Ionis Pharmaceuticals Inc (IONS) 2025 Q1 法說會逐字稿

Good morning, and welcome to the Ionis first quarter 2025 financial results conference call. As a reminder, this call is being recorded.

早安，歡迎參加 Ionis 2025 年第一季財務業績電話會議。提醒一下，本次通話正在錄音。

At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.

現在，我想將電話轉給投資者關係高級副總裁韋德沃克 (Wade Walke)，讓他主持電話會議。請開始。

Thank you, Amy. Before we begin, I encourage everyone to go to the Investors section of the Ionis website to view the press release and related financial tables that we will be discussing today, including a reconciliation of our GAAP to non-GAAP financials.

謝謝你，艾米。在我們開始之前，我鼓勵大家造訪 Ionis 網站的「投資者」部分，查看我們今天將要討論的新聞稿和相關財務表，包括我們的 GAAP 與非 GAAP 財務狀況的對帳。

We believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany today's call. With me this morning are Brett Monia, our Chief Executive Officer; Kyle Jenne, Chief Global Product Strategy Officer; and Beth Hougen, Chief Financial Officer.

我們相信非公認會計準則財務結果更能反映我們業務的經濟狀況以及我們如何管理業務。我們也在網站上發布了今天電話會議的幻燈片。今天早上和我一起的還有我們的執行長 Brett Monia； Kyle Jenne，首席全球產品策略長；以及財務長 Beth Hougen。

Richard Geary, Chief Development Officer; Eugene Schneider, Chief Clinical Development Officer; Eric Swayze, Executive Vice President of Research; and Jonathan Birchall, Chief Commercial Officer, will also join us for the Q&A portion of our call.

Richard Geary，首席開發長；尤金‧施耐德 (Eugene Schneider)，首席臨床開發官； Eric Swayze，研究執行副總裁；首席商務官喬納森·伯查爾 (Jonathan Birchall) 也將參加我們電話會議的問答環節。

I would like to draw your attention to Slide 3, which contains our forward-looking language statement. During this call, we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consider the risk factors contained in our SEC filings for additional detail.

我想提請您注意投影片 3，其中包含我們的前瞻性語言聲明。在本次電話會議中，我們將根據我們目前的預期和信念做出前瞻性陳述。這些聲明受一定風險和不確定性的影響，我們的實際結果可能有重大差異。我鼓勵您考慮我們提交給美國證券交易委員會 (SEC) 的文件中包含的風險因素，以獲取更多詳細資訊。

And with that, I'll turn the call over to Brett.

說完這些，我會把電話轉給布雷特。

Thanks, Wade. Good morning, everyone, and thanks for joining us today. Before we discuss our Q1 earnings and recent progress, I want to take a moment to acknowledge the rapidly evolving environment we're living in today.

謝謝，韋德。大家早安，感謝大家今天加入我們。在我們討論第一季的收益和最近的進展之前，我想花點時間來了解我們今天所處的快速變化的環境。

Recent changes at the FDA and the introduction of new tariff policies have introduced a degree of uncertainty with the potential for a disruption in our industry. Despite these external uncertainties, Ionis remains well positioned to execute on our strategic priorities, including all of our many value-driving catalysts coming up this year and next.

FDA 最近的變化和新關稅政策的推出帶來了一定程度的不確定性，有可能對我們的行業造成乾擾。儘管存在這些外部不確定性，Ionis 仍然能夠很好地執行我們的策略重點，包括今年和明年即將推出的眾多價值驅動催化劑。

We remain focused on our purpose to drive meaningful value for all Ionis stakeholders by successfully bringing better futures to people with serious diseases. We are executing very well against all our strategic priorities.

我們始終專注於我們的目標，透過成功地為患有嚴重疾病的人們帶來更美好的未來，為所有 Ionis 利害關係人創造有意義的價值。我們在所有策略重點方面都執行得非常好。

A clear example of our ongoing successes is the completion of two strategic licensing transactions recently which enabled us to substantially increase our 2025 financial guidance. This includes higher expected revenue and cash along with improved operating loss.

我們持續取得成功的一個明顯例子是最近完成的兩項策略授權交易，這使我們能夠大幅提高 2025 年的財務指導。這包括更高的預期收入和現金以及改善的經營虧損。

Raising guidance this early in the year reflects our confidence in our ability to continue executing well, including our ability to deliver transformational medicines to patients even amid the current volatility and our commitment and expectation to drive long-term value for shareholders.

今年年初就提高績效指引反映了我們對繼續良好執行的能力的信心，包括即使在當前動盪時期我們仍有能力向患者提供變革性藥物，以及我們致力於為股東創造長期價值的承諾和期望。

We achieved a major milestone for Ionis with our first independent commercial launch now successfully underway. I'm pleased to share that in its first full quarter on the market, TRYNGOLZA, the first and only FDA-approved treatment for familial chylomicronemia syndrome exceeded expectations.

我們的首次獨立商業發布現已成功進行，為 Ionis 實現了一個重要的里程碑。我很高興地告訴大家，TRYNGOLZA 作為第一個也是唯一一個獲得 FDA 批准的治療家族性乳糜微粒血症綜合症的藥物，在上市的第一個完整季度就超出了預期。

This encouraging start reflects our commercial team's thoughtful planning, outstanding execution and highlights the commercial capabilities that we have built. Right behind TRYNGOLZA is our second independent launch, donidalorsen for hereditary angioedema, or HAE, which is rapidly approaching. The team is laser-focused on ensuring success.

這一令人鼓舞的開端反映了我們商業團隊的周到規劃、出色的執行力，凸顯了我們已經建立的商業能力。緊隨 TRYNGOLZA 之後的是我們的第二個獨立上市藥物，用於治療遺傳性血管性水腫（HAE）的 donidalorsen，該藥物即將上市。該團隊全心全意致力於確保成功。

Donidalorsen has the potential to become a preferred treatment for HAE, and we remain on track to launch in the third quarter. These launches are just beginning. We're poised to report data from two Ionis-owned Phase III programs later this year, which, if positive, will enable us to continue delivering a steady cadence of important medicines to even more patients.

Donidalorsen 有可能成為治療 HAE 的首選藥物，我們仍有望在第三季推出該藥物。這些發布才剛開始。我們準備在今年稍後報告 Ionis 旗下兩個 III 期項目的數據，如果結果呈陽性，這些數據將使我們能夠繼續為更多患者穩定地提供重要藥物。

These are a second indication for olezarsen severe hypertriglyceridemia, or sHTG, a large population with high unmet need; and zilganersen for Alexander's disease, a severe, rare leukodystrophy with no approved therapies. Collectively, these four programs represent needed patient breakthroughs and multibillion-dollar revenue potential for Ionis.

這是 olezarsen 治療嚴重高三酸甘油酯血症（sHTG）的第二個適應症，該疾病涉及大量未滿足的醫療需求；以及用於治療亞歷山大病的 zilganersen，這是一種嚴重且罕見的腦白質營養不良症，目前尚無獲批的治療方法。總的來說，這四個項目代表著 Ionis 所需的患者突破和數十億美元的收入潛力。

Additionally, in the next three years, we expect four launches from our late-stage partnered medicines currently in development to treat a range of serious life-threatening diseases. These medicines are poised to significantly increase our revenues by expanding the reach of Ionis discovered medicines to more patients that are in need.

此外，在未來三年內，我們預計將推出四種目前正在開發的後期合作藥物，用於治療一系列嚴重的危及生命的疾病。這些藥物將擴大 Ionis 發現藥物的覆蓋範圍，惠及更多有需要的患者，從而大幅增加我們的收入。

With the recent launch of TRYNGOLZA and our upcoming independent and partner launches, Ionis is on a path to bring important medicines to patients for years to come, positioning us to achieve substantial and sustained revenue growth and positive cash flow.

隨著最近推出的 TRYNGOLZA 以及我們即將推出的獨立和合作夥伴推出的產品，Ionis 將在未來幾年為患者提供重要的藥物，使我們能夠實現可觀且持續的收入增長和正現金流。

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

說完這些，我會把電話轉給凱爾。

Thank you, Brett. With our first independent launch underway and three additional independent launches planned in the next two years, our commercial team is executing on a focused agenda with substantial growth potential.

謝謝你，布雷特。我們的首次獨立發布正在進行中，並且計劃在未來兩年內進行另外三次獨立發布，我們的商業團隊正在執行具有巨大成長潛力的重點議程。

We're well positioned to build on the early success of TRYNGOLZA while we prepare for our other upcoming launches. Donidalorsen for HAE is on track for anticipated approval in August, followed by olezarsen for sHTG, which is on pace for Phase III data in the third quarter and a potential launch next year. Let's start with TRYNGOLZA which had an encouraging debut in the first quarter.

我們已做好準備，在 TRYNGOLZA 早期成功的基礎上再接再厲，為其他即將推出的產品做好準備。用於 HAE 的 Donidalorsen 預計於 8 月獲得批准，用於 sHTG 的 olezarsen 緊隨其後，預計將於第三季度獲得 III 期數據，並可能在明年上市。讓我們從 TRYNGOLZA 開始吧，它在第一季表現令人鼓舞。

Our commercial team executed seamlessly delivering on all initial launch objectives and exceeding expectations with over $6 million in net product sales in the first quarter. In this first full quarter on the market, we saw strong patient uptake driven by multiple factors.

我們的商業團隊順利完成了所有初始發布目標，並超越預期，第一季淨產品銷售額超過 600 萬美元。在上市的第一個完整季度，我們看到受多種因素推動的患者接受度強勁成長。

First, we successfully converted nearly all of the US expanded access and clinical trial patients to commercial product.

首先，我們成功地將幾乎所有美國擴大進入和臨床試驗患者轉化為商業產品。

Second, as TRYNGOLZA is the first and only approved FDA treatment for FCS, early uptake benefited from patients who had been previously diagnosed and were waiting for treatment.

其次，由於 TRYNGOLZA 是首個也是唯一一個獲得 FDA 批准的 FCS 治療藥物，早期採用該藥物有利於先前已被診斷並等待治療的患者。

And third, our patient finding efforts ahead of launch paid off contributing to scripts from newly identified and diagnosed FCS patients.

第三，我們在產品發布前尋找患者的努力得到了回報，為新發現和診斷的 FCS 患者提供了處方。

Physician engagement has also gained meaningful traction. We've been encouraged by the initial breadth of physicians prescribing TRYNGOLZA with scripts from a mix of specialists across the country. At the end of Q1, the initial prescriber mix included approximately 50% cardiologists and 25% endocrinologists with [lipidologists] and internal medicine HCPs comprising the rest.

