Ionis Pharmaceuticals Inc (IONS) 2025 Q2 法說會逐字稿

Good morning, and welcome to Ionis second-quarter 2025 financial results conference call. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead up the call. Please go ahead.

早安，歡迎參加 Ionis 2025 年第二季財務業績電話會議。提醒一下，本次通話正在錄音。現在，我想將電話轉給投資者關係高級副總裁 Wade Walke 來主持電話會議。請繼續。

Thanks, Steve. 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 we will be discussing today, including a reconciliation of GAAP to non-GAAP financials. 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.

謝謝，史蒂夫。在我們開始之前，我鼓勵大家前往 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 GAAP 與非 GAAP 財務報表的對帳。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。

With me this morning are Brett Monia, Chief Executive Officer; Kyle Jenne, Chief Global Product Strategy Officer; Richard Geary, Chief Development Officer; and Beth Hougen, Chief Financial Officer; Eugene Schneider, our Chief Clinical Development Officer; and Eric Swayze, Executive Vice President of Research, will also join us for the Q&A portion of the call.

今天早上與我一起參加會議的還有執行長 Brett Monia、首席全球產品策略長 Kyle Jenne、首席開發長 Richard Geary 和財務長 Beth Hougen、我們的首席臨床開發長 Eugene Schneider 和研究執行副總裁 Eric Swayze，他們也將參加電話會議的問答環節。

I would like to draw your attention to Slide 3, which contains 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 consult 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。我鼓勵您查閱我們向美國證券交易委員會提交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 thank you for joining us on today's call. We have continued to build strong momentum across our business, highlighted by the excellent early commercial performance of our first independent launch Tryngolza, the first and only FDA-approved treatment for familial chyloymicronemia syndrome.

謝謝，韋德。大家早安，感謝你們參加今天的電話會議。我們的業務持續保持強勁發展勢頭，其中最突出的是我們的首款獨立上市藥物 Tryngolza，這是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徵的藥物，其早期商業表現十分出色。

Tryngolza exceeded revenue expectations during the second quarter on the market, underscoring its strong therapeutic profile, our well-executed commercial strategy as well as the significant unmet need Tryngolza is addressing. The revenue and commercial performance of Tryngolza to date, along with our confidence in Tryngolza's continued commercial success supports the increase in our financial guidance for 2025 which Beth will cover in more detail shortly.

Tryngolza 在第二季的市場收入超出了預期，突顯了其強大的治療特性、我們執行良好的商業策略以及 Tryngolza 正在解決的重大未滿足需求。Tryngolza 迄今為止的收入和商業表現，以及我們對 Tryngolza 持續商業成功的信心，支持我們提高 2025 年的財務指導，Beth 很快就會對此進行更詳細的介紹。

We're also pleased that Tryngolza recently received deposits of CHMP opinion paving a way to bring this transformative therapy to patients. Shifting gears, we anticipate Donidalorsen for erector angioedema or HAE will be our second independent launch by receiving FDA approval next month. Based on the progress of the review, we believe the approval and subsequent launch remains on track.

我們也很高興 Tryngolza 最近收到了 CHMP 的意見，為將這種變革性療法帶給患者鋪平了道路。換個角度來看，我們預期 Donidalorsen 用於治療豎脊肌血管性水腫或 HAE，並將於下個月獲得 FDA 批准，成為我們第二個獨立推出的產品。根據審查進展，我們相信批准和後續啟動工作仍在按計劃進行。

Donidalorsen has the potential to become a preferred prophylactic therapy for many HAE patients with strong efficacy and on safety and tolerability in the pivotal studies, a patient-friendly autoinjector and a convenient dosing schedule of monthly or every other month self-administration. We're well positioned to launch Donidalorsen filing approval.

Donidalorsen 有可能成為許多 HAE 患者的首選預防療法，因為其在關鍵研究中具有強大的療效和安全性和耐受性，是一種患者友好的自動注射器，並且具有每月或每隔一個月自行給藥的便捷給藥時間表。我們已準備好啟動 Donidalorsen 備案審批。

Additionally, our Phase III pipeline continues to advance well, with data expected later this year from two wholly owned Ionis programs. If positive, these results would support the continued steady cadence of independent launches next year, bringing important new treatments to patients. These include a second indication for Olezarsen in severe hypertriglyceridemia or sHTG, a condition of a large patient population and significant unmet need and Zilganersen for Alexander's disease is severe where [mupidystrophy] with no approved disease-modifying therapies. Together, these programs in addition to two holes in STS and Donidalorsen and HAE represent major breakthroughs for patients and represent a multibillion-dollar revenue potential for Ionis.

此外，我們的第三階段管道繼續順利推進，預計今年稍後將公佈兩個全資 Ionis 項目的數據。如果結果呈陽性，這些結果將支持明年獨立產品上市的持續穩定節奏，為患者帶來重要的新治療方法。其中包括 Olezarsen 的第二種適應症，用於治療嚴重高三酸甘油酯血症或 sHTG，這是一種患者群體龐大且存在巨大未滿足需求的疾病，而 Zilganersen 則用於治療嚴重的亞歷山大病，這種疾病 [mupidystrophy] 目前尚無批准的疾病改良療法。總而言之，除了 STS 和 Donidalorsen 的兩個漏洞以及 HAE 之外，這些項目還為患者帶來了重大突破，並為 Ionis 帶來了數十億美元的收入潛力。

Additionally, by the end of 2027, we anticipate four potential launches from our rich late-stage partner pipeline, targeting serious life-threatening conditions for both rare and highly prevalent diseases. These will further expand the impact and reach of Ionis discovered medicines and have the potential to meaningfully increase total revenue. With our strong momentum across the business, including Travolta and our upcoming independent and partner launches, Ionis is well positioned to bring transformative medicines to patients for years to come and, in turn, achieve sustained revenue growth.

此外，到 2027 年底，我們預計將從豐富的後期合作夥伴管道中推出四種潛在的產品，針對罕見疾病和高度流行的嚴重危及生命的疾病。這些將進一步擴大 Ionis 發現的藥物的影響力和覆蓋範圍，並有可能大幅增加總收入。憑藉我們整個業務的強勁發展勢頭，包括 Travolta 以及我們即將推出的獨立和合作夥伴產品，Ionis 已做好準備，在未來幾年為患者提供變革性藥物，進而實現持續的收入成長。

Thank you, Brett. With our first independent launch now well underway and a second launch right around the corner, our commercial team is executing on our strategy to capitalize on these significant growth opportunities. Tryngolza reported $19 million in net product sales for the second quarter, reflecting a threefold increase in revenues quarter-over-quarter.

謝謝你，布雷特。我們的首次獨立發布現已順利進行，第二次發布也即將到來，我們的商業團隊正在執行我們的策略，以利用這些重大的成長機會。Tryngolza 報告稱，第二季淨產品銷售額為 1,900 萬美元，環比收入增長了三倍。

In the second quarter, Tryngolza continued to build launch momentum. This was a result of several factors, including effective patient identification efforts, a strong product profile, favorable payer dynamics and overwhelmingly positive HCP reported experience. Our patient identification initiatives are paying off. The breadth and depth of unique physicians prescribing Tryngolza continues to grow and meet prescribe the therapy to two or more patients underscoring the positive experience of both clinicians and patients.

第二季度，Tryngolza 繼續增強發布勢頭。這是多種因素共同作用的結果，包括有效的患者識別工作、強大的產品形象、有利的付款人動態以及 HCP 報告的極其積極的體驗。我們的患者識別措施正在取得成效。開立 Tryngolza 處方的獨特醫生的廣度和深度不斷增長，並且會為兩名或兩名以上的患者開立該療法，強調了臨床醫生和患者的積極體驗。

This demand also expands a broad mix of specialties with cardiologists and endocrinologists representing roughly 50% and 30% of prescribers, respectively, and lipidologists and internal medicine providers making up the balance. Overall, physician feedback remains highly favorable with significant benefits have remained favorable.

這種需求也擴大了專科醫生的種類，其中心臟病專家和內分泌學家分別佔處方者的約 50% 和 30%，脂質學家和內科醫生則佔剩餘部分。總體而言，醫生的回饋仍然非常好，並且顯著的益處仍然令人欣喜。

To date, the coverage mix for patients entering goals is approximately 60% commercial and 40% government. Importantly, patients whether clinically diagnosed or genetically confirmed have gained access. Patients have obtained coverage through a growing number of formal policies or via the medical exception process. This highlights both the urgent unmet need and payers' willingness to support access even before formal policies are in place. Additionally, over 90% of patients have paid $0 out-of-pocket since launch and time lines for patients obtaining the medicine are consistently beating our aggressive internal benchmarks.

到目前為止，進入目標的患者的保險範圍大約為 60% 來自商業，40% 來自政府。重要的是，無論是臨床診斷還是基因確診的患者都可以獲得治療。患者透過越來越多的正式保險或醫療例外程序獲得了保險。這凸顯了迫切的未滿足需求以及付款人在正式政策出台之前支持獲取醫療服務的意願。此外，自推出以來，超過 90% 的患者自付費用為 0 美元，患者獲得藥物的時間一直超過我們積極的內部基準。

Nearly all patients have opted into our Ionis Every Step Support program, a testament to the value the program is providing. We established the Ionis Every Step Support program to ensure a positive patient experience by providing disease and nutrition education, auto injector training and reimbursement support among other offerings.

幾乎所有患者都選擇加入我們的 Ionis Every Step Support 計劃，證明了該計劃所提供的價值。我們建立了 Ionis Every Step Support 計劃，透過提供疾病和營養教育、自動注射器培訓和報銷支援等服務來確保患者獲得積極的體驗。

For health care providers, the program provides helpful support from insurance authorizations and coverage coordination to reauthorizations and refills. Proud of Tryngolza's early momentum in to focus on our patient finding efforts and HCP education. Our customer-facing team has reached over 3,000 physicians and over 30,000 HCPs have been targeted through our omnichannel capabilities, both intended to further increase awareness of FCS, expand patient identification and educate on the potential benefits of Tryngolza treatment.

對於醫療保健提供者，該計劃提供了從保險授權和覆蓋範圍協調到重新授權和補充的有益支援。為 Tryngolza 早期專注於患者尋找工作和 HCP 教育的勢頭感到自豪。我們的全通路客戶服務團隊已涵蓋超過 3,000 名醫生，並瞄準超過 30,000 名 HCP，旨在進一步提高人們對 FCS 的認識、擴大患者識別範圍並普及 Tryngolza 治療的潛在益處。

Backed by an experienced and high-performing team, we are well positioned to continue to take advantage of our first mover position to bring Tryngolza to patients in need and keep them on treatment. Just in FCS, we are advancing toward a potential blockbuster opportunity in severe hypertriglyceridemia with Olezarsen. SHTG represents a large patient population, many of whom struggle to manage their triglyceride levels with current treatments. In the US alone, more than 1 million people have high-risk sHTG and includes individuals with triglyceride levels above 880 or above 500 with a history of acute pancreatitis.

