Ionis Pharmaceuticals, Inc. (IONS) 2026 Q3 法說會逐字稿

Good morning, and welcome to Ionis' third-quarter 2026 financial results conference call. As a reminder, today's event 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 off the call. Please begin.

早安，歡迎參加 Ionis 2026 年第三季財務業績電話會議。提醒各位，今天的活動將會錄音。此刻，我想把電話交給投資人關係資深副總裁 Wade Walke 來開場。請開始。

Thank you, Chris. 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.

謝謝你，Chris。在開始之前，我鼓勵大家前往 Ionis 官網的投資人專區，查看我們今天將討論的新聞稿與相關財務表格，包括 GAAP 與非 GAAP 財務數據的調節表。我們認為非 GAAP 財務結果更能反映我們業務的經濟實質，以及我們管理業務的方式。我們也已在網站上張貼了配合今天電話會議的簡報投影片。

With me this morning are Brett Monia, Chief Executive Officer; Kyle Jenne, Chief Global Product Strategy Officer; Holly Kordasiewicz, Chief Development Officer; and Beth Hougen, Chief Financial Officer. 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. As a result, you are cautioned not to rely on these forward-looking statements. I encourage you to consult the risk factors contained in our SEC filings for additional detail.

今天早上與我一同出席的有：執行長 Brett Monia；全球產品策略長 Kyle Jenne；開發長 Holly Kordasiewicz；以及財務長 Beth Hougen。我想請各位注意第 3 張投影片，其中包含我們的前瞻性陳述聲明。在本次電話會議中，我們將做出以前瞻性陳述為主的發言，這些陳述係基於我們目前的預期與信念。這些陳述受到若干風險與不確定性影響，我們的實際結果可能會有重大差異。因此，提醒各位不要依賴這些前瞻性陳述。我也鼓勵各位查閱我們向 SEC 提交文件中的風險因素，以取得更多細節。

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

接下來，我把電話交給 Brett。

Thanks, Wade. Good morning, everyone, and thank you for joining us on today's call. Through the first three quarters of 2026, Ionis has continued to evolve and grow as a commercial stage biotechnology company, achieving numerous important milestones. In addition, TRYNGOLZA for FCS and DAWNZERA for HAE, our Ionis-owned commercial portfolio now includes TRYNGOLZA for severe hypertriglyceridemia, or sHTG, our first launch in a large patient population, and ZANVASTRO, our first independent launch in neurology.

謝謝，Wade。各位早安，也感謝各位參加今天的電話會議。在 2026 年前三季，Ionis 持續演進並成長為一家處於商業化階段的生技公司，達成多項重要里程碑。此外，除了用於 FCS 的 TRYNGOLZA 與用於 HAE 的 DAWNZERA 之外，我們 Ionis 自有的商業化產品組合如今也包含用於重度高三酸甘油脂血症（severe hypertriglyceridemia，sHTG）的 TRYNGOLZA——這是我們首次在大型病患族群中的上市產品——以及 ZANVASTRO——我們在神經領域的首次獨立上市。

Although two recent Phase III readouts did not deliver the outcomes we hoped for, we have achieved a number of other important firsts for patients across our business that position us for further growth. This includes the approval of HIBSAGO for chronic hepatitis B virus in the US and Japan, and positive Phase III results for sefaxersen in IgA nephropathy and ulefnersen in FUS-ALS.

儘管近期兩項第三期試驗讀出未能帶來我們所期望的結果，我們仍在整體業務中為病患達成了其他多項重要的「首次」，並使我們具備進一步成長的定位。其中包括 HIBSAGO 在美國與日本獲准用於慢性 B 型肝炎病毒，以及 sefaxersen 在 IgA 腎病變與 ulefnersen 在 FUS-ALS 的第三期試驗正面結果。

Our substantial progress keeps us on track to achieve our full-year 2026 total revenue, operating loss, and cash guidance. And DAWNZERA's continued positive momentum supports our confidence in achieving its 2026 product sales guidance. For TRYNGOLZA, we are lowering our 2026 full-year revenue guidance to approximately $50 million to reflect a more gradual launch ramp than we had anticipated. As the first and only treatment approved to reduce triglycerides and the risk of acute pancreatitis in people living with sHTG, TRYNGOLZA requires HCPs to adopt a new approach to patient care, which takes time.

我們的重大進展使我們仍按計畫達成 2026 全年總營收、營業虧損與現金指引。而 DAWNZERA 持續的正向動能，也支持我們對達成其 2026 年產品銷售指引的信心。至於 TRYNGOLZA，我們將 2026 全年營收指引下調至約 5,000 萬美元，以反映上市爬坡速度較我們原先預期更為循序漸進。作為首個且目前唯一獲准可降低 sHTG 患者三酸甘油脂並降低急性胰臟炎風險的治療，TRYNGOLZA 需要醫療照護專業人員（HCP）採用新的病患照護方式，而這需要時間。

In these early days, we are encouraged by the fundamentals underlying the launch, including strong physician enthusiasm. We are refining our launch tactics to translate this enthusiasm into action. We have identified key executional priorities and implemented specific initiatives across these priorities, which Kyle will discuss in detail.

在上市初期，我們對支撐上市表現的基本面感到鼓舞，其中包括醫師高度的熱忱。我們正在精進上市策略，以將這份熱忱轉化為實際行動。我們已辨識關鍵的執行優先事項，並在各項優先事項上推動具體措施，Kyle 將會詳細說明。

Importantly, we remain confident in TRYNGOLZA's multibillion dollar peak sales potential. Beyond TRYNGOLZA, Kyle will provide further perspective on DAWNZERA and share initial insights on ZANVASTRO. Holly will then go over our recent pipeline progress, and Beth will review our third-quarter results and outlook for the rest of 2026. And with that, I'll turn the call over to Kyle.

重要的是，我們仍對 TRYNGOLZA 具備數十億美元等級的峰值銷售潛力充滿信心。除了 TRYNGOLZA 之外，Kyle 也將進一步說明 DAWNZERA，並分享對 ZANVASTRO 的初步觀察。接著 Holly 會回顧我們近期的研發管線進展，Beth 則會檢視第三季業績與 2026 年剩餘期間的展望。接下來，我把電話交給 Kyle。

Thank you, Brett. I'd like to start by recognizing our highly engaged commercial team for their dedication to bringing important medicines to patients. Their deep expertise, strong commitment to each of our launches, and clear priorities to expand physician adoption and help patients access treatment gives us confidence in our ability to drive growth across our commercial portfolio.

謝謝你，Brett。我想先肯定我們高度投入的商業團隊，他們致力於將重要藥物帶給病患。他們深厚的專業、對每一項上市產品的堅定承諾，以及清楚的優先事項——擴大醫師採用並協助病患取得治療——讓我們對推動整體商業化產品組合的成長充滿信心。

Following TRYNGOLZA's June approval for sHTG, HCPs continue to express strong enthusiasm for TRYNGOLZA's compelling clinical profile, including placebo-adjusted mean reductions in triglycerides of up to 72% and a favorable safety and tolerability profile. These triglyceride reductions resulted in a profound reduction in acute pancreatitis events by up to 91%.

在 TRYNGOLZA 於 6 月獲准用於 sHTG 之後，HCP 持續對 TRYNGOLZA 具吸引力的臨床特性表達高度熱忱，包括相較安慰劑校正後的三酸甘油脂平均降幅最高可達 72%，以及良好的安全性與耐受性表現。這些三酸甘油脂的降低，帶來急性胰臟炎事件最高可達 91% 的顯著下降。

Physicians also appreciate the dosing flexibility and are prescribing both the 50- and 80-milligram doses, allowing them to tailor treatment to individual patient needs. For patients, TRYNGOLZA offers the convenience of a once monthly autoinjector that can be self-administered in about 10 seconds. We are seeing HCPs prescribe TRYNGOLZA for high-risk sHTG patients who are the focus of our initial commercial efforts. These are patients with triglyceride levels of 880 milligrams per deciliter or higher or 500 or higher with a history of acute pancreatitis or other comorbidities.

醫師也重視給藥劑量的彈性，並同時開立 50 毫克與 80 毫克劑量，使其能依個別病患需求量身調整治療。對病患而言，TRYNGOLZA 提供每月一次的自動注射器便利性，約 10 秒即可自行施打。我們看到 HCP 正在為高風險 sHTG 病患開立 TRYNGOLZA，而這些病患正是我們初期商業化努力的重點。這些病患的三酸甘油脂濃度為每分升 880 毫克或以上，或為 500 或以上且有急性胰臟炎病史或其他共病。

We are also seeing prescribing beyond our initial focus, consistent with the broad sHTG label. Our post-launch market research reinforces HCP's strong intent to prescribe TRYNGOLZA. As we establish a new treatment paradigm, we are focused on translating the strong intent to prescribe into action, with three executional priorities designed to increase prescribing and help patients move efficiently from prescription to treatment.

我們也看到處方超出初期聚焦範圍，這與 sHTG 標籤適應症的廣泛性一致。我們上市後的市場研究再次印證 HCP 對開立 TRYNGOLZA 具有強烈意願。隨著我們建立新的治療典範，我們聚焦於將強烈的處方意願轉化為實際行動，並設定三項執行優先事項，以提升處方量並協助病患更有效率地從開立處方走向實際治療。

First, we are focused on broadening the prescriber base, specifically among high-priority physicians who care for high-risk sHTG patients. We are accelerating our education efforts across these specialists and practice teams to increase their understanding of the burden of sHTG, the risk of acute pancreatitis and TRYNGOLZA's demonstrated ability to reduce that risk.

第一，我們聚焦於擴大開立處方的醫師基礎，特別是在照護高風險 sHTG 病患的高優先級醫師族群中。我們正加速對這些專科醫師與診所團隊的教育推廣，以提升他們對 sHTG 疾病負擔、急性胰臟炎風險，以及 TRYNGOLZA 已證實可降低該風險之能力的理解。

In parallel, we are supporting patient education through HCP conversations with their patients and patient-support program so that people living with sHTG better understand their disease. The importance of treatment, and the role TRYNGOLZA can play in reducing triglycerides and the risk of acute pancreatitis. Our field teams are meeting more frequently with high-priority HCPs who have not yet prescribed to instill a sense of urgency into patient identification and treatment.

同時，我們也透過 HCP 與病患的對話以及病患支持計畫，支援病患教育，讓 sHTG 病友更了解自身疾病。治療的重要性，以及 TRYNGOLZA 在降低三酸甘油脂與急性胰臟炎風險方面可扮演的角色。我們的外勤團隊正更頻繁地與尚未開立處方的高優先級 HCP 會面，以強化病患辨識與治療的急迫感。

The goal is to help physicians incorporate TRYNGOLZA into routine care for appropriate patients. From sHTG approval to the end of September, approximately 1,500 prescribers across all anticipated specialties had prescribed TRYNGOLZA. In the weeks since our field team put these initiatives into action, our initial prescriber base has started to broaden further.