醫生的參與也獲得了有意義的進展。看到全國各地眾多醫生開出 TRYNGOLZA 處方，我們深受鼓舞。在第一季末，初始處方者組合中約有 50% 是心臟病專家，25% 是內分泌專家，其餘為脂質學家和內科 HCP。

Physicians have also reported positive and deeply moving feedback, including one doctor who shared that he was over the moon that this was the lowest as patient's TG levels have ever been.

醫生們也報告了積極且令人感動的回饋，其中一位醫生表示，他非常高興，因為這是患者三酸甘油酸酯水平有史以來最低的一次。

On the access front, coverage and reimbursement dynamics have been favorable. The coverage split for patients on TRYNGOLZA to date is just over 60% commercial and just under 40% government. Importantly, patients whether clinically diagnosed or genetically confirmed have received timely access with most receiving coverage through the medical exception process based on clinical diagnosis.

在獲取方面，覆蓋範圍和報銷動態一直很有利。迄今為止，TRYNGOLZA 患者保險覆蓋範圍中，商業保險略高於 60%，政府保險略低於 40%。重要的是，無論是臨床診斷或基因確診的患者都能夠及時獲得醫療服務，大多數患者都可以透過基於臨床診斷的醫療例外程序獲得醫療保障。

This underscores both the urgency of the high unmet need and payer willingness to support access ahead of establishing formal policies. As payers establish coverage policies over the next several months, it will be important that these policies support both clinical and genetic diagnosis pathways.

這強調了未滿足需求的緊迫性以及付款人在製定正式政策之前支持獲取醫療服務的意願。隨著付款人在未來幾個月內制定承保政策，這些政策支持臨床和基因診斷途徑將非常重要。

To this end, our market access team is actively engaging with payers to enable continued patient access. Through the first quarter, the team had already engaged with payers representing the vast majority of covered lives in the US and are working towards getting additional policies in place.

為此，我們的市場准入團隊正在積極與付款人合作，以確保患者能夠繼續獲得服務。在第一季度，該團隊已經與代表美國絕大多數受保人群的付款人進行了接觸，並正在努力製定更多政策。

We're also seeing positive trends beyond coverage, including reimbursement time lines that have exceeded our internal benchmarks. And in the first full quarter of launch, nearly 90% of patients had zero out-of-pocket costs highlighting the effectiveness of our Ionis Every Step Support program.

我們也看到了保險範圍之外的正面趨勢，包括報銷時間已經超過了我們的內部基準。在推出後的第一個完整季度，近 90% 的患者自付費用為零，凸顯了我們的 Ionis Every Step Support 計畫的有效性。

Ionis Every Step has been instrumental in delivering high-quality experience for both patients and providers. More than 90% of patients have opted in, receiving support that includes disease and nutrition education, auto-injector administration training, reimbursement support and more.

Ionis Every Step 在為患者和醫療服務提供者提供高品質體驗方面發揮了重要作用。超過 90% 的患者選擇加入，獲得包括疾病和營養教育、自動注射器管理培訓、報銷支援等支援。

For health care providers, the program streamlines prescribing by handling insurance authorization and coverage assistance as well as coordinating delivery, reauthorizations and refills. We're proud of TRYNGOLZA's early momentum, but we know we're still in the early innings. The vast majority of the estimated 3,000 people living with FCS in the USremain unidentified.

對於醫療保健提供者來說，該計劃透過處理保險授權和承保援助以及協調交付、重新授權和補充來簡化處方流程。我們為 TRYNGOLZA 的早期勢頭感到自豪，但我們知道我們仍處於早期階段。美國約有 3,000 名 FCS 患者，其中絕大多數仍未確定身分。

To close that gap, we're continuing to focus on our patient finding efforts and HCP education, targeting physicians who treat patients with severe hypertriglyceridemia to increase FCS awareness. At the same time, our payer engagement efforts will continue to focus on establishing broad durable access.

為了縮小這一差距，我們將繼續致力於患者尋找工作和 HCP 教育，針對治療嚴重高三酸甘油酯血症患者的醫生，以提高 FCS 意識。同時，我們的付款人參與工作將繼續致力於建立廣泛且持久的准入。

Backed by an experienced and high-performing team, we are well positioned to build on our first mover advantage to bring TRYNGOLZA to patients in need and keep them on treatment. Building on our foundation in FCS, we're advancing toward the blockbuster opportunity in sHTG with olezarsen.

在經驗豐富、績效優異的團隊的支持下，我們有能力利用先發優勢，將 TRYNGOLZA 帶給有需要的患者並讓他們繼續接受治療。在 FCS 的基礎上，我們正​​與 olezarsen 一起向 sHTG 中的重磅機會邁進。

Like FCS, sHTG is a serious condition defined by triglyceride levels over 500 milligrams per deciliter, well above the normal level of less than 150 milligrams per deciliter. These levels are easily determined through routine fasting blood tests. sHTG affects a broad population with many people unable to adequately manage their triglycerides with currently available treatments.

與 FCS 類似，sHTG 是一種嚴重疾病，其三酸甘油酯水平超過每分升 500 毫克，遠高於每分升低於 150 毫克的正常水平。這些水平可以透過常規空腹血液檢查輕鬆確定。 sHTG 影響的人群十分廣泛，許多人無法透過現有的治療方法充分控制三酸甘油酯。

This is particularly true for individuals with high-risk sHTG, defined as triglyceride levels greater than 880 milligrams per deciliter or greater than 500 milligrams per deciliter with a history of acute pancreatitis or other comorbidities. There are more than one million of these especially vulnerable people in the US, which represents our initial target population for olezarsen assuming approval.

對於高風險 sHTG 患者尤其如此，高風險 sHTG 患者的三酸甘油酯水平定義為每分升超過 880 毫克或每分升超過 500 毫克，且有急性胰臟炎或其他合併症病史。美國有超過一百萬這樣的特別脆弱人群，這代表了我們在獲得批准的情況下對 olezarsen 的最初目標人群。

As we heard during our recent KOL panel, sHTG represents a significant unmet medical need and physicians are eager for better treatment options, especially those that can reduce TGs down below pancreatitis risk levels.

正如我們在最近的 KOL 小組討論中聽到的那樣，sHTG 代表著一個重大的未滿足的醫療需求，醫生渴望獲得更好的治療方案，特別是那些可以將 TG 降低到胰腺炎風險水平以下的治療方案。

For example, [Dr. Allan Brown], a leading cardiologist focused on lipid management showed that sHTG can be devastating, with patients experiencing recurrent pancreatitis attacks despite best efforts. His primary goal is to reduce the risk of acute pancreatitis, which carries significant mortality and morbidity.

例如，[Dr.專注於脂質管理的領先心臟病專家艾倫·布朗 (Allan Brown) 表示，sHTG 可能具有毀滅性，儘管患者盡了最大努力，但仍會反覆出現胰腺炎發作。他的主要目標是降低急性胰臟炎的風險，這種疾病會導致大量死亡和發病。

Importantly, all three panelists agreed that APOC3 inhibition offers a promising new therapeutic pathway with the potential to help patients dramatically reduce their triglycerides and the associated risk of acute pancreatitis.

重要的是，三位小組成員一致認為，APOC3 抑制提供了一種有希望的新治療途徑，有可能幫助患者大幅降低三酸甘油酯和相關的急性胰臟炎風險。

This view is also shared by other physicians who we've engaged with, including recent discussions at the American Academy of Cardiology Annual Conference with KOLs and community cardiologists. With this conviction to treat, we believe olezarsen is well positioned to meet the needs of people with sHTG and we're making excellent progress across clinical and commercial fronts as we prepare for an anticipated launch next year where we also have first-mover advantage.

我們接觸過的其他醫生也持這種觀點，包括最近在美國心臟學會年會上與關鍵意見領袖和社區心臟科醫生的討論。憑藉這種治療信念，我們相信 olezarsen 能夠滿足 sHTG 患者的需求，並且我們在臨床和商業方面取得了優異的進展，我們正在為明年的預期上市做準備，我們也擁有先發優勢。

We expect data from our supportive safety study, ESSENCE, in the second quarter. We then expect to report data in the third quarter from our global pivotal sHTG studies. These pivotal studies, CORE and CORE2, are being conducted in our target sHTG population defined by triglycerides greater than 500 milligrams per deciliter.

我們預計在第二季獲得支持性安全研究 ESSENCE 的數據。我們預計將在第三季報告全球關鍵 sHTG 研究的數據。這些關鍵研究 CORE 和 CORE2 正在我們的目標 sHTG 族群中進行，該族群定義為三酸甘油酯大於 500 毫克/分升。

Baseline characteristics were recently published in the American Heart Journal showing that fasting, median triglycerides at baseline in CORE and CORE2 were 836 and 749 milligrams per deciliter, respectively. And across the two studies, nearly half of participants had baseline TG levels of greater than 880, even though all participants were receiving standard of care therapy.

《美國心臟雜誌》最近發表了基線特徵，顯示 CORE 和 CORE2 的基線空腹三酸甘油酯中位數分別為每分升 836 毫克和 749 毫克。在兩項研究中，儘管所有參與者都接受了標準護理治療，但仍有近一半參與者的基線 TG 水平高於 880。

Additionally, 22% and 13% of participants had a history of pancreatitis in the last 10 years prior to enrollment in CORE and CORE2, respectively. Importantly, both studies are well powered to show a significant reduction in triglycerides and it's this reduction that we expect will lead to improvements in clinical outcomes for patients. Assuming positive data, we plan to submit an sNDA before year-end.

此外，在參加 CORE 和 CORE2 之前的 10 年內，分別有 22% 和 13% 的參與者有胰臟炎病史。重要的是，這兩項研究都有充分的證據證明三酸甘油酯顯著降低，我們預計這種降低將改善患者的臨床療效。假設數據積極，我們計劃在年底前提交 sNDA。

We're also expanding olezarsen's reach. We recently broadened our partnership with Sobi who will commercialize olezarsen in most markets outside the US, including in Europe, which is on pace for an FCS approval decision later this year.

我們也在擴大 olezarsen 的影響力。我們最近擴大了與 Sobi 的合作夥伴關係，Sobi 將在美國以外的大多數市場（包括歐洲）將 olezarsen 商業化，歐洲將在今年稍後獲得 FCS 批准決定。

This agreement expands the reach of TRYNGOLZA to more patients globally, while providing us the opportunity to earn milestone payments and royalties up to the mid-20% range. This significant first-mover advantage in both FCS and sHTG compelling real-world data and Phase III results in FCS and confidence in the upcoming data for sHTG we believe olezarsen is well positioned to become the standard of care in both indications, transforming treatment for thousands of people and driving long-term growth for Ionis.

