福泰製藥 (VRTX) 2026 Q2 法說會逐字稿

Good day and welcome to the Vertex Pharmaceuticals second quarter 2026 earnings call. (Operator Instructions) Please note this event is being recorded. I would now like to turn the conference over to Ms. Susie Lisa. Please go ahead.

各位好，歡迎參加 Vertex Pharmaceuticals 2026 年第二季財報電話會議。(操作員指示) 請注意，本活動將被錄音。現在我想把會議交給 Susie Lisa 女士。請開始。

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 Second Quarter 2026 Financial Results Conference Call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President; Charlie Wagner, Chief Operating Officer and Chief Financial Officer; and Duncan McKechnie, Chief Commercial 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.

各位晚安。我叫 Susie Lisa，身為投資人關係資深副總裁，我很高興歡迎各位參加我們 2026 年第二季財務結果電話會議。今晚的電話會議中，將由 Vertex 執行長兼總裁 Reshma Kewalramani 博士、營運長兼財務長 Charlie Wagner，以及商務長 Duncan McKechnie 發表事先準備的談話。我們建議您在收聽本次電話會議時，同步開啟網路直播投影片。本次電話會議將被錄音，並會在我們的網站提供重播。

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, the proposed acquisition of Crinetics Pharmaceuticals and the expected benefits of that transaction and Vertex's future financial performance, are based on management's current assumptions. Actual outcomes and events could differ materially.

我們將在本次電話會議中作出前瞻性陳述，相關風險與不確定性已在今日新聞稿及我們向美國證券交易委員會提交的文件中詳述。這些陳述（包括但不限於）關於 Vertex 已上市之囊性纖維化、鐮狀細胞疾病、β-地中海型貧血及中重度急性疼痛藥物、我們的研發管線、擬收購 Crinetics Pharmaceuticals 以及該交易的預期效益，與 Vertex 未來財務表現等，均係基於管理層目前的假設。實際結果與事件可能會有重大差異。

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. I'll now turn the call over to Reshma.

我也要提醒各位，我們今晚在電話會議中將檢視的部分財務結果與財測指引，是以非 GAAP 基礎呈現。現在把電話交給 Reshma。

Thanks, Susie. Good evening, all, and thank you for joining us on the call today. Vertex's second quarter performance was excellent, with strong momentum in the commercial portfolio, rapid progress across our R&D pipeline, and the announcement of the definitive agreement to acquire Crinetics Pharmaceuticals, which brings rare endocrine diseases as a fifth pillar to Vertex. Second quarter total revenue grew 12% year-on-year, driven by the strength of our cystic fibrosis portfolio and the growing contributions from our newer products, CASGEVY and JOURNAVX.

謝謝你，Susie。各位晚安，感謝今天加入我們的電話會議。Vertex 第二季表現非常出色，商業產品組合動能強勁、研發管線各項進展迅速，並宣布已簽署確定性協議收購 Crinetics Pharmaceuticals，為 Vertex 增添「罕見內分泌疾病」作為第五大支柱。第二季總營收年增 12%，主要受惠於囊性纖維化產品組合的強勁表現，以及新產品 CASGEVY 與 JOURNAVX 的貢獻持續成長。

As I've previously highlighted, this is a year of execution for Vertex across commercial, clinical and regulatory. And on each of those fronts, we advanced significantly in the second quarter. Commercially, we delivered strong revenue growth across all diseases, made meaningful progress in reimbursed access and continue to execute on near-term launch planning to drive the next phase of growth.

如我先前強調，對 Vertex 而言，今年是商業、臨床與法規三方面的執行之年。而在第二季，我們在上述各面向都取得了顯著進展。在商業方面，我們在所有疾病領域皆實現強勁營收成長，在給付可及性方面取得實質進展，並持續推進近期上市規劃，以帶動下一階段的成長。

Clinically, we continue to make significant progress in advancing our pipeline, including completing enrollment in the AGLOW Phase 2 study of VX-407 in ADPKD, tracking to complete enrollment in the AMPLITUDE Phase 3 study in AMKD by the end of this year and reporting results from the interim analysis cohort of AMPLITUDE in the beginning of 2027. We also remain on track to release results later this year from a proof-of-concept study in DM1 and an expanded population for AMKD in the AMPLIFIED trial as well as the initial patient data from VX-828 in CF.

在臨床方面，我們持續在推進研發管線上取得重大進展，包括完成 VX-407 用於 ADPKD 的 AGLOW 第二期研究收案；並按計畫在今年底前完成 AMKD 的 AMPLITUDE 第三期研究收案，且預計於 2027 年初公布 AMPLITUDE 期中分析隊列的結果。我們也仍按計畫在今年稍晚公布 DM1 概念驗證研究結果、AMPLIFIED 試驗中 AMKD 擴大族群的結果，以及 VX-828 於囊性纖維化（CF）的初始病患數據。

On the regulatory front, the BLA for Pove in IgAN was accepted in the US with a November 30 PDUFA date. We achieved expanded labeling in record time for CASGEVY in patients ages 2 to 11 in the US. And I'm very pleased to share that as we continue to dose the Phase 1, 2, 3 study of zimislecel in type 1 diabetes, the IND was cleared for the blood type O islet cells in our T1D program, VX-017. We expect initiation of the VX-017 Phase 1, 2 study in the near term.

在法規方面，Pove 用於 IgAN 的 BLA 已在美國獲受理，PDUFA 日期為 11 月 30 日。我們也在美國以創紀錄的速度，讓 CASGEVY 取得 2 至 11 歲病患的擴大適應症標示。此外，我很高興分享：在我們持續為 zimislecel 用於第一型糖尿病的第 1/2/3 期研究進行給藥之際，我們 T1D 計畫 VX-017 的 O 型血胰島細胞 IND 已獲核准放行（cleared）。我們預期將在近期啟動 VX-017 第 1/2 期研究。

Finally, with the announced acquisition of Crinetics Pharmaceuticals, we look forward to multiple benefits of the deal, establishing a fifth pillar in rare endocrine diseases, adding to our innovative R&D pipeline, accelerating revenue growth and enhancing long-term earnings. Tonight, I'll limit my R&D comments to new news in CF, renal and type 1 diabetes and close with some additional remarks regarding the Crinetics acquisition.

最後，隨著宣布收購 Crinetics Pharmaceuticals，我們期待此交易帶來多重效益：在罕見內分泌疾病建立第五大支柱、擴充我們具創新性的研發管線、加速營收成長並提升長期獲利。今晚我將把研發相關評論限於囊性纖維化、腎臟與第一型糖尿病的新進展，並在最後補充一些關於收購 Crinetics 的說明。

Let me start with CF, where we continue to extend our market leadership. Data we presented at ECFS reinforced that ALYFTREK best restores CFTR function amongst the available CFTR modulators. In particular, among children with CF under 12 years of age, the majority across all eligible genotypes achieve a sweat chloride less than 30 millimoles, which is the median among CF carriers.

我先從囊性纖維化（CF）談起，我們持續延伸市場領導地位。我們在 ECFS 發表的數據再次證實，在現有的 CFTR 調節劑中，ALYFTREK 對 CFTR 功能的恢復效果最佳。特別是在 12 歲以下的 CF 兒童中，涵蓋所有符合條件的基因型，多數病患的汗氯可降至低於 30 毫莫耳，這也是 CF 帶因者的中位數水準。

This is remarkable because at these sweat chloride levels, CF carriers do not exhibit manifestations of disease. In addition, we have initiated global regulatory submissions for ALYFTREK in children, ages two to five. Global regulatory submissions for TRIKAFTA in patients ages one to two are also in progress.

這非常令人驚豔，因為在這樣的汗氯水準下，CF 帶因者並不會出現疾病表徵。此外，我們已啟動 ALYFTREK 用於 2 至 5 歲兒童的全球法規送件。TRIKAFTA 用於 1 至 2 歲病患的全球法規送件也正在進行中。

Turning to our next wave in CF and VX-828, our next-generation 3.0 CFTR modulator recently completed dosing in the patient cohort and data are expected in the second half of this year. Behind VX-828, we continue to advance additional correctors in the NextGen 3.0 family and both VX-581 and VX-272 are in healthy volunteer studies. Let me close on CF with this. Our ultimate goal has been consistent for two-plus decades to bring patients to carrier levels of sweat chloride.

接著談我們在 CF 的下一波產品與 VX-828。這款下一代 3.0 CFTR 調節劑近期已完成病患隊列給藥，預計於今年下半年取得數據。在 VX-828 之後，我們持續推進 NextGen 3.0 家族中的其他校正劑（correctors），其中 VX-581 與 VX-272 皆已進入健康受試者研究。關於 CF，我最後想說的是：二十多年來，我們的終極目標始終一致——讓病患的汗氯降至帶因者水準。

Frankly, ALYFTREK's remarkable results, where nearly two-thirds of younger patients achieved sweat chloride levels less than 30 millimole per liter and for patients ages 12 plus more than 75% achieved sweat chloride levels within the carrier range of CFTR function means we are very close to that goal.

坦白說，ALYFTREK 的卓越結果——近三分之二的年幼病患汗氯低於每公升 30 毫莫耳，且 12 歲以上病患中超過 75% 的汗氯達到 CFTR 功能的帶因者範圍——意味著我們已非常接近這個目標。

Given the improvements in sweat chloride, ppFEV1, pulmonary exacerbations, hospitalizations, lung transplant and survival that we have seen in patients in clinical trials and/or the real world, we recognize that the unmet need is far lower today and the bar for any medicine to beat ALYFTREK is very, very high.

鑑於我們在臨床試驗及／或真實世界中所見的汗氯、ppFEV1、肺部急性惡化、住院、肺移植與存活率等方面的改善，我們認知到目前未被滿足的需求已大幅降低，而任何藥物若要超越 ALYFTREK 的門檻都非常、非常高。

Thus, as we develop our next-gen 3.0 and Beyond programs, we will evaluate multiple regimens in Phase 1 in cohorts of patients with CF. However, we will only advance assets into Phase 2 in Beyond that show promise to beat ALYFTREK. In other words, to bring even more patients to sweat chloride levels less than 30 millimoles across all genotypes with once-daily dosing and excellent drug-like properties, including drug-drug interactions. Anything less would not be competitive.

因此，在我們開發下一代 3.0 與 Beyond 計畫時，將在第 1 期於 CF 病患隊列中評估多種治療方案。然而，我們只會把在 Beyond 中展現出有望超越 ALYFTREK 的資產推進至第 2 期。換言之，我們的目標是：以每日一次給藥、並具備優異的藥物特性（包括藥物交互作用）為前提，讓更多不同基因型的病患汗氯降至低於 30 毫莫耳。任何未達此水準者都不具競爭力。

Moving now to our renal franchise, where we have four programs in mid- and late-stage development, povetacicept in IgAN and primary membranous nephropathy, inaxaplin in APOL1-mediated kidney disease and VX-407 in ADPKD, or autosomal dominant polycystic kidney disease. Let me start with the most advanced program and significant milestone. In late May, the FDA accepted our BLA for Pove in IgAN and assigned a PDUFA date of November 30 of this year.