目標是協助醫師將 TRYNGOLZA 納入適當病患的例行照護中。自 sHTG 獲准至 9 月底，涵蓋所有預期專科領域的處方醫師約有 1,500 位曾開立 TRYNGOLZA。自從我們的外勤團隊將這些措施付諸行動後的數週內，我們的初始處方醫師基礎已開始進一步擴大。

Second, we are focused on increasing the depth of prescribing among HCPs who are early adopters of TRYNGOLZA. Since the sHTG launch to the end of September, approximately 24% of prescribers had written more than one prescription. Prescribers want to see how a patient responds to treatment before prescribing more broadly, consistent with how HCPs often adopt new specialty medicines. We saw a similar pattern when we launched in FCS, where physicians became more confident prescribing TRYNGOLZA as they gained experience and observed its impact.

第二，我們專注於提升早期採用 TRYNGOLZA 的醫療照護專業人員（HCP）之處方深度。自 sHTG 上市至九月底，約有 24% 的開立處方者已開立超過一張處方。處方者希望先觀察病人對治療的反應，再更廣泛地開立處方，這與 HCP 採用新型專科藥物的常見方式一致。我們在 FCS 上市時也看到類似模式：隨著醫師累積經驗並觀察到其影響，他們對開立 TRYNGOLZA 的信心提高。

While the sHTG population is much broader, our FCS experience gives us confidence that TRYNGOLZA's novel mechanism of action and groundbreaking patient outcomes can support broader prescribing over time. Our field team is executing on this priority by following up with prescribers to discuss their initial treatment experience and support them in identifying additional patients who may benefit from TRYNGOLZA.

雖然 sHTG 族群更為廣泛，但我們在 FCS 的經驗讓我們有信心，TRYNGOLZA 的新穎作用機轉與突破性的病人治療結果，能隨時間推進而支持更廣泛的處方使用。我們的外勤團隊正透過與處方者追蹤溝通，討論其初始治療經驗，並協助他們辨識可能受益於 TRYNGOLZA 的其他病人，以落實此一優先事項。

Notably, we have seen recent increases in repeat prescribing, suggesting these efforts are starting to have an impact. Third, we are working to make the path from prescription to treatment more efficient. As expected at this early stage of the launch, a majority of TRYNGOLZA prescriptions required a medical exception. Some physicians are hesitant to prescribe newly approved therapies broadly before formal coverage is in place, a pattern seen in other specialty launches, especially in the cardiovascular space.

值得注意的是，我們近期看到重複開立處方有所增加，顯示這些努力開始產生影響。第三，我們正致力於讓從開立處方到開始治療的流程更有效率。如同在上市初期所預期，多數 TRYNGOLZA 處方需要醫療例外核准。在正式給付尚未到位前，一些醫師對於廣泛開立新核准療法仍持保留態度；這種模式在其他專科藥物上市時也曾出現，尤其是在心血管領域。

To address this, our dedicated access team is educating physician offices on the reimbursement process and payer requirements. Additionally, we have a quick-start program that enables patients to begin TRYNGOLZA treatment while coverage is being secured. The program has been well received, with meaningful utilization to date, and we expect it to continue to expand.

為因應此情況，我們專責的給付通路團隊正在教育醫師診所了解報銷流程與付款方要求。此外，我們設有快速啟動（quick-start）計畫，使病人在給付核定期間即可開始 TRYNGOLZA 治療。該計畫迄今反應良好，使用量具實質意義，我們預期其將持續擴大。

Ionis Every Step, our patient support program, also helps eligible patients navigate the insurance process and access treatment. We are working with payers to establish coverage policies, and are making good progress. By the end of September, plans representing 33% of commercial lives had added the sHTG indication for TRYNGOLZA to their formularies. Importantly, all current policies provide coverage aligned with the broad TRYNGOLZA label for adults with triglyceride levels of 500 or higher, extending beyond the high-risk patients who represent our initial commercial focus.

Ionis Every Step（我們的病人支持計畫）也協助符合資格的病人完成保險流程並取得治療。我們正與付款方合作建立給付政策，且進展良好。截至九月底，代表 33% 商業保險涵蓋人數的保險計畫，已將 TRYNGOLZA 的 sHTG 適應症納入其處方集（formulary）。重要的是，所有現行政策皆提供與 TRYNGOLZA 成人適應症標籤一致的給付：三酸甘油脂濃度達 500 或以上者皆可涵蓋，範圍延伸至超出我們初期商業重點之高風險病人。

As payers review the reimbursement policies for TRYNGOLZA, we are on track for additional policies to take effect this year, with more expected throughout 2027. As we address these early launch dynamics, we remain confident in TRYNGOLZA's potential to achieve more than $3 billion in peak annual sales. That confidence begins with the substantial unmet need.

隨著付款方審查 TRYNGOLZA 的報銷政策，我們按計畫推進，預期今年將有更多政策生效，並在 2027 年持續增加。在我們處理這些上市初期動態的同時，我們仍對 TRYNGOLZA 達成超過 30 億美元年峰值銷售額的潛力充滿信心。這份信心首先來自龐大的未被滿足醫療需求。

More than 3 million people in the US have sHTG, including approximately 1 million high-risk sHTG patients. TRYNGOLZA's efficacy, dosing flexibility, and self-administered auto-injector provide a compelling profile for these patients. As we establish a new treatment paradigm and build the market, our priorities are clear: broaden and deepen prescribing, and improve payer access to simplify the path to treatment. While we recognize it will take some time for these initiatives to deliver accelerating prescription volume, we are confident our actions position TRYNGOLZA for future growth.

美國有超過 300 萬人罹患 sHTG，其中約 100 萬人為高風險 sHTG 病人。TRYNGOLZA 的療效、給藥彈性，以及可自行施打的自動注射器，為這些病人提供了具吸引力的產品特性。在我們建立新的治療典範並打造市場之際，我們的優先事項很明確：擴大並加深處方使用，並改善付款方可近性以簡化治療路徑。雖然我們了解這些措施需要一些時間才能帶來處方量加速成長，但我們有信心，我們的行動將使 TRYNGOLZA 具備未來成長的有利定位。

Outside the US, Sobi is continuing to advance the launch in FCS, while preparing for the upcoming anticipated broader launch in sHTG, following the recent positive CHMP opinion. Turning to DAWNZERA. The launch continues to gain momentum, with product sales increasing substantially each quarter since launch. DAWNZERA has continued to capture a meaningful share of the US HAE prophylaxis market, where adoption is largely driven by patients switching therapies.

在美國以外，Sobi 持續推進 FCS 的上市，同時在近期 CHMP 給出正面意見後，為預期即將到來、在 sHTG 的更廣泛上市做準備。接著談 DAWNZERA。上市持續增溫，自上市以來產品銷售每季皆大幅成長。DAWNZERA 持續在美國 HAE 預防市場取得具意義的市占，而其採用主要由病人轉換治療所驅動。

We are seeing a growing base of repeat prescribers alongside adoption by patients with different treatment histories. In addition to growth from patients switching from other prophylactic therapies, we have also seen patients initiate DAWNZERA treatment who were previously only using on-demand treatment or who were treatment naive.

我們看到重複開立處方者的基礎持續擴大，同時也有不同治療歷程的病人開始採用。除了來自病人由其他預防性療法轉換所帶動的成長外，我們也看到先前僅使用按需（on-demand）治療、或先前未曾接受治療（treatment naive）的病人開始啟用 DAWNZERA。

Physician and patient feedback has been positive, highlighting DAWNZERA's strong efficacy and favorable safety, differentiated RNA-targeted mechanism and compelling switch data. Its patient-friendly profile, including dosing every four or eight weeks with a self-administered auto-injector is also resonating with physicians and patients.

醫師與病人的回饋正面，強調 DAWNZERA 具強勁療效與良好安全性、差異化的 RNA 標的作用機轉，以及具說服力的轉換治療數據。其以病人為友善的特性也引起醫師與病人共鳴，包括每四週或八週給藥一次，並可使用自動注射器自行施打。

DAWNZERA has been a key driver of commercial revenue growth through the third quarter. Its growing base of repeat prescribers and adoption across patients with different treatment histories give us confidence in continued growth ahead. Outside the US, DAWNZERA access has continued to expand through our partners. This progress includes the recent approval in Canada and advancement of the European launch with positive reimbursement decisions in multiple countries and additional market access activities underway.

DAWNZERA 一直是推動第三季商業營收成長的關鍵動能。其重複開立處方者基礎持續擴大，且在不同治療歷程的病人中皆有採用，讓我們對未來持續成長更具信心。在美國以外，DAWNZERA 的可近性也透過合作夥伴持續擴大。此進展包括近期在加拿大獲准，以及歐洲上市的推進：多國取得正面的報銷決策，並有更多市場准入活動正在進行。

Turning to ZANVASTRO. The recent approval provides children and adults with Alexander disease, the first FDA-approved disease-modifying treatment for this progressive and often fatal neurological disorder. As planned, we were able to get ZANVASTRO into the channel shortly after approval, and I'm pleased to share that the first patients have received commercial treatment.

接著談 ZANVASTRO。近期的核准為亞歷山大病（Alexander disease）的兒童與成人帶來首個 FDA 核准、可改變疾病進程的治療，適用於這種進行性且常致命的神經系統疾病。如同規劃，我們在核准後不久即讓 ZANVASTRO 進入供應通路，我也很高興分享，首批病人已接受商業用藥治療。

Our launch is centered on four priorities. First, we are working to transition patients receiving ZANVASTRO through the clinical study or expanded access program to commercial therapy while ensuring continuity of care. This will take time as patients await their next quarterly dose, institutions navigate reimbursement and some patients move to treatment centers closer to home.

我們的上市聚焦於四項優先事項。第一，我們正協助將透過臨床研究或擴大使用計畫接受 ZANVASTRO 的病人，轉換至商業治療，同時確保照護的連續性。這將需要時間，因為病人需等待下一次每季給藥、醫療機構需處理報銷流程，且部分病人會轉至離家更近的治療中心。

Second, we are engaging physicians who care for patients already diagnosed with Alexander disease to provide education on ZANVASTRO and support access for appropriate patients. Although exact prevalence is not well understood, the US prevalence is estimated to be approximately 300 people, with about half identified through medical claims.

第二，我們正與照護已確診亞歷山大病病人的醫師互動，提供 ZANVASTRO 的教育並支持合適病人的治療可近性。雖然確切盛行率尚不清楚，但估計美國盛行人數約 300 人，其中約一半可透過醫療理賠資料辨識。

Third, we are raising disease awareness to help identify additional undiagnosed patients. Our focus is on approximately 25 neurology centers, including 12 leukodystrophy centers of excellence, with disease education extending to physicians outside this network. Fourth, we are working with payers and treatment centers to establish coverage and access. ZANVASTRO is administered quarterly by intrathecal injection and reimbursed as a medical benefit. So providing education on the buy-and-bill process is an important part of our launch execution.

