us to apply alpha to the testing of the trial's key secondary endpoints.

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，在招募開始後僅一年多就實現了這一里程碑。在這項研究中，我們有兩個獨立的主要終點，即血紅素反應和鐮狀細胞疼痛危機的分析率。達到任一主要終點都使我們能夠將 alpha 應用於試驗的關鍵次要終點的測試。

With our secondary endpoints, we are using a variety of measures to assess mitapivat's potential in improving how patients feel and function. We expect to report topline results from this Phase 3 study in late 2025 with a potential regulatory filing and US approval in 2026. 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 crisis, and making patients feel better.

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。我們預計將於 2025 年底報告該 3 期研究的主要結果，並可能在 2026 年提交監管備案並獲得美國批准。我們相信，mitapivat 有潛力成為一流的治療方法，旨在透過改善貧血、減少鐮狀細胞疼痛危機和讓患者感覺更好來滿足這種疾病中未滿足的巨大需求。

Beyond mitapivat, we aim to further address the broad range of disease manifestations in diverse areas of unmet need in sickle cell disease. Since not every patient will respond to a given therapy, we see an opportunity to expand the patient population with complementary approaches. To that end, tebapivat, which is a potent PK activator, currently being explored as a potential treatment option for low-risk MDS may also hold promise in sickle cell disease.

除了 mitapivat 之外，我們還致力於進一步解決鐮狀細胞疾病中未滿足需求的各個領域的廣泛疾病表現。由於並非每個患者都會對特定療法產生反應，我們看到了透過補充方法擴大患者群體的機會。為此，tebapivat（一種強效的PK活化劑）目前正在被探索作為低風險MDS的潛在治療選擇，也可能對鐮狀細胞疾病有希望。

We are planning to begin enrollment in a Phase 2 study of tebapivat in sickle cell disease in the coming months. This will be a randomized placebo-controlled dose-finding study, including a total of 56 patients. Patients will be randomized to either 2.55 or 7.5 milligrams of tebapivat QD or placebo.

我們計劃在未來幾個月內開始招募 tebapivat 治療鐮狀細胞疾病的 2 期研究。這將是一項隨機安慰劑對照的劑量探索研究，共包括 56 名患者。患者將隨機分配接受 2.55 或 7.5 毫克 tebapivat QD 或安慰劑。

The primary endpoint will be a hemoglobin response as defined by an increase of at least 1 gram per deciliter from week 10 to 12 compared to baseline and secondary endpoints will include the hemolysis and patient-reported outcomes evaluating how patients feel and function. We expect data from this study will provide proof of concept for tebapivat and enable us to select the dose for Phase 3.

主要終點是血紅蛋白反應，定義為與基線相比，從第 10 週到第 12 週每分升至少增加 1 克，次要終點包括溶血和患者報告的結果，評估患者的感覺和功能。我們期望這項研究的數據將為 tebapivat 提供概念證明，並使我們能夠選擇第 3 階段的劑量。

As I mentioned, tebapivat is also being evaluated in a Phase 2b study in lower-risk MDS, where we aim to deliver the first oral therapy that addresses anemia due to ineffective erythropoiesis in the disease. MDS 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. We are on track to complete enrollment in this study later this year with a data readout planned for early next year.

正如我所提到的，tebapivat 也正在針對低風險 MDS 進行 2b 期研究評估，我們的目標是提供首個針對該疾病中因紅血球生成不完全導致的貧血的口服療法。MDS 影響美國和歐盟 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%。我們預計將於今年稍晚完成這項研究的招募，並計劃於明年年初公佈數據。

And finally, two items to note in our early-stage pipeline programs. For AG-181 targeting phenylketonuria, we are progressing to studying multiple ascending doses in our ongoing healthy volunteer study midyear. We are also on track to file an IND mid-2025 for AG-236, our siRNA targeting TMPRSS6, intended for the treatment of polycythemia vera. So, we are quite excited about the progress planned across the entire portfolio this year. With that, I will now turn the call over to Tsveta.

最後，在我們的早期管道項目中有兩點需要注意。對於針對苯酮尿症的 AG-181，我們正在年中進行健康志願者研究，研究多種遞增劑量。我們也計劃在 2025 年中期為 AG-236 提交 IND，AG-236 是我們的 siRNA，針對 TMPRSS6，旨在治療真性紅血球增多症。因此，我們對今年整個投資組合的計劃進展感到非常興奮。現在，我將發言權交給茨維塔。

Thanks, Sarah. Our commercial organization is driven by the potential to expand PYRUKYND indications to include both thalassemia and sickle cell disease by 2026. In thalassemia, we are aiming to deliver the first therapy indicated to treat all subtypes of the disease. And with sickle cell disease, our goal is to deliver a novel oral therapy that improves anemia, reduces vaso-occlusive crisis, or VOCs, and improves fatigue. Across these indications, we believe PYRUKYND represents a multibillion-dollar opportunity.

謝謝，莎拉。我們的商業組織致力於在 2026 年前將 PYRUKYND 適應症擴大到包括地中海貧血和鐮狀細胞疾病。對於地中海貧血，我們的目標是提供第一個能夠治療該疾病所有亞型的療法。對於鐮狀細胞疾病，我們的目標是提供一種新型口服療法，以改善貧血、減少血管閉塞危像或 VOC，並改善疲勞。根據這些跡象，我們相信 PYRUKYND 代表著數十億美元的商機。

Looking at the upcoming potential launch of thalassemia in the US, the underlying market dynamics in thalassemia support a significant opportunity for PYRUKYND. Thalassemia patients are diagnosed and known to the health care system. The burden of disease is well-characterized. And there are well-established KOLs and patient advocacy groups. All these elements will help drive adoption.

縱觀美國即將推出的地中海貧血治療藥物，地中海貧血的潛在市場動態為 PYRUKYND 提供了重大機會。地中海貧血患者已被診斷並被醫療保健系統所知。疾病負擔已被充分描述。此外，還有成熟的關鍵意見領袖 (KOL) 和病人權益團體。所有這些因素將有助於推動採用。

We are now just four months away from a potential US approval, and our team is working diligently to prepare for a potential launch. First, we are executing a robust disease state education campaign focused on both patients and health care providers. Our campaign highlights thalassemia disease pathophysiology, long-term complications and burden, and the importance of frequent monitoring and management. Additionally, it embraces the cultural diversity of the thalassemia patient community.