接著談我們的腎臟產品線。目前我們有四個處於中後期開發階段的計畫：povetacicept 用於 IgAN 與原發性膜性腎病（primary membranous nephropathy）、inaxaplin 用於 APOL1 介導的腎臟疾病，以及 VX-407 用於 ADPKD（即常染色體顯性多囊腎病）。我先從最先進的計畫與一項重要里程碑談起。5 月下旬，FDA 受理我們 Pove 用於 IgAN 的 BLA，並指定今年 11 月 30 日為 PDUFA 日期。

As a reminder, the RAINIER Phase 3 interim analysis was a home run, delivering statistically significant and clinically meaningful results across the primary and all secondary endpoints with a favorable safety profile and consistency in the primary endpoint of change from baseline in proteinuria across all groups.

提醒各位，RAINIER 第三期期中分析可說是大獲全勝：在主要終點與所有次要終點上皆達到統計顯著且具臨床意義的結果，安全性概況良好，且在所有族群中，主要終點（蛋白尿相較基線的變化）表現一致。

We are in the final stages of launch readiness. Duncan will provide more details regarding our approach and excitement to go to market with Pove's differentiated profile of potentially best-in-class efficacy, a well-tolerated safety profile and patient-centric administration through small volume once-monthly dosing via an auto-injector at home. We are also advancing Pove internationally. We have completed the regulatory submission for accelerated approval of Pove in IgAN in Saudi Arabia, where Pove has received breakthrough designation.

我們已進入上市準備的最後階段。Duncan 將就我們的策略與期待提供更多細節，說明我們如何以 Pove 具差異化的特性進入市場：具潛在同級最佳的療效、良好耐受的安全性概況，以及以病患為中心的給藥方式——透過自動注射器在家中以小容量每月一次給藥。我們也正在推進 Pove 的國際布局。我們已完成在沙烏地阿拉伯就 Pove 用於 IgAN 申請加速核准的法規送件；在當地，Pove 已獲得突破性療法認定。

Turning to Pove in membranous nephropathy, our OLYMPUS Phase 2, 3 pivotal trial is well underway. The Phase 2 portion is complete and the Phase 3 portion initiated last quarter. I'm pleased to share that the IDMC has completed its review and selected the Phase 3 dose, 80 milligrams subcutaneously every four weeks.

接著談 Pove 在膜性腎病（membranous nephropathy）方面的進展，我們的 OLYMPUS 第 2/3 期關鍵性試驗正在順利推進。第 2 期部分已完成，第 3 期部分已於上季啟動。我很高興分享，IDMC 已完成審查並選定第 3 期劑量：每四週皮下注射 80 毫克。

We hold fast track, orphan drug designation and EMA PRIME designations for Pove in membranous. Stepping briefly outside of renal, on Pove in myasthenia gravis, I'm also pleased to share that the 30-patient Phase 2 proof-of-concept study is on track to complete enrollment by the end of this year. Recall this study evaluates 80 milligrams and 240-milligram doses of Pove versus placebo for 12 weeks.

Pove 用於膜性腎病已取得快速通道、孤兒藥資格與 EMA PRIME 認定。稍微離開腎臟領域，談到 Pove 用於重症肌無力（myasthenia gravis），我也很高興分享，這項 30 名受試者的第 2 期概念驗證研究正按計畫於今年底前完成收案。請記得，該研究評估 Pove 80 毫克與 240 毫克劑量相較安慰劑、為期 12 週的療效。

Turning now to inaxaplin in AMKD. On AMPLITUDE, our pivotal Phase 2, 3 study in AMKD, we completed enrollment of the interim analysis cohort in September of last year and are on track to complete full enrollment by the end of this year. The interim analysis will be conducted following 48 weeks of treatment, and we remain on track to share these IA results in early 2027.

現在轉到 inaxaplin 用於 AMKD。在 AMPLITUDE——我們在 AMKD 的關鍵性第 2/3 期研究中——我們已於去年 9 月完成期中分析隊列的收案，並按計畫於今年底前完成全部收案。期中分析將在治療 48 週後進行，我們仍按計畫於 2027 年初分享這些 IA 結果。

If positive, we would be positioned to file for potential accelerated approval in the US thereafter. AMPLIFIED is our Phase 2b basket study of inaxaplin in AMKD patients with either lower proteinuria or AMKD patients with diabetes, expanded patient populations not studied in AMPLITUDE. The AMPLIFIED study has completed enrollment and dosing, and we expect to share results this fall.

若結果為正向，我們之後將具備在美國申請潛在加速核准的條件。AMPLIFIED 是我們針對 inaxaplin 的第 2b 期籃式研究，納入蛋白尿較低的 AMKD 病患，或合併糖尿病的 AMKD 病患——這些是在 AMPLITUDE 中未研究的擴大族群。AMPLIFIED 研究已完成收案與給藥，我們預期於今年秋季分享結果。

Lastly, in the renal portfolio is VX-407 in ADPKD, or autosomal dominant polycystic kidney disease. Our AGLOW Phase 2 study has completed enrollment. This is a proof-of-concept study with up to 52 weeks of treatment. We are excited about the potential for VX-407 in ADPKD and look forward to sharing more information as dosing continues and the data matures. Let me now touch on type 1 diabetes.

腎臟產品組合最後一項是 VX-407 用於 ADPKD（常染色體顯性多囊腎病）。我們的 AGLOW 第 2 期研究已完成收案。這是一項概念驗證研究，治療期最長可達 52 週。我們對 VX-407 在 ADPKD 的潛力感到振奮，並期待在持續給藥、數據逐步成熟之際分享更多資訊。接下來我簡要談談第一型糖尿病。

We had very constructive meetings with the FDA following our voluntary pause in order to conduct a manufacturing analysis of zimislecel. As we shared on our Q1 call, we have resumed dosing patients in the zimislecel Phase 1, 2 ,3 study.

在我們自願暫停以進行 zimislecel 製造分析後，我們與 FDA 進行了非常具建設性的會議。如同我們在第一季電話會議中所分享的，我們已恢復在 zimislecel 第 1/2/3 期研究中的病患給藥。

The new news today is that the FDA has cleared the IND for VX-017, our Type O or universal donor cell product. VX-017 has a similar target product profile to zimislecel, but is designed for people of all blood types and we expect the VX-017 Phase 1, 2 study to initiate in the near term.

今天的新消息是，FDA 已核准 VX-017 的 IND；VX-017 是我們的 O 型（或通用捐贈者）細胞產品。VX-017 的目標產品特性與 zimislecel 類似，但其設計適用於所有血型人群；我們預期 VX-017 第 1/2 期研究將在近期啟動。

By designing and bringing to market VX-017, another allogeneic, off-the-shelf, glucose responsive insulin producing, fully differentiated islet cell therapy, in this case, for any blood type, we anticipate doubling our market opportunity from about 60,000 to about 120,000 patients.

透過設計並將 VX-017 推向市場——另一項同種異體、現成即用、具葡萄糖反應性的胰島素分泌、完全分化的胰島細胞療法（此處為適用任何血型）——我們預期可將市場機會由約 60,000 名病患擴大至約 120,000 名病患，等同翻倍。

A silver lining to the pause we took in the zimislecel Type A program is that the Type O program time differential versus zimislecel has shortened. Type O is making rapid progress. And thus, we are considering options to further streamline our regulatory strategy and commercialization approach. We expect to provide updated T1D plans, including timelines later this year.

我們在 zimislecel A 型計畫所採取的暫停措施有一個正面效應：O 型計畫相較於 zimislecel 的時間差已縮短。O 型計畫進展迅速。因此，我們正在評估進一步精簡法規策略與商業化方式的選項。我們預期將於今年稍晚提供更新的第一型糖尿病（T1D）計畫（含時程）。

We also continue to progress our serial innovation work focused on improved immunosuppression and hypoimmune programs to make our potentially one-and-done curative therapy available to even more patients with type 1 diabetes.

我們也持續推進一系列創新工作，聚焦於改善免疫抑制與低免疫原性（hypoimmune）計畫，以使我們可能一次治癒（one-and-done）的療法能惠及更多第一型糖尿病病患。

Let me close with a few words on our announced acquisition of Crinetics Pharmaceuticals, which we detailed in a separate call last month. Crinetics is an excellent strategic fit for Vertex with its focus on serious endocrine diseases, high unmet need, validated targets and well-understood causal biology as well as a strong people and culture fit.

最後，我想用幾句話談談我們已宣布收購 Crinetics Pharmaceuticals 一事；我們已在上個月的另一場電話會議中詳細說明。Crinetics 對 Vertex 具有極佳的策略契合度：其聚焦嚴重的內分泌疾病、高度未被滿足的需求、已驗證的標的與充分理解的致病生物學，同時在人員與文化上也高度契合。

We believe the two lead assets, PALSONIFY and Atumelnant, together represent a peak sales opportunity of about $5 billion. Both are small molecules that address serious diseases for patients treated by a concentrated group of specialized endocrinologists. This fits directly within Vertex's proven, efficient, specialty commercial model.

我們相信兩項領先資產 PALSONIFY 與 Atumelnant 合計代表約 50 億美元的峰值銷售機會。兩者皆為小分子藥物，針對嚴重疾病，且病患主要由一群相對集中的專科內分泌科醫師治療。這與 Vertex 已驗證、效率高的專科商業模式完全契合。

We enter this transaction from a position of strength. We view CF as a long-duration franchise with sustained growth. We continue to expect both CASGEVY and JOURNAVX to be multibillion-dollar assets and we anticipate our emerging renal franchise could one day rival CF in revenue. In addition, we have a broad and deep pipeline in earlier stages of development.

我們以強勁的態勢進入這筆交易。我們將 CF 視為具長期延續性的事業體，並可持續成長。我們仍預期 CASGEVY 與 JOURNAVX 皆將成為數十億美元級資產，並預期我們新興的腎臟事業體未來有一天在營收上可與 CF 匹敵。此外，我們在更早期開發階段亦擁有廣泛且深厚的研發管線。

The Crinetics acquisition will add to this innovation pipeline and enhance our revenue growth and long-term earnings profile by adding a fifth commercial pillar in rare endocrine diseases. The transaction is expected to close in the third quarter, and we really look forward to welcoming the talented Crinetics team to Vertex. With that, I'll turn the call over to Duncan for a commercial update.

收購 Crinetics 將為此創新管線增添動能，並透過在罕見內分泌疾病領域新增第五個商業支柱，強化我們的營收成長與長期獲利結構。預期該交易將於第三季完成交割，我們非常期待歡迎才華洋溢的 Crinetics 團隊加入 Vertex。接下來，我將把電話會議交給 Duncan，請他提供商業面更新。

Thanks very much, Reshma. Our commercial story this quarter is one of building momentum across each of our franchises, supported by the appropriate investments to drive growth. We are very excited for the close of the Crinetics acquisition and for Vertex to establish a new pillar in specialty endocrine diseases like acromegaly, CAH and Cushing's syndrome. Crinetics Q2 results were excellent, with strong growth in PALSONIFY revenue and patients treated, but I will hold any further comments until after the deal closes.