第三，我們正提升疾病認知，以協助找出更多尚未診斷的病人。我們的重點鎖定約 25 家神經科中心，其中包括 12 家白質失養症（leukodystrophy）卓越中心，並將疾病教育延伸至此網絡之外的醫師。第四，我們正與付款方及治療中心合作建立給付與可近性。ZANVASTRO 以鞘內注射方式每季給藥一次，並以醫療給付（medical benefit）方式報銷。因此，提供關於「先採購後請款」（buy-and-bill）流程的教育，是我們上市執行的重要一環。

Our Ionis Every Step program for ZANVASTRO is tailored to the Alexander disease community, providing education and assistance, navigating the reimbursement process for patients and families and access and reimbursement support for health care providers and site staff. We expect uptake to increase as patients from our clinical studies and expanded access program transition to commercial treatment. Additional patients are identified and access is established.

我們針對 ZANVASTRO 的 Ionis Every Step 計畫，依亞歷山大病社群需求量身打造，提供教育與協助，協助病人與家屬處理報銷流程，並為醫療照護提供者與院所人員提供可近性與報銷支援。隨著臨床研究與擴大使用計畫中的病人轉換至商業治療，我們預期使用量將增加。同時也將辨識更多病人並建立可近性。

Outside the US, (inaudible) is planning for regulatory filings in the EU and Japan next year, with additional submissions to follow. Across our multiple ongoing launches, our priorities are clear. Our team is focused, energized, and committed to delivering on these priorities for patients.

在美國以外，（聽不清）正規劃於明年在歐盟與日本進行法規申請，後續將有更多送件。在我們多項持續進行的上市工作中，我們的優先事項很明確。我們的團隊專注、充滿動能，並致力於為病人達成這些優先事項。

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

接下來，我把電話會議交給 Holly。

Thanks, Kyle. This quarter, we made important progress across our wholly owned and partnered pipeline, advancing medicines with the potential to transform care for people with serious diseases. At the European Society of Cardiology Congress in August, we presented new data, reinforcing our leadership in the management of severe hypertriglyceridemia. This included positive long-term data for TRYNGOLZA, the first and only approved treatment to reduce triglycerides and the risk of acute pancreatitis and adults with sHTG. In the CORE and CORE2 open-label extension study, TRYNGOLZA delivered substantial and sustained triglyceride reductions for up to two years of treatment.

謝謝你，Kyle。本季我們在自有與合作的研發管線上都取得了重要進展，推進多項有潛力改變重症患者照護的藥物。在 8 月的歐洲心臟病學會（ESC）年會上，我們發表了新的數據，進一步鞏固我們在重度高三酸甘油酯血症管理領域的領導地位。其中包括 TRYNGOLZA 的正向長期數據；TRYNGOLZA 是首個且目前唯一獲核准、可降低三酸甘油酯並降低成人 sHTG 急性胰臟炎風險的治療。在 CORE 與 CORE2 的開放標籤延伸研究中，TRYNGOLZA 在長達兩年的治療期間帶來顯著且持續的三酸甘油酯降低。

More than 90% of patients achieved levels below 500 milligrams per deciliter, and nearly 60% achieved normal levels. Patients also achieved persistent reductions in the risk of acute pancreatitis, and the safety and tolerability profile remained favorable. These findings further strengthen TRYNGOLZA's clinical profile, reinforcing its durability and long-term safety profile, both of which are essential when treating a chronic disease like sHTG.

超過 90% 的患者達到低於每分升 500 毫克的水準，且近 60% 達到正常水準。患者的急性胰臟炎風險也持續降低，安全性與耐受性概況仍然良好。這些發現進一步強化 TRYNGOLZA 的臨床特性，凸顯其療效持久性與長期安全性概況；在治療如 sHTG 這類慢性疾病時，兩者都至關重要。

Beyond sHTG, our leading neurology pipeline continues to make exceptional progress, highlighted by the recent approval of ZANVASTRO. ZANVASTRO is the first and only disease-modifying treatment for Alexander disease, an ultrarare, progressive and often fatal neurological disorder. We were pleased that the FDA approved ZANVASTRO with a broad label for children and adults. This approval builds on our long history of discovering and developing first-in-class treatments for rare neurological diseases.

除 sHTG 之外，我們領先的神經科學研發管線也持續取得卓越進展，近期 ZANVASTRO 的核准即為亮點。ZANVASTRO 是首個且目前唯一可改變疾病進程的 Alexander 病治療；Alexander 病是一種極罕見、進行性且常致命的神經系統疾病。我們很高興 FDA 以涵蓋兒童與成人的廣泛適應症標籤核准 ZANVASTRO。此項核准建立在我們長期致力於發現與開發同類首創（first-in-class）罕見神經疾病治療的歷史之上。

Today, our leading neurology pipeline includes seven wholly owned medicines targeting challenging diseases such as Dravet syndrome, Prion disease and Angelman syndrome. In light of the recent results from the ASPIRE study of apazunersen, our view of obudanersen for Angelman syndrome and our design of the Phase III REVEAL study.

目前，我們領先的神經科學研發管線包含 7 項自有藥物，鎖定如 Dravet 症候群、朊蛋白疾病（Prion disease）與 Angelman 症候群等具挑戰性的疾病。鑑於 apazunersen 的 ASPIRE 研究近期結果，我們重新審視 obudanersen 用於 Angelman 症候群的看法，以及我們對第三期 REVEAL 研究的設計。

Obudanersen is the product of Ionis chemistry and know-how in delivering breakthrough treatments for CNS diseases, experiences that led to SPINRAZA, QALSODY and ZANVASTRO, groundbreaking approved medicines for devastating neurological diseases.

Obudanersen 是 Ionis 化學平台與在中樞神經系統（CNS）疾病突破性治療遞送方面專業能力的成果；這些經驗促成了 SPINRAZA、QALSODY 與 ZANVASTRO 等具里程碑意義、已獲核准用於嚴重神經疾病的藥物。

We are evaluating an 80-milligram dose in REVEAL, which was the maximum dose we evaluated in the Phase I/II HALOS open-label extension study. Based on our data, we believe that the apazunersen dose in ASPIRE was not high enough to be efficacious. Equally important is our choice of endpoint. The primary endpoint in REVEAL study is expressive communication measured using the Bayley 4. We selected this endpoint because expressive communication brings stable and natural history data, but show robust improvement with obudanersen treatment [HALOS].

我們在 REVEAL 中評估 80 毫克劑量，這是我們在第一/二期 HALOS 開放標籤延伸研究中評估的最高劑量。根據我們的數據，我們認為 ASPIRE 中 apazunersen 的劑量不足以產生療效。同樣重要的是我們對終點指標的選擇。REVEAL 研究的主要終點為以 Bayley 4 量表衡量的表達性溝通能力。我們選擇此終點，因為表達性溝通具備穩定且有自然病程（natural history）數據可對照，但在接受 obudanersen 治療後可呈現明顯改善 [HALOS]。

With up to two years of treatment data in HALOS, we continue to see durable improvements in expressive communication and other functional domains relative to natural history. We plan to publish an update of our long-term extension study soon and look forward to Phase III results in the second half of next year.

在 HALOS 中累積長達兩年的治療數據後，相較於自然病程，我們仍持續看到表達性溝通及其他功能領域的持久改善。我們計畫近期發表長期延伸研究的更新結果，並期待明年下半年公布第三期結果。

While our partner pipeline had two Phase III disappointments, it also delivered recent approvals and two positive Phase III readouts since our last update. HIBSAGO, partnered with GSK, was recently approved in the US and Japan as the first-in-class treatment offering unprecedented functional cure rates in chronic hepatitis B, a disease affecting millions of people worldwide.

雖然我們的合作夥伴研發管線有兩項第三期試驗未達預期，但自上次更新以來也帶來近期核准，以及兩項正向的第三期讀出結果。與 GSK 合作的 HIBSAGO 近期已在美國與日本獲核准，作為同類首創治療，為慢性 B 型肝炎提供前所未有的功能性治癒率；此疾病影響全球數百萬人。

Sefaxersen, partnered with Roche, met the primary endpoint in the interim analysis of the Phase III IMAgINATION study in adults with IgA nephropathy, with favorable safety and tolerability consistent with prior data. Roche plans to share the data with health authorities, with a potential US approval next year.

與 Roche 合作的 sefaxersen，在 IgA 腎病變成人患者的第三期 IMAgINATION 研究期中分析中達成主要終點，且安全性與耐受性良好，與既有數據一致。Roche 計畫與衛生主管機關分享數據，並可能於明年在美國獲核准。

We also announced positive Phase III FUSION top line results for ulefnersen, partnered with Otsuka in people with FUS-ALS, a rare and rapidly progressive form of ALS that affects a broad age range. These results bring us closer to what could be the first disease-modifying treatment for FUS-ALS.

我們也公布與大塚（Otsuka）合作的 ulefnersen 之第三期 FUSION 試驗主要結果（top line）為正向，研究對象為 FUS-ALS 患者；FUS-ALS 是一種罕見且進展迅速的 ALS 亞型，影響年齡範圍廣泛。這些結果使我們更接近可能成為首個可改變 FUS-ALS 疾病進程的治療。

Looking ahead, our pipeline offers multiple opportunities to build on our progress. Next year, in addition to the Phase III results for obudanersen, our growing mid-stage pipeline of wholly owned medicines are advancing to a proof-of-concept data readout that could enable us to further expand our late-stage pipeline. We also anticipate further regulatory progress that will expand the global reach of our marketed medicines.

展望未來，我們的研發管線提供多項機會以延續並擴大既有進展。明年，除 obudanersen 的第三期結果外，我們持續成長的中期自有藥物管線也將推進至概念驗證（proof-of-concept）數據讀出，這可能使我們得以進一步擴充後期研發管線。我們也預期將有更多法規進展，擴大已上市藥物的全球觸及範圍。

This includes the planned launch of TRYNGOLZA for sHTG in the EU and the continued launch of HIBSAGO and potential approvals and launches for sefaxersen and ulefnersen next year. Our recent progress reinforces the strength of our R&D engine and our confidence in the next wave of opportunities to reach more patients.

其中包括計畫在歐盟推出用於 sHTG 的 TRYNGOLZA、持續推進 HIBSAGO 的上市，以及明年 sefaxersen 與 ulefnersen 可能的核准與上市。我們近期的進展再次印證研發引擎的實力，並強化我們對下一波機會、以觸及更多患者的信心。

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

接下來，我把電話會議交給 Beth。

Thank you, Holly. The substantial progress we've made this year is reflected in our third-quarter financial results, with growing revenue across our diverse revenue streams and continued investment in our launches and pipeline to drive future growth. And recent advances in several late-stage partnered programs provide additional opportunities ahead.