現在距離美國可能批准僅剩四個月的時間，我們的團隊正在努力為可能的發布做準備。首先，我們正在進行一項針對患者和醫療保健提供者的強有力的疾病狀態教育活動。我們的活動強調地中海貧血疾病的病理生理學、長期併發症和負擔以及頻繁監測和管理的重要性。此外，它還涵蓋了地中海貧血患者群體的文化多樣性。

I'm proud to report that our team has organized several highly attended patient programs in Cantonese, Mandarin, and Arabic. Feedback from the community has been overwhelmingly positive, and we are planning additional programs as we prepare for launch.

我很自豪地報告，我們的團隊已經用粵語、普通話和阿拉伯語組織了幾次參與度很高的患者專案。來自社群的回饋非常積極，我們在準備發佈時正在計劃更多的計劃。

Second, we have rightsized our cross-functional team to ensure a successful launch in this larger yet still rare market. For example, for PK deficiency, we have had a sales team of 20 professionals. And for thalassemia, we have strategically grown the sales organization to approximately twice that size.

其次，我們調整了跨職能團隊的規模，以確保在這個規模更大但仍稀缺的市場中成功推出產品。例如，針對PK缺陷，我們已經擁有一支由20名專業人員組成的銷售團隊。對於地中海貧血，我們已策略性地將銷售組織規模擴大到約兩倍。

This team is fully on board, focusing on disease state education and detailed account profiling to enable a focused and effective launch shortly after approval. And third, our market access team is actively engaging and educating payers on thalassemia through pre-approval information exchange meetings to facilitate disease understanding and support patient access. Feedback from payer research and these interactions has been positive, with recognition of the unmet need and the strength of the product profile.

團隊全力投入工作，重點關注疾病狀況教育和詳細的帳戶分析，以便在獲得批准後不久就能有重點、有效地啟動。第三，我們的市場准入團隊正在透過批准前資訊交流會議積極參與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。付款人研究和這些互動的回饋都是正面的，承認了未滿足的需求和產品概況的優勢。

We expect the majority of patients to be on commercial plans. As a reminder, the initial coverage of PYRUKYND in thalassemia will be through medical exception process while policies are still being established. Given our experience and strong track record in PK deficiency, we are well-positioned to navigate the medical exception process and replicate the success we have had with PK deficiency.

我們預計大多數患者都會選擇商業計劃。提醒一下，在政策仍在製定期間，對地中海貧血症患者 PYRUKYND 的初步覆蓋將透過醫療例外程序進行。鑑於我們在 PK 缺乏症方面的經驗和良好的記錄，我們完全有能力駕馭醫療例外流程並複製我們在 PK 缺乏症方面取得的成功。

There are approximately 6,000 adults diagnosed with thalassemia in the US, with most patients diagnosed before adulthood. 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.

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。

Within that population, we estimate that PYRUKYND's initial launch focus will address approximately 65% of the adult thalassemia patient population. 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 who are non-transfusion-dependent but already are experiencing complications or debilitating fatigue.

在該族群中，我們估計 PYRUKYND 的初始發布重點將針對約 65% 的成年地中海貧血患者群體。我們希望那些因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不依賴輸血但已出現併發症或嚴重疲勞的患者。

We conducted market research to identify top clinical characteristics health care providers will consider when prescribing PYRUKYND. Four key attributes were identified as most important; impact on hemoglobin levels, reduction in transfusion burden, improvement of fatigue, and iron overload. Taking into account these elements, PYRUKYND's profile is well-positioned for each of these important criteria.

我們進行了市場調查，以確定醫療保健提供者在開立 PYRUKYND 處方時會考慮的最重要的臨床特徵。四個關鍵屬性被確定為最重要的：對血紅素水平的影響、減少輸血負擔、改善疲勞和鐵超載。考慮到這些因素，PYRUKYND 的概況對於每個重要標準都有良好的定位。

Central to our messaging is the transformative profile of PYRUKYND in thalassemia, characterized by a number of firsts. This is potentially the first therapy for 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 as quickly as possible to people suffering from thalassemia.

我們資訊的核心是 PYRUKYND 在治療地中海貧血的變革性特徵，其特徵是具有多項首創性。這可能是針對 α 型和 β 型地中海貧血患者的首個療法、首個針對該疾病的口服療法、首個證明可改善非輸血依賴患者生活品質的療法，以及首個證明可減輕輸血負擔的效果可持續 36 週的療法。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 revenue for the first quarter. In the first quarter of 2025, we generated $8.7 million in net PYRUKYND revenue compared to $8.2 million in the first quarter of last year. In the US, a total of 234 patients have completed a prescription enrollment form, including 11 in the first quarter of 2025, a 5% increase versus the prior quarter. This has translated into 136 net patients on therapy, also an increase of 5% versus the prior quarter, and we continue to see strong persistence.

最後，讓我簡要介紹一下第一季的營收狀況。2025 年第一季度，我們的 PYRUKYND 淨收入為 870 萬美元，而去年第一季為 820 萬美元。在美國，共有 234 名患者完成了處方登記表，其中 2025 年第一季有 11 名患者，比上一季增加了 5%。這意味著接受治療的淨患者人數為 136 人，比上一季增加了 5%，而且我們繼續看到強勁的持久性。

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

我們相信，透過此次發表會我們不斷加強的能力將奠定基礎，幫助我們最大限度地發揮美國在 2025 年針對地中海貧血和 2026 年針對鐮狀細胞疾病的發布潛力。最後，我們為能夠為世界各地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。說完這些，我將把電話轉給塞西莉亞。

Thanks, Tsveta. Our first quarter 2025 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.

