福泰製藥 (VRTX) 2025 Q3 法說會逐字稿

Good day, and welcome to the Vertex Pharmaceuticals third-quarter 2025 earnings call. (Operator Instructions) Please note this event is being recorded.

大家好，歡迎參加 Vertex Pharmaceuticals 2025 年第三季財報電話會議。（操作說明）請注意，本次活動正在錄影。

I would now like to turn the conference over to Ms. Susie Lisa. Please go ahead, ma'am.

現在我將把會議交給蘇西·麗莎女士。請便，女士。

Good evening, all. My name is Susie Lisa, and as the Senior Vice President of Investor Relations, it is my pleasure to welcome you to our third quarter 2025 financial results conference call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President; Duncan McKechnie, Chief Commercial Officer; and Charlie Wagner, Chief Operating and Financial Officer. We recommend that you access the webcast slides as you listen to this call. The call is being recorded, and a replay will be available on our website.

各位晚上好。我叫蘇西‧麗莎，身為投資人關係資深副總裁，我很高興歡迎各位參加我們2025年第三季財務業績電話會議。在今晚的電話會議上，Vertex 的執行長兼總裁 Reshma Kewalramani 博士、首席商務長 Duncan McKechnie 和營運長兼財務長 Charlie Wagner 將發表事先準備好的演講。我們建議您在收聽本次電話會議的同時，請查看網路直播投影片。通話正在錄音，錄音回放將在我們的網站上提供。

We will make forward-looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission. These statements, including, without limitation, those regarding Vertex's marketed medicines for cystic fibrosis, sickle cell disease, beta thalassemia and moderate to severe acute pain, our pipeline and Vertex's future financial performance are based on management's current assumptions.

我們將在本次電話會議上發表前瞻性聲明，這些聲明受到今天新聞稿和我們向美國證券交易委員會提交的文件中詳細討論的風險和不確定性的影響。這些聲明，包括但不限於有關 Vertex 已上市的用於治療囊性纖維化、鐮狀細胞病、β 地中海貧血和中度至重度急性疼痛的藥物、我們的研發管線以及 Vertex 未來的財務業績的聲明，均基於管理層目前的假設。

Actual outcomes and events could differ materially. I would also note that select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis.

實際結果和事件可能與此有重大差異。我還要指出，我們今晚電話會議上將要討論的部分財務業績和指引是以非公認會計準則 (non-GAAP) 為基礎編制的。

I'll now turn the call over to Reshma.

現在我將把電話交給雷什瑪。

Thanks, Susie. Good evening, all, and thank you for joining us on the call today. Vertex delivered strong performance across the board in Q3 with $3.08 billion in revenue, reflecting double-digit growth versus Q3 2024. As we continue to extend our leadership in CF, we're also diversifying our revenue base by product and by geography with the growing global momentum of CASGEVY and the broad uptake JOURNAVX in acute pain across a wide range of prescribers, pain types and settings of care.

謝謝你，蘇西。各位晚上好，感謝各位今天參加我們的電話會議。Vertex 在第三季全面表現強勁，營收達 30.8 億美元，與 2024 年第三季相比實現了兩位數成長。隨著我們在 CF 領域不斷擴大領先地位，我們也透過 CASGEVY 在全球範圍內日益增長的勢頭以及 JOURNAVX 在急性疼痛治療​​領域在眾多處方醫生、疼痛類型和護理環境中的廣泛應用，實現了產品和地域收入基礎的多元化。

Concurrently, we are forward planning for the fourth vertical of Vertex's growth. Centered on renal diseases and poeticize in multiple indications, starting with Pove in immunoglobulin A nephropathy or IgAN. Moving to the pipeline and starting with CF. Our long-standing goals in CF have been threefold: one, bring forward a medicine that can treat CF patients who make some amount of CFTR protein.

同時，我們正在為 Vertex 的第四個垂直成長領域進行前瞻性規劃。以腎臟疾病為中心，並針對多種適應症進行詩意化，首先是針對免疫球蛋白 A 腎病變或 IgAN 的 Pove。接下來進入管道環節，從CF開始。我們在 CF 領域的長期目標有三點：一是研發出一種可以治療產生一定量 CFTR 蛋白的 CF 患者的藥物。

Two, bring forward a medicine that restores CFTR function to normal levels as measured by sweat chloride and to do so from as early in life as possible, so patients have the potential to live a long and healthy life like people who carry just one CF allele. And three, bring forward a medicine for the last 5% of CF patients who do not make any CFTR protein at all.

第二，研發出一種藥物，能夠使 CFTR 功能恢復到正常水平（以汗液氯化物衡量），並且越早開始治療越好，這樣患者就有可能像只攜帶一個 CF 等位基因的人一樣，過上長壽健康的生活。第三，為最後 5% 完全不產生 CFTR 蛋白的 CF 患者研發出藥物。

We are making progress on all three fronts. First, ALYFTREK treats more mutations than TRIKAFTA. The number of patients newly eligible for CFTR modulator that treats the underlying cause of their disease is approximately 400 more patients in the US and approximately 4,000 more patients in the EU than TRIKAFTA. In total, 95% of all patients are eligible or will be eligible for ALYFTREK as we make our way to lower age groups.

我們在所有三個方面都取得了進展。首先，ALYFTREK 可以治療的突變比 TRIKAFTA 多。在美國，符合接受 CFTR 調節劑治療其疾病根本原因的患者人數比 TRIKAFTA 多出約 400 人；在歐盟，符合接受 CFTR 調節劑治療的患者人數比 TRIKAFTA 多出約 4000 人。總的來說，95% 的患者現在或將來都有資格接受 ALYFTREK 治療，因為我們正逐步將治療對象擴展到更低的年齡層。

Second, ALYFTREK, which launched in the US late last year and is launching in Europe now has seen a strong response from patients and physicians who are excited for a once-daily medicine that can bring sweat chloride levels down in patients ages six-plus to the lowest levels achieved of any CFTR modulator in this age group, two additional points to make on sweat chloride.

其次，ALYFTREK 於去年底在美國上市，現在正在歐洲上市，受到了患者和醫生的強烈迴響。他們對這種每日一次的藥物感到興奮，該藥物可以將 6 歲及以上患者的汗液氯化物水平降低到該年齡段所有 CFTR 調節劑所能達到的最低水平。關於汗液氯化物，還有兩點要說明。

We recently completed the pivotal study for TRIKAFTA for the one- to two-year patient population and the results are remarkable. The study's primary endpoint was safety, and the data were consistent with the established safety profile of this medicine. The secondary endpoint was reduction in sweat chloride. The baseline sweat chloride was about 100 millimoles per liter, and over the course of the 24-week study, there was a mean reduction of more than 70 millimoles per liter from baseline through week 24.

我們最近完成了針對 TRIKAFTA 的一至兩年患者群體的關鍵性研究，結果令人矚目。研究的主要終點是安全性，數據與該藥物已建立的安全性特徵一致。次要終點是汗液氯化物含量降低。基線汗液氯化物含量約為每公升 100 毫摩爾，在為期 24 週的研究過程中，從基線到第 24 週，平均每公升減少了 70 毫摩爾以上。

Furthermore, nearly 70% of patients in the study achieved levels of sweat chloride below the 30 millimole per liter threshold, the level considered normal. This magnitude of sweat chloride improvement is unprecedented, and the largest reduction we have seen with any CFTR modulator in any population to date.

此外，該研究中近 70% 的患者汗液氯化物水平低於每公升 30 毫摩爾的閾值，該水平被認為是正常的。汗液氯化物改善的幅度是前所未有的，也是迄今為止我們在任何人群中使用 CFTR 調節劑所觀察到的最大降幅。

We are on track to make global regulatory submissions for TRIKAFTA in this population of one- to two-year-olds in the first half of 2026. Additionally, as we serially innovate, we continue to develop new CFTR regimens with the aim of reaching our long-standing objective of bringing the majority of patients of any age with CF to normal levels of sweat chloride. As I just discussed with the TRIKAFTA one- to two-year-old study, we are already there in our youngest patients.

我們正按計畫於 2026 年上半年向全球監管機構提交針對 1 至 2 歲兒童的 TRIKAFTA 產品申請。此外，隨著我們不斷創新，我們持續開發新的 CFTR 療法，旨在實現我們長期以來的目標，即使大多數任何年齡層的 CF 患者的汗液氯化物水平達到正常水平。正如我剛才在 TRIKAFTA 一至兩歲兒童研究中討論的那樣，我們已經在最年輕的患者身上實現了這一點。

And in our ALYFTREK Phase III study of six-11 year-olds, more than 50% of patients got to normal levels of sweat chloride. VX-828, our NextGen 3.0 CFTR corrector is the most efficacious we have ever studied in vitro to enter the clinic. I am pleased to share we have now initiated the CF cohort in the VX-828 study. And third, regarding our final goal, VX-522, which we're developing for the 5,000 or so patients who cannot benefit from our CFTR modulators, we have resumed enrollment and dosing in the MAD portion of that Phase I/II study.

在我們針對 6 至 11 歲兒童進行的 ALYFTREK III 期研究中，超過 50% 的患者汗液氯化物水平恢復正常。VX-828，我們的下一代 3.0 CFTR 矯正劑，是我們迄今為止在體外研究過的最有效的藥物，即將進入臨床應用。我很高興地宣布，我們現在已經啟動了 VX-828 研究中的 CF 隊列。第三，關於我們的最終目標 VX-522，我們正在為大約 5000 名無法從我們的 CFTR 調節劑中受益的患者開發該藥物，我們已經恢復了該 I/II 期研究的 MAD 部分的入組和給藥。

Moving then to pain. In acute pain, during the quarter, we completed enrollment in 2 Phase IV trials evaluating JOURNAVX initiated preoperatively and as part of multimodal approaches to acute pain management. The interim analysis for one study will be shared at a medical conference later this week, and top line results for JOURNAVX show safety and efficacy, consistent with the pivotal program, accompanied by substantial reductions in opioid use following aesthetic or reconstructive procedures with approximately 90% of participants being opioid-free compared to less than 10% after similar procedures per the literature.

然後是疼痛。在急性疼痛方面，本季我們完成了 2 項 IV 期試驗的入組，這些試驗評估了術前啟動的 JOURNAVX 以及作為急性疼痛管理多模式方法的一部分的 JOURNAVX。一項研究的中期分析將於本週晚些時候在醫學會議上公佈，JOURNAVX 的主要結果顯示，該療法具有安全性和有效性，與關鍵性研究項目一致，同時在美容或重建手術後大幅減少了阿片類藥物的使用，約 90% 的參與者無需服用阿片類藥物，而文獻報道，類似手術後這一比例不到 10%。

In neuropathic pain, the first DPN Phase III study is well underway, and we have completed work that sets up the initiation of the second DPN Phase III study later this month. Transitioning now to the kidney portfolio. Renal Medicine is experiencing a renaissance in drug development, and Vertex seeks to be a leader in the field. With our differentiated R&D approach, grounded in causal human biology, validated targets and biomarkers that translate, we have a broad portfolio of innovative therapies with transformative potential for patients with serious kidney diseases.