謝謝你，Holly。我們今年取得的重大進展反映在第三季財務結果上：多元收入來源全面成長，同時持續投資於產品上市與研發管線，以推動未來成長。此外，數項後期合作計畫的近期進展也帶來更多前瞻性機會。

Overall, our results and outlook keep us on track to achieve our full-year total revenue, operating loss and cash guidance. Revenues in the third quarter and year-to-date were $243 million and $757 million, respectively, representing year-over-year growth of 55% and 64% compared to the same period last year, excluding the $280 million onetime payment we received for sapablursen last year.

整體而言，我們的業績表現與展望使我們維持在達成全年總營收、營業虧損與現金指引的軌道上。第三季與年初至今的營收分別為 2.43 億美元與 7.57 億美元；若排除去年因 sapablursen 收到的一次性 2.80 億美元款項，與去年同期相比分別年增 55% 與 64%。

Commercial revenue increased to $136 million in the third quarter and $363 million year to date, up 18% and 23%, respectively, from the same period last year. Notably, commercial revenue outpaced R&D revenue in the third quarter. These increases were driven primarily by DAWNZERA, with product sales of $37 million in the third quarter and $79 million year to date.

商業化營收於第三季增至 1.36 億美元、年初至今為 3.63 億美元，較去年同期分別成長 18% 與 23%。值得注意的是，第三季商業化營收超越研發（R&D）營收。這些成長主要由 DAWNZERA 帶動，第三季產品銷售額為 3,700 萬美元、年初至今為 7,900 萬美元。

DAWNZERA product sales have increased each quarter since launch, including increasing approximately 40% in the third quarter. TRYNGOLZA generated product sales of $9 million in the third quarter, its first full quarter following the approval for sHTG, and $41 million year to date. As Brett mentioned, we are lowering our full year TRYNGOLZA net product sales guidance to approximately $50 million.

DAWNZERA 自上市以來每季產品銷售額皆持續成長，其中第三季約成長 40%。TRYNGOLZA 在第三季創造 900 萬美元產品銷售額，這是其因 sHTG 核准後的首個完整季度；年初至今為 4,100 萬美元。如 Brett 所提，我們將全年 TRYNGOLZA 淨產品銷售額指引下調至約 5,000 萬美元。

With the launch underway, our third-quarter results also included initial product revenues for ZANVASTRO. Our partner portfolio continued to serve as a financial amplifier, generating revenue of $107 million in the third quarter and $394 million year to date, reflecting milestones for multiple partners as programs advanced.

隨著上市推進，我們第三季結果亦納入 ZANVASTRO 的初始產品營收。合作夥伴組合持續發揮財務放大器作用，第三季貢獻營收 1.07 億美元、年初至今為 3.94 億美元，反映多家合作夥伴計畫推進所帶來的里程碑收入。

Operating expenses increased as expected in the third quarter and year to date compared to the same period last year, driven by investments in the commercialization of TRYNGOLZA, DAWNZERA, and ZANVASTRO. We also continued to invest in our advancing wholly owned pipeline supporting the next wave of opportunities. We ended the third quarter with $1.9 billion in cash and investments.

如預期，第三季與年初至今的營業費用較去年同期增加，主要由 TRYNGOLZA、DAWNZERA 與 ZANVASTRO 商業化投資所驅動。我們也持續投資於推進中的自有研發管線，以支撐下一波機會。第三季末，我們持有現金與投資合計 19 億美元。

Our year-to-date results and fourth-quarter outlook keep us on track to achieve our 2026 total revenue of $875 million to $900 million, underpinned by strong momentum from DAWNZERA and substantial contributions from our partnered programs. We continue to expect DAWNZERA net product sales of $110 million to $120 million.

我們年初至今的業績表現與第四季展望，使我們持續按計畫達成 2026 年總營收 8.75 億至 9.00 億美元的目標，這主要受惠於 DAWNZERA 的強勁動能以及合作計畫的重大貢獻。我們仍預期 DAWNZERA 淨產品銷售額為 1.10 億至 1.20 億美元。

As we establish a new treatment paradigm in sHTG, our updated TRYNGOLZA net product sales guidance reflects a more gradual initial launch. Our guidance also takes into account the expansion of our Quick Start program, which helps patients begin treatment while coverage is being secured. We expect this program will support both broader adoption and revenue growth over time as patients transition to paid therapy. Importantly, we remain confident in TRYNGOLZA's potential to deliver sustained long-term revenue growth and multibillion dollar peak sales.

隨著我們在 sHTG 建立新的治療典範，我們更新後的 TRYNGOLZA 淨產品銷售指引反映了較為循序漸進的初期上市節奏。我們的指引亦納入 Quick Start 計畫的擴大，該計畫可在保險給付核准期間協助病患先行開始治療。我們預期此計畫將在病患轉為自費/付費治療後，隨時間推進同時支持更廣泛的採用與營收成長。重要的是，我們仍對 TRYNGOLZA 帶來可持續的長期營收成長與數十億美元峰值銷售的潛力充滿信心。

Our partner programs also continued to deliver meaningful value through R&D revenue and royalty streams. For example, in the fourth quarter, we earned a $30 million milestone payment following HIBSAGO's recent US approval, and we expect to begin earning royalties as the global launch gets underway. On the expense side, we continue to expect full-year operating expenses to increase in the low teens percentage range compared to last year, driven primarily by sales and marketing investments in our ongoing launches.

我們的合作計畫也持續透過研發（R&D）收入與權利金收入帶來顯著價值。例如，在第四季，因 HIBSAGO 近期獲得美國核准，我們取得 3,000 萬美元的里程碑款，且隨著全球上市展開，我們預期將開始取得權利金收入。在費用方面，我們仍預期全年營運費用相較去年將以低十位數百分比區間成長，主要由我們持續上市推進所需的銷售與行銷投資所驅動。

We project R&D expenses to remain consistent with last year as several late-stage studies conclude and resources are deployed across our advancing wholly owned pipeline. With strong revenue generation from multiple sources and prudent expense management, we continue to project a non-GAAP operating loss of $425 million to $475 million. This is similar to our 2025 operating loss after adjusting for the onetime sapablursen license.

我們預估研發費用將與去年大致持平，因多項後期研究即將結束，資源也將配置於我們持續推進的自有產品線（wholly owned pipeline）。在多元來源的強勁營收挹注與審慎的費用管理下，我們仍預期非 GAAP 營業虧損為 4.25 億至 4.75 億美元。在調整一次性 sapablursen 授權影響後，該水準與我們 2025 年的營業虧損相近。

And finally, we continue to project a year-end cash balance of greater than $1.6 billion. Our financial outlook reflects the strength of our diversified revenue streams, with growing commercial revenues and contributions from our partnered programs. It also reflects investments in our advancing pipeline to drive continued growth. Importantly, we remain committed to achieving sustained positive cash flow and continuing to create value for patients and shareholders. And with that, I'll turn the call back over to Brett.

最後，我們仍預期年底現金餘額將高於 16 億美元。我們的財務展望反映了多元化收入來源的強勁表現，包括成長中的商業化收入以及合作計畫的貢獻。同時也反映我們對推進中產品線的投資，以帶動持續成長。重要的是，我們仍致力於達成可持續的正向現金流，並持續為病患與股東創造價值。接下來我把電話交回給 Brett。

Thank you, Beth. Our growing commercial portfolio and the continued progress across our rich diverse pipeline demonstrate the strength of Ionis' science and its potential to address the significant unmet needs of patients. For TRYNGOLZA, we remain confident in its multibillion-dollar peak sales potential, and we're taking action to translate HCP enthusiasm into broader adoption.

謝謝你，Beth。我們不斷成長的商業化產品組合，以及多元且豐富的產品線所取得的持續進展，展現了 Ionis 科學實力，以及其滿足病患重大未被滿足需求的潛力。就 TRYNGOLZA 而言，我們仍對其數十億美元峰值銷售潛力充滿信心，並正採取行動，將醫療照護專業人員（HCP）的熱忱轉化為更廣泛的採用。

DAWNZERA continues to demonstrate a significant growth trajectory, and ZANVASTRO extends our leadership in neurology. With a growing portfolio of marketed medicines, a rich pipeline, and a team with the capabilities to deliver, we are executing on multiple value drivers for continued growth. We're confident in Ionis' outlook and are committed to turning these opportunities into sustained positive cash flow and creating lasting value for patients and our shareholders.

DAWNZERA 持續展現顯著的成長軌跡，而 ZANVASTRO 進一步鞏固我們在神經科領域的領導地位。憑藉日益擴大的已上市藥物組合、豐富的產品線，以及具備交付能力的團隊，我們正推動多項價值驅動因素以實現持續成長。我們對 Ionis 的前景充滿信心，並致力於將這些機會轉化為可持續的正向現金流，為病患與股東創造長期價值。

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

接下來，我們開放提問。

(Operator Instructions) Jay Olson, Oppenheimer.

(接線員指示) Jay Olson，Oppenheimer。

For TRYNGOLZA, could you help separate physician adoption from the operational steps between prescription and paid treatment? And maybe talk about where you see the greatest friction today, in terms of identifying appropriate patients or securing coverage or converting prescriptions into starts? And which leading indicators should we keep an eye on?

針對 TRYNGOLZA，你能否協助區分醫師採用情況與從開立處方到開始付費治療之間的作業流程步驟？也請談談你認為目前最大的摩擦點在哪裡：是在辨識合適病患、取得給付核准，或是將處方轉換為實際開始治療？以及我們應該關注哪些領先指標？

Thanks, Jay. Kyle, do you want to touch on the key challenges that we're addressing for TRYNGOLZA launch and as well as the KPIs?

謝謝你，Jay。Kyle，你要不要談談我們在 TRYNGOLZA 上市推進中正在處理的關鍵挑戰，以及相關 KPI？

Yes. Thanks, Jay. Let me first start by addressing the market overall. There is a significant unmet need here in this market, obviously, greater than 3 million patients overall and greater than 1 million that are at high risk for sHTG, which is our initial launch focus. We've got a differentiated label. We've got very strong clinical data, including a 72% reduction in triglyceride levels, up to 91% reduction in pancreatitis events and a number needed to treat of approximately 20 in the overall patient population and four in the highest risk patient population.

好的。謝謝你，Jay。我先從整體市場談起。這個市場存在顯著的未被滿足需求，整體病患人數顯然超過 300 萬，其中超過 100 萬人屬於 sHTG 高風險族群，這也是我們初期上市的重點。我們擁有具差異化的適應症標示（label）。我們也有非常強勁的臨床數據，包括三酸甘油酯（triglyceride）水準降低 72%、胰臟炎（pancreatitis）事件最多降低 91%，以及在整體病患族群中約 20 的治療必要數（number needed to treat），在最高風險病患族群中則為 4。

The focus here, obviously, in the first quarter, is to build a market with the first-of-its-kind treatment in this large population. We had approximately 1,500 prescribers as of the end of September. 24% of those prescribers had written more than one prescription. And this is the only approved treatment right now to reduce triglycerides and the risk of acute pancreatitis in people living with sHTG.