謝謝，茨維塔。我們的 2025 年第一季財務業績可以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-Q 中。現在，請允許我花一點時間來提供一些背景資訊並強調幾個關鍵點。

First quarter 2025 net PYRUKYND revenue was $8.7 million, an increase of 6% compared to $8.2 million in the first quarter of 2024. Compared to the fourth quarter of 2024, revenues decreased by 19%, primarily due to the benefit of year-end stocking and adjustments to certain revenue reserves that we previously noted for Q4. Importantly, as Tsveta detailed, we saw an increase in both new prescriptions and new patient starts in the first quarter since the January label update, which we see as a strong testament to the product's profile.

2025 年第一季 PYRUKYND 淨收入為 870 萬美元，較 2024 年第一季的 820 萬美元成長 6%。與 2024 年第四季相比，營收下降了 19%，這主要是由於年終備貨的好處以及我們之前在第四季度提到的某些收入儲備的調整。重要的是，正如 Tsveta 所詳述的那樣，自 1 月份標籤更新以來，我們在第一季度看到新處方和新患者數量都有所增加，我們認為這是對產品形象的有力證明。

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 also experience quarter-to-quarter variability. As a reminder, with our focus on thalassemia disease state education as we prepare for our September 7 PDUFA date, we continue to expect 2025 revenues for PK deficiency to be relatively flat compared to 2024.

預計總收入與淨收入的年增長率一般在 10% 至 20% 之間，與其他罕見疾病藥物的上市情況一致，並且也將經歷季度間變化。提醒一下，在我們為 9 月 7 日的 PDUFA 日期做準備時，我們將重點關注地中海貧血疾病狀態教育，我們仍然預計 2025 年 PK 缺乏症的收入與 2024 年相比相對持平。

Regarding thalassemia, it is worth noting that it can take several weeks, particularly at launch between a prescription enrollment form and the 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.

關於地中海貧血，值得注意的是，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，我們預計第四季度的收入將更加不完整，這應該被納入 2025 年收入預期模型中。

Obviously, we are eager for the September 7 PDUFA date to arrive and the team is well-prepared for it. And looking forward to 2026 and beyond, we are optimistic about the team's ability to translate the favorable market dynamics that Tsveta described earlier into a significant revenue trajectory for thalassemia.

顯然，我們迫切希望 9 月 7 日的 PDUFA 日期到來，並且團隊已經為此做好了充分的準備。展望 2026 年及以後，我們對團隊將 Tsveta 先前描述的有利市場動態轉化為地中海貧血的顯著收入軌蹟的能力充滿信心。

Returning to the first quarter results, cost of sales for the quarter was $1.1 million. R&D expenses were $72.7 million for the first quarter, an increase of $4.1 million compared to the first quarter of 2024. This was primarily attributed to an increase in workforce-related expenses and costs associated with the clinical trials of tebapivat in lower-risk MDS and sickle cell disease, partially offset by lower costs associated with the clinical trials of mitapivat in thalassemia and pediatric PKD.

回顧第一季的業績，本季的銷售成本為 110 萬美元。研發第一季的支出為 7,270 萬美元，與 2024 年第一季相比增加了 410 萬美元。這主要歸因於與勞動力相關的費用以及與 tebapivat 在低風險 MDS 和鐮狀細胞疾病中的臨床試驗相關的成本的增加，但與 mitapivat 在地中海貧血和兒童 PKD 中的臨床試驗相關的成本降低部分抵消了這一增加。

SG&A expenses were $41.5 million for the first quarter, an increase of $10.5 million compared to the prior year quarter. This was primarily driven by an increase in commercial-related activities, including headcount as we prepare for the potential approval of PYRUKYND in thalassemia later this year. We are closely monitoring the potential for new tariffs to increase our operating expenses, but at this time, we do not anticipate a material impact. Please see our 10-Q filing later today for additional related disclosures.

第一季銷售、一般及行政費用為 4,150 萬美元，較去年同期增加 1,050 萬美元。這主要是由於商業相關活動的增加，包括員工人數的增加，因為我們準備在今年稍後批准 PYRUKYND 用於治療地中海貧血。我們正在密切關注新關稅增加我們營運費用的可能性，但目前，我們預計不會產生重大影響。請參閱我們今天稍後提交的 10-Q 文件，以了解更多相關揭露。

We ended the first quarter with cash, cash equivalents, and marketable securities of approximately $1.4 billion. As Brian mentioned, we expect this balance, together with anticipated product revenue and interest income, will provide the financial independence for potential PYRUKYND launches in thalassemia and sickle cell disease, advancing existing programs and opportunistically expanding our pipeline through both internally and externally discovered assets.

第一季結束時，我們的現金、現金等價物和有價證券總額約為 14 億美元。正如 Brian 所提到的，我們預計這種平衡，加上預期的產品收入和利息收入，將為 PYRUKYND 在治療地中海貧血和鐮狀細胞病方面的潛在進展提供財務獨立性，推進現有項目，並透過內部和外部發現的資產機會性地擴大我們的產品線。

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 this year, we are confident that our balance sheet will continue to enable us to execute from a position of strength. I will now turn the call back over to Brian.

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格的現金分配方法，為支持 PYRUKYND 未來的潛在推出做好準備。隨著我們今年朝著更多潛在價值創造里程碑邁進，我們相信，我們的資產負債表將繼續使我們能夠保持強勁勢頭。我現在將電話轉回給布萊恩。

Thanks, Cecilia. We believe the remainder of 2025 will be incredibly exciting for Agios based on the potential approval and launch of PYRUKYND in thalassemia, a critical Phase 3 readout in sickle cell disease and important anticipated progress across our mid- and early-stage pipeline.

謝謝，塞西莉亞。我們相信，2025 年剩餘時間對於 Agios 來說將是無比激動人心的一年，因為 PYRUKYND 可能獲得批准並上市用於治療地中海貧血，這是鐮狀細胞病的關鍵 3 期讀數，而且我們中期和早期管道預計將取得重要進展。

In closing, I'd like to briefly reinforce our fortunate position of having a very strong balance sheet, which provides us with the ability to independently execute across our key priorities. We remain committed to disciplined cash allocation and long-term shareholder value creation as we all navigate the current market environment. With that, I'd like to now open the call for questions. Operator, please open the line.