非常感謝你，Reshma。本季我們的商業故事，是在各個事業體中持續累積動能，並以適當投資來推動成長。我們非常期待 Crinetics 收購案完成，也期待 Vertex 在肢端肥大症、CAH 與庫欣氏症候群等專科內分泌疾病領域建立新的支柱。Crinetics 第二季表現非常出色，PALSONIFY 的營收與治療病患數皆強勁成長，但在交易完成前我將暫不做進一步評論。

So tonight, let me start with CF. CF continues to perform very well. Global CF revenue grew 11% year-over-year in the second quarter with balanced growth across the US and internationally and continued strength from both ALYFTREK and TRIKAFTA. ALYFTREK performance has been excellent and crossed another significant milestone, exceeding $1 billion in revenue in the first half of 2026. In the US, we continue to see patients initiating ALYFTREK who are new to therapy, returning to therapy and patients switching from TRIKAFTA.

今晚我先從 CF 談起。CF 持續表現非常亮眼。第二季全球 CF 營收年增 11%，美國與國際市場皆呈現均衡成長，且 ALYFTREK 與 TRIKAFTA 兩者皆維持強勁表現。ALYFTREK 的表現非常出色，並達成另一個重要里程碑：在 2026 年上半年營收突破 10 億美元。在美國，我們持續看到開始使用 ALYFTREK 的病患包括新開始治療者、回到治療者，以及由 TRIKAFTA 轉換而來的病患。

The majority of ALYFTREK revenue continues to come from these TRIKAFTA switch patients, which reflects the benefits of ALYFTREK and our success establishing ALYFTREK as the new standard of care. We're pleased with the pace at which physicians and patients are embracing ALYFTREK given its improved sweat chloride profile and once daily dosing. We've seen accelerated uptake of ALYFTREK from the recent approvals in rare mutations as well as patients rolling off our open-label extension studies.

ALYFTREK 的大部分營收仍來自這些由 TRIKAFTA 轉換的病患，這反映了 ALYFTREK 的效益，以及我們成功將 ALYFTREK 建立為新的照護標準。鑑於其改善的汗氯（sweat chloride）表現與每日一次給藥，我們對醫師與病患採用 ALYFTREK 的速度感到滿意。我們也看到 ALYFTREK 的採用加速，動能來自近期在罕見突變上的核准，以及病患從我們的開放標籤延伸研究中結束後轉入常規用藥。

Outside the US, the ALYFTREK European launches remain very strong with no requirement for augmented liver monitoring in the EU, we are seeing rapid uptake by patients in Europe, transitioning from TRIKAFTA or one of our other CFTR modulators.

在美國以外，ALYFTREK 在歐洲的上市推進仍然非常強勁，且在歐盟無需加強肝功能監測；我們看到歐洲患者快速採用，從 TRIKAFTA 或我們其他 CFTR 調節劑轉換至 ALYFTREK。

In fact, in Germany and the UK, more than one in three eligible CF patients are now benefiting from ALYFTREK. Globally, the CF growth drivers for the remainder of 2026 are clear: continued ALYFTREK uptake, the label expansion into rare mutations, younger patients and additional geographies.

事實上，在德國與英國，符合資格的 CF 患者中已有超過三分之一正在受益於 ALYFTREK。放眼全球，2026 年剩餘期間 CF 的成長驅動因素很明確：ALYFTREK 持續滲透、適應症標籤擴展至罕見突變、更年幼患者以及更多地理市場。

Shifting to heme and CASGEVY, where the momentum continues to build. During the second quarter, we delivered $76 million in CASGEVY revenue, reflecting approximately 75% sequential growth versus quarter 1, 2026, and over 150% year-over-year growth. This was in line with our expectations based on our visibility into patient scheduling patterns.

接著談到血紅素疾病領域與 CASGEVY，其動能持續增強。第二季我們實現 CASGEVY 收入 7,600 萬美元，較 2026 年第一季約成長 75%（季增），且較去年同期成長逾 150%。這與我們基於對患者排程模式可見度所做的預期一致。

The strength of the CASGEVY franchise continues to build. New data on CASGEVY at EHA with simultaneous publication in the New England Journal of Medicine demonstrated its transformative potential in pediatric patients as well as durable benefits, reinforcing the importance of early intervention to prevent the complications of sickle cell disease and beta thalassemia in children.

CASGEVY 產品線的強勢仍在持續累積。在 EHA 公布並同步發表於《新英格蘭醫學期刊》的 CASGEVY 新數據，顯示其在兒科患者中的變革性潛力以及持久療效，進一步凸顯及早介入的重要性，以預防兒童鎌狀細胞疾病與 β 地中海貧血的併發症。

Stemming from this compelling data, last month CASGEVY became the first and only gene therapy FDA approved to treat children as young as two years old in both sickle cell disease and beta thalassemia. CASGEVY received supplemental approval in the US in a record 53 days post-filing, and our first pediatric patient has already initiated therapy and conducted cell collection. Outside the US, CASGEVY regulatory submissions in the 5 to 11 age group are now complete in Saudi Arabia and the United Kingdom.

基於這些具說服力的數據，上月 CASGEVY 成為首個且目前唯一獲 FDA 核准、可治療最小至 2 歲兒童之鎌狀細胞疾病與 β 地中海貧血的基因療法。CASGEVY 在美國於遞交申請後僅 53 天即獲補充核准，創下紀錄；我們的首位兒科患者已開始治療流程並完成細胞採集。在美國以外，CASGEVY 針對 5 至 11 歲族群的法規申請目前已在沙烏地阿拉伯與英國完成提交。

On the reimbursement front, we are seeing strong trends in initiations in Germany after reaching a historic reimbursement agreement there as well as continued strong uptake in the UK, Italy and the Middle East following the negotiations of sustainable access agreements. The CASGEVY story continues to be one of an increasingly robust pipeline of patients initiating the treatment journey.

在給付方面，我們在德國達成具里程碑意義的給付協議後，看到啟動治療的強勁趨勢；同時在英國、義大利與中東地區，於完成可持續可近性協議的談判後，滲透也持續強勁。CASGEVY 的故事持續展現為：啟動治療旅程的患者管線愈發強健。

There were more CASGEVY infusions in the first half of 2026 than in all of 2025. Second quarter 2026 was also the third sequential quarter with more than 100 patient initiations, which enhances our visibility to continued growth for the rest of this year and early 2027 as patients continue to move through cell collection, editing and infusion.

2026 年上半年 CASGEVY 的輸注次數已超過 2025 年全年。2026 年第二季亦是連續第三個季度，患者啟動治療人數超過 100 人，這提升了我們對今年剩餘期間及 2027 年初持續成長的可見度，因患者將持續推進細胞採集、編輯與輸注流程。

Quarter-to-quarter variability in CASGEVY revenue will continue and reflects the timing of patient infusions as people choose to receive their infusions when it best suits them. As we look forward, we expect continued CASGEVY momentum with the pipeline of patients at every stage continuing to build. CASGEVY is well positioned to contribute meaningfully to our $500 million non-CF revenue goal this year and to achieve its stand-alone multibillion-dollar potential.

CASGEVY 收入的季度間波動仍將持續，並反映患者輸注時點的差異，因為人們會選擇在最適合自己的時間接受輸注。展望未來，我們預期 CASGEVY 動能將延續，且各階段患者管線將持續擴大。CASGEVY 已具備良好條件，能在今年對我們 5 億美元的非 CF 收入目標做出實質貢獻，並實現其獨立的數十億美元級別潛力。

Turning to JOURNAVX in moderate-to-severe acute pain, where our launch continues to gain traction. In the second quarter, JOURNAVX generated $50 million in revenue, reflecting sequential revenue growth of approximately 70% and sequential prescription growth of approximately 45% versus quarter 1, 2026. Unpacking Q2 performance, revenue was positively impacted by channel build after we've seen a drawdown in quarter one.

接著談到 JOURNAVX 在中度至重度急性疼痛領域的進展，我們的上市推進持續取得進展。第二季 JOURNAVX 產生 5,000 萬美元收入，較 2026 年第一季約成長 70%（季增），處方量較前一季約成長 45%。拆解第二季表現，收入受到通路補庫存的正面影響，因我們在第一季曾看到庫存下滑。

At this stage in an acute product launch, we continue to expect some quarterly volatility in inventory build and drawdown as full-line wholesalers and retail channel buying patterns normalize to reflect formulary adoption, physician awareness and seasonality in elective surgeries.

在急性用藥產品上市的此階段，隨著全線批發商與零售通路的採購模式逐步常態化，以反映處方集採納、醫師認知度以及選擇性手術的季節性，我們仍預期庫存建立與去化將帶來一定的季度波動。

We are building a pain franchise for the long term and are focused on the following four critical markers of success: prescription growth, breadth and depth of prescribers, the addition of JOURNAVX to hospital and IDN pathways and broad payer coverage. These are the building blocks of a sustainable, long-term, multibillion-dollar business.

我們正以長期視角打造疼痛產品線，並聚焦以下四項關鍵成功指標：處方成長、開立醫師的廣度與深度、JOURNAVX 納入醫院與 IDN 的臨床路徑，以及廣泛的支付方覆蓋。這些是建立可持續、長期、數十億美元級別業務的基石。

We are extremely pleased with the prescription growth we continue to build, which is ahead of our forecast for 2026. The breadth and depth of prescriptions across a wide range of settings of care as well as the clinical impact of JOURNAVX continue to be very strong and all bode well for the long-term growth of JOURNAVX in acute pain.

我們對持續累積的處方成長感到非常滿意，且其表現優於我們對 2026 年的預測。在多元照護場景中的處方廣度與深度，以及 JOURNAVX 的臨床影響仍然非常強勁，這些都預示 JOURNAVX 在急性疼痛領域的長期成長前景良好。

The consequence of this rapid prescription growth is that we are seeing greater use of the PSP program than we forecast as securing unrestricted payer access and physician education catches up with prescription growth. Let me break down what I mean by that. At this point, we have a total of 260 million lives covered out of a total possible of approximately 320 million.

這種快速的處方成長所帶來的結果是：在確保支付方無限制可近性與醫師教育追趕處方成長的同時，我們看到 PSP 計畫的使用量高於我們的預期。我來說明我所指的是什麼。目前，在總計約 3.2 億可覆蓋人數中，我們已覆蓋 2.6 億人。

Of the 260 million covered lives, 180 million of them have unrestricted coverage. This means that there are 60 million lives yet to be covered and about 80 million lives who have coverage, but with some form of restriction, making some of them eligible for the PSP program.

在這 2.6 億已覆蓋人數中，有 1.8 億人享有無限制覆蓋。這表示仍有 6,000 萬人尚未被覆蓋，另有約 8,000 萬人雖有覆蓋但存在某種限制，使其中部分人符合 PSP 計畫資格。

These restrictions are usually very minor in nature, such as a 14-day quantity limit or a prior authorization to indication. As we continue to educate physicians and their office staff about the quantity limits and prior authorizations, we expect the PSP to be triggered less frequently and therefore, more revenue to be recognized. Let me now provide you with some more details on prescriptions, prescribers and access before concluding our thinking on the PSP program and gross-to-net.

這些限制通常性質非常輕微，例如 14 天用量上限，或需針對適應症進行事前授權。隨著我們持續教育醫師及其診所人員了解用量上限與事前授權流程，我們預期 PSP 被觸發的頻率將降低，因此可認列的收入將增加。在我們就 PSP 計畫與毛到淨（gross-to-net）做結論前，我先提供更多關於處方、開立者與可近性的細節。

In terms of prescriptions, quarter two, 2026 JOURNAVX prescriptions totaled approximately 535,000 and just over 900,000 for the first half of 2026. The prescriptions continue to be split roughly 50-50 between the hospital and retail channels. In both channels, monthly prescriptions were approximately 50,000 in January and doubled to approximately 100,000 in each channel in June.

