Arrowhead Pharmaceuticals Inc (ARWR) 2025 Q4 法說會逐字稿

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call.

女士們、先生們，歡迎參加 Arrowhead Pharmaceuticals 的電話會議。

(Operator Instructions)

（操作說明）

I will now hand the conference call over to Vince Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead, Vince.

現在我將把電話會議交給 Arrowhead 的投資人關係副總裁 Vince Anzalone。請繼續，文斯。

Thank you, [Andrew]. Good afternoon and thank you for joining us today to discuss Arrowhead's results for its 2025 fiscal year ended September 30, 2025.

謝謝你，[安德魯]下午好，感謝各位今天蒞臨，與我們共同探討 Arrowhead 截至 2025 年 9 月 30 日的 2025 財年業績。

With us today from management are President and CEO, Dr. Chris Anzalone, who will provide an overview; Bruce Given, outgoing Chief Medical Scientist, who will provide an overview of the REDEMPLO FDA approval; Andy Davis, Senior Vice President and Head of the Global Cardiometabolic franchise, who will provide an update on commercialization activities; Dr. James Hamilton, Chief Medical Officer and Head of R&D, who will discuss our development programs; and Dan Apel, Chief Financial Officer, who will review the financials.

今天出席我們管理層會議的有：總裁兼首席執行官克里斯·安扎隆博士，他將作概述；即將卸任的首席醫學科學家布魯斯·吉文，他將概述 REDEMPLO 獲得 FDA 批准的情況；高級副總裁兼全球心血管代謝業務負責人安迪·戴維斯，他將介紹商業化活動的最新進展；首席醫學官兼研發負責人詹姆斯·漢密爾頓，他將回顧我們的財務狀況。

Following management's prepared remarks, we will open up the call to questions.

在管理階層發言結束後，我們將開放提問環節。

Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934.

在開始之前，我想提醒各位，今天電話會議期間發表的評論包含1933年證券法第27A條和1934年證券交易法第21E條所指的某些前瞻性陳述。

All statements, other than statements of historical facts, are forward-looking statements; and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statements.

除歷史事實陳述外，所有其他陳述均為前瞻性陳述；這些陳述受到許多風險和不確定性的影響，可能導致實際結果與任何前瞻性陳述中表達的結果有重大差異。

For further details concerning these risks and uncertainties, please refer to our SEC filings, including our most recent annual report on Form 10-K and our quarterly reports on Form 10-Q.

有關這些風險和不確定性的更多詳情，請參閱我們向美國證券交易委員會提交的文件，包括我們最新的 10-K 表格年度報告和 10-Q 表格季度報告。

I'd now like to turn the call over to Chris Anzalone, President and CEO of the company. Chris?

現在我想把電話交給公司總裁兼執行長克里斯·安札隆。克里斯？

Thanks, Vince. Good afternoon, everyone. Thank you for joining us today.

謝謝你，文斯。大家下午好。感謝您今天蒞臨。

Before we begin, I'd like to announce that this will be Bruce Given's final earnings call. He's been a valuable member of the Arrowhead team for almost 15 years. He will continue to help Arrowhead as a trusted adviser. But now that REDEMPLO has received its first FDA approval, he will be stepping back from day-to-day operational responsibilities. Hopefully, he can finally enjoy his time and retirement -- or his re-retirement, which is probably more accurate.

在開始之前，我想宣布這將是布魯斯吉文的最後一次財報電話會議。近 15 年來，他一直是 Arrowhead 團隊的重要成員。他將繼續作為值得信賴的顧問為 Arrowhead 提供幫助。但現在 REDEMPLO 已獲得 FDA 的首次批准，他將逐步退出日常營運職責。希望他最終能夠享受他的退休生活——或者更準確地說，是他的「再退休」生活。

His contribution to Arrowhead's success, both current and future, have been critical. We owe him a heartfelt thank you.

他對 Arrowhead 的成功，無論是現在還是將來，都做出了至關重要的貢獻。我們衷心感謝他。

Later in the call, you will hear from Bruce who will discuss the REDEMPLO FDA approval, which he came back to Arrowhead and out of retirement to help us get across the finish line. Bruce leaves us in a strong position, with a very strong group of leaders across the organization. As you all know, James Hamilton has already assumed much of Bruce's prior responsibilities as Chief Medical Officer and Head of R&D.

在稍後的通話中，您將聽到 Bruce 的發言，他將討論 REDEMPLO 獲得 FDA 批准一事。為了幫助我們最終完成這項任務，他重返 Arrowhead 公司，結束了退休生活。當布魯斯離開時，我們擁有強大的實力，整個組織都有一群非常優秀的領導團隊。正如大家所知，詹姆斯·漢密爾頓已經接替了布魯斯之前擔任首席醫療官和研發主管的大部分職責。

Thank you, again, Bruce, for getting us to today. Thank you, James, for taking us into the next chapter for Arrowhead.

再次感謝你，布魯斯，讓我們走到今天。謝謝詹姆斯，帶我們進入了《箭頭》的下一個篇章。

Let's now turn to our business and what progress we've made during the recent period. This has been a very busy and enormously productive in the last few months.

現在讓我們來看看我們的業務以及最近一段時間我們的進展。過去幾個月我一直非常忙碌，但也取得了巨大的成就。

The most impactful change is the FDA approval of REDEMPLO. On November 18, we announced that the FDA approved our REDEMPLO, indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome or FCS.

影響最大的變化是 FDA 批准了 REDEMPLO。11 月 18 日，我們宣布 FDA 批准了我們的 REDEMPLO，該藥物適用於作為飲食的輔助療法，以降低患有家族性乳糜微粒血症或 FCS 的成年人的甘油三酯水平。

FCS is a severe rare disease, with an estimated 6,500 people in the United States living with genetic or clinical FCS, characterized by triglyceride levels that can be 10 times to 100 times higher than normal, leading to a substantially higher risk of developing acute, recurrent, and potentially fatal pancreatitis.

FCS 是一種嚴重的罕見疾病，據估計，美國有 6500 人患有遺傳性或臨床 FCS，其特徵是三酸甘油酯水平比正常水平高 10 到 100 倍，導致急性、復發性且可能致命的胰臟炎的風險大大增加。

This is Arrowhead's first FDA-approved medicine, marking a major milestone for the company, as it transitions into commercial stage. REDEMPLO is the first and only FDA-approved siRNA medicine for people living with FCS and can be self-administered at home with a simple sucutaneous injection once every three months. REDEMPLO was the first and only FDA-approved medicine to be backed by adequate and well-controlled studies that include patients with genetically diagnosed and clinically diagnosed FCS.

這是 Arrowhead 公司首款獲得 FDA 批准的藥物，標誌著該公司邁入商業化階段，具有里程碑式的意義。REDEMPLO 是第一個也是唯一一個獲得 FDA 批准的用於治療 FCS 患者的 siRNA 藥物，患者可以每三個月在家中進行一次簡單的皮下注射。REDEMPLO 是第一個也是唯一一個獲得 FDA 批准的藥物，背後有充分且控制良好的研究支持，這些研究包括基因診斷和臨床診斷的 FCS 患者。

After many months of preparation, our commercial team was able to hit the ground running. I'm happy to report that we have the drug in the channel, a mere week after approval.

經過數月的準備，我們的商務團隊得以迅速展開工作。我很高興地報告，該藥物在獲得批准後僅一周就已進入市場。

We also launched Rely On REDEMPLO, a patient support program, providing support services and resources for patients at each stage of the treatment journey with REDEMPLO, including financial assistance options for eligible patients.

我們也推出了 Rely On REDEMPLO 患者支援計劃，為 REDEMPLO 治療過程中各個階段的患者提供支援服務和資源，包括為符合條件的患者提供經濟援助選項。

In addition, we also announced the One-REDEMPLO pricing model that creates one consistent price across current and potential future indications. This is important. We are committed to sustainable innovation. This requires a rational drug pricing, according to the value of medicine offers to patients and healthcare systems. It also means that we will not ask different patients to pay different amounts for the same drug, based solely on what disease they've been diagnosed with.

此外，我們還宣布了 One-REDEMPLO 定價模型，該模型為當前和潛在的未來適應症創建了一個統一的價格。這很重要。我們致力於永續創新。這就需要根據藥品對病人和醫療保健系統的價值，制定合理的藥品價格。這也意味著，我們不會僅僅根據患者被診斷出的疾病，就要求他們為同一種藥物支付不同的費用。

REDEMPLO is a pancreatitis drug. When we think about pricing, we look to those patient populations who are at a greatest risk of acute TG-related pancreatitis. The patients we are serving now are also those at greatest risk of pancreatitis, people with FCS. This includes those with the defined set of mutations, as well as those who share the same level of (inaudible) and symptoms but with more heterogeneous and often less well-characterized genetic backgrounds, who we refer to as clinically defined or phenotypic FCS.

REDEMPLO 是一種治療胰臟炎的藥物。在考慮定價時，我們會關注那些急性 TG 相關胰臟炎風險最大的患者族群。我們現在服務的患者也是胰臟炎風險最高的族群，也就是患有家族性乳糜瀉的人。這包括那些具有特定突變集的人，以及那些具有相同程度（聽不清楚）症狀但遺傳背景更加異質且通常特徵不太明確的人，我們稱他們為臨床定義或表型 FCS。

The broader patient population wiith substantially increased risk of acute pancreatitis are those with persistent colonic anemia; meaning, fasting triglycerides greater than 880 milligrams per deciliter. We believe there are approximately 750,000 of these patients in the US. While they often have less day-to-day symptoms in FCS patients, they are clearly at high risk for acute pancreatitis.

急性胰臟炎風險顯著增加的更廣泛患者群體是那些患有持續性結腸貧血的人；這意味著空腹三酸甘油酯大於每分升 880 毫克。我們認為美國大約有 75 萬名這類患者。雖然 FCS 患者的日常症狀通常較少，但他們顯然有發生急性胰臟炎的高風險。

The One-Redemplo pricing model has these patients in mind. The $60,000 annual WACC price is designed to provide real value to patients and healthcare systems in this population.

One-Redemplo 的定價模式正是考慮到這些患者的需求。每年 60,000 美元的 WACC 價格旨在為該人群中的患者和醫療保健系統提供真正的價值。

Our SHASTA-3 and SHASTA-4 Phase 3 studies are designed to support an sNDA in this population. While those studies are ongoing and we are actively serving the FCS population, we will have time to help payers properly appreciate REDEMPLO's value. Payers will have time to plan and budget for its possible eventual adoption, pending regulatory review and approval.

我們的 SHASTA-3 和 SHASTA-4 第三階段研究旨在支持針對該族群的補充新藥申請 (sNDA)。雖然這些研究仍在進行中，我們也積極為 FCS 人群提供服務，但我們仍將有時間幫助支付者充分了解 REDEMPLO 的價值。在監管部門審查和批准之前，支付方將有時間進行規劃和預算，以應對其最終可能採用的情況。

Outside of REDEMPLO, we have also made good progress with two other pipeline programs in the cardiometabolic space, zodasiran and ARO-DIMER-PA.

除了 REDEMPLO 之外，我們在心血管代謝領域的另外兩個在研項目 zodasiran 和 ARO-DIMER-PA 上也取得了良好的進展。

We'll start with zodasiran. During the recent period, we dosed the first subject in the YOSEMITE Phase 3 clinical trial of zodasiran, our clinical candidate being developed as a potential treatment for homozygous familial hypercholesterolemia or HoFH.

我們先從 zodasiran 開始。最近，我們為 YOSEMITE 3 期臨床試驗中的第一位受試者註射了 zodasiran，我們的臨床候選藥物正在開發中，預計將用於治療純合子家族性高膽固醇血症 (HoFH)。

HoFH is a rare genetic condition that leads to severely elevated LDL cholesterol and early onset cardiovascular disease. YOSEMITE (inaudible) 60 subjects over the age of 12 will be randomized to receive four doses once every three months of the 200-milligram zodasiran for placebo. The primary endpoint is the percent change from baseline to (inaudible) in (inaudible) LDL-C.