最後，我想簡要地強調我們擁有非常強勁的資產負債表的幸運地位，這使我們能夠獨立執行我們的關鍵優先事項。在當前的市場環境下，我們依然致力於嚴格的現金分配和長期股東價值創造。現在，我想開始提問。接線員，請接通線路。

(Operator Instructions) Gregory Renza, RBC Capital Markets.

（操作員指示）Gregory Renza，RBC Capital Markets。

Congrats on the progress. Brian, it's really helpful to hear your confirmation about no advisory committee for the September PDUFA. I'm just curious if you can comment on, first, has that mid-cycle review happened? I think it should have already occurred. Just wanted to get clarity on that.

恭喜你取得進展。布萊恩，聽到您確認 9 月 PDUFA 中沒有諮詢委員會，真的很有幫助。我只是好奇您是否可以評論一下，首先，中期審查是否已經進行？我認為它應該已經發生了。只是想弄清楚這一點。

And secondly, what are the next steps? As you mentioned, the engagement with FDA has been strong as you think about labeling and the next steps of the late cycle. Thanks so much.

其次，下一步該怎麼做？正如您所提到的，當您考慮標籤和後期週期的後續步驟時，與 FDA 的合作一直很緊密。非常感謝。

Yes, sure. And as you noted, we're really pleased with how we're progressing. It's been very consistent with the FDA and the fact that we were able to say at this time, it's been communicated, no Ad Comm, but of course, it's an ongoing regulatory review. Sarah, do you want to add color from your perspective?

是的，當然。正如您所說，我們對我們的進展感到非常滿意。這與 FDA 的要求非常一致，事實上我們此時可以說，已經進行了溝通，沒有 Ad Comm，但當然，這是一個持續的監管審查。莎拉，你想從你的角度添加一些色彩嗎？

No, it's exactly what you just said. I think we are pleased with the process. We are engaged with the agencies, right, because we've filed in multiple regions. And everything is progressing. We're very much looking forward to our PDUFA date of September 7.

不，正是你剛才所說的。我認為我們對這個過程感到滿意。我們正在與這些機構合作，因為我們已在多個地區提交了申請。一切都在進步。我們非常期待 9 月 7 日的 PDUFA 日期。

And I will just take the opportunity, Greg, to reinforce the fact that I think you heard the excitement in Tsveta's voice. We're now four months away from the PDUFA. And I must say the commercial team is very prepared, and we're very much looking forward to getting to that date and then hopefully having the opportunity to serve the patients who count on us.

格雷格，我只是想藉此機會強調一下，我認為你已經聽出了茨維塔聲音中的興奮。現在距離 PDUFA 還剩四個月的時間。我必須說，商業團隊已經做好了充分的準備，我們非常期待這一天的到來，並希望有機會為依賴我們的患者提供服務。

And maybe a quick follow-up. Just broadly with the sickle cell community and as you think about especially tebapivat and the enrollment there, how has the Oxbryta wean off the current market conditions? How is that, in your view, impacted the recruitment of trials, the sickle cell community as they sort of transition and await for new options in the marketplace?

或許還會有快速的跟進。就鐮狀細胞疾病患者群體而言，當您考慮特別是 tebapivat 及其招生情況時，Oxbryta 如何擺脫當前的市場狀況？您認為這對試驗招募和鐮狀細胞疾病患者族群有何影響？他們正處於轉型期，等待市場上出現新的選擇。

Sure. You bet. Sarah can start and then Tsveta might want to add a little color too on sickle cell in general and the opportunity in front of us.

當然。當然。莎拉可以開始，然後茨維塔可能也想對鐮狀細胞疾病的整體情況和我們面前的機會添加一些色彩。

Yes. And so, from our perspective, of course, we were disappointed when Oxbryta was withdrawn because we really are looking for all drugs that can potentially provide benefit for patients. And hope that sickle cell disease patients ultimately will have many options to choose from. From our perspective on the clinical trial conduct, we have not observed any changes as it relates to our programs

是的。因此，從我們的角度來看，當 Oxbryta 被撤回時我們當然感到失望，因為我們確實在尋找所有可能為患者帶來益處的藥物。並希望鐮狀細胞疾病患者最終能夠擁有多種選擇。從我們對臨床試驗實施的角度來看，我們沒有觀察到與我們的計劃相關的任何變化

Yes. And just to add to Sarah, of course, from us commercially, sickle cell disease is a large market. There are over 100,000 patients in the US. The withdrawal of Oxbryta was devastating for the community, and that just strengthens the unmet medical need.

是的。當然，莎拉還要補充一點，從我們的商業角度來看，鐮狀細胞疾病是一個巨大的市場。美國有超過10萬名患者。Oxbryta 的撤出對社區來說是毀滅性的，這只會加劇未滿足的醫療需求。

We are excited about the potential opportunity to have two products on the market to serve that community and for us to continue to grow the number of patients who can benefit from an innovative therapy. When it comes to kind of the sentiment, of course, we're going to take that into account as our launch preparations and the engagement with the community. They deserve the trust and respect and we'll continue to do so.

我們很高興有機會在市場上推出兩種產品來服務該社區，並繼續增加可從創新療法中受益的患者數量。當談到這種情緒時，我們當然會在發布準備和與社群的互動中考慮到這一點。他們值得信任和尊重，我們將繼續這樣做。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Congrats on the progress in the quarter. Maybe first, since you alluded to it a couple of times, maybe you could just remind us about your plans for launching mitapivat ex-US. When could these approvals come through for that?

恭喜本季取得的進展。首先，既然您提到過幾次，也許您可以提醒我們一下您在美國以外推出 mitapivat 的計劃。這些批准什麼時候能通過？

And do you think it would make sense to try and keep the economics in-house by leaving the launches yourself given the strong balance sheet? And then I've got a follow-up.