在神經性疼痛方面，第一個 DPN III 期研究正在順利進行，我們已經完成了相關工作，為本月稍後啟動第二個 DPN III 期研究做好了準備。現在過渡到腎臟產品組合。腎臟醫學藥物研發正經歷復興，Vertex 力求成為該領域的領導者。我們採用差異化的研發方法，以人類因果生物學為基礎，採用可轉化的已驗證靶點和生物標誌物，擁有廣泛的創新療法組合，這些療法具有改變嚴重腎臟病患者命運的潛力。

Our clinical pipeline has first-in-class or best-in-class assets for four kidney diseases, three of which are already in or approaching pivotal development. VX-407 for autosomal dominant polycystic kidney disease, or ADPKD, inaxaplin for APOL1-mediated kidney disease or AMKD, pove for IgAN and pove for primary membranous nephropathy. Starting with VX-407 ADPKD, where the Phase II proof-of-concept study was initiated earlier this quarter.

我們的臨床研發管線擁有針對四種腎臟疾病的同類首創或同類最佳資產，其中三種已進入或即將進入關鍵性開發階段。VX-407 用於治療常染色體顯性多囊性腎病變 (ADPKD)，inaxaplin 用於治療 APOL1 介導的腎病變 (AMKD)，pove 用於治療 IgAN，pove 用於治療原發性膜性腎病變。首先是 VX-407 ADPKD，該藥物的 II 期概念驗證研究已於本季稍早啟動。

Recall, there are approximately 300,000 patients with ADPKD in the US and Europe. These patients have limited treatment options and no approved therapies that treat the underlying cause of this disease. We believe that up to 10% of patients with ADPKD may be eligible for treatment with VX-407, a first-in-class small molecule protein folding corrector. VX-407 is designed to target the root cause of ADPKD by restoring PC1 protein function. This Phase II proof-of-concept study is a single-arm trial of 24 patients that evaluates the effect of VX-407 on height adjusted total kidney volume.

據了解，美國和歐洲約有 30 萬名 ADPKD 患者。這些患者的治療選擇有限，目前尚無核准的療法可以治療這種疾病的根本原因。我們認為，高達 10% 的 ADPKD 患者可能符合接受 VX-407（一種首創的小分子蛋白質折疊矯正劑）治療的條件。VX-407 旨在透過恢復 PC1 蛋白功能來解決 ADPKD 的根本原因。這項 II 期概念驗證研究是一項單臂試驗，納入 24 名患者，旨在評估 VX-407 對身高調整後腎臟總體積的影響。

The second kidney program to highlight is inaxaplin for primary AMKD, a disease that affects 150,000 patients in the US and EU. Enrollment in the interim analysis cohort of the amplitude pivotal study has completed. The patients in this cohort are now being treated for 48 weeks, after which we will conduct the interim analysis. And if positive, we will be poised to submit for potential accelerated approval in the US.

第二個要重點介紹的腎臟治療計畫是用於治療原發性 AMKD 的 inaxaplin，這種疾病影響著美國和歐盟的 15 萬名患者。振幅關鍵研究的中期分析隊列招募工作已完成。該組患者目前正在接受 48 週的治療，之後我們將進行中期分析。如果結果呈陽性，我們將準備向美國提交加速審批申請。

Additionally, we are running the amplified study, which is a Phase II proof-of-concept study of inaxaplin in patients with AMKD with moderate proteinuria or patients with AMKD and diabetes, populations not being studied in the amplitude trial. AMPLIFIED is on track to complete enrollment by the end of this year.

此外，我們正在進行一項擴展研究，這是一項 II 期概念驗證研究，旨在研究 inaxaplin 對伴有中度蛋白尿的 AMKD 患者或 AMKD 合併糖尿病患者的療效，這些人群並未在 Amplitude 試驗中進行研究。AMPLIFIED計畫預計在今年年底前完成招生。

Now turning to povetacicept. The lead and first indication for pove is IgAN, a disease impacting more than 300,000 diagnosed patients in the US and Europe and over 1 million patients globally. There are 4 points to highlight in this program. First, we completed enrollment of the interim analysis cohort of the RAINIER Phase 3 trial earlier this year. Second, the FDA has granted pove breakthrough therapy designation and rolling review for our BLA.

現在來說說波維他西普。pove 的主要適應症是 IgAN，影響著美國和歐洲超過 30 萬名確診患者，以及全球超過 100 萬名患者。本節目有 4 個重點需要強調。首先，我們在今年稍早完成了 RAINIER 3 期試驗中期分析隊列的招募工作。其次，FDA 已授予我們的生物製品許可申請 (BLA) 突破性療法認定和滾動審查資格。

Third, we have completed the studies to support the launch of pove for at-home self-administration with a subcutaneous auto-injector. Lastly, the new news I'm very pleased to share tonight is that we have completed full enrollment in the RAINIER Phase 3 trial. The trial enrolled approximately 600 patients in approximately 15 months, the fastest of any contemporary Phase 3 study in IgAN and is a testament to the significant opportunity ahead for pove.

第三，我們已經完成了支持推出用於家庭自我給藥的皮下自動注射器的 pove 的研究。最後，我今晚非常高興地宣布，RAINIER 第三階段試驗已完成全部受試者招募。該試驗在約 15 個月內招募了約 600 名患者，是目前 IgAN 3 期研究中最快的，證明了 pove 未來擁有巨大的發展機會。

Here's the outlook when you put these four major milestones together with the rolling review that the FDA is granted, we will begin our submission for potential accelerated approval before the end of this year. Once the interim analysis cohort completes 36 weeks of treatment, assuming the results are positive, we will complete our BLA submission for potential accelerated approval in the US in the first half of 2026.

如果將這四個主要里程碑與 FDA 授予的滾動審查結合起來，我們預計在今年年底前開始提交加速批准的申請。一旦中期分析隊列完成 36 週的治療，假設結果是積極的，我們將在 2026 年上半年完成 BLA 申請，以期在美國獲得加速批准。

We have used a priority review voucher, and thus, we have certainty that pove's BLA in the IgAN indication will receive an expedited priority review in the US. That is a six-month review versus a traditional 10-month review. Next and consistent with this pipeline and product potential, we are pleased to have initiated the pivotal study for the second potential renal indication for pove in primary membranous nephropathy.

我們使用了優先審評券，因此，我們確信 pove 的 IgAN 適應症的 BLA 將在美國獲得快速優先審查。這是每六個月一次的評估，而不是傳統的每十個月一次的評估。接下來，基於此研發管線和產品潛力，我們很高興啟動了針對原發性膜性腎病變這一第二個潛在腎臟適應症的關鍵性研究。

There are approximately 150,000 patients with membranous nephropathy in the US and Europe and nearly 500,000 globally. Today, there are no approved therapies that treat the underlying cause of this disease, leaving a significant patient population with high unmet need. Pove was recently granted Fast Track designation by the FDA in membranous nephropathy and our Phase 2, 3 adaptive study OLYMPUS, is now underway.

美國和歐洲約有 15 萬名膜性腎病變患者，全球約有 50 萬名患者。目前，尚無核准的療法可以治療這種疾病的根本原因，導致大量患者的需求未被滿足。Pove 近期獲得了 FDA 授予的膜性腎病快速通道資格，我們的 2 期、3 期適應性研究 OLYMPUS 目前正在進行中。

One final note in R&D regarding Zimislecel in type 1 diabetes. While we have completed enrollment in the pivotal trial for T1D, we have temporarily postponed completion of dosing while we work through an internal manufacturing analysis. As this is an ongoing pivotal trial, it is critical to maintain study integrity, and so we won't be providing any additional detail. I look forward to updating you once dosing is complete.

關於齊美萊塞在第 1 型糖尿病研發的最後一點說明。雖然我們已經完成了 1 型糖尿病關鍵性試驗的受試者招募，但由於我們正在進行內部生產分析，因此暫時推遲了給藥的完成。由於這是一項正在進行的關鍵性試驗，保持研究的完整性至關重要，因此我們不會提供任何其他細節。給藥完成後，我會及時向您報告情況。

In closing, Vertex now has seven commercialized medicines. Five programs in Phase III development and an exciting earlier-stage R&D pipeline. Accordingly, as we drive to achieve our R&D milestones, we're executing on the concurrent work of getting our approved medicines to more patients around the globe and preparing for additional near-term potential launches.

最後，Vertex 目前已有七種商業化藥品。五個項目處於 III 期研發階段，以及令人振奮的早期研發管線。因此，在我們努力實現研發里程碑的同時，我們也在同步推動已獲批准的藥物惠及全球更多患者，並為近期可能推出的其他藥物做好準備。

To tell you more about our commercial efforts, I'll now turn over the call to Duncan.

為了更詳細地向大家介紹我們的商業舉措，我現在將電話交給鄧肯。

Thanks very much, Reshma. I will focus my comments tonight on the CF franchise, global launches of ALYFTREK and CASGEVY the US launch of JOURNAVX and commercial planning for our potential launches in four serious kidney diseases, the first of which will be pove in IgAN.

非常感謝，雷什瑪。今晚我將重點討論 CF 產品線、ALYFTREK 和 CASGEVY 的全球上市、JOURNAVX 的美國上市以及我們針對四種嚴重腎臟疾病的潛在上市的商業計劃，其中第一個上市的將是 IgAN。

Beginning with CF, our CF franchise delivered strong double-digit growth this quarter as we continue to grow the number of eligible patients taking our CFTR modulators. This reflects the ongoing launch of the ALYFTREK, progress with younger patients and patients with rare mutations, enhanced survival benefits of our therapies and expansion into new geographies, such as Brazil and Turkey.

從 CF 開始，我們的 CF 產品線在本季度實現了強勁的兩位數成長，因為我們不斷增加服用 CFTR 調節劑的合格患者數量。這反映了 ALYFTREK 的持續推出、在年輕患者和罕見突變患者方面取得的進展、我們療法的生存獲益的提高以及向巴西和土耳其等新地區的擴張。

Focusing on ALYFTREK, our fifth therapy approved to treat the underlying cause of CF. We believe ALYFTREK is the best CFTR modulator available for eligible patients given that when compared to standard of care TRIKAFTA, ALYFTREK provides further improvements in CFTR function as measured by sweat chloride is indicated for additional rare mutations and offers the convenience of once-daily dosing.

重點介紹 ALYFTREK，這是我們獲批用於治療囊性纖維化根本病因的第五個療法。我們認為 ALYFTREK 是目前符合條件的患者可用的最佳 CFTR 調節劑，因為與標準治療藥物 TRIKAFTA 相比，ALYFTREK 可進一步改善 CFTR 功能（以汗液氯化物衡量），適用於其他罕見突變，並且每日一次給藥非常方便。

The US launch of ALYFTREK is progressing well across all patient groups. We have seen particularly rapid uptake in those patients who are naive to CFTR modulators and the vast majority of previously untreated patients in the US have now been initiated on the ALYFTREK.

