Arrowhead Pharmaceuticals Inc (ARWR) 2026 Q1 法說會逐字稿

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call. (Operator Instructions)

女士們、先生們，歡迎參加 Arrowhead Pharmaceuticals 的電話會議。（操作說明）

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

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

Thank you, Victor. Good afternoon, and thank you for joining us today to discuss Arrowhead's results for its fiscal 2026 first quarter, ended December 31, 2025. With us today from management, our President and CEO, Dr. Chris Anzalone, who will provide an overview; 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 give over a review of the financials. Following management's prepared remarks, we will open the call to questions.

謝謝你，維克多。下午好，感謝各位今天蒞臨，與我們共同探討 Arrowhead 公司截至 2025 年 12 月 31 日的 2026 財年第一季業績。今天與我們一同出席的管理層有：總裁兼首席執行官克里斯·安扎隆博士，他將作概述；高級副總裁兼全球心血管代謝特許經營負責人安迪·戴維斯，他將介紹商業化活動的最新進展；首席醫療官兼研發負責人詹姆斯·漢密爾頓博士，他將討論我們的研發項目；以及首席財務官丹·阿佩爾，他將回顧財務狀況。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. All statements other than statements of historical fact 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. 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.

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。除歷史事實陳述外，所有其他陳述均為前瞻性陳述，並受諸多風險和不確定性的影響，這些風險和不確定性可能導致實際結果與任何前瞻性陳述中表達的結果存在重大差異。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, and thank you for joining us today. We had another quarter of strong execution across all areas of our business, and we are well-positioned to build on this progress throughout 2026 and beyond. In fact, the recent months have included some of the more significant achievements in Arrowhead's history. Let's talk about some of these.

謝謝你，文斯。各位下午好，感謝各位今天參加我們的節目。我們又一個季度在業務的各個方面都取得了強勁的執行力，我們已做好充分準備，在 2026 年及以後繼續保持這一發展勢頭。事實上，最近幾個月，Arrowhead 取得了一些歷史上較為重要的成就。我們來談談其中的一些問題。

First, on November 18, 2025, Arrowhead received its first regulatory approval and began the next phase of growth as a commercial company marketing its own medicines. The FDA approved Redemplo as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome, or FCS. FCS is a severe, rare disease with an estimated 6,500 people in the US living with genetic or clinical FCS, characterized by TG levels that can be 10-100 times higher than normal, leading to a substantially higher risk of developing acute, recurrent, and potentially fatal pancreatitis.

首先，在 2025 年 11 月 18 日，Arrowhead 獲得了第一個監管批准，並作為一家銷售自有藥物的商業公司開始了下一階段的成長。FDA 批准 Redemplo 作為飲食輔助療法，用於降低患有家族性乳糜微粒血症綜合症 (FCS) 的成年人的三酸甘油酯水平。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 TG 水平比正常水平高 10-100 倍，從而導致發生急性、復發性且可能致命的胰臟炎的風險大大增加。

This approval was supported by clinical data from the Phase III PALISADE study in adults with either clinically diagnosed or genetically confirmed FCS. The PALISADE study demonstrated deep and durable reductions in TGs with a median reduction of 80% from baseline and a lower numerical incidence of acute pancreatitis events compared to placebo. Arrowhead launched Redemplo independently in the US with a one Redemplo pricing model that creates one consistent price across current and potential future indications. This is important.

該批准得到了 PALISADE III 期研究的臨床數據支持，該研究對象為臨床診斷或基因確診的 FCS 成年患者。PALISADE 研究顯示，TG 水平顯著且持久降低，較基線水平中位數降低了 80%，且與安慰劑相比，急性胰臟炎事件的發生率更低。Arrowhead 在美國獨立推出了 Redemplo，採用統一的 Redemplo 定價模式，為當前和未來潛在的適應症創造一個一致的價格。這很重要。

We're committed to sustainable innovation, and this requires rational drug pricing according to the value a medicine offers to patients and healthcare systems. Redemplo is a pancreatitis drug, and when we think about pricing, we look to those patient populations at greatest risk of acute TG-related pancreatitis. We've only had drug in channel for about 10 weeks, which included Thanksgiving, Christmas, and New Year's holidays, so it is difficult to infer too much about launch. However, initial trends in prescriptions, payer interactions, and shipments have been encouraging.

我們致力於永續創新，而這需要根據藥物為患者和醫療保健系統帶來的價值進行合理的藥品定價。Redemplo 是一種治療胰臟炎的藥物，我們在考慮定價時，會關注那些急性 TG 相關胰臟炎風險最大的患者族群。該藥物進入管道才約 10 週，其中包括感恩節、聖誕節和新年假期，因此很難對上市情況做出過多推論。然而，處方、支付方互動和出貨方面的初步趨勢令人鼓舞。

To date, over 100 prescriptions for Redemplo have been received from a diverse prescriber base, with geographically balanced uptake across the US. Early patient starts fall into three categories: patients transitioning from our expanded access program, patients naive to the APOC3 class, and patients switching from Olezarsen. In addition, Redemplo shipments are being made for patients with clinically diagnosed and genetically confirmed FCS.

迄今為止，Redemplo 已收到 100 多張來自不同處方醫生的處方，在美國各地的使用情況均衡。早期患者開始治療分為三類：從我們的擴大准入計劃過渡的患者、未接觸過 APOC3 類藥物的患者以及從 Olezarsen 轉用的患者。此外，Redemplo 也向臨床診斷和基因確診的 FCS 患者發貨。

In addition to FDA approval, we announced in January 2026 that Redemplo also received approval for the treatment of FCS from Health Canada and from the Chinese National Medical Products Administration. Redemplo will be available later this year in Canada, and we anticipate it will be marketed independently by Arrowhead. Pending regulatory review and approval, we expect to potentially launch Redemplo later this year in select EU countries and in the UK. In Greater China, Redemplo will be marketed by Sanofi.

除了獲得 FDA 批准外，我們在 2026 年 1 月宣布，Redemplo 還獲得了加拿大衛生部和中國國家藥物管理局的批准，用於治療 FCS。Redemplo 將於今年稍晚在加拿大上市，我們預計它將由 Arrowhead 獨立進行市場推廣。待監管部門審查和批准後，我們預計今年稍後在部分歐盟國家和英國推出 Redemplo。在大中華區，Redemplo 將由賽諾菲負責市場推廣。

Our cardiometabolic pipeline is off to a good start with Redemplo and the ongoing Phase III study of Zodasiran in homozygous familial hypercholesterolemia, or HoFH. We are actively expanding this pipeline with a number of discovery programs and importantly, three clinical programs. ARO-INHBE and ARO-ALK7, being developed as potential treatments for obesity, are in Phase I and II studies. We also recently initiated a Phase I/II study of ARO-DimerPA in patients with mixed hyperlipidemia.

我們的心血管代謝產品線開局良好，Redemplo 和正在進行的 Zodasiran 治療純合子家族性高膽固醇血症 (HoFH) 的 III 期研究都取得了進展。我們正在積極拓展這一產品線，包括多個研發項目，更重要的是，還有三個臨床項目。ARO-INHBE 和 ARO-ALK7 正在被開發為治療肥胖症的潛在療法，目前處於 I 期和 II 期研究階段。我們最近也啟動了 ARO-DimerPA 在混合型高血脂症患者的 I/II 期研究。

For our initial obesity candidates, we recently announced some early interim clinical data. ARO-INHBE enhanced weight loss and fat reduction versus Tirzepatide alone in obese patients with Type II diabetes. More specifically, two administrations of ARO-INHBE at the 400 mg dose in combination with Tirzepatide achieved approximately twofold better weight loss at week 16 than Tirzepatide alone. This appears to be high-quality weight loss, as we saw an approximately threefold reduction in each of total fat, visceral fat, and liver fat measures based on week 12 MRI versus Tirzepatide alone in these patients.

對於我們首批肥胖症候選患者，我們最近公佈了一些早期中期臨床數據。在患有 II 型糖尿病的肥胖患者中，ARO-INHBE 比單獨使用 Tirzepatide 更能減輕體重和減少脂肪。更具體地說，兩次給予 400 毫克劑量的 ARO-INHBE 與 Tirzepatide 聯合治療，在第 16 週時，其減重效果比單獨使用 Tirzepatide 好約兩倍。這似乎是高品質的減肥，因為我們根據第 12 週的 MRI 結果發現，與單獨使用替拉帕肽相比，這些患者的總脂肪、內臟脂肪和肝臟脂肪指標都減少了約三倍。

The ARO-ALK7 Phase I/II study is approximately two quarters behind the ARO-INHBE study, but early data are encouraging. We believe this is the first RNAi therapeutic to show adipocyte gene target silencing in a clinical trial, and we've seen dose-dependent reductions in adipose ALK7 mRNA, with a mean reduction of minus 88% at the 200 mg dose at week 8, and a maximum reduction of minus 94%.