HoFH 是一種罕見的遺傳性疾病，會導致 LDL 膽固醇嚴重升高和心血管疾病早期。優勝美地（聽不清楚）60 名 12 歲以上的受試者將被隨機分配，每三個月接受一次 200 毫克佐達西蘭，共接受四劑，作為安慰劑。主要終點是 LDL-C 從基線到（聽不清楚）的百分比變化（聽不清楚）。

The Phase 2 data in this patient population were encouraging. We hope to have this study fully enrolled in 2026, completed the study in 2027, a successful enabling-NDA filing by the end of 2027, and launch in 2028.

該患者族群的二期臨床試驗數據令人鼓舞。我們希望這項研究能在 2026 年完成受試者招募，在 2027 年完成研究，在 2027 年底前成功提交新藥申請，並在 2028 年正式上市。

The next pipeline program is in cardiometabolic is AERO-DIMER-PA. During the last quarter, we filed a request for regulatory clearance to initiate a Phase 1/2 clinical trial of AERO-DIMER-PA, being developed as potential treatment for atherosclerotic cardiovascular disease or ASCVD, due to mixed hyperlipidemia in which both LDL cholesterol and triglycerides are elevated.

下一個正在研究的心血管代謝藥物是 AERO-DIMER-PA。上個季度，我們提交了監管部門批准申請，以啟動 AERO-DIMER-PA 的 1/2 期臨床試驗。 AERO-DIMER-PA 正在開發中，作為治療動脈粥狀硬化性心血管疾病 (ASCVD) 的潛在藥物，用於治療 LDL 膽固醇和三酸甘油酯均升高的混合型高脂血症。

This is a very large population without proper treatment options. We believe there are approximately 20 million people in the US with mixed hyperlipidemia. AERO-DIMER-PA is a dual-function RNAi therapeutic, designed to silence expression of the PCSK9 and [APOC3G] in the liver, that's designed to reduce both LDL-C and TGs. This represents an important step forward for the RNAi field, as we believe it is the first clinical candidate to target two genes simultaneously in one molecule; and an important step forward for preventative cardiology, as both LDL and TG have epidemiologic support as being important drivers of ASCVD risk.

這是一個非常龐大的群體，卻缺乏合適的治療方案。我們認為美國約有 2000 萬人患有混合型高血脂症。AERO-DIMER-PA 是一種雙功能 RNAi 療法，旨在抑制肝臟中 PCSK9 和 [APOC3G] 的表達，從而降低 LDL-C 和 TG。這代表著 RNAi 領域向前邁出了重要一步，因為我們相信它是第一個同時靶向一個分子中兩個基因的臨床候選藥物；對於預防心臟病學而言，這也是向前邁出的重要一步，因為 LDL 和 TG 都有流行病學證據支持它們是 ASCVD 風險的重要驅動因素。

Both these programs fit well strategically with our growing commercial focus on the cardiometabolic space and on physicians to treat these patients.

這兩個計畫在策略上都非常契合我們日益增長的商業重點——心血管代謝領域以及治療這些患者的醫生。

Also, during the quarter, we expanded our clinical pipeline in CNS. We filed a CTA to initiate a Phase 1/2 clinical trial of ARO-MAPT as potential treatment for [tauopathies], including Alzheimer's is. ARO-MAPT is Arrowhead's first therapy to utilize a new proprietary delivery system, which, in preclinical studies, has achieved blood-brain barrier penetration and deep (inaudible) across the CNS, including deep brain regions, after subcutaneous injections.

此外，本季我們也擴大了中樞神經系統領域的臨床研發管線。我們已提交 CTA，啟動 ARO-MAPT 作為治療 [tau 蛋白疾病]（包括阿茲海默症）的潛在療法的 1/2 期臨床試驗。ARO-MAPT 是 Arrowhead 公司首個採用新型專有輸送系統的療法，在臨床前研究中，皮下注射後，該療法已實現穿透血腦屏障並深入（聽不見）中樞神經系統，包括深部腦區。

Non-clinical evaluations in monkeys with subcutaneous administration of ARO-MAPT using clinically translatable doses have shown better than 75% knockdown of the tissue level MAPT mRNA in CNS. Importantly, monkey tissue-level knockdown has translated into CSF tau protein reductions, with duration of effect supported by either monthly or quarterly subcutaneous-dose readiness. This is an exciting program. We look forward to initiating the study shortly.

在猴子身上進行的皮下注射 ARO-MAPT 的非臨床評估（使用臨床可轉化劑量）顯示，中樞神經系統中 MAPT mRNA 的組織水平敲低率超過 75%。重要的是，猴子組織水平的敲低已轉化為腦脊髓液 tau 蛋白的減少，並且每月或每季皮下注射劑量均能維持效果持續時間。這是一個令人興奮的項目。我們期待盡快啟動這項研究。

We also continue to make good progress on our first two obesity programs, ARO-INHBE and ARO-ALK7. Together, we have randomized 192 patients, all with the BMI greater than 30.

我們在前兩個肥胖症計畫 ARO-INHBE 和 ARO-ALK7 方面也持續取得良好進展。我們共隨機抽取了 192 位患者，所有患者的 BMI 均大於 30。

Because we started ARO-INHBE earlier, it is about two quarters further into the Phase 1 study in the (inaudible). Our plan has been to share early data at the end of the year but due to travel schedules and the holidays, this will push a couple of weeks later into the early part of January. We also expect to have more fulsome data toward the end of the first half of 2026.

由於我們較早啟動了 ARO-INHBE 項目，因此目前該藥物的 1 期臨床試驗已經進行了大約兩個季度。（聽不清楚）我們原本計劃在年底分享早期數據，但由於旅行安排和假期，這將推遲幾週，到一月初。我們也預計在 2026 年上半年末將獲得更完整的數據。

We also made important progress in [business] development. First, as we announced yesterday, we earned a $200 million milestone payment from Sarepta, following the drug safety committee review and subsequent authorization to dose escalate and achievement of the second prespecified patient enrollment target for ARO-DM1. This follows a $100 million milestone earned previously when Arrowhead reached the first of two prespecified enrollment targets and subsequent authorization to dose escalate in a Phase 1/2 clinical study of ARO-DM1.

我們在業務發展方面也取得了重要進展。首先，正如我們昨天宣布的那樣，在藥物安全委員會審查並隨後授權增加劑量以及達到 ARO-DM1 的第二個預先指定的患者招募目標之後，我們從 Sarepta 獲得了 2 億美元的里程碑付款。此前，Arrowhead 公司已達到兩個預先設定的入組目標中的第一個，並隨後獲准在 ARO-DM1 的 1/2 期臨床研究中增加劑量，從而獲得了 1 億美元的里程碑。

This partnership continues to be productive. We look forward to continued progress.

這種合作關係持續卓有成效。我們期待繼續取得進展。

In addition to progress on Sarepta partnership, we announced a new global licensing collaboration agreement with Novartis for ARO-SNCA, Arrowhead's preclinical stage siRNA therapy against (inaudible) for the treatment of (inaudible). 1The collaboration includes a limited number of additional targets outside our pipeline that will utilize Arrowhead's proprietary TRiM platform.

除了在與Sarepta的合作方面取得進展外，我們還宣布與諾華就ARO-SNCA達成一項新的全球許可合作協議。 ARO-SNCA是Arrowhead公司針對（聽不清楚）的臨床前階段siRNA療法，用於治療…（聽不清楚）1此次合作包括我們現有研發管線之外的少量其他靶點，這些靶點將利用Arrowhead公司專有的TRiM平台。

Arrowhead received a $200 million upfront payment from Novartis and is also eligible to receive development, regulatory, and sales milestone payments of up to $2 billion. Arrowhead is further eligible to receive tiered royalties on commercial sales up to low-double digits.

Arrowhead 從諾華公司獲得了 2 億美元的預付款，並且還有資格獲得高達 20 億美元的開發、監管和銷售里程碑付款。Arrowhead 還有資格獲得商業銷售的分級版稅，最高可達兩位數低段。

As I mentioned before, the recent approval of REDEMPLO is clearly the most important recent development. Arrowhead has been busy across the pipeline in key business development during the recent period. Business development and licensing is critical to our business model so we are pleased to have these two significant deals closed this year.

正如我之前提到的，REDEMPLO 的近期獲準顯然是最近最重要的進展。最近一段時間，Arrowhead 在各個關鍵業務拓展方面都非常活躍。業務拓展和授權許可對我們的商業模式至關重要，因此我們很高興今年完成了這兩項重要的交易。

With that overview, I'd now like to turn the call over to Bruce Given. Bruce?

概述完畢，現在我想把電話交給布魯斯·吉文。布魯斯？

Thanks, Chris. Good afternoon, everyone.

謝謝你，克里斯。大家下午好。

I'm happy to give my final update to Arrowhead shareholders at such an important time and with Arrowhead in such a position of strength. We have built something truly unique and powerful at Arrowhead.

我很高興在這個重要的時刻，在 Arrowhead 處於如此強勁的地位之際，向 Arrowhead 的股東們提供最後的更新報告。我們在Arrowhead打造了真正獨特而強大的東西。

With the first FDA approval behind us, it feels like the right time for me to step back into retire.

隨著首個FDA批准的完成，我覺得現在是我重新退休的好時機了。

So let's review some of the key parts of the recent FDA approval that we announced last week. Mostly, I'll discuss the label and information contained in the packages.

那麼，讓我們回顧一下我們上周宣布的FDA最新批准的一些關鍵部分。我主要會討論包裝上的標籤和資訊。

REDEMPLO is approved as an adjunct to diet to reduce triglycerides in adults with FCS. The recommended dose of REDEMPLO is 25 milligrams. It could be self-administered at home by subcutaneous injection, once every three months.

REDEMPLO 已獲批准作為飲食的輔助療法，用於降低患有 FCS 的成年人的三酸甘油酯水平。REDEMPLO 的建議劑量為 25 毫克。患者可在家中自行皮下注射，每三個月一次。

REDEMPLO has no contraindications, warranties, or precautions. The most common adverse reactions include hyperglycemia, headache, nausea, and injection-site reactions.

REDEMPLO 沒有禁忌症、保證或註意事項。最常見的不良反應包括高血糖、頭痛、噁心和注射部位反應。

The FDA submission was supported by clinical data from the Phase 3 PALISADE study in patients with both genetic FCS and those with the same clinical manifestations of disease but without solely a genetic cause referred to as clinically diagnosed FCS. The blinded portion of the trial compared a year of therapy with plozasiran or placebo dosed every three months; and tested two doses of plozasiran versus placebo.

FDA 的申請得到了 PALISADE 3 期研究的臨床數據支持，該研究納入了患有遺傳性 FCS 的患者以及具有相同臨床表現但並非完全由遺傳原因引起的患者（稱為臨床診斷的 FCS）。此試驗的盲法部分比較了每三個月服用一次 plozasiran 或安慰劑一年的治療效果；並測試了兩種劑量的 plozasiran 與安慰劑的療效。

The primary endpoint was change in median triglycerides at 11. There were also multiplicity-controlled secondary end points, all of which were statistically significant, including, notably, the (inaudible) of acute pancreatitis for which the 25- to 50-milligram doses were combined for comparison to placebo, as called for in the analysis plan. Plozasiran achieved deep and durable reductions in median triglycerides as early as one month, when the first measurement was taken.

主要終點是 11 歲時三酸甘油酯中位數的變化。此外，還有多重性控制的次要終點，所有這些終點都具有統計學意義，其中特別值得注意的是急性胰臟炎（聽不清楚），根據分析計劃的要求，將 25 至 50 毫克劑量合併起來與安慰劑進行比較。Plozasiran 在首次測量後一個月就實現了三酸甘油酯中位數的深度和持久性降低。

Overall, these reductions were around 80% from baseline. Reductions largely maintained medium triglyceride levels below the usual guideline-directed threshold of 500 milligrams per deciliter throughout the year of treatment.