ALYFTREK 在美國的上市進展順利，所有患者群體均取得了良好效果。我們發現，對於那些從未接受過 CFTR 調節劑治療的患者來說，這種療法的接受度尤其高，而且美國絕大多數以前未接受過治療的患者現在都已經開始接受 ALYFTREK 治療。

We also see continued uptake by those patients who have previously discontinued one of our other CFTR modulators. Lastly, the pace of transition patients primarily those switching from TRIKAFTA remains steady and represents the majority of patients on ALYFTREK in the quarter.

我們也看到，那些先前停止使用我們其他 CFTR 調節劑的患者也繼續接受這種藥物。最後，過渡患者的步伐（主要是從 TRIKAFTA 轉用的患者）保持穩定，並且佔本季度 ALYFTREK 患者的大多數。

Outside the US, the early launch of ALYFTREK is off to a strong start in multiple European countries where patients have reimbursed access England, Ireland, Germany and Denmark. And the feedback has been very positive, both in terms of the clinical profile and once daily dosing.

在美國以外，ALYFTREK 在多個歐洲國家（包括英國、愛爾蘭、德國和丹麥）的早期上市取得了強勁的開端，這些國家的患者可以獲得報銷。無論是臨床表現或是每日一次的給藥方式，回饋都非常正面。

And as Reshma mentioned, there are nearly 10 times as many newly eligible patients in Europe with rare mutations for TRIKAFTA and ALYFTREK than in the US and no additional liver monitoring requirements. Overall, we are pleased with the response to ALYFTREK and continue to expect that the majority of patients around the globe will transition to ALYFTREK over time given its multiple benefits.

正如 Reshma 所提到的，在歐洲，符合 TRIKAFTA 和 ALYFTREK 罕見突變條件的新患者數量幾乎是美國的 10 倍，而且沒有額外的肝臟監測要求。總體而言，我們對 ALYFTREK 的市場反應感到滿意，並繼續期望鑑於其諸多優勢，全球大多數患者最終都會過渡到 ALYFTREK。

Moving to CASGEVY, our transformative onetime treatment for patients with severe sickle cell disease and beta thalassemia. The momentum continues to build as we enter the last few months of 2025. As a result, we have a clear line of sight to over $100 million in CASGEVY revenue this year and significant growth in 2026. Importantly, we have seen continued progress in securing access to CASGEVY around the world, with the notable recent addition of reimbursement in Italy for TDT and SCD.

轉向 CASGEVY，我們為重度鐮狀細胞疾病和β地中海貧血患者提供的變革性一次性治療。隨著我們進入2025年的最後幾個月，這股勢頭仍在持續增強。因此，我們有信心今年 CASGEVY 的營收將超過 1 億美元，並在 2026 年實現顯著成長。重要的是，我們在確保世界各地都能獲得 CASGEVY 方面取得了持續進展，尤其值得一提的是，最近義大利已開始對 TDT 和 SCD 進行報銷。

Italy has the second largest population in the world of TDT patients at approximately 5,000 patients, about half of whom are eligible for CASGEVY. As further evidence of CASGEVY building momentum across all three regions, the US, Europe and the Middle East, I'm pleased to report that since launch and through the end of quarter 3, 2025 nearly 300 patients have been referred by their physicians to an ATC to initiate the treatment process.

義大利是世界上TDT患者人數第二多的國家，約有5,000名患者，其中約一半符合CASGEVY的條件。為了進一步證明 CASGEVY 在美國、歐洲和中東這三個地區的發展勢頭強勁，我很高興地報告，自推出以來，截至 2025 年第三季末，已有近 300 名患者由他們的醫生轉診至 ATC 開始治療過程。

More than 160 patients now have had their first cell collection. This includes 110 in the first nine months of 2025, double our full year 2024 total. And a total of 39 patients have received their infusions of CASGEVY edited cells, including 10 patients in the third quarter of 2025. We see continued growth in ATC's onboarding and initiating patients in the US, Europe and the Middle East as the treatment teams become more familiar with the process. Through the end of September, 25 ATCs had initiated more than five patients and at least one ATC in each of the three regions had initiated 20 or more patients.

目前已有超過160名患者完成了首次細胞採集。其中包括 2025 年前九個月的 110 輛，是 2024 年全年總數的兩倍。總共有 39 名患者接受了 CASGEVY 編輯細胞的輸注，其中包括 2025 年第三季的 10 名患者。隨著治療團隊對流程越來越熟悉，我們看到 ATC 在美國、歐洲和中東的入組和啟動患者數量持續成長。截至 9 月底，25 個 ATC 已為 5 名以上患者啟動治療，三個地區中至少有一個 ATC 已為 20 名或更多患者啟動治療。

Given the very well understood duration of the treatment journey and the fact that we now have significant numbers of patients at every stage in the process, CASGEVY has a strong outlook, and we are excited to serve the growing numbers of patients through the end of this year into 2026 and beyond.

鑑於治療過程的持續時間已得到充分了解，並且我們現在在治療過程的每個階段都有大量患者，CASGEVY 的前景十分樂觀，我們很高興能夠為不斷增長的患者群體提供服務，直至今年年底，直至 2026 年及以後。

Now shifting to the launch of JOURNAVX in moderate to severe acute pain. We continue to see a very positive reaction to this novel non-opioid option for the treatment of moderate to severe acute pain. As a reminder, our goals in 2025 were firstly secure broad payer coverage. Secondly, ensure hospital and health system access through P&T reviews and formulary adoption.

現在轉向推出 JOURNAVX，用於治療中度至重度急性疼痛。我們持續看到人們對這種治療中度至重度急性疼痛的新型非鴉片類藥物療法給予非常正面的回饋。再次提醒大家，我們 2025 年的目標首先是確保廣泛的支付方覆蓋。其次，透過藥事委員會審查和處方集採納，確保醫院和衛生系統能夠獲得藥物。

And thirdly, drive broad usage of JOURNAVX across a range of physician and pain types with a seamless experience for physicians and patients alike. We are executing well on all fronts, and I'll now provide some details. We continue to make good progress with payers. As of mid-October, across commercial and government payers, over 170 million lives of reimbursed access to JOURNAVX, up from the 150 million we discussed on our Q2 call.

第三，推動 JOURNAVX 在各類醫師和疼痛類型中的廣泛應用，為醫師和患者提供無縫體驗。我們在各個方面都進展順利，現在我將提供一些細節。我們與支付方的合作持續取得良好進展。截至 10 月中旬，透過商業和政府支付方，超過 1.7 億人次獲得了 JOURNAVX 的報銷服務，高於我們在第二季度電話會議上討論的 1.5 億人次。

With commercial payers, our negotiations continue to progress favorably. We have formal coverage under two of the three large national PBMs and are working to add the third. In Medicare, we continue to engage with plans to secure coverage. And for Medicaid patients through mid-October, we now have a total of 19 states, up from 16 last quarter that are providing access to JOURNAVX without prior authorization or step edit requirements.

與商業支付方的談判持續取得良好進展。我們已正式加入三大全國性藥品福利管理機構中的兩家，目前正努力加入第三家。在聯邦醫療保險方面，我們繼續與各計劃進行溝通，以確保獲得保險覆蓋。對於 Medicaid 患者而言，截至 10 月中旬，目前共有 19 個州（高於上一季的 16 個州）無需事先授權或步驟編輯要求即可存取 JOURNAVX。

We continue to expect that coverage across commercial, Medicare and Medicaid payers will expand through the balance of 2025 and into 2026. Note that even after national payers grant formal coverage for JOURNAVX, it can take time to ensure that all lives are covered in their downstream plans. Therefore, we plan to extend our patient support program, or PSP, into 2026 to ensure that if a physician makes the decision to prescribe JOURNAVX for their patient with acute pain, the patient will receive the medicine.

我們繼續預計，在 2025 年剩餘時間和 2026 年，商業保險、聯邦醫療保險和聯邦醫療補助的覆蓋範圍將持續擴大。請注意，即使國家支付方正式批准了 JOURNAVX 的承保範圍，也需要一段時間才能確保所有受益人都納入其後續計劃的承保範圍。因此，我們計劃將我們的患者支援計劃（PSP）延長至 2026 年，以確保如果醫生決定為患有急性疼痛的患者開立 JOURNAVX 處方，患者將能夠獲得該藥物。

Recall the PSP only kicks in for those patients without coverage or with highly restricted coverage. So if a patient's plan reimburses JOURNAVX, the PSP program is not triggered. Secondly, we're making excellent progress with P&T committees at the approximately 150 healthcare systems and 2,000 hospitals we're targeting, more than 750 hospitals and approximately 90 of the 150 targeted large health care systems have now added JOURNAVX to their formularies, protocols or order sets.

請記住，PSP 僅適用於沒有醫療保險或醫療保險覆蓋範圍非常有限的患者。因此，如果患者的保險計劃報銷 JOURNAVX，則不會觸發 PSP 計劃。其次，我們在與大約 150 個醫療保健系統和 2000 家醫院的藥事委員會合作方面取得了顯著進展，超過 750 家醫院和大約 90 個目標大型醫療保健系統已將 JOURNAVX 添加到其處方集、方案或醫囑集中。

Thirdly, we continue to see broad adoption of JOURNAVX by a wide range of physicians, including orthopedic surgeons, plastic surgeons, anesthesiologists, pain specialists and dentists. They're using JOURNAVX in a wide range of pain settings, including surgical and nonsurgical procedures, such as joint replacement and repair, shoulder surgeries, fractures and sprains and dental procedures.

第三，我們看到 JOURNAVX 被包括骨科醫生、整形外科醫生、麻醉師、疼痛專家和牙醫在內的眾多醫生廣泛採用。他們正在各種疼痛治療中使用 JOURNAVX，包括手術和非手術治療，例如關節置換和修復、肩部手術、骨折和扭傷以及牙科手術。

In hospital systems and clinics that have adopted JOURNAVX, we have received impressive feedback from physicians in terms of very significantly reduced or eliminated opioid usage, consistent with the Phase 4 study results Reshma mentioned earlier. Reports from patients also continue to be very positive in terms of how well JOURNAVX manage their pain in addition to being well tolerated.

在採用 JOURNAVX 的醫院系統和診所中，我們收到了醫生們令人印象深刻的回饋，他們表示阿片類藥物的使用量顯著減少或消除，這與 Reshma 先前提到的 4 期研究結果一致。患者的回饋也持續非常積極，他們認為 JOURNAVX 能夠很好地控制疼痛，而且耐受性良好。

We also continue to see that JOURNAVX is promotionally responsive to our field representative calls as well as our digital engagement with physicians. There is a clear correlation between frequency of calls and depth of prescription writing by physicians. For these reasons, and as we discussed last quarter, we're planning to add 150 additional representatives in the first quarter of 2026, which will enable us to increase our frequency of calls with existing prescribers and expand our coverage to additional physicians.