就處方而言，2026 年第二季 JOURNAVX 處方總量約為 53.5 萬張，2026 年上半年合計略高於 90 萬張。處方仍大致以醫院通路與零售通路各占約 50% 的比例分布。在兩個通路中，月度處方量於 1 月約為 5 萬張，至 6 月在各通路均倍增至約 10 萬張。

In terms of prescribers, we added approximately 18,000 new HCP prescribers to JOURNAVX in Q2 '26, and are pleased that JOURNAVX is now on 1,400 hospital and 130 IDN pathways in terms of formulary, protocol or order sets.

就開立醫師而言，我們在 2026 年第二季為 JOURNAVX 新增約 18,000 名 HCP 開立者；同時我們也很高興 JOURNAVX 目前已在 1,400 家醫院與 130 個 IDN 的路徑中納入（以處方集、治療方案或醫囑集的形式）。

These are important metrics as we seek to convert practices and continue to embed the use of JOURNAVX among our target physicians. We've also made further progress with respect to access. We recently signed agreements to expand reimbursed access to JOURNAVX with two additional Medicare Part D plans, effective from July 1. With these additions, three of the big four Medicare Part D plans now provide covered access alongside the three large commercial PBMs.

在我們尋求轉化診所並持續將 JOURNAVX 的使用嵌入目標醫師族群之際，這些都是重要指標。在可近性方面我們也取得進一步進展。我們近期與另外兩個 Medicare Part D 計畫簽署協議，以擴大 JOURNAVX 的可給付可近性，自 7 月 1 日起生效。加上這些新增項目後，四大 Medicare Part D 計畫中的三個如今已提供覆蓋可近性，並與三家大型商業 PBM 並列。

As mentioned, this brings the total covered lives for JOURNAVX to approximately 260 million out of a total possible of 320 million and within that, approximately 180 million lives with unrestricted access. Our goal continues to be to ensure the prescribing experience for physicians and patients is as seamless as possible in a market where the delivery of the medicine is highly time-sensitive.

如前所述，這使 JOURNAVX 的覆蓋人數總計達到約 2.6 億人（在約 3.2 億可覆蓋人數中），其中約 1.8 億人享有無限制可近性。我們的目標仍是確保在藥品交付高度講求時效的市場中，醫師與患者的開立與取得體驗盡可能順暢無縫。

We will continue to work to educate physicians to navigate the minimal quantity limits and prior authorizations that exist and secure ever broader coverage. In the meantime, we will maintain the PSP program so that patients who are prescribed JOURNAVX can get it. We continue to see this as a strategic choice as we seek to convert physician practices away from decades of reliance on opioids to ongoing and sustained use of JOURNAVX for many years to come.

我們將持續努力教育醫師，以便其能因應現有的最低限度用量上限與事前授權，並爭取更廣泛的覆蓋。同時，我們將維持 PSP 計畫，讓被開立 JOURNAVX 的患者能取得藥物。我們仍將此視為一項策略性選擇，因為我們希望將醫師診療模式從數十年對鴉片類藥物的依賴轉向，並在未來多年持續且穩定地使用 JOURNAVX。

As a result, we continue to expect gross to net to normalize in line with other branded oral medicines, but now in the first half of 2027. To conclude on pain, we also continue to be on track to exceed our goal of more than tripling the 550,000 prescriptions and more than tripling revenue from 2025 into 2026 as well as delivering more than $500 million in revenue from CASGEVY and JOURNAVX combined in 2026.

因此，我們仍預期毛額到淨額（gross to net）將與其他品牌口服藥物一致地回歸常態，但時間點現改為在2027年上半年。最後就疼痛領域作結，我們也仍按計畫推進，預期將在2025年至2026年間把55萬張處方量提高到超過三倍，並將營收提高到超過三倍，同時在2026年由CASGEVY與JOURNAVX合計實現超過5億美元的營收。

Let me conclude with an update on our commercial readiness in renal and specifically Pove in IgAN. With the FDA's acceptance of our BLA and the November 30 PDUFA date, we are in the final stages of commercial launch preparation. We're investing in our renal franchise and the nephrology community for the long term, given our innovative pipeline of multiple potentially transformative kidney disease medications that address the underlying causes of serious renal conditions.

最後我以腎臟領域的商業化準備情況作結，特別是Pove在IgAN上的進展。隨著FDA受理我們的BLA以及11月30日的PDUFA日期，我們已進入商業上市準備的最後階段。鑑於我們具創新性的產品線中有多項可能帶來變革的腎臟疾病藥物、可針對嚴重腎臟疾病的根本原因，我們正以長期視角投資於腎臟事業群與腎臟科社群。

Our goal is for Pove to be physicians first choice among disease-modifying therapies for IgAN and we know from our market research and from nephrologist feedback that physicians are looking for treatments that meaningfully and rapidly reduce proteinuria, have a favorable tolerability profile and offer a seamless treatment experience from access through patient support to convenient dosing.

我們的目標是讓Pove成為醫師在IgAN疾病修飾治療（disease-modifying therapies）中的第一選擇；我們也從市場研究與腎臟科醫師回饋得知，醫師正在尋找能夠顯著且快速降低蛋白尿、具良好耐受性，並且從取得用藥到病患支持再到便利給藥皆能提供無縫治療體驗的療法。

We believe Pove has the winning trifecta of efficacy, tolerability and ease of use for patients and physicians alike. With dual BAFF APRIL inhibition, Pove has clear best-in-class potential and delivers effectively on all the needs we've heard from the community in research and advisory boards making it the ideal first choice after baseline therapy with ACEi, ARBs and SGLT2s.

我們相信Pove同時具備療效、耐受性與易用性這三大優勢，對病患與醫師皆然。透過雙重BAFF/APRIL抑制，Pove具備明確的同類最佳（best-in-class）潛力，並能有效滿足我們在研究與諮詢委員會中從社群所聽到的各項需求，使其成為在以ACEi、ARB與SGLT2為基礎治療之後的理想第一選擇。

We have completed the hiring of our renal field force of whom about 90% have nephrology experience and was built with the breadth of our renal pipeline in mind. We anticipate that we will have the largest field force among the novel APRIL or APRIL BAFF therapies for IgAN. Our payer conversations are also proceeding well.

我們已完成腎臟領域外勤團隊的招募，其中約90%具腎臟科相關經驗，且建置時已將我們腎臟產品線的廣度納入考量。我們預期在針對IgAN的新型APRIL或APRIL/BAFF療法中，我們將擁有最大的外勤團隊。我們與付款方（payer）的對話進展也相當順利。

In the US, approximately 70% of patients with IgAN have commercial coverage. From our engagements with payers, their awareness of IgAN and the new BAFF APRIL inhibitors is high. Payers understand the unmet need, have a good understanding of the KDIGO guidelines and how the new therapies fit into treatment pathways.

在美國，約70%的IgAN病患擁有商業保險。從我們與付款方的互動來看，他們對IgAN以及新的BAFF/APRIL抑制劑的認知度很高。付款方理解未被滿足的醫療需求，並對KDIGO指引以及新療法如何納入治療路徑有良好理解。

Payers are also very aware of the strength of the Pove Phase 3 interim analysis data and Pove's November 30 PDUFA date. Our market access teams continue to actively engage with payers to prepare for the upcoming launch of Pove. Additionally, we will provide robust patient support programs drawing on our decades of experience in CF.

付款方也非常清楚Pove第三期（Phase 3）期中分析數據的強度，以及Pove的11月30日PDUFA日期。我們的市場准入團隊持續積極與付款方互動，為Pove即將上市做準備。此外，我們也將憑藉在囊性纖維化（CF）領域數十年的經驗，提供完善的病患支持方案。

Pove in IgAN is the first component of our emerging renal franchise, and we're excited to bring it to nephrologists and to their patients. We believe Pove's trifecta of efficacy, tolerability and ease of use delivers exactly what nephrologists are seeking.

Pove在IgAN上的布局是我們新興腎臟事業群的第一個組成部分，我們很期待將其帶給腎臟科醫師及其病患。我們相信Pove在療效、耐受性與易用性上的三大優勢，正好提供腎臟科醫師所尋求的一切。

And just as we've done for over a decade in CF, Pove's success will be driven by a field force delivering a high-science sell, fueled by a potentially best-in-class product, broad reimbursement and robust high-quality patient programs. We are very excited to commercialize Pove in IgAN and begin building a multibillion-dollar renal franchise at Vertex. I'll now turn the call over to Charlie to review the financials.

而且正如我們在CF領域十多年來所做的一樣，Pove的成功將由外勤團隊以高科學含量的銷售方式所驅動，並以可能同類最佳的產品、廣泛的給付覆蓋，以及強而有力且高品質的病患方案作為支撐。我們非常期待將Pove在IgAN上商業化，並在Vertex開始打造一個數十億美元規模的腎臟事業群。接下來我把電話交給Charlie，請他回顧財務表現。

Thanks, Duncan. As Reshma noted, Vertex's second quarter results demonstrate our consistent strong performance and attractive growth profile. Second quarter 2026 total revenue of $3.3 billion increased 12% year-over-year with growth balanced between the US and international markets. As expected, Q2 2026 revenue growth reflects an approximate 170 basis point benefit from foreign exchange rates.

謝謝你，Duncan。如Reshma所提，Vertex第二季的結果展現了我們一貫的強勁表現與具吸引力的成長輪廓。2026年第二季總營收為33億美元，年增12%，成長在美國與國際市場之間相對均衡。如預期，2026年第二季的營收成長反映了外匯匯率帶來約170個基點的正面效益。

Q2 '26, Global CF revenue grew 11% year-over-year, and new disease areas also contributed with CASGEVY delivering $76 million compared to $30 million in Q2 of 2025 and JOURNAVX revenue of $50 million compared to $12 million in Q2 of 2025.

2026年第二季，全球CF營收年增11%；新疾病領域亦有貢獻，其中CASGEVY貢獻7,600萬美元（相較於2025年第二季的3,000萬美元），JOURNAVX營收為5,000萬美元（相較於2025年第二季的1,200萬美元）。

As a reminder, Q2 '25 results also included $21 million of collaboration revenue. Q2 '26, US CF revenue grew 9% year-over-year, led by strong volume growth from ALYFTREK uptake, continued performance from TRIKAFTA and higher realized net price. Outside the US, CF revenue grew 12% year-over-year, driven by strong ALYFTREK launches, timing of orders in certain geographies as well as the benefit from FX.

提醒一下，2025年第二季的結果亦包含2,100萬美元的合作收入。2026年第二季，美國CF營收年增9%，主要由ALYFTREK滲透率提升帶來的強勁量增、TRIKAFTA的持續表現，以及更高的已實現淨價格所帶動。在美國以外，CF營收年增12%，受惠於ALYFTREK強勁上市推進、部分地區訂單時點因素，以及外匯帶來的效益。

Note that global CF revenue growth for the first half of 2026 was 8%, including the benefit of prior year US price increases and foreign exchange. We expect both of these factors to contribute less to growth in the second half of the year. Our second quarter 2026 gross margin was 85.6%, an expected sequential step-down from Q1 of '26.