ARO-ALK7 I/II 期研究比 ARO-INHBE 研究落後約兩個季度，但早期數據令人鼓舞。我們相信這是第一個在臨床試驗中顯示脂肪細胞基因靶向沉默的 RNAi 療法，我們觀察到脂肪組織 ALK7 mRNA 呈劑量依賴性降低，在第 8 週 200 毫克劑量下平均降低 88%，最大降低 94%。

While these are very intriguing data, they are early and incomplete, so we have substantial work ahead of us before we get too excited about how these candidates could eventually be used. We will continue to run both phase one and two studies. We are expanding existing cohorts to increase power, and we are adding new cohorts to better understand these candidates and underlying biology. We intend to report additional results later in 2026.

雖然這些數據非常有趣，但它們還處於早期階段，並不完整，因此在我們對這些候選藥物最終可能如何應用感到興奮之前，我們還有大量工作要做。我們將繼續進行一期和二期研究。我們正在擴大現有隊列以提高統計效力，並增加新的隊列以更好地了解這些候選者及其潛在的生物學特性。我們計劃在 2026 年稍後公佈更多結果。

ArrowDimer-PA is being developed as a potential treatment for atherosclerotic cardiovascular disease, or ASCVD, due to mixed hyperlipidemia, where both LDL cholesterol and triglycerides are elevated. We believe there are approximately 20 million people in the US with mixed hyperlipidemia, and this is a patient population without adequate treatment options. We recently announced that we dosed the first patients in the phase 1/2 clinical trial of ArrowDimer-PA, which is a dual functional RNAi therapeutic designed to silence expression of the PCSK9 and APOC3 genes, thus designed to reduce both LDL cholesterol 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 TGs have epidemiologic support as being important drivers for ASCVD risk.

ArrowDimer-PA 正在被開發為治療由混合型高脂血症引起的動脈粥樣硬化性心血管疾病 (ASCVD) 的潛在療法，在這種疾病中，低密度脂蛋白膽固醇和三酸甘油酯均升高。我們認為美國約有 2,000 萬人患有混合型高血脂症，而這群患者缺乏足夠的治療選擇。我們最近宣布，我們已對 ArrowDimer-PA 的 1/2 期臨床試驗中的首批患者進行了給藥。 ArrowDimer-PA 是一種雙功能 RNAi 療法，旨在沉默 PCSK9 和 APOC3 基因的表達，從而降低 LDL 膽固醇和 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在一個分子中同時靶向兩個基因的臨床候選藥物，也是預防心臟病學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。

We expect to have interim data for ARO-DimerPA in the second half of 2026. If we see good LDL and TG reduction in a well-tolerated manner, we may have something truly special for a very large and currently underserved patient population. Outside of cardiometabolic, we made important advances in our CNS portfolio, specifically in programs that utilize a new proprietary delivery system designed to achieve blood-brain barrier, or BBB, penetration, utilizing subcutaneous administration.

我們預計將於 2026 年下半年獲得 ARO-DimerPA 的中期數據。如果 LDL 和 TG 能以良好的耐受性降低，我們或許就能為數量龐大且目前服務不足的患者群體帶來真正特別的東西。除了心血管代謝領域，我們在中樞神經系統產品組合方面取得了重要進展，尤其是在利用新型專有輸送系統（旨在透過皮下給藥實現血腦屏障 (BBB) 穿透）的計畫中。

In non-clinical studies across multiple animal models, we saw deep target gene knockdown across the CNS, including deep brain regions. This underscores Arrowhead's leadership in the delivery of siRNA to multiple tissues and cell types throughout the body, utilizing the proprietary TRiM Platform. Our first wholly-owned program using the BBB platform is ARO-MAPT, being developed as a potential treatment for tauopathies, including Alzheimer's disease.

在多個動物模型的非臨床研究中，我們觀察到中樞神經系統（包括深部腦區）中目標基因的深度敲低。這凸顯了 Arrowhead 利用其專有的 TRiM 平台，將 siRNA 輸送到全身多種組織和細胞類型的領先地位。我們第一個完全自主研發的採用 BBB 平台的計畫是 ARO-MAPT，它正在被開發為治療 tau 蛋白疾病（包括阿茲海默症）的潛在療法。

During the last quarter, we announced that we dosed the first subjects in a Phase I/II clinical trial that will include healthy volunteers and Alzheimer's patients. ARO-MAPT targets the tau protein in the brain, which has good biological validation as a potential driver of pathology and has emerged as a promising target for Alzheimer's Disease and additional tauopathies. We anticipate interim clinical data from the healthy volunteer portion of the study should be available in 2026, with data from the Alzheimer's patients to follow in 2027. This is a very exciting program for us. The second program to use our BBB delivery system is SRP-1005, formerly called ARO-HTT, for the treatment of Huntington's Disease. This program is partnered with Sarepta, which recently announced the submission of its CTA for study SRP-1005-101, also known as INSIGHT, in approximately 24 participants.

上個季度，我們宣布已對包括健康志願者和阿茲海默症患者在內的 I/II 期臨床試驗的首批受試者進行了給藥。ARO-MAPT 靶向大腦中的 tau 蛋白，該蛋白作為潛在的病理驅動因素，已得到良好的生物學驗證，並已成為阿茲海默症和其他 tau 蛋白疾病的一種有希望的目標。我們預計，研究的健康志願者部分的臨床中期數據將於 2026 年公佈，阿茲海默症患者的數據將於 2027 年公佈。這對我們來說是一個非常令人興奮的項目。第二個使用我們 BBB 輸送系統的項目是 SRP-1005（以前稱為 ARO-HTT），用於治療亨丁頓舞蹈症。該計畫與 Sarepta 合作，Sarepta 最近宣布提交了其 SRP-1005-101 研究（也稱為 INSIGHT）的 CTA，該研究約有 24 名參與者。

While our cardiometabolic and CNS work by no means encompasses everything we are doing, they are areas of substantial focus and potential value drivers in the near, mid-, and long term. Within these areas, we are addressing three of the greatest public health challenges of our time: obesity, cardiovascular disease, and neurodegenerative conditions.

雖然我們的心血管代謝和中樞神經系統研究工作遠非我們所做的一切，但它們是我們重點關注的領域，也是近期、中期和長期潛在的價值驅動因素。在這些領域，我們正在應對當今社會三大公共衛生挑戰：肥胖、心血管疾病和神經退化性疾病。

Now I'd like to move on to some key events during the recent period that have dramatically strengthened our balance sheet and give us the necessary resources to push multiple programs toward commercialization. We anticipate being funded through multiple potential independent and partner launches. These meaningfully increase revenue opportunities for the company and push us toward becoming cash flow positive and self-sustaining from commercial sales.

現在我想談談近期發生的一些關鍵事件，這些事件極大地增強了我們的資產負債表，並為我們提供了必要的資源，以推動多個項目走向商業化。我們預計將透過多個潛在的獨立項目和合作夥伴項目獲得資金。這些舉措顯著增加了公司的收入機會，並推動我們實現現金流為正，並依靠商業銷售自給自足。

Since our last reporting period, we have completed transactions with gross proceeds of $1.33 billion. Let's break that down. First, we completed a global licensing and collaboration agreement with Novartis for ARO-SNCA, Arrowhead's preclinical-stage siRNA therapy against Alpha-synuclein for the treatment of Synucleinopathies, such as Parkinson's Disease. The collaboration includes a limited number of additional targets outside our pipeline that will utilize Arrowhead's proprietary TRiM Platform. Arrowhead received a $200 million upfront payment 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.

自上一個報告期間以來，我們已完成交易，總收益達 13.3 億美元。讓我們來詳細分析一下。首先，我們與諾華公司就 ARO-SNCA 達成了一項全球許可和合作協議。 ARO-SNCA 是 Arrowhead 公司針對 α-突觸核蛋白的臨床前階段 siRNA 療法，用於治療突觸核蛋白疾病，例如帕金森氏症。此次合作包括我們研發管線之外的少量其他靶點，這些靶點將利用 Arrowhead 專有的 TRiM 平台。Arrowhead 已收到 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。

Second, we earned $200 million milestone payment from Sarepta following a drug safety committee review and subsequent authorization to dose escalate and achievement of the second pre-specified patient enrollment target for ARO-DM1. Third, we closed concurrent public offerings of $700 million aggregate principal amount of 0% coupon convertible senior notes and $230 million of common stock. Both offerings were several times oversubscribed and priced at company-friendly terms.