顯然，第一季的重點是在這個龐大族群中，為同類首創（first-of-its-kind）的治療建立市場。截至 9 月底，我們約有 1,500 位開立處方的醫師。其中 24% 的醫師開立過不只一張處方。而目前這是唯一獲核准、可降低 sHTG 病患三酸甘油酯並降低急性胰臟炎風險的治療。

So it's taking some time for HCPs to adopt this new approach, to see the response from patients once they put the patient on to TRYNGOLZA for the first time. And we've got a couple of key priorities that I referenced in my remarks, but I'll reiterate. First and most importantly is to get more HCPs to prescribe for the first time so that they can gain this experience with a new modality and see the outcome in that patient that they're treating. Number two, those that have prescribed one time, we're trying to broaden the depth of prescribing, helping them to understand additional patients in their practice that might be able to benefit, so deepening that base and increasing repeat prescribing.

因此，醫療照護專業人員（HCP）採用這種新方法需要一些時間，尤其是在他們第一次讓病患使用 TRYNGOLZA 後，觀察到病患反應之後。我們有幾項我在發言中提到的關鍵優先事項，我再重申一次。第一且最重要的是，讓更多 HCP 第一次開立處方，讓他們能累積對新治療模式的使用經驗，並在其治療的病患身上看到結果。第二，對於已經開立過一次處方的醫師，我們希望擴大其開立深度，協助他們辨識診所中其他可能受益的病患，進一步加深基礎並提高重複開立。

And then the access component. And Jay, you were just asking about that. We had 33% of commercial plans come on board in the first quarter of the sHTG launch. So they obviously have added sHTG to their policy and included the 50-milligram dose along with the 80-milligram dose, which is important for HCPs to have dosing flexibility, which they very much appreciate with the profile of the drug.

接著是可近性（access）的部分。Jay，你剛剛也問到這點。在 sHTG 上市的第一季，我們已有 33% 的商業保險計畫加入。因此他們顯然已將 sHTG 納入其給付政策，並同時納入 50 毫克劑量與 80 毫克劑量；這對 HCP 來說很重要，因為能提供劑量調整的彈性，而他們也非常重視這項藥物特性。

So our real focus here is on those three components, getting HCPs to gain initial experience, those that gain experience to treat more patients. And then finally, the ease of access and getting payer policies to come on board, which is exactly what we're executing against.

所以我們真正的重點就在這三個面向：讓 HCP 取得初次使用經驗、讓已取得經驗者治療更多病患。最後則是提升可近性，推動付款方（payer）給付政策到位，而這正是我們目前的執行重點。

I continue to be very encouraged by the enthusiasm from HCPs as we do build this market with the compelling profile that TRYNGOLZA has. And the early experiences that we have in the first quarter, we want to build on that and make sure that, that continues through the end of this year. And 2027 is going to be a very important year for us as we continue to establish this brand in a new market.

在我們以 TRYNGOLZA 具吸引力的產品特性來建立這個市場的過程中，我仍然非常受到 HCP 熱忱的鼓舞。而我們在第一季的早期經驗，我們希望在此基礎上持續擴大，並確保這股動能能延續到今年年底。2027 年將是非常關鍵的一年，因為我們將持續在新市場中建立這個品牌。

And Jay, the metrics to continue to monitor are really the ones that we highlighted so far today. I mean, our prescriber base, repeat prescribers, payer coverage and, of course, quarterly revenue.

Jay，持續追蹤的指標其實就是我們今天到目前為止強調的那些。也就是我們的開立醫師基礎、重複開立者、付款方給付覆蓋率，當然還有每季營收。

Yanan Zhu, Wells Fargo.

Yanan Zhu，富國銀行。

I was wondering -- and thanks for the color on the TRYNGOLZA launch. I was wondering looking at the 4Q -- implied 4Q number, it seems to be flat from third quarter. Does that -- it seems to imply no new patients added. Is that a function of estimate being very approximate? Or is there any other dynamics? And in general, can you comment on what are -- has the trend been since the beginning of the fourth quarter?

我想請教一下——也謝謝你們分享 TRYNGOLZA 上市的補充說明。我在看第4季——推算出的第4季數字時，似乎與第3季持平。這是否——看起來意味著沒有新增病患。這是因為估算非常粗略所致嗎？還是有其他動態因素？另外，整體而言，你們能否評論一下——自第4季開始以來的趨勢如何？

Yes. Thanks, Yanan. This is Kyle. I'll address that. There are a few factors, I think, that could impact Q4 revenues. And Beth mentioned this in her remarks. Number one is the Quick Start program. We believe that, that program will be used and has been used effectively up to this point and will continue to be used in Q4. So it's the timing of those patients started and the use of Quick Start.

好的。謝謝你，Yanan。我是 Kyle。我來回應這個問題。我認為有幾個因素可能會影響第4季營收。Beth 在她的發言中也提到過。第一是 Quick Start 計畫。我們相信，該計畫截至目前已被有效運用，並且會在第4季持續使用。因此，這涉及這些病患啟動治療的時間點以及 Quick Start 的使用情況。

Number two, we're still navigating the medical exception process, which can take time for many of these patients, right? We are very encouraged by our payer access and the way that payers are coming on board and the fact that payers are adding TRYNGOLZA per the labeled indication of greater than 500. The payers are also, when they're putting policies in place, the criteria for use is consistent with the clinical trial design. So being on background therapy, for example, of a [5] (inaudible) omega-3 compliance with diet, et cetera.

第二，我們仍在處理醫療例外（medical exception）流程，對許多病患而言這可能需要時間，對吧？我們對於付款方（payer）可及性，以及付款方逐步加入的情況感到非常振奮；而且付款方正依照核准標示適應症（>500）將 TRYNGOLZA 納入給付。付款方在制定政策時，其使用條件也與臨床試驗設計一致。例如需在背景治療上（background therapy），如 [5]（聽不清）omega-3、遵循飲食等。

So the policies are coming on board, but that will take time. And then the third component is just around seasonal dynamics. We've got the holidays and things that are happening right now. So there could be just some limited number of days with patients coming into the office.

因此，相關政策正在到位，但這需要時間。第三個因素則與季節性動態有關。目前有假期等因素正在發生。因此，可能只是病患到診的天數有所減少。

But I think the first signs of progress, I think, that everyone should be looking to is what Brett just emphasized, is that we want to see more prescribers come on board, which we are seeing in the fourth quarter already. We want to see more repeat prescribing, which we are seeing already in the fourth quarter. And then we want to see that payer access and coverage continue to improve, which I believe will happen not only in the fourth quarter, but also as we advance the launch in 2027.

但我認為大家應該關注的第一個進展訊號——正如 Brett 剛才強調的——是我們希望看到更多處方醫師加入，而我們在第4季已經看到這點。我們希望看到更多重複開立處方，而我們在第4季也已經看到。接著我們希望付款方可及性與給付覆蓋持續改善；我相信這不僅會在第4季發生，隨著我們在 2027 年推進上市，也會持續改善。

Thanks, Kyle. Just to add to that, Yanan. I just want to make the point. The obvious point is demand is increasing for TRYNGOLZA. And we're also very pleased with the persistency that TRYNGOLZA is demonstrating. Patients are staying on TRYNGOLZA. We're quite encouraged by that. It's really -- that's all matched up against the dynamics that Kyle highlighted, specifically as well as the fact that we're still very early on in the launch in a market that we're creating, right?

謝謝，Kyle。我再補充一下，Yanan。我只是想強調一點。很明顯的一點是，TRYNGOLZA 的需求正在增加。而且我們也對 TRYNGOLZA 所展現的持續用藥率（persistency）感到非常滿意。病患正在持續使用 TRYNGOLZA。我們對此相當受到鼓舞。這一切——都需要與 Kyle 所提到的動態因素相互對照，尤其還有一點是：我們仍處於上市初期，而且是在一個我們正在創造的市場中，對吧？

It's a brand-new market. We have a fantastic drug that is going to -- we believe, is addressing the needs of a very large patient population with high unmet need. But we're balancing demand persistency along with the dynamics that Kyle highlighted.

這是一個全新的市場。我們有一款非常出色的藥物——我們相信——它正在滿足一個規模非常大的病患族群需求，而該族群存在高度未被滿足的醫療需求。但我們需要在需求與持續性，和 Kyle 所提到的動態因素之間取得平衡。

Jason Gerberry , Bank of America.

Jason Gerberry，美國銀行。

Maybe two for Beth. Just curious how investors should be thinking about maybe cash runway, your burn level against sort of the $2 billion cash on hand and need for any additional licensing or financing instruments. Is that contingent on launch trajectory? I know there was some prior breakeven commentary. So just curious how to think about it in that context. And then how do you foresee that launch evolving in 2027 from a revenue recognized perspective? Just any commentary you guys are willing to provide on the current consensus, which is roughly, I think, $370 million.

我有兩個問題想問 Beth。想了解投資人應該如何看待現金續航力（cash runway）：你們目前約 20 億美元的現金部位，相對於燒錢水準（burn level），以及是否需要任何額外授權或融資工具。這是否取決於上市推進的軌跡？我知道之前有一些關於損益兩平（breakeven）的評論。所以想請教在這個脈絡下應該如何思考。另外，從營收認列（revenue recognized）的角度，你們如何預期 2027 年的上市會如何演變？也請你們就目前市場共識（consensus）提供任何願意分享的看法；我記得大約是 3.7 億美元。

Let me start with that one, Jason, on the 2027 guidance, if you will. We'll look forward to providing that guidance when we get to the February year-end earnings call, as we always do. So stay tuned for that. As far as cash runway goes, we're -- we ended this quarter with $1.9 billion. We anticipate ending the full year with greater than $1.6 billion.

Jason，關於 2027 年指引（guidance）這題，我先回答。我們會如同以往，在二月的全年財報電話會議時提供相關指引，敬請期待。所以請持續關注。至於現金續航力，我們本季結束時有 19 億美元。我們預期全年結束時將超過 16 億美元。

Obviously, that's all really important for us to continue to invest and execute on the commercial launches, in particular, TRYNGOLZA, as well as advancing the pipeline and our technology. We'll continue to be in a period of investment for the next short while as our commercial products ramp towards peak. And so we'll be obviously very aware of ensuring that we're well capitalized to be able to support that investment. And that means we'll be looking, as we always do, at our needs for financing. And if we do, we'll be very careful and very cognizant of cost of capital and dilution as important factors and considerations. So just as far as positive cash flow, that's still something we're highly committed to.