請注意，2026年上半年全球CF營收成長為8%，其中包含前一年美國提價與外匯的效益。我們預期這兩項因素在下半年對成長的貢獻將降低。我們2026年第二季毛利率為85.6%，較2026年第一季出現符合預期的季減。

This step down reflects the impact of product mix as well as manufacturing network investments in various products. As our new products, particularly CASGEVY, increase in revenue contribution with higher cost of goods sold than our small-molecule CF products, we continue to expect full year gross margin of just under 86%, roughly in line with this quarter's result. The impact from product mix and manufacturing network investment costs will be more pronounced in the second half than they were in the first half of 2026.

此一季減反映了產品組合的影響，以及我們在多項產品上的製造網絡投資。隨著新產品（尤其是CASGEVY）在營收中的占比提高，而其銷貨成本高於我們的小分子CF產品，我們仍預期全年毛利率略低於86%，大致與本季結果一致。產品組合與製造網絡投資成本的影響在2026年下半年將比上半年更為明顯。

Turning to operating expenses. We continue to invest appropriately given the attractive opportunity presented by our ongoing and near-term launches as well as our attractive mid- and late-stage pipeline. Second quarter non-GAAP R&D expense of $889 million increased 1% year-over-year with steady progress across multiple Phase 3 studies and the earlier-stage pipeline. Non-GAAP SG&A expense of $520 million increased 45% year-over-year, driven primarily by commercial investment split roughly evenly between pain and renal.

接著談營業費用。鑑於我們正在進行與近期即將到來的上市所帶來的吸引人機會，以及我們具吸引力的中後期產品線，我們持續進行適當投資。第二季非GAAP研發費用為8.89億美元，年增1%，多項第三期研究與早期產品線均穩步推進。非GAAP銷售、一般及行政（SG&A）費用為5.20億美元，年增45%，主要由商業化投資所帶動，且約平均分配於疼痛與腎臟兩大領域。

We also recorded $21 million in acquired IPR&D expense in the quarter. Note that while R&D continues to account for nearly two-thirds of our operating expenses, the modest growth rate reflects that we are in a period where we can redeploy dollars from programs that wind down to fund programs that are new or scaling up. In contrast, much of our commercial spending is to build new businesses and thus is incremental, as reflected in the higher year-over-year growth rates when compared to R&D spending.

本季我們亦認列2,100萬美元的取得之在研研發（acquired IPR&D）費用。請注意，雖然研發仍占我們營業費用近三分之二，但其溫和的成長率反映我們正處於可將資金自逐步結束的專案重新配置，以資助新啟動或擴大規模專案的階段。相較之下，我們多數商業支出是為建立新事業而新增的投入，因此屬增量支出，這也反映在相較研發支出更高的年增率上。

Our second quarter 2026 non-GAAP effective tax rate was 21.1%, including some one-time expenses. Year-to-date, our non-GAAP effective tax rate was 20.4%, within our guidance range of 19.5% to 20.5%. Our second quarter 2026 non-GAAP earnings per share of $4.73 represents 5% growth versus prior year, reflecting strong revenue growth as well as investments in our pipeline and commercial capabilities.

我們2026年第二季非GAAP有效稅率為21.1%，其中包含部分一次性費用。年初至今，我們的非GAAP有效稅率為20.4%，落在我們19.5%至20.5%的指引區間內。我們2026年第二季非GAAP每股盈餘為4.73美元，較去年成長5%，反映強勁的營收成長以及我們對產品線與商業能力的投資。

Turning to the balance sheet. We ended the quarter with approximately $13.6 billion in cash and investments. During the second quarter, we deployed approximately $455 million to repurchase roughly 1 million shares.

接著看資產負債表。本季結束時，我們持有約136億美元的現金與投資。在第二季期間，我們動用約4.55億美元回購約100萬股股份。

This activity reflects our ongoing commitment to returning value to shareholders while maintaining the flexibility to act on strategic growth opportunities. Of course, our top priority for capital deployment remains investing in innovation as evidenced by our recent announcement to acquire Crinetics for approximately $8.8 billion net of cash acquired.

此一活動反映我們在維持因應策略性成長機會之彈性的同時，持續致力於回饋股東價值。當然，我們資本配置的首要優先事項仍是投資創新，正如我們近期宣布以約88億美元（扣除取得之現金後）收購Crinetics所示。

Now turning to guidance. Given our strong first half performance and the momentum across the business, we are raising our full year 2026 total revenue guidance to a range of $13.1 billion to $13.2 billion, 2026 revenue guidance reflects continued strong performance from the CF franchise, including ALYFTREK and TRIKAFTA as well as growing year-over-year contributions from CASGEVY and JOURNAVX.

現在轉到財測指引。鑑於我們上半年強勁的表現以及全業務的動能，我們將2026全年總營收指引上調至131億至132億美元區間。2026年營收指引反映CF事業群（franchise）持續強勁的表現，包括ALYFTREK與TRIKAFTA，以及CASGEVY與JOURNAVX逐年成長的貢獻。

We continue to expect revenue of $500 million or greater from our non-CF products, and our outlook also continues to include an expected 150 basis point benefit from foreign exchange net of our hedging program.

我們仍預期非CF產品營收將達到或高於5億美元；此外，我們的展望仍包含外匯因素在扣除避險計畫影響後，預計帶來150個基點的淨利多。

As I previously mentioned, we continue to expect full year gross margin of just under 86%. On operating expenses, we are reiterating our combined non-GAAP operating expense guidance of $5.65 billion to $5.75 billion, though we now expect to be at the high end of that range.

如我先前提到的，我們仍預期全年毛利率略低於86%。在營業費用方面，我們重申合併後的非GAAP營業費用指引為56.5億至57.5億美元，但我們目前預期將落在該區間的高端。

This reflects continued investment in our late-stage clinical pipeline and the commercial infrastructure and activities that support our new launches and revenue diversification. We continue to expect our non-GAAP effective tax rate to be in the range of 19.5% to 20.5% for the full year 2026.

這反映我們持續投資於後期臨床研發管線，以及支援新產品上市與營收多元化的商業化基礎建設與相關活動。我們仍預期2026全年非GAAP有效稅率將落在19.5%至20.5%區間。

I would note that today's guidance does not yet reflect the pending Crinetics acquisition, which is expected to close in the third quarter. Given the anticipated timing, we expect the impact to 2026 revenue and non-GAAP operating expenses to be relatively modest, and we will provide updated guidance for 2026 around the time of closing. As a reminder, we expect to fund the transaction through a combination of cash on hand and proceeds from a $4.5 billion term loan, and we expect the transaction to become accretive to non-GAAP operating income in 2029.

我想指出，今日的指引尚未反映仍在進行中的Crinetics收購案，該交易預計於第三季完成交割。考量預期時程，我們預期其對2026年營收與非GAAP營業費用的影響相對有限，並將在交割前後提供2026年的更新指引。提醒一下，我們預期將以手上現金與45億美元定期貸款（term loan）所得款項的組合來為該交易提供資金，並預期該交易將於2029年起對非GAAP營業利益具增益（accretive）。

In summary, Vertex delivered strong second quarter results. Our commercial launches and diversification are gaining momentum, and we continue to invest with discipline in both innovation and commercialization. Overall, our financial performance and outlook remain compelling, with expanding CF leadership, heme and pain scaling, renal on the doorstep of launch and the addition of a fifth pillar in specialty endocrine through the pending Crinetics acquisition, Vertex is exceptionally well positioned for continued growth.

總結來說，Vertex交出強勁的第二季成果。我們的商業化上市與多元化策略正加速推進，我們也持續以嚴謹紀律投入創新與商業化。整體而言，我們的財務表現與展望仍具吸引力：CF領導地位持續擴大，血液疾病（heme）與疼痛業務規模化成長，腎臟領域已臨近上市門檻；再加上透過待完成的Crinetics收購案，在專科內分泌領域新增第五大支柱，Vertex已具備極佳條件以延續成長。

Our high success rate in R&D and our disciplined specialty commercial model allow us to maintain industry-leading margins even as we step up investments to support our launches and pipeline. With this unique profile, we are well positioned to continue expanding our impact for patients, investors and all stakeholders. We look forward to updating you on our continued progress across multiple disease areas with key upcoming milestones detailed on slide 19.

我們在研發上的高成功率，以及具紀律的專科商業化模式，使我們即便加大投資以支援產品上市與研發管線，仍能維持業界領先的利潤率。憑藉這一獨特定位，我們已做好準備，持續擴大對病患、投資人及所有利害關係人的影響力。我們期待在第19頁投影片所列的多項即將到來的重要里程碑上，向各位更新我們在多個疾病領域的持續進展。

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

接下來我請Susie開始問答環節。

(Operator Instructions)

(接線員指示)

Salveen Richter, Goldman Sachs.

Salveen Richter，高盛。

Two for me. One is you announced that the Phase 2, 3 OLYMPUS study for Pove in pMN is going to move to Phase 3 with an 80-milligram dose every four weeks. Can you frame what signal this was based on and whether you or the DSMB or what you or the DSMB saw on the Phase 2b portion to move forward?

我有兩個問題。第一個是，你們宣布針對pMN中Pove的第2/3期OLYMPUS研究將以每四週一次80毫克劑量推進至第3期。能否說明這是基於什麼訊號？以及你們或DSMB（資料安全監測委員會）在第2b期部分看到了什麼，才決定繼續往前？

And then on the pain front, it was really nice to see the progress here. Maybe help us understand where the bottlenecks lie now or what needs to be worked on with regard to formulary as well as the payer dynamics as you look at co-pay, et cetera.

第二個關於疼痛領域，很高興看到這裡的進展。也請協助我們理解，目前瓶頸在哪裡，或在處方集（formulary）以及支付方動態（payer dynamics）方面，像是自付額（co-pay）等，還有哪些需要努力的地方？

Sure thing, Salveen. Let me kick us off with the first question, which is about Pove in membranous. The Phase 2 is complete, the Phase 3 was already initiated, you might recall, a couple of months ago as we designed it as a seamless Phase 2, 3. The DSMB was asked to base their decision, and it was their decision because we do not have access to the unblinded data to look at on efficacy PLA2R, which is the biomarker equivalent in membranous as Gd-IgA1 is to IgAN.

當然可以，Salveen。我先回答第一個問題，也就是膜性腎病（membranous）中Pove的部分。第2期已完成，而第3期其實你可能記得，我們在幾個月前就已啟動，因為我們將其設計為無縫銜接的第2/3期。DSMB被要求基於其判斷做出決定，而且那是他們的決定，因為我們無法取得未揭盲（unblinded）數據來查看療效端的PLA2R；在膜性腎病中，PLA2R相當於IgAN中的Gd-IgA1，是對應的生物標記（biomarker）。

Of course, they had full access to the safety results as they made their decision. I suppose in many ways, it's not surprising that they picked the 80-milligram dose given the RUBY-3 results, where you could see that the 80 milligrams had a very nice reduction in PLA2R, but that's how the decision was made.

當然，他們在做出決定時可完整取得安全性結果。某種程度上，他們選擇80毫克劑量並不令人意外，因為從RUBY-3結果可看到80毫克能相當明顯地降低PLA2R；決策就是如此形成的。

Study is well on its Phase 3 portion, and we look forward to getting that study enrolled and completed. Duncan, I'm going to turn it over to you for a little commentary on JOURNAVX scripts and what more we're working on.