其次，在藥物安全委員會審查並隨後授權增加劑量以及實現 ARO-DM1 的第二個預先指定的患者招募目標後，我們從 Sarepta 獲得了 2 億美元的里程碑付款。第三，我們同時完成了總額為 7 億美元的 0% 息可轉換優先票據和 2.3 億美元的普通股的公開發行。兩項產品都獲得了數倍於預期的認購，而且定價對公司非常有利。

As I mentioned at the beginning of the call, we demonstrated strong execution across all areas of our business. We received regulatory approval in three different countries. We launched our first commercial product. We continued to grow our cardiometabolic portfolio. We had encouraging early results from our obesity programs. We advanced our TRIM platform and CNS pipeline, and we meaningfully improved our financial position to push these and other programs forward. It has been a productive last few months at Arrowhead, with so much potential to continue this strong progress in 2026 and beyond.

正如我在電話會議開始時所提到的，我們在業務的各個領域都展現了強大的執行力。我們已獲得三個不同國家的監管部門批准。我們推出了首款商業產品。我們持續拓展心血管代謝產品組合。我們的肥胖症防治計畫已經取得了令人鼓舞的初步成果。我們推進了 TRIM 平台和 CNS 產品線，並顯著改善了財務狀況，以推動這些項目和其他項目向前發展。過去幾個月，Arrowhead 取得了豐碩的成果，2026 年及以後很有可能繼續保持強勁的發展勢頭。

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

概述完畢，現在我想把電話交給安迪戴維斯。安迪？

Thank you, Chris, and good afternoon, everyone. It has been just over two months since the approval of Redemplo on November 18, 2025, and we are very pleased with the progress we are seeing. I'd like to share some early insights across healthcare provider engagement, patient dynamics, and payer developments.

謝謝你，克里斯，大家下午好。自從 Redemplo 於 2025 年 11 月 18 日獲得批准以來，已經過了兩個多月，我們對目前的進展感到非常滿意。我想分享一些關於醫療服務提供者參與度、病患動態和支付方發展的初步見解。

I'll start with healthcare provider engagement. As a reminder, we are targeting approximately 5,000 healthcare professionals through personal promotion, complemented by a much broader omni-channel effort. Early prescribing has been led by preventive cardiologists and endocrinologists, who together account for approximately 70% of total prescriptions, with the remainder coming from internal medicine physicians focused on lipid disorders. In addition, advanced practice providers, including nurse practitioners and physician associates, working within multidisciplinary care teams, are playing a meaningful role in patient identification and treatment decisions.

我先從醫療服務提供者的參與說起。再次提醒大家，我們正透過個人推廣的方式，瞄準約 5,000 名醫療保健專業人員，並輔以更廣泛的全通路推廣活動。早期處方主要由預防心臟病專家和內分泌專家主導，他們合計佔處方總數的約 70%，其餘處方則來自專注於脂質紊亂的內科醫生。此外，包括執業護理師和醫師助理在內的高級執業人員在多學科護理團隊中工作，在患者識別和治療決策中發揮重要作用。

Turning to patient dynamics. As Chris mentioned, over 100 prescriptions for Redemplo have been received to date. We see this as a very strong start that exceeded our expectations for the early months of the launch. We are also seeing geographically balanced uptake across the United States. Early patient starts fall into three categories: patients transitioning from our expanded access program, patients naive to the APOC3 class, and patients switching from Olezarsen.

轉向患者動態分析。正如克里斯所提到的，到目前為止，我們已經收到了超過 100 張 Redemplo 的處方。我們認為這是一個非常強勁的開局，超越了我們對產品上市初期幾個月的預期。我們也看到，美國各地的市場接受度也呈現均衡分佈。早期患者開始治療分為三類：從我們的擴大准入計劃過渡的患者、未接觸過 APOC3 類藥物的患者以及從 Olezarsen 轉用的患者。

Class-naive patients represent the overwhelming majority of starts, with expanded access and switch patients contributing evenly to the remainder. Patients receiving Redemplo include both clinically diagnosed and genetically confirmed FCS, with the majority not required to submit genetic testing to gain access. Importantly, a high proportion of patients are enrolling in the Rely on Redemplo patient support program, and in the fiscal first quarter, patients eligible for co-pay assistance paid $0 out of pocket.

初次接受此類治療的患者佔絕大多數，而擴大准入和轉診患者則平均佔剩餘部分。接受 Redemplo 治療的患者包括臨床診斷和基因確診的 FCS 患者，其中大多數患者無需提交基因檢測即可獲得治療。值得注意的是，很大一部分患者都參加了 Rely on Redemplo 患者支援計劃，並且在第一財季，符合共同支付援助條件的患者無需自付 0 美元。

Next, I'll touch on payer developments. While it is still early, we remain encouraged by positive payer feedback on both the clinical profile of Redemplo and our unified one Redemplo pricing approach. We are actively engaged with the largest payers, and discussions to date reflect a willingness to cover Redemplo to label, including access based on either genetic or clinical diagnosis of FCS. I'd like to conclude with a brief comment on execution.

接下來，我將談談支付方的發展。雖然現在下結論還為時過早，但我們仍然對支付方對 Redemplo 的臨床表現和我們統一的 Redemplo 定價方式的正面回饋感到鼓舞。我們正在積極與最大的支付方進行溝通，迄今為止的討論表明，他們願意按標籤支付 Redemplo 的費用，包括基於 FCS 的基因或臨床診斷的獲取途徑。最後，我想就執行方面簡單談談我的看法。

Within days of FDA approval, we had product available in the channel for FCS patients. Our Redemplo care coordinators, rare disease specialists, and field reimbursement navigators were deployed on day one to support prescribers and patients, and our payer account team continues to work closely with customers to minimize access barriers. The teams are off to a great start, and our teams are highly encouraged by early stakeholder feedback. This feedback further reinforces the key differentiating attributes of Redemplo.

FDA批准後幾天內，我們就透過管道向FCS患者提供了產品。從第一天起，我們的 Redemplo 護理協調員、罕見疾病專家和現場報銷導航員就被部署到位，為處方醫生和患者提供支持，我們的支付方客戶團隊也繼續與客戶密切合作，以最大限度地減少獲取障礙。各團隊開局良好，早期利害關係人的回饋也大大鼓舞了我們的團隊。這項回饋進一步強化了 Redemplo 的關鍵差異化屬性。

As a reminder, in the PALISADE study, Redemplo reduced triglycerides by 80% from baseline as early as month 1 and maintained this reduction with minimal variability through 12 months of treatment. In addition, the numerical incidence of acute pancreatitis was lower in Redemplo-treated patients than in placebo. The US-approved prescribing information includes no contraindications, no warnings, and no precautions. And Redemplo can be self-administered at home once every 3 months, just four injections per year.

提醒一下，在 PALISADE 研究中，Redemplo 早在第 1 個月就使三酸甘油酯較基線降低了 80%，並在 12 個月的治療期間保持了這種降低，且波動很小。此外，接受 Redemplo 治療的患者急性胰臟炎的發生率低於接受安慰劑治療的患者。美國批准的處方資訊中沒有禁忌症、警告和注意事項。Redemplo 可以每 3 個月在家中自行注射一次，每年只需注射四次。

With that, I'll turn the call over to James Hamilton to discuss the R&D portfolio.

接下來，我將把電話交給詹姆斯·漢密爾頓，讓他來討論研發項目組合。

Thank you, Andy. I'd like to start with a review of the Redemplo FDA approval and information in the label and contained in the package insert. Redemplo is approved as an adjunct to diet to reduce triglycerides in adults with FCS. The recommended dose of Redemplo is 25 milligrams, and it can be self-administered at home by subcutaneous injection once every three months. Redemplo has no contraindications, warnings, or precautions in the US FDA-approved label. The most common adverse reaction includes hyperglycemia, headache, nausea, and injection site reactions.

謝謝你，安迪。我想先回顧一下 Redemplo 的 FDA 批准情況以及標籤和包裝說明書中包含的資訊。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，可每三個月在家中進行一次皮下注射。Redemplo 在美國 FDA 批准的標籤上沒有任何禁忌症、警告或註意事項。最常見的不良反應包括高血糖、頭痛、噁心和注射部位反應。

Redemplo was studied in patients with both genetic FCS and clinically diagnosed FCS in the Phase III PALISADE study. Patients achieved deep and durable reductions in median triglycerides of around 80% from baseline, with reductions largely maintained below the guideline-directed threshold of 500 milligrams per deciliter throughout the year of treatment.