總體而言，這些減少幅度比基線水準高出約 80%。治療期間，三酸甘油酯水平基本上保持在低於每分升 500 毫克的常規指導閾值以下。

500 milligrams per deciliter is the recognized threshold where the risk of pancreatitis increases, relative to a normal population. Importantly, patients with genetic FCS versus clinical FCS showed similar reductions from baseline.

每分升 500 毫克是公認的閾值，超過這個閾值，胰臟炎的風險就會相對於正常人群增加。重要的是，遺傳性 FCS 患者與臨床 FCS 患者的基線下降幅度相似。

We see the clinical FCS population having the same high unmet need as the genetic FCS group. As such, we think it is crucial to have shown that both patient populations showed similar large reductions from baseline in triglycerides with REDEMPLO therapy.

我們發現臨床 FCS 患者群體與遺傳性 FCS 患者群體一樣，存在著同樣高的未滿足醫療需求。因此，我們認為至關重要的是要證明，兩組患者在使用 REDEMPLO 治療後，三酸甘油酯水平較基線均有類似的顯著下降。

Plozasiran is also labeled as having reduced the rate of adjudicated pancreatitis events versus placebo, a very welcome finding for FCS patients and their caregivers; and an important validation of the reductions in triglycerides can, in fact, lead to reductions of (inaudible).

Plozasiran 也被認為能夠降低經裁定的胰臟炎事件發生率（與安慰劑相比），這對家族性乳糜瀉患者及其照護者來說是一個非常令人欣喜的發現；此外，降低三酸甘油酯水平確實可以降低胰臟炎事件發生率，這一發現也得到了重要的驗證。（聽不清楚）

Let me close by saying that it's gratifying to have been a part of Arrowhead from the early days of our siRNA developments; and part of the plozasiran program and its inception and, again, over the last several years.

最後我想說，能夠從 siRNA 開發的早期階段就成為 Arrowhead 的一份子，我感到非常榮幸；能夠參與 plozasiran 計畫的啟動和發展，以及最近幾年的發展，我感到非常榮幸。

More importantly, it's exciting to hear the enthusiasm about this new medicine for patients, caregivers, and physicians.

更重要的是，聽到病人、照護人員和醫生對這種新藥的熱情，令人振奮。

I'd also like to wish all of you an enjoyable Thanksgiving holiday.

我也想祝大家感恩節假期愉快。

I'll now turn the call over to Andy Davis. Andy?

現在我將把電話交給安迪戴維斯。安迪？

Thank you, Bruce.

謝謝你，布魯斯。

It's been exactly one week since the commercial launch of REDEMPLO. The early feedback we've received from healthcare professionals, patient societies, and payers has been very encouraging. We hear lots of enthusiasm about the differentiating attributes of REDEMPLO, which generally fall in five value pillars, some of which the team has touched on briefly already.

REDEMPLO 正式上市至今已整整一週。我們從醫療專業人士、患者協會和支付方收到的早期回饋非常令人鼓舞。我們聽到了很多關於 REDEMPLO 差異化屬性的熱情，這些屬性大致可歸納為五大價值支柱，其中一些支柱團隊已經簡要提及。

First, the reduction in triglycerides is both significant and sustained. In PALISADE, REDEMPLO reduced triglycerides by an unprecedented minus 80% from baseline as early as month one; and maintained this marked production, with minimal variation throughout the full 12-month treatment period. This compared to a minus 17% reduction in the pooled placebo group.

首先，三酸甘油酯的降低既顯著又持久。在 PALISADE 研究中，REDEMPLO 在第一個月就使三酸甘油酯水平比基線降低了前所未有的 80%；並且在整個 12 個月的治療期間，保持了這種顯著的降低幅度，且波動極小。相較之下，安慰劑組的合併結果為-17%的減少。

With REDEMPLO, patients now have real hope -- many, for the first time -- of achieving triglyceride levels below guideline-directed risk thresholds associated with acute pancreatitis, such as 500 milligrams per deciliter.

有了 REDEMPLO，患者現在有了真正的希望——許多患者是第一次——可以將三酸甘油酯水平降低到與急性胰臟炎相關的指南指導的風險閾值以下，例如每分升 500 毫克。

In PALISADE, 50% of patients at the 25-milligram dose achieved TG levels below 500 milligrams per deciliter, with approximately 75% achieving levels below 880 milligrams per deciliter at month 10.

在 PALISADE 研究中，接受 25 毫克劑量治療的患者中，50% 的患者在第 10 個月時 TG 水平低於每分升 500 毫克，約 75% 的患者 TG 水平低於每分升 880 毫克。

Second, the numerical incidence of acute pancreatitis in patients treated with REDEMPLO was lower compared with placebo. As we all know, this is the outcome of most importance for healthcare professionals, patients, and payers.

第二，接受 REDEMPLO 治療的患者發生急性胰臟炎的數值發生率低於接受安慰劑治療的患者。我們都知道，這對醫療專業人員、病患和支付者來說，是最重要的結果。

Third, REDEMPLO demonstrated favorable safety and tolerability. Importantly, the US-approved package insert contains no contraindications, no warnings, and no precautions associated with the use of REDEMTILO.

第三，REDEMPLO 表現出良好的安全性和耐受性。重要的是，美國批准的包裝說明書中沒有關於使用 REDEMTILO 的任何禁忌症、警告和注意事項。

Fourth, REDEMPLO can be self-administered at home, with a simple subcutaneous injection, once every three months; just four injections per year. Physicians tell us this infrequent dosing schedule is likely to reduce the treatment burden on physicians, patients, and caregivers.

第四，REDEMPLO 可以在家中自行注射，只需每三個月進行一次簡單的皮下注射；每年只需注射四次。醫生告訴我們，這種不頻繁的給藥方案可能會減輕醫生、患者和照護者的治療負擔。

And fifth, early feedback on the One-REDEMPLO pricing model has been positive. As Chris highlighted, this model creates one consistent price $60,000, per patient per year across current and potential future indications, such as severe hypertriglyceridemia. Again, this means that we will not ask different patients to pay different amounts for the same drug, based solely on what disease they have.

第五，One-REDEMPLO 定價模式的早期回饋是正面的。正如克里斯所強調的那樣，該模型為每位患者每年設定了一個統一的價格 60,000 美元，適用於當前和未來可能出現的適應症，例如嚴重的三酸甘油酯過高症。再次強調，這意味著我們不會因為患者患有某種疾病就要求他們為同一種藥物支付不同的費用。

We have been in important discussions with payers and early signs for market access are encouraging. As a reminder, we believe there are an estimated 6,500 people in the US living with genetic or clinical FCS.

我們與支付方進行了重要的討論，市場准入的早期跡象令人鼓舞。提醒大家，據估計，美國約有 6500 人患有遺傳性或臨床性 FCS。

The prescriber base comprises specialist physicians such as lipidologists, endocrinologists, preventive cardiologist, and internal medicine physicians with a focus on lipid disorders. These specialists often operate within multidisciplinary teams that may include gastroenterologists, advanced practice providers, and specialized dietitians. At launch, we are targeting approximately 5,000 healthcare professionals through personal engagement.

處方醫生群體包括脂質學家、內分泌學家、預防心臟病學家和專注於脂質失調的內科醫生等專家。這些專家通常在多學科團隊中工作，團隊成員可能包括腸胃病學家、高級執業醫師和專業營養師。在專案啟動初期，我們計劃透過個人互動的方式，鎖定約 5000 名醫療保健專業人員。

Finally, our Rely On REDEMPLO patient support program is operational and designed to make every step of the journey easier. This program is designed to assist patients and physicians with insurance verification, financial assistance options, a first-dose starter kit, and supplemental injection training.

最後，我們的 Rely On REDEMPLO 患者支援計畫已投入運營，旨在讓康復之路的每一步都更加輕鬆。該計劃旨在幫助患者和醫生進行保險核實、了解經濟援助方案、獲得首劑入門包和補充注射培訓。

We launched just one week ago but our care coordinators are already actively processing REDEMPLO start forms, conducting patient welcome calls, and engaging payers to obtain approvals.

我們雖然才上線一周，但我們的護理協調員已經積極處理 REDEMPLO 啟動表格、進行患者歡迎電話，並與付款方接洽以獲得批准。

As Chris stated, we're happy to announce that we already have drug available in channel, ahead of schedule.

正如克里斯所說，我們很高興地宣布，我們的藥物已經提前上架管道。

I will now turn the call over to James Hamilton to discuss the broader R&D portfolio. James?

現在我將把電話交給詹姆斯漢密爾頓，讓他討論更廣泛的研發組合。詹姆斯？

Thank you, Andy.

謝謝你，安迪。

I'd like to give a quick review of the status of our late-stage Phase 3 studies and also, describe the design in a couple of our early-stage programs.

我想快速回顧一下我們後期 3 期研究的進展情況，並介紹我們幾個早期專案的設計。

Let's start with the suite of Phase 3 studies of plozasiran, designed to potentially support supplemental NDA filing to expand the label beyond genetic and clinical FCS. SHASTA-3 and SHASTA-4 are Phase 3 studies, designed to compare reductions in triglycerides with 25 milligrams plus aspirin compared with placebo over 12 months of treatment. Between the two studies, we enrolled approximately 750 patients.

讓我們從 plozasiran 的 3 期研究系列開始，這些研究旨在支持補充 NDA 申請，以將標籤擴展到遺傳和臨床 FCS 之外。SHASTA-3 和 SHASTA-4 是 3 期研究，旨在比較服用 25 毫克阿斯匹靈與服用安慰劑 12 個月後三酸甘油酯的降低情況。這兩項研究共招募了約 750 名患者。

In addition, the MIRROR-3 study enrolled approximately 1,400 patients. This study in patients with mixed hyperlipidemia is designed to supplement the safety database when we file an sNDA for plozasiran in severe hypertriglyceridemia. We are not planning to seek approval in the mixed hyperlipidemia patient population.

此外，MIRROR-3 研究招募了約 1400 名患者。這項研究旨在補充混合型高脂血症患者的安全性資料庫，以便我們在向嚴重高三酸甘油脂血症患者提交 plozasiran 的補充新藥申請時使用。我們不打算尋求在混合型高脂血症患者群體中獲得批准。

We completed enrollment in the global SHASTA-3 and SHASTA-4, as well as MIRROR-3 Phase 3, clinical studies in June of 2025. We anticipate completing the primary portions of these studies in mid-2026, with top-line data expected in the third quarter of '26. If successful, we plan to make submissions before the end of 2026 for regulatory review and potential approval.

我們於 2025 年 6 月完成了全球 SHASTA-3 和 SHASTA-4 以及 MIRROR-3 第三階段臨床研究的受試者招募。我們預計將於 2026 年年中完成這些研究的主要部分，並預計在 2026 年第三季獲得初步數據。如果成功，我們計劃在 2026 年底前提交監管審查和可能的批准申請。

The SHTG program also features a study named SHASTA-5 to directly assess the ability of plozasiran to reduce the risk of acute pancreatitis as the primary endpoint in SHTG patients at high risk of acute pancreatitis. We are currently enrolling patients in that study.

SHTG 計畫還包括一項名為 SHASTA-5 的研究，旨在直接評估 plozasiran 降低急性胰臟炎風險的能力，這是 SHTG 高危險性胰臟炎患者的主要終點。我們目前正在招募患者參與這項研究。

Of note, we will also be assessing pancreatitis risk reductions in SHASTA-3 and SHASTA-4, a key secondary endpoint. But SHASTA-5 is the first event-driven study to assess acute pancreatitis as the primary endpoint.

值得注意的是，我們還將評估 SHASTA-3 和 SHASTA-4 中胰臟炎風險的降低情況，這是關鍵的次要終點。但 SHASTA-5 是首個以急性胰臟炎為主要終點的事件驅動型研究。

I'd also like to provide an update on our obesity programs, ARO-INHBE and ARO-ALK7. Both of these programs target the known Activin pathway that is involved in signaling to [adipocytes] to store fat.