該研究的第3期部分進展順利，我們期待完成收案並完成研究。Duncan，我把問題交給你，請你補充一下JOURNAVX處方量（scripts）以及我們還在推進哪些工作。

Salveen, so as you know, our goal with JOURNAVX is to fundamentally transform how pain is treated and to move physician practices away from decades of reliance on opioids. In terms of our progress, we're very pleased with the prescription numbers that we're seeing. We are also very pleased with the increased number of hospitals that have adopted JOURNAVX, now 1,400 or so with 130 IDNs, having it on formularies and we have also now secured two additional Medicare Part D plans to cover JOURNAVX starting from July 1.

Salveen，如你所知，我們對JOURNAVX的目標是從根本上改變疼痛治療方式，讓醫師的臨床實務擺脫數十年對鴉片類藥物（opioids）的依賴。就進展而言，我們對目前看到的處方數據非常滿意。我們也很高興看到採用JOURNAVX的醫院數量增加，目前約1,400家、涵蓋130個整合式醫療體系（IDNs），已將其納入處方集（formularies）；此外，我們也新增取得兩個Medicare Part D計畫的給付，自7月1日起開始涵蓋JOURNAVX。

So overall, our progress is very well and going very well. And I would add that those prescriptions are coming from a broad range of physician types and being used in a broad range of pain types consistent with our label. In terms of the payer side and access, we're very pleased with the coverage that we've secured to date, 200 -- 260 million lives, and that's ahead of those two Medicare Part D plans coming in.

因此整體而言，我們的進展非常好，而且持續向前。我也補充，這些處方來自多種類型的醫師，並在符合我們適應症標籤（label）的多種疼痛類型中使用。在支付方與可近性（access）方面，我們對目前已取得的給付覆蓋非常滿意，涵蓋2億至2.6億人次（lives），而這還不包含上述兩個即將加入的Medicare Part D計畫。

And I would say we have obviously more work to do to secure the final elements of access for JOURNAVX. And we also have to make sure that those patients whose physicians might have, say, a quantity limit are able to navigate that in order to ensure the patient can secure access. In the meantime, we have the PSP program in place and anticipate that we'll continue to see prescriptions transition to increasing growth in revenue in the second half of 2026.

我會說，我們顯然還有更多工作要做，以完成JOURNAVX可近性的最後幾個環節。我們也必須確保，若某些病患的醫師遇到例如用量上限（quantity limit）之類的限制，病患能夠順利因應，以確保取得用藥。同時，我們已建立PSP計畫，並預期在2026年下半年，處方量將持續轉化為營收的加速成長。

And indeed, as we've communicated before that our gross to net will ultimately normalize at the same level as our oral branded medicines in the pharmaceutical arena. So we're very happy with the progress. We have a little bit more work to do, but we are very happy with where we're at right now in terms of physician adoption, payer coverage and hospital usage.

而且，正如我們先前溝通過的，我們的總額到淨額（gross to net）最終將正常化至與製藥領域其他口服品牌藥相同的水準。因此我們對進展非常滿意。我們還有一點工作要做，但就醫師採用、支付方覆蓋與醫院使用而言，我們對目前的狀況非常滿意。

Geoffrey Meacham, Citibank.

Geoffrey Meacham，花旗銀行。

Have two quick ones. The first one is CF on 828 or the other assets in Phase 1, what are some of the clinical attributes you're looking for? I wasn't sure if you're looking for perhaps a not only better treatment effect or if there is a potential to not need liver monitoring, for example, in future combos.

我有兩個簡短問題。第一個是關於CF的828或其他處於第1期的資產，你們在臨床上主要在尋找哪些特性？我不確定你們是否在尋求不只是更好的治療效果，或例如在未來的聯合療法中有可能不需要肝功能監測等。

Second question on JOURNAVX. You guys have had substantial discussions with payers, hospital systems, physicians on acute pain. But in these conversations, have you gotten any perspectives or context on DPN like what the clinical profile needs to show as we look to the data end of the year, beginning of next year, what the access and reimbursement could look like in this setting?

第二個問題關於JOURNAVX。你們已與支付方、醫院體系、以及醫師就急性疼痛進行了大量討論。但在這些對話中，你們是否有得到任何對DPN的觀點或背景脈絡，例如當我們看向今年底、明年初的數據時，臨床特徵需要呈現什麼樣的表現，以及在此情境下可近性與給付（reimbursement）可能會是什麼樣子？

Sure thing, Geoff. Let me take the second question first. On JOURNAVX, we have been hyper-focused on JOURNAVX in acute pain to make sure that we get all of those reimbursement contracts done and get access. So I think it would be just very fair to say, we've spent all of our time hyper focused on acute pain. We'll have more to say on where we are with DPN, the data, what payers are looking for, what doctors are looking for, et cetera, in the coming months. But for here and now, it's acute pain.

當然可以，Geoff。我先回答第二個問題。關於 JOURNAVX，我們一直高度聚焦於 JOURNAVX 在急性疼痛領域，確保把所有那些給付／報銷合約都完成並取得可近性。所以我覺得很公平地說，我們把所有時間都高度聚焦在急性疼痛上。至於我們在 DPN 的進展、數據、付款方在看什麼、醫師在看什麼等等，我們會在接下來幾個月有更多可以分享的內容。但就目前而言，重點是急性疼痛。

On VX-828 and the next-gen molecule, so just to give you all of the numbers, VX-828 is the first of the next next-gen. The second and third are 581, VX-581 and VX-272. We are looking for potential improvement in efficacy, i.e., more people who can get down to less than 30 millimoles. And of course, we're looking for safety as well. So the monitoring will depend on what the results in the clinical trial are. So sure, there's opportunity for monitoring to be different with this VX-828 program.

關於 VX-828 與下一代分子，為了把數字都提供給各位，VX-828 是下一代中的第一個。第二與第三個是 581，也就是 VX-581，以及 VX-272。我們在尋求療效上可能的提升，也就是讓更多人能降到低於 30 毫摩爾。當然，我們也同樣在看安全性。因此，監測方式將取決於臨床試驗結果。所以沒錯，VX-828 計畫在監測上確實有機會與以往不同。

It just depends on what the actual results are through the clinical trial program. Last thing to say, once daily dosing, really good-looking DDIs as well as other drug-like properties remain really important as I mentioned in my prepared remarks.

這完全取決於臨床試驗計畫中實際得到的結果。最後再補充一點：如我在事先準備的發言中提到的，每日一次給藥、看起來非常不錯的藥物－藥物交互作用（DDI），以及其他類藥性質，仍然非常重要。

Jessica Fye, JP Morgan.

Jessica Fye，JP Morgan。

Maybe for Reshma. I'm curious if you expect to see material differentiation on eGFR across the new IgAN products like Pove and its competitors? And if so, over what time horizon do you think any differentiation on that endpoint would become apparent?

也許這題給 Reshma。我想了解的是，對於像 Pove 以及其競品等新的 IgAN 產品，你是否預期在 eGFR 上會出現實質性的差異化？如果會的話，你認為在多長的時間範圍內，這個終點的差異化會變得明顯？

Sure thing, Jess. As we've discussed before, in IgAN in particular, but you could say this for homogeneous proteinuric kidney diseases in general. Good reductions in proteinuria should, based on everything we know, result in stabilization of GFR. I expect that to be the case with APRIL BAFF inhibitors as well. I think so that your question is asking a very important second point.

當然可以，Jess。如我們先前討論過的，特別是在 IgAN，但其實對一般同質性的蛋白尿型腎臟疾病也適用。根據我們所知的一切，蛋白尿若能良好下降，應該會帶來 GFR 的穩定。我也預期 APRIL/BAFF 抑制劑會是如此。我想你的問題其實在問第二個非常重要的點。

And to me, the most important point. What is the differentiation we can expect between various molecules if you have more reduction in proteinuria or hematuria or in the case of IgA nephropathy, Gd-IgA1, these inciting antibodies.

而對我而言，這也是最重要的一點。如果某些分子能帶來更大的蛋白尿或血尿下降，或在 IgA 腎病的情境下，能降低 Gd-IgA1 這些致病誘發抗體，那麼我們可以期待不同分子之間會有什麼樣的差異化？

And I think for that, the answer is it's really about time to ESRD. That's to say time to dialysis, transplantation or death. And I do expect that the medicine that has the stronger reductions in proteinuria, the medicine that gets more patients to less than 0.5 or 0.3, better improvements in hematuria and Gd-IgA1 are more likely to have an improved profile when it comes to that ultimate endpoint.

我認為答案其實在於到達 ESRD 的時間。也就是到需要透析、移植或死亡的時間。我確實預期：在蛋白尿下降幅度更強、能讓更多患者降到低於 0.5 或 0.3、在血尿與 Gd-IgA1 上改善更好的藥物，在那個最終終點上更可能呈現更佳的表現。

Proteinuria, one-year GFR, two-year GFR, these are all endpoints on the way to the ultimate endpoint. And I think that's where you'll see the real differentiation.

蛋白尿、一年 GFR、兩年 GFR，這些都是通往最終終點過程中的各個終點。而我認為真正的差異化會在那裡顯現。

Cory Kasimov, Evercore ISI.

Cory Kasimov，Evercore ISI。

Wanted to ask about inaxaplin in the AMPLITUDE study? And what kind of data would be necessary in that interim analysis to file for accelerated approval? Basically, like what constitutes the win with this first data look.

我想問關於 AMPLITUDE 研究中的 inaxaplin？以及在那次期中分析中，需要什麼樣的數據才能申請加速核准？基本上，第一次看數據時，什麼情況算是「勝利」？

Sure thing. Cory, I think you're asking about AMPLITUDE. So the core study that's now in Phase 3 in patients with two APOL1 alleles, moderate-to-heavy proteinuria and depressed GFR. We were really pleased and remain very pleased that the agency has provided, and we have an agreement with the agency for a potential accelerated approval based on the primary endpoint at the time of the IA, which is one-year GFR.

當然可以。Cory，我想你問的是 AMPLITUDE。這是一項目前在第 3 期的核心研究，納入具有兩個 APOL1 等位基因、蛋白尿中度至重度且 GFR 降低的患者。我們非常高興，而且至今仍然非常高興，主管機關已提供意見，且我們與主管機關就一項潛在的加速核准達成一致：可在期中分析（IA）時，以主要終點——一年 GFR——作為基礎。

So that's what our agreement is based on. Obviously, we're also going to look at the proteinuria, but the agreement with the agency for the potential to file for accelerated approval based on the interim analysis is one-year GFR.

所以我們的共識是建立在這個基礎上。當然，我們也會看蛋白尿，但與主管機關就「可基於期中分析提出加速核准申請」所達成的共識，是以一年 GFR 為準。

Brian Abrahams, RBC Capital Markets.

Brian Abrahams，RBC Capital Markets。

Congrats on the quarter. On pain, we've seen some data published recently from another NaV1.8. And I'm just curious how you see the acute pain dynamics playing out with additional entrants into the market potentially? And then secondarily, just on zimi. Just wondering if you could talk about the potential impact to launch timing if you do end up syncing the filing with VX-017.