在經驗豐富、績效優異的團隊的支持下，我們有能力繼續利用我們的先發優勢，將 Tryngolza 帶給有需要的患者並讓他們繼續接受治療。僅在 FCS，我們就正利用 Olezarsen 朝向嚴重高三酸甘油酯血症的潛在重磅藥物機會邁進。SHTG 代表龐大的患者群體，其中許多人難以透過目前的治療方法控制三酸甘油酯水平。光是在美國，就有超過 100 萬人患有高風險 sHTG，其中包括三酸甘油酯高於 880 或高於 500 且有急性胰臟炎病史的個體。

With a significant first-mover advantage, we believe Olezarsen is well positioned to address the unmet needs of patients with severe hypertriglyceridemia. Our commercial team is making excellent progress as we prepare for a potential launch next year.

憑藉著顯著的先發優勢，我們相信 Olezarsen 能夠很好地滿足嚴重高三酸甘油酯血症患者未滿足的需求。我們的商業團隊正在為明年的可能上市做準備，並取得了良好的進展。

Donidalorsen, our second independent launch has the potential to transform the treatment paradigm for individuals with HAE as the first and only RNA-targeted prophylactic medicine. More than 20,000 people in the US and in Europe are estimated to have HAE with approximately 7,000 people in the US alone. Most patients are currently on prophylactic treatment.

Donidalorsen 是我們獨立推出的第二款產品，作為第一種也是唯一一種針對 RNA 的預防藥物，它有可能改變 HAE 患者的治療模式。據估計，美國和歐洲有超過 20,000 人患有 HAE，光是美國就有約 7,000 人。大多數患者目前正在接受預防性治療。

However, many HAE patients remain unsatisfied with up to 20% of patients switching therapies each year in search of a more effective and convenient option, highlighting a need for new treatments with enhanced profiles. We believe Donidalorsen is uniquely positioned to meet this demand.

然而，許多 HAE 患者仍然不滿意，每年有多達 20% 的患者更換治療方法以尋求更有效、更方便的選擇，這凸顯了對具有增強特性的新治療方法的需求。我們相信 Donidalorsen 具有獨特的優勢來滿足這一需求。

The Donidalorsen clinical data have shown durable efficacy and favorable safety and tolerability profile with a patient-friendly monthly or every other month self-administration with an auto-injector. Importantly, as we prepare to bring Donidalorsen to market, we are applying the same disciplined and innovative approach that has made the Tryngolza launch a success.

Donidalorsen 臨床數據顯示其具有持久的療效和良好的安全性和耐受性，患者可以每月或每隔一個月使用自動注射器自行注射。重要的是，當我們準備將 Donidalorsen 推向市場時，我們採用了與 Tryngolza 成功上市相同的嚴謹和創新的方法。

We have deployed our field team who are educating and anticipated approval of Donidalorsen and are energized to successfully execute the launch. Meanwhile, our market access team is actively engaging with payers and our -- continues to lay the essential groundwork to ensure a smooth and successful launch.

我們已經部署了現場團隊，他們正在對 Donidalorsen 進行培訓並期待獲得批准，並有動力成功執行發射任務。同時，我們的市場准入團隊正在積極與付款人接觸，並繼續奠定必要的基礎，以確保順利和成功地推出產品。

Our experience and scalable commercial organization is already delivering excellent results, so the early success seen with the launch of Tryngolza and FCS. As we build on this momentum, we remain focused on maximizing Tryngolza's full potential while preparing to successfully execute teaches by the end of next year, including Donidalorsen in the coming weeks, enabling Ionis to reach more people in need with our medicines.

我們的經驗和可擴展的商業組織已經取得了優異的成果，因此 Tryngolza 和 FCS 的推出也取得了早期的成功。在這一勢頭的基礎上，我們將繼續致力於最大限度地發揮 Tryngolza 的全部潛力，同時準備在明年年底前成功實施教學，包括未來幾週的 Donidalorsen，使 Ionis 能夠將我們的藥品送到更多有需要的人手中。

With that, I'll now turn it over to Richard.

現在，我將把發言權交給理查。

Thank you, Kyle. We are making excellent progress across our pipeline, positioning Ionis to deliver on our mission of bringing transformational medicines for years to come. Let me start with the recent updates from our wholly owned pipeline. As a reminder, Donidalorsen is currently under regulatory review in both the US and EU, with submission supported by its robust clinical data.

謝謝你，凱爾。我們的整個產品線都取得了巨大進展，這使得 Ionis 能夠在未來幾年內履行我們的使命，帶來變革性的藥物。首先，我要介紹我們全資擁有的管道的最新動態。提醒一下，Donidalorsen 目前正在接受美國和歐盟的監管審查，其提交的申請有其可靠的臨床數據支持。

We remain confident in the August 21 PDUFA date based on the engagement we've had with the FDA at this stage in the process. Pending approval, we look forward to making this potential best-in-class prophylactic treatment available to people living with HAE.

根據我們在此階段與 FDA 的接觸，我們對 8 月 21 日的 PDUFA 日期仍然充滿信心。等待批准後，我們期待為患有 HAE 的人提供這種潛在的最佳預防性治療方法。

Beyond its approved use in FCS, Olezarsen is also being evaluated for the treatment of severe hypertriglyceridemia or sHTG, with three separate Phase III studies supporting our planned sNDA filing, assuming positive data. Line results from the ESSENCE study which will help satisfy the regulatory safety requirements for the broad HTG population.

除了獲準用於 FCS 之外，Olezarsen 還正在接受治療嚴重高甘油三酯血症或 sHTG 的評估，假設獲得積極的數據，則有三項獨立的 III 期研究支持我們計劃的 sNDA 申請。ESSENCE 研究的一系列結果將有助於滿足廣大 HTG 族群的監管安全要求。

ESSENCE primarily enrolled patients with triglyceride levels between 150 and 500 milligrams per deciliter, a level of dry glycerides that is generally not associated with high risk for acute pancreatitis. In contrast, the CORE and CORE2 studies exclusively enrolled sHTG patients. Participants in these studies had triglycerides that were greater than 500-milligram per deciliter with approximately 43% of the participants across both studies with triglycerides greater than 880-milligram per deciliter at baseline triglycerides at this level for acute pancreatitis.

ESSENCE 主要招募三酸甘油酯水平在每分升 150 至 500 毫克之間的患者，這種乾甘油酯水平通常不會與急性胰臟炎的高風險相關。相較之下，CORE 和 CORE2 研究專門招募了 sHTG 患者。這些研究中的參與者的三酸甘油酯水平高於每分升 500 毫克，兩項研究中約有 43% 的參與者的基線三酸甘油酯水平高於每分升 880 毫克，而處於此水平的三酸甘油酯可導致急性胰臟炎。

The ESSENCE study met its primary end point showing statistically significant placebo-adjusted mean reductions in triglyceride levels of 61% and 58% at six months with the 80- and 50-milligram monthly dosing, respectively. The vast majority of participants thus reaching the normal range, also had all key secondary endpoints stated a favorable safety and tolerability profile.

ESSENCE 研究達到了其主要終點，結果顯示，在每月服用 80 毫克和 50 毫克劑量的情況下，經安慰劑調整後，六個月內三酸甘油酯水平平均降低 61% 和 58%，具有統計學意義。因此，絕大多數參與者都達到了正常範圍，並且所有關鍵的次要終點都顯示出良好的安全性和耐受性。

The results from this study were recently accepted as a hotline session at the ESC Congress 2025, and we look forward to sharing additional details from the study then. The Phase I, these studies remain on track with top line results expected in September. We believe this indication [reputable] to adequately manage their triglycerides with current therapies. Physician feedback continues to highlight strong, underscoring the potential value of Olezarsen in this population.

這項研究的結果最近被接受為 2025 年 ESC 大會的熱線會議，我們期待屆時分享研究的更多細節。第一階段的研究仍在進行中，預計將於 9 月獲得最終結果。我們相信這種跡象表明，目前的療法足以控制他們的三酸甘油酯。醫生的回饋繼續強烈強調了 Olezarsen 在這一人群中的潛在價值。

Importantly, this feedback indicates that physicians understand that lowering triglycerides will reduce the risk of acute pancreatitis and that they would prescribe Olezarsen, if approved, based solely on its ability to substantially lower triglycerides. Although the CORE and CORE2 studies were not designed as AP outcome studies, we are seeing acute pancreatitis events on a blinded basis.

重要的是，該回饋表明醫生明白降低三酸甘油酯將減少急性胰臟炎的風險，如果獲得批准，他們會開出 Olezarsen，僅僅因為它能夠顯著降低三酸甘油酯。儘管 CORE 和 CORE2 研究並非設計為 AP 結果研究，但我們在盲法基礎上觀察了急性胰臟炎事件。

As a result, we expect to have accumulated more combined pancreatitis events for CORE and CORE2 than we had in the FCS balance study. This gives us confidence we could have sufficient data to observe at least a favorable Zilganersen, our medicine to treat Alexander's disease, an ultrarare leukodystrophy that profoundly impacts patients and families who today have no approved disease-modifying treatments. The Phase III study remains on track, and we're looking forward to sharing data later this year.

因此，我們預期 CORE 和 CORE2 中累積的胰臟炎事件將比 FCS 平衡研究中的更多。這使我們有信心，我們可以獲得足夠的數據來觀察至少有利的 Zilganersen，這是我們治療亞歷山大病的藥物，亞歷山大病是一種極為罕見的腦白質營養不良症，對目前尚無獲批的疾病改良療法的患者和家庭產生了深遠的影響。第三階段研究仍在進行中，我們期待在今年稍後分享數據。

Given the ultra-rare nature of this disease, we implemented an innovative clinical development strategy for Zilganersen using a seamless Phase I to Phase III study design. This is the first study of a disease-modifying therapy ever conducted in this patient group. And while this approach allows us to move efficiently toward a potential registration-enabling study, it also means that the upcoming readout will represent the first clinical data in patients with Alexander's disease.