我們還發現，JOURNAVX 對我們的現場代表電話以及我們與醫生的數位化互動都做出了積極的推廣回應。醫生打電話的頻率與處方開立的深度之間有明顯的關聯。鑑於這些原因，正如我們上個季度討論的那樣，我們計劃在 2026 年第一季增加 150 名代表，這將使我們能夠增加與現有處方醫生的通話頻率，並將我們的服務範圍擴大到更多醫生。

And to raise awareness of JOURNAVX among consumers, we have a wide range of communication initiatives ongoing, including a partnership with basketball Superstar, Jayson Tatum as he shares his JOURNAVX treatment journey experience post is Achilles injury during the playoffs last season.

為了提高消費者對 JOURNAVX 的認識，我們正在進行一系列傳播活動，包括與籃球巨星傑森·塔圖姆合作，讓他分享上賽季季後賽跟腱受傷後使用 JOURNAVX 治療的經歷。

Finally, as evidence of the growing reception in the marketplace, there have now been more than 300,000 prescriptions filled for JOURNAVX across the retail and hospital settings as of mid-October. We continue to have high confidence that there is a significant unmet need for an effective non-opioid option to treat moderate to severe acute pain, and we're in the early days of creating another multibillion-dollar franchise for Vertex.

最後，作為市場接受度不斷提高的證據，截至 10 月中旬，JOURNAVX 在零售和醫院環境中已開出超過 30 萬張處方。我們仍然非常有信心，對於治療中度至重度急性疼痛，存在著巨大的未滿足的、有效的非阿片類藥物選擇需求，我們正處於為 Vertex 打造另一個數十億美元特許經營權的早期階段。

I'll close with some comments on our commercial planning for our potential launches in renal medicine, where we have begun the build-out of our commercialization team. We expect that our renal franchise will become a significant growth driver and value generator for Vertex over the next several years. I'll focus my comments this evening on our first step in that direction, pove in IgAN.

最後，我想就我們在腎臟醫學領域的潛在產品上市的商業計劃發表一些看法，我們已經開始組建商業化團隊。我們預計，在未來幾年內，我們的腎臟業務將成為 Vertex 的重要成長動力和價值創造者。今晚我將重點談談我們朝著這個方向邁出的第一步，即 IgAN 的進展。

We believe that pove offers a unique combination of attributes with a compelling clinical and patient profile. Firstly, pove is a fusion protein specifically engineered for better tissue penetration and to deliver optimized, targeted dual inhibition of the BAFF and APRIL cytokines. In the Ruby III clinical data we've seen to date, pove delivers substantial reductions in Gd-IgA1, hematuria and proteinuria.

我們相信，pove 具有獨特的屬性組合，並擁有引人注目的臨床和患者概況。首先，pove 是一種融合蛋白，經過專門設計，能夠更好地穿透組織，並實現對 BAFF 和 APRIL 細胞因子的最佳化靶向雙重抑制。從我們目前看到的 Ruby III 臨床數據來看，pove 可顯著降低 Gd-IgA1、血尿和蛋白尿。

Secondly, among the APRIL only or dual BAFF APRIL inhibitors, pove has the most convenient dosing and administration for patients. Every four weeks, at home administration via a subcutaneous auto-injector and the lowest dosage volume of less than 0.5 milliliters. And thirdly, pove is the only dual BAFF APRIL inhibitor in pivotal trials for multiple serious kidney diseases, IgAN and pMN.

其次，在僅含 APRIL 或雙重 BAFF APRIL 抑制劑的藥物中，pove 對患者而言給藥和使用最為方便。每四周在家使用皮下自動注射器給藥，最低劑量小於 0.5 毫升。第三，pove 是目前唯一一種針對多種嚴重腎臟疾病（IgAN 和 pMN）進行關鍵性試驗的雙重 BAFF APRIL 抑制劑。

We believe pove has a superior mechanism of action, a superior clinical profile and will deliver a superior patient experience. In short, we believe pove holds best-in-class potential. We're excited to build out our renal franchise and prepare for commercialization in our fifth disease area with pove as a potential best-in-class treatment for IgAN.

我們相信，pove 具有更優越的作用機制、更優越的臨床特性，並將為患者帶來更優越的體驗。簡而言之，我們相信 pove 具有一流的潛力。我們很高興能夠拓展我們的腎臟產品線，並準備在我們的第五個疾病領域進行商業化，其中 pove 有望成為 IgAN 的一流治療藥物。

I'll now turn the call over to Charlie to review the financials.

現在我將把電話交給查理，讓他審核財務數據。

Thanks, Duncan. Vertex's Q3 2025 double-digit revenue growth demonstrates our consistent strong performance and attractive growth profile. Third quarter 2025 total revenue increased 11% year-over-year to $3.08 billion. US revenue growth of 15% year-over-year was driven in CF by ongoing patient demand and favorable net pricing versus prior year. As well as contributions from ALYFTREK, CASGEVY and JOURNAVX.

謝謝你，鄧肯。Vertex 2025 年第三季兩位數的營收成長顯示我們持續強勁的業績和具有吸引力的成長前景。2025年第三季總營收年增11%至30.8億美元。CF 業務收入年增 15%，主要得益於患者持續的需求以及與前一年相比有利的淨定價。此外，還有 ALYFTREK、CASGEVY 和 JOURNAVX 的貢獻。

Revenue outside the US grew 4% year-on-year, including mid-single-digit CF growth and a contribution from CASGEVY. Included in Q3, '25 total global revenue and the regional growth rates was $17 million of CASGEVY revenue and $20 million from JOURNAVX. Third quarter 2025 combined non-GAAP R&D acquired IP R&D and SG&A expenses were $1.28 billion compared to $1.08 billion in the third quarter of 2024.

美國以外的營收年增 4%，其中包括中等個位數的現金流成長以及 CASGEVY 的貢獻。2025 年第三季全球總營收和區域成長率包含 CASGEVY 的 1,700 萬美元收入和 JOURNAVX 的 2,000 萬美元收入。2025 年第三季非 GAAP 研發、收購智慧財產權研發及銷售、一般及行政費用合計為 12.8 億美元，而 2024 年第三季為 10.8 億美元。

Non-GAAP operating expenses increased 19% year-on-year, driven primarily by the continued advancement of our broad later-stage pipeline, including the acceleration of pove development programs as well as the build-out of commercial capabilities in pain. Acquired IP R&D expenses were $55 million compared to $15 million in the third quarter of 2024. Third quarter 2025 non-GAAP operating income was $1.38 billion compared to $1.31 billion in the third quarter of 2024.

非GAAP營運費用年增19%，主要得益於我們廣泛的後期產品線的持續推進，包括加速推進pove開發項目以及在疼痛領域建立商業能力。收購智慧財產權研發費用為 5,500 萬美元，而 2024 年第三季為 1,500 萬美元。2025 年第三季非 GAAP 營業收入為 13.8 億美元，而 2024 年第三季為 13.1 億美元。

Third quarter 2025 non-GAAP effective tax rate was 17.6%, including benefits from R&D tax credits as a result of last year's Alpine acquisition. Third quarter 2025 non-GAAP net income was $1.24 billion compared to $1.14 billion in Q3 of '24. Third quarter 2025 non-GAAP earnings per share were $4.80, an increase of 10% compared to $4.38 in the third quarter of 2024.

2025 年第三季非 GAAP 實際稅率為 17.6%，其中包括去年收購 Alpine 所獲得的研發稅收抵免收益。2025 年第三季非 GAAP 淨收入為 12.4 億美元，而 2024 年第三季為 11.4 億美元。2025 年第三季非 GAAP 每股收益為 4.80 美元，比 2024 年第三季的 4.38 美元增加了 10%。

We ended the quarter with $12 billion in cash and investments after deploying approximately $1.1 billion to repurchase more than 2.7 million shares in the third quarter. Year-to-date, we have spent over $1.9 billion to repurchase approximately 4.5 million shares. Our priorities for cash deployment remain unchanged, innovation and growth fueled by investments, both internal and external, with a second priority of share repurchases.

第三季末，我們持有現金和投資120億美元，此前我們已投入約11億美元回購了超過270萬股股票。今年迄今為止，我們已花費超過 19 億美元回購了約 450 萬股股票。我們的現金部署重點依然不變，創新和成長是透過內部和外部投資推動的，其次是股票回購。

Now switching to guidance. With only one quarter remaining in 2025, we are updating our financial guidance for revenue, operating expenses and taxes. We now expect 2025 total revenue to be in a range of $11.9 billion to $12 billion versus prior guidance of $11.85 billion to $12 billion, representing growth of approximately 8% to 9% for the full year at current exchange rates.

現在切換到指導環節。2025 年只剩下最後一個季度了，我們正在更新收入、營運支出和稅收的財務預期。我們現在預計 2025 年總收入將在 119 億美元至 120 億美元之間，而先前的預期為 118.5 億美元至 120 億美元，按當前匯率計算，全年增長約 8% 至 9%。

This outlook reflects our expectation for continued growth from our portfolio of CF medicines, including the ongoing launch of ALYFTREK in the US and recent launches in Europe. As Duncan mentioned, full year revenue guidance also includes over $100 million of CASGEVY revenue as we treat more patients in geographies where we have secured regulatory approval and reimbursement.

這項展望反映了我們對 CF 藥物組合持續成長的預期，包括 ALYFTREK 在美國的持續上市以及最近在歐洲的上市。正如鄧肯所提到的那樣，全年收入預期還包括超過 1 億美元的 CASGEVY 收入，因為我們在已獲得監管批准和報銷的地區治療了更多患者。

In addition, guidance reflects further contribution from JOURNAVX in the fourth quarter due to growing prescription volumes. We are also refining guidance for combined non-GAAP R&D acquired IP R&D and SG&A expenses and now expect operating expenses of approximately $5 billion to $5.1 billion versus prior guidance of $4.9 billion to $5 billion for the full year.

此外，由於處方量成長，JOURNAVX 在第四季度也做出了進一步貢獻，業績指引也反映了這一點。我們也正在調整非GAAP研發、收購智慧財產權研發及銷售、一般及行政費用的合併預期，目前預計全年營運費用約為50億至51億美元，而先前的預期為49億至50億美元。

This is primarily due to the acceleration in pove development programs across multiple indications and increased investment in commercial and marketing activities to support the launch of JOURNAVX. There is no change to our estimate of approximately $100 million in projected IPR&D charges for the full year, including the recently announced collaboration with Enlaza.

這主要是由於在多個適應症中加速推進藥物研發項目，以及增加對商業和行銷活動的投資，以支持 JOURNAVX 的上市。我們對全年預計知識產權研發費用的估計約為 1 億美元，其中包括最近宣布與 Enlaza 的合作，這一估計沒有變化。

We continue to expect an immaterial cost impact from tariffs in 2025 based on what we know today due to our significant US presence and our geographically diverse supply chain. Of course, given the dynamic nature of the tariff situation, including the potential for sector-specific tariffs, this outlook is subject to change.