顯然，這對我們持續投資並執行商業化上市非常重要，特別是 TRYNGOLZA，同時也要推進產品線（pipeline）與我們的技術。在接下來一段時間，隨著商業產品朝向峰值（peak）爬坡，我們仍將處於投資期。因此，我們會非常注意確保資本充足，以支撐這些投資。這也意味著我們會一如既往地評估融資需求。若需要融資，我們會非常謹慎，並將資金成本（cost of capital）與稀釋（dilution）視為重要因素與考量。至於正向現金流（positive cash flow），這仍是我們高度承諾要達成的目標。

We want to achieve sustained and -- achieve positive cash flow and sustained positive cash flow. And obviously, the timing of that is dependent on the TRYNGOLZA launch ramp. But based on the recent Phase III setbacks and the slower-than-anticipated TRYNGOLZA launch, we do expect the timing to shift from 2028 to 2029. However, our goal is to continue to balance investment and growth with operating discipline and to achieve that sustained positive cash flow.

我們希望達成正向現金流，並且——達成可持續的正向現金流。而其時間點顯然取決於 TRYNGOLZA 上市爬坡的速度。但基於近期第三期（Phase III）挫折以及 TRYNGOLZA 上市進度慢於預期，我們確實預期時間點將從 2028 年延後至 2029 年。然而，我們的目標是持續在投資與成長之間取得平衡，同時維持營運紀律，並達成可持續的正向現金流。

Gary Nachman, Canaccord Genuity.

Gary Nachman，Canaccord Genuity。

Just back on TRYNGOLZA. So what portion of the physicians that you're targeting are high priority docs? And how often do you need to communicate with them in terms of frequency to increase their prescribing? And if you want to expand breadth and depth of prescribing, do you have the right sales team in place in order to be able to do that? And then just if there is some net pricing pressure that we're seeing into 4Q, maybe from Quick Start, just -- how should we think of that? And when could it normalize? Would it be next year or the year after now that you have that program in place?

再回到 TRYNGOLZA。你們鎖定的醫師中，有多少比例是高優先級醫師？為了提高他們的處方量，你們需要以多高的頻率與他們溝通？如果你們想擴大處方的廣度與深度，是否已配置正確的銷售團隊來做到這點？另外，如果我們在第4季看到一些淨定價壓力（net pricing pressure），可能來自 Quick Start，那麼——我們應該如何看待？何時可能回歸正常？在你們已經有該計畫的情況下，會是明年，還是後年？

Yes. Thanks, Gary. A couple of things. Field force size is absolutely adequate for the size of the opportunity for the high-risk sHTG patient population that we're starting with. We've got a couple hundred representatives out there that can address about 20,000 of the highest sHTG treaters in the United States. Now the increasing frequency that we're focused on are on our Tier 1 HCPs, which are a subset of that. And we know that these HCPs see the highest volume of high-risk sHTG patients.

是的。謝謝你，Gary。有幾點。就我們目前切入的高風險 sHTG 病患族群機會規模而言，外勤團隊（field force）的人數絕對足夠。我們有數百位業務代表，能夠覆蓋美國約 20,000 位治療 sHTG 人數最多的醫師。目前我們著重提升拜訪頻率的是我們的第一級（Tier 1）醫療照護專業人員（HCPs），他們是其中的一個子集合。而我們知道，這些 HCP 會接觸到最高量的高風險 sHTG 病患。

So we're trying to do exactly what you described, which is deploy those representatives to those offices more frequently so that HCPs will get their first experience with the first patient and then broaden the prescribing from there. We also have a field access team that is supporting the reimbursement and access process with those offices, which is the other dynamic here.

因此我們正嘗試做你所描述的事情，也就是更頻繁地把這些代表派到那些診所，讓醫療照護專業人員（HCP）能先從第一位病患開始累積使用經驗，然後再由此擴大處方。我們也有一支外勤市場准入團隊，協助這些診所在給付與准入流程上的支援，這也是此處的另一個關鍵動態。

And so we believe that when HCPs gain experience using this new modality and they see the clinical outcomes with these patients combined with a smooth process in terms of getting those patients started on treatment, we believe that, that will unlock more patients for them to be able to treat appropriately with TRYNGOLZA.

因此我們相信，當HCP在使用這種新治療模式上累積經驗，並看到這些病患的臨床結果，再加上在讓病患開始治療的流程上能夠順暢推進，我們相信這將解鎖更多病患，使他們能夠以TRYNGOLZA進行適當治療。

In terms of frequency, it varies, right? Some of the early adopters, you're seeing 5 or 6 times, I think some of the others may take upwards of 10-plus times to be seen before they come on board. Part of that is education around the product. Some of that is education around reimbursement. And some of that is around the appropriate patient to treat. And we really are focused on the high-risk sHTG patient population that are at the highest risk of having an acute pancreatitis event.

就拜訪頻率而言，確實會有所不同。有些早期採用者，你會看到我們拜訪5到6次；我想另外一些可能需要被拜訪10次以上才會加入。其中一部分是產品相關的教育。有些是給付／報銷相關的教育。還有一些是關於適合治療的病患族群。而我們確實聚焦在高風險的嚴重高三酸甘油脂血症（sHTG）病患族群，也就是急性胰臟炎事件風險最高的族群。

In terms of the Quick Start program, that will be an ongoing situation for us because those will be patients that are able to go on free drug for a period of time while reimbursement comes into play for that patient or access is secured. So we'll see that now and moving forward in terms of patients benefiting from that program and helping them get on drug quickly while they're navigating the reimbursement process.

就Quick Start計畫而言，這對我們會是持續性的安排，因為在病患的給付開始生效或取得准入之前，這些病患可以在一段期間內使用免費藥物。因此我們現在以及未來都會看到病患受惠於該計畫，協助他們在處理給付流程的同時，能更快開始用藥。

June Lee, UBS.

June Lee，瑞銀（UBS）。

It's reassuring that the demand for TRYNGOLZA is increasing. But as you broaden the prescriber base, is there a particular specialty you're targeting? And is it different than the prescribers you were already targeting for FCS indication? And for the prescribers who need quote on quote, educating -- education, what exactly is the difficulty in understanding the value proposition of TRYNGOLZA. And secondly, what were some unexpected hurdles that led you to cut your guidance?

TRYNGOLZA的需求正在增加，這點令人安心。但當你擴大處方醫師基礎時，有沒有特定鎖定的專科？這是否不同於你們先前針對FCS適應症所鎖定的處方者？另外，對於那些需要所謂「教育」的處方者而言，他們在理解TRYNGOLZA的價值主張上，具體的困難是什麼？第二，你們下修財測指引時，遇到了一些出乎意料的障礙是哪些？

Yeah. In terms of the specialties, very consistent with FCS, but a broader number of HCPs that we're reaching at this point. We were reaching about 3,000 mix of cardiologists, endocrinologists, and lipid specialists for FCS. As we expanded the sales team last year, we're now reaching, as I mentioned, about 20,000 cardiologists, endocrinologists, and lipidologists. The largest percentage of those is cardiology just because of the size of that specialty population.

是的。就專科別而言，與FCS非常一致，但我們目前觸及的HCP數量更廣。在FCS方面，我們大約觸及3,000名心臟科、內分泌科與脂質專科醫師的組合。隨著我們去年擴編銷售團隊，如我提到的，我們現在觸及約20,000名心臟科、內分泌科與脂質專科（lipidologists）醫師。其中占比最大的是心臟科，主要因為該專科族群規模較大。

The education is more about building a market here, right? There is HCP enthusiasm when they learn about TRYNGOLZA. They do see that TRYNGOLZA has a compelling profile. It has a broad indication of greater than 500. It also has acute pancreatitis as outcomes and reduction in AP in the indication statement. So there is HCP enthusiasm and a belief and a compelling profile.

教育更多是在於建立市場，對吧？當HCP了解TRYNGOLZA時，他們確實很有熱忱。他們也看到TRYNGOLZA具備很有吸引力的特性。它的適應症涵蓋範圍很廣，門檻是大於500。此外，在適應症敘述中也包含急性胰臟炎的結果指標以及急性胰臟炎（AP）降低。因此HCP是有熱忱的，也相信其特性具說服力。

When you get down to the underlying numbers, reductions of triglycerides of up to 72% on top of standard of care that they're using today, up to a 91% reduction in acute pancreatitis and getting approximately 50% -- excuse me, 60% of patients to goal is very encouraging for these HCPs. So the education is more about which patients do I treat? When am I going to see those patients? And then when am I going to prescribe TRYNGOLZA for the first time in order to gain this clinical experience? And that just takes a little bit of time is what we're learning here.

當你深入看底層數據，在現行標準治療之上，三酸甘油脂最高可降低72%，急性胰臟炎最高可降低91%，並且約有50%——抱歉，是60%的病患可達到目標值，這些都讓HCP非常振奮。所以教育更多是在於：我該治療哪些病患？我什麼時候會看到那些病患？以及我什麼時候會第一次開立TRYNGOLZA，以便累積臨床使用經驗？而我們正在學到的是，這確實需要一點時間。

Yeah. And on the -- on the guidance, it's really nothing more, June, than the slower-than-expected launch ramp. We're very pleased with the enthusiasm by HCPs to prescribe, demand is increasing, and we're very pleased with payer coverage to date. We're getting coverage on agreements that we have gotten in place so far to label, which means a very broad label, 500 milligrams per deciliter triglycerides and above. So the metrics are lining up positively. It's just a slower launch ramp than what we initially expected.

是的。至於——關於指引（guidance），June，原因其實很單純，就是上市初期的爬坡速度比預期慢。我們對HCP開立處方的熱忱感到非常滿意，需求正在增加，而且我們也對目前的保險支付方（payer）涵蓋情況感到很滿意。就目前已簽訂的協議而言，我們正取得與標籤一致的給付涵蓋，也就是非常廣的標籤：三酸甘油脂500毫克/分升及以上。因此各項指標都在正向對齊。只是上市爬坡比我們最初預期更慢。

Mike Ulz, Morgan Stanley.

Mike Ulz，摩根士丹利（Morgan Stanley）。

Maybe another one on TRYNGOLZA. Looks like, out of the gate, you're getting some nice breadth there in terms of the prescribers and starting to see some depth. But as we move forward into next year, what's the key to sort of driving greater depth? Is it just more experience? Is there something else? Is it education? Maybe a little bit more color on your thoughts there.

再問一題TRYNGOLZA。看起來一開始你們在處方者廣度上就取得不錯的進展，也開始看到一些深度。但展望明年，推動更大處方深度的關鍵是什麼？只是更多使用經驗嗎？還是有其他因素？是教育嗎？能否再多談一些你們的想法。

Yeah. I think there are a couple of things there, Mike. Experience is one. And what we're seeing is some of these HCPs are treating the most severe patient first, right, history of AP, for example. So I think that they potentially could start with the highest risk patient and then start moving beyond that to patients that are just greater than 880 or patients that are over 500 with comorbidities, for example.