我也想向大家介紹一下我們的肥胖症計畫 ARO-INHBE 和 ARO-ALK7 的最新進展。這兩個程序都針對已知的激活素通路，該通路參與向[脂肪細胞]發出信號以儲存脂肪。

ARO-INHBE inhibits one of the ligands in the pathway (inaudible) ARO-ALK7 inhibits the receptor on the (inaudible) that these ligands bind. Essentially, we are trying to reduce the message sent to store fat and the way the message is received at (inaudible).

ARO-INHBE 抑制該路徑中的一種配體（聽不清楚），ARO-ALK7 抑制這些配體結合的受體（聽不清楚）。本質上，我們試圖減少發送到儲存設備的資訊量以及接收資訊的方式。（聽不清楚）

ARO-INHBE started enrolling patients in December 2024 and ATO-ALK7 initiated in May of 2025. Both programs are currently in Phase 1/2a first-in-human dose-escalating studies to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics. Both programs include [Part 1], designed to assess single and multiple doses as monotherapy. [Part 2] is designed to assess multiple doses, in combination with (inaudible).

ARO-INHBE 於 2024 年 12 月開始招募患者，ATO-ALK7 於 2025 年 5 月開始。目前這兩個項目均處於第 1/2a 期首次人體劑量遞增研究階段，以評估安全性、耐受性、藥物動力學和藥效學。這兩個項目都包含[第一部分]，旨在評估單次和多次給藥作為單一療法的效果。 [第二部分]旨在評估多次給藥合併其他療法的效果。（聽不清楚）

As ARO-INHBE started about two quarters earlier, we have more mature data in that study. The study is nearly fully enrolled. We are on schedule and currently planning to share initial data from this program around the first week of 2026. This is a rather robust first-in-man study that's collecting multiple measures of drug activity and pathway activity. We are eager to share initial findings.

由於 ARO-INHBE 研究開始時間早了大約兩個季度，因此研究的數據更加成熟。該研究已接近完成招募。我們目前正按計劃進行，並計劃在 2026 年第一周左右分享該專案的初步數據。這是一項相當嚴謹的首次人體試驗，它收集了藥物活性和通路活性的多項指標。我們迫不及待地想與大家分享初步研究結果。

We were originally planning on sharing first data around the end of the year but due to the holidays and travel, the first week of January were the best for all schedules.

我們原本計劃在年底前後分享第一批數據，但由於假期和旅行，一月份的第一周對所有人來說都是最佳時間安排。

For ARO-ALK7, we intend to provide a brief snapshot of early safety and target engagement results from that study.

對於 ARO-ALK7，我們打算簡要介紹研究的早期安全性和標靶結合結果。

Both targets have strong genetic validation. Both programs have yielded promising results in preclinical studies. So it will be interesting to see similarities and differences in patient response in clinical trials.

這兩個標靶都具有很強的遺傳學驗證性。這兩個項目在臨床前研究中均取得了令人鼓舞的結果。因此，觀察臨床試驗中患者反應的異同將會很有趣。

I will now turn the call over to Dan Apel.

現在我將把電話交給丹·阿佩爾。

Thank you, James. Good afternoon, everyone.

謝謝你，詹姆斯。大家下午好。

I'll provide a brief outline of our financial results.

我將簡要概述一下我們的財務表現。

As we reported today, our net loss for fiscal year 2025 was $2 million or a loss of $0.01 per share, based on $133.8 million fully diluted weighted average shares outstanding. This near-breakeven result compares with a net loss of approximately $599 million or a loss of $5 per share, based on $119.8 million fully diluted weighted average shares outstanding in fiscal year 2024.

正如我們今天報導的那樣，根據 1.338 億股完全稀釋加權平均流通股計算，我們 2025 財年的淨虧損為 200 萬美元，即每股虧損 0.01 美元。這接近損益平衡的結果與 2024 財年淨虧損約 5.99 億美元或每股虧損 5 美元（基於 1.198 億股完全稀釋加權平均流通股）相比，可知虧損接近損益兩平。

Revenue for fiscal year 2025 totaled $829 million and was driven entirely by our license and collaboration agreements with Sarepta, Sanofi, and GSK. Of the $829 million, roughly $697 million pertained to the Sarepta arrangement; of that, $697 million $587 million relates to the ongoing recognition of initial Sarepta consideration; (inaudible) [$4 million] relates to the achievement of the first DM1 milestone; and $16 million related to the reimbursement of current collaboration program costs.

2025 財年的營收總計 8.29 億美元，完全得益於我們與 Sarepta、賽諾菲和葛蘭素史克的授權和合作協議。在 8.29 億美元中，約有 6.97 億美元與 Sarepta 安排有關；其中，6.97 億美元 5.87 億美元與持續確認 Sarepta 初始對價有關；（聽不清楚）[400 萬美元] 與實現第一個 DM1 里程碑有關；1600 萬美元與償還當前合作計劃成本有關。

Sditionally, the license Sanofi for Greater China (inaudible) plozasiran contributed $130 million to our fiscal 2025 revenue. Lastly, to round things out, we recorded $2.6 million earlier in the year related to a milestone payment under the GSK HBV agreement.

此外，賽諾菲在大中華區的許可（聽不清楚）plozasiran 為我們 2025 財年的收入貢獻了 1.3 億美元。最後，為了使情況更加完整，我們記錄了今年稍早與 GSK HBV 協議項下的里程碑付款相關的 260 萬美元。

Turning to expenses, total operating expenses for fiscal year 2025 were approximately $731 million compared to $605 million for fiscal 2024, an increase of $126 million. The year-over-year increase was driven by $101 million of R&D expenses and $25 million of higher SG&A costs, both of which I will explain in brief.

再來看支出，2025 財年的總營運支出約為 7.31 億美元，而 2024 財年為 6.05 億美元，增加了 1.26 億美元。年增幅主要由 1.01 億美元的研發支出和 2,500 萬美元的銷售、管理及行政費用增加所致，我將簡要解釋這兩點。

The key drivers of research and development spend included costs to run our clinical trials, our clinical manufacturing costs, as well as expense expenses related to active programs in the preclinical stage.

研發支出的主要驅動因素包括臨床試驗的運作成本、臨床生產成本以及與處於臨床前階段的活躍項目相關的費用。

2025 R&D costs were heavily impacted by our Phase 3 clinical trials for plozasiran and SHTG. It's worth noting that in fiscal year 2025, nearly two-thirds of our clinical trial spend can be attributed to the late-stage development of plozasiran and SHTG.

2025 年研發成本受到 plozasiran 和 SHTG 的 3 期臨床試驗的嚴重影響。值得注意的是，在 2025 財年，我們近三分之二的臨床試驗支出可歸因於 plozasiran 和 SHTG 的後期開發。

As we have mentioned, the SHTG registration of studies are now fully enrolled. We expect data to read out next year. Accordingly, the majority of remaining Phase 3 registration of clinical trial costs are expected to occur over the next 12 months.

正如我們之前提到的，SHTG 研究註冊現已全部完成。我們預計明年將公佈數據。因此，剩餘的 3 期臨床試驗註冊費用的大部分預計將在未來 12 個月內發生。

Our SG&A costs increased by $25 million year over year, driven primarily by our preparations for the commercialization of REDEMPLO.

我們的銷售、管理及行政費用比去年同期增加了 2500 萬美元，主要原因是我們為 REDEMPLO 的商業化所做的準備。

All of us here at Arrowhead are enormously proud of the capabilities we have built to commercialize REDEMPLO, not only in our commercial function but also across regulatory; supply chain; order to cash; and, indeed, across all of our enabling support functions.

我們 Arrowhead 的所有人都為我們為 REDEMPLO 的商業化所建立的能力感到無比自豪，這不僅體現在我們的商業職能方面，還體現在監管、供應鏈、訂單到現金以及我們所有的支援職能方面。

Turning now to cash flow, net cash provided by operating activities during fiscal year 2025 was $180 million compared with net cash used in operating activities of $463 million in the prior year for a net positive change year over year of $643 million. This increase in cash from operating activities was driven by cash received from licensing and collaboration agreements, partially offset by the aforementioned increase in R&D and SG&A costs.

現在來看看現金流，2025 財年經營活動產生的現金淨額為 1.8 億美元，而上一年經營活動使用的現金淨額為 4.63 億美元，較去年同期成長 6.43 億美元。經營活動現金流量的增加主要得益於授權及合作協議所帶來的現金收入，但部分則被上述研發及銷售、管理及行政費用的增加所抵銷。

Turning to the balance sheet, our cash and investments between the available-for-sale securities totaled $919 million as of September 30, 2025, compared to $681 million as of September 30, 2024. The increase in our cash and investments was primarily related to our licensing and collaboration agreement with Sarepta, Sanofi, and GSK, partly offset by our ongoing cash burn.

從資產負債表來看，截至 2025 年 9 月 30 日，我們的現金和可供出售證券投資總額為 9.19 億美元，而截至 2024 年 9 月 30 日為 6.81 億美元。我們的現金和投資增加主要與我們與 Sarepta、賽諾菲和葛蘭素史克的許可和合作協議有關，但部分被我們持續的現金消耗所抵消。

Our common shares outstanding as of the end of the quarter were $135.7 million, down $2.4 million from the prior quarter due mainly to the repurchase of shares from Sarepta.

截至本季末，我們已發行的普通股為 1.357 億美元，比上一季減少了 240 萬美元，這主要是由於從 Sarepta 回購了股份。

I use this opportunity to reiterate two developments that are subsequent to the fiscal year and meeting up today, which were financially meaningful for Arrowhead and our balance sheet:

我藉此機會重申本財年及今天會議之後發生的兩項重要進展，這兩項進展對Arrowhead及其資產負債表具有重要的財務意義：

Firstly, as Chris mentioned earlier on the call, we announced a licensing and collaboration agreement with Novartis for ARO-SNCA, Arrowhead's preclinical-0stage siRNA program targeting alpha (inaudible) for the treatment of synucleinopathies, such as Parkinson's disease.

首先，正如 Chris 先前在電話會議上提到的，我們宣布與諾華公司就 ARO-SNCA 達成許可和合作協議。 ARO-SNCA 是 Arrowhead 的臨床前 0 階段 siRNA 項目，針對 alpha（聽不清楚），用於治療突觸核蛋白疾病，例如帕金森氏症。

Novartis will also be able be to select a limited number of additional collaboration targets, outside of Arrowhead's current pipeline, to be developed using our proprietary TRiM platform. The closing occurred last month. We have already received $200 million in the bank as an upfront payment.

諾華還可以選擇在 Arrowhead 目前的研發管線之外，利用我們專有的 TRiM 平台開發數量有限的其他合作目標。交易於上個月完成。我們已經收到銀行帳戶裡的2億美元預付款。

As a reminder, we also got to receive up to $2 billion in future milestone payments from Novartis, as well as royalties on commercial sales.

提醒一下，我們還將從諾華公司獲得高達 20 億美元的未來里程碑付款，以及商業銷售的特許權使用費。

Secondly, just yesterday, we announced we earned our second development milestone under the Sarepta collaboration agreewmnt of ARO-DM1. As Chris mentioned, this trigger a $200 million obligation from Sarepta that will be recorded in the first quarter of fiscal 2026. We expect to receive the cash in January of 2026. This is, of course, additional to the $100 million earned for the first DM1 milestone in fiscal quarter-four 2025.

其次，就在昨天，我們宣布我們根據與 Sarepta 的合作協議 ARO-DM1 實現了第二個開發里程碑。正如克里斯所提到的，這將導致 Sarepta 產生 2 億美元的債務，該債務將在 2026 財年第一季計入帳目。我們預計將於 2026 年 1 月收到這筆款項。當然，這還不包括 2025 財年第四季第一個 DM1 里程碑所獲得的 1 億美元營收。

Finally, we are not providing detailed financial guidance at this time for the coming fiscal year. Beyond reiterating that while we view the launch of REDEMPLO as a truly transformational event for the company, we do not anticipate that the commercial sales of REDEMPLO will have a substantial impact on our financial statements in fiscal year 2026.