鑑於這種疾病的極為罕見的性質，我們針對 Zilganersen 實施了創新的臨床開發策略，採用了無縫的 I 期至 III 期研究設計。這是針對此患者族群進行的首次疾病改良療法研究。雖然這種方法使我們能夠有效地進行潛在的註冊研究，但這也意味著即將獲得的讀數將代表亞歷山大病患者的第一批臨床數據。

As such, there is a higher degree of uncertainty associated with this readout compared to other medicines we are advancing in late-stage development. Assuming positive data and approval, Zilganersen would represent the first of what we expect to be many more independent launches from our leading neurology pipeline.

因此，與我們正在後期開發的其他藥物相比，該讀數的不確定性程度更高。假設獲得積極的數據和批准，Zilganersen 將代表我們領先的神經病學產品線中更多獨立推出的產品中的第一個。

ION582 an investigational medicine for the treatment of people living with Angelman syndrome is the newest addition to our late-stage pipeline. Angelman syndrome is a serious and rare neurodevelopmental disorder that leads to significant and lifelong physical and cognitive impairments and impacts tens of thousands of people living with this disorder. Supported by the Phase I/II open-label HALOS study results, we recently dosed the first patient in the global Phase III REVEAL study. We plan to have this study fully enrolled next year.

ION582 是一種用於治療天使症候群患者的試驗藥物，也是我們後期研發管線中的最新成員。天使症候群是一種嚴重且罕見的神經發育障礙，會導致嚴重的終生身體和認知障礙，影響成千上萬患有這種疾病的人。在 I/II 期開放標籤 HALOS 研究結果的支持下，我們最近在全球 III 期 REVEAL 研究中為第一位患者進行了給藥。我們計劃明年讓這項研究全面展開。

Turning to our partnered programs. We are pleased that higher-dose nusinersen is one step closer to market with FDA and EMA regulatory submissions under review. If the well-characterized profile of SPINRAZA established over the past 10 years -- 10-plus years and the positive data from higher dose SPINRAZA, we believe SPINRAZA is well positioned to continue to bring benefit to SMA patients around the world. Our partner, Biogen also recently shared positive top line interim results from the Phase I study of Salanersen, an investigational antisense medicine being developed for the potential treatment of spinal muscular atrophy.

轉向我們的合作計劃。我們很高興看到，隨著 FDA 和 EMA 監管申請的審查，高劑量 nusinersen 距離上市又更近了一步。如果 SPINRAZA 在過去 10 多年中建立起良好的特性，並且獲得了更高劑量 SPINRAZA 的積極數據，我們相信 SPINRAZA 能夠繼續為世界各地的 SMA 患者帶來好處。我們的合作夥伴 Biogen 最近也分享了 Salanersen 第一階段研究的積極中期結果，Salanersen 是一種正在開髮用於治療脊髓性肌肉萎縮症的試驗性反義藥物。

Leveraging the same mechanism of action is SPINRAZA, we designed Salanersen with novel Ionis chemistry to achieve strong efficacy and once yearly dosing. In children previously treated with gene therapy, once yearly dosing with both the 40- and 80-milligram doses were well tolerated and led to rapid and substantial slowing of neurodegeneration as shown by reductions in neurofilament.

利用與 SPINRAZA 相同的作用機制，我們設計了採用新型 Ionis 化學成分的 Salanersen，以實現強效療效和每年一次的給藥。對於先前接受過基因治療的兒童，每年服用一次 40 毫克和 80 毫克劑量的藥物耐受性良好，並且導致神經退化性變迅速且顯著減緩，如神經絲減少所示。

Exploratory clinical outcome data also showed that children in the study achieved meaningful improvements in function and attained new milestones. Biogen is actively engaging with regulatory agency to align on the Phase III study design. Notably, the initiation of a Phase III study would trigger a $45 million milestone payment to Ionis. Additionally, are relatively higher than for SPINRAZA.

探索性臨床結果數據還顯示，研究中的兒童在功能方面取得了有意義的改善並達到了新的里程碑。Biogen 正積極與監管機構合作，以協調第三階段研究設計。值得注意的是，第三階段研究的啟動將觸發向 Ionis 支付 4,500 萬美元的里程碑付款。此外，其含量也相對高於 SPINRAZA。

If approved, Salanersen would also substantially extend the life for the Ionis Biogen SMA franchise. The progress of this program underscores Ioni's deep expertise in oligonucleotide medicinal chemistry and reinforces the strength of our broader neurology.

如果獲得批准，Salanersen 還將大大延長 Ionis Biogen SMA 特許經營權的壽命。該計畫的進展凸顯了 Ioni 在寡核苷酸藥物化學方面的深厚專業知識，並增強了我們更廣泛的神經病學實力。

It also validates our approach as we advance new medicines with next-generation chemistries, including follow-on medicines for our wholly owned programs. With multiple data readouts and regulatory milestones expected this year and next, our advancing pipeline underscores the strength of our science and our commitment to addressing serious diseases.

它也驗證了我們利用下一代化學技術來推進新藥研發的方法，包括我們全資擁有專案的後續藥物。隨著今年和明年預計將有多個數據讀數和監管里程碑，我們不斷推進的研發管線凸顯了我們的科學實力和我們應對嚴重疾病的承諾。

With that, Beth.

就這樣，貝絲。

Thank you, Richard. I'm pleased to report that for the second time this year, we are significantly raising our 2025 financial guidance. This time driven by strong revenue performance to date, including the early launch success of Tryngolza and an improved outlook for the year.

謝謝你，理查。我很高興地報告，今年我們第二次大幅提升 2025 年財務指引。此次成長得益於迄今為止強勁的收入表現，包括 Tryngolza 的早期成功上市以及今年前景的改善。

In the second quarter, we earned revenue of $452 million, a two-fold increase year-over-year and $584 million for the first six months of 2025, an increase of nearly 70% versus prior year. The strong second quarter revenue we earned also enabled us to generate $154 million in non-GAAP net income for the quarter.

第二季度，我們的營收為 4.52 億美元，年增兩倍，2025 年前六個月的營收為 5.84 億美元，比前一年增長近 70%。我們第二季的強勁收入也使我們本季實現了 1.54 億美元的非 GAAP 淨收入。

As you heard from Kyle, the early Tryngolza launch continues to perform $3 million in product sales, representing a threefold increase over the first quarter. Royalty revenues increased by approximately 10% to $70 million in the second quarter, anchored by meaningful contributions from both SPINRAZA and Wainua. We also generated substantial revenue from our R&D collaborations, including the $280 million upfront payment for the [Sapoblursen] license, a medicine outside of our core areas of focus.

正如您從凱爾那裡聽到的，早期推出的 Tryngolza 繼續實現 300 萬美元的產品銷售額，比第一季增長了三倍。第二季特許權使用費收入成長約 10%，達到 7,000 萬美元，主要得益於 SPINRAZA 和 Wainua 的重大貢獻。我們也從研發合作中獲得了可觀的收入，其中包括為[Sapoblursen]許可證支付的 2.8 億美元預付款，該藥物不在我們的核心關注領域之內。

Nearly 100% of this revenue dropped directly to the bottom line, underscoring the important financial contributions of our partner pipeline. Total non-GAAP operating expenses in the second quarter increased 8% year-over-year, highlighting our commitment to disciplined investment and driving operating leverage.

幾乎 100% 的收入都直接落到了底線，凸顯了我們合作夥伴通路的重要財務貢獻。第二季非公認會計準則總營運費用年增 8%，凸顯了我們對嚴謹投資和推動營運槓桿的承諾。

As planned, our sales and marketing expenses increased year-over-year, driven by 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 costs. R&D expenses decreased year-over-year as several of our late-stage studies have recently concluded. Importantly, we continue to strategically fund our advancing pipeline with more than 2/3 of our top expenses funding our late-stage programs.

根據計劃，我們的銷售和行銷費用同比增長，這得益於我們對 Tryngolza 美國上市的投資以及即將上市 Donidalorsen 的準備。我們的銷售、一般及行政費用還包括 Wainua 銷售和行銷成本中的少數份額。由於我們的幾項後期研究最近已經結束，研發費用較去年同期下降。重要的是，我們繼續為不斷推進的研發管線提供策略性資金，其中超過三分之二的最高支出用於資助我們的後期專案。

Based on our continued execution across the board, we have increased our revenue guidance range by $100 million and now expect to generate between $825 million and $850 million in revenue this year. Importantly, our improved revenue guidance is driving our improved operating loss and cash guidance for the year.

基於我們持續的全面執行，我們將收入預期範圍提高了 1 億美元，目前預計今年的收入將在 8.25 億美元至 8.5 億美元之間。重要的是，我們改善的收入預期正在推動我們今年的經營虧損和現金預期的改善。

Our revenue guidance includes sizable commercial revenue supported by SPINRAZA and the continued strong Tryngolza performance. We expect to generate between $75 million and $80 million in Tryngolza product sales this year. We are also on track to add initial product revenue from our second launch with the FDA action date for Donidalorsen set for August 21.

我們的收入預期包括 SPINRAZA 支持的可觀商業收入和 Tryngolza 持續強勁的表現。我們預計今年 Tryngolza 產品的銷售額將在 7,500 萬至 8,000 萬美元之間。隨著 FDA 將 Donidalorsen 的批准日期定於 8 月 21 日，我們也有望從第二次產品發布中增加初始產品收入。

Given the timing of approval, we anticipate Donidalorsen will modestly contribute to revenues this year with a greater contribution next year. We continue to project our full year 2025 operating expenses to increase in the high single-digit percentage range compared to last year driven by investments to support the success of our multiple ongoing and planned launches. With the increase to our revenue guidance, we now project an operating loss between $300 million and $325 million, and a year-end cash balance of approximately $2 billion, both substantially in guidance as full year projected revenue is growing faster than projected operating expenses.

考慮到批准的時間，我們預計 Donidalorsen 今年將對收入做出適度貢獻，明年的貢獻將更大。我們繼續預測，2025 年全年營運費用將比去年增加高個位數百分比，這得益於為支持我們正在進行的和計劃中的多項產品的成功而進行的投資。隨著我們收入預期的增加，我們現在預計營業虧損將在 3 億美元至 3.25 億美元之間，年底現金餘額約為 20 億美元，這兩個數字都基本符合預期，因為全年預計收入的增長速度快於預計的營運支出。

The strength of our balance sheet reinforces our disciplined capital management, which enables us to continue to invest for growth. To maintain the strength, we plan to refinance our 2026 convertible debt ahead of the maturity date. As always, we are rigorously evaluating a number of options against our objectives to minimize cost of capital, preserve our cash to support our products and pipeline and maintain operational flexibility.