在 III 期 PALISADE 研究中，研究人員對患有遺傳性 FCS 和臨床診斷的 FCS 的患者進行了 Redemplo 研究。患者的三酸甘油酯中位數較基線水平顯著且持久地降低了約 80%，並且在整個治療年中，三酸甘油酯水平基本上保持在指南規定的每分升 500 毫克閾值以下。

Importantly, patients with genetic FCS versus clinical FCS showed similar reductions from baseline. We see the clinical FCS population as having the same high unmet need as the genetic FCS group, and as such, we think it's crucial to have shown that both patient populations showed similar large reduction from baseline in triglycerides.

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。我們認為臨床 FCS 族群與遺傳 FCS 族群一樣，都存在著很高的未滿足需求，因此，我們認為證明這兩個患者群體的三酸甘油酯水平較基線均有類似的顯著下降至關重要。

In PALISADE, treated patients also had a reduced rate of adjudicated acute pancreatitis events, a very welcome finding for FCS patients and their caregivers, and an important validation that reduction in triglycerides can in fact lead to reductions in pancreatitis. In addition to FCS, we are also investigating plozasiran in patients with severe hypertriglyceridemia or SHTG. We announced last quarter that the FDA granted breakthrough therapy designation to investigational plozasiran as an adjunct to diet to reduce triglycerides in adults with SHTG.

在 PALISADE 研究中，接受治療的患者確診急性胰臟炎事件的發生率也降低了，這對 FCS 患者及其照護者來說是一個非常令人欣喜的發現，並且有力地驗證了降低三酸甘油酯水平確實可以降低胰臟炎的發生率。除了 FCS 之外，我們也正在研究 plozasiran 對重度高三酸甘油酯血症或 SHTG 患者的療效。我們上個季度宣布，FDA 授予研究性藥物 plozasiran 突破性療法認定，作為飲食的輔助療法，用於降低患有 SHTG 的成年人的三酸甘油酯水平。

Breakthrough therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on clinically significant endpoints. This is another important step for the program.

突破性療法認定是一個旨在加快藥物開發和審查的過程，這些藥物旨在治療嚴重的疾病，並且初步臨床證據表明，該藥物在具有臨床意義的終點方面可能比現有療法有顯著的改善。這是該專案的另一個重要步驟。

The global Phase III studies of plozasiran designed to support the supplemental NDA filing to expand the label beyond genetic and clinical FCS are the SHASTA-3 and SHASTA-4 studies, which enrolled approximately 750 patients, and NEAR-3, which enrolled 1,400 patients. We're also enrolling patients in SHASTA-5 to directly assess the the ability of plozasiran to reduce the risk of acute pancreatitis as the primary endpoint. We remain on schedule to complete the blinded portion of the SHASTA-3, SHASTA-4, and NEAR-3 phase III clinical studies in mid-2026. We expect top line data to be available in the third quarter of 2026, with planned sNDA submission for SHTG before the end of the year.

為支持補充新藥申請，將 plozasiran 的適應症擴展到遺傳和臨床 FCS 以外的全球 III 期研究，包括 SHASTA-3 和 SHASTA-4 研究（招募了約 750 名患者）以及 NEAR-3 研究（招募了 1400 名患者）。我們也在 SHASTA-5 研究中招募患者，以直接評估 plozasiran 降低急性胰臟炎風險的能力，這是主要終點。我們仍按計劃在 2026 年年中完成 SHASTA-3、SHASTA-4 和 NEAR-3 III 期臨床研究的盲法部分。我們預計將於 2026 年第三季獲得主要數據，並計劃在年底前提交 SHTG 的補充新藥申請 (sNDA)。

We presented the study design and baseline characteristics of the SHASTA-3 and SHASTA-4 studies at the 23rd World Congress Insulin Resistance, Diabetes, and Cardiovascular Disease in December of 2025. I'd like to spend a moment to go over a few key parts of that poster. The primary endpoint of the SHASTA studies and the accepted regulatory endpoint is TG lowering versus placebo. Plozasiran has been highly active in all patient populations studied, so these studies are overpowered to show TG lowering. One of the additional objectives and key secondary endpoints of SHASTA-3 and SHASTA-4 studies includes the assessment of acute pancreatitis rates.

我們在 2025 年 12 月舉行的第 23 屆世界胰島素抗性、糖尿病和心血管疾病大會上介紹了 SHASTA-3 和 SHASTA-4 研究的研究設計和基線特徵。我想花點時間講解那張海報的幾個關鍵部分。SHASTA 研究的主要終點和公認的監管終點是 TG 降低與安慰劑相比。Plozasiran 在所有研究的患者群體中都表現出高度活性，因此這些研究足以證明其能降低 TG 水平。SHASTA-3 和 SHASTA-4 研究的額外目標和關鍵次要終點之一是評估急性胰臟炎的發生率。

To be clear, the study was not designed or prospectively powered to demonstrate AP rate reduction after just a year of treatment. However, there are a meaningful number of SHTG patients enrolled that would be considered at high risk for AP. Specifically, among the two studies, which will be pooled for AP event assessment, 37% of enrolled patients reported TGs greater than 880 milligrams per deciliter, accepted high risk threshold for AP. In addition, 20% of enrolled patients had a prior medical history of pancreatitis.

需要說明的是，研究的設計或前瞻性樣本量並不是為了證明治療一年後AP發生率會降低。然而，有相當數量的 SHTG 患者入組，他們被認為有很高的 AP 風險。具體來說，在兩項研究中（將合併用於 AP 事件評估），37% 的入組患者報告 TG 大於 880 毫克/分升，這是公認的 AP 高風險閾值。此外，20% 的入組患者有胰臟炎病史。

Lastly, we are seeing AP events in the studies. We are, of course, still blinded and have about another 4 months before the last patient reaches the end of the blinded period, but overall, the studies are progressing as planned. Chris mentioned the interim obesity results from our ARO-INHBE and ARO-ALK7 programs earlier, but I'd like to add some color and talk about what we are adding to these programs. First, these early results were very encouraging.

最後，我們在研究中看到了AP事件。當然，我們目前仍處於盲法狀態，距離最後一位患者完成盲法期還有大約 4 個月的時間，但總體而言，研究正在按計劃進行。Chris 之前提到了我們 ARO-INHBE 和 ARO-ALK7 計畫的中期肥胖症研究結果，但我想補充一些細節，談談我們正在為這些項目添加什麼。首先，這些初步結果非常令人鼓舞。

The next steps would be to investigate whether and where there is a therapeutic benefit, and in the patient segments and treatment settings where it may be applicable. To review, the interim clinical trial results represent the first demonstration in humans that the Activin E ALK-7 pathway, a genetically validated pathway that regulates adipose fat storage, may potentially be harnessed therapeutically to improve body composition and enhance weight loss versus Tirzepatide treatment alone in obese patients with type 2 diabetes mellitus.

下一步將調查是否存在治療益處以及在何處存在治療益處，以及在哪些患者群體和治療環境中可能適用。回顧來看，中期臨床試驗結果首次在人體中證實，Activin E ALK-7 路徑（一種經基因驗證的調節脂肪儲存的路徑）可能具有治療潛力，可以改善肥胖 2 型糖尿病患者的身體組成並增強減肥效果，優於單獨使用替拉帕肽治療。

This patient population typically experiences less weight loss with increased therapy. They're less likely to reach weight loss targets and need more effective treatment options. Importantly, ARO-INHBE, in combination with Tirzepatide, achieved approximately twofold weight loss and approximately threefold reduction in visceral fat, total fat, and liver fat versus Tirzepatide alone in obese diabetics. We saw signals that the pathway was active in the non-diabetics as well, but based on early data, the diabetic signal, particularly in combination with Tirzepatide, appeared to be the clearest.

這類患者族群通常隨著治療劑量的增加，體重減輕的幅度反而較小。他們不太可能達到減肥目標，需要更有效的治療方案。重要的是，在肥胖糖尿病患者中，ARO-INHBE 與 Tirzepatide 聯合使用，與單獨使用 Tirzepatide 相比，體重減輕了約兩倍，內臟脂肪、總脂肪和肝臟脂肪減少了約三倍。我們看到有跡象表明，該通路在非糖尿病患者中也處於活躍狀態，但根據早期數據，糖尿病訊號，特別是與替拉帕肽聯合使用時，似乎最為明顯。

We are already in the planning and execution stage of the following next steps: increasing numbers of patients in the Phase I diabetic cohorts, including longer follow-up to better understand drug durability and activity out to one year, and initiating monotherapy cohorts in obese diabetic patients. We expect to have more data later in 2026 from these programs as we see data from the new expanded scope of the Phase I/II studies.