最後，我們目前不提供下一財年的詳細財務指引。除了重申雖然我們認為 REDEMPLO 的推出對公司而言是一件真正具有變革意義的事件之外，我們預計 REDEMPLO 的商業銷售不會對我們 2026 財年的財務報表產生重大影響。

We also believe our cash runway, even in the absence of any further capital from new deals or other sources and all the while funding a broad ambitious set of commercial clinical programs, to be sufficient to extend into fiscal year 2028.

我們也相信，即使沒有來自新交易或其他來源的進一步資金，並且同時還要資助一系列雄心勃勃的商業臨床項目，我們的現金儲備也足以支撐到 2028 財年。

With that, I will now turn the call back to Chris.

接下來，我將把電話轉回給克里斯。

Thanks, Dan.

謝謝你，丹。

Arrowhead has been working to bring important medicines to patients in need for over 15 years. As Bruce mentioned, it's very gratifying to see REDEMPLO approved by the FDA and the overwhelmingly encouraging feedback we received from the FCS community.

15 年來，Arrowhead 一直致力於為有需要的患者提供重要的藥物。正如 Bruce 所提到的，看到 REDEMPLO 獲得 FDA 批准，以及我們從 FCS 社群收到的壓倒性的鼓勵性回饋，我們感到非常欣慰。

While REDEMPLO is just one part of a large pipeline that we've created to help potentially millions of patients in a diverse set of disease areas, we spent years building the TRiM platform to enable us to bring RNAi where it is needed. We are now able to address seven different cell types and have current clinical programs in five of these.

雖然 REDEMPLO 只是我們為幫助數百萬不同疾病領域的患者而創建的龐大產品線的一部分，但我們花了數年時間構建 TRiM 平台，使我們能夠將 RNAi 帶到需要的地方。我們現在能夠處理七種不同的細胞類型，目前已針對其中五種進行臨床計畫。

Further, we will meet our 20 in 25 goal, whereby we will have 20 individual drugs candidates in clinical trials by the end of this year. Our partner has been helpful (inaudible) judicious, with approximately half of our clinical pipeline wholly owned and have partnered.

此外，我們將實現 20 in 25 的目標，即到今年年底，我們將有 20 個獨立的候選藥物進入臨床試驗階段。我們的合作夥伴一直非常樂於助人（聽不清楚）且謹慎，我們臨床研發管線中大約一半的產品都是完全由我們擁有和合作開發的。

We have late-stage studies ongoing, again, both independently and with partners, that may potentially lead to multiple new commercial loans over the next few years. In addition, we have a strong financial position that enables us to properly invest in our growth today and in the future.

我們目前正在進行後期研究，既有獨立研究，也有與合作夥伴共同進行的研究，這些研究有可能在未來幾年內促成多筆新的商業貸款。此外，我們擁有雄厚的財務實力，使我們能夠對當前和未來的發展進行適當的投資。

We believe we now have everything we need to be in the next class of large and ultimately profitable biotech companies.

我們相信，我們現在已經具備成為下一代大型且最終獲利的生技公司所需的一切條件。

Thanks for joining us today. I would now like to open the call to your questions. Operator?

感謝您今天收看我們的節目。現在我想接受大家的提問。操作員？

(Operator Instructions)

（操作說明）

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

Bruce, congrats in your re-retirement, I should say. All the best in your next chapter.

布魯斯，我應該說，恭喜你再退休。祝你在人生的下一個階段一切順利。

And then, maybe if I can stick with you, can you just maybe talk about what's the plan to show a benefit in terms of acute pancreatitis for plozasiran? Are you confident just the [3] and [4] in Q3 2026 can actually hit acute pancreatitis? Or is the base-case scenario those two trials are maybe under power to show a benefit and you actually need SHASTA-5 to actually hit on acute pancreatitis, (inaudible) enriched for (inaudible) pancreatities.

然後，如果我可以繼續問您這個問題，您能否談談普洛扎西蘭在治療急性胰臟炎方面的療效計劃是什麼？您確信 2026 年第三季的 [3] 和 [4] 真的能夠治療急性胰臟炎嗎？或者，基本情況是，這兩項試驗可能沒有足夠的統計效力來顯示益處，而實際上需要 SHASTA-5 才能真正治療急性胰臟炎，（聽不清楚）富含（聽不清楚）胰臟。

The only reason why I'm asking is it looks like you doubled the size of the end, I should say, in the SHASTA-5 trial, according to click (inaudible), as of Monday last week. Again, any color there, much appreciated.

我問這個問題的唯一原因是，根據上週一的點擊（聽不清楚）顯示，在 SHASTA-5 試驗中，你們似乎將末端的尺寸增加了一倍。再次感謝大家提供任何顏色。

Sure, Luca. Thank you for your kind regards.

當然可以，盧卡。謝謝你的好意。

SHASTA-3 and 4 were powered on the basis of triglyceride reduction, which is the primary endpoint. We did not specifically powered SHASTA-3 and 4 for pancreatitis.

SHASTA-3 和 4 的研究以三酸甘油酯降低為主要終點。我們沒有專門針對胰臟炎研發 SHASTA-3 和 4。

However, it was on our mind; and, as was also done in the core studies, there is the intent and by design, the capability, to pull both SHASTA-3 and 4 for evaluating versus placebo on reduction of pancreatitis.

然而，我們一直都在考慮這個問題；而且，正如核心研究中所做的那樣，我們有意願也有能力將 SHASTA-3 和 4 都拿出來，與安慰劑相比，評估其在減少胰臟炎方面的作用。

Of course, we only have one dose of plozasiran instead of two different doses like we had, for instance, in the Phase 2 program.

當然，我們只有一種劑量的 plozasiran，而不是像我們在第 2 期臨床試驗項目中有兩種不同的劑量。

There's, I would say, reasonably good power for seeing a difference in acute pancreatitis. But we're not dependent on it because we've designed SHASTA-5, specifically, to obviously be able to have a primary endpoint of acute pancreatitis.

我認為，它具有相當不錯的功效，可以區分急性胰臟炎。但我們並不依賴它，因為我們專門設計了 SHASTA-5，使其能夠以急性胰臟炎為主要終點。

We did change the design in SHASTA-5, recently, to making a more generalizable population in patients with persistent (inaudible) and a history of pancreatitis. The original design was a much more enriched population. But it would have actually been less representative than the duly designed trial.

最近，我們在 SHASTA-5 中改變了設計，使其更具普遍性，納入了持續性（聽不見的）胰臟炎病史患者。最初的設計所設想的人口組成要豐富得多。但實際上，它不如精心設計的審判更具代表性。

So it's not so much a matter that we've increased power so much as we broadened the power the patient population to be more inclusive of the high-risk population in SHTG.

所以，與其說我們增加了權力，不如說我們擴大了病患群體的權力範圍，使其更能包容SHTG中的高危險群。

We certainly -- we oftentimes refer to it as a (inaudible) approach. There's obviously a decent chance that we will show statistical significance in the SHASTA-3 and 4 programs. But we're not entirely dependent on that because of SHASTA-5, which is a study -- the first of its kind (inaudible) specifically designed to demonstrate a benefit versus placebo in acute pancreatitis.

我們當然——我們經常稱之為（聽不清楚）方法。顯然，我們在 SHASTA-3 和 4 專案中很有可能取得統計學意義上的顯著成果。但我們並不完全依賴於此，因為 SHASTA-5 是一項研究——首個專門設計用於證明其對急性胰臟炎患者有益的研究（聽不清楚）。

Prakhar Agrawal, Cantor Fitzgerald.

普拉哈·阿格拉沃爾，坎托·菲茨杰拉德。

Congrats on the quarter, as well as the updates throughout the quarter.

恭喜本季取得的成績，以及本季以來發布的各項更新。

Maybe on the obesity side, I had a couple of questions. On (inaudible) for the update early next year, if you can just provide more details on how much data will be disclosed, especially on the (inaudible) side. How much follow-up will you have on (inaudible) for both monotherapy and combo cohorts?

關於肥胖問題，我有一些疑問。關於（聽不清楚）明年年初的更新，如果您能提供更多關於將披露多少數據的細節，特別是（聽不清楚）方面。您將對單藥治療組和合併治療組進行多少追蹤？ （聽不清楚）

Also, the same question on ARO-ALK7, what cohorts will be disclosed and will there be any weight loss data at all from ALK7 early in the year?

另外，關於 ARO-ALK7 也有同樣的問題，將會公佈哪些隊列，以及今年年初是否會有任何關於 ALK7 的減肥數據？

Yeah. Sure, Prakhar. This is James. I can cover that.

是的。當然可以，普拉卡爾。這是詹姆斯。我可以負責這件事。

For (inaudible), it's a little bit ahead, as Chris mentioned, probably by a couple of quarters. The study is nearly fully enrolled. We have a good amount of data in both the SAD and MAD healthy volunteer or obese healthy volunteer cohorts. We'll have biomarker data, MRI data, as well as safety in those cohorts.

對於（聽不清楚）來說，正如克里斯所提到的，它稍微領先一點，可能領先兩格。該研究已接近完成招募。我們在 SAD 和 MAD 健康志願者或肥胖健康志願者隊列中都有相當多的數據。我們將獲得這些隊列的生物標記數據、MRI 數據以及安全性數據。

And then, the combo cohorts are almost fully enrolled. I think we're waiting on a few more diabetic patients to enroll the highest-dose combo cohorts. That should have -- probably not through end of study but ample post-dose follow-up in both the diabetic and the non-diabetic cohorts from (inaudible).

然後，組合隊列幾乎全部招募完畢。我認為我們還在等待更多醣尿病患者加入最高劑量合併治療組。應該如此——或許無法在研究結束時得出結果，但應該對糖尿病患者和非糖尿病患者群體進行充分的給藥後隨訪。（聽不清楚）

And then, ALK 7 will be a little bit more limited, focused mostly on monotherapy, safety, and knockdown data -- knockdown of target for that study.

然後，ALK 7 的研究範圍會稍微窄一些，主要集中在單藥治療、安全性和基因敲低數據上——研究的目標是基因敲低標靶。

Yeah. Keep in mind here that we want to present data that are interpretable. We're not going to have all cohorts. We're not going to have all patient data in all cohorts, even if they're fully enrolled. We don't get data in real time, necessarily. And so you'll have probably two bites of the apple -- maybe three bites. But, certainly, two bites of the apple.

是的。請記住，我們希望呈現的數據是可解釋的。我們不可能召集到所有群體。即使所有隊列都已全部入組，我們也不可能獲得所有隊列的所有患者資料。我們不一定能即時取得數據。所以你可能只能吃兩口蘋果——也許三口。但可以肯定的是，至少吃了兩口蘋果。

Our goal here (inaudible) data is to give you an idea about how these are going and then, the (inaudible) should come out once we have the more fulsome data set in the later in '26.

我們在這裡的目標是（聽不清楚）提供數據，讓您了解這些進展情況，然後，一旦我們在 2026 年晚些時候獲得更完整的數據集，（聽不清楚）就會發布。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特，傑富瑞。

Congrats on the progress. Best wishes, Bruce, in retirement.

恭喜你取得進展。祝福布魯斯退休生活一切順利。

I was going to ask a follow-up to Luca's question earlier. We're expecting to see the patient baseline profile for your SHTG pivotals next week. What are your estimates on AP events accrual, based on your patient's baseline characteristics; and also, your change in plans to broaden AP adjudication criteria.?