是的。我想有幾個因素，Mike。經驗是一個。我們看到的是，有些HCP會先治療最嚴重的病患，例如有AP病史的病患。因此我認為他們可能會先從最高風險病患開始，接著再擴展到三酸甘油脂大於880的病患，或是大於500且有共病（comorbidities）的病患等。

But we believe that really to help these HCPs unlock these patients, they need to see the clinical outcomes of using this new treatment that they've never had access to. And number two, the process in order to get coverage and access needs to be smooth and straightforward for their offices. And those are the two really key things that we're working through these offices with here on the outset and then talk to them about more patients that could potentially benefit and how they could broaden their prescribing.

但我們相信，要真正幫助這些HCP解鎖這些病患，他們需要看到使用這種他們過去從未能取得的新治療所帶來的臨床結果。第二，取得給付涵蓋與准入的流程，對他們的診所而言必須順暢且直接。而這兩點正是我們在一開始就與這些診所共同推進的兩個關鍵事項，接著再與他們討論更多可能受益的病患，以及他們如何擴大處方。

Jessica Fye, JPMorgan.

Jessica Fye，摩根大通（JPMorgan）。

You've been talking about the TRYNGOLZA launch progressing a little bit slower than you initially thought. Can you talk about how you think about the timeline to get to that $3 billion US-peak target? And then my follow-up still related to TRYNGOLZA would just be, can you talk about specific Quick Start expansion changes that you're making?

你們一直在談TRYNGOLZA的上市進展比最初預期慢一些。能否談談你們如何看待達到美國峰值30億美元目標的時間軸？另外，我的追問同樣與TRYNGOLZA相關：能否談談你們正在進行的Quick Start計畫擴充，具體有哪些變更？

So I'll touch on peak, Jess. And we have not, up to this point, provided any insight into -- to time to peak. But what I'll mention is the large-patient population that is addressable here of greater than 3 million patients, 1 million of which are at high risk of acute pancreatitis. And there's an opportunity for TRYNGOLZA to address a significant unmet need here. And I've been through the profile a couple of times in terms of what the strength of the profile of TRYNGOLZA represents.

Jess，我先談峰值（peak）。截至目前，我們尚未就——達到峰值所需時間提供任何說明。但我想提的是，這裡可觸及的病患族群非常龐大，超過300萬名病患，其中有100萬名屬於急性胰臟炎高風險族群。TRYNGOLZA有機會在此滿足重大的未被滿足醫療需求。而我也已經就TRYNGOLZA特性強度所代表的意義，談過幾次。

But we do believe that we will continue to build this market. The HCP enthusiasm will continue to grow. We will get more experience with new prescribers and those prescribers that have written will prescribe more, and access will open up over time. But this is a function of building a new market that has never been in existence before.

但我們確實相信，我們將會持續打造這個市場。醫療照護專業人員（HCP）的熱情將會持續升溫。我們會在新的開立處方醫師以及已經開立過處方的醫師身上累積更多經驗；而那些已經開立過的醫師也會開立更多處方，且隨著時間推移，可近性將逐步開放。但這本質上是建立一個過去從未存在過的新市場的過程。

The Quick Start expansion point, I don't want to get into a lot of the details there just because it's a competitive space. But obviously, we have a number of different programs to make sure that patients can get on treatment and get on treatment quickly and able to stay on treatment long term. And I think that's important for our patient services program, and it's important for the patients that can benefit from those types of programs.

關於 Quick Start 擴展的部分，我不想談太多細節，主要是因為這是一個競爭激烈的領域。但很明顯地，我們有多項不同的方案，確保病患能夠開始治療、快速開始治療，並且能夠長期持續治療。我認為這對我們的病患服務計畫很重要，對能從這類計畫中受益的病患也同樣重要。

And on the time line, I'll just add. Thanks, Kyle. Jess, it's important to remember that we are three months into -- these numbers represent three months into a launch, delivering a medicine that is providing benefit to patients that the physicians have never had experience with before, right? And that requires education, that requires patient -- physicians to bring patients in, to get the triglycerides measured and then get them on to medicine. We're looking forward to 2027. We think 2027 will be a very important year for TRYNGOLZA.

另外在時間軸方面，我再補充一下。謝謝你，Kyle。Jess，重要的是要記得，我們才剛上市三個月——這些數字代表的是上市三個月的表現；我們正在提供一種能為病患帶來效益、但醫師過去從未有使用經驗的藥物，對吧？這需要教育，也需要——醫師把病患帶進來、測量三酸甘油脂，然後讓病患開始用藥。我們期待 2027 年。我們認為 2027 年將會是 TRYNGOLZA 非常重要的一年。

Eric Joseph, Citi.

Eric Joseph，花旗（Citi）。

Just a couple more on TRYNGOLZA. Would be curious to know, on the payer access dynamic so far, if you could speak to the success rate of getting on formulary? Have there been any refusals or any plans to cover TRYNGOLZA for sHTG? And what's your expectation as to when the outstanding formulary reviews could complete?

再問幾個關於 TRYNGOLZA 的問題。我想了解一下，到目前為止在付款方可近性的動態上，你們能否談談進入處方集（formulary）的成功率？是否有任何拒絕，或任何計畫拒絕為 sHTG 承保 TRYNGOLZA？以及你們預期尚未完成的處方集審查大概何時會結束？

Yeah. Thanks, Eric. So we have not had significant pushback or challenges or issues related to our payer negotiations up to this point. As I mentioned, the end of Q3 through the end of September, we had 33% of commercial plans within a three-month period already begin putting policies in place for sHTG and adding the 50-milligram dose, so the 50 and 80 were available.

好的，謝謝你，Eric。到目前為止，我們在付款方談判方面並沒有遇到顯著的阻力、挑戰或問題。如我提到的，從第三季末到九月底，在三個月期間內，我們已有 33% 的商業保險計畫開始針對 sHTG 建立相關政策，並納入 50 毫克劑量，因此 50 與 80 毫克都可使用。

We believe, on a pricing standpoint, we priced at $40,000 WAC, and that took place on April 1 of this year. We priced exactly for this reason, which was to make sure that we had coverage to label, which is for all patients greater than 500, and we wanted to make sure that we reduce the blocks and limitations where payers didn't put in place restrictions around history of AP or being a high-risk patient over [880] for example.

我們認為，在定價方面，我們將 WAC 定價為 40,000 美元，並於今年 4 月 1 日生效。我們之所以這樣定價，正是為了確保能依標籤取得給付——也就是適用於所有三酸甘油脂大於 500 的病患；同時我們希望降低阻礙與限制，避免付款方設下限制，例如要求有急性胰臟炎（AP）病史，或必須是例如高風險、數值高於 [880] 的病患等。

And I think we've been very successful at working with payers and talking about the patient population that's addressable here and putting policies in place that reflect the broad label. And also, obviously, the prior authorization criteria being consistent with the clinical trial design, which is typically what we are seeing with these plans. So we're very encouraged by payer access coming on board. We believe we will have more coverage in access open up at the end of this year and going on throughout 2027. So we're in a good place as it relates to access.

我認為我們在與付款方合作方面非常成功，能夠就此處可涵蓋的病患族群進行溝通，並建立反映廣泛標籤適用範圍的政策。此外，事前授權（prior authorization）的條件也與臨床試驗設計一致，而這通常正是我們在這些保險計畫中所看到的。因此，我們對付款方可近性逐步到位感到非常鼓舞。我們相信在今年底以及整個 2027 年期間，將會有更多給付與可近性逐步開放。所以就可近性而言，我們目前處於良好狀態。

Akash Tewari, Jefferies.

Akash Tewari，Jefferies。

This is what I'm trying to parse out, I think on September in an investor transcript, you were saying July and August were good months when you're thinking about scripts for TRYNGOLZA. And then obviously, the implied guidance cut today is a pretty stark contrast. Can you talk about -- when you were talking about July, August being good months, how are you defining that? And then what really kind of broke down? And I think my concern is really if July and August were good months, that we're actually seeing a downward trajectory in terms of demand as we go into September and the back half of the year? And then also, I know you went away from PANTHERx to multiple specialty pharmacies. How much of that maybe has played a role with uptake here? Do you feel like patients need more high-touch service?

我想釐清的是：我記得在 9 月的一份投資人逐字稿中，你們提到在思考 TRYNGOLZA 的處方量時，7 月和 8 月是表現不錯的月份。但今天隱含的指引下修顯然形成相當強烈的對比。你能談談——當你說 7、8 月是好月份時，你是如何定義「好」的？然後到底是哪個環節出了問題？我真正擔心的是，如果 7、8 月是好月份，那我們是否在 9 月以及下半年看到需求呈現下滑趨勢？另外，我知道你們從 PANTHERx 轉向多家專科藥局。這在多大程度上可能影響了目前的導入速度？你們是否覺得病患需要更多高接觸式服務？

Thanks, Akash. So early comments during the early part of the launch really reflected the data that we had available at that time. We are very pleased with the label we received with the indication statement including acute pancreatitis reduction. And we also -- we're seeing a great deal of enthusiasm by HCPs for the overall drug profile and their desire to prescribe at the time.

謝謝你，Akash。所以在上市初期的早期評論，確實反映了當時我們所掌握的可用數據。我們對所獲得的標籤非常滿意，因為適應症敘述包含降低急性胰臟炎的內容。而且我們也——當時看到 HCP 對整體藥物特性有高度熱情，並且有意願開立處方。

But remember, we were a few weeks into the launch at that time. So it was really based on what we are hearing from the HCP community and their enthusiasm for TRYNGOLZA, which continues today. Now we just have to bring these patients through and get them on to cover drug. With regard to the pharmacies, specialty pharmacies and so on, Kyle, would you take that?

但請記得，當時我們才上市幾週。所以那主要是基於我們從 HCP 社群聽到的回饋，以及他們對 TRYNGOLZA 的熱情——而這份熱情至今仍在。現在我們只是需要把這些病患導入流程，讓他們真正用上有給付的藥物。至於藥局、專科藥局等相關問題，Kyle，你來回答可以嗎？

Yeah. The multiple SPs, Akash, we have the right programs in place. We have the Ionis Every Step program, right, our patient support program, to make sure that patients are educated from the disease state standpoint, product standpoint and that we also have programs in place to help financial situations, if necessary, in order for those patients to get on and stay on treatment. So I think we've got the right programs there.