我們已經進入以下後續步驟的規劃和執行階段：增加 I 期糖尿病隊列中的患者數量，包括延長隨訪時間以更好地了解藥物的持久性和活性長達一年，以及啟動肥胖糖尿病患者的單藥治療隊列。我們預計在 2026 年晚些時候，隨著 I/II 期研究的新擴展範圍的數據公佈，我們將從這些項目中獲得更多數據。

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, and good afternoon, everyone. I'll provide a brief outline of our financial picture. As we reported today, net income for the quarter ended December 31, 2025, was $30.8 million, for an income of $0.22 per share based on 140.7 million fully diluted weighted average shares outstanding. This compares to a net loss of $173.1 million, or loss of $1.39 per share for the quarter ended December 31, 2024, based on 124.8 million fully diluted weighted average shares outstanding at that time.

謝謝你，詹姆斯，大家下午好。我將簡要概述一下我們的財務狀況。正如我們今天報導的那樣，截至 2025 年 12 月 31 日的季度淨收入為 3,080 萬美元，以 1.407 億股完全稀釋加權平均流通股計算，每股收益為 0.22 美元。相較之下，截至 2024 年 12 月 31 日的季度淨虧損為 1.731 億美元，即每股虧損 1.39 美元，當時的完全稀釋加權平均流通股數為 1.248 億股。

Revenue for the quarter totaled $264 million, driven primarily by our licensing collaborations agreements with Sarepta and Novartis. Of this amount, approximately $229 million related to the Sarepta collaboration, and this included $181 million from the achievement of the second D-one milestone, $32 million from the ongoing recognition of the initial Sarepta consideration, and $17 million related to reimbursement of incurred collaboration program costs.

本季營收總計 2.64 億美元，主要得益於我們與 Sarepta 和 Novartis 的授權合作協議。其中約 2.29 億美元與 Sarepta 合作有關，包括 1.81 億美元來自實現第二個 D-one 里程碑，3200 萬美元來自對 Sarepta 初始對價的持續確認，以及 1700 萬美元與已發生的合作計劃費用的報銷有關。

In addition, we recognized $34 million of the $200 million upfront payment we received from Novartis under our global licensing and collaboration agreement with them. The remainder of that $200 million will be deferred over time as we fulfill our preclinical collaboration obligations. Finally, on revenue, we also recorded our first commercial sale of plozasiran in FCS. As both Chris and Andy have mentioned, we are very encouraged with the feedback and uptake we are seeing with patients and providers. For now, we are not disclosing specific sales numbers until such time as they become a meaningful driver to our financials.

此外，我們確認了根據與諾華公司簽訂的全球許可和合作協議，從諾華收到的 2 億美元預付款中的 3,400 萬美元。剩餘的 2 億美元將分期支付，以履行我們的臨床前合作義務。最後，在收入方面，我們也記錄了 plozasiran 在 FCS 的首次商業銷售。正如 Chris 和 Andy 所提到的，我們對病患和醫療服務提供者的回饋和接受程度感到非常鼓舞。目前，在銷售數據對我們的財務狀況產生實質影響之前，我們不會透露具體的銷售數字。

Turning to expenses, total operating expenses for the quarter were approximately $223 million, compared to $164 million in the prior year quarter, representing an increase of $59 million year-over-year. This increase was driven by $40 million of higher R&D expenses and $19 million of higher SG&A expenses. To break that down, the deep increase in R&D expense was primarily attributable to, as planned, higher clinical costs associated with our Phase III registrational studies for plozasiran in SHTG, as well as increased clinical supply chain costs. Nearly half of our clinical trial spend in the quarter was associated with our three registrational SHTG studies, namely Shasta-III, Shasta-IV, and Europe, which again should read out in the summer.

再來看支出，本季總營運支出約 2.23 億美元，而去年同期為 1.64 億美元，較去年同期成長 5,900 萬美元。這一增長是由研發支出增加 4,000 萬美元及銷售、管理及行政費用增加 1,900 萬美元所致。具體來說，研發費用的大幅增加主要歸因於（如計劃的那樣）與我們針對 SHTG 的 plozasiran III 期註冊研究相關的較高臨床成本，以及臨床供應鏈成本的增加。本季我們臨床試驗支出的近一半與我們的三項註冊性 SHTG 研究有關，即 Shasta-III、Shasta-IV 和 Europe，這些研究結果應該會在夏季公佈。

SG&A expenses increased year-over-year compared to the prior year's fiscal first quarter, primarily driven by investments to support the commercialization of Redemplo. As previously discussed, in advance of the US launch, we built robust commercial capabilities to fully support FCS, and importantly, capabilities that were intentionally designed to be highly leverageable downstream should we obtain approval for plozasiran in SHTG and zodasiran in HoFH.

與去年同期相比，銷售、一般及行政費用年增，主要原因是為支持 Redemplo 的商業化而進行的投資。如前所述，在美國上市之前，我們建立了強大的商業能力，以全面支持 FCS，更重要的是，這些能力是特意設計成可以高度利用的，以便在我們獲得 plozasiran 用於 SHTG 和 zodasiran 用於 HoFH 的批准後，下游能夠充分利用。

Turning now to the balance sheet. Cash and investments totaled $917 million as of December 31, 2025. Common shares outstanding at quarter end were 137.4 million. To be clear, the reported cash balance does not include the $200 million that we earned for the DM1 second milestone, which was received in January, nor does it include the $50 million anniversary payment that we expect to receive from Sarepta on or before February 10.

現在來看資產負債表。截至 2025 年 12 月 31 日，現金及投資總額為 9.17 億美元。截至季末，流通在外的普通股為1.374億股。需要說明的是，報告的現金餘額不包括我們在 1 月收到的 DM1 第二階段里程碑的 2 億美元，也不包括我們預計在 2 月 10 日或之前從 Sarepta 收到的 5000 萬美元週年紀念付款。

Finally, and importantly, the cash balance of about $917 million also does not include the financing transaction announced in early January, consisting of a concurrent offering of convertible senior notes and common stock, along with associated capped call transactions. As Chris mentioned, these were on company-friendly terms in the sense that the convertible was 0% coupon and the initial conversion premium was 35%. Said another way, the 0% coupon means the notes will not bear regular interest, and the principal amount of the notes will not accrete. The initial conversion price represents a significant premium of approximately 35% over the public offering price per share of common stock in the common stock offering.

最後，也是非常重要的一點，約 9.17 億美元的現金餘額還不包括 1 月初宣布的融資交易，該交易包括同時發行可轉換優先票據和普通股，以及相關的上限選擇權交易。正如克里斯所提到的，這些條款對公司非常有利，因為可轉換債券的票息為 0%，初始轉換溢價為 35%。換句話說，0% 票息意味著票據不會產生定期利息，票據的本金也不會增加。初始轉換價格較普通股發行中每股普通股的公開發行價格溢價約 35%。

Moreover, the private capped calls will prevent any dilution to existing shareholders up to an 85% of the premium over the offering price, or roughly $119. We estimate that the total cost of capital of that convertible at any share price below that $119 to be very attractively below 1.5%. All that is to say that we have very significantly and efficiently strengthened our balance sheet, which provides additional flexibility to support ongoing clinical development, current and future commercialization activities, and other long-term strategic priorities.

此外，私人上限選擇權將防止現有股東的權益被稀釋，最高可達發行價溢價的 85%，約 119 美元。我們估計，該可轉換債券在任何低於 119 美元的股價下的總資本成本都將非常有吸引力地低於 1.5%。總而言之，我們已顯著有效地加強了資產負債表，從而為持續的臨床開發、當前和未來的商業化活動以及其他長期策略重點提供了更大的靈活性。

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

簡要概述完畢，現在我將把電話轉回給克里斯。

Thanks, Dan. This is indeed an exciting time to be an Arrowhead or an Arrowhead shareholder. We're coming off an historic period for the company, where we executed extremely well, and all the hard work of the last several years is starting to pay off. While 2025 was productive, we look to the remainder of 2026 and the years ahead to be even more transformational. Let's look at some key 2026 events that we anticipate could be important value-creating events for the company and our shareholders. Commercial sales progress for Redemplo. Q3 2026 readout of phase III, Shasta-III and Shasta-IV studies of Plozasiran in patients with SHTG, which we believe has the potential to be a $3-$4 billion commercial opportunity.