根據我們目前掌握的信息，由於我們在美國擁有重要的業務以及我們地理多元化的供應鏈，我們仍然預計 2025 年關稅對成本的影響微乎其微。當然，鑑於關稅情勢的動態性，包括可能出台針對特定產業的關稅，這一前景可能會改變。

And finally, we are lowering our expected full year 2025 non-GAAP effective tax rate guidance from a range of 20.5% to 21.5% to a revised range of 17% to 18% to incorporate several onetime tax benefits. These benefits include those recognized in Q3 from Alpine related R&D tax credits as well as anticipated recognition in Q4 '25 of previously deferred tax benefits.

最後，我們將 2025 年全年非 GAAP 實際稅率預期範圍從 20.5% 至 21.5% 下調至 17% 至 18%，以納入幾項一次性稅收優惠。這些收益包括第三季確認的與 Alpine 相關的研發稅收抵免，以及預計在 2025 年第四季確認的先前遞延的稅收收益。

In closing, Vertex yet again delivered strong results in Q3 '25, growing and diversifying our revenue with the launch of two new products in the US, ALYFTREK and JOURNAVX, the launch of ALYFTREK in Europe and the continued global launch of CASGEVY. We also made significant pipeline progress across the portfolio in mid- and late-stage clinical development, including pove's pipeline and a product potential and continued advancement. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17. We look forward to updating you on our progress on future calls.

最後，Vertex 在 2025 年第三季再次取得了強勁的業績，透過在美國推出兩款新產品 ALYFTREK 和 JOURNAVX，在歐洲推出 ALYFTREK，以及繼續在全球推出 CASGEVY，實現了營收的成長和多元化。我們在產品組合的中後期臨床開發方面也取得了重大進展，包括 pove 的產品線和產品潛力以及持續的進步。這些以及其他預期在多個疾病領域取得持續進展的里程碑事件詳見第 17 張投影片。我們期待在以後的電話會議中向您報告我們的進度。

I'll now ask Susie to begin the Q&A.

現在我請蘇西開始問答環節。

Thanks, Charlie. And apologies, we understand there were issues with the webcast. And for that, we're sorry, working with our vendor Chorus Call. We'll also look to get the transcript out as soon as possible. Chuck, can you please give the Q&A instructions?

謝謝你，查理。很抱歉，我們了解到網路直播出現了一些問題。為此，我們深感抱歉，我們與供應商 Chorus Call 合作。我們也會盡快把成績單寄出去。查克，你能給我問答環節的說明嗎？

(Operator Instructions)

（操作說明）

Geoff Meacham, Citibank.

傑夫‧米查姆，花旗銀行。

Hey guys, afternoon, thanks for the question. I just have two quick ones. On ALYFTREK. Just wanted to get maybe a bit of a status update. Do you think you're hitting a tipping point with regard to kind of patient switching or those that are maybe kind of new starts and just curious about the monitoring requirement, whether that's sort of eased a little bit.

各位下午好，謝謝你們的提問。我只有兩個簡短的問題。在 ALYFTREK 上。只是想了解最新情況。你認為在病患轉診或新病患（他們可能只是好奇監測要求是否有所放鬆方面）方面，你是否正處於轉折點？

And then the second thing is, as you guys look forward, Reshma, I know your nephrologist by training. So as you get closer to the pove dataset. Maybe just help us with kind of how you're thinking about the differentiation here versus the many BAFF, APRIL type of assets here? I know obviously, it's data dependent. I want to get your high-level comments?

其次，雷什瑪，展望未來，我認識你的腎臟科醫生，我們都是受過專業訓練的。所以，當你越來越接近 pove 資料集時。或許您可以幫我們說說，您是如何看待這裡與眾多 BAFF、APRIL 類型資產之間的差異的？我知道，這顯然取決於數據。我想聽聽你們的高層次意見？

You bet. Geoff, let me ask Duncan to take the question on ALY and I'll come back for pove.

當然。傑夫，我請鄧肯回答關於ALY的問題，我稍後回來回答。

Good afternoon, Geoff. So yes, as far as ALYFTREK is concerned, I would say that the vast majority of the newly eligible patients in the US have now started on ALYFTREK. And we're seeing the discontinued and transition patients transition nicely over to ALYFTREK as physicians are navigating the monitoring requirements over the first few months.

下午好，傑夫。所以，就 ALYFTREK 而言，我認為美國絕大多數符合條件的新患者現在都已經開始接受 ALYFTREK 治療。我們看到，隨著醫生們在最初幾個月逐步適應監測要求，那些停用或過渡治療的患者順利過渡到了 ALYFTREK。

The pace of transitions remain steady, and we're very happy with the progress. Outside the US, we're also seeing strong uptake in those countries with access. And I would add that in the 10 months since the launch of the ALYFTREK it's generated close to $0.5 billion of sales in revenue. So overall, we're pretty happy with the pace of progress on ALYFTREK.

過渡進程保持穩定，我們對所取得的進展非常滿意。在美國以外，我們也看到在那些能夠獲得醫療服務的國家，這種趨勢非常明顯。我還要補充一點，自 ALYFTREK 推出以來的 10 個月裡，它已經創造了近 5 億美元的銷售收入。總的來說，我們對 ALYFTREK 的進展速度相當滿意。

Geoff, on povetacicept, let me focus my comments IgAN. It is really very exciting. The data that we're going to share at the ASM, which is this coming week, is more patients' worth of data and longer follow-up. And you should look for the endpoint of proteinuria, hematuria, you should also look for the pharmacodynamic marker in IgAN, which is called Gd-IgA1. I'm very, very excited about these results.

Geoff，關於 povetacicept，我想把我的評論集中在 IgAN 上。真是太令人興奮了。我們將在下週舉行的 ASM 會議上分享的數據，包含了更多患者的數據和更長的追蹤時間。你應該尋找蛋白尿、血尿的終點，你也應該尋找 IgAN 的藥效學標記物，即 Gd-IgA1。我對這些結果感到非常非常興奮。

To me, if you think about IgAN and what it means, it is a chronic disease that unfortunately results in death, dialysis or transplantation, that's what ends up happening to our patients. And so what we're really trying to do here is get those autoantibodies under control in order to mitigate that end point. If you look at the disease, it's a disease of elevated APRIL levels and elevated BAFF levels.

在我看來，如果你想想 IgAN 及其意義，它是一種慢性疾病，不幸的是，它會導致死亡、透析或移植，這就是我們的病人最終的結局。因此，我們真正想要做的就是控制這些自體抗體，以減輕最終的後果。從疾病本身來看，這是一種 APRIL 水平升高和 BAFF 水平升高的疾病。

It's not the case that just one of those two cytokines is elevated. So it makes all the sense in the world to me to inhibit both, which is what pove does. The next thing to look at is the preclinical data, and you've heard me say before, the reason we were so excited about Alpine and pove because it was specifically engineered for higher tissue distribution, potency and binding affinity.

並非只有這兩種細胞激素中的一種升高。所以對我來說，抑制這兩者都是完全合理的，而這正是 pove 的作用。接下來要看的是臨床前數據，你們之前也聽我說過，我們對 Alpine 和 pove 如此興奮的原因是，它是專門為提高組織分佈、效力和結合親和力而設計的。

And then you translate that to the early data that we see in the clinic through RUBY-3. And it looks really good. Last thing I'll say is for patients who have this a chronic disease. The important thing is that they have a medicine, a biologic that they can take over time that is best for them. And from all of the data, not only in market research for IgAN patients, but you look at biologics in the marketplace is about the dosing small volume.

然後，我們將這些數據轉化為我們在 RUBY-3 臨床試驗中看到的早期數據。看起來真不錯。最後我想說的是，對於那些患有這種慢性疾病的患者來說。重要的是，他們有一種藥物，一種可以長期服用的、最適合他們的生物製劑。從所有數據來看，不僅是 IgAN 患者的市場研究，你看看市場上的生物製劑，都是關於小劑量給藥的問題。

It's about having an auto-injector and monthly dosing, which are key, and that's what we have with pove. Last thing to say, I do think nephrologists are also going to be interested in the fact that we've already started our Phase 2/3 trial in membranes. So all in all, it's pretty neat.

關鍵在於擁有自動注射器和每月一次的給藥方式，而這正是 Pove 所擁有的。最後我想說的是，我認為腎臟科醫生也會對我們已經開始進行膜的 2/3 期試驗這一事實感興趣。總而言之，這很棒。

Great. Thank you.

偉大的。謝謝。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Good afternoon. Thanks for taking my question. Just a follow-up on Jeff's here with the pove data. With all those markers that we're going to look at in the longer-term Phase 2 data, maybe put that in context for us about how to think about the read-through to eGFR benefit and just kind of overall positioning as we look to these other two drugs that are out there or more?

午安.謝謝您回答我的問題。這裡補充一下 Jeff 提供的 pove 數據。考慮到我們將在長期 2 期數據中觀察的所有指標，或許可以為我們解釋一下如何看待 eGFR 獲益的解讀，以及當我們考慮其他兩種或更多藥物時，整體定位是什麼？

And then secondly, on the pain franchise, you talked for a bit about getting that third PBM on board prior to really opening up distribution. Could you just help us understand what's being finalized on that end?

其次，關於疼痛治療產品線，你談到了在真正開放分銷之前，如何讓第三家藥品福利管理公司 (PBM) 參與其中。您能否幫我們了解那邊最終敲定的是什麼？

Yes. Let me take the pove question first, Salveen, then I'll ask Duncan to comment on the last of the 3 PBMs. So Salveen in many renal diseases, including in IgAN, there's a very strong association of correlation between reductions in proteinuria and stabilization eGFR. And I expect that, that will hold up in all of these Phase 3 data that we see.

是的。Salveen，我先回答pove問題，然後我會請Duncan評論3個PBM中的最後一個。因此，在許多腎臟疾病中，包括 IgAN，Salveen 蛋白尿減少與 eGFR 穩定之間有非常強烈的相關性。我預計，在所有這些第三階段的數據中，這一點都會得到證實。

I think the important thing to note though is that while the final end point, that's to say even for traditional approval is eGFR showing the stabilization of eGFR. What we're really trying to do for our patients is to prevent those long-term complications of death, dialysis and transplantation, it's just that the endpoint if we measure that would take too long, so the agency has accepted eGFR stabilization of that is the fine end point.

但我認為需要注意的是，最終終點，也就是說，即使是傳統的審批，也是 eGFR 顯示 eGFR 穩定性。我們真正想為患者做的，是預防死亡、透析和移植等長期併發症，只是如果我們測量這些終點，需要的時間太長，所以該機構已經接受了 eGFR 穩定作為良好的終點。

And so when you look at all of the evidence that's been generated over the course of time, the medicine that has the best reductions in proteinuria in hematuria, in this Gd-IgA1. I think that's the medicine that's going to be best for patients. If you think about the long-term outcomes. But I do think that the association of proteinuria and eGFR will hold, and I expect that you will see that. Duncan.