我本來想就盧卡之前提出的問題問一個後續問題。我們預計下週將收到您SHTG關鍵試驗的患者基線資料。根據病患的基線特徵，您對AP事件的累積數量有何估計？另外，您在擴大AP裁決標準方面的計劃變更方面有何變化？

Maury, I think it's a little bit hard to answer the question, just because we have adapted our protocols now to go ahead and adopt the -- to modify (inaudible) criteria since those have been accepted by both FDA and EMA -- here in the US, at least payers.

莫里，我認為這個問題有點難以回答，因為我們現在已經調整了我們的方案，以繼續採用——修改（聽不清楚）標準，因為這些標準已被美國食品藥品監督管理局 (FDA) 和歐洲藥品管理局 (EMA) 接受——至少在美國，支付方已經接受了這些標準。

This is really going to be our first experience with using that particular scale, which makes it a little hard to estimate exactly how many events we will have. So it's hard to say.

這將是我們第一次使用這種特定的規模，因此很難準確估計我們會有多少場活動。所以很難說。

What you will see next week is you will see the percentage of patients that had a history of pancreatitis that were enrolled in the study. Based on that, that -- I think you'll see that there's a good chance that we'll have the necessary number of events.

下週您將看到，參與這項研究的、有胰臟炎病史的患者所佔的百分比。基於此，我認為你會發現我們很有可能舉辦足夠數量的賽事。

But I'm a little bit uncomfortable trying to give any real predictions, when we're using a scale that we haven't used before.

但是，當我們使用以前從未使用過的尺度時，我不太願意做出任何真正的預測。

Jason Gerberry, Bank of America.

傑森‧格伯里，美國銀行。

This is [Gina], on for Jason. Congrats on all the progress this quarter. Just a couple from us.

這是吉娜，她替傑森上場。恭喜本季取得的所有進展。我們兩個就說這兩點吧。

First on your ARO-MAPT program, can you maybe just discuss which aspects of the drug is differentiated from (inaudible) recently failed anti-tau antibody and what [comp] still gives you the confidence in the target after the failure?

首先，關於您的 ARO-MAPT 項目，您能否討論一下該藥物與最近失敗的抗 tau 抗體有哪些不同之處，以及在失敗之後，是什麼[比較]仍然讓您對該靶點充滿信心？

And then, just based on your current cash position and the progress that you've made on these partners -- partnership milestone triggers, do you have any maybe updates on your visibility on launching a CVOT study? Is that more tied to seeing how the FCS and potential TG launches are progressing?

那麼，根據您目前的現金狀況以及您在這些合作夥伴方面取得的進展——合作里程碑觸發因素，您對啟動 CVOT 研究有任何更新資訊嗎？這是否更多地與觀察 FCS 和潛在的 TG 發射進展有關？

And then, can you just remind us, like, any potential milestone triggers from the Sarepta programs that you're expecting in 2026?

那麼，您能否提醒我們一下，您預計 Sarepta 專案在 2026 年會有哪些潛在的里程碑觸發事件？

All right. I (inaudible) three questions. James want to take the first one.

好的。我（聽不清楚）三個問題。詹姆斯想拿第一個。

Sure. Yeah. I'll take the first 1 on the MAPT program.

當然。是的。我選 MAPT 計畫的第一個名額。

The J&J antibody, the monoclonal, as well as other monoclonals, our IV-administrated monoclonal antibodies, probably a small fraction of those molecules cross the blood-brain barrier; and then, are primarily focused on binding to extracellular (inaudible) that's been released for damaged cells or has been secreted and that can propagate (inaudible) find it to tau outside of the cell.

強生公司的抗體、單株抗體以及其他單株抗體，我們靜脈注射的單株抗體，可能只有一小部分分子能夠穿過血腦障壁；然後，它們主要集中在與受損細胞釋放或分泌的細胞外物質（聽不清楚）結合，這些物質可以傳播（聽不清楚），並在細胞外找到 tau 蛋白。

Our approach is very different. We use a targeting ligand to facilitate delivery of the siRNA across the blood-brain barrier into the neuron and silence the expression of tau. So we're turning off the faucet for all of the expression in preventing the (inaudible) to form in the first place.

我們的方法截然不同。我們使用標靶配體來促進 siRNA 穿過血腦屏障進入神經元，從而抑制 tau 蛋白的表達。所以，我們從源頭阻止了（聽不清楚）的形成，從而切斷了所有表達的途徑。

We should get that -- over time, be able to reduce the level of intracellular tau and extracellular tau, whereas the monoclonal antibodies are really just able to get the extracellular tau.

我們應該能夠隨著時間的推移，降低細胞內 tau 蛋白和細胞外 tau 蛋白的水平，而單株抗體實際上只能去除細胞外 tau 蛋白。

That's the key differentiator.

這是關鍵區別所在。

On the other two questions, I'll answer the last one first, the Serapta (inaudible). We are eligible to receive the first of $50 million annuities in February. We expect that over the next several months.

至於另外兩個問題，我先回答最後一個，即塞拉普塔。（聽不清楚）我們有資格在二月領取第一筆 5000 萬美元的年金。我們預計未來幾個月內會出現這種情況。

That's correct? February, right, Dan?

沒錯吧？二月，對吧，丹？

Yeah.

是的。

On the visibility on the CVOT -- so that CVOT, as you know, is for the DIMER. That's a big opportunity for us. And so we are moving as quickly as we can to that CVOT. We'll have a good idea, I think, this summer, if we have a drug.

關於 CVOT 的可見性——如您所知，CVOT 是用於 DIMER 的。這對我們來說是一個絕佳的機會。因此，我們正在盡最大努力盡快推進CVOT專案。我認為，今年夏天我們就能很清楚知道我們是否研發出了這種藥物。

We'll know (inaudible) knockdown. We'll know (inaudible) knockdown. We'll know LDL decreases. We'll triglyceride decreases.

我們將知道（聽不清楚）擊倒。我們將知道（聽不清楚）擊倒。我們將知道低密度脂蛋白膽固醇（LDL）降低了。三酸甘油酯會降低。

So given what those data look like, I think, again, as early as this summer, I think we'll know if we have something that really could be an important treatment (inaudible) mixed hyperlipidemia patients.

所以根據這些數據來看，我認為，最早在今年夏天，我們就能知道我們是否找到了一種真正可以治療（聽不清楚）混合型高血脂患者的重要療法。

Should that be successful, should now look good, we are not waiting on anything to start those studies other than finishing the Phase 1/2. Our plan is to be able to roll directly into pivotal studies after the Phase 1/2 studies. Again, should they all go well and there's nothing gating there other than the data looking good.

如果成功的話，現在看來情況不錯，除了完成 1/2 期試驗之外，我們無需等待任何事情即可開始這些研究。我們的計劃是在完成 1/2 期研究後，直接進入關鍵性研究。再說一遍，如果一切順利，除了數據看起來不錯之外沒有其他障礙的話。

We also are hoping to have parallel pivotal studies, one that will be a CVOT and one that we'll be looking at simply lowering LDL over the course of the year. As you know, that has been an approval endpoint in the past for (inaudible) inhibitors. We think that could be a good way to get to market very quickly; and, frankly, help us to pay for the CVOT.

我們也希望進行平行的關鍵性研究，一項是心血管結局試驗 (CVOT)，另一項則是研究在一年內降低低密度脂蛋白膽固醇 (LDL) 水平的情況。如您所知，這在過去一直是（聽不清楚）抑制劑的批准終點。我們認為這可能是快速進入市場的好方法；坦白說，還能幫助我們支付 CVOT 的費用。

That's our plan now. We'll have a much better idea about how quickly we can move in the summertime, once we start to see those data. We're really looking forward to seeing those data.

這就是我們現在的計劃。一旦我們開始看到這些數據，我們就能更了解夏季期間我們可以以多快的速度推進工作。我們非常期待看到這些數據。

Edward Tenthoff, Piper Sandler.

愛德華·滕索夫，派珀·桑德勒。

Great. Bruce, wishing you all the best. James, wishing you all the best of luck. It really is a super exciting time for the company.

偉大的。布魯斯，祝你一切順利。詹姆斯，祝你一切順利。對公司而言，這確實是一個令人無比令人興奮的時刻。

I wanted to get a sense, just with respect to upcoming data readouts next year, specifically asking, do you think you'll have your first look from the AERO-DIMER-PA next year? What other data sets beyond the obesity data in the first half should we be thinking about?

我想了解明年即將公佈的數據，具體來說，您認為明年您能從 AERO-DIMER-PA 獲得第一手數據嗎？除了上半年的肥胖數據之外，我們還應該考慮哪些其他數據集？

Thanks, Dan. We have a bunch of, I think, potentially, a very interesting data readout throughout 2026. As you mentioned, obesity will be the first. As I mentioned, we should have two bites of that Apple or thereabouts.

謝謝你，丹。我認為，我們在 2026 年可能會獲得很多非常有趣的數據讀數。正如你所提到的，肥胖將是首要問題。正如我之前提到的，我們應該吃兩口蘋果，或差不多兩口。

We'll have our first early data set in the very first part of January. And then, as the data mature in both those programs, say, towards the end of the second quarter, something around then, we'll have a much larger data set. We think those are important.

我們將在1月初獲得第一批早期資料集。然後，隨著這兩個專案中的數據日趨成熟，比如說，到了第二季末左右，我們將擁有一個更大的資料集。我們認為這些很重要。

In the summertime, we expect to have DIMER data. We think those are extraordinarily important. The idea that we might have a drug candidate that can simultaneously the lower LDL and triglycerides to treat the 20 million or so people in the United States with mix hyperlipidemia is a very exciting opportunity. Again, I think we'll know if we have something that could really fit there in the summertime.

預計夏季我們將獲得 DIMER 數據。我們認為這些極為重要。我們或許能找到一種候選藥物，可以同時降低低密度脂蛋白和三酸甘油酯，從而治療美國約 2000 萬患有混合型高脂血症的人，這是一個非常令人興奮的機會。我想，到了夏天，我們就能知道我們是否有真正適合那裡的東西了。

Also, in the summertime, I think we'll have our first bit of ARO-MAPT data. We'll be looking for tau levels in (inaudible). That, also, would be extraordinarily exciting. We can be, at once, sitting on one of the most exciting potential Alzheimer's drugs in the clinic. Hopefully, we'll be de-risking the entire blood barrier platform that can enable us to treat a variety of CNS diseases. And so that's an important readout.

另外，我認為在夏季，我們將獲得第一批 ARO-MAPT 數據。我們將尋找 tau 蛋白質水平（聽不清楚）那也將會非常令人興奮。我們可能同時掌握著臨床上最令人興奮的阿茲海默症潛在藥物之一。希望我們能夠降低整個血腦屏障平台的風險，從而使我們能夠治療各種中樞神經系統疾病。所以這是一項重要的數據。

Of course, also in the third quarter or so, we expect to have the readout for SHASTA-3 and 4 that are designed to enable the (inaudible) by the end of the year. And then, of course, at the end of the year, we expect to have file our (inaudible).

當然，我們也預計在第三季左右，就能獲得 SHASTA-3 和 4 的讀數，它們旨在實現（聽不清楚）到今年年底。當然，到了年底，我們預計還要提交我們的…（聽不清楚）

Look, there will be other things happening during the year. But those, to me, like, the primary ones.(inaudible) in the market (multiple speakers).

你看，一年中還會發生其他事情。但對我來說，這些才是市場上最主要的。 （聽不清楚）（多位發言者）

We will be really looking forward to seeing how -- the adoption curve that REDEMPLO is going to have.

我們非常期待看到 REDEMPLO 的普及曲線會如何發展。

Great. Any update on (inaudible), just to be comprehensive?

偉大的。關於（聽不清楚）有什麼最新進展嗎？為了全面起見，請問一下？

Yeah. Thank you. Yes. As you know, Ed, the data, so far, for (inaudible) has been enticing. We've seen that we can knockdown (inaudible) deeply, both looking at circulating biomarkers, as well as tau. That's super interesting.