該協議將 TRYNGOLZA 的覆蓋範圍擴大到全球更多患者，同時為我們提供了獲得高達 20% 左右的里程碑付款和特許權使用費的機會。FCS 和 sHTG 方面的顯著先發優勢、FCS 的令人信服的真實世界數據和 III 期結果以及對即將發布的 sHTG 數據的信心，我們相信 olezarsen 完全有能力成為這兩種適應症的治療標準，改變成千上萬人的治療方法，並推動 Ionis 的長期增長。

Turning to donidalorsen, our second anticipated independent launch, we see compelling opportunity to advance the prophylactic treatment for people with hereditary angioedema.

談到我們預期的第二款獨立上市產品 donidalorsen，我們看到了推進遺傳性血管性水腫患者預防性治療的絕佳機會。

We're applying the same discipline and focus that is driving a successful TRYNGOLZA launch as we prepare to bring donidalorsen to market. More than 20,000 people in the US and Europe are estimated to have HAE. In the US, most of these patients are on prophylactic treatment. As this market continues to evolve, up to 20% of patients annually have switched treatments in search of more effective and convenient options, signaling that current therapies aren't adequately addressing patients' needs.

當我們準備將 donidalorsen 推向市場時，我們運用了與成功推出 TRYNGOLZA 相同的紀律和重點。據估計，美國和歐洲有超過 20,000 人患有 HAE。在美國，大多數此類患者都接受預防性治療。隨著該市場的不斷發展，每年有多達 20% 的患者更換治療方法，以尋求更有效、更便捷的選擇，這表明當前的治療方法並不能充分滿足患者的需求。

Additionally, a recent Harris poll found that 9 in 10 HAE patients surveyed are interested in trying new prophylactic therapies and we believe donidalorsen is uniquely positioned to meet that demand if approved. With strong clinical data, a patient-friendly auto-injector and monthly or every other month dosing, we believe donidalorsen checks all the boxes that people with HAE are looking for in a next-generation prophylactic treatment.

此外，最近的哈里斯民意調查發現，受訪的 10 名 HAE 患者中有 9 名有興趣嘗試新的預防療法，我們相信，如果獲得批准，donidalorsen 將具有獨特的優勢來滿足這一需求。憑藉強大的臨床數據、患者友好的自動注射器以及每月或每隔一個月的劑量，我們相信 donidalorsen 滿足了 HAE 患者在下一代預防性治療中所尋求的所有條件。

We're building momentum ahead of launch by drawing on learnings and infrastructure from our ongoing TRYNGOLZA and WAINUA launches. This includes expanding our Ionis every step patient support program to address the unique needs of HAE patients to ensure they have a seamless treatment experience. We've already hired a substantial portion of our field-facing team and remain on track to complete hiring and training ahead of the anticipated approval.

我們正在利用正在進行的 TRYNGOLZA 和 WAINUA 發布的經驗和基礎設施，為發布做好準備。這包括擴展我們的 Ionis 每一步患者支援計劃，以滿足 HAE 患者的獨特需求，確保他們獲得無縫的治療體驗。我們已經僱用了相當一部分現場團隊，並預計在預期批准之前完成招募和培訓。

Our market access team is actively engaging with payers and our medical affairs team has also been laying the groundwork for a successful launch. Their efforts include showcasing our robust donidalorsen clinical data and Ionis' technology at key medical conferences.

我們的市場准入團隊正在積極與付款人接觸，我們的醫療事務團隊也一直在為成功發布奠定基礎。他們的努力包括在重要的醫學會議上展示我們強大的 donidalorsen 臨床數據和 Ionis 的技術。

For example, at the recent [Quad AI] meeting, we delivered 11 poster presentations and had robust engagement at our booth, including a dedicated space for unbranded HAE disease awareness campaign. We also capitalized on the conferences San Diego location by welcoming physicians to our campus for deeper in-person education about Ionis' science and technology.

例如，在最近的 [Quad AI] 會議上，我們進行了 11 場海報展示，並在我們的展位上獲得了熱烈的反響，其中包括一個專門用於無品牌 HAE 疾病宣傳活動的空間。我們也充分利用聖地牙哥會議的地理位置，歡迎醫生來到我們的校園，接受有關 Ionis 科學技術的更深入的面對面教育。

Physician feedback continues to be positive, particularly regarding our SWITCH study, which we believe could be a key differentiator in a competitive space. The study showed that people switching to donidalorsen from other prophylactic treatments experienced a further reduction in attacks and 84% of those surveyed said they preferred donidalorsen compared to their previous prophylactic treatment.

醫生的回饋持續積極，特別是關於我們的 SWITCH 研究，我們相信這可能是競爭領域中的關鍵差異化因素。研究表明，從其他預防性治療轉為使用 donidalorsen 的患者，其發病率進一步降低，84% 的受訪者表示，與先前的預防性治療相比，他們更喜歡 donidalorsen。

While we recognize that converting people from existing therapies will take time, we're confident that donidalorsen represents a compelling opportunity to be the preferred prophylactic treatment for many HAE patients. We're excited about the road ahead and well positioned to bring donidalorsen to people who need it, assuming approval.

雖然我們認識到讓人們放棄現有療法需要時間，但我們相信 donidalorsen 代表著一個極具吸引力的機會，可以成為許多 HAE 患者的首選預防性治療方法。我們對未來的道路充滿期待，如果獲得批准，我們將把 Donidalorsen 帶給需要它的人。

Our highly experienced, efficient and scalable commercial organization is delivering tangible results with the TRYNGOLZA-FCS launch underway. And as we build on these efforts, we're focused on maximizing TRYNGOLZA's full potential while preparing to successfully execute on our three additional launches planned over the next two years with more to follow positioning Ionis for sustained growth and long-term success.

我們經驗豐富、高效且可擴展的商業組織正在透過正在進行的 TRYNGOLZA-FCS 推出取得實際成果。在這些努力的基礎上，我們專注於最大限度地發揮 TRYNGOLZA 的全部潛力，同時準備成功執行未來兩年內計劃的另外三次產品發布，並推出更多產品，為 Ionis 的持續增長和長期成功奠定基礎。

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

說完這些，我現在將電話轉給貝絲。

Thank you, Kyle. I am pleased to share today that we are increasing our 2025 financial guidance across all metrics, including raising revenue by more than 20% due to our strong first quarter results and recent successful licensing transactions.

謝謝你，凱爾。今天我很高興地告訴大家，我們將提高 2025 年所有指標的財務指導，包括由於我們第一季的強勁業績和最近成功的許可交易，收入將增加 20% 以上。

We earned $132 million of revenue in the first quarter, which increased 10% year-over-year. More than half of our revenue came from commercial products which grew 28% compared to the same period last year. Our increasing revenue reflected the encouraging early performance of the TRYNGOLZA launch marking the first time in our company's history, we've reported product revenue.

我們第一季的營收為 1.32 億美元，年增 10%。我們超過一半的收入來自商業產品，與去年同期相比成長了28%。我們不斷增長的收入反映了 TRYNGOLZA 上市初期令人鼓舞的表現，這標誌著我們公司歷史上首次報告產品收入。

In the first full quarter of the launch, TRYNGOLZA generated over $6 million in product sales exceeding expectations. As Kyle discussed, we saw a good uptake from patients awaiting treatment and from newly identified patients.

在上市後的第一個完整季度，TRYNGOLZA 的產品銷售額超過 600 萬美元，超出預期。正如凱爾所討論的，我們看到等待治療的患者和新確診患者的治療進展良好。

Our commercial revenue also included $48 million in SPINRAZA royalties from substantial SPINRAZA product sales, which increased 25% year-over-year. Additionally, we earned $9 million in WAINUA royalties. We and our partner, AstraZeneca, expect WAINUA revenue to grow this year, driven by strong US demand and an expanding global footprint following the recent EU approval.

我們的商業收入還包括大量 SPINRAZA 產品銷售產生的 4,800 萬美元 SPINRAZA 特許權使用費，較去年同期成長 25%。此外，我們還獲得了 900 萬美元的 WAINUA 版稅。我們和我們的合作夥伴阿斯特捷利康預計，受美國強勁需求和歐盟近期批准後全球業務不斷擴大的推動，WAINUA 今年的營收將成長。

The remainder of our revenue came from programs under our R&D collaborations underscoring the important financial contributions of our partnered pipeline. You may have noticed we've streamlined the revenue section of our P&L.

我們的其餘收入來自於我們的研發合作項目，這凸顯了我們合作夥伴管道的重要財務貢獻。您可能已經注意到，我們簡化了損益表的收入部分。

We did this to reflect our new chapter as a commercial stage biotech and to plan for numerous independent launches in the coming years. Total non-GAAP operating expenses increased less than 5%, reflecting our commitment to disciplined investment and driving operating leverage.

我們這樣做是為了反映我們作為商業階段生物技術的新篇章，並計劃在未來幾年內推出眾多獨立產品。非公認會計準則總營運費用增幅不到 5%，反映了我們對嚴格投資和推動營運槓桿的承諾。

As planned, our sales and marketing expenses increased year-over-year, reflecting our investments in the US launch of TRYNGOLZA and preparations for the upcoming launch of donidalorsen. Our SG&A expenses also included our minority portion of WAINUA's sales and marketing expenses.

根據計劃，我們的銷售和行銷費用同比增長，反映了我們對美國推出 TRYNGOLZA 的投資以及即將推出 donidalorsen 的準備工作。我們的銷售、一般及行政費用還包括 WAINUA 銷售和行銷費用中的少數份額。

R&D expenses decreased year-over-year as several of our late-stage studies recently concluded. Importantly, we continue to appropriately fund our advancing pipeline with a large majority of our total R&D expenses funding our late-stage programs.

由於我們的幾項後期研究最近結束，研發費用較去年同期下降。重要的是，我們繼續為我們的推進管道提供適當的資金，其中大部分研發費用用於資助我們的後期專案。

Building on our strong first quarter results, we recently completed licensing transactions for sapablursen and ex US commercialization rights for olezarsen that meaningfully enhanced our financial outlook. This is the reason we are substantially increasing our 2025 guidance.