考慮到強勁的資產負債表，您是否認為嘗試將產品發布留在公司內部並控制經濟效益是合理的？然後我有一個後續行動。

Yeah. Thanks, Alec. I'm going to let Tsveta take over on that question. I will just start by reinforcing by far, the two most important geographies for thalassemia, is first, the US and secondly, the Gulf region, GCC. And we are very well-prepared with regard to both of those.

是的。謝謝，亞歷克。我打算讓茨維塔來回答這個問題。我首先要強調的是，迄今為止，地中海貧血最重要的兩個地區是美國，其次是海灣地區（GCC）。我們對這兩方面都做好了充分的準備。

Yeah, absolutely. So, when it comes to ex-US, as Sarah noted, we have submitted to four regulatory authorities, UAE, Saudi Arabia, and Europe from a commercial launch preparation and priority. Saudi or the GCC region is the next priority for us.

是的，絕對是如此。因此，正如莎拉所說，當談到美國以外時，我們已經從商業發布準備和優先考慮的角度向阿聯酋、沙烏地阿拉伯和歐洲四個監管機構提交了申請。沙烏地阿拉伯或海灣合作委員會地區是我們的下一個優先事項。

When we look at the ex-US opportunity, when you think about launch and timing and uptake, I would say that especially the Gulf countries, they are a lot more similar to the European market. So, it takes some time from approval to actually get on formularies, get access to patients and see the uptake.

當我們審視美國以外的機會時，當你考慮發布、時機和吸收時，我會說，特別是海灣國家，它們與歐洲市場更相似。因此，從批准到實際進入處方集、供患者使用並看到療效需要一些時間。

We have a very strong partner in the Gulf with NewBridge, which we believe that they will be very well-positioned to combine our strong expertise and knowledge in thalassemia with their strong expertise and knowledge in the region to execute on our behalf successfully.

我們在海灣地區擁有非常強大的合作夥伴 NewBridge，我們相信他們能夠很好地將我們在地中海貧血方面的強大專業知識與他們在該地區的強大專業知識結合起來，代表我們成功地執行任務。

And on economics, maybe Cecilia, you can touch on that.

關於經濟學，塞西莉亞，也許你可以談談這個。

Yes, Alec, on the economics, as we announced last year, we have the partnership with NewBridge. This is, I'll call it, a revenue split, which allows us to leverage a little bit the best of both worlds, as Sarah said, NewBridge knowledge of the region with our team support knowledge of the product. And it's an efficient way for capital deployment for us. For Europe, we plan to do something very similar in terms of the structure, and we'll provide an update when we do so.

是的，亞歷克，就經濟而言，正如我們去年宣布的那樣，我們與 NewBridge 建立了合作夥伴關係。這就是，我稱之為收入分成，它使我們能夠充分利用兩全其美的優勢，正如莎拉所說，NewBridge 對該地區的了解與我們團隊支持對產品的了解相結合。這對我們來說是一種有效的資本配置方式。對於歐洲，我們計劃在結構方面做一些非常相似的事情，完成後我們會提供更新資訊。

And then maybe one, great to see Krishnan joining the team. Curious if bringing him on board to lead corporate strategy represents any shifts in kind of the way you're thinking or allocating resources going forward, either through increased BD or areas of pipeline focus?

然後也許一個，很高興看到克里希南加入團隊。好奇的是，讓他加入領導公司策略是否代表您未來的思維方式或資源分配方式的某種轉變，無論是透過增加 BD 還是管道重點領域？

Yes. Thanks. I'm really happy to have Krishnan on board. He's a very experienced leader across, as I noted in my earlier comments, multiple companies, senior roles, very well-connected individual. And we're just delighted to have him on the team.

是的。謝謝。我很高興 Krishnan 能加入我們。正如我在之前的評論中提到的那樣，他是一位非常有經驗的領導者，在多家公司擔任高階職位，人脈很廣。我們非常高興他能加入我們的團隊。

To answer your question, it's not a shift. It's really building capabilities and a reinforcement of our real focus for corporate strategy, capital allocation specifically. And in order of priority, first, it's getting these launches right.

回答你的問題，這不是轉變。這確實是為了建立能力，並強化我們對企業策略、特別是資本配置的真正關注。按照優先順序，首先，要正確完成這些發射。

We're really excited, as we've noted, about thalassemia now with the PDUFA just four months away. We are equally excited about the RISE UP data that will play out at the end of this year, and that could present a back-to-back launch scenario with sickle cell launch towards the end of 2026. We also are not a one-product company.

正如我們所注意到的，我們對地中海貧血感到非常興奮，因為距離 PDUFA 僅有四個月的時間了。我們同樣對今年底發布的 RISE UP 數據感到興奮，這可能會呈現與 2026 年底鐮狀細胞發射連續發射的情景。我們也不是一家單一產品的公司。

We're really proud to talk about the middle and earlier part of our pipeline today. And so that's a key priority. And third is BD. Any healthy biopharma biotech company should always be looking at how to continue to build out the pipeline. And we have a very strong balance sheet.

今天，我們非常自豪地談論我們管道的中期和早期部分。所以這是一個關鍵的優先事項。第三個是 BD。任何健康的生物製藥生物技術公司都應該始終關注如何繼續建立產品線。我們的資產負債表非常強勁。

As I noted, we will be extremely disciplined because we have internal opportunities that sets a very high bar. But Krishnan really adds to that capability. And again, we're just delighted to have him on the team.

正如我所指出的，我們將極其自律，因為我們擁有設定極高標準的內在機會。但克里希南確實增強了這種能力。再次，我們非常高興他能加入我們的團隊。

Divya Rao, TD Cowen.

Divya Rao，TD Cowen。

This is Divya on for Mark. I'll add my congrats on all the progress. Just one question from us. Have you seen any changes to your communication frequency with the FDA given the recent reshuffling that's been happening at the agency? And then, is there a deadline for when the FDA needs to inform you of a potential Ad Comm?

這是 Divya 為 Mark 表演的。我要對所有的進步表示祝賀。我們只想問一個問題。鑑於 FDA 最近正在進行的改組，您與 FDA 的溝通頻率有任何變化嗎？那麼，FDA 需要何時通知您潛在的 Ad Comm 呢？是否有一個最後期限？

So, thanks, Divya, for the question. So no, our communication with the agency on our programs has been the same as before. So I think it is a normal back and forth in the context of -- especially for the filing, it's a normal back and forth communication with questions and answers.