謝謝你，丹。對於Arrowhead公司或Arrowhead公司的股東來說，這的確是一個令人興奮的時刻。公司剛經歷了一段歷史性的時期，我們執行得非常出色，過去幾年的所有努力都開始得到回報。儘管 2025 年碩果累累，但我們期待 2026 年剩餘時間以及未來的幾年將更具變革性。讓我們來看看 2026 年的一些關鍵事件，我們預計這些事件可能會為公司和我們的股東創造重要的價值。Redemplo的商業銷售進度。2026 年第三季將公佈 Plozasiran 治療 SHTG 患者的 III 期 Shasta-III 和 Shasta-IV 研究結果，我們認為這有可能帶來 30 億至 40 億美元的商業機會。

Second half 2026 readout for ARO-DimerPA, targeting PCSK9 and APOC3 for LDL and TG lowering, which may address mixed hyperlipidemia, a population of potentially 20 million patients in the US. Additional ARO-INHBE and ARO-ALK7 data presented in 2026 that may build on the already encouraging early data for this novel non-incretin strategy and early ARO-MAPT data in 2026, potentially providing validation for this drug candidate and our emerging CNS pipeline with systemic delivery via subcutaneous administration.

2026 年下半年將公佈 ARO-DimerPA 的試驗結果，該藥物針對 PCSK9 和 APOC3，用於降低 LDL 和 TG，可能有助於治療混合型高脂血症，美國可能有多達 2000 萬名患者患有此病。2026 年公佈的 ARO-INHBE 和 ARO-ALK7 的更多數據可能會建立在目前令人鼓舞的早期數據基礎上，以支持這種新型非腸促胰島素策略；2026 年公佈的 ARO-MAPT 的早期數據也可能為該候選藥物和我們正在開發的通過皮下給藥進行全身給藥的中樞神經系統藥物管線提供驗證。

These are just a few potentially important events in 2026 alone. If you fast-forward 1-3 years, we expect many more opportunities in our pipeline to build value and potential, commercial launches, both independently and with partners.

以上僅列舉了2026年可能發生的一些重要事件。如果快進 1-3 年，我們預計我們的產品線中將有更多機會來創造價值和潛力，並進行商業發布，無論是獨立發布還是與合作夥伴共同發布。

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

感謝各位今天參加我們的節目，現在想開放提問環節。操作員？

(Operator Instructions)

（操作說明）

Mike Ulz, Morgan Stanley.

麥克烏爾茲，摩根士丹利。

Maybe just one on Redemplo. Can you just give a little bit more color on the breakdown between the different categories of patients transitioning from expanded access, naive, and switch? And then maybe on the latter, in terms of switch, just any key reasons you're seeing a switch, and does it have anything to do with, you know, coverage and pricing?

或許在 Redemplo 上就有一個。您能否更詳細地介紹一下從擴大進入、初治和轉換治療過渡到其他治療的不同類別患者之間的組成？那麼，關於後者，就切換而言，您認為導致切換的主要原因是什麼？這是否與覆蓋範圍和定價有關？

Thanks, Mike. This is Andy. Yeah, I can comment that the vast majority of patient origination is from APOC3 naive segment, with the remaining balance split roughly 50/50 between those that are coming from switch and those that are transitioning off of the expanded access program.

謝謝你，麥克。這是安迪。是的，我可以評論說，絕大多數患者來自 APOC3 初次接觸者群體，其餘患者大致各佔一半，一半來自轉換治療方案的患者，一半來自從擴大准入計劃過渡的患者。

As it relates to switch, we're seeing switch patients that are coming both from efficacy, but also from safety, as the two principal drivers for why physicians might be considering Redemplo as an alternative. I hope that helps.

就轉換治療而言，我們看到轉換治療的患者既出於療效考慮，也出於安全性考慮，這是醫生考慮 Redemplo 作為替代方案的兩個主要驅動因素。希望對您有幫助。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特，傑富瑞。

Hi, congrats on the progress, and thanks for taking my question. I'll ask one on obesity. Just wondering if you've had discussions with FDA about the development path, or when would it make sense to do this? And what could timelines for your Phase II start look like? And do you need to have all the data, including combo data, in hand before you can determine next steps for the development path?

您好，恭喜您取得進展，感謝您回答我的問題。我問一個關於肥胖的問題。我想知道您是否與FDA討論過研發路徑，或者什麼時候進行這樣的討論比較適合？那麼，你們第二階段的啟動時間表會是什麼樣的呢？在確定下一步開發計畫之前，是否需要掌握所有數據，包括組合數據？

Yeah, sure, Maury. I can take that. This is James. Probably middle of the year, we would be having some of those discussions with FDA. I don't think we need all of the data from all of the cohorts. As I mentioned in the prepared remarks, we had expanded some of these cohorts, so they'll be going on, some of them -- for a longer period of time. And so, FDA conversations probably middle of -- around middle of the year, and then we'd be looking to file an IND shortly thereafter.

是啊，當然，莫里。我可以接受。這是詹姆斯。大概年中的時候，我們會和FDA進行一些相關的討論。我認為我們不需要所有隊列的所有數據。正如我在準備好的演講稿中所提到的，我們已經擴大了其中一些小組的規模，所以其中一些小組將會繼續進行更長的活動。因此，我們可能會在年中左右與 FDA 進行討論，然後我們會在不久之後提交 IND 申請。

Andrea Newkirk, Goldman Sachs.

安德里亞·紐柯克，高盛集團。

Maybe I can ask you one here on the ARO-DimerPA asset. Just as we think about the data sets that's coming later this year, just curious if you might be willing to speculate or share what you are looking for, or how you've defined a TPP, what level of reduction in LDL-C and trigs you're hoping to see, and then how that might inform a go, no-go decision for advancing the asset forward, and what extent of reduction would give you confidence that you could then see that translation to a benefit on MACE?

或許我可以在這裡問你一個關於 ARO-DimerPA 資產的問題。正當我們思考今年稍後即將公佈的數據集時，我很好奇您是否願意推測或分享一下您正在關注的內容，或者您​​是如何定義目標產品（TPP）的，您希望看到低密度脂蛋白膽固醇（LDL-C）和觸發因素降低到什麼程度，以及這些因素如何影響您對推進該資產的決策，以及將其降低到什麼程度才能讓您確信將其轉化為主要行為？

We'll see. I think, we probably don't have to reach the level of reduction in terms of APOC3 and triglycerides that we're seeing with Volanesorsen, for example, as something less than that, with the combination of the LDL cholesterol reductions would probably be sufficient. So I think if you look at some of the monkey data that we presented, in the dyslipidemic monkeys, we were seeing reductions in, in LDL and in triglycerides of around 40%-50%. So, I mean, so I think something like that, if you could do both of those, that'd be really encouraging. But we'll see what the data show later this year.

我們拭目以待。我認為，我們可能不必像 Volanesorsen 那樣將 APOC3 和三酸甘油酯降低到如此高的水平，因為降低 LDL 膽固醇的效果可能就足夠了。所以我覺得，如果你看一下我們展示的一些猴子數據，在血脂異常的猴子中，我們看到低密度脂蛋白和三酸甘油酯降低了約 40%-50%。所以，我的意思是，如果你能做到這兩點，那將非常令人鼓舞。但我們將在今年稍後看看數據會如何顯示。

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

Well, thanks so much. Hi, team. This is Cassie on for Luca. Congrats on strong Redemplo launch and progress. A question also on ARO-INHBE and ARO-ALK7, since we just talked about the regulatory path. And I appreciate early days, but how are you thinking about potential pricing for ARO-INHBE and ARO-ALK7?

非常感謝。大家好。這是卡西替盧卡上場。恭喜 Redemplo 成功上線並取得良好進展。因為我們剛才討論了監管途徑，所以還有一個關於 ARO-INHBE 和 ARO-ALK7 的問題。我很欣賞現在的情況，但是您認為 ARO-INHBE 和 ARO-ALK7 的潛在定價是多少？

I mean, Lilly now offers their Zepbound via LillyDirect at $300 a month, and the compounders announced today that you can get oral Wegovy basically at the same monthly price as the Ozempic. So what is your latest thinking on pricing, and how should we think about costs for ARO-INHBE and ARO-ALK7? Thanks so much.

我的意思是，禮來公司現在透過 LillyDirect 以每月 300 美元的價格提供 Zepbound，而配藥商今天宣布，口服 Wegovy 的價格基本上與 Ozempic 相同。那麼，您對定價的最新想法是什麼？我們應該如何考慮 ARO-INHBE 和 ARO-ALK7 的成本？非常感謝。

Thanks. It is as you expected. It's way too early for us to think about that. We're inheriting the biology here to see how these drug candidates could potentially work in various patient populations. Until we have a better understanding of that, it's really too early to speculate on potential pricing.