基於我們強勁的第一季業績，我們最近完成了 sapablursen 的許可交易以及 olezarsen 的美國以外商業化權利，這顯著改善了我們的財務前景。這就是我們大幅提高 2025 年指導價的原因。

Last week, we finalized the licensing of sapablursen, a medicine outside of our core disease areas of cardiology and neurology and generating $280 million. This transaction enables us to remain focused on realizing the potential of the medicines that we plan to independently bring to patients while further strengthening our financial position.

上週，我們完成了 sapablursen 的許可，這是一種不屬於我們心臟病學和神經病學核心疾病領域的藥物，創造了 2.8 億美元的收入。這項交易使我們能夠繼續專注於實現我們計劃獨立帶給患者的藥物的潛力，同時進一步加強我們的財務狀況。

Additionally, we are eligible to earn significant milestone payments as sapablursen advances together with royalties up to the mid-teen percentage range on future product sales. As a result of the substantial license fees, which exceeded the probabilized revenue included in our original guidance, we are increasing our revenue guidance by more than 20%.

此外，我們有資格獲得大筆里程碑付款，例如 sapablursen 預付款以及未來產品銷售額高達 15% 左右的版稅。由於授權費用大幅增加，超過了我們最初預期的預期收入，因此我們將收入預期提高了 20% 以上。

We now expect to earn revenue in the $725 million to $750 million range for the year. Our revenue guidance also includes sizable commercial revenue anchored by stable SPINRAZA royalties and growing WAINUA royalties. And with our first independent launch underway, we expect increasing product revenues as the year progresses.

我們現在預計今年的營收將在 7.25 億美元至 7.5 億美元之間。我們的收入預期還包括由穩定的 SPINRAZA 特許權使用費和不斷增長的 WAINUA 特許權使用費支撐的可觀的商業收入。隨著我們首次獨立推出新產品，我們預計隨著時間的推移，產品收入將會增加。

As the TRYNGOLZA launch progresses, it's important to remember that FCS is a rare disease with most patients still unidentified and undiagnosed. Therefore, our focus remains on disease education and patient identification, both of which will take time.

隨著 TRYNGOLZA 的上市進程，重要的是要記住 FCS 是一種罕見疾病，大多數患者仍未被識別和診斷。因此，我們的重點仍然是疾病教育和患者識別，這兩者都需要時間。

We're also on track to add initial product revenue from our second launch with the FDA action date for donidalorsen set for August 21. In addition to the sapablursen revenue, we will recognize in Q2, we expect to earn additional R&D revenue from partnered programs later this year. We continue to project our full year 2025 operating expenses to increase in the high single-digit percentage range compared to last year.

隨著 FDA 將 8 月 21 日批准 donidalorsen，我們也有望透過第二次產品發布來增加初始產品收入。除了我們將在第二季確認的 sapablursen 收入外，我們預計今年稍後將從合作項目中獲得額外的研發收入。我們繼續預測 2025 年全年營運費用將比去年增長高個位數百分比範圍。

This increase will be driven by SG&A expenses as we invest to support the success of our multiple ongoing and planned launches. We project our R&D expenses to remain steady this year similar to last year. As several of our late-stage studies have recently concluded or are wrapping up this year, we are able to reallocate our resources toward our next wave of opportunities, including ION582 for Angelman syndrome, which we expect to start Phase III development shortly.

由於我們投資以支持我們正在進行和計劃中的多個產品的成功推出，因此銷售、一般及行政費用 (SG&A) 將推動這一成長。我們預計今年的研發費用將與去年保持穩定。由於我們的幾項後期研究最近已經結束或即將在今年結束，我們能夠將資源重新分配到下一波機會中，包括用於治療 Angelman 綜合徵的 ION582，我們預計該藥物將很快開始 III 期開發。

Since our license fee revenue drops entirely to our bottom line, we are improving our non-GAAP operating loss guidance by nearly 25% to less than $375 million. And we now expect to end the year with $1.9 billion in cash.

由於我們的授權費收入完全計入我們的底線，我們將非公認會計準則營業虧損預期提高了近 25%，至不到 3.75 億美元。我們預計今年底的現金餘額將達到 19 億美元。

Our strength in balance sheet and commitment to drive operating leverage positions us well to advance our strategic priorities in this dynamic macroeconomic environment. Looking beyond 2025, we are confident in our ability to deliver sustained revenue growth.

我們的資產負債表實力和推動經營槓桿的承諾使我們能夠在這種動態的宏觀經濟環境中很好地推進我們的戰略重點。展望2025年以後，我們有信心實現持續的營收成長。

The late-stage programs we have in our pipeline today represent a significant opportunity with combined peak sales potential in the multibillion-dollar range. We expect our Ionis-owned medicines to generate more than $3 billion in peak annual product sales. This, of course, means that we will continue making investments to bring these medicines to patients.

我們目前處於研發階段的後期專案代表著重大機遇，其總高峰銷售潛力可達數十億美元。我們預計，Ionis 旗下藥品的年產品銷售額高峰將超過 30 億美元。當然，這意味著我們將繼續投資，將這些藥物帶給患者。

On top of our substantial product revenue opportunity, our late-stage partner of medicines could contribute over $2 billion annually in peak royalties. Notably, nearly all of these medicines are on track to deliver Phase III data either this year or next year, setting the stage for potential launches soon after.

除了我們龐大的產品收入機會之外，我們的後期藥品合作夥伴每年還可以貢獻超過 20 億美元的高峰特許權使用費。值得注意的是，幾乎所有這些藥物都將在今年或明年提供第三階段的數據，為不久後的潛在上市奠定基礎。

Together, these upcoming launches are poised to reach hundreds of thousands of patients worldwide and in turn, position Ionis to deliver significant top line growth and reach sustainable positive cash flow, turning scientific innovation into long-term value for shareholders.

總之，這些即將推出的產品將惠及全球數十萬名患者，使 Ionis 實現顯著的收入成長和可持續的正現金流，將科學創新轉化為股東的長期價值。

And with that, I'll turn the call back over to Brett.

說完這些，我會把電話轉回給布雷特。

Thank you, Beth. We've accomplished a great deal to get us where we are today, a fully integrated, commercial-stage biotech company with our first independent launch well underway.

謝謝你，貝絲。我們取得了巨大的成就，才有了今天的成就，我們是一家完全整合的商業階段生物技術公司，而我們的首次獨立發布正在順利進行中。

Slide 25 is off to an excellent start, including the US TRYNGOLZA launch. With additional upcoming launches anticipated, including donidalorsen for HAE and a deep commitment to innovation, we're well positioned to drive accelerating value.

Slide 25 開局良好，包括美國 TRYNGOLZA 的推出。隨著預計即將推出更多產品，包括 HAE 的 donidalorsen 以及對創新的深度承諾，我們已準備好推動價值的加速成長。

It's through Ionis' innovation that we've established a proven discovery and development engine, which has provided us with a pipeline of medicines with transformational potential. Our pipeline continues to deliver. We are on track for olezarsen and zilganersen Phase III data later this year that if positive would expand the reach of our medicines to even more patients.

透過 Ionis 的創新，我們建立了經過驗證的發現和開發引擎，它為我們提供了具有轉化潛力的藥物管道。我們的管道繼續交付。我們將在今年稍後公佈 olezarsen 和 zilganersen 第三階段的數據，如果結果呈陽性，我們的藥物將涵蓋更多患者。

And with many additional Phase III data readouts expected next year, we're well positioned to continue bringing a steady cadence of medicines to patients. Our scalable and experienced commercial organization is executing well, as demonstrated by the encouraging start to the TRYNGOLZA launch.

預計明年將會有更多第三階段數據公佈，我們已做好準備，繼續為患者提供穩定的藥物。我們的可擴展且經驗豐富的商業組織運作良好，TRYNGOLZA 上市的良好開端就證明了這一點。

Furthermore, our commercial organization has established a solid foundation to support multiple planned product launches in the future. And based on recent successful licensing transactions, along with our first quarter results and disciplined financial management, we significantly increased our 2025 financial guidance.

此外，我們的商業組織已經建立了堅實的基礎，以支持未來計劃推出的多種產品。基於最近成功的授權交易，以及我們的第一季業績和嚴格的財務管理，我們大幅提高了 2025 年的財務指引。

Importantly, the progress we've made puts us on a clear path to achieving positive cash flow supported by our expectations for substantial top line revenue growth.

重要的是，我們所取得的進展使我們走上了實現正現金流的明確道路，這得益於我們對大幅營收成長的預期。

And with that, we'll now open the call up for questions.

現在，我們將開始回答問題。

(Operator Instructions) Jay Olson, Oppenheimer.

（操作員指示）傑伊·奧爾森，奧本海默。

We're curious about olezarsen and any overlap between physician prescribers for FCS and sHTG and how you plan to leverage that? And then related to that, would approximately 20% pancreatitis history for the patients enrolled in your pivotal sHTG studies provide sufficient power to show AP reduction and what level of AP reduction are you targeting?

我們對 olezarsen 以及 FCS 和 sHTG 的醫生處方之間是否存在重疊以及您計劃如何利用這一點感到好奇？與此相關的是，在您關鍵的 sHTG 研究中，大約 20% 的患者有胰臟炎病史，這是否足以證明 AP 減少，以及您目標的 AP 減少程度是多少？

Thanks, Jay. Kyle will take the overlap of prescribers for FCS, sHTG, and I'll touch on the AP question you had.

謝謝，傑伊。凱爾 (Kyle) 將負責 FCS、sHTG 處方重疊問題，我將談論您提出的 AP 問題。

Yeah. Thanks, Jay. First, I mean, the TRYNGOLZA launch is really off to an encouraging start. The execution by the commercial team has been very strong. I'm very pleased with where we're at right now.

是的。謝謝，傑伊。首先，我的意思是，TRYNGOLZA 的推出確實有一個令人鼓舞的開始。商業團隊的執行力非常強。我對我們目前的狀況非常滿意。

As we discussed, we've been able to convert the [EAP] and OLE patients, those that have been waiting for a therapy have begun getting treatment, and we are also identifying new patients. The current targets that we have are a few thousand physicians, as you would expect, based on the type that are treating FCS today.

正如我們所討論的，我們已經能夠轉化 [EAP] 和 OLE 患者，那些一直在等待治療的患者已經開始接受治療，而且我們也在尋找新的患者。正如您所期望的，根據目前治療 FCS 的類型，我們目前的目標是數千名醫生。

These are our cardiologists and endocrinologists and they're seeing sHTG patients, but they're also seeing FCS patients. So that's kind of the runway to get us to sHTG. When you get to sHTG, the population expands, obviously, upwards of north of a million patients and as we go there, the overlap is quite significant.