恭喜本季表現。在疼痛方面，我們最近看到另一個 NaV1.8 的一些已發表數據。我想了解，若未來有更多競爭者可能進入市場，你怎麼看急性疼痛的競爭態勢會如何發展？其次，關於 zimi。如果你們最後決定把申報與 VX-017 同步，你能否談談對上市時程可能造成的影響？

Yes. Thanks for the kind words, Brian. Maybe I'll do the pain one first and then come on to type 1 diabetes. I did see the publication. And maybe, Brian, what I'd say is that ever since Vertex published VX-150, which you'll remember was the molecule circa 2017 or so. We saw a spike in others following our footsteps and pursuing NaV1.8 as a target. And what I'll say is that we decided not to advance 150 -- VX-150 because we didn't think it had, as I described at the time, the perfect drug-like molecule, properties that we were looking for and we bypassed 150 in favor of what is now suzetrigine or VX-548.

好的。謝謝你的好話，Brian。我先回答疼痛的部分，接著再談第一型糖尿病。我確實看到了那篇發表。Brian，我想說的是，自從 Vertex 發表 VX-150（你會記得那大約是 2017 年左右的分子）之後，我們看到其他公司跟隨我們的腳步，開始把 NaV1.8 作為標的。而我要說的是，我們當時決定不推進 150——VX-150，因為我們認為它不具備我當時所描述的、我們所尋求的那種「完美的類藥分子」特性，因此我們跳過 150，轉而推進現在的 suzetrigine 或 VX-548。

So we know the space very well. We know the molecule well, and we know that every time we publish a patent, there is a slew of followers. Maybe if you say, well, what's the takeaway from that, I think that there is a high appetite in the biopharma industry to make nonopioids.

所以我們非常了解這個領域。我們很了解這個分子，也知道每次我們發表一項專利，就會有一大批追隨者。如果要說從中得到什麼結論，我認為生物製藥產業對於開發非鴉片類止痛藥的需求非常高。

There is high unmet need for non-opioid effective pain medicines that have not only the right efficacy, but the right safety tolerability, drug-like properties profile. And I really like where we are well on the market with JOURNAVX, and I'm very much looking forward to the possibility of NaV1.7, NaV1.8 combination. And I've never felt better in Vertex history for the fact that may come to pass for us to be able to bring that to the clinic.

市場對於非鴉片類、有效的止痛藥有很高的未被滿足需求；而且不只是要有正確的療效，還要有正確的安全性與耐受性，以及類藥性質的整體特徵。我非常喜歡我們目前在市場上推進 JOURNAVX 的位置，也非常期待 NaV1.7 與 NaV1.8 聯合用藥的可能性。而在 Vertex 的歷史上，我從未像現在這樣有信心，這件事可能會實現，讓我們能把它帶進臨床。

Switching then to the type 1 diabetes program. So let me just say what I said in my prepared remarks. I may have gotten a little quick there. The zimislecel program is in Phase 1, 2, 3, back up in dosing. And because it's a type A program, it serves about 60,000 people in the US and Europe. The 017 program because it is Type O, has the potential to serve 120,000 people because it's the universal donor type O.

接著切換到第一型糖尿病計畫。我先重申我在事先準備的發言中說過的內容。我剛才可能講得有點快。zimislecel 計畫目前處於第 1、2、3 期，並且已恢復給藥。由於它是 A 型計畫，可服務美國與歐洲約 60,000 人。而 017 計畫因為是 O 型，作為通用捐贈者 O 型，具有服務 120,000 人的潛力。

And now what we're trying to do is see if we can get the type O program to go even faster and bring that program out either first or very close behind. That's what we're working on in terms of both the regulatory approach and the commercial approach. I don't have a time line for you today, but we should be able to tell you our exact plans with time lines in the back half of this year. But I am very excited about the opportunity to perhaps bring type O out first or very, very close behind.

而我們現在要做的是看看能否讓 O 型計畫進展得更快，讓該計畫要嘛先推出、要嘛非常接近地跟在後面推出。這就是我們在法規策略與商業策略上正在努力的方向。我今天沒有辦法給你一個時間表，但我們應該能在今年下半年告訴你我們確切的計畫與時間表。不過，我對於也許能讓 O 型先推出、或非常非常接近地跟在後面推出的機會感到非常興奮。

Evan Seigerman, BMO.

Evan Seigerman，BMO。

Congrats on the progress, so you've maintained the expectation for at least $500 million of non-CF revenue this year, while CASGEVY and JOURNAVX delivered roughly $125 million this quarter. So as you think about the path to this target, should we expect that the majority of the upside comes from accelerating patient starts with CASGEVY, continued growth with JOURNAVX or kind of a relatively balanced contribution from both franchises.

恭喜進展順利。你們今年仍維持至少 5 億美元的非 CF 營收目標，而 CASGEVY 與 JOURNAVX 本季合計貢獻約 1.25 億美元。因此，當你們思考達成該目標的路徑時，我們是否應預期大部分的上行來自於 CASGEVY 病患啟動治療的加速、JOURNAVX 的持續成長，或是兩個產品線相對均衡的貢獻？

Evan, I'll ask Charlie, if he wants to make any additional comments on our guidance on the $500 million.

Evan，我請 Charlie 看看他是否願意就我們 5 億美元指引再補充一些評論。

Yes, Evan, thanks. As you pointed out, so far in the first half of the year, CASGEVY and JOURNAVX combined delivered about $200 million in revenue. So we're well on our way to achieving our target of $500 million-plus in that first half. CASGEVY has been a bigger contributor than JOURNAVX, but I'm not willing to give further color on the balance of the year other than to say we're very confident in getting to that $500 million plus.

好的，Evan，謝謝。如你所指出的，今年上半年截至目前，CASGEVY 與 JOURNAVX 合計帶來約 2 億美元營收。因此，我們正穩步朝上半年達成 5 億美元以上目標前進。CASGEVY 的貢獻大於 JOURNAVX，但除了表示我們對達成 5 億美元以上非常有信心之外，我不願就下半年兩者的占比提供更多細節。

Michael Yee, UBS.

Michael Yee，UBS。

I guess the IgAN competitor data to your eGFR data is hot off the press, and it's out there on the tape, and you can see that the approved product has essentially a stabilization of eGFR, if not slightly above the baseline. So to what extent Reshma, given that you have an approval coming up soon, should we think about comparing the two, either from a launch perspective or perhaps given the strong numbers that they're putting up, it speaks to the significant market opportunity and you can get equivalent share? Maybe just talk a little bit about the data that the competitor is putting up and how you think about your launch?

我想 IgAN 競品的數據相對於你們的 eGFR 數據是剛出爐的，市場上也已經在傳，你可以看到已獲核准的產品基本上讓 eGFR 穩定，甚至略高於基線。所以 Reshma，鑑於你們很快也將迎來核准，我們應該在多大程度上把兩者拿來比較——不論是從上市推廣的角度，或是考量到他們公布的強勁數據，這也反映出龐大的市場機會，而你們也能取得相當的市占？能否談談競品今天公布的數據，以及你們如何看待自己的上市？

Sure thing. Mike, the -- I did just see the eGFR data, but I've just seen the top-line number. And as you say, it shows a stabilization right around 0. That is what we should expect given the proteinuria reduction. So that seems very much in line.

當然可以。Mike，關於——我確實剛看到 eGFR 數據，但只看到了最上層的結果數字。如你所說，它顯示大約在 0 附近的穩定。考量到蛋白尿的下降，這正是我們應該預期的結果。所以看起來非常一致。

With regard to what it means for the povetacicept IgAN program, I would say all the more reason if anybody needed a little bit more conviction, you can certainly look at these data that were presented today, look at the proteinuria reduction, look at the GFR and reconfirm for yourself that significant reductions in proteinuria should and have resulted in GFR stabilization.

至於這對 povetacicept 的 IgAN 計畫意味著什麼，我會說：如果有人還需要更多信心，那今天公布的這些數據更能提供理由——你可以看看所呈現的數據、看看蛋白尿下降、看看 GFR，並再次自行確認：蛋白尿的大幅降低應該、而且確實會帶來 GFR 的穩定。

So it makes a lot of sense to me. For what I see for Pove, I see us putting up very strong numbers on proteinuria, numerically, the best out there, 52% change from baseline in terms of proteinuria reduction, 70-plus percent reductions in hematuria and 70-plus percent reductions in Gd-IgA1.

所以對我而言非常合理。就我看到的 Pove 而言，我們在蛋白尿方面的數據非常強，從數值上看是目前最好的：蛋白尿相較基線下降 52%，血尿下降 70% 以上，Gd-IgA1 也下降 70% 以上。

That bodes very well for Pove. And then I'll emphasize, Mike, the patient-centric attributes of delivery once-monthly, small-volume, 0.46 ml via an auto injector. And I think when you put all of that together, real excitement for me for what Pove may bring to patients once the PDUFA date comes and goes, and we have the opportunity to launch.

這對 Pove 非常有利。另外我也要強調，Mike，從以病患為中心的給藥特性來看：每月一次、小容量、0.46 ml，透過自動注射器給藥。我認為把這些因素綜合起來，一旦 PDUFA 日期到來並過去、我們有機會上市時，我對 Pove 能為病患帶來的價值感到非常振奮。

Tazeen Ahmad, Bank of America.

Tazeen Ahmad，美國銀行。

Are you still planning on presenting additional data from the RAINIER study this year? And if so, what level of data? And where could that be? And then secondly, for Pove in gMG, it's becoming an increasingly competitive space. So how are you thinking about what additional benefit your drug could provide into this space either with efficacy, safety or dosing frequency?

你們今年仍計畫公布 RAINIER 研究的更多數據嗎？如果是，會是什麼層級的數據？可能會在哪裡發表？第二個問題，Pove 在 gMG 的領域競爭愈來愈激烈。你們如何思考你們的藥物能在這個領域提供哪些額外益處——不論是療效、安全性或給藥頻率？

Yes, on RAINIER. We are planning to present data. The conferences don't like it when we suggest the name when submissions have been made, but acceptances haven't come through yet. So maybe I'll just leave it at, yes, we plan to present the full RAINIER IA data set. We're looking forward to do so. I'll say at a fall conference, and I'll leave it to your imagination for which one.

是的，關於 RAINIER。我們計畫發表數據。在投稿已送出但尚未收到接受通知前，會議主辦方通常不喜歡我們先透露會議名稱。所以我就先說到這裡：是的，我們計畫發表完整的 RAINIER IA 數據集。我們很期待能夠發表。我會說是在秋季的一個會議上，至於是哪一個就留給你想像。

On gMG and Pove, this one is really exciting. And you gave me three options for why we're excited about Pove in gMG: efficacy, safety or patient benefits administration, all three. This is another one of those trifectas that Duncan has talked about. On efficacy, there is another molecule, a wild-type TACI, so not engineered for optimal potency, binding affinity or tissue distribution. That has already shown substantial efficacy benefit.

至於 gMG 與 Pove，這真的非常令人興奮。你給了我三個我們對 Pove 在 gMG 感到興奮的理由選項：療效、安全性或以病患為中心的給藥便利性——答案是三者皆是。這也是 Duncan 提過的那種「三重優勢」。在療效方面，已有另一個分子——野生型 TACI，並非為了最佳效力、結合親和力或組織分布而工程化——已展現出顯著的療效益處。

And remember, that's a wild-type TACI compared to Pove, which is an engineered TACI. So that's on efficacy. On safety, Pove does not need to have a cycle on and a cycle off. That gives real benefit on safety, but that also has the secondary benefit on efficacy because you don't have that off period where the autoantibodies are allowed to return.