我們資產負債表的強勁增強了我們嚴格的資本管理，使我們能夠繼續投資以實現成長。為了保持實力，我們計劃在到期日之前對 2026 年可轉換債務進行再融資。像往常一樣，我們正在根據我們的目標嚴格評估多種選擇，以盡量減少資本成本，保留現金以支持我們的產品和管道，並保持營運靈活性。

We have historically used convertible debt and believe it remains an attractive option for us. With multiple product launches ahead, a rich pipeline and continued disciplined investments, we are well positioned to achieve significant revenue growth resulting in sustained positive cash flow in the next few years positioning Ionis for substantial value creation in both the near and longer term.

我們過去一直使用可轉換債務，並相信它對我們來說仍然是一個有吸引力的選擇。隨著多款產品的推出、豐富的產品線和持續的嚴謹投資，我們已做好準備，實現顯著的收入增長，從而在未來幾年內持續保持正現金流，從而使 Ionis 在短期和長期內都能創造巨大的價值。

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。

Another period of strong execution and momentum for Ionis. The continued excellent performance of Tryngolza highlight the strength of our commercial execution and the value of our innovative science and addressing serious unmet needs.

Ionis 又迎來了強勁執行力和強勁發展勢頭的時期。Tryngolza 持續優異的表現凸顯了我們商業執行的實力以及我們創新科學的價值和解決嚴重未滿足需求的能力。

As we prepare for the potential approval and launch of Donidalorsen, the deep and advancing Phase III pipeline, we are well positioned to deliver a steady cadence of independent and partnered launches over the next few years. These upcoming milestones reflect the significant progress we're making towards delivering additional transformative medicines to people with serious diseases and building a sustainable, high-growth company.

在我們為 Donidalorsen（深入推進的第三階段管道）的潛在批准和啟動做準備時，我們已做好準備，在未來幾年內穩步推進獨立和合作的啟動。這些即將到來的里程碑反映了我們在為患有嚴重疾病的人提供更多變革性藥物和建立可持續的高成長公司方面所取得的重大進展。

Before I conclude, I'd like to provide two additional announcements. On October 7, we will be hosting an Innovation Day in New York City to highlight our pipeline, our drug discovery capabilities and will provide additional insights into our ongoing and upcoming independent launches.

在結束之前，我想再宣布兩條訊息。10 月 7 日，我們將在紐約市舉辦創新日活動，重點介紹我們的產品線和藥物研發能力，並提供對我們正在進行和即將推出的獨立產品的更多見解。

We'll provide additional information as they get closer for what we believe will be a highly informative event. Additionally, we are eager in the CORE in CORE2 Phase III studies in HCG. Given that we expect to report the results of both studies at one time in September, we will be initiating a quiet period starting to more, July 31.

隨著我們相信這將是一次資訊量很大的活動，我們將提供更多資訊。此外，我們熱切希望參與 CORE2 第三階段的 HCG 研究。鑑於我們預計將於 9 月同時報告這兩項研究的結果，我們將從 7 月 31 日起進入靜默期。

Our quiet period will be lifted upon data announcement and with that, we'll now open it up for questions

資料公佈後，靜默期將結束，現在我們將開放提問

(Operator Instructions) Gary Nachman, Raymond James.

（操作員指示）Gary Nachman、Raymond James。

Congrats on the strong quarter. So first, just talk a bit more about how the Tryngolza FCS launch is going in terms of finding these new patients and getting them through the reimbursement process and on drug. So what gives you confidence we'll see that strong sequential growth in the back half of the year based on the fiscal year guidance of $75 million to $80 million. So for us a little bit more on that. And then on the upcoming sHTG readout in September just what level of trig lowering are you expecting to see?

恭喜本季業績強勁。首先，請您稍微談談 Tryngolza FCS 的推出情況，包括如何找到這些新患者並幫助他們完成報銷流程和用藥。那麼，是什麼讓您有信心，根據 7500 萬美元至 8000 萬美元的財政年度指導，我們將在下半年看到強勁的連續增長。因此我們對此進行更詳細的介紹。那麼，在即將於 9 月發布的 sHTG 讀數中，您預計會看到什麼程度的觸發降低？

What are you powered to see? And what do you believe will be considered clinically meaningful in these patients that physicians want to say? And it sounds like you're still confident there'll be enough pancreatitis events across both studies to show a positive trend. Do you think physicians need to see that to use it for severe high trigs bearing in the physician community on that?

你有能力看到什麼？您認為醫師對這些病人說的話具有臨床意義嗎？聽起來您仍然相信這兩項研究中會有足夠的胰臟炎事件來顯示出正面的趨勢。您是否認為醫生需要看到這一點，並將其用於治療醫生群體中嚴重的高三叉神經痛？

Thanks, Gary. Kyle, would you start with the FCS launch? What we expect in the second half of the year?

謝謝，加里。凱爾，你能先從 FCS 的發布開始嗎？我們對下半年有何期待？

Thanks, Gary. So as we communicated, we're really off to an encouraging start, again, with the FCS launch in Tryngolza for the first half of the year. the $19 million in Q2 and a threefold increase over the previous quarter really demonstrates the early momentum that we're very proud of.

謝謝，加里。因此，正如我們所傳達的，隨著 FCS 在 Tryngolza 的推出，我們再次迎來了一個令人鼓舞的開端。第二季的 1900 萬美元和比上一季成長三倍確實證明了我們非常自豪的早期發展勢頭。

The product profile, first of all, is playing through very effectively. The reductions in and APOCIII, reductions in triglycerides, improvements in acute pancreatitis or reduction in risk of acute pancreatitis and reductions in hospitalizations, I mean all of these things stack up very, very favorably in terms of the receptivity for Tryngolza and the FCS population.

首先，產品簡介的展示非常有效。和 APOCIII 的減少、三酸甘油酯的減少、急性胰臟炎的改善或急性胰臟炎風險的降低以及住院率的減少，我的意思是，就 Tryngolza 和 FCS 人群的接受度而言，所有這些因素都非常非常有利。

In addition to that, a very strong commercial strategy, as I referenced, our customer-facing team has over 3,000 physicians that they're interacting with currently. Our marketing and our omnichannel capabilities were reaching greater than 30,000 HCPs right now with that education.

除此之外，正如我所提到的，我們有一個非常強大的商業策略，我們的客戶團隊目前正在與 3,000 多名醫生互動。透過這種教育，我們的行銷和全通路能力目前已經涵蓋了超過 30,000 名 HCP。

And then you also asked about reimbursement, access is going extremely well, either clinically diagnosed or genetically confirmed patients are going through the process and getting reimbursement very quickly. Patient out-of-pocket expenses, greater than 90% of those patients are paying $0 out of pocket. So overall, what we're seeing is very strong execution from a very strong program.

然後您也詢問了報銷情況，報銷流程非常順利，無論是臨床診斷還是基因確診的患者都可以很快完成報銷流程並獲得報銷。患者自付費用方面，超過 90% 的患者自付費用為 0 美元。所以總的來說，我們看到的是一個非常強大的計劃的非常強大的執行力。

In terms of the second half, the real focus is on additional patient identification and continuing to get those patients diagnosed. And through the activities of our commercial team, be it customer-facing and/or our omnichannel and marketing capabilities we expect that to continue, but to continue to identify these upwards of 3,000 patients that potentially have FCS is going to some work, and we expect that we'll continue that growth throughout the rest of the year.

就下半年而言，真正的重點是進一步識別患者並繼續對這些患者進行診斷。透過我們商業團隊的活動，無論是面向客戶還是全通路和行銷能力，我們都希望這種情況能夠持續下去，但繼續識別這 3,000 多名可能患有 FCS 的患者需要做一些工作，我們預計我們將在今年剩餘時間內繼續保持這種增長。

Thanks, Kyle. Gary, the triglyceride lowering that we're expecting in sHTG is probably going to be similar to what we saw in ESSENCE. Where we saw 58% to 62% reduction based on the dose 50 year versus 80 milligrams. And what we know based on extensive work we've done with the lipid specialists or the cardiologists or the endocrinologists that manage these patients what they're looking for are any substantial reductions in triglycerides on top of the treatments they're already giving their patients quite omega-3, fatty acids or fibrates.

謝謝，凱爾。加里，我們預期 sHTG 中的三酸甘油酯降低可能與我們在 ESSENCE 中看到的類似。我們發現，與 80 毫克劑量相比，50 毫克劑量減少了 58% 至 62%。根據我們與管理這些患者的脂質專家、心臟病專家或內分泌學家所做的大量工作，我們知道他們所尋求的是在他們已經為患者提供大量 Omega-3、脂肪酸或貝特類藥物的治療基礎上大幅降低三酸甘油酯。

So they're already recognized that these patients need to be treated, and they're not getting much triglycerides lowering to the existing treatments, so they want something to produce a substantial lowering of triglycerides. Anything north of 50% is a big win in this patient population on top of standard of care and that is what we expect.

因此，他們已經認識到這些患者需要接受治療，但現有的治療方法並不能顯著降低三酸甘油酯，因此他們希望找到一種能夠顯著降低三酸甘油酯的藥物。對於該患者群體來說，在標準護理的基礎上，任何超過 50% 的治療率都是一個巨大的勝利，這也是我們所期望的。

With respect to AP events and what we're hearing from physicians, we're hearing exactly what I just said, is that substantially lower that these patients are in harm's way for acute pancreatitis that can be fatal and we need to lower their triglycerides substantially to get them out that way. They don't need to see the AP advance. However, with that said, although the CORE and CORE2 studies were not the AP outcome studies, we are seeing, as Richard mentioned in his formal remarks, we are seeing on a blinded basis, acute pancreatitis events.

關於 AP 事件以及我們從醫生那裡聽到的消息，我們聽到的正是我剛才所說的，即這些患者面臨可能致命的急性胰臟炎的危險，我們需要大幅降低他們的三酸甘油酯，才能讓他們擺脫這種危險。他們不需要看到 AP 預付款。然而，話雖如此，儘管 CORE 和 CORE2 研究不是 AP 結果研究，但正如理查德在正式發言中提到的那樣，我們在盲法基礎上看到了急性胰臟炎事件。

And we expect to have more accumulated AP events in the combined CORE and CORE2 study than we had in the FCS BALANCE study. This gives us confidence we could have sufficient data to observe at least a favorable trend in Olezarsen's impact on AP within these studies, and we look forward to discussing more when we read out the data in September.