因此，當你審視隨著時間的推移而產生的所有證據時，你會發現，在減少血尿中的蛋白尿方面效果最好的藥物是 Gd-IgA1。我認為這是最適合患者的藥物。如果你考慮長遠結果的話。但我認為蛋白尿與 eGFR 之間的關聯性仍然存在，我希望你也能看到這一點。鄧肯。

Salveen, so I think it's important to note that we're building a long-term pain franchise here where, clearly, we want to secure broad access for patients, but we also want to ensure long-term value of our medicines. So we feel very happy with the progress we've made so far in securing 170 million lives for JOURNAVX in a relatively short period of time.

Salveen，所以我認為需要指出的是，我們正在建立一個長期的疼痛治療體系，顯然，我們希望確保患者能夠廣泛獲得這些藥物，但我們也希望確保我們的藥物具有長期價值。因此，我們對在相對較短的時間內為 JOURNAVX 保障 1.7 億人的生命安全所取得的進展感到非常滿意。

I would say that we're in productive ongoing conversations with the third PBM. And obviously, we'll keep you updated as we have news there. And as you know, in the meantime, patients who are not covered can get JOURNAVX through the patient support program. So overall, we're pleased with the access progress to date. It will continue to expand over the balance of 2025 and 2026.

我認為我們正在與第三家藥品福利管理機構進行富有成效的持續對話。當然，一旦有相關消息，我們會及時通知您。如您所知，同時，沒有醫療保險的患者可以透過患者援助計劃獲得 JOURNAVX。總的來說，我們對目前的無障礙設施建設進展感到滿意。在 2025 年剩餘時間和 2026 年，它將繼續擴張。

And in the meantime, of course, a key performance indicator is continued physician uptake and prescription growth while we secure access. And on that point, although you didn't ask, I would just reference the prescription growth we saw 10,000 prescriptions in quarter 1, 90,000 prescriptions in quarter two, 170,000 prescriptions in quarter three, and of course, several thousand in October. So we're very happy with the acceleration we're seeing in prescriptions while we finalize access.

當然，同時，關鍵的績效指標是醫生持續接受治療和處方量持續成長，同時確保我們能夠獲得治療。關於這一點，雖然你沒有問，但我只想提一下處方增長情況：第一季處方量為 10,000 張，第二季度為 90,000 張，第三季度為 170,000 張，當然，10 月份也有幾千張。因此，在最終確定准入條件的同時，我們對處方數量的加速成長感到非常滿意。

Jessica Fye, JPMorgan.

潔西卡費伊，摩根大通。

Hey guys, good afternoon and thanks for taking my question. I was wondering if you could just touch on what your current priorities are as it relates to capital allocation and specifically on the business development front, is there a phase of development you feel as the sweet spot for assets that Vertex brings in?

各位好，下午好，感謝你們回答我的問題。我想請您談談您目前在資本配置和業務發展方面的優先事項，特別是您認為Vertex收購的資產在哪個發展階段最為理想？

Charlie?

查理？

Yes, Jessica, no change in our priorities for capital allocation. We've said for some time now, our top priority is to reinvest in the business, both internally and externally to drive innovation and growth. That continues to be true. We are investing in our pipeline right now in commercialization. We are making capital investments in support of the business as well, and that remains the top priority.

是的，傑西卡，我們的資本配置優先事項沒有改變。我們一直以來都強調，我們的首要任務是增加對業務的再投資，包括內部投資和外部投資，以推動創新和成長。情況依然如此。我們目前正在投資我們的產品線，以實現商業化。我們也在進行資本投資以支持業務發展，這仍然是我們的首要任務。

A secondary priority for us is share buybacks. We were very active in the third quarter, taking advantage of the volatility in the stock price after the last earnings call. So we were out there buying aggressively in the quarter at prices that we think are quite attractive. And so that combination of reinvestment in the business, as well as share buybacks will continue to be the priority going forward.

我們的第二要務是股票回購。我們在第三季非常活躍，利用了上次財報電話會議後的股價波動。因此，本季我們積極買入，價格我們認為相當有吸引力。因此，對業務進行再投資以及股票回購仍將是未來的優先事項。

In terms of whether we are looking for assets of any specific stage of development, here, I think you know with our sandbox approach, we are always looking for the best technology and the best assets in any of the disease areas where we are focused. That sometimes takes the form of enabling technology.

至於我們是否在尋找處於特定發展階段的資產，我想您也知道，透過我們的沙盒方法，我們始終在我們關注的任何疾病領域尋找最好的技術和最好的資產。有時，這種現象會以技術賦能的形式出現。

Sometimes it takes the form of programs that are either preclinical or in the clinic. We were certainly very happy with the Alpine acquisition last year. If we could find something like that again, we would certainly be interested but we are open to all types of deals that move our strategy forward in our different disease areas.

有時，它會以臨床前或臨床項目的形式出現。我們對去年收購 Alpine 的交易感到非常滿意。如果我們能再次找到類似的機會，我們當然會很感興趣，但我們對能夠推動我們在不同疾病領域策略發展的各種交易都持開放態度。

Evan Seigerman, BMO Capital.

Evan Seigerman，BMO Capital。

Hi guys, thank you so much for taking my question. I want to touch on the competitive profile, pove. We talked about having an auto-injector and Q4 week dosing. Can you put the context of how important this is maybe in relationship to other competitive products that could be on the market? And why you think this could give you a competitive advantage?

大家好，非常感謝你們回答我的問題。我想談談競爭格局，pove。我們討論了使用自動注射器和每 4 週給藥一次的方案。能否說明一下這件事的重要性，例如它與市場上其他競爭產品之間的關係？你認為這能為你帶來競爭優勢的原因是什麼？

Yes. Evan, I'll take team that with Duncan said he can give you a commercial perspective. The auto-injector once-monthly dosing in small volumes are really, really important. Of course, this means we've already stopped through safety, efficacy benefit risk and a really good-looking clinical profile.

是的。艾文，我會選擇鄧肯所在的團隊，他說他可以從商業角度給你一些建議。每月一次的小劑量自動注射器給藥真的非常非常重要。當然，這意味著我們已經從安全性、有效性、風險和良好的臨床概況等方面進行了評估。

But especially in diseases where you're using a biologic this administration set of features just cannot be underestimated. Now I'll turn it over to Duncan to tell you about some examples in the field and maybe some market research as well, Duncan.

但尤其是在使用生物製劑治療疾病時，這套給藥方案的特性絕對不容小覷。現在我把麥克風交給鄧肯，讓他來跟大家講講這個領域的一些例子，也許還會介紹一些市場調查的內容。

Yes. Thank you for the question. So I mean, I would step back a little bit and just make the point that for a variety of reasons and attributes, we believe that pove offers best-in-class potential in terms of its mechanism of action, the way it's been specifically engineered for the disease the compelling clinical profile and then as you allude to, the patient profile, the key here is that it's dosed every four weeks at a very low volume. It can be administered at home.

是的。謝謝你的提問。所以我的意思是，我想稍微退後一步，指出由於各種原因和特性，我們相信 pove 在作用機制、針對該疾病專門設計的療法、引人注目的臨床概況以及您提到的患者概況方面，都具有一流的潛力。關鍵在於，它每四週以非常低的劑量給藥一次。可以在家中進行操作。

And those attributes are incredibly important, especially in biologics. They're being shown to significantly reduce patient burden, improve adherence and increased treatment satisfaction in other biologics previously launched. So we do think, although it sounds unimportant. Actually, this is a very important differentiator for pove alongside the mechanism of action and the excellent clinical data that we're seeing. So we're super excited to be bringing it to market. And for all of those reasons, we do think it has best-in-class potential.

這些特性極為重要，尤其是在生物製劑領域。研究表明，與其他已上市的生物製劑相比，它們能顯著減輕患者負擔，提高依從性，並提升治療滿意度。所以我們確實這麼認為，雖然這聽起來無關緊要。事實上，除了作用機制和我們所看到的優秀臨床數據之外，這也是pove一個非常重要的區別因素。所以我們非常興奮能將它推向市場。基於以上所有原因，我們認為它具有成為同類最佳產品的潛力。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi guys, good evening. Thanks for taking my question. Can you just provide some clarity on what the FDA had seen thus far that let them give you the confidence to start the filing early and get this breakthrough designation for pove?

大家好，晚上好。謝謝您回答我的問題。您能否詳細說明一下，FDA 目前看到了哪些信息，讓您有信心提前提交申請並獲得 pove 的突破性療法認定？

Yes, sure thing. So, we've had the opportunity to complete what's called a pre-BLA meeting. In other words, we've had the opportunity to sit with the agency, review all of the data to date, talk through what the filing submission, what's called the will look like. So they have access to all of our data and our plans for how we expect to be filing after we went through that meeting, that's when we got the breakthrough designation.

好的，沒問題。因此，我們有機會完成了所謂的 BLA 預備會議。換句話說，我們有機會與該機構坐下來，審查迄今為止的所有數據，討論提交的文件（即所謂的「遺囑」）應該是什麼樣子。所以，在那次會議之後，他們就能取得我們所有的數據和我們預期的申報計劃，也就是在那次會議之後，我們獲得了突破性認定。

It's also when we received their endorsement for rolling submission. I would say that if the reason they have granted us breakthrough enrolling is probably the same as for most medicines that get it. They see unmet need. They see a medicine that is attractive and can treat the disease at hand and that they have enthusiasm to receive the filing so that they can plan their workload.

也是在那時，我們收到了他們對滾動提交的支持。我認為，他們授予我們突破性招募資格的原因可能與大多數獲得該資格的藥物相同。他們看到了未被滿足的需求。他們看到一種有吸引力且能治療當前疾病的藥物，並且他們熱切希望收到該藥物，以便安排他們的工作。

Terence Flynn, Morgan Stanley.

Terence Flynn，摩根士丹利。

Great, thanks for taking the question. I was just wondering, Reshma, if there's any update on the NOPAIN Act and what you guys are doing on that front. And then I know you mentioned there's some Phase 4 data for JOURNAVX that's coming up here. Are we going to see anything on time to discharge setting? I know that's something that some physicians have asked about in the past.

太好了，謝謝你回答這個問題。雷什瑪，我只是想問，關於《無痛法案》有沒有什麼最新進展，以及你們在這方面正在做些什麼。我知道您提到過，JOURNAVX 的一些第四階段數據即將公佈。我們會看到任何關於按時出院安排的資訊嗎？我知道過去有些醫生問過這個問題。

Yes. Sure. Terence. On the no pain final list, it was supposed to be out on October 31. So last week Friday, and we understand that it's been postponed because of the government shutdown. We continue to advocate vigorously for the inclusion of JOURNAVX. And as we've talked before, while the dollar number may be small for hospital outpatient or surge center for Medicare patients.