這些是我們的心臟科醫生和內分泌專家，他們不僅接診 sHTG 患者，還接診 FCS 患者。這就是讓我們進入 sHTG 的跑道。當談到 sHTG 時，人口顯然會擴大，患者人數將超過一百萬，而且當我們到達那裡時，重疊會相當明顯。

They're still cardiologists, endocrinologists and lipidologists treating these patients. They are currently being treated with suboptimal therapies and not getting the goal. And what we're hearing, and we heard this from the KOL panel that we did on April 14 is that there is the realization that reducing triglycerides is directly correlated to and physicians are well aware of that, and they're looking for a better treatment option and we're looking forward to potentially having positive data and an approval for olezarsen to be able to help those patients.

他們仍然是治療這些患者的心臟科醫生、內分泌學家和脂質學家。他們目前正在接受次優療法治療，但並未達到治療目的。我們從 4 月 14 日的 KOL 小組討論中得知，人們意識到降低三酸甘油酯與疾病直接相關，醫生也很清楚這一點，他們正在尋找更好的治療方案，我們期待可能獲得積極的數據和對 olezarsen 的批准，以便能夠幫助這些患者。

Thanks, Kyle. Jay, obviously, you're referring to the AP baseline event data that we reported in our baseline demographics clinical trial design study that we published earlier this month, where we had 22% in CORE and 13% in CORE2 patients with a history of AP over the last 10 years.

謝謝，凱爾。傑伊，顯然，您指的是我們本月早些時候發表的基線人口統計臨床試驗設計研究中報告的 AP 基線事件數據，其中 CORE 中有 22% 的患者和 CORE2 中有 13% 的患者在過去 10 年內有 AP 病史。

The -- I want to emphasize before I get into expectations for AP data from those studies that this is a substantial unmet medical need, large patient population that health care providers are ready to treat patients with sHTG even without AP data in hand.

在我對這些研究的 AP 數據進行預期之前，我想強調的是，這是一個巨大的未滿足的醫療需求，大量患者群體，即使沒有 AP 數據，醫療保健提供者也準備治療 sHTG 患者。

This is a large market opportunity, a large unmet need and what we heard in our HCP panel, and we've heard from other HCPs that they are looking for a medicine that will substantially reduce triglycerides on top of standard of care, which is exactly how our trial is designed and that is the opportunity there.

這是一個巨大的市場機遇，一個巨大的未滿足的需求，我們從我們的 HCP 小組那裡聽說，我們也從其他 HCP 那裡聽說，他們正在尋找一種可以在標準治療的基礎上大幅降低甘油三酯的藥物，這正是我們的試驗設計方式，這就是其中的機會。

Now with that said, AP is, of course, is a secondary endpoint and our study as a secondary endpoint, is not powered for AP. But we're doing everything we can to increase the powering for the study. For example, we are combining CORE and CORE2 in our secondary analysis of AP events.

話雖如此，AP 當然是次要終點，而我們作為次要終點的研究並非針對 AP。但我們正在盡一切努力增加研究的動力。例如，我們在對 AP 事件進行二次分析時結合了 CORE 和 CORE2。

And we're looking at AP events at 12 months, whereas the triglyceride primary endpoint is at six months. We're extending -- we're looking at the maximum amount of time in patients to look at AP data. And of course, the FCS data is also encouraging for TRYNGOLZA where we reported significant reductions in acute pancreatitis events in our BALANCE study.

我們正在觀察 12 個月時的 AP 事件，而三酸甘油酯的主要終點是 6 個月時的 AP 事件。我們正在延長——我們正在研究患者查看 AP 數據的最長時間。當然，FCS 數據對於 TRYNGOLZA 來說也是令人鼓舞的，我們在 BALANCE 研究中報告了急性胰臟炎事件顯著減少。

So take all that into account, but really what we are laser focused on is to demonstrate substantial reductions of triglycerides in sHTG patients, which is what are looking for to prescribe a medicine like olezarsen.

所以，請考慮所有這些因素，但我們真正關注的是證明 sHTG 患者的三酸甘油酯大幅降低，這正是我們開出 olezarsen 等藥物的目的。

Gary Nachman, Raymond James.

蓋瑞納赫曼、雷蒙詹姆斯。

So on donidalorsen, just talk a bit more about what you're doing ahead of the PDUFA date internally to prepare for that launch. For patients that are going to be switching, how you're thinking about that transition, I guess, in the first year of launch?

那麼在 donidalorsen 上，請再多談談您在 PDUFA 日期之前內部為發布所做的準備工作。對於即將轉換的患者，我想您是如何考慮在推出的第一年進行這種轉變的？

And just in terms of access, how long do you think that process is going to take? And then just as a follow-up [here], Brett, on the macro dynamics. You just highlighted it briefly, but just talk a bit more what you think the expected impact from tariffs is going to be to the overall business just based on the current trade policy?

就訪問而言，您認為過程需要多長時間？然後，作為後續問題，布雷特，關於宏觀動態。您剛才簡單強調了這一點，但請再多談談，僅根據當前的貿易政策，您認為關稅對整體業務的預期影響是什麼？

And just in terms of your conversations with FDA, if you're seeing any sort of signs of potential delays, whether with PDUFA dates or starting clinical studies?

就您與 FDA 的對話而言，您是否看到任何潛在延遲的跡象，無論是 PDUFA 日期還是開始臨床研究？

Great. Kyle, donidalorsen launch?

偉大的。凱爾，多尼達洛森發射？

Yeah. What we know about the HAE market is this is largely an unsatisfied market. We see approximately 20% of patients that are moving between prophylactic treatments in the US on an annual basis. We also recently released the Harris Poll that showed that 9 out of 10 patients are interested in trying new therapies in this space.

是的。我們對 HAE 市場的了解是，這基本上是一個尚未滿足的市場。我們每年都會看到美國大約有 20% 的患者在預防性治療之間轉換。我們最近也發布了哈里斯民意調查，結果顯示，十分之九的患者有興趣嘗試該領域的新療法。

So there's definitely an opportunity here in the donidalorsen profile in terms of efficacy, tolerability and convenience is offered all in one single treatment. And when we start talking about switching patients and the dynamic of why patients want to switch, it's one of those three reasons that they're looking for something new and different.

因此，就療效、耐受性和便利性而言，donidalorsen 絕對有機會在一次治療中實現所有功能。當我們開始談論更換病人以及病人想要更換的原因時，這是他們尋求新的和不同的東西的三個原因之一。

We're going to be able to provide donidalorsen in a way that demonstrates reductions in attacks, improve tolerability, and they're only going to have to take the treatment every four or every eight weeks. So the profile is very, very strong there. In terms of switching patients, what we need to do is we need patients to advocate for themselves and we need physicians to understand what these patients are experiencing.

我們將能夠以一種能夠減少發作、提高耐受性的方式提供 donidalorsen，並且患者只需每四週或每八週接受一次治療。因此，那裡的形象非常非常強大。在轉換病人方面，我們需要做的是，我們需要病人為自己爭取權益，我們需要醫生了解這些病人正在經歷什麼。

And that's the work that we're doing right now. we're being informed by patients, and we're also beginning to communicate directly with HCPs what the need is in this market and setting ourselves up to be able to talk about how and why to switch these patients and why it's important for that to happen.

這就是我們現在正在做的工作。我們從患者那裡獲得訊息，我們也開始直接與 HCP 溝通這個市場的需求，並做好準備，能夠討論如何以及為什麼要轉換這些患者，以及為什麼這樣做很重要。

But this is a switch market. We will begin the ramp, hopefully, in Q4, and we anticipate peak sales being greater than $500 million for donidalorsen. And with the concentrated prescriber base, we can have a very targeted sales force to go out and do that, which is currently being hired and trained and going to be deployed well in advance of the PDUFA date.

但這是一個轉換市場。我們希望在第四季度開始擴大規模，並預計 donidalorsen 的峰值銷售額將超過 5 億美元。憑藉集中的處方者基礎，我們可以擁有一支非常有針對性的銷售隊伍來開展這項工作，目前正在招聘和培訓這支銷售隊伍，並將在 PDUFA 日期之前提前部署。

Thanks Kyle. To your other question, Gary, we are obviously carefully monitoring changes that the new administration is bringing both at the FDA and at the macro level on tariffs, et cetera. At the FDA, today, we're pleased to report that we've had no changes in any of the programs that we've been discussing with the FDA.

謝謝凱爾。關於您的另一個問題，加里，我們顯然正在密切關注新政府在 FDA 以及關稅等宏觀層面上帶來的變化。今天，在 FDA，我們很高興地報告，我們與 FDA 討論的任何項目均未發生任何變化。

Everything is on track. As mentioned earlier, donidalorsen's PDUFA is on track for August 21, and the discussions we're having are the exact -- the discussions we should be having at this stage of the review process. Same is true for our other discussions with the FDA INDs and so on.

一切都在按計劃進行。如前所述，Donidalorsen 的 PDUFA 將於 8 月 21 日按計劃進行，我們正在進行的討論正是我們在審查過程的這個階段應該進行的討論。我們與 FDA IND 等的其他討論也是如此。

So everything appears to be going well with the FDA at this time despite the changes that are occurring that we'll, of course, keep on monitoring that. With respect to other changes, tariffs, et cetera, that too, we have not seen any meaningful impact on our business to date. That includes costs or that we have to potentially absorb for drugs that are already launched or future drugs. With respect to commercial supply and clinical supply, that was also going very well.

因此，儘管發生了一些變化，但目前 FDA 的一切似乎都進展順利，我們當然會繼續監測。至於其他變化，如關稅等，迄今為止我們還沒有看到對我們的業務產生任何重大影響。其中包括成本，或我們必須承擔已經推出的藥物或未來藥物的成本。就商業供應和臨床供應而言，進展也非常順利。

We have sufficient supplies in place to support the TRYNGOLZA launch and the donidalorsen launch, and they're ready to go and support those launches for the near term. And for our clinical trials, we have -- we make drug here at Ionis as well as with some CMOs, but we have a lot of redundancies in the supply chain to support our clinical trial studies with respect to supply.

我們有足夠的物資來支援TRYNGOLZA的發射和donidalorsen的發射，它們已經準備好在近期為這些發射提供支援。對於我們的臨床試驗，我們在 Ionis 以及與一些 CMO 合作生產藥物，但在供應方面，我們的供應鏈中存在大量冗餘，以支持我們的臨床試驗研究。

So it's obviously a fluid situation that we're monitoring very carefully and building contingencies to manage. However, to date, we have not had any impact with respect to tariffs or with the FDA on our business.