謝謝。正如你所料。現在考慮這個問題還為時過早。我們正在研究這裡的生物學原理，以了解這些候選藥物在不同患者群體中的潛在療效。在我們對此有更深入的了解之前，現在就對潛在的定價進行推測還為時過早。

Prakhar Agrawal, Cantor.

Prakhar Agrawal，坎托爾。

Congrats on the quarter and the progress. So I think, James, you mentioned that, about the pancreatitis event rates in the ongoing Phase 3/4 trials. Maybe if you can talk about the blinded AP events that you're seeing in those trials and whether it's in the same ballpark of what Ionis saw? And just a follow-up to that, would you expect the placebo event rate on AP reduction to perform similarly to Olezarsen core trials, given the population looks similar, or are there any, nuances that we should be aware of?

恭喜本季取得的成績和進展。所以，詹姆斯，我想你剛才提到了正在進行的 3/4 期試驗中的胰臟炎事件發生率。或許您可以談談您在這些試驗中觀察到的盲法AP事件，以及它是否與Ionis觀察到的事件處於同一水平？還有一個後續問題，考慮到人群相似，您是否預期安慰劑組在降低 AP 方面的事件發生率會與 Olezarsen 核心試驗的結果相似？或者是否存在我們應該注意的細微差別？

Yes, so on the first one, we're not gonna give any additional details on event rates, or the number of events that we've seen, other than to say that we are seeing events. On the second question, I mean, I think it's rational to look at in the cohort two placebo rate, that the population was similar to ours. So they are obviously different studies, but the population was similar.

是的，所以對於第一點，我們不會提供關於事件發生率或我們已經看到的事件數量的任何其他細節，只會說我們正在看到事件發生。關於第二個問題，我的意思是，我認為觀察第二組安慰劑組的發生率是合理的，因為該組人群與我們組人群相似。所以它們顯然是不同的研究，但研究人群相似。

Jason Gerberry, Bank of America.

傑森‧格伯里，美國銀行。

You mentioned payer feedback for Redemplo. I believe that was in the context of FCS. But I'm curious if in those discussions, SHTG came up at all, and whether that price point that you guys have for FCS is appropriate for a market the size of SHTG and the likely benefits that APOC3 would provide. It seems pretty de-risked at this point, but just kind of curious if those discussions came up and how the view was on the $60,000 price point.

您提到了Redemplo的付款方回饋。我相信那是在家庭與消費者科學（FCS）的背景下發生的。但我很好奇，在那些討論中，SHTG 是否被提及，以及你們為 FCS 設定的價格是否適合 SHTG 這樣的市場規模以及 APOC3 可能帶來的收益。目前看來風險已經相當低了，但我只是有點好奇是否討論過這些，以及大家對 6 萬美元的價格點有何看法。

This is Andy. Appreciate the question. I won't get into the details of any specific payer discussions, only to say that our team is laser focused on ensuring we can gain coverage and access for those patients that have FCS, either genetically confirmed or clinically diagnosed. I would just add that the payers with whom we're discussing represent over 90% of US lives, and both the clinical teams and the economic teams recognize the clinical value and the economic value of Redemplo at the one Redemplo price that we've previously announced.

這是安迪。感謝您的提問。我不會透露任何具體的付款方討論細節，只想說我們的團隊正全力以赴，確保能夠為那些患有 FCS 的患者（無論是基因確診還是臨床診斷）獲得保險和醫療服務。我還要補充一點，我們正在討論的支付方代表了美國 90% 以上的人口，臨床團隊和經濟團隊都認可 Redemplo 的臨床價值和經濟價值，而 Redemplo 的價格是我們之前宣布的。

You mentioned, the size of the SHTG market. We think there are somewhere around 3.5 million people with triglycerides above 500, but that market is not all created equal. When we look at our at least initial target market there, and we look at how we price Redemplo, it is really focused on those very high-risk individuals, those maybe 750,000 to maybe 1 million people who have triglycerides above 880, or a history of pancreatitis. That's -- at least initially, that is the real core market. That's -- those are the patients who really need this new medicine.

您提到了SHTG市場的規模。我們認為大約有 350 萬人的三酸甘油酯水平高於 500，但這個群體中的每個人情況都不盡相同。當我們審視我們至少最初的目標市場，以及我們如何為 Redemplo 定價時，它實際上專注於那些高風險人群，大約 75 萬到 100 萬人，他們的甘油三酯高於 880，或者有胰臟炎病史。至少在初期，這才是真正的核心市場。也就是說，這些患者才是真正需要這種新藥的。

So, again, don't get lost in the 3 million to 4 million people with trigs above 500. Really focus on the high risk group. That's who we're focusing on, at least initially.

所以，再次提醒大家，不要迷失在三角函數值超過 500 的 300 萬到 400 萬人之中。重點關注高風險族群。至少在初期，我們會專注在這些人身上。

Patrick Trucchio, H.C. Wainwright.

派崔克·特魯基奧，H.C. 溫賴特。

My question is on ARO-MAPT. I'm just curious, with the interim data from the healthy volunteer portion, and then with the patient data to follow, I'm wondering what specific elements of the healthy volunteer data, safety, CSF, tau knockdown or downstream biomarkers, would most likely increase your confidence in this program, and as well, the data we should look for in patients to follow? And if you could also just talk about just the confidence this would give in the CNS targeting and platform overall, and how we should expect the CNS platform to develop from here.

我的問題與 ARO-MAPT 有關。我只是好奇，根據健康志願者部分的初步數據，以及後續的患者數據，我想知道健康志願者數據（安全性、腦脊髓液、tau蛋白敲低或下游生物標誌物）中的哪些具體要素最有可能增強您對該計畫的信心，以及我們應該在後續的患者數據中尋找哪些數據？如果您還能談談這將給中樞神經系統靶向治療和整個平台帶來的信心，以及我們應該如何期待中樞神經系統平台從此發展，那就太好了。

This is James. So maybe I'll take the second question first. We don't have any data in the clinic yet, any data from humans. But we do have data using the platform with multiple different targets in multiple different monkey studies, and they're pretty consistent in terms of the drug concentration that we get in various CNS regions and and the knockdown we're able to achieve even in the deep brain. So that is helpful and certainly, enhances our confidence. But of course, the large leap in confidence will come once we see the clinical data.

這是詹姆斯。那我或許會先回答第二個問題。我們目前還沒有任何臨床數據，沒有任何來自人體的數據。但我們確實有使用該平台在多個不同的猴子研究中針對多個不同靶點獲得的數據，這些數據在我們在各種中樞神經系統區域獲得的藥物濃度以及我們即使在大腦深處也能實現的基因敲低方面都相當一致。這很有幫助，也確實增強了我們的信心。當然，只有看到臨床數據，信心才會大幅提升。

To your first question, I think the key data that we anticipate being confidence building, of course, safety, and then the CSF knockdown will be key in the healthy volunteers. There's not a lot of other downstream biomarkers to measure in the healthy volunteers, but then going forward into the patient cohorts, we can measure some of the phospho-tau varieties in the blood, also in the CSF, and then, of course, we can look at tau PET. Although those readouts will take a while to see the tau PET signals in the patients, I think seeing a reduction in tau PET signal will be really very encouraging.

對於你的第一個問題，我認為我們預期的關鍵數據是建立信心，當然還有安全性，然後腦脊髓液的抑制對於健康志願者來說至關重要。對於健康志願者來說，沒有太多其他下游生物標記可以測量，但對於患者群體，我們可以測量血液和腦脊髓液中的一些磷酸化 tau 蛋白，當然，我們還可以進行 tau 蛋白 PET 掃描。雖然還需要一段時間才能在患者身上看到 tau PET 訊號，但我認為看到 tau PET 訊號減少將是非常令人鼓舞的。

Edward Tenthoff, Piper Sandler.

愛德華·滕索夫，派珀·桑德勒。

So thanks for all the detail. I'm really excited to see the pipeline advancing. I'm wondering when it comes to the recognition of revenues, at this point, are you guys anticipating breaking out a cost of goods sold line? I'm sure a lot of the manufacturing expenses have already been expensed to R&D, but I'm just trying to think about how you're planning on reporting COGS going forward. And will you break out Redemplo product sales in the future too?