是的。當然。特倫斯。在“無痛”最終名單上，它原定於 10 月 31 日發布。所以，原定於上週五舉行的活動，據我們了解，由於政府停擺而被推遲了。我們繼續大力倡導將 JOURNAVX 納入其中。正如我們之前討論過的，雖然對於醫院門診或醫療保險患者的臨時救治中心來說，金額可能很小。

We think that the principle is really important. The NOPAIN Act was literally designed for a medicine like JOURNAVX. So we continue to have our conversations, but the list -- the finalization of that list and the release of that list has been delayed. I don't have an updated timeline for when it will be out. On the Phase IV data, we've now completed enrollment in 2 Phase IV studies.

我們認為原則非常重要。《無痛法案》簡直就是為像 JOURNAVX 這樣的藥物而設計的。因此，我們仍在繼續進行討論，但名單的最終確定和發布已被推遲。我目前還沒有最新的發佈時間表。關於 IV 期數據，我們目前已完成 2 項 IV 期研究的入組。

One is multimodal therapy and use prior to and postop aesthetic and reconstructive surgeries and another one is in orthopedic and general surgeries. The data that you're going to see later this week is in the aesthetic and reconstructive surgery area. And the trust of the data is about opioid reduction compared to what's seen in the literature. We have a whole host of additional studies coming that look at a variety of other endpoints, including discharge, but those data are not ready just yet.

一種是多模式療法，用於術前和術後美容及重建手術；另一種是用於骨科和普通外科手術。本週稍後您將看到的數據是關於美容和重建手術領域的。而數據的可信度在於，與文獻中所描述的情況相比，鴉片類藥物的使用有所減少。我們還有一系列其他研究即將開展，這些研究將著眼於各種其他終點，包括出院，但這些數據尚未準備就緒。

David Risinger, Leerink Partners.

David Risinger，Leerink Partners。

Thanks very much. I'm Edward calling on behalf of David Risinger. So two questions, please. For JOURNAVX, how many of the 170 million lives have unrestricted access and how many commercial lives are covered by the major PBMs. And the second question on the next-generation CF candidate VX-828. Can You provide more details on the PPP news ahead and also the timing for data disclosure?

非常感謝。我是愛德華，我代表大衛瑞辛格打電話。請容許我問兩個問題。對 JOURNAVX 而言，1.7 億人中有多少人享有不受限制的醫療服務？有多少商業人壽保險由主要藥品福利管理機構 (PBM) 承保？第二個問題是關於下一代CF候選機型VX-828。您能否提供更多關於PPP專案後續進展以及資料公佈時間的詳細資訊？

Let me take the VX-828 question first, and I'll turn it over to Duncan to talk to you about JOURNAVX. So on VX-828, the important thing to know is it is the most efficacious medicine in vitro that we had ever studied and you know that our in vitro systems in CF have translated time and again, not only qualitatively but quantitatively to what we see in the clinic. So 828 is the most efficacious that we've seen so far.

我先回答 VX-828 的問題，然後把問題交給 Duncan，讓他來跟大家談談 JOURNAVX。因此，關於 VX-828，需要了解的重要一點是，它是我們研究過的體外療效最好的藥物，而且你知道，我們在 CF 中的體外系統已經一次又一次地轉化，不僅在定性上，而且在定量上，與我們在臨床上看到的結果相符。所以，828 是我們目前為止所見過的最有效的。

You should expect to see data next year. We're in the patient cohort now. I'll give you more specific time lines in the coming months, but you should see data next year. And in terms of what we're looking for, look, it is getting hard to do better than what we have today. The data that I described at TRIKAFTA one- to two-year-old is truly remarkable and unprecedented.

預計明年就能看到數據。我們現在屬於患者群體。未來幾個月我會給出更具體的時間表，但明年你們應該就能看到數據了。至於我們所追求的，你看，現在想要做得比目前擁有的更好已經越來越難了。我在 TRIKAFTA 上描述的一到兩歲兒童的數據確實非常出色，前所未有。

But if it is possible to do better and by that, I mean bring more patients across all age groups to lower levels of sweat chloride, i.e., higher levels of CFTR protein function, that's what we are committed to do, and that's what we're looking for with VX-828, Duncan a couple of words on JOURNAVX. And the 170 million lives and tell us about the kind of coverage.

但如果能夠做得更好，我的意思是讓所有年齡層的更多患者達到更低的汗液氯化物水平，即更高的 CFTR 蛋白功能水平，這就是我們致力於去做的事情，也是我們用 VX-828 所追求的目標。鄧肯，關於 JOURNAVX，請說幾句。1.7億人的生活狀況，以及他們所受到的報道類型。

Yes. So thank you for the question. So to answer it, of the 170 million lives, 113 million are unrestricted. So as I've communicated before, all of the contracts that we have done all of the agreements we have in place are for no prior authorization, no step edit.

是的。謝謝你的提問。所以要回答這個問題，在1.7億條生命中，有1.13億條生命不受限制。正如我之前所溝通的，我們簽訂的所有合約、我們現有的所有協議都無需事先授權，無需任何步驟修改。

So we're very pleased indeed with that progress. And as I alluded to, in one of the earlier questions. We continue to make progress with the third PBM, where we're in active conversations and indeed with the Medicare plans as well.

所以我們對這項進展感到非常滿意。正如我在前面某個問題中提到的。我們在與第三家藥品福利管理機構 (PBM) 的合作中繼續取得進展，我們正在積極與他們進行對話，實際上我們也在與聯邦醫療保險計劃進行對話。

Philip Nadeau, TD Cowen.

Philip Nadeau，TD Cowen。

Good afternoon. Thanks for taking our questions. Two commercial questions for us. First, on JOURNAVX, based on prescription trends and the prescription numbers that you said, it seems like gross to net continues to be quite high. Can you give us a sense of where it currently is and where it could be in 2026?

午安.謝謝您回答我們的問題。我們有兩個商業方面的問題。首先，根據 JOURNAVX 的處方趨勢和您所說的處方數量，毛利與淨利之比似乎仍然很高。您能否大致介紹一下它目前處於什麼狀態，以及到 2026 年可能會發展成什麼樣子？

And then second, on ALYFTREK, you said a couple of times steady transition from TRIKAFTA to ALYFTREK. When do you think you'd be in a position to give formal guidance, say, three years from now, some percentage of TRIKAFTA patients will be transitioned to ALYFTREK?

其次，關於 ALYFTREK，你曾多次提到從 TRIKAFTA 到 ALYFTREK 的平穩過渡。您認為何時才能給予正式指導意見，例如，三年後，一定比例的 TRIKAFTA 患者將過渡到 ALYFTREK？

Sure thing. So let me take the second question first, and I'll turn it over to Charlie for gross to net. As you heard Duncan say, in the coming couple of years, we expect the majority of patients around the globe to who are on TRIKAFTA to transition to ALYFTREK. Because we believe ALYFTREK is the best available CFTR modulator. Charlie, a couple of words on gross to net and JOURNAVX.

當然可以。那麼，我先回答第二個問題，然後把計算毛利到淨利的問題交給查理。正如你聽到鄧肯所說，在接下來的幾年裡，我們預計全球大多數正在接受 TRIKAFTA 治療的患者將過渡到接受 ALYFTREK 治療。因為我們相信 ALYFTREK 是目前最好的 CFTR 調節劑。Charlie，關於毛利到淨利和 JOURNAVX，有幾句話要說。

Yes, Phil. So the three drivers, of course, gross to net are payer discounts, wholesaler discounts and the impact of the patient support program with that last one being most significant in 2025. While we are working to expand payer coverage and finish some of the contracting work that Duncan talked about, the patient support program continues to be very active, and that's resulting in elevated gross to net for the time being. We're not yet ready to give guidance for 2026 on that until we've landed on the mix and the book of business with payers. I think it would be early to say anything about that for next year.

是的，菲爾。因此，從毛利到淨利，三個驅動因素當然是付款方折扣、批發商折扣和患者支持計劃的影響，其中最後一個因素在 2025 年最為顯著。雖然我們正在努力擴大支付方覆蓋範圍並完成鄧肯提到的一些合約工作，但患者支援計劃仍然非常活躍，這導致目前毛利與淨利之比有所上升。在我們確定了與付款方的業務組合和業務安排之前，我們還無法就 2026 年的情況給予指導意見。我覺得現在談論明年的事情還為時過早。

Great, thanks for taking our questions.

太好了，謝謝你們回答我們的問題。

Paul Matteis, Stifel.

Paul Matteis，Stifel。

Hi there, thanks so much for taking our questions. This is Julian on for Paul. I just wondering if there's any updated thinking around the potential development of suzetrigine in chronic pain following the update that you provided last quarter.

您好，非常感謝您回答我們的問題。這裡是朱利安替保羅發言。我想知道，繼您上個季度提供的最新資訊之後，關於舒澤三嗪在慢性疼痛治療​​方面的潛在發展，是否有任何新的想法。

Just wondering if there's any other indications you're pursuing or if there's any other way in which you're considering potentially even acquiring an asset to play in the space longer term as there's been greater interest from competitors?

我想知道您是否還有其他跡象表明您正在尋求某種途徑，或者您是否正在考慮以其他方式收購資產，以便在該領域長期發展，因為競爭對手對此表現出了更大的興趣？

Yes. No new updates for you on suzetrigine in the peripheral neuropathic pain area. We are hyper-focused on getting our DPN study number two up and running to secure the DPN indication, which -- for which there is a clear pathway concrete next steps for us to take and an ability to serve 2 million patients. With regard to our ideas for how to expand to the broader P&P market, there's a couple of things there.

是的。關於舒澤曲林治療週邊神經性疼痛，目前沒有新的進展資訊。我們正全力以赴地推進第二項 DPN 研究，以確保 DPN 適應症的獲得——為此，我們有明確的下一步具體步驟，並且有能力為 200 萬患者提供服務。關於我們如何拓展到更廣泛的P&P市場，有幾點需要考慮。

We're working through what we believe would be the most efficient way to get there. We're also thinking through time lines for our NaV1.8 inhibitors, i.e., JOURNAVX and our NaV1.7s and the possibility of combination. So more to come on that. PNP remains very interesting to us. But the focus now is on securing the DPN indication, getting the second DPN study diabetic peripheral neuropathy study up and running. And I do think that we'll be completing both those studies by the end of next year.

我們正在研究我們認為到達那裡的最有效方法。我們也正在考慮 NaV1.8 抑制劑（即 JOURNAVX）和 NaV1.7 抑制劑的研發時間表以及合併用藥的可能性。關於這一點，後續還會有更多討論。PNP 仍然讓我們非常感興趣。但現在的重點是確保 DPN 適應症，啟動並進行第二項 DPN 研究（糖尿病週邊神經病變研究）。而且我認為我們將在明年年底前完成這兩項研究。

Great. Thank you.