所以，感謝 Divya 提出這個問題。所以，我們與該機構就我們的專案進行的溝通與以前一樣。因此，我認為這是一種正常的來回溝通——特別是對於歸檔而言，這是一種正常的來回溝通，有問答。

So as you know, the PDUFA date is September 7, and it's -- as the review is ongoing, an agency always has the opportunity to request for an advisory committee. To date, though, they have informed us that there is no advisory committee planned and that the review is still ongoing.

如您所知，PDUFA 日期是 9 月 7 日，並且 - 由於審查仍在進行中，因此機構始終有機會請求成立諮詢委員會。但到目前為止，他們告訴我們，沒有計劃成立諮詢委員會，審查仍在進行中。

And Divya, I'll just take the opportunity to give credit to the FDA because we know that there have been a lot of dynamics. But I think this also reinforces that this is a high-unmet need area where we have two stellar studies that read out last year. And the data that we've put into our file really aligns beautifully with what we hear consistently is the unmet need that we're trying to fulfill. So we're appreciative of that continued focus and really pleased with how we're progressing.

迪維亞，我想藉此機會對 FDA 表示讚揚，因為我們知道他們已經取得了許多進展。但我認為這也強調了這是一個高度未滿足需求的領域，我們去年在這個領域進行了兩項出色的研究。我們放入文件中的數據與我們不斷聽到的資訊完全一致，這就是我們正在努力滿足的未滿足的需求。因此，我們很感激大家的持續關注，並且對我們的進展感到非常滿意。

Hiro Nagayumi, Cantor.

Hiro Nagayumi，領唱者。

This is Hiro on behalf of Eric Schmidt here at Cantor. I wanted to ask a bit about the rationale and conviction for starting the Phase 2 tebapivat study in sickle cell in mid-2025 prior to the Phase 3 readout of PYRUKYND in late 2025.

我是 Hiro，代表 Cantor 的 Eric Sc​​hmidt。我想問一下在 2025 年底 PYRUKYND 第三階段讀數之前於 2025 年中期啟動鐮狀細胞 tebapivat 第二階段研究的理由和信念。

Yes. I think -- again, Hiro, that's going to be two-part. Sarah should start with tebapivat itself and why we're excited about it. And then Tsveta can add more about what we're trying to achieve in sickle cell for the patient community in general, which clearly needs more, not fewer options ahead.

是的。我認為——Hiro，這將分為兩部分。莎拉應該從 tebapivat 本身開始講解，並解釋為什麼我們對此感到興奮。然後，茨維塔可以進一步介紹我們在鐮狀細胞疾病方面為廣大患者群體所取得的成就，顯然，患者群體需要更多而不是更少的選擇。

So Hiro, like we were very pleased with the Phase 1 data that we have generated in for tebapivat in sickle cell disease. And when you look at drug development at that program specifically, that allows us to move forward to a Phase 2, which we're very excited about starting mid-year.

所以 Hiro，我們對 tebapivat 治療鐮狀細胞疾病的第一階段數據感到非常滿意。當你具體研究該計畫的藥物開發時，你會發現這使我們能夠進入第二階段，我們對年中開始的第二階段感到非常興奮。

And then, of course, within drug development, this is where Tsveta's organization and the R&D organization, we work very closely together because we will always design our trials towards the product profile that we believe can make meaningful change. And with that, I'll hand it over to Tsveta.

當然，在藥物開發領域，Tsveta 的組織和研發組織密切合作，因為我們始終會根據我們認為可以帶來有意義改變的產品概況來設計試驗。現在，我將把發言權交給茨維塔。

Absolutely. So the way I think about it is really in three steps. The first one is it's a 100,000 patient population with a very large unmet medical need. And when you think about like this market, it can easily absorb and it's of the need of multiple therapies. The second one is the fact that we hear it loud and clear from KOLs and physicians and experts in the field.

絕對地。所以我認為它實際上分為三個步驟。首先，它有 10 萬名患者，並且存在大量未滿足的醫療需求。當你考慮這個市場時，它很容易吸收，而且需要多種療法。第二個事實是，我們從關鍵意見領袖、醫生和該領域的專家那裡清楚地聽到了這一點。

Not every patient will respond to every single therapy. So they would like to have many options so they can choose from and find the best options for their therapy. And when it comes to timing and the co-positioning of the two products, we are actually looking to grow the patient population with our portfolio of products.

並非所有患者都會對每種療法產生反應。因此，他們希望擁有多種選擇，以便能夠找到最適合自己治療方案。當涉及兩種產品的時機和共同定位時，我們實際上希望透過我們的產品組合來增加患者數量。

We'll actually, more specifically, as Sarah said, position tebapivat after we have the mitapivat data, the RISE UP data. So starting now will allow us to actually have the two data sets and make the best informed decisions for us how to move forward with Phase 3.

實際上，更具體地說，正如 Sarah 所說，在獲得 mitapivat 數據（即 RISE UP 數據）後，我們將定位 tebapivat。因此，從現在開始我們將能夠真正擁有這兩組資料集，並為我們做出如何推進第三階段的最佳明智決策。

And I think folks listening in may know Tsveta's background, too, but in prior life, Tsveta has a lot of experience building lasting franchises that have a very similar dynamic of serving an even greater patient population. So we're looking to leverage her expertise in that regard.

我想聽眾可能也了解茨維塔的背景，但在過去的生活中，茨維塔在建立持久特許經營權方面擁有豐富的經驗，這些特許經營權具有非常相似的動力，可以為更多的患者群體提供服務。因此我們希望在這方面利用她的專業知識。

Emily Bodnar, HC Wainwright.

艾米莉·博德納、HC·溫賴特。

I guess for thalassemia, maybe if you can touch a bit on your plans for marketing for non-transfusion-dependent patients compared to transfusion-dependent patients, particularly on the non-transfusion side since those patients currently don't have any treatments?