我們預計，在 CORE 和 CORE2 聯合研究中累積的 AP 事件將比 FCS BALANCE 研究中累積的更多。這使我們有信心，我們可以擁有足夠的數據來觀察到這些研究中 Olezarsen 對 AP 的影響至少呈有利趨勢，我們期待在 9 月讀出數據時進行更多討論。

Okay. Great. And then just one quick one on doni with the PDUFA coming up on August 21. Just you're in labeling discussions. So how you feel relative to your expectations, if you think the switch data will make it on there if it will be once every month and once every other month dosing, that option will be available for patients. And it sounds like you're ready to launch basically right after approval. So just confirm everything is in place for that?

好的。偉大的。然後，關於 Doni 的簡短問答，PDUFA 將於 8 月 21 日出台。只是你正在參與標籤討論。因此，相對於您的期望，您的感覺如何？如果您認為轉換資料會出現在那裡，如果每個月一次，每隔一個月一次給藥，那麼該選項將適用於患者。聽起來您基本上在獲得批准後就可以啟動了。那麼只需確認一切就緒即可嗎？

I'll start. This is Richard. We're definitely on track for the PDUFA date on August 21, everything that we've been discussing with FDA indicates that, that date is on track. And then I can't speak to the launch, although everything looks to be in place, and we're excited about it. I think your other question in regard to what we get in the label is a matter of negotiation, it always is.

我先開始了。這是理查德。我們肯定會按照 PDUFA 的日期 8 月 21 日進行，我們與 FDA 討論的所有內容都表明，該日期正在按計劃進行。然後我不能談論發布會，儘管一切看起來都準備就緒，我們對此感到興奮。我認為您關於我們在標籤中得到什麼的另一個問題是一個談判的問題，它始終如此。

And so we work with the agency. That's certainly been our position, let's get that in there, but we don't need it in the label because it is published. And now that we have a publication and it's related to the work that was done in the clinical trials, we have an opportunity to promote on that.

因此我們與該機構合作。這當然是我們的立場，讓我們把它放進去，但我們不需要它出現在標籤中，因為它已經發布了。現在我們有了一份出版物，它與臨床試驗中所做的工作有關，我們有機會推廣它。

Kyle, maybe you could touch on the launch preparations.

凱爾，也許你可以談談發射準備。

In terms of launch readiness, we're building on the synergies from our FCS capabilities. Our medical affairs teams have been out interacting with allergists and immunologists treating HAE. Our sales team is now in place, market access abilities. So everything is ready to go in terms of launch readiness.

在發射準備方面，我們正在利用 FCS 能力的綜效。我們的醫療事務團隊一直在與治療 HAE 的過敏症專家和免疫學家進行交流。我們的銷售團隊現已到位，市場拓展能力增強。因此，就發射準備而言，一切已準備就緒。

As Richard was describing the program from a regulatory standpoint, the overall totality of the data here for Donidalorsen is very, very strong from an efficacy standpoint, in terms of the durability and control of attacks, the tolerability using the easy-to-use, self-administered auto-injector by the patient and convenience. Here, we have a program with the longest dosing interval available or potentially that will be available for patients living with HAE.

正如理查德從監管角度描述該計劃時所說，從療效的角度來看，Donidalorsen 的整體數據非常非常強大，包括發作的持久性和控制性、患者使用易於使用、自行注射的自動注射器的耐受性和便利性。在這裡，我們有一個具有最長給藥間隔的方案，或者可能適用於患有 HAE 的患者。

The Switch study is going to be helpful. This is in United States. The majority of patients are on a prophylactic treatment today. And what we were able to demonstrate is that, number one, patients are willing to switch.

Switch 研究將會有所幫助。這是在美國。目前大多數患者正在接受預防性治療。我們能夠證明的是，首先，患者願意轉換治療方案。

Number two, they can do so safely and move over to Donidalorsen, they can have an additional reduction of upwards of 62% improvement from baseline on an existing and 84% of the patients said that they preferred Donidalorsen over the existing treatment that they were on once they were switched. So the totality of the data combined with the timing of the launch year upcoming, hopefully, on August 21, we'll be ready to go.

第二，他們可以安全地轉用 Donidalorsen，他們的病情可以在現有治療基礎上額外減少 62% 以上，並且 84% 的患者表示，一旦轉用 Donidalorsen，他們更喜歡使用 Donidalorsen 而不是他們正在使用的現有治療。因此，結合所有數據以及即將到來的發射年份（希望是 8 月 21 日），我們就可以做好準備了。

Yanan Zhu, Wells Fargo Securities.

朱亞南，富國證券。

Great. Congrats on a very strong quarter. Perhaps a first question about CORE and CORE2. So I think I heard in the prepared remarks that the cumulative AP rate on a blended basis is now above what you saw in FCS. So I just want to confirm.

偉大的。恭喜本季業績表現強勁。這也許是關於 CORE 和 CORE2 的第一個問題。因此，我認為我在準備好的發言中聽到，混合基礎上的累積 AP 率現在高於您在 FCS 中看到的水平。所以我只是想確認一下。

It seems like in the BALANCE study, you had 13 events and just wanted to get a sense of in the CORE and CORE2 was across 1,000-plus patients. Are we thinking about the rate above that? And could you also give us a sense that based on the CORE, CORE2 patient profile, what is the expected AT rate in untreated population like that so that we can help us prepare for the data and the AP data? And I've a follow-up on the FCS and sHTG launch dynamic.

似乎在 BALANCE 研究中，您有 13 個事件，只是想了解 CORE 的情況，而 CORE2 涉及 1,000 多名患者。我們是否考慮過高於該水準的利率？您能否告訴我們，根據 CORE、CORE2 患者概況，未經治療族群的預期 AT 率是多少，以便我們為數據和 AP 數據做好準備？我對 FCS 和 sHTG 的發布動態進行了追蹤。

Yanan, so you said the rate is higher. It's about the rate, the rate is lower, of course, in HCG. I think that's what you knew that. What we're talking about is the accumulated number of AP events in the CORE and CORE2 studies combined. And I can confirm that there'll be more events in CORE, CORE2 combined FCS BALANCE study. As far as what we think the AP, I mean, we don't really know what the AP rate is -- this study will be the first actually really definitively provide information on what the AP event rate is in sHTG. Is that right, Eugene?

延安，所以你說利率比較高。當然，這與比率有關，HCG 的比率較低。我想這就是你所知道的。我們所討論的是 CORE 和 CORE2 研究中 AP 事件的累積數量。我可以確認，CORE、CORE2 聯合 FCS BALANCE 研究將會有更多事件。至於我們對 AP 的看法，我的意思是，我們並不真正知道 AP 發生率是多少——這項研究將首次真正明確地提供有關 sHTG 中 AP 事件發生率的信息。是這樣的嗎，尤金？

Yes, absolutely right. There's no outcome data can inform us. We're early awaiting the CORE and CORE2 readout.

是的，完全正確。沒有結果數據可以告訴我們。我們很早就在等待 CORE 和 CORE2 的讀數。

Got it. Got it Yes, yes. And on the FCS launch and potentially the later launch of sHTG. Congrats on a very strong second quarter of launch in FCS. It feels like the opportunity in FCS is actually pretty sizable given this momentum.

知道了。明白了 是的，是的。以及關於 FCS 發射和可能稍後發射的 sHTG。恭喜 FCS 在第二季取得了非常強勁的成績。鑑於這種勢頭，感覺 FCS 的機會實際上相當大。

Can you talk about is this opportunity relative to your anticipation? Is it bigger or in line? And more importantly, as we think about you going into SHTG with a much reduction in the pricing presumably across the board for both indications. Any strategy to protect the FCS opportunity in terms of timing of launch and also any way to manage the pricing change? That would be super helpful.

您能談談這個機會是否與您的預期有關嗎？是更大還是一致？更重要的是，當我們考慮您進入 SHTG 時，兩種適應症的價格大概都會大幅降低。就發佈時間而言，有什麼策略可以保護 FCS 機會？還有什麼方法可以管理價格變動？那將會非常有幫助。

Yes. Let me first talk about the FCS population that you described. I still believe that it's representative up to 3,000 potential patients. It's still early innings. The majority of these patients still are not diagnosed.

是的。我先來談談您所描述的FCS人群。我仍然相信它能夠代表多達 3,000 名潛在患者。現在還只是比賽的初期。大多數患者仍未得到診斷。

Obviously, several hundred patients have either participated in a clinical trial or we're waiting for a medication because they had been previously diagnosed and needed a treatment. First mover advantage here is very important, not only in FCS but also sHTG. So our work for the first half of this year was to convert our clinical trial patients, which we did effectively to help those patients that were previously identified with FCS to go on to treatment.

顯然，數百名患者要么參加了臨床試驗，要么正在等待藥物，因為他們之前已被診斷並需要治療。先發優勢在這裡非常重要，不僅在 FCS 方面，而且在 sHTG 方面。因此，我們今年上半年的工作是轉化臨床試驗患者，我們有效地幫助了那些先前被診斷為 FCS 的患者繼續接受治療。

And then to continue to expand our patient identification efforts, we've been spending a lot of time on that, as I referenced in terms of reaching greater than 3,000 HCPs with our sales team and reaching greater than 30,000 HCPs through our education related to our marketing and our omnichannel efforts. So we're continuing to educate.

然後，為了繼續擴大我們的患者識別工作，我們在這方面投入了大量時間，正如我所提到的，我們的銷售團隊接觸了 3,000 多名 HCP，並透過與我們的行銷和全通路工作相關的教育接觸了 30,000 多名 HCP。因此，我們將繼續進行教育。

The time that we're spending on FCS specifically is with physicians that are treating SHTG patients. And so what we're doing is having conversations around the implications of high triglycerides and how these patients present and ultimately looking for a phenotype of an FCS patient in order to either clinically diagnose them or get a genetic confirmation of their disease.

我們在 FCS 上花費的時間專門用於與治療 SHTG 患者的醫生在一起。因此，我們正在進行的討論是圍繞高三酸甘油酯的含義以及這些患者的表現進行，並最終尋找 FCS 患者的表型，以便對其進行臨床診斷或對其疾病進行基因確認。

So that work is ongoing, and that's what we'll need to do through the second half of this year. We provided the guidance of $75 million to $80 million this year, which represents not only the patients that we've converted already in the first half, but the ongoing efforts that we believe will be successful with through the second half of this year. So I believe that the FCS population is in line up to 3,000 that we've represented up to this point.