偉大的。謝謝。

Gena Wang, Barclays.

吉娜·王，巴克萊銀行。

Thank you for taking my questions. So maybe I would just have one quick question regarding the Poly data later this week. I know you cannot disclose anything. Regarding the actual data. But just wondering, given if we look at Vera data, they're already setting eGFR, but are pretty high, basically flat or the slow is relatively I think a slope is minus 0.1%. So here, do you think with your drug profile, do you think it could actually improve the eGFR over the longer treatment?

謝謝您回答我的問題。所以，或許我本週稍後會有一個關於 Poly 數據的問題。我知道你不能透露任何事。關於實際數據。但我只是好奇，如果我們看 Vera 的數據，他們已經設定了 eGFR，但數值相當高，基本上是平的，或者說速度相對較慢，我認為斜率為 -0.1%。那麼，根據你的藥物方案，你認為長期治療真的能改善eGFR嗎？

Yes. Gena, I do understand your question. I think -- you'll be pleased with the data that we show at ASN later this week, I certainly am. I would say the same thing that I said to Salveen reductions in premier in a number of homogeneous renal diseases with proteinuria that translated to stabilization of eGFR.

是的。吉娜，我明白你的問題。我認為——你會對我們本週晚些時候在 ASN 上展示的數據感到滿意，我肯定很滿意。我對 Salveen 的評價與我對他的評價相同，即在一些伴有蛋白尿的同質性腎臟疾病中降低 Premier 水平可使 eGFR 穩定下來。

And so I think that, that will happen. I think the more important question is, over the long term, as we treat our patients with IgAN or membranous and we have medicines that can get patients to lower levels of proteinuria completely eliminate if not decrease, hematuria, gets a low levels of these [ab-baring] Gd-IgA antibodies. I think that's where we're going to see practice move. And I think you're already seeing that with KDIGO guidelines, for example. I won't jump ahead of the data coming at ASN, but you will see eGFR data from the povetacicept IgAN program.

所以我認為，這會發生。我認為更重要的問題是，從長遠來看，當我們治療患有 IgA 腎病或膜性腎病的患者時，我們有藥物可以使患者的蛋白尿水平降低，完全消除（如果不能減少）血尿，並使這些[ab-baring] Gd-IgA 抗體的水平降低。我認為這就是我們將會看到的實踐方向。我認為，例如 KDIGO 指南就體現了這一點。我不會搶在 ASN 公佈數據之前妄下斷言，但您將會看到來自 povetacicept IgAN 項目的 eGFR 數據。

Thank you.

謝謝。

Mohit Bansal, Wells Fargo.

莫希特·班薩爾，富國銀行。

Great, thank you very much for taking my question. And I would also emphasize or asked a question around the BD here. I would love to understand your thought process here given that, I mean, you said that if we find something like pove, we would go for it.

太好了，非常感謝您回答我的問題。我還要強調一下或問一個關於BD的問題。我很想了解你的想法，因為你說過，如果我們找到類似 pove 的東西，我們就會去做。

I think the only challenge is that Vertex is not a small company anymore. So maybe is there a chance that you would look at bigger deals in that $5 billion to $10 billion range as well? Or given your cash position, you think you would probably be nimble and small when it comes to BD at this point?

我認為唯一的挑戰是 Vertex 不再是一家小公司了。那麼，您是否也有可能考慮一下金額在 50 億美元到 100 億美元之間的更大交易呢？或者，考慮到你目前的現金狀況，你認為在業務拓展方面，你現在可能會採取靈活且規模較小的策略嗎？

This is Reshma. Sorry, sorry. I'm sorry, Mohit. I think Charlie summarized it really well. Our BD strategy is very much in lockstep with our internal innovation strategy. It's all about the Sandbox diseases and our approach to R&D, high unmet need, the biomarkers that translate from bench to bedside as well as targets that are validated, be it a genetic or pharmacology efficient clinical development and regulatory pathways and specialty markets. That is the -- those are the guiding principles that have led us to where we are. And you can bet that we're going to keep going with the same. It's not about the size. It's all about fit with R&D strategy.

這是雷什瑪。對不起，對不起。對不起，莫希特。我覺得查理總結得很好。我們的業務拓展策略與內部創新策略高度一致。這一切都與沙盒疾病和我們的研發方法、未滿足的高需求、從實驗室到臨床轉化的生物標誌物以及經過驗證的靶點有關，無論是基因還是藥理學，高效的臨床開發和監管途徑以及專業市場。這就是──這些是引領我們走到今天的指導原則。可以肯定的是，我們將繼續採取同樣的做法。這與大小無關。一切都取決於與研發策略的契合度。

Got it. Thank you.

知道了。謝謝。

Myles Minter, William Blair.

邁爾斯·明特，威廉·布萊爾。

Hi, This is Jake on for Myles. I have a couple for you. First, I wanted to ask you about any updates to your DM1 program when or how much data we can expect and then sort of how you're evaluating that program given the recent acquisition of Avidity.

大家好，我是傑克，替麥爾斯報道。我這裡有幾張給你。首先，我想問您的 DM1 計劃是否有任何更新，以及我們可以期待多少數據，然後鑑於最近收購了 Avidity，您是如何評估該計劃的。

And then on CASGEVY, can you remind us as patients are going through the process and then enrolling into this long-term follow-up study, your policy for disclosing adverse events would those be both from the preconditioning regimen or from the editing regimen or both?

關於 CASGEVY，您能否提醒我們，當患者經歷治療過程並參與這項長期追蹤研究時，貴方揭露不良事件的政策是包括預處理方案、編輯方案還是兩者兼具？

Yes. Let's maybe do CASGEVY first. For all of the clinical trial patient data, whether it's in the primary, let's call it, the primary sickle cell disease and beta thal studies [CLIN-1] and [CLIN-2] or if it's in the long-term follow-up study, they get reported through the clinical trial system. For commercially treated patients, they get reported as physicians may report through to either the company or to the FDA in the normal manner.

是的。我們或許可以先做《卡斯吉維》。所有臨床試驗患者數據，無論是在主要研究（我們稱之為原發性鐮狀細胞病和β地中海貧血研究 [CLIN-1] 和 [CLIN-2]）中，還是在長期追蹤研究中，都會透過臨床試驗系統進行報告。對於接受商業治療的患者，他們的治療情況會按照正常程序報告給公司或 FDA。

DM1 is an exciting program for us. You might recall that the way we set up the study in order to be most efficient and fastest to pivotal development if the data are supportive, is we did a SAD/MAD directly in patients. We've completed the SaaS portion of DM1, and we're in the MAD portion now. I expect that we'll be able to complete the study and have results next year. And what that means is because we are in patients, it will be safety and efficacy.

DM1 對我們來說是一個令人興奮的項目。您可能還記得，為了最有效率、最快地推進關鍵性開發（如果數據支援），我們進行這項研究的方式是直接在患者身上進行 SAD/MAD。我們已經完成了 DM1 的 SaaS 部分，現在正在進入 MAD 部分。我預計我們明年就能完成這項研究並獲得結果。這意味著，因為我們是在患者身上進行的，所以安全性和有效性將是關鍵。

William Pickering, Bernstein.

威廉‧皮克林，伯恩斯坦。

Hi, thank you very much for taking my question. I have two about pove and pMN if I may. The first is if you could discuss the competitive landscape in that indication and perhaps compared to IgAN? And then the second is how you define the pMN addressable market. I think that Biogen has estimated only 36,000 patients in the US, which seems a bit more conservative than your combined US and EU number would imply?

您好，非常感謝您回答我的問題。如果可以的話，我想問兩個關於pove和pMN的問題。首先，您能否討論一下該適應症的競爭格局，並或許可以將其與 IgAN 進行比較？其次，如何定義 pMN 的目標市場。我認為 Biogen 估計美國祇有 36,000 名患者，這似乎比你所說的美國和歐盟加起來的數字要保守一些？

Yes. So with regard to membranous, there are some similarities between IgAN nephropathy and membranous the most compelling is that they are both B-cell mediated diseases where there's autoantibody formation and that the autoantibodies end up depositing in the kidney, which leads to the kidney dysfunction. The way that membranous and IgAN are different is clearly in prevalent.

是的。因此，就膜性腎病變而言，IgAN腎病變和膜性腎病變之間存在一些相似之處，最引人注目的是它們都是B細胞介導的疾病，其中會產生自身抗體，並且自身抗體最終會沉積在腎臟中，從而導致腎功能障礙。膜性腎病變和 IgA 腎病變之間的差異顯而易見。

There's about 700,000 people with IgAN, for example, in China. It's a really significant disease in Asia I think the estimates are something like 300,000 in the Western world, while membranous is more like 150,000 in the Western world. The competitive landscape is also different much more competitive intensity in IgAN nephropathy, likely because it's a larger patient population.

例如，在中國，約有70萬人患有IgA腎病變。我認為這在亞洲是一種非常嚴重的疾病，據估計，西方世界的病例數約為 30 萬，而膜性骨髓瘤在西方世界的病例數約為 15 萬。IgA腎病領域的競爭格局也截然不同，競爭強度大得多，這可能是因為IgA腎病患者群體更大。

To the best of my knowledge, we're the only APRIL/BAFF, for example, in pivotal development for membranous. And I do think exactly for the reason that these are both B cell-mediated diseases, I think a drug like Poly has best-in-class potential in membranous. And in the APRIL/BAFF class, we're in the lead because we are already initiated in the Phase 2/3. I hope that helps.

據我所知，例如，我們是唯一將 APRIL/BAFF 應用於膜性腫瘤關鍵開發的公司。而且我認為，正因為這兩種疾病都是 B 細胞介導的，所以像 Poly 這樣的藥物在膜性乳癌方面具有同類最佳的潛力。在 APRIL/BAFF 課程中，我們處於領先地位，因為我們已經進入了第二/第三階段。希望對您有幫助。

This concludes our question-and-answer session. I would like to turn the conference back over to management for any closing remarks.

我們的問答環節到此結束。我想把會議交還給管理階層，請他們作總結發言。

Thanks, everyone, for joining. Apologies again for the technical issues. We'll look to have the replay up as soon as possible. And with that, Chuck, if you can give that information. Thank you.

謝謝大家的參與。再次為技術問題向您致歉。我們會盡快上傳回放。查克，如果你能提供這些資訊的話。謝謝。

The conference has now concluded. Thank you for attending today's presentation. A replay of today's event will be available shortly after the call concludes by dialing 1 (877) 344-7529 or 1 (412) 317-0088. Using replay access code 10196553. Thank you for your participation. You may now disconnect.

會議已經結束。感謝各位參加今天的報告會。本次活動的重播將在電話會議結束後不久提供，撥打 1 (877) 344-7529 或 1 (412) 317-0088 即可收聽。使用重播存取代碼 10196553。感謝您的參與。您現在可以斷開連線了。