是的。謝謝。是的。艾德，你知道，到目前為止，（聽不清楚）的數據一直很誘人。我們已經看到，無論是觀察循環生物標記還是 tau 蛋白，我們都可以大幅降低（聽不清楚）。這太有意思了。

Where we've struggled is looking for biomarkers to show potential clinical benefit. And so rather than running directly into a large asthma or (inaudible) Phase 2, we were hoping to have a baby step to see some evidence of that.

我們遇到的困難在於尋找能夠顯示潛在臨床益處的生物標記。因此，我們不希望直接陷入嚴重的氣喘或（聽不清楚）第二階段，而是希望邁出一小步，看看能否看到一些跡象。

And so we have started a challenge study. I don't expect to have data in '26, maybe at the very end of '26, but we've just started that. And so my hope is that that will show us that knocking down range is an important thing.

因此，我們啟動了一項挑戰性研究。我預計 2026 年不會有數據，也許要到 2026 年底才能有，但我們才剛開始這項工作。所以我希望這能向我們表明，縮小射程是一件重要的事情。

Look, it's been an undrugged target for some time. Now, we can drug it. So now, let's see let's see what that does for us.

你看，它已經是一個長期未被濫用的靶子了。現在我們可以給它下藥了。那麼現在，讓我們看看這能為我們帶來什麼好處。

I think at the end of that, we can then ask ourselves, do we want to build out a pulmonary franchise or do we want to partner that? I think a positive challenge study readout would allow us to partner that under attractive terms.

我認為最後我們可以問自己，我們是想建立肺科特許經營權，還是想與之合作？我認為，如果挑戰性研究結果積極，我們將能夠以有吸引力的條件與之合作。

Mani Foroohar, Leerink Partners.

Mani Foroohar，Leerink Partners。

Congrats on the progress on the first product launch. Best wishes also to Bruce on his re-retirement, though something tells me you're going to pop up again soon. I don't think you're done with us.

祝賀首款產品發布取得進展。也祝布魯斯再次退休一切順利，不過我總覺得你很快就會再次出現。我覺得你還沒完事兒。

Aporopos of the question, can I -- I want to follow up on the broader pipeline. I know Ted touched on new Arrowhead study, et cetera. How do we think about Arrow DIMER application, in terms of pursuing CVOT and the right target for that technology?

關於這個問題，我可以——我想跟進更廣泛的管道情況。我知道泰德提到了Arrowhead公司的新研究等等。我們如何看待 Arrow DIMER 的應用，從追求 CVOT 和該技術的正確目標來看？

Where are the right places for you to put that to work now that you've got a very different place in terms of your balance sheet?

既然你的資產負債表已經發生了很大的變化，那麼你該在哪裡運用這些資源呢？

Actually, Bruce, do you want to take where that can fit?

實際上，布魯斯，你想把這件事放在合適的位置嗎？

Yeah. I'm happy to take that.

是的。我很樂意接受。

Obviously, we're excited about plozasiran and (inaudible) inhibition, generally, for patients with severe hypertriglyceridemia. That's been, essentially, a very, very poorly treated population for a long time.

顯然，我們對 plozasiran 和（聽不清楚）抑制劑總體上治療重度高三酸甘油酯血症患者感到興奮。從本質上講，這部分人群長期以來都受到了非常非常糟糕的對待。

LDL, the LDL side of the equation, on the other hand, has been really a different story. Other than HOFH, there is a pretty good number of tools in the tool chest for dealing with LDL, the patients on that LDL side of the equation, especially patients with heterozygous familial hypercholesterolemia, which is a pretty good size population for instance.

另一方面，低密度脂蛋白（LDL）的情況則截然不同。除了 HOFH 之外，還有很多工具可以用來治療 LDL，治療 LDL 患者，特別是患有雜合子家族性高膽固醇血症的患者，這是一個相當大的群體。

But the 20-some million patients in the US alone that have mixed hyperlipidemia has been an interesting population. We could address the LDL part. We've done really a terrible job, historically, of being able to address the triglyceride piece of that. The (inaudible) analysis that have been done (inaudible) CVOT has shown that for the same LDL reduction, you can really rank order the risk that patients have by how high the triglycerides are.

但光在美國就有兩千多萬患有混合型高血脂症的患者，這是一個很有趣的族群。我們可以討論低密度脂蛋白（LDL）部分的問題。從歷史上看，我們在處理三酸甘油酯問題上做得非常糟糕。已進行的（聽不清楚）分析（聽不清楚）CVOT 表明，對於相同的 LDL 降低，您可以根據三酸甘油酯的高低對患者的風險進行排序。

Of course, the Mendelian randomization data has also said that triglycerides are independent predictor of events and mortality in that mixed hyperlipidemia population. It is huge. It's a very good population. So there's never really been a very good way of addressing both sides of the problem in mixed hyperlipidemia, both the LDL and the triglycerides.

當然，孟德爾隨機化數據也表明，三酸甘油酯是混合型高血脂症族群中事件和死亡率的獨立預測因子。它非常巨大。這是一個非常好的人口群。因此，對於混合型高血脂症，一直沒有很好的方法來同時解決低密度脂蛋白和三酸甘油酯的問題。

Here, we're talking about a drug that could potentially do it with a single, say, quarterly injection, get both their LDL and their triglycerides, probably on top of the (inaudible). I think you're going to always have a statin there if the patients can tolerate it.

這裡我們討論的是一種藥物，它可能只需單次注射（例如每季注射一次），就能降低患者的低密度脂蛋白膽固醇和三酸甘油酯水平，而且可能還能達到其他效果。（聽不清楚）我認為，如果患者能夠耐受，那麼你肯定會一直給他們服用他汀類藥物。

But you could have a daily (inaudible) at a quarterly DIMER injection and potentially treat that 20 million patients to low-risk levels of LDL and triglycerides. That would be quite an amazing opportunity, I think, from a marketing perspective compared to what you can do today, which is you can probably get the LDL taken care of today but you probably can't do much at all worthwhile in the triglycerides.

但是，您可以每天（聽不清楚）或每季注射一次 DIMER，並有可能將 2000 萬患者的 LDL 和三酸甘油酯水平降低到低風險水平。我認為，從行銷的角度來看，這將是一個非常棒的機會，與你今天所能做的相比，你現在或許可以解決低密度脂蛋白膽固醇的問題，但你可能在三酸甘油酯方面做不了什麼有意義的事情。

This is what makes this to us such an interesting proposition.

這正是我們認為這個提議如此有趣的原因。

Yeah. As you know, Mani, what we used to -- our former strategy was to make plozasiran and REDEMPLO a (inaudible). Step 1 is FCS; step 2 (inaudible) HCG, step 3, after CVOT, would be this -- would be to be a part treatment in mid hyperlipidemia.

是的。如你所知，馬尼，我們過去的做法——我們之前的策略是讓 plozasiran 和 REDEMPLO 成為（聽不清楚）第一步是 FCS；第二步（聽不清楚）HCG，第三步，在 CVOT 之後，將是這樣的——這將是中度高血脂治療的一部分。

Once we were able to perfect, at least in animals, the DIMER platform, it didn't make sense any longer. We like the idea of keeping REDEMPLO as a pure-play pancreatitis drug, full-stop. Now, I think we'll have a tool to more completely treat that next hyperlipidemia population, should this time translate well from animals to humans.

一旦我們能夠完善 DIMER 平台（至少在動物身上），它就沒有存在的必要了。我們喜歡將 REDEMPLO 定位為純粹的胰臟炎藥物，僅此而已。現在，我認為我們將擁有一種工具，可以更全面地治療下一批高血脂症患者，前提是這次的研究能從動物身上成功轉化到人類身上。

That's helpful. As a follow-up, when you think about potential DIMER applications, et cetera, how are you thinking about the data next year from Horizon and potentially applications of combining what hopefully will be a validated (inaudible) target with other approaches to risk elevating elements of a lipid profile?

那很有幫助。作為後續問題，當您考慮 DIMER 的潛在應用等時，您如何看待明年 Horizo​​​​n 的數據，以及將有望得到驗證的（聽不清的）靶點與其他方法結合起來以降低脂質譜風險因素的潛在應用？

Yeah. Sure. Of course, our siRNA targeting (inaudible) is partnering with Amgen. So we would have to work with them on any DIMER applications. But there are other applications beyond, of course, (inaudible) and [AOCI].

是的。當然。當然，我們的 siRNA 標靶治療（聽不清楚）正在與安進公司合作。因此，在任何 DIMER 應用方面，我們都必須與他們合作。當然，除此之外還有其他應用，（聽不清楚）[AOCI]。

We're looking at other DIMERS in the CV space, both turning the (inaudible) and [extrahepatic] cell types. So this is probably not the only DIMER that you'll see out of Arrowhead.

我們正在研究 CV 空間中的其他 DIMERS，包括（聽不清楚）和[肝臟以外]細胞類型。所以這可能不是你在 Arrowhead 看到的唯一一款 DIMER。

Patrick Trucchio, H.C. Wainwright.

派崔克·特魯基奧，H.C. 溫賴特。

Congrats on the progress. I have a few follow-up questions.

恭喜你取得進展。我還有幾個後續問題。

Just the -- first is just regarding REDEMPLO. I'm wondering if the FDA has provided clarity on what level of pancreatitis evidence will be required for a future of pancreatitis risk reduction claim in the -- particularly, in the high-risk SHTG patient population.

首先，關於 REDEMPLO 的問題。我想知道 FDA 是否已明確說明，未來在降低胰臟炎風險方面需要提供何種程度的胰臟炎證據——尤其是在高風險的 SHTG 患者群體中。

Separately, I'm wondering if there's been discussions around potential pediatric pathway, just given FCS presents in childhood.

另外，我想知道是否有人討論過可能的兒科治療途徑，因為 FCS 也可能出現在兒童時期。

And then, just a follow-up on the MAPT program, I'm wondering what level of CSF tau knockdown or biomarker response would you consider clear clinical proof of concept in humans, just given, I think, you have greater than 75% knockdown in the [NHP] data?

然後，關於 MAPT 項目，我想跟進一下，鑑於我認為你們在 [NHP] 數據中已經實現了超過 75% 的腦脊髓液 tau 蛋白敲低或生物標誌物反應，您認為達到什麼水平的腦脊液 tau 蛋白敲低或生物標誌物反應才能算是人類明確的臨床概念證明？

Bruce, let me take the (inaudible) first; and then, take that to you.

布魯斯，要我先拿走（聽不清楚）；然後，再把那個拿給你。

The (inaudible) level of AP that we think the FDA is required to have it on the label.

我們認為，FDA 必須將 AP 含量標註在標籤上（聽不清楚）。

Yeah. We have that discussion with the FDA -- specifically, what it would take to get a claim per se. I'm not sure we really felt that was necessary. I think physicians have no real question about the relationship of triglycerides to pancreatitis risk, especially now that it's been has been proven. Payers haven't seemed to be concerned about that either, at least in the US.

是的。我們會與 FDA 進行討論——具體來說，就是要獲得索賠資格需要哪些條件。我不確定我們當時是否真的覺得有必要這麼做。我認為醫生們對於三酸甘油酯與胰臟炎風險之間的關係並沒有什麼真正的疑問，尤其是在這種關係已經被證實之後。至少在美國，支付方似乎也不擔心這一點。

So I'm not sure what the value of a claim would be. Of course, at this point, it's untested, whether the agency would consider providing that claim. I don't know that we've really thought of it as being necessary, Patrick, to be clear.

所以我不太確定索賠金額會是多少。當然，目前還無法確定該機構是否會考慮提供這種索賠。派崔克，說實話，我並不認為我們真的覺得有必要這麼做。

In (inaudible). But Patrick, is your question on SHTG or FCS?

在（聽不清楚）但派崔克，你的問題是關於SHTG還是FCS？

It's around, actually, the high-risk SHTG patient population?

實際上，它主要針對的是高風險SHTG患者族群？

Yeah. But the answer is the same, I think. We, at least, have not approached -- asking that when they give a claim, what it would take to get that claim? It's very possible that what they would require is something like SHASTA-5.