所以這項工作正在進行中，這也是我們今年下半年需要做的事情。我們今年的指導金額為 7500 萬至 8000 萬美元，這不僅代表了我們上半年已經轉化的患者，還代表了我們相信將在今年下半年取得成功的持續努力。因此我相信，FCS 人口與我們目前所代表的 3,000 人相符。

As it relates to sHTG, this is a much broader patient population, obviously, in the treating physician population is much more significant. Greater than 1 million patients have high-risk sHTG, which is inclusive, obviously, of patients over 500 with a history of AP or patients over 880 milligrams per deciliter. So there's a lot of effort already around education in this population and working to identify these potential patients within these practices as we go out and have these interactions. As it relates to the pricing dynamic, we're still working through that.

由於它與 sHTG 相關，因此患者群體的範圍更為廣泛，顯然，在治療醫生群體中，其重要性更為顯著。超過 100 萬名患者患有高風險 sHTG，顯然包括有 AP 病史的 500 歲以上的患者或每分升超過 880 毫克的患者。因此，我們在針對這一人群的教育方面已經付出了很多努力，並在我們進行這些互動時努力在這些實踐中識別這些潛在患者。由於它與定價動態有關，我們仍在努力解決這個問題。

There's more work for us to understand in terms of the data, which we are still waiting for. And then we'll work obviously with the payer community to understand the budget impact of the patient population, their interpretation of the data. and obviously, the value that, that represents to patients. So that's the work that we will do going into next year. And ultimately, we will announce price upon the approval of the SHTG pending positive outcome there.

在數據方面我們還有很多工作要了解，我們仍在等待。然後，我們顯然會與付款人社群合作，了解患者群體的預算影響、他們對數據的解釋，以及這對患者來說顯然代表的價值。這就是我們明年要做的工作。最後，我們將在 SHTG 批准並取得積極成果後公佈價格。

Congrats on the quarter again.

再次恭喜本季取得佳績。

[Stephen Ido], TD Securities.

[Stephen Ido]，道明證券。

This is Stephen Ido on for Yaron Werber. Congrats again on fantastic quarter. One more on Doni and on competition specifically. It looks like TAKHZYRO seems to be grew well on the [genre] launch, which was approved on June 16. Obviously, that drug has a couple of disadvantages including monthly dosing versus your doni is two months and also requiring a loading dose, which doni does not. Any visibility on the competition and maybe insights from there on what the Donidalorsen launch could look like?

這是 Stephen Ido 代替 Yaron Werber 上場的比賽。再次恭喜您取得如此出色的季度業績。再談多尼和比賽的具體情況。看起來 TAKHZYRO 在 6 月 16 日獲得批准的 [類型] 發布中發展良好。顯然，該藥物有幾個缺點，包括每月服用一次，而您的 doni 藥物需要兩個月服用，並且還需要負荷劑量，而 doni 藥物則不需要。對競爭對手有什麼了解嗎？從那裡可以了解 Donidalorsen 的發布嗎？

Yes, I'd be happy to talk about that. This is -- I think what we know in this marketplace and what's come through very clear is that patients on existing prophylactic treatments are not completely satisfied and that they would be willing to switch to a new therapy. A recent Harris Poll said that greater than 90% of patients actually would look to switch to an improved therapy.

是的，我很樂意談論這個。這是——我認為我們在這個市場上所知道的以及非常清楚的是，接受現有預防性治療的患者並不完全滿意，他們願意轉換到新的療法。哈里斯民意調查最近的一項研究表明，超過 90% 的患者實際上希望嘗試改進的治療方法。

And I think you're seeing that play out with the newly approved treatment already, and we would expect to see the same from Donidalorsen. The profile overall with Donidalorsen is very strong, as I mentioned, not only the efficacy data but also the ability for patients to self-administer.

我認為你已經看到了新批准的治療方法的效果，我們期望在 Donidalorsen 身上也能看到同樣的效果。正如我所提到的，Donidalorsen 的整體表現非常出色，不僅具有療效數據，而且患者還可以自行服用。

As you pointed out, this therapy is going to be potentially prescribed every four weeks or every eight weeks depending upon how patients present and how stable they are with their disease. So that is, again, another key differentiator here. And then finally, I'll just mention the switch study. I mean what we have demonstrated is that patients are willing to switch. When they do so, they can do so safely.

正如您所指出的，這種療法可能會每四周或每八週進行一次，這取決於患者的表現以及病情的穩定性。所以，這又是另一個關鍵的區別因素。最後，我只想提一下轉換研究。我的意思是，我們已經證明患者願意轉換。當他們這樣做時，他們可以安全地這樣做。

They have the potential to improve the control of their disease. And ultimately, when they've ended up on Donidalorsen, they preferred it. over the treatment that they were on. So I believe from a competitive point, we're in really good shape, and we've got a great team. We've hired a sales organization that has experience in the allergy and immunology space, many of whom have direct HAE experience for many years and they know the treating physicians, and they've got not only existing relationships, but they understand how to competitively sell.

他們有潛力改善對疾病的控制。最終，當他們接受 Donidalorsen 治療時，他們更喜歡這種治療方法，而不是之前所接受的治療。因此，我相信從競爭的角度來看，我們的狀態非常好，而且我們擁有一支優秀的團隊。我們聘請了在過敏和免疫學領域經驗豐富的銷售團隊，其中許多人擁有多年的直接 HAE 經驗，他們了解治療醫生，他們不僅擁有現有的關係，而且懂得如何進行有競爭力的銷售。

So we're really excited about the upcoming launch potentially with the approval on August 21.

因此，我們對即將於 8 月 21 日獲得批准的新產品感到非常興奮。

Mike Ulz, Morgan Stanley.

摩根士丹利的麥克烏爾茲。

Congratulations on the strong quarter as well. Maybe just a question on the Phase III sHTG core data. Previously, you suggested data 3Q, you're narrowing that a little bit to September. I guess first question, just any -- what's the rationale there? Or anything behind that?

也祝賀本季業績強勁。也許只是關於第三階段 sHTG 核心數據的一個問題。之前，您建議使用第三季的數據，現在您將範圍縮小到九月。我想第一個問題是──其理由是什麼？或者這背後有什麼？

And then secondly, last quarter, do you suggest that AP data might not be available in the top line release? I guess just maybe give us a sense of what level of AP data you plan to share in the top line release in September?

其次，上個季度，您是否認為 AP 資料可能無法在頂線發布中提供？我想也許可以讓我們了解一下您計劃在 9 月發布的頂線新聞中分享什麼級別的 AP 數據？

Sure, Mike. So the -- just refining the timeline to September from the second half of the year is just blocking and tackling. Getting the studies completed database locked, they've cleaned and all that. So we just felt it was appropriate to provide more specificity on the exact timing. So nothing significant behind there, except operational in conducting studies.

當然，麥克。因此，將時間表從下半年推遲到 9 月只是一種阻礙和解決措施。鎖定已完成研究的資料庫，然後進行清理等等。因此，我們覺得有必要提供更具體的確切時間資訊。因此，除了進行研究之外，這背後沒有什麼重要的事。

We will provide a statement on AP in our top line press release. Our primary endpoint, again, is triglyceride lowering. We will provide top line information on triglycerides as well as safety -- overall safety, and we'll provide a statement on AP. What's also, I think even more important is that we will provide and present the full data set at a medical congress in the second half of this year. And we look to publish the data in the second half of this year as well.

我們將在美聯社的頭條新聞稿中提供一份聲明。我們的主要終點是降低三酸甘油酯。我們將提供有關甘油三酯以及安全性（總體安全性）的頂級信息，並且我們將在 AP 上提供聲明。而且我認為更重要的是，我們將在今年下半年的醫學會議上提供並展示完整的數據集。我們也希望在今年下半年發布這些數據。

Andy Chen, Wolfe.

安迪陳，沃爾夫。

Brandon on for Andy. On Wainua polyneuropathy, where do you think those patients are coming from? Do you think that they are -- you're winning new -- winning new to brand share or stealing patients from [Anylam]? If you can provide any quantitative splits on those details, that would be great.

布蘭登替換安迪上場。關於 Wainua 多發性神經病變，您認為這些患者來自哪裡？你認為他們是在贏得新的品牌份額還是在搶走患者[Anylam]？如果您能提供這些細節的量化細分，那就太好了。

I'd be happy to talk about that, Brandon. Thanks. This is Kyle again. First, I'll just say, Wainua continues to perform very well. From demand, the polyneuropathy market is a growth market.

我很樂意談論這個，布蘭登。謝謝。這又是凱爾。首先，我只想說，Wainua 的表現一直非常出色。從需求來看，多發性神經病變市場是一個成長型市場。

The majority of these patients are not diagnosed yet, and that's exactly where AstraZeneca is spending the time is looking for and educating HCPs around hereditary polyneuropathy patients. $44 million in Q2, which obviously was growth over Q1. The feedback that we're getting from HCPs as continuing to be very positive around the quality of life in [FC] and the control of the polyneuropathy symptoms on a consistent basis.

這些患者中的大多數尚未得到診斷，而這正是阿斯特捷利康花時間尋找和教育遺傳性多發性神經病變患者的 HCP 的地方。第二季為 4,400 萬美元，顯然比第一季有所成長。我們從 HCP 那裡得到的回饋表明，他們對 [FC] 的生活品質和多發性神經病變症狀的控制持續非常積極。

The ability to self-administer with an auto-injector continues to be a differentiating factor. And physicians and patients very much appreciate the opportunity to manage their disease on their own without having to come into the HCP's office in order to have a simple injection provided to that patient.

使用自動注射器進行自我注射的能力仍然是一個區別因素。醫生和患者非常感激有機會自行管理疾病，而不必來到 HCP 辦公室為患者進行簡單的注射。

So in a simple response here, these are new-to-brand patients. These are patients that are newly identified predominantly. We are seeing some switches as you would expect, and we are seeing some combination use along with patients that are progressing on the state today. But really, our focus is growing the polyneuropathy market and making sure that newly identified patients get described Wainua.

因此，簡單來說，這些都是新品牌患者。這些患者主要是新確診的患者。正如您所期望的，我們看到了一些轉換，並且我們看到了一些組合使用以及今天病情正在好轉的患者。但實際上，我們的重點是擴大多發性神經病變市場並確保新確診的患者得到 Wainua 的描述。

Gena Wang, Barclays

巴克萊銀行的王吉娜

Also congrats on a very strong quarter. So I have two questions regarding Tryngolza. When I look at the guidance, $75 million to $80 million, even if we use $80 million seems every quarter's 3Q for only $75 million growth. So maybe give us a little bit more color. Are you -- is the guidance too conservative? Or is there reason that why the new patient add-on was slow down compared to 2Q over 1Q. So that's the first question.