而且請記得，那是野生型 TACI；相較之下，Pove 是工程化的 TACI。這是療效面。在安全性方面，Pove 不需要有一段用藥週期、再一段停藥週期。這在安全性上帶來實質益處，同時也在療效上有次要好處，因為你不會有那段停藥期讓自體抗體得以回升。

And the third is same thing, auto injector. We have to figure out whether it's the 80 milligrams or 240 milligrams, but in either case, it will be auto-injector, once-monthly at-home low-volume dosing. So of your options, I expect Pove to be better across the board on all three dimensions.

第三點也是同樣的：自動注射器。我們還需要確認是 80 毫克或 240 毫克，但無論哪一種，都會是自動注射器、每月一次、在家中、低容量給藥。所以在你提到的三個面向上，我預期 Pove 會全面更具優勢。

Phil Nadeau, TD Cowen.

Phil Nadeau，TD Cowen。

There's a lot of focus on the upcoming data from one of your competitors where we're going to get incremental sweat chloride reductions above TRIKAFTA. We're curious to hear Vertex's opinion on how you're going to interpret that data?

市場非常關注你們某位競爭對手即將公布的數據，據說會在 TRIKAFTA 之上帶來額外的汗氯（sweat chloride）下降幅度。我們想聽聽 Vertex 對於你們將如何解讀該數據的看法？

Is there a level of sweat chloride reduction that would get your attention or Reshma, as you've suggested in the prepared remarks, is it more about simply the proportion of patients who get to less than 30 millimoles per liter and the exact reduction maybe isn't as meaningful because it can be influenced by things like baseline characteristics?

是否存在某個汗氯下降幅度會引起你們注意？或者 Reshma，如你在事先準備的發言中所暗示的，重點其實更在於有多少比例的病患能降到每公升 30 毫摩爾以下，而具體下降幅度可能沒那麼重要，因為它會受到基線特徵等因素影響？

Yes. Phil, I think you have it right on our perspective. Where we sit today with ALYFTREK. We already know we can get two-thirds of patients to less than 30 millimoles. That's that normal or carrier threshold. And furthermore, if you think about as all physiologic parameters do, there is a Gaussian distribution around that median sweat chloride 30 millimoles. If you superimpose across all age groups, the ALYFTREK data on the carrier data, more than 75% of people across age groups overlap that distribution.

是的。Phil，我認為你對我們的觀點掌握得很準。以我們目前對 ALYFTREK 的立場來看。我們已經知道可以讓三分之二的病患降到 30 毫摩爾以下。那就是正常或帶因者（carrier）的門檻。此外，正如所有生理參數一樣，在汗氯中位數 30 毫摩爾附近會呈現高斯分布。如果你把 ALYFTREK 在各年齡層的數據與帶因者數據疊加比較，跨年齡層有超過 75% 的人落在重疊的分布範圍內。

So with those kind of data, I think that the bar is exceptionally high and rests on getting more patients to less than 30 millimoles. That is the mark and that's the mark that we or anyone else has to hit in order to have a competitive medicine. And of course, it goes without saying it has to be safe, it has to be well tolerated. It has to have good DDIs, it has to be once daily. But on pure efficacy, it has to be a molecule that gets more patients to less than 30 millimoles in terms of sweat chloride.

因此，在這樣的數據之下，我認為門檻非常高，關鍵在於讓更多病患降到 30 毫摩爾以下。這就是標準，也是我們或任何其他人要做出具競爭力藥物所必須達到的標準。當然不言而喻，它必須安全、必須耐受性良好。必須有良好的藥物交互作用（DDIs）表現，必須是每日一次。但就純粹療效而言，它必須是一個能讓更多病患在汗氯指標上降到 30 毫摩爾以下的分子。

Terence Flynn, Morgan Stanley.

Terence Flynn，摩根士丹利。

I have another one on inaxaplin. I was just wondering if you can help set expectations for the upcoming AMPLIFIED Phase 2 trial? And then how to think about any read-through to AMPLITUDE?

我還有一個關於 inaxaplin 的問題。我想請教您是否能協助我們對即將進行的 AMPLIFIED 第二期試驗建立預期？另外，該如何看待其對 AMPLITUDE 的任何延伸解讀（read-through）？

Yes. So AMPLIFIED is the study that's Phase 2. It's the expanded AMKD population. By that, I mean, it's the population with two APOL1 alleles. And in one arm of the basket study, it's two APOL1 alleles diabetes and in the other arm, it's two APOL1 alleles, and let's call it, modest proteinuria, so low-grade proteinuria. The way I would frame it up is the study is completed. We are on track for us to be able to share results this fall.

好的。所以 AMPLIFIED 是一項第二期研究。它涵蓋擴大的 AMKD 族群。我的意思是，這是帶有兩個 APOL1 等位基因的族群。在這個籃式研究（basket study）的其中一個組別，是兩個 APOL1 等位基因且合併糖尿病；另一個組別則是兩個 APOL1 等位基因，並且我們稱之為輕度蛋白尿，也就是低度蛋白尿。我會這樣表述：該研究已完成。我們進度如期，預計可在今年秋季分享結果。

And what I'd be looking for and looking to understand is can we derive benefit on proteinuria when you have very modest proteinuria to start with. So this is 0.2 grams to 0.7 grams of protein as opposed to 0.7 grams and above. And of course, it all comes down to what the mean entry baseline level of protein is. Or in the case of diabetes, can we alter the proteinuria when you have second kidney disease involved.

而我會關注並希望理解的是：當起始蛋白尿非常輕微時，我們是否仍能在蛋白尿上獲得效益。也就是 0.2 克到 0.7 克的蛋白，相較於 0.7 克以上。當然，最終都取決於入組時的平均基線蛋白水平。或者在糖尿病的情況下，當合併第二種腎臟疾病時，我們是否能改變蛋白尿。

These are questions worth studying, but there are clearly different populations than AMPLITUDE, which is why we specifically did not include them in the Phase 2 original study of inaxaplin and equally why we didn't include them in the Phase 3 study called AMPLITUDE.

這些都是值得研究的問題，但它們顯然與 AMPLITUDE 的族群不同；這也是為什麼我們在 inaxaplin 原始的第二期研究中刻意未納入這些族群，同樣也為什麼我們在名為 AMPLITUDE 的第三期研究中未納入它們。

So we're super excited to look at these results. We're going to learn a lot and I'm very, very, very happy, and I think you'll see the wisdom of our approach, given what has happened in the field for others to keep these populations, which are expanded populations separate and look at each one individually in this basket AMPLIFIED study.

所以我們非常期待看到這些結果。我們會學到很多，而我也非常、非常、非常高興；我想，鑑於其他人在這個領域所發生的情況，你會看到我們做法的明智之處：將這些擴大族群分開，並在這項 AMPLIFIED 籃式研究中逐一、個別地評估每一個族群。

Mohit Bansal, Wells Fargo.

Mohit Bansal，富國銀行。

Just maybe a question for Duncan, if you want to help with the prescription trends here for JOURNAVX, so obviously, prescription growth is very strong. But how should we think about the prescribing behavior in terms of how many days of therapy physicians are writing? Has it changed at all in last few quarters or so because it does seem like you have good access, you have good prescription, but probably -- this is probably a missing piece, which could improve here.

可能有個問題想請 Duncan 協助說明 JOURNAVX 的處方趨勢：很明顯處方成長非常強勁。但我們應該如何看待醫師在開立療程天數方面的處方行為？過去幾個季度左右是否有任何變化？因為看起來你們的可及性很好、處方量也不錯，但可能——這可能是一個缺失環節，若改善的話可能會帶來提升。

To answer your question specifically, as I think we've communicated before, in hospitals, the prescription duration is around about five days or so. In retail, it's around about 12, 14 days. So on average, you net out at around about 10 or 11 days or so for each JOURNAVX prescription. And candidly, that dynamic has not changed since the launch because it's really driven by the dynamics of the institution that the patient is in rather than anything else. So to answer your question simply, those are the numbers, and it has not changed over the last few months.

針對你的問題具體回答：如同我們先前溝通過的，在醫院端，處方療程長度大約是 5 天左右。在零售端，大約是 12 到 14 天。因此平均下來，每張 JOURNAVX 處方大約是 10 或 11 天左右。坦白說，自上市以來這個動態並沒有改變，因為它主要是由病人所在機構的特性所驅動，而不是其他因素。所以簡單回答你的問題：就是這些數字，而且過去幾個月沒有變化。

Ellie Merle, Barclays.

Ellie Merle，巴克萊。

So in terms of the DM1 program, what would be good data at the data update in the second half? And how are you thinking about it in the context of the broader competitive landscape in DM1?

那麼就 DM1 計畫而言，下半年資料更新時，什麼樣的數據會是好的數據？以及在 DM1 更廣泛的競爭格局下，你們是如何思考這件事的？

Sure, Ellie. Maybe I can take that one. In DM1, as you know, there hasn't been a clear correlation between the various endpoints that others in the field have looked at, albeit with different approaches. What people have tended to do in their Phase 2 studies to get an early read is look at splicing, a functional endpoint called vHOT and another functional endpoint called QMT, vHOT is sort of how long does it take to open/close your hand and QMT is a measure of muscle function.

當然，Ellie。也許我來回答這題。在 DM1 方面，如你所知，對於同領域其他人所觀察的各種終點（儘管採用不同方法），目前並沒有明確的相關性。大家在第二期研究中為了早期讀出，往往會看剪接（splicing）、一個稱為 vHOT 的功能性終點，以及另一個稱為 QMT 的功能性終點；vHOT 大致上是測量你打開/握緊手需要多久，而 QMT 是肌肉功能的衡量指標。

And what I would say is that of all of those, splicing is an important one, and we certainly are looking at splicing and these measures of muscle function are also something that we're looking at. The reason I like this approach compared to anything else has more to do with mechanism of action.

而我想說的是，在這些指標之中，剪接是一個重要指標，我們當然也會觀察剪接；這些肌肉功能的衡量指標也是我們正在觀察的。我之所以喜歡這種做法，相較於其他方法，更多是與作用機制有關。

And that has to do with the fact that it's an oligo, which others are also trying but it's an oligo linked to a circular peptide to a nuclear localizing domain peptide which we believe will allow it to get into the cell and get into the nucleus where it has to do its work.

這與其為寡核苷酸（oligo）有關——其他人也在嘗試——但我們的是一個寡核苷酸，連結到一個環狀胜肽，再連結到一個核定位域胜肽；我們相信這將使其能進入細胞並進入細胞核，在那裡完成其必須進行的作用。

So that is a plus. And I would also say some of the other programs in order to get into the cell have used mechanisms that have some safety tolerability concerns, and that has not been a concern through the circular peptide program that we use. So for the efficacy endpoints in Phase 2 splicing, and we will also look at these QMT and vHOT endpoints, albeit in small numbers of patients.

所以這是一個優勢。我也想說，其他一些計畫為了進入細胞而採用的機制，存在一些安全性與耐受性方面的疑慮；而我們所使用的環狀胜肽平台，迄今並未出現這方面的疑慮。因此在第二期的療效終點方面，我們會看剪接，也會看這些 QMT 與 vHOT 終點，儘管病人數會比較少。

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