是的。但我認為答案是一樣的。至少我們還沒有問過——當他們提出索賠時，需要什麼條件才能獲得索賠？他們需要的很可能是類似 SHASTA-5 的東西。

But the SHASTA-5 was really designed primarily on the possibility that the payers in countries outside the US might require an actual dedicated outcome study. So it was more payer-focused than it was regulatory-focused.

但 SHASTA-5 的設計初衷主要是為了回應美國以外國家的支付方可能需要進行專門的結果研究這一可能性。所以它更側重於支付方，而不是監管機構。

We really were not committed, one way or the other, about whether it be submitted to regulators asking for a label change. We were more interested, really, in protecting the possibility that there would be payers outside of the US that would require a specific proof of concept in a dedicated study.

我們當時並沒有真正下定決心，是否要向監管機構提交申請，要求更改標籤。我們真正感興趣的是，要保護美國以外的支付方能夠要求在專門的研究中提供具體的概念驗證的可能性。

So we really haven't raised this with regulators anywhere on a global basis at this point.

所以目前為止，我們還沒有在全球範圍內向任何監管機構提出過這個問題。

Do you want to address the (inaudible) question?

你想回答這個（聽不清楚）問題嗎？

The (inaudible) question, we absolutely plan to do pediatric work in FCS. We we have those plans in place. We have a pediatric plan in Europe and in the US. The only thing pulling us back, right now, is just that we have to have a formulation that we can use for weight-based dosing.

（聽不清楚）問題，我們絕對計劃在 FCS 中進行兒科工作。我們已經制定了這些計劃。我們在歐洲和美國都有兒科保險計劃。目前唯一阻礙我們的是，我們需要一種可以用於按體重給藥的配方。

That's just -- we're in the process of getting that formulation put together. So that we can go ahead and do those studies. But we're absolutely planning on doing that.

我們正在製定方案。這樣我們就可以繼續進行這些研究了。但我們絕對有這個計劃。

James, do you want to talk about (inaudible) knockdown?

詹姆斯，你想談談（聽不清楚）擊倒嗎？

Yeah. Sure. In terms of what we're looking for -- based on the (inaudible) data, as you mentioned, at the tissue level, we were seeing 75%-plus reductions and similar reductions in the CSF in monkeys.

是的。當然。就我們正在尋找的結果而言——根據（聽不清楚的）數據，正如您所提到的，在組織層面，我們看到了 75% 以上的減少，猴子的腦脊髓液中也有類似的減少。

We typically translate well from (inaudible) into the clinic, into the humans. I think, based on some of the other data out there with the (inaudible) administered [ASO], they were able to achieve CSF reductions of about 50% to 60%.

我們通常能很好地將（聽不清楚）轉化為臨床應用，轉化為人類應用。我認為，根據其他一些關於（聽不清楚）施用[ASO]的數據，他們能夠使腦脊髓液減少約 50% 至 60%。

Those CSF reductions corresponded to new movements in tau (inaudible) signals. So I think that's probably where we're aiming for in our clinical study -- is at least 50% to 60% reduction in the CSF.

腦脊髓液的減少與 tau（聽不見的）訊號的新運動相對應。所以我認為，這大概就是我們在臨床研究中要達到的目標——腦脊髓液至少減少 50% 到 60%。

That's what others have shown. That seems to have translated into a meaningful (inaudible) path signal.

其他人已經證明了這一點。這似乎轉化為了一個有意義的（聽不見的）路徑訊號。

Andrea Newkirk, Goldman Sachs.

安德里亞·紐柯克，高盛集團。

Maybe one more on the REDEMPLO launch. Recognize it's only been about a week since the approval but now that you have launched, just curious if you'd be willing to comment on your expectations for the cadence of the initial launch here in FCS. How you think it may be similar or different from that of the Tryngolza launch, particularly in the context of the significant pricing differential that you have?

或許再補充一篇關於 REDEMPLO 發布的文章。我知道距離獲得批准才過去一周左右，但既然你們已經上線了，我只是好奇你們是否願意談談對FCS初期上線節奏的預期。您認為它與 Tryngolza 的上市有何相似之處或不同之處，尤其是在價格差異顯著的情況下？

Yeah. Happy to take that, Andrea. This is Andy.

是的。樂意接受，安德烈。這是安迪。

We do have very high ambitions for the REDEMPLO launch, expected it to be best-in-class. As you know, there are a number of reasons why we believe that to be the case, largely around the attributes of REDEMPLO that we do believe make it a special molecule in this category.

我們對 REDEMPLO 的發布寄予厚望，希望它能成為同類產品中的佼佼者。如您所知，我們認為情況確實如此的原因有很多，主要圍繞著 REDEMPLO 的特性，我們認為這些特性使其成為該類別中的一種特殊分子。

We talked about, obviously, the significant and sustained TG reduction. We've talked about the reduced incidence of acute pancreatitis. But even more importantly, we hear a lot of positive feedback around the safety and tolerability profile -- so no contraindications, no warnings, and no precautions. We do have a lot of physicians and patients who are enthusiastic about the once everythree month dosing regimen.

我們當然也談到了三酸甘油酯的顯著和持續下降。我們已經討論過急性胰臟炎發生率降低的問題。但更重要的是，我們聽到了很多關於安全性和耐受性的正面回饋——因此沒有禁忌症、沒有警告、也沒有預防措施。我們有許多醫生和患者對每三個月一次的給藥方案表示歡迎。

So with those product attributes, we have very high ambitions for the launch of REDEMPLO in FCS, specifically.

因此，憑藉這些產品特性，我們對 REDEMPLO 在 FCS 領域的推出抱持著非常高的期望。

Mike Ulz, Morgan Stanley.

麥克烏爾茲，摩根士丹利。

Congratulations on all the progress, as well.

也祝賀你們取得的所有進展。

Maybe just a follow-up on the SHASTA-3 and 4 studies. You mentioned adopting the modified (inaudible) criteria. Just curious now that you've seen some more detail around the core studies, are you considering any adjustments or fine-tuning to your studies, going forward?

或許只是 SHASTA-3 和 4 研究的後續研究。您提到要採用修改後的（聽不清楚）標準。既然您已經了解了核心學習的更多細節，我很好奇，您是否考慮對未來的學習進行任何調整或微調？

Other than adapting the (inaudible) criteria, I think we're feeling pretty good about the design. It was negotiated with the FDA. I don't think we saw anything in core that would cause us to see to change anything else. There's nothing that comes to mind.

除了調整（聽不清楚）標準之外，我認為我們對設計相當滿意。這是與美國食品藥物管理局協商的結果。我認為核心內容中沒有任何內容會導致我們需要改變其他任何東西。我想不出什麼好點子。

James, would you see it any differently -- closely this to --?

詹姆斯，你的看法會有什麼不同嗎——與此密切相關——？

Yeah. I agree. It didn't inspire any changes in the protocol.

是的。我同意。它並未促使協議做出任何改變。

Madison El-Saadi, B. Riley.

麥迪遜·埃爾-薩迪，B. 萊利。

I wanted to ask about your neuromuscular franchise. Just given your [integrin-targeted] delivery mechanism, which one could assume maybe safer and perhaps more targeted on TfR-mediated approach. Should we expect PK knockdown and splice correction data comparable to the peer benchmark levels?

我想諮詢一下你們的神經肌肉特許經營項目。鑑於你採用的[整合素靶向]遞送機制，可以推測它可能比 TfR 介導的方法更安全，也可能更具針對性。我們是否可以預期 PK 敲低和剪接校正數據與同類基準水準相當？

Relatedly, wondering which dose do you anticipate observing really optimal biomarker activity. I believe, previously, you said that even a low dose may be active.

另外，我想知道您預計哪種劑量能夠觀察到最佳的生物標記活性。我記得你之前說過，即使是低劑量也可能有效。

Sure. I think most of that will defer to Sarepta. I probably can't comment on the dose where we'd expect to see maximum knockdown. We don't know that yet. So I wouldn't want to venture a guess there yet.

當然。我認為大部分問題將由薩雷普塔決定。我可能無法評論達到最大擊倒效果所需的劑量。我們目前還不知道。所以我現在還不想妄下結論。

In terms of the knockdown, I think that is probably -- a goal is to have something that looks be similar to or equivalent to what others have shown for (inaudible) knockdown and splice correction with this platform.

就擊倒而言，我認為目標可能是——目標是使之看起來與其他人在這個平台上展示的（聽不清楚）擊倒和拼接校正效果相似或相當。

Got it. And then, if I may, are there any (inaudible) cells associated with hitting a certain threshold? Or are there milestones largely related to the regulatory progression?

知道了。那麼，如果可以的話，請問是否有與達到某個閾值相關的（聽不清楚）細胞？或者說，是否存在與監管進程密切相關的里程碑？

Yeah. It will base (inaudible) on regulatory and commercial. There are no activity-based or [PD]-based milestones.

是的。它將基於（聽不清楚）監管和商業因素。沒有基於活動或[PD]的里程碑。

Joseph Thome, TD Cowen.

Joseph Thome，TD Cowen。

Just another quick one on the DIMER. Just curious, based on your work in SHTG, what proportion of patients are already on an anti-PCSK9 treatment? Is this an undertreated population on both sides?

關於DIMER的另一個簡短說明。我只是好奇，根據您在SHTG的工作，目前有多少比例的患者正在接受抗PCSK9治療？雙方族群是否都存在治療不足的情況？

And then, can you give us an indication in terms of the triglyceride and LDL cutoffs that you're looking at in patients enrolled into the early DIMER study?

那麼，您能否就早期 DIMER 研究中納入的患者所關注的三酸甘油酯和 LDL 臨界值給出一些說明？

Sure. Yeah. I think, based on the work that we've done, a lot of those patients may be on a statin, probably less so on (inaudible) rates. A very (inaudible) on PCSK9 is actually not that commonly used in that population.

當然。是的。我認為，根據我們所做的工作，許多患者可能正在服用他汀類藥物，但（聽不清楚）率可能較低。PCSK9 的嚴重（聽不清楚）其實在該族群中並不常用。

In terms of the cutoffs in the inclusion criteria, we allow patients in that study with mixed hyperlipidemia and triglycerides up to 80% so there's a pretty high threshold; and they have to have either a non-HDL of 100 or an LDL greater than 70 to get into the study.

就納入標準而言，我們允許混合型高脂血症患者和三酸甘油酯高達 80% 的患者參與研究，因此門檻相當高；而且他們必須滿足非高密度脂蛋白膽固醇 (non-HDL) 為 100 或低密度脂蛋白膽固醇 (LDL) 大於 70 才能進入研究。

They have to have true mixed hyperlipidemia, both high triglycerides and high -- non-HDL or LDL cholesterol.

他們必須患有真正的混合型高血脂症，即三酸甘油酯高，且非高密度脂蛋白膽固醇（或低密度脂蛋白膽固醇）也高。

I'll now hand the call back over to President and CEO, Chris Anzalone, for any closing remarks.

現在我將把電話交還給總裁兼執行長克里斯·安札隆，請他作總結發言。

Thanks very much for joining us today.

非常感謝您今天蒞臨。

Again, thank you to Bruce for all he has brought to the company. He is re-retiring. He is not going to be gone, however. I do trust that he will still be around and helping us out, going forward.

再次感謝布魯斯為公司所做的一切。他要再次退休了。但他不會離開。我相信他以後還會繼續幫助我們。

Again, thanks to Bruce. Thanks to James for continued and ongoing leadership.

再次感謝布魯斯。感謝詹姆斯一直以來的領導。

Again, thank you, all, for joining us today. I hope you have a pleasant Thanksgiving holiday.

再次感謝各位今天蒞臨。祝您感恩節假期愉快。

Ladies and gentlemen, thank you for participating. This does conclude today's program. You may now disconnect.

女士們、先生們，感謝各位的參與。今天的節目到此結束。您現在可以斷開連線了。