也祝賀本季業績非常強勁。所以我有兩個關於 Tryngolza 的問題。當我查看指導意見時，7500 萬美元到 8000 萬美元，即使我們使用 8000 萬美元，似乎每個季度的第三季度也只有 7500 萬美元的增長。所以也許可以給我們多一點色彩。您——這個指導是否過於保守了？或者為什麼第二季新患者增加速度比第一季放緩？這是第一個問題。

And the second, I don't know if you can comment. I think should the total cumulative events for quarter one and quarter two will be more than 13%. So giving certainly different disease and the price history of AP in the two studies -- so maybe like how much more? Are we talking about the total AP events still in the teens? Or could that be in 20s.

第二，我不知道您是否可以發表評論。我認為第一季和第二季的累計事件總數應該會超過 13%。因此，考慮到兩項研究中 AP 的疾病和價格歷史肯定不同——那麼可能有多大差異？我們討論的 AP 事件總數是否仍處於十幾歲的水平？或者可能是 20 多歲。

Thanks, Gena. Beth, do you want to touch on the $75 million to $80 million guidance?

謝謝，吉娜。貝絲，你想談談 7,500 萬至 8,000 萬美元的指導價嗎？

Yes. Actually, I think I'll just pass that to Kyle because that's in his hat. He's responsible for that.

是的。實際上，我想我會把它傳給凱爾，因為它在他的帽子裡。他對此負有責任。

So I think what's most important here is the way that we progress throughout the launch, right? As I referenced, we converted the clinical trial patients, we've been working very effectively with patients that were identified prior to the approval in order to get those patients formally diagnosed and put on to treatment.

所以我認為這裡最重要的是我們在整個發布過程中取得的進展，對嗎？正如我所提到的，我們轉換了臨床試驗患者，我們一直與批准前確定的患者進行非常有效的合作，以便讓這些患者得到正式診斷並接受治療。

So you had a number of patients that were identified. So where we're at right now at the launch is really looking for newly identified and newly diagnosed patients, right, in order to penetrate deeper into that up to 3,000 FCS patient population that we believe exists in the US. So that takes some time. It takes a lot of education and it takes a lot of conversations.

因此，您已經確定了一些患者。因此，我們現在啟動的重點實際上是尋找新發現和新診斷的患者，以便更深入地了解我們認為存在於美國的多達 3,000 名 FCS 患者群體。所以這需要一些時間。這需要大量的教育，也需要大量的對話。

And then it also takes a little bit of time for physicians to get potential patients into the practice in order to be either clinically or genetically confirmed with their condition. So we've done a nice job throughout the first half of the year. We expect to continue to identify these patients, but it just might take us a little bit of time because of the complexity of the rare disease that we're dealing with in being first to market and having a great product with positive physician and patient experience is helping us to increase that patient identification over time.

然後，醫生也需要花一點時間讓潛在患者接受治療，以便透過臨床或基因方式確認他們的病情。因此，我們整個上半年都做得很好。我們希望繼續識別這些患者，但這可能需要一點時間，因為我們處理的罕見疾病非常複雜，作為第一個將產品推向市場的產品，擁有良好的醫生和患者體驗有助於我們隨著時間的推移提高患者識別率。

Yes. Thanks, Kyle. And on your second question, Gena, we're not going to go more than that. I mean, in this call today, we confirmed that we will see more AP events in the quarter or two studies combined. And we saw in FCS balance when we confirmed that we will make a statement summarizing, to some extent, top line summary of AP findings in CORE and CORE2. We're not going to go further than how many more AP events we see. We look forward to sharing the data in September.

是的。謝謝，凱爾。關於你的第二個問題，吉娜，我們不會再進一步討論。我的意思是，在今天的電話會議中，我們確認我們將在本季度或兩個研究結合起來看到更多的 AP 事件。當我們確認將發表一份聲明，在某種程度上總結 CORE 和 CORE2 中 AP 調查結果的頂線摘要時，我們在 FCS 平衡中看到了這一點。我們不會比我們看到的 AP 事件數量走得更遠。我們期待在九月分享數據。

Luca Issi, RBC.

盧卡·伊西，RBC。

Well, great. Congrats on the great quarter here. Maybe, Brett, if I can circle back on one statement you made earlier, the physicians appreciate that triglyceride they're the bad guys, so to speak, and they don't need to see stats on acute pancreatitis. Is that a US comment?

嗯，太好了。恭喜本季取得如此出色的成績。布雷特，也許，如果我可以回到你之前說過的一句話，醫生們知道三酸甘油酯是壞人，可以這麼說，他們不需要看急性胰臟炎的統計數據。這是美國的評論嗎？

Or do you think that is applicable also to the rest of the world I guess, in a scenario where you don't show static or strong trend on AP. How should we think about the uptake of this drug outside the United States? And then I know I'm probably pushing my luck here, but you mentioned you'll have a statement on AP in the press release will that be a qualitative statement or a quantitative statement?

或者您認為這也適用於世界其他地區，在 AP 上沒有顯示靜態或強勁趨勢的情況下。我們該如何看待這種藥物在美國以外的應用？然後我知道我可能在這裡碰運氣，但你提到你會在新聞稿中對 AP 發表聲明，那是定性聲明還是定量聲明？

We're not going to go more than that, Luca, on what we're going to say. We're going to -- we will speak to our findings in CORE and CORE2 on AP in our top line press release and share for the full data set at a medical congress this year. So just going to hold off on that one.

盧卡，我們不會再多說了。我們將在美聯社的頭條新聞稿中介紹我們在 CORE 和 CORE2 中的研究結果，並在今年的醫學大會上分享完整的數據集。所以，我先暫緩一下這個。

Your first question is very -- is an important question. because really what you're getting is payer dynamics outside of the US. That's really -- Kyle will address that. But I can tell you that in the US, and I have spent a lot of time with the specialists over the last two years who treat sHTG patients.

您的第一個問題非常重要，因為您真正了解的是美國以外的付款人動態。這確實是——凱爾會解決這個問題。但我可以告訴你，在美國，過去兩年我花了很多時間與治療 sHTG 患者的專家在一起。

They do not -- they are convinced that they need to get patients on the most effective triglyceride lowering agents possible if they're sHTG patients because they are convinced they know that their patients are in harm's way for acute pancreatitis. In fact, they're already treating them. They're treating them with everything they have, whether it be fibrates or omega-3s, they're just not effective.

他們沒有——他們確信，如果患者是 sHTG 患者，他們需要讓患者服用最有效的降低三酸甘油酯的藥物，因為他們確信他們知道他們的患者正處於急性胰臟炎的危險之中。事實上，他們已經在治療了。他們用盡一切辦法治療，無論是貝特類藥物還是 Omega-3 脂肪酸，但都沒有效果。

So they're looking for something on top of standard of care. As a reminder, our CORE and CORE2 studies are on top of standard of care -- that to get their triglycerides down. And that's true for payers in the United States, too. outside the US, let maybe focus on Europe, it's more complex, right?

因此，他們正在尋找高於標準護理的東西。提醒一下，我們的 CORE 和 CORE2 研究是基於標準護理的——即降低三酸甘油酯。對於美國的付款人也是如此。在美國以外，我們也許關注歐洲，情況更複雜，對吧？

It is. From a regulatory standpoint, though, obviously, triglyceride lowering is going to be sufficient for a label in the EU and that filing is there. And we've obviously positive CHMP opinion and optimistic about the outcome and where that goes in terms of the approval.

這是。然而，從監管角度來看，顯然降低三酸甘油酯就足以在歐盟獲得標籤，並且已經提交了相關文件。我們顯然對 CHMP 持積極態度，對結果以及批准的進展持樂觀態度。

So from a payer and reimbursement dynamic standpoint in the European countries, for example, it's really about the breadth of the population that you're ultimately going to be able to treat. Who to treat and why to treat those patients, right, is the key thing here in order to demonstrate outcomes in the patient population.

因此，從歐洲國家的付款人和報銷動態角度來看，這實際上與最終能夠治療的人口廣度有關。為了展示患者群體的結果，關鍵在於治療誰以及為什麼治療這些患者。

One thing that's very positive already is if we are able to secure an indication in Europe is we've got FCS. FCS already has AP data. It already has very strong hospitalization data and so we've got information to be able to substantiate pricing and reimbursement from an FCS standpoint. We also have a very strong partner in Sobi many years, and they've navigated pricing and reimbursement very successfully in the FCS population already across numerous countries across Europe. And I think we're very optimistic that we'll be able to continue that success with the program like Tryngolza.

已經非常積極的一件事是，如果我們能夠在歐洲獲得認可，那麼我們就獲得了 FCS。FCS 已經擁有 AP 資料。它已經擁有非常強大的住院數據，因此我們擁有從 FCS 角度證實定價和報銷的資訊。多年來，Sobi 也是我們非常強大的合作夥伴，他們已經在歐洲眾多國家的 FCS 人群中非常成功地解決了定價和報銷問題。我認為我們非常樂觀，我們能夠透過像 Tryngolza 這樣的計畫繼續取得成功。

So then the question becomes sHTG if you have a potential label expansion and what do you need to show there. Outcomes in AP are obviously going to be important for the broad population but could you potentially look at a different population, a little bit more narrow than anybody over 500, for example, patients that are at high-risk sHTG such as patients over 880 patients with 500 in the history of AP or potentially patients with other comorbidities.

那麼問題就變成了，如果您有潛在的標籤擴展，您需要在那裡展示什麼。AP 的結果顯然對廣大人群很重要，但您是否可以考慮不同的人群，比 500 歲以上的人稍微狹窄一點，例如，高風險 sHTG 患者，如 880 歲以上的患者，有 500 年 AP 病史的患者或可能患有其他合併症的患者。

So there are a lot of dynamics and things to think through there. And pending the data, obviously, we'll work through putting that body of evidence together and supporting Sobi in their pricing and reimbursement efforts across each country as they go to launch.

因此，有很多動態和事情需要考慮。顯然，在獲得數據之後，我們將努力匯總這些證據，並支持 Sobi 在各個國家推出定價和報銷服務。

David Lebowitz, Citi.

花旗銀行的 David Lebowitz。

Given the strong early ramp of Tryngolza and FCS. Are you -- how are you thinking about the pricing change that would inevitably happen when it gets approved for severe hyper triglycerides. Is it just going to be a pretty prompt drop or are you going to try to find some way to observe the revenues while you're dropping the price and ramping up?