我想對於地中海貧血，也許您可以談談針對非輸血依賴性患者和輸血依賴性患者的營銷計劃，特別是在非輸血方面，因為這些患者目前沒有任何治療方法？

Yeah. Perfect. Tsveta.

是的。完美的。茨維塔。

So first of all, I'll start with how excited we are about the potential launch in thalassemia, which is just four months away. We have deployed the team, and I can say that we are ready for launch. So that's really, really exciting and energizing.

首先，我要說的是，我們對地中海型貧血治療藥物的潛在上市感到非常興奮，該藥物將在四個月後上市。我們已經部署了團隊，我可以說我們已經做好了啟動的準備。這真的非常令人興奮和振奮。

When it comes to the market itself, I just want to mention very quickly, it's a really attractive rare disease market. Patients are diagnosed and known to the health care system. There is a good understanding and characterization of the unmet need across both transfusion-dependent and non-transfusion-dependent patients.

談到市場本身，我只想快速提一下，這是一個非常有吸引力的罕見疾病市場。患者得到診斷並被醫療保健系統所了解。對於輸血依賴性患者和非輸血依賴性患者的未滿足需求有很好的理解和描述。

Our disease state education actually primarily focuses on the non-transfusion-dependent patients, which actually relates to your question. And of course, there are well-established KOLs and patient advocacy groups that will help us drive adoption.

我們的病情教育實際上主要集中在不依賴輸血的患者，這實際上與您的問題有關。當然，還有知名的關鍵意見領袖 (KOL) 和病人權益團體來幫助我們推動採用。

When it comes in terms of prioritization and different approaches for both patient populations, we believe PYRUKYND has a strong value proposition across both transfusion-dependent and non-transfusion-dependent patients. Our initial launch focus will actually be equally deployed against the transfusion-dependent patients. But also on the non-transfusion-dependent patients, which have hemoglobin levels less than 10 already have developed complications or are experiencing debilitating fatigue.

當談到針對兩類患者群體的優先順序和不同方法時，我們相信 PYRUKYND 對輸血依賴患者和非輸血依賴患者都具有強大的價值主張。我們最初的啟動重點實際上將同樣針對輸血依賴患者。但對於不依賴輸血的患者來說，他們的血紅素水平低於 10 已經出現併發症或正在經歷嚴重的疲勞。

And the reason for that is that these patients are already in an active engagement and communications with their health care providers. They are likely to hear about the therapy first. And we see them as a good starting point for our commercial uptake.

原因在於這些患者已經與他們的醫療保健提供者進行了積極的接觸和溝通。他們很可能首先聽說這種療法。我們認為它們是我們商業應用的一個好起點。

Andrew Berens, Leerink Partners.

安德魯貝倫斯，Leerink Partners。

This is Amanda on for Andy. It seems that you're starting to discuss more tebapivat more frequently in sickle cell disease and are slated to start the Phase 2. Is there any color that you can provide on kind of differences on how you're thinking of like patients going into that study and the tebapivat study versus RISE UP or any endpoints, differences there that might be a focus?

這是 Amanda 為 Andy 主持的節目。看來您開始更頻繁地討論鐮狀細胞疾病中的 tebapivat，並且計劃開始第 2 階段。您能否提供一些細節，說明您對參與研究的患者以及 tebapivat 研究與 RISE UP 或任何終點的不同看法，這些不同之處可能成為關注的焦點？

Any learnings that you're taking into this new trial? And also, have tebapivat shown any signs of impacting the liver in these early studies? Or how are you thinking about that?

您在這次新的試驗中學到什麼了嗎？此外，在這些早期研究中，tebapivat 是否顯示出對肝臟有影響的跡象？或者您對此有何看法？

Sure, Amanda. I'll just start by making a comment that we will follow a very staged process to guide us on how we continue to differentiate, but perhaps Sarah can just add a little bit on the design itself for the Phase 2 and then thoughts ahead.

當然，阿曼達。我首先要說的是，我們將遵循一個分階段的過程來指導我們如何繼續實現差異化，但莎拉也許可以對第二階段的設計本身以及未來的想法做一點補充。

So the Phase 2 for tebapivat is sort of a classic dose-finding study, which we're looking for proof of concept of tebapivat by looking at a hemoglobin response. So, it's a very standard development in sickle cell disease, I would say.

因此，tebapivat 的第 2 階段是一種經典的劑量探索研究，我們透過觀察血紅蛋白反應來尋找 tebapivat 的概念證明。所以，我想說，這是鐮狀細胞疾病的一個非常標準的發展。

As Tsveta and I discussed earlier, I think this is really about -- we're in a phase that the drug has shown promise in a Phase 1. So now we're bringing it forward to a Phase 2 so it can continue to establish its benefit risk profile.

正如 Tsveta 和我之前討論的那樣，我認為這實際上是——我們正處於該藥物在第一階段顯示出前景的階段。因此，現在我們將其推進到第二階段，以便可以繼續確定其效益風險狀況。

And so far, we have not observed a liver signal on tebapivat. But we will continue to accrue safety data in that program. And then as Tsveta highlighted earlier, between each development phase, we work very closely with our commercial team to make sure that the trials we design can meet the product profile that commercial is requesting to be met at the end of the trial.

到目前為止，我們還沒有在 tebapivat 上觀察到肝臟訊號。但我們將繼續在該計劃中累積安全數據。正如 Tsveta 之前所強調的那樣，在每個開發階段之間，我們都與我們的商業團隊密切合作，以確保我們設計的試驗能夠滿足商業團隊在試驗結束時要求滿足的產品概況。

And that will be driven by how the market evolves and how the population is growing and the unmet need within that patient population. And so that is a little bit too early now to discuss because, obviously, Phase 3 comes after Phase 2.

這將取決於市場如何發展、人口如何成長以及患者群體中未滿足的需求。現在討論這個還為時過早，因為很明顯，第三階段是在第二階段之後。

And again, this is -- follows our disciplined approach with capital allocation. We don't want to get ahead of ourselves. Just as last year, we waited for the ENERGIZE data readout before we started building our commercial team, very similar approach here as we look to build a sickle cell franchise. We will learn more from the Phase 2, and then we'll make the right decisions at that time.