因此，這顯然是一個不穩定的情況，我們正在非常仔細地監控並制定應急措施來應對。然而，到目前為止，關稅或 FDA 尚未對我們的業務產生任何影響。

Debjit Chattopadhyay, Guggenheim.

查托帕迪亞 (Debjit Chattopadhyay)，古根漢。

On the FCS launch, how confident is the team on the 2,000-plus FCS patient estimate and how quickly can you convert these patients to commercial therapy before you have significant price erosion with the launch in sHTG?

關於 FCS 的推出，團隊對超過 2,000 名 FCS 患者的估計有多大信心，以及在 sHTG 推出導致價格大幅下降之前，您能多快將這些患者轉化為商業治療？

[Kyle] take that, please?

[Kyle] 請拿著這個好嗎？

Yeah. Happy to take that. I think while the epidemiology varies between [1 and 13 per million], we're fairly confident in those 3,000 that genesis of your question, though, really is how quickly can we identify them. I think as Kyle outlined, we obviously had clinical trial patients that we've been able to convert on to cover product very quickly. In the prelaunch phase, we were definitely very successfully engaging with our target audience and identifying FCS patients, and that's helped drive our initial uptake in the product.

是的。很高興接受這個。我認為，雖然流行病學的發生率在每百萬 1 到 13 人之間，但我們對這 3,000 人相當有信心，但您提出的問題的真正根源在於我們能多快識別出他們。我認為正如凱爾所概述的那樣，我們顯然有臨床試驗患者，我們能夠很快地將其轉化為覆蓋產品。在預發布階段，我們確實非常成功地與目標受眾互動並確定了 FCS 患者，這有助於推動我們對產品的初步採用。

But in every month as more and more physicians become aware, we're finding more and more patients. And that's very encouraging for the outlook that we've got for FCS. I definitely think this is an underserved community with a very debilitated disease.

但隨著每個月越來越多的醫生意識到這一點，我們發現越來越多的病人。這對我們對 FCS 的前景來說非常令人鼓舞。我確實認為這是一個醫療資源匱乏的社區，患有一種非常嚴重的疾病。

And as that awareness grows, both amongst HCPs, but importantly, through a lot of the work we're doing with omnichannel, we're going to find more and more patients in the next 18 months prior to the sHTG launch. Obviously, with positive data and potential approval from the FDA.

隨著這種意識的增強，不僅在 HCP 中，更重要的是，透過我們在全通路進行的大量工作，我們將在 sHTG 推出之前的 18 個月內找到越來越多的患者。顯然，有積極的數據和 FDA 的潛在批准。

As soon as that indication expands, we'll be addressing the far larger population. The specifics of FCS become less apparent.

一旦該跡象擴大，我們將針對更大規模的人口進行工作。FCS 的具體細節變得不那麼明顯。

And price erosion?

價格下降了嗎？

Yeah. In terms of price, we priced at the FCS launch appropriately with the 3,000 patient population out there, right? And that's how we ended up at the price point that we did and the value that TRYNGOLZA brings to that patient population.

是的。就價格而言，我們為 FCS 的發布製定的定價是針對那裡的 3,000 名患者群體而言是合適的，對嗎？這就是我們最終確定的價位以及 TRYNGOLZA 為患者群體帶來的價值。

As we think about moving forward for sHTG that population is going to be exponentially higher, right, 1 million plus addressable in terms of the population. If we look at the marketplace, typically, drugs that have 1 million or so patients addressable are in the specialty pricing range of $10,000 to $20,000, for example, we've got some work to do to figure out what the pricing will be ultimately in this category based on the data that supports the program itself, which we'll know later this year.

當我們考慮推進 sHTG 時，人口數量將會呈指數級增長，就人口而言，可解決的數量將超過 100 萬。如果我們看一下市場，通常情況下，可以覆蓋 100 萬左右患者的藥物的特殊定價範圍在 10,000 美元到 20,000 美元之間，例如，我們需要做一些工作來根據支持該計劃本身的數據來確定最終的定價，我們將在今年晚些時候知道。

And we'll go back and do some more research and then obviously announce the price when we receive approval for the sHTG indication.

我們會回去做更多的研究，然後在獲得 sHTG 適應症批准後公佈價格。

Yeah. Again, we're very encouraged by the TRYNGOLZA launch to date. It is early days, of course, but we expect to be commercializing TRYNGOLZA in FCS for 1.5 years to 2 years before sHTG commercialization will kick in.

是的。再次，我們對 TRYNGOLZA 迄今為止的推出感到非常鼓舞。當然，現在還為時過早，但我們預計在 sHTG 商業化開始之前，TRYNGOLZA 將在 FCS 中商業化 1.5 到 2 年。

Jessica Fye, JPMorgan.

潔西卡費伊（Jessica Fye），摩根大通。

I just had a couple. Forgive me if I missed this, but was there any channel stocking for TRYNGOLZA captured in that 1Q number? And if so, can you quantify that? Second one, can you just elaborate a little bit more on the sources of upside to the revenue guidance and how much of that is driven by commercial product performance versus the licensing deal.

我剛剛吃了幾個。如果我錯過了這一點，請原諒我，但是在第一季中是否有任何 TRYNGOLZA 的渠道庫存？如果是的話，您能量化嗎？第二，您能否更詳細地闡述收入預期上升的來源，以及其中有多少是由商業產品表現而不是授權協議所推動的。

And lastly, you kind of touched on this, but maybe just a little more specific. Can you just talk about the manufacturing footprint for TRYNGOLZA, donidalorsen and how you think about possible exposure to tariffs?

最後，您稍微提到了這一點，但也許可以更具體一些。您能否談談 TRYNGOLZA、donidalorsen 的製造足跡以及您如何看待可能受到關稅影響？

Sure. So channel stocking, Kyle, for TRYNGOLZA?

當然。那麼 Kyle，TRYNGOLZA 的通路庫存是多少？

Yeah. The TRYNGOLZA sales is currently directly correlated to demand. There was not a large stock end of inventory. It's [adequately] being managed for the contract that we have in place with the specialty pharmacy, and it's really reflected by demand.

是的。TRYNGOLZA 的銷售目前與需求直接相關。庫存量並不大。我們與專業藥局簽訂的合約正在充分管理，而且需求確實反映了這一點。

You want to add anything to that, Beth, as well as then talk about the revenue guidance?

貝絲，你想補充些什麼嗎，然後談談收入指引？

Sure. I would just second what Kyle said that the team has done a wonderful job at managing inventories. And of course, with a rare disease drug like TRYNGOLZA, you want to make sure that you're keeping those inventory levels as low as you possibly can and driving inventory in the channel from demand, which is exactly what the team is doing.

當然。我完全同意凱爾的說法，該團隊在管理庫存方面做得非常出色。當然，對於像 TRYNGOLZA 這樣的罕見疾病藥物，您要確保將庫存水平保持在盡可能低的水平，並根據需求推動渠道庫存，這正是團隊正在做的事情。

On the revenue guidance, it's based on, obviously, a strong Q1 but the vast majority of that raise is related to the licensing transactions we did for sapablursen with (inaudible) in the OUS commercial licensing to Sobi for olezarsen.

在收入指引方面，顯然是基於強勁的第一季度業績，但絕大部分增長與我們為 sapablursen 所做的許可交易有關，其中（聽不清）在 OUS 商業許可中我們向 Sobi 授予了 olezarsen 許可。

So that -- those transactions where, as you can imagine, probabilized in our initial guidance of more than $600 million in revenue and with the now completion of those transactions, we're increasing our guidance to reflect 100% probability and flowing that through not only revenue but to our operating loss and to our cash guidance as well.

因此，正如您所想像的，這些交易在我們最初的指導中可能帶來超過 6 億美元的收入，而隨著這些交易的完成，我們將提高指導以反映 100% 的概率，並且不僅將其計入收入，還計入我們的經營虧損和現金指導。

Yeah. And regarding manufacturing, Jess, we have number of sources for supplying our drugs for both clinical trials as well as for the commercial launches, including South Korea, Europe and the US. As I mentioned earlier to one of the other questions, we're well stocked in supply already to support the TRYNGOLZA launches as well as the anticipated launch for donidalorsen. So (inaudible) that's in place. we're continuing to monitor any potential impact.

是的。關於製造，傑西，我們有多個來源為臨床試驗和商業發布提供藥物，包括韓國、歐洲和美國。正如我之前在另一個問題中提到的那樣，我們已經有足夠的庫存來支持 TRYNGOLZA 的推出以及 donidalorsen 的預期推出。所以（聽不清楚）一切就緒了。我們將繼續監測任何潛在的影響。

But right now, there has not been any. And that includes on tariffs as well. Really, we haven't -- we're watching it very carefully, but we are not experiencing any meaningful impacts. And our guidance stays the same. We just improved our guidance, and that's also factoring in any potential impact of tariffs.

但目前還沒有任何進展。這也包括關稅。確實，我們沒有——我們正在非常仔細地觀察，但我們沒有感受到任何有意義的影響。我們的指導保持不變。我們剛剛改進了我們的指導，這也考慮了關稅的任何潛在影響。

Jason Gerberry, Bank of America.

美國銀行的 Jason Gerberry。

This is Chi on for Jason. Maybe just on a follow-up on TRYNGOLZA, can you unpack a little bit between the conversion that you see from your expanded excess and newly identified patients that were previously not enrolled in any of the prior clinical trials and understood that this is a market that requires some market building.

這是 Jason 的 Chi on。也許只是在對 TRYNGOLZA 進行後續跟進時，您能否稍微解釋一下從擴大的超額治療和之前未參加任何臨床試驗的新確定患者中看到的轉化情況，並了解這是一個需要進行一些市場建設的市場。

Are you seeing a steady case [and enough] new starts? And just a quick follow-up on your Angelman, you guys have it on track for 2Q Phase III start. Are there any outstanding needed to execute before the Phase III start?

您是否看到了穩定的案例[和足夠的]新開工？關於 Angelman 的快速跟進，你們已經按計劃開始了第二季的第三階段。第三階段開始前還有什麼未完成的事情需要執行嗎？

Okay. Thanks, Chi. I'll take the Angelman's question as it's a brief answer, and then Kyle will take the question with respect to conversion of EAP, OLE patients and so I'll start. So the Angelman Phase III study is on track for a time on-time initiation. As a reminder, we had excellent discussions and completion of conversations with the FDA last year.