鑑於 Tryngolza 和 FCS 早期的強勁表現。您如何看待當該藥物被批准用於治療嚴重高甘油三酯時不可避免地會發生的價格變化？價格是否會迅速下降，還是在降價和漲價的同時，您會嘗試尋找某種方法來觀察收入？

Yes. Thanks, David. So our pricing work is ongoing. We've got more work to do there. What we've communicated up to this point is in a disease that has 3 million to 4 million patients.

是的。謝謝，大衛。所以我們的定價工作仍在進行中。我們還有很多工作要做。到目前為止，我們所傳達的訊息是一種有 300 萬到 400 萬患者的疾病。

Typically, the US payers are accepting of a price somewhere in the $10,000 to $20,000 price range. However, when we're looking at sHTG specifically, and the data that Olezarsen can potentially have in the sHTG population, we'd like to go back to the payers and do more testing and understand exactly where this price point could land based on the value to patients and the value to the payers.

通常，美國付款人接受的價格在 10,000 美元到 20,000 美元之間。然而，當我們專門研究 sHTG 以及 Olezarsen 在 sHTG 人群中可能擁有的數據時，我們希望回到付款人那裡並進行更多測試，並根據對患者的價值和對付款人的價值準確了解這個價格點可能落在哪裡。

So there's more work to do. In terms of the execution of that, the FCS population ultimately will be consumed within the sHTG population. So it will become anybody over 500 would be within the sHTG population.

所以還有很多工作要做。就其執行而言，FCS 族群最終將在 sHTG 族群中被消耗。因此，年齡超過 500 的任何人都屬於 sHTG 人口。

So there is a question around how do you execute that and the pricing dynamics? And do you bring the price down. I think regardless of what the decision is there, if we do it immediately or if it's done over time, what we do know is that the sHTG population is quite substantial. And I think what we believe is that we'll be able to maintain enough patient population to be able to continue the revenues that we're producing at the time of an sHTG potential approval.

那麼問題是如何執行這個目標以及定價動態？你能降低價格嗎？我認為，無論做出什麼決定，無論是立即執行還是隨著時間的推移，我們都知道 sHTG 人口相當龐大。我認為，我們相信，我們將能夠維持足夠的患者數量，以便能夠在 sHTG 潛在批准時繼續產生收入。

Jay Olson, Oppenheimer.

傑伊·奧爾森，奧本海默。

Congrats on the quarter, and thank you for providing this update. Now that you have the early successful launch experience with Tryngolza and you have several other launches that you're planning in the near term. How does that impact your thinking about your earlier stage pipeline and deciding between out-licensing earlier-stage assets versus retaining full ownership and launching them independently? And then as a follow-up, can you discuss any plans to build out your ex-US infrastructure for any future global product launches in the long term?

恭喜本季取得佳績，感謝您提供此更新。現在您已經擁有 Tryngolza 早期成功發射的經驗，並且您還計劃在近期進行其他幾次發射。這對您對早期階段產品線的思考以及在授權早期階段資產和保留全部所有權並獨立推出它們之間做出的決定有何影響？然後作為後續問題，您能否討論一下為未來的全球產品發布而長期構建美國以外基礎設施的任何計劃？

Thank you, Jay. We have an abundance of riches when it comes to our late-stage pipeline, our wholly owned pipeline, our partner pipeline, it's a nice combination there and our first independent launch is off to a really good start, and we're expecting Donidalorsen to be equally successful as well as sHTG coming up next year.

謝謝你，傑伊。我們的後製產品線、全資產品線和合作夥伴產品線都十分豐富，這是一個很好的組合，而且我們的第一個獨立產品發布已經有了一個很好的開端，我們預計 Donidalorsen 和明年的 sHTG 也會取得同樣的成功。

With that said, our research organization is incredibly innovative and prolific. We have to continue to bring in potentially transformational medicines continuously into the early-stage pipeline and bring them to Phase III development in due course. Our focus remains, as we set out 5 years ago, 5.5 years ago, to do is to prioritize the wholly owned pipeline. We'll continue to do so, and we will focus on cardiology and cardio metabolic diseases as well as neurology.

話雖如此，我們的研究機構非常具有創新精神和成果。我們必須繼續將具有轉化潛力的藥物持續引入早期研發管線，並在適當的時候將其帶入第三階段開發。我們的重點仍然是，正如我們 5 年前、5.5 年前所製定的那樣，優先考慮全資擁有的管道。我們將繼續這樣做，並將重點放在心臟病學、心臟代謝疾病以及神經病學。

We will always have room for exceptions like (inaudible), we have such an excellent looking drug like Donidalorsen, but those will be our focus. Those areas will be our focus. And it will be the priority. With that said, we still need to ensure that we live within our means. We have -- our resources are limited.

我們總是會有例外的餘地，例如（聽不清楚），我們有像 Donidalorsen 這樣看起來非常出色的藥物，但這些將是我們的重點。這些領域將是我們的重點。這將是優先事項。話雖如此，我們仍然需要確保量入為出。我們的資源是有限的。

We are committed to achieving positive cash flow in the next few years. And although we will prioritize our wholly owned pipeline early stage through Phase III development, there will always be assets that either are outside of our means or outside of our priority areas where we will make decisions to partner. A lot of interest in partnering with Ionis these days. Our platform is delivering over and over again.

我們致力於在未來幾年實現正現金流。儘管我們將優先考慮我們全資擁有的早期到第三階段的開發管道，但總會有一些資產超出我們的能力範圍或超出我們的優先領域，我們將決定與這些資產進行合作。最近，很多人對與 Ionis 合作很感興趣。我們的平台正在一次又一次地交付成果。

A great example of that is the transaction that we did earlier this year. (inaudible) with [Ono], $280 million upfront. And we did that because it's outside of our areas of focus. Hematology is not a focused area for us. So you'll see us continue to partner, but that's not our priority.

一個很好的例子就是我們今年早些時候與[Ono]進行的交易（聽不清楚），預付了 2.8 億美元。我們這樣做是因為它超出了我們的關注範圍。血液學不是我們的重點領域。所以你會看到我們繼續合作，但這不是我們的首要任務。

Our priority is our wholly owned pipeline early to late stage and our launches. With respect to outside the US, I'd like to just put that one on pause. We're thrilled with the early launch of Tryngolza, and we're looking forward to Donidalorsen and sHTG launches in the US. And we'll know when it's fine to emerge from the US and maybe start building external or ex-US commercial infrastructure.

我們的首要任務是全資擁有從早期到晚期的管道以及我們的產品發布。對於美國以外的地區，我想暫停這項措施。我們對 Tryngolza 的早期推出感到非常興奮，我們期待 Donidalorsen 和 sHTG 在美國的推出。我們將知道何時可以脫離美國並開始建立外部或美國以外的商業基礎設施。

But now is not in time to be distracting to that. We need to get these launches right. We're committed to get these launches right, and we'll do so. With that said, we, of course, as internally on when and what that asset might be that we emerge from the US market with but we're in the early inning of those discussions.

但現在還不是分心的時候。我們需要正確完成這些發射。我們致力於正確完成這些發布，我們將會做到這一點。話雖如此，我們當然會在內部討論何時以及從美國市場推出何種資產，但我們仍處於討論的初期階段。

Super helpful. Congrats again on the launch.

非常有幫助。再次恭喜發表會成功舉行。

Akash Tewari, Jefferies.

Akash Tewari，傑富瑞。

This is Aki on for Akash Tewari. So in the BALANCE study, it looks like there was a kind of leaked through towards the end of the study in the 80-milligram arm in a patient who did have triglycerides lowered on the drug whereas placebo events seem to cluster earlier on in the first half of the study. I understand it's really small in here, but how do you have ESSENCE some sense of how blinded events are tracking in CORE 1 and 2 how confident are you that this kind of variability won't be a swing factor on AP powering in CORE 1 and 2?

這是 Akash Tewari 的 Aki。因此，在 BALANCE 研究中，似乎在研究結束時，80 毫克組的患者中出現了某種洩漏，該患者的三酸甘油酯在服藥後確實降低了，而安慰劑事件似乎在研究的前半部分聚集在一起。我知道這裡真的很小，但是你如何讓 ESSENCE 了解盲目事件在 CORE 1 和 2 中的追蹤情況，你有多大信心這種變化不會成為 CORE 1 和 2 中 AP 供電的搖擺因素？

I'll start and then Eugene, please jump in. We're doing everything we can to power -- to increase the power for AP in our study possible. AP analysis will be combined CORE and CORE2. And will be at the 12-month time point. That's correct, right, Eugene?

我先開始，然後有請尤金加入。我們正在盡一切努力來增強我們研究中 AP 的力量。AP分析將結合CORE和CORE2。並將處於12個月的時間點。沒錯，對吧，尤金？

So although the primary endpoint for triglycerides is six months. The AP secondary endpoint will be in 12 months and with CORE and CORE2 combined. So we'll have the -- what we're trying to do is maximize time and maximize patient numbers.

因此，儘管三酸甘油酯的主要終點是六個月。AP 次要終點將在 12 個月內，並將 CORE 和 CORE2 結合起來。因此，我們要做的是最大限度地利用時間並最大限度地增加患者數量。

The Maximal Power will be achieved by combining CORE and CORE2 and ensuring that the (inaudible) much larger than to (inaudible)

最大功率將透過結合 CORE 和 CORE2 來實現，並確保（聽不清楚）遠大於（聽不清楚）

Debjit Chattopadhyay, Guggenheim Partners.

古根漢合夥人公司 (Guggenheim Partners) 的 Debjit Chattopadhyay。

I'm just wondering if the second interim analysis in the LPA Horizon study has happened already, and I believe this was after 745 events?

我只是想知道 LPA Horizo​​n 研究中第二次中期分析是否已經進行，我相信這是在 745 次事件之後？

Yes, it has, and there are no more interim analyses planned for the pelacarsen HORIZON study. So we're fully expecting that study to read out in the first half of next year. And we're very much looking to sell the thermalysis that we completed.

是的，並且沒有計劃對 pelacarsen HORIZON 研究進行更多中期分析。因此，我們完全期待這項研究結果能在明年上半年公佈。我們非常希望能出售我們完成的熱分析成果。

So with that, I think we'll close the call. I'd like to thank everybody for joining us today. We look forward to building on our strong momentum throughout the year, sharing additional achievements, progress along the way and -- so next time we talk. Thank you again for joining, and have a great day, everybody.

因此，我想我們可以結束通話了。我要感謝大家今天的出席。我們期待全年保持強勁勢頭，分享更多成就和進步——下次我們再談。再次感謝大家的加入，祝福大家有個愉快的一天。