再次強調，這遵循了我們嚴謹的資本配置方法。我們不想超越自己。就像去年一樣，我們等待 ENERGIZE 數據讀數後才開始組建商業團隊，這與我們希望建立鐮狀細胞特許經營權的方法非常相似。我們將從第二階段學到更多，然後做出正確的決定。

Tess Romero, JPMorgan.

摩根大通的泰絲·羅梅羅。

Double-clicking back to a prior question, can you confirm or not if you have completed the mid-cycle meeting? And if so, can you comment on any high-level discussion you have had around labeling? And is there a scenario where REMS is needed? Or can you rule this out at this point?

雙擊回到先前的問題，能否確認是否已完成中期會議？如果是的話，您能否評論一下有關標籤的任何高層討論？是否存在需要 REMS 的場景？或者你現在可以排除這種可能性嗎？

Thanks, Tess, for the question. So, the process with the FDA, they will announce to you the end date of the review, which is the PDUFA goal date of September 7. So, we're really working towards that with them. And along the way, you have different touch points, which may or may not be meetings or questions, et cetera. It's a less defined process than, for instance, the EMA at which certain point you can submit your filing and then you receive questions that's very specific date, et cetera.

謝謝 Tess 提出這個問題。因此，在與 FDA 的流程中，他們會向您宣布審查的結束日期，即 PDUFA 目標日期 9 月 7 日。所以，我們確實正在與他們一起努力實現這一目標。在這個過程中，您會遇到不同的接觸點，這些接觸點可能是會議、問題等等，也可能不是。與 EMA 等相比，它的流程定義不太明確，在 EMA 中，您可以在某個時間點提交文件，然後您會收到有關非常具體的日期等的問題。

What we have mentioned before is that we have a collaborative engagement with the FDA. We're receiving questions back and forth. This is part of the standard process that we feel it's a very normal engagement at this point in time with the agency. Again, like I think the only thing that I would really anchor towards to is the September 7 date at this point in time.

我們之前提到過，我們與 FDA 有合作關係。我們收到了大量的問題。這是標準流程的一部分，我們認為這是目前與該機構的非常正常的合作。再說一次，我認為目前我唯一真正關注的日期是 9 月 7 日。

The labeling negotiations, as we've mentioned, the review is ongoing, right? To date, they have not informed us that there will be an advisory committee. But the review is ongoing, as we've mentioned. Labeling negotiations typically go later in the process of a review cycle. So, it's too early for that.

正如我們所提到的，標籤談判的審查正在進行中，對嗎？到目前為止，他們還沒有通知我們將成立一個諮詢委員會。但正如我們所提到的，審查仍在進行中。標籤談判通常在審查週期的後期進行。所以，現在還為時過早。

In regards to REMS or not, I think you can only really fully be certain when you have reached your PDUFA goal date on what the ultimate label shows and what will be required. But I think right now, we're very pleased with where we are. And it's, from our perspective, just a normal process.

至於是否使用 REMS，我認為只有在達到 PDUFA 目標日期時，您才能真正完全確定最終標籤上顯示的內容以及所需的內容。但我認為，我們對目前的狀況非常滿意。從我們的角度來看，這只是一個正常的過程。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

This is Lydia on for Salveen. Congrats on all the progress. Maybe just another one on the potential thalassemia launch. Could you just comment on any anticipated evolution of PYRUKYND pricing in the context of payer feedback, the existing price in PKD, and the patient population here?

我是 Salveen 的 Lydia。祝賀你取得的所有進展。也許這只是關於潛在地中海貧血症的另一個發布。您能否根據付款人的反饋、PKD 的現有價格以及這裡的患者群體，對 PYRUKYND 定價的預期變化進行評論？

Thank you for the question. I can't wait for the September 7 PDUFA date, and for us to talk a little bit more specifics about pricing then. But of course, any pricing decision will be anchored in the value proposition of the product, the label that we get.

謝謝你的提問。我迫不及待地等待 9 月 7 日的 PDUFA 日期，然後我們再討論更多有關定價的細節。但當然，任何定價決策都將以產品的價值主張和我們獲得的標籤為基礎。

Based on where we stated today, thalassemia is a rare disease. And from a payer perspective, we don't expect that category to be managed. All the interactions and the payer research that we've done indicate that there is a good understanding of the unmet medical need and very positive feedback on the product profile. We have a very strong market access team, and I'm very confident we can navigate the pricing opportunity with thalassemia very well.

根據我們今天所述，地中海貧血是一種罕見疾病。從付款人的角度來看，我們不希望該類別受到管理。我們進行的所有互動和付款人研究都表明，人們對未滿足的醫療需求有很好的了解，並且對產品概況有非常積極的回饋。我們擁有一支非常強大的市場進入團隊，我非常有信心我們可以很好地掌握地中海貧血的定價機會。

I'm not showing any further questions at this time. I would now turn the call over back to Brian for any closing remarks.

我目前沒有其他問題。現在我將把電話轉回給布萊恩，請他做最後發言。

All right. Thanks a lot, Victor, and thank you very much, everybody, for participating in today's call. We are, as we've noted, four months into another busy year, and we're four months away from the PDUFA date for thalassemia, which is very exciting.

好的。非常感謝，維克多，也非常感謝大家參加今天的電話會議。正如我們所注意到的，我們已經進入了另一個繁忙的一年的四個月，距離地中海貧血的 PDUFA 日期還有四個月的時間，這非常令人興奮。

So, we really believe that at Agios, we're poised to deliver transformative new therapies for patients and create significant long-term value to our shareholders. So, thanks again, and we look forward to speaking with all of you again real soon.

因此，我們堅信，在 Agios，我們已準備好為患者提供變革性的新療法，並為我們的股東創造重大的長期價值。所以，再次感謝，我們期待很快能再次與大家交談。

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

感謝大家參加今天的會議。該計劃確實就此結束。您現在可以斷開連線。祝大家有個愉快的一天。