好的。謝謝，Chi。我將簡短地回答 Angelman 的問題，然後 Kyle 將回答有關 EAP、OLE 患者轉換的問題，所以我將開始。因此，Angelman 第三階段研究將按時啟動。提醒一下，去年我們與 FDA 進行了非常愉快的討論並完成了對話。

We aligned on our Phase III trial design. We think we have the right trial design. We have the right drug, the right chemical platform to get the study started in the first half of this year, which means it will get started in this quarter. So very soon. We're well on our way.

我們對第三階段試驗設計進行了調整。我們認為我們的試驗設計是正確的。我們擁有合適的藥物和合適的化學平台，可以在今年上半年開始研究，這意味著它將在本季開始。所以很快。我們進展順利。

And what we've also said is that our expectation is to complete enrollment in 2026. So we expect to enroll fairly quickly.

我們也說過，我們預計將在 2026 年完成招生。因此，我們期望能夠很快完成招生。

Yeah. Thanks, Brett. In terms of the TRYNGOLZA launch, very strong patient uptake in Q1 as we were referencing and it's demand driven. The conversion of EAP and OLE patients was obviously a main focus here in moving those patients on to commercial drug. As we mentioned, the majority of those patients converted over which was exactly what we expected to have happen.

是的。謝謝，布雷特。就 TRYNGOLZA 的推出而言，正如我們所提到的，第一季患者的接受度非常高，而且這是由需求驅動的。顯然，EAP 和 OLE 患者的轉化是這裡的主要焦點，以便讓這些患者轉而使用商業藥物。正如我們所提到的，大多數患者都轉變了，這正是我們預期會發生的情況。

The second area of patient population we talked about are those that were waiting for treatment, right? This was kind of the pent-up patients that have been treated for years. And unfortunately, didn't have a therapeutic option available. Those have also -- many of them have started on treatment as well. And then the identification of new patients is really what we're going to be focused on moving forward.

我們討論的第二個患者群體是那些等待治療的患者，對嗎？這是一種被壓抑了多年的病人。不幸的是，沒有可用的治療選擇。他們中的許多人也已經開始接受治療。那麼，識別新患者才是我們下一步真正要關注的重點。

That's the main focus of our work. But in Q1, we had patients from all three of those buckets, but the predominant patient populations were coming from the EAP OLE and the pent-up demand patients that had already been identified.

這是我們工作的重點。但在第一季度，我們有來自所有這三個群體的患者，但主要患者群體來自 EAP OLE 和已經確定的被壓抑的需求患者。

So our focus really is getting new patients diagnosed, new patients treated and working them through the payer channel, which we're doing very effectively right now. Jonathan, maybe you can add a little bit?

因此，我們的重點實際上是讓新患者得到診斷、接受治療並透過付款管道為他們提供服務，目前我們做得非常有效。喬納森，也許你可以補充一點？

Yeah. Perhaps a little bit of color. We're definitely having success engaging with HCPs to actually find both patients that were identified prior to launch and converting them to cover product, number one. But also number two is the awareness gets out there finding new patients and becoming aware of patients that we weren't aware of at launch. So that's super encouraging in the first quarter of our launch.

是的。也許有一點點顏色。首先，我們確實成功地與 HCP 合作，找到了在產品推出之前就已確定的患者，並將其轉化為覆蓋產品。但第二點是，人們的意識開始傳播，找到新的患者，並意識到我們在推出時不知道的患者。因此，這對於我們推出產品的第一季來說非常令人鼓舞。

Yaron Werber, TD Cowen.

Yaron Werber，TD Cowen。

Maybe just a couple of questions from me. This one's on WAINUA, can you give us a little bit of a sense, the Part D redesign, now that it's in effect and it's capping patients to $2,000 out of pocket. How does that going to -- do you think sort of impact uptake under Part D?

我可能只想問幾個問題。這是關於 WAINUA 的問題，您能否給我們稍微介紹一下 D 部分的重新設計，現在它已經生效，並且將患者的自付金額限制在 2,000 美元。您認為這會對 D 部分產生怎樣的影響？

And then on TRYNGOLZA, do you have any sense -- I mean, the $6 million is really a great number. That sounds like it's a good baseline from here onwards. From here on, do you already have patients who you think are going to come on board pretty quickly that are diagnosed? Or as we kind of think ahead about growth in patient identification, maybe give us some qualitative view on how fast that can be?

然後關於 TRYNGOLZA，你有什麼感覺嗎——我的意思是，600 萬美元確實是一個很大的數字。聽起來從現在開始這是一個很好的基礎。從現在開始，您是否已經有一些您認為很快就會確診的患者？或者當我們提前思考患者識別的增長時，也許可以給我們一些關於其速度有多快的定性看法？

Yeah. Let me touch on WAINUA first. AstraZeneca continues to see very strong US demand for WAINUA. The redesign of Medicare Part D impacted some of the Q1 revenue, but there are a lot of positives that you just emphasized in terms of the out-of-pocket change that's happening.

是的。首先讓我談談 WAINUA。阿斯特捷利康繼續看到美國對 WAINUA 的需求非常強勁。醫療保險 D 部分的重新設計影響了第一季的部分收入，但就正在發生的自付費用變化而言，有許多積極因素。

First of all, I think you're going to see an increased volume from new patient starts because of this. We're seeing cardiologists and neurologists prescribe WAINUA and what they're telling us is that it's going to, number one, increase the number of patients they can treat because of affordability; and number two, they feel like it's going to increase the compliance rates for those patients as well because they're going to be able to afford their medication moving forward.

首先，我認為由於這個原因，你會看到新病人的數量增加。我們看到心臟科醫生和神經病學家開出 WAINUA 處方，他們告訴我們，首先，由於價格便宜，這將增加他們可以治療的患者數量；第二，他們覺得這也會提高這些患者的依從率，因為他們將能夠負擔得起未來的藥物費用。

So I think that has a significant advantage and opportunity for patients overall, and we knew us specifically to be able to demonstrate revenue growth quarter-over-quarter as we move forward in 2025. I think we're very optimistic about that.

因此，我認為這對患者整體來說具有顯著的優勢和機會，我們特別清楚，隨著 2025 年的到來，我們能夠實現收入逐季度增長。我認為我們對此非常樂觀。

In terms of the TRYNGOLZA question, again, greater than $6 million in the first quarter. We just talked about the three patient buckets that, that came from. But we do have additional patients that are being identified currently that are potentially going to go on to TRYNGOLZA. This takes a lot of work, right, 3,000 potential patients in the US.

關於 TRYNGOLZA 的問題，第一季的金額再次超過 600 萬美元。我們剛剛討論了這三個病人桶的由來。但我們目前正在確定其他可能繼續使用 TRYNGOLZA 的患者。這需要做大量的工作，對吧，美國有 3,000 名潛在患者。

We're doing a lot of work, not only with our customer-facing teams but also with our omnichannel efforts and the education that we're doing with our medical affairs groups at congresses in different meetings. So those are the things that we're doing to get the word out about the new treatment option available, how to diagnose FCS patients.

我們正在進行大量工作，不僅與我們的客戶服務團隊合作，還與我們的全通路努力以及我們在不同會議的大會上與醫療事務小組一起進行的教育合作。所以，我們正在做的事情就是宣傳可用的新治療方案以及如何診斷 FCS 患者。

But it's going to take some time and some work, but we are encouraged by the number of patients that are coming forward, and we'll work them on treatment this quarter and moving forward throughout the year.

但這需要一些時間和工作，但我們對前來就診的患者數量感到鼓舞，我們將在本季度以及全年為他們提供治療。

Thanks, Kyle. Remember Yaron that WAINUA is now launched outside the US and Europe as well. So we're expecting continued revenue growth. And based on strong patient demand, not only in the US but also in other geographies as well for -- in 2025 and going forward.

謝謝，凱爾。請記住，Yaron，WAINUA 現在也已在美國和歐洲以外推出。因此我們預計收入將持續成長。並且基於強勁的患者需求，不僅在美國，在其他地區也是如此——2025 年及以後。

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

This is [Cassie] on for Luca. And this question will be on TTR cardiomyopathy. We appreciate the early days as cardio transform has yet to read out. But were you surprised by an item not lowering pricing when they got label expansion for cardiomyopathy. And are you planning to follow the same playbook?

這是 [Cassie] 為 Luca 表演的。這個問題是關於TTR心肌病變的。我們很珍惜早期的時光，因為心臟轉變尚未讀出。但是，當該產品的標籤擴展到心肌病變時，您是否對該產品沒有降低價格感到驚訝？您打算遵循同樣的策略嗎？

Or is there a scenario where you compete with them by lowering the price? Any color there would be much appreciated.

或者是否有透過降低價格與他們競爭的情況？無論什麼顏色，我都會非常感激。

Yeah. In terms of (inaudible) strategy, I wasn't too surprised by that. I believe they've got a balance of patients that are hereditary polyneuropathy patients. And I think they're trying to maintain a price in order to manage their revenues now and moving forward. And it's up to them kind of how that market evolves, I think, and what they're able to get coverage on for cardiomyopathy, I think that's yet to be determined.

是的。就（聽不清楚）策略而言，我對此並不太感到驚訝。我相信他們擁有均衡的遺傳性多發性神經病變患者群體。我認為他們試圖維持價格是為了管理現在和未來的收入。我認為，市場如何發展取決於他們，而他們能夠獲得哪些針對心肌病變的保障，我認為這還有待確定。

In terms of the strategy for WAINUA, that's ultimately AstraZeneca's decision in terms of how they navigate that. I'm sure there are a lot of learnings in this market. And as the market continues to evolve, we'll take a look in terms of reimbursement and coverage and physician and patient feedback and figure out what the right price point is for WAINUA based on the benefit and value that it delivers.

就 WAINUA 的策略而言，這最終取決於阿斯特捷利康如何應對。我確信這個市場有很多值得學習的地方。隨著市場的不斷發展，我們將從報銷和保險範圍以及醫生和患者的反饋角度進行研究，並根據 WAINUA 帶來的益處和價值確定其合適的價格點。

David Lebowitz, Citi.

花旗銀行的 David Lebowitz。

When you look at the core trials and the baseline AP data, I'm curious as to how the analysis in the trials will actually be carried out. Is it going to be strictly based on baseline for the overall population relative to reductions, whether it be additional studies or analysis on patients that actually had baseline AP events to reduce but over the smaller denominator.