非常感謝您提供的所有細節。看到專案進展順利，我感到非常興奮。我想知道，在確認收入方面，你們目前是否打算單獨列出銷售成本？我相信很多製造費用已經計入研發費用了，但我只是想了解你們未來打算如何報告銷售成本。未來你們也會公佈 Redemplo 產品的銷售數據嗎？

Yeah, so as you pointed out, the cost of goods sold, part of the launch are gonna be in the R&D, and that's the majority of what we're gonna see in the short term. We said in the prepared remarks, we're not gonna disclose this actively until such time as there are meaningful drivers. So we will at some point, not gonna hazard a guess as to when that will be. But then you would at that point, you would normally see then sort of that traditional product growth and product cost sense.

是的，正如你所指出的，銷售成本的一部分將用於研發，這將是我們短期內看到的大部分成本。我們在事先準備好的演講稿中說過，在有意義的驅動因素出現之前，我們不會主動揭露此事。所以，我們遲早會這麼做，但我不會妄加猜測具體時間。但到了那個時候，你通常會看到那種傳統的產品成長和產品成本的概念。

Joseph Thome, TD Cowen.

Joseph Thome，TD Cowen。

Maybe just based on the differential biology of activin E and ALK7, can you talk a little bit about your expectation to see monotherapy weight loss in obese, non-diabetic patients with the ALK7 program? And then a point of clarification, when you talk about the expansions of the studies in terms of including that monotherapy diabetic population and expanding the overall size, was that for the activin E and ALK7 programs already, both of them?

或許僅基於激活素 E 和 ALK7 的差異生物學特性，您能否談談您對使用 ALK7 方案治療肥胖、非糖尿病患者單藥治療的減肥效果有何預期？然後，我想澄清一點，當您談到擴大研究範圍，包括納入單藥治療糖尿病人群並擴大總體規模時，激活素 E 和 ALK7 計畫是否都已經如此了？

Yeah, I think, well, we don't really have expectations in terms of monotherapy weight loss. We'll see what happens. I think we've said just a few times that we view these studies as hypothesis generating. So we'd like to see if there's an early signal and then potentially expand cohorts to confirm that signal. So can't really predict ahead of time what we're going to see. Then on your second question, the addition of the monotherapy cohort, we did add that in the Activin E study, that we will likely add that in the ALK7 study as well.

是的，我認為，嗯，我們對單一療法減肥並沒有太大的期望。我們拭目以待。我想我們已經說過幾次了，我們認為這些研究是為了提出假設。所以我們希望看看是否有早期訊號，然後有可能擴大隊列以確認該訊號。所以，我們無法提前預測將會看到什麼。關於你的第二個問題，即單藥治療組的加入，我們在 Activin E 研究中確實加入了單藥治療組，我們也可能會在 ALK7 研究中加入單藥治療組。

Mani Foroohar, Leerink Partners.

Mani Foroohar，Leerink Partners。

I had a little bit of technical issue there earlier, so not sure if this was asked earlier, but could you give us a breakdown of the EAP versus non-EAP patients out of the 100-plus prescriptions? And how should we think about the total pool of EAP patients rolling on to commercial drug? Is that -- is there a tail of that remaining? And I have a follow-up question.

我之前遇到了一些技術問題，所以不確定之前是否有人問過這個問題，但您能否提供一下 100 多張處方中 EAP 患者和非 EAP 患者的細分數據？我們該如何看待從 EAP 病患群體轉而使用商業藥物的情況？那——還有後續嗎？我還有一個後續問題。

This is Andy. At this time, we're not gonna provide any further details aside from the previous remarks, which the vast majority of patients are APOC3 naive. That gives us a lot of optimism about our ability to identify and diagnose both genetically confirmed and clinically diagnosed FCS patients. And again, with respect to the balance, we do see that fairly evenly split between those patients transitioning off of the expanded access program and those that are coming via switch.

這是安迪。目前，除了先前提到的絕大多數患者都是 APOC3 初治患者之外，我們不會提供任何其他細節。這讓我們對識別和診斷基因確診和臨床診斷的 FCS 患者的能力充滿信心。再說，就平衡而言，我們看到從擴大准入計劃過渡到其他計劃的患者與透過轉換計劃加入的患者人數相當接近。

Okay, that's helpful. And as a separate question, what are the expectations we should have over the next 12-18 months around potential datasets, or admittedly, perhaps early on novel tissue types and further expansion of the platform?

好的，這很有幫助。另外，對於未來 12-18 個月內可能出現的資料集，或者更確切地說，對於新的組織類型和平台的進一步擴展，我們應該抱持怎樣的期望？

That's a good question, Manny. We've not given any guidance on that at this point. I think we have enough exciting stuff with more INHBE now, seven data with initial MAPT data, with initial dimer data, with chapters three and four reading out, and with sample sales, that we feel pretty good about those things.

問得好，曼尼。目前我們尚未就此給出任何指導意見。我認為我們現在有了足夠多的令人興奮的東西，包括更多的 INHBE、七項數據（包括初步 MAPT 數據、初步二聚體數據）、第三章和第四章的宣讀以及樣品銷售，我們對這些事情感覺相當不錯。

But you know us, Manny, we are always developing the platform, and we are always expanding the insights, and so I can't -- it's possible that you may hear something about where we're going with the platform, as well as maybe new candidates within the existing platform. I just can't give you any guidance on when that might be. I apologize.

但你知道我們，曼尼，我們一直在開發平台，一直在擴展洞察，所以我不能——你可能會聽到一些關於我們平台發展方向的消息，以及現有平台內的新候選人。我無法告訴你具體時間。我道歉。

Madison El-Saadi, B. Riley.

麥迪遜·埃爾-薩迪，B. 萊利。

On the more prescriptions you mentioned, I'm curious, how many of those do you expect to be converted to paid drug? And how long does it take to get from prescription to drug in body? And then relatedly, how should we think about the pace of both patient onboarding and competitive switching? Is this kind of a leading indicator for SHTG dynamic?

關於您提到的更多處方，我很好奇，您預計其中有多少會轉化為付費藥品？從處方到藥物進入人體需要多長時間？那麼，我們該如何看待病患入院和競爭對手轉換的速度呢？這是否可以作為SHTG動態的領先指標？

Thanks, Madison. Happy to comment. What we're seeing are really high-quality prescriptions in the sense that we believe these prescriptions truly represent either genetically confirmed or clinically diagnosed FCS patients. So we do have high confidence that a significant proportion of those prescriptions will, in time, translate into drug shipments and drug in patients.

謝謝你，麥迪遜。樂意發表意見。我們看到的確實是高品質的處方，因為我們相信這些處方確實代表了基因確診或臨床診斷的 FCS 患者。因此，我們非常有信心，這些處方中的很大一部分最終會轉化為藥品發貨，並最終讓患者使用上藥。

As far as the time it takes from prescription to drug shipment, again, that does vary by patient, by insurance, and by prior authorization. But I would say in general, we're able to do that within just a couple of weeks from prescription to patient receiving drug. So I've been incredibly pleased with the patient identification, including both genetic and clinically diagnosed, and incredibly pleased with the operational execution from the team in converting prescriptions to shipped medicine.

從處方到藥品出貨所需的時間，同樣會因病患、保險和事先授權的不同而有所差異。但總的來說，從開處方到病人拿到藥，我們通常只需要幾週。因此，我對患者識別工作（包括基因診斷和臨床診斷）感到非常滿意，也對團隊將處方轉化為藥品運輸的營運執行工作感到非常滿意。

And also just broadly, be careful about reading too much into where we are right now. We've only been actively in market for 10 weeks now. So we're still working with payers. We're still working with physicians to get comfortable prescribing this. We're still informing and educating patients and prescribers about the medicine. So we have a long way to go. Let's see where we are more towards the end of the year. We have a pretty small sample set at this point.

此外，總的來說，不要對我們目前的處境過度解讀。我們正式進入市場至今只有10週。所以我們仍在與付款方合作。我們仍在與醫生合作，以便他們能夠放心地開立這種藥物。我們仍在向患者和處方醫生普及有關這種藥物的知識。所以我們還有很長的路要走。讓我們看看到年底時情況會如何。目前我們的樣本量還很小。

Thank you. I'm not showing any further questions in the queue. I would now like to turn it back over to Chris for any closing remarks.

謝謝。隊列中不再顯示任何其他問題。現在我想把發言權交還給克里斯，讓他做最後的總結發言。

Thanks, everyone, for joining us today. We look forward to speaking with you next quarter.

感謝各位今天蒞臨。我們期待下個季度與您再次溝通。

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

感謝您參加今天的會議。節目到此結束。您現在可以斷開連線了。祝大家今天過得愉快。