好的。Akash，關於多家專科藥局（SP），我們已經建立了正確的方案。我們有 Ionis Every Step 計畫，也就是我們的病患支持計畫，確保病患在疾病狀態與產品層面都能獲得教育；同時我們也有方案在必要時協助財務狀況，讓這些病患能開始治療並長期持續治療。所以我認為我們在這方面已經有合適的方案。

As it relates to expanding the SPs. The SPs are doing very well. We've got four SPs that address some of the largest payers as well. And we believe that we've got the right SPs to help us make sure that the prescription process gets navigated and we get drug to patients. But we've also got our field access team out there working directly with offices on the reimbursement process and making sure that we're educating around which plans have policies in place and what the criteria for use are for those respective plans. And so that HCP office education is another key component to this beyond just the SP expansion as well.

至於擴增 SP 的部分，這些 SP 的表現非常好。我們有四家 SP，也涵蓋了一些最大的付款方。我們相信我們選擇了合適的 SP，能協助我們確保處方流程被順利引導，並把藥物送到病患手上。但我們也有外勤可近性團隊，直接與診所合作處理給付流程，並確保我們在教育方面到位——包括哪些保險計畫已建立政策，以及各計畫的使用條件為何。因此，除了 SP 擴增之外，對 HCP 診所端的教育也是另一個關鍵組成。

David Lebowitz, BMO Capital Markets.

David Lebowitz，BMO Capital Markets。

When you try to bucket how the launch is going in various groups, there's a lot of talk about the high-risk patients above 880, about the patients above 500, what about the patients that specifically have had pancreatitis events have we seen any uptick -- notable uptick in that group?

當你們嘗試把上市進展分成不同族群來看時，市場上談了很多關於高風險、數值高於 880 的病患，也談到數值高於 500 的病患；那麼對於那些特別曾發生胰臟炎事件的病患，我們是否看到該族群有任何上升——明顯的上升？

Yeah. Thanks, David. We are absolutely laser-focused on the high-risk sHTG patients here out of the gate to establish TRYNGOLZA and to begin building this market. The patients above 500 with history of AP are a cornerstone of that focus. And our sales team and our medical affairs team, obviously, educating HCPs around the need to treat those patients and the risk, now that these patients have had one AP event, of subsequent events going up exponentially in terms of risk potential.

好的，謝謝你，David。我們在一開始就絕對高度聚焦於高風險的 sHTG 病患，以建立 TRYNGOLZA 的定位並開始打造這個市場。三酸甘油脂高於 500 且有 AP 病史的病患，是這項聚焦策略的基石。而我們的業務團隊與醫學事務團隊也正在教育 HCP：需要治療這些病患及其風險——因為一旦這些病患已經發生過一次 AP 事件，後續再次發生事件的風險在潛在風險上會呈指數型上升。

So we are seeing those patients get prescriptions. Some of it is an office dynamic of when those appointments are scheduled and when those patients are coming in to see their HCPs, so it's a timing situation, but that is a really strong focus of our communications and our education and the launch in order to build this market and get TRYNGOLZA treated -- or get patients treated with TRYNGOLZA for the right reasons.

因此，我們看到這些病患正在取得處方。其中一部分是門診端的運作節奏，取決於這些門診預約何時安排，以及這些病患何時回診見他們的醫療照護專業人員（HCP），所以這是一個時點上的問題；但這確實是我們溝通、教育以及上市推廣的重點，以便建立這個市場，並讓 TRYNGOLZA 得到治療——或者說，讓病患基於正確的原因接受 TRYNGOLZA 治療。

Ellie Merle, Barclays.

Ellie Merle，巴克萊。

Maybe just to take a step back, could you highlight like, I guess, what exactly contributed to the slower-than-expected launch versus what you had initially anticipated? Is this driven by, like reimbursement factors, use of free drug? Or is this slower-than-expected demand? And if you break that out or characterize that a little bit, I think that would be helpful. And then just again on the Quick Start program. You did mention that there's been meaningful utilization. If you could give us any color or characterize, I guess, what proportion of overall start on free drug? And I guess your expectations for the average duration that patients will be on free drug before converting to paid?

也許先退一步來看，你們能否說明一下，我想，究竟是哪些因素導致上市進度比你們最初預期更慢？這是由報銷／給付因素、免費用藥的使用所驅動嗎？還是需求本身就比預期更慢？如果你們能把這些因素拆開或稍微描述一下，我想會很有幫助。另外再回到 Quick Start 計畫。你們提到已有相當程度的使用。如果可以的話，能否提供一些補充資訊或描述一下，例如整體起始治療中有多少比例是從免費用藥開始？以及你們對於病患在轉為付費之前，平均會使用免費用藥多久的預期？

Yes. Kyle, want to reiterate what's driving the slower than expected launch?

好的。Kyle，你想再重申一下是什麼在推動上市進度比預期更慢嗎？

Yeah. Thanks, Ellie. I'll just revert back. We're building a market here. That's the first thing, right? HCPs, the majority, some that have treated FCS have experience using TRYNGOLZA, but the majority of these HCPs that we're calling on are learning about a new modality, a new product, and trying to make sure that they understand which patients to treat and the potential value of treating those patients. So it's about market building and creating this market.

是的。謝謝你，Ellie。我就回到先前的說法。我們正在建立一個市場。這是第一點，對吧？醫療照護專業人員（HCP）方面，多數中有一部分曾治療過 FCS，對使用 TRYNGOLZA 有經驗，但我們拜訪的大多數 HCP 正在認識一種新的治療方式、一個新產品，並且我們要確保他們了解該治療哪些病患，以及治療這些病患的潛在價值。所以這關乎市場建構與創造這個市場。

It requires HCP education, which is exactly what we're doing with our field team with personal promotion. It also takes non-personal promotion like our omnichannel capabilities and the way that we are educating through digital means, which is really important here as well to drive awareness and an understanding of sHTG and TRYNGOLZA. And then there's also the patient dynamics.

這需要對 HCP 進行教育，而這正是我們的外勤團隊透過面對面推廣所做的事。同時也需要非面對面推廣，例如我們的全通路（omnichannel）能力，以及我們透過數位方式進行教育的作法；這在此也非常重要，用以提升對 sHTG 與 TRYNGOLZA 的認知與理解。此外，還有病患端的動態因素。

So we're doing a lot of work to educate patients, not only through omnichannel, but also through our patient advocacy work and the engagements that we're having with different groups in order to make sure people understand what sHTG is, what risks are associated with sHTG and the potential benefits of being treated with TRYNGOLZA would look like.

因此，我們也投入大量工作來教育病患，不僅透過全通路，也透過我們的病患倡議工作，以及我們與不同團體的互動，以確保大家了解 sHTG 是什麼、sHTG 相關的風險有哪些，以及接受 TRYNGOLZA 治療可能帶來的潛在效益會是什麼樣子。

So that's really what's taking time, I think, in terms of the process to build the market. In terms of Quick Start, I don't want to get into really any more details surrounding that program. I mean, it's a program that I think is important for patients to be able to get on treatment quickly, and for HCPs to be able to assess how patients are doing and to make sure that patients can stay on treatment long term. So it's an important program for patients and HCPs.

所以我認為，真正需要時間的是建立市場的流程。至於 Quick Start，我不想再深入談這個計畫的更多細節。我的意思是，我認為這是一個重要的計畫，讓病患能夠快速開始治療，也讓 HCP 能夠評估病患的狀況，並確保病患能夠長期持續治療。所以這對病患與 HCP 都是重要的計畫。

Myles Minter, William Blair.

Myles Minter，William Blair。

This is Jake on for Myles. Should [redumplo] be approved in sHTG? Do you expect them to take similar headwinds in initial uptake? Or is this just the curse of being the lead blocker here? And then maybe a follow-up for Beth. You changed your breakeven guidance from 2028 to 2029, I just wanted to confirm that the TRYNGOLZA uptake was the key driver there and that there were no other factors for update on that guidance?

我是代替 Myles 的 Jake。如果 [redumplo] 在 sHTG 獲批，你們預期他們在初期採用上也會遇到類似的逆風嗎？還是這只是作為先行者（lead blocker）所必然承受的「詛咒」？另外可能有個給 Beth 的追問：你們把損益兩平指引從 2028 年改到 2029 年，我只是想確認，TRYNGOLZA 的採用進度是主要驅動因素，且在該指引更新上沒有其他因素需要補充？

Thanks, Jake. I'll start, Beth, feel free to jump in. But as Beth said in her prepared remarks, our shift to 2029 cash flow breakeven was related to the slower-than-expected ramp -- launch ramp for TRYNGOLZA, but it was also impacted, as was stated by the disappointment -- Phase III disappointments for eplontersen in ATT or cardiomyopathy and pelacarsen for (inaudible) CVD.

謝謝你，Jake。我先回答，Beth 也歡迎補充。不過正如 Beth 在事先準備的發言中所說，我們將現金流損益兩平時間點延後至 2029 年，與 TRYNGOLZA 上市爬坡（launch ramp）慢於預期有關，但也受到影響——如同所提到的失望結果——包括 eplontersen 在 ATT 或心肌病變的第三期試驗失利，以及 pelacarsen 在（聽不清）CVD 的第三期失利。

That guidance to achieve cash flow breakeven will be driven among -- in addition to pipeline successes in large part by TRYNGOLZA launch as we go forward. As far as competitor programs, we have no comments on what they should expect. We see no reason why they would be in any different position than we are with respect to the dynamics that we're facing for the TRYNGOLZA launch to date. What we're thrilled about, of course, is the compelling product profile that we have for TRYNGOLZA, which has shown unprecedented reductions in triglycerides and acute pancreatitis (inaudible) safety, tolerability and convenience.

達成現金流損益兩平的指引，除了仰賴研發管線在很大程度上的成功之外，也將在很大程度上由 TRYNGOLZA 後續的上市表現所驅動。至於競品計畫，我們不評論他們應該預期什麼。就我們目前在 TRYNGOLZA 上市所面臨的各項動態而言，我們看不出他們會處於與我們不同的處境。當然，我們非常振奮的是 TRYNGOLZA 具備極具吸引力的產品特性，已展現前所未有的三酸甘油酯降低幅度，以及急性胰臟炎（聽不清），並具備安全性、耐受性與便利性。

So stay tuned. We're looking forward to 2027 for the launch of TRYNGOLZA. It's a very important year. And like I said, we're very much looking forward to it. With that, I think we're going to end the call. Thanks, everybody, for joining us today. We look forward to sharing our progress as we further advance our launches and the next wave of medicines from our pipeline. Have a good day, everybody.

所以敬請期待。我們期待 2027 年 TRYNGOLZA 的上市。那將是非常重要的一年。如我所說，我們非常期待。那麼，我想我們將結束本次電話會議。感謝各位今天加入。我們期待在持續推進上市工作，以及推動研發管線下一波藥物的同時，與各位分享我們的進展。祝各位有美好的一天。

The conference has now concluded. Thank you for attending today's presentation, and you may now disconnect.

本次電話會議現在結束。感謝您參加今天的簡報，您現在可以中斷連線。