當您查看核心試驗和基線 AP 數據時，我很好奇試驗中的分析實際上是如何進行的。它是否會嚴格地基於總體人群的基​​線來減少，無論是額外的研究還是對實際上有基線 AP 事件減少但分母較小的患者的分析。

I'm curious to what's prespecified and what could possibly be accepted by the FDA for labeling consideration?

我很好奇預先規定了什麼以及 FDA 可能接受什麼來進行標籤考慮？

Eugene?

尤金？

Yeah. Thanks for the question. So certainly, the analysis of AP events, the prespecified analysis, we'll look at all events happening during the 12 months exposure in a trial and obviously comparing the active arm versus placebo.

是的。謝謝你的提問。因此，當然，AP 事件的分析，預先指定的分析，我們將查看試驗中 12 個月暴露期間發生的所有事件，並顯然將活性組與安慰劑進行比較。

We will look at population that had a baseline or at baseline reported historical events, but that's a much smaller subgroup. So I guess, the answer is that the overall analysis will look at all events happening during the trial comparing the olezarsen patients.

我們將研究具有基線或在基線報告歷史事件的人口，但這是一個小得多的子群體。所以我猜，答案是整體分析將考慮試驗期間發生的所有事件，並與 olezarsen 患者進行比較。

And I believe, if I recall, Eugene, we'll also be looking at AP in patients above and below [80] in the analysis as well.

而且我記得，尤金，我們也將在分析中關注 [80] 以上和以下患者的 AP。

Right. Yeah.

正確的。是的。

So we'll be carving up the AP data based on history of AP and without and so on. As far as the labeling discussions and getting AP in the label, I mean that's a data-driven outcome that we'll have to talk about with the FDA.

因此，我們將根據 AP 的歷史記錄和非 AP 歷史記錄等來劃分 AP 資料。至於標籤討論和在標籤中獲得 AP，我的意思是這是一個數據驅動的結果，我們必須與 FDA 討論。

But again, as I emphasized earlier, we believe that this is a very substantial unmet need and a very sizable market opportunity for Ionis based on triglyceride lowering. But these patients are suffering from acute pancreatitis, and we have a substantial number of patients with a history of AP enrolled in our study. So we think we have the right trial design that if we can see it, we have a potential to see it.

但正如我之前強調的那樣，我們認為，對於 Ionis 來說，這是一個非常大的未滿足需求，也是一個基於降低三酸甘油酯的非常大的市場機會。但這些患者患有急性胰臟炎，我們的研究中招募了相當數量的有 AP 病史的患者。因此我們認為我們有正確的試驗設計，如果我們能夠看到它，我們就有可能看到它。

Yeah, I'll just add, we have AP in the label now for TRYNGOLZA, which is in the FCS population but that's very beneficial. And then the read-through in terms of the connection between triglycerides and lowering of acute pancreatitis, we know from the recent KOL panel that we just had that's well understood, as Brett and Eugene just described.

是的，我只想補充一點，我們現在在 TRYNGOLZA 的標籤上標註了 AP，它適用於 FCS 人群，但這非常有益。然後，從最近的 KOL 小組討論中我們可以了解到，關於三酸甘油酯和降低急性胰臟炎之間的聯繫，這一點已經得到很好的理解，正如 Brett 和 Eugene 剛才所描述的那樣。

Mani Foroohar, Leerink.

Mani Foroohar，Leerink。

This is [Lily Young] on for Mani. First question, digging a little more into the patients and the scripts for TRYNGOLZA. So you mentioned that the majority of patients were from the open-label extension as well as the EAP program.

我是 [Lily Young]，為 Mani 表演。第一個問題，請進一步了解患者和 TRYNGOLZA 的處方。您提到大多數患者來自開放標籤擴展以及 EAP 計劃。

But in terms of the remaining patients with the newly diagnosed and previously diagnosed patients, could you give a little more color on the distribution there between newly diagnosed and previously diagnosed as well as your expectations on how it will evolve quarter-to-quarter?

但是，就剩餘的新診斷患者和先前診斷患者而言，您能否詳細說明新診斷患者和先前診斷患者的分佈情況，以及您對季度變化的預期？

I don't have too much additional color to add. We're not going to disclose the exact patient numbers or the percentages at this point in time. But we are encouraged the patient finding work that we've done, the identification of new patients so far, and we believe we'll be able to add incremental patients quarter-over-quarter as we move forward throughout the year.

我沒有太多額外的顏色可以添加。目前我們不會透露確切的患者人數或百分比。但我們對我們所做的患者尋找工作以及迄今為止新患者的確定感到鼓舞，我們相信，隨著全年的推進，我們將能夠逐季度增加患者數量。

The launch is going very well, as we talked about, strong patient uptake and strong demand and good payer coverage. So I think we're in a great place.

正如我們所說的，發布會進展非常順利，患者接受度高，需求強勁，付款人覆蓋面良好。所以我認為我們處於一個很好的位置。

Yeah. And just to clarify, I don't think we said that the majority of patients are from the open-label extension. What we said was that we have that we have, obviously, patients in the open-label extension study from the Phase III trial, which had 66 patients in balance. And in the US -- and then, of course, we're focused on the US segment of that and the majority of those patients have converted over to commercial, but that doesn't necessarily represent the overall patient population that is on TRYNGOLZA commercially today.

是的。需要澄清的是，我認為我們並沒有說大多數患者來自開放標籤擴展。我們所說的是，我們顯然有來自 III 期試驗的開放標籤擴展研究中的患者，該研究共有 66 名患者。而在美國——當然，我們專注於美國市場，其中大多數患者已經轉向商業治療，但這並不一定代表目前使用 TRYNGOLZA 商業治療的整體患者群體。

Going forward, it's going to be newly identified patients that's what we've emphasized because those patients that were already diagnosed as well as the clinical trial patients was -- we did a good job. We have -- we are doing a good job converting our patients. But going forward, it's all about patient identification. So we have a lot of work to do.

展望未來，我們將重點放在新確診的患者，因為那些已經確診的患者以及臨床試驗患者——我們做得很好。我們在轉變患者方面做得很好。但展望未來，一切都與患者識別有關。所以我們還有很多工作要做。

Yeah. One thing I'll add is we're definitely finding new patients just to be transparent around that. I mean it's very difficult to seek a diagnosis for a condition where it doesn't ultimately change the treatment. So as awareness builds, clinical experience builds, there's far more motivation to see these patients, and they're definitely out there, they definitely exist.

是的。我要補充一點，我們一定會找新患者，只是為了保持透明。我的意思是，對於一種最終不會改變治療方法的疾病來說，尋求診斷是非常困難的。因此，隨著意識的增強和臨床經驗的積累，人們會更有動力去探望這些病人，而且他們肯定就在那裡，肯定存在。

I think we have time for one more question.

我想我們還有時間再回答一個問題。

Mike Ulz, Morgan Stanley.

摩根士丹利的麥克烏爾茲。

Maybe just a follow-up on olezarsen and sHTG. It looks like you narrowed the timing of that data slightly for the CORE and CORE2 studies, the 3Q from the second half previously. Just curious. Any reason behind that? And then secondly, maybe just clarify, will that initial update from those studies include the 12-month AP data?

也許只是對 olezarsen 和 sHTG 的後續。看起來您稍微縮小了 CORE 和 CORE2 研究的資料時間範圍，也就是之前下半年的第三季。只是好奇。這背後有什麼原因嗎？其次，也許需要澄清的是，這些研究的初步更新是否包括 12 個月的 AP 數據？

Thanks, Mike. No, nothing really behind it, just as we get closer to the data readouts, and we get through everything we need to get through all the blocking and tackling to read out the top line data, we provide more clarity. So yes, we are -- we have provided more precision. Q2 ESSENCE data, Q3 CORE and CORE2 top line data.

謝謝，麥克。不，這背後沒有什麼特別的，只是當我們越來越接近數據讀數時，我們透過所有需要的阻礙和解決來讀出頂線數據，我們提供更清晰的資訊。是的，我們——我們提供了更高的精度。Q2 ESSENCE 資料、Q3 CORE 和 CORE2 頂線資料。

With respect to AP readouts, we don't expect AP in the ESSENCE study, of course, just to confirm that. These are mildly elevated patients with triglyceride, they don't have them in many AP events. This is a safety study to support these exposure database that's necessary for a highly prevalent disease in the eyes of the FDA.

關於 AP 讀數，我們當然不期望 ESSENCE 研究中會出現 AP，只是為了確認這一點。這些患者的三酸甘油酯輕度升高，在許多 AP 事件中他們都沒有出現這種情況。這是一項安全性研究，旨在支持 FDA 認為對於一種高度流行的疾病所必需的暴露資料庫。

So really, we're focused on triglyceride lowering in that study and safety. And I just also want to emphasize that the percent reductions in triglycerides that we expect in essence is not a reflection of what we would expect in CORE, sHTG and that's because these patients are only mildly elevated. So we get good -- we're expecting good substantial reductions in TGs, but not to the magnitude of what we would expect in CORE.

因此，我們實際上專注於降低該研究中的三酸甘油酯和安全性。我還想強調的是，我們預期的三酸甘油酯百分比降低本質上並不反映我們在 CORE、sHTG 中所預期的情況，這是因為這些患者的三酸甘油酯僅輕度升高。因此，我們得到了好消息——我們預計 TG 將大幅減少，但不會達到我們預期的 CORE 的幅度。

In the top line data for CORE and CORE2. We're still working that out, whether we will have the AP data in time for that top line data, but we'll be focused on there principally triglyceride reductions and safety for CORE and CORE2. And if we have the AP data at that time, we will certainly share it in our top line announcement later this year.

頂行資料為 CORE 和 CORE2。我們仍在研究是否能及時獲得 AP 數據以獲得頂線數據，但我們將主要關注 CORE 和 CORE2 的三酸甘油酯降低和安全性。如果我們當時有美聯社的數據，我們肯定會在今年稍後的頭條公告中分享。

So thanks for the question, Mike. Thanks, everybody, for participating in all the great questions. I'd like to really emphasize that looking forward, we're excited about building on our momentum throughout the year and sharing our additional achievements with all of you along the way. So thanks again for participating, and we'll talk soon. Have a great day.

謝謝你的提問，麥克。感謝大家參與回答這些精彩的問題。我想特別強調的是，展望未來，我們很高興能夠在全年保持這一勢頭，並與大家分享我們所取得的更多成就。再次感謝您的參與，我們很快就會再談。祝你有美好的一天。

Goodbye.

再見。