福泰製藥 (VRTX) 2025 Q2 法說會逐字稿

Good day and welcome to the Vertex Pharmaceuticals second quarter 2025 earnings call. (Operator Instructions) Please note that this event is being recorded. I would now like to turn the conference over to Susie Lisa. Please go ahead, ma'am.

大家好，歡迎參加 Vertex Pharmaceuticals 2025 年第二季財報電話會議。（操作員指示）請注意，此事件正在被記錄。現在我想將會議交給 Susie Lisa。請繼續，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 second 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.

大家晚上好。我叫蘇西麗莎 (Susie Lisa)，身為投資者關係資深副總裁，我很高興歡迎您參加我們的 2025 年第二季財務業績電話會議。在今晚的電話會議上發表準備好的演講的嘉賓有 Vertex 執行長兼總裁 Reshma Kewalramani 博士、首席商務官 Duncan McKechnie 和首席營運兼財務長 Charlie Wagner。

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. 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.

我們建議您在收聽此電話會議時存取網路廣播投影片。這次通話正在錄音，重播將在我們的網站上提供。我們將在本次電話會議上做出前瞻性陳述，這些陳述將受到今天的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。

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.

這些聲明包括但不限於有關 Vertex 上市的囊性纖維化、鐮狀細胞病、β地中海貧血和中度至重度急性疼痛藥物、我們的產品線和 Vertex 未來財務業績的聲明，均基於管理層當前的假設。

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. I will now turn the call over to Reshma.

實際結果和事件可能會有重大差異。我還要指出的是，我們將在今晚的電話會議上審查的部分財務結果和指導都是按照非 GAAP 基礎呈現的。現在我將把電話轉給 Reshma。

Thanks, Susie. Good evening all, and thank you for joining us on the call today. As anticipated, momentum accelerated, and we executed with very strong performance across the board, growing and diversifying revenue with multiple new product launches, driving advancement of programs in pivotal development and progressing the earlier stage R&D pipeline.

謝謝，蘇西。大家晚上好，感謝您今天參加我們的電話會議。正如預期的那樣，發展勢頭加速，我們在各個方面都表現強勁，透過推出多款新產品來實現收入的成長和多樣化，推動關鍵開發項目的進展，並推進早期研發管道的建設。

We continue to reach more patients with more products and delivered $2.96 billion in revenue in the second quarter, representing 12% growth versus Q2 2024. We remain sharply focused on commercialization across multiple disease areas and expansion of our patient reach.

我們繼續透過更多產品覆蓋更多患者，第二季度實現了 29.6 億美元的收入，較 2024 年第二季度增長 12%。我們仍然高度重視多個疾病領域的商業化以及擴大患者覆蓋範圍。

We are pleased with the first six months of launch performance as well as physician and patient feedback on both ALYFTREK in CF and JOURNAVX in acute pain as well as the building global momentum for CASGEVY, our gene-edited therapy for sickle cell disease and beta-thalassemia.

我們對上市後前六個月的表現以及醫生和患者對 ALYFTREK 在 CF 治療和 JOURNAVX 在急性疼痛治療中的反饋感到滿意，同時也對我們針對鐮狀細胞病和β-地中海貧血的基因編輯療法 CASGEVY 的全球發展勢頭感到滿意。

In addition to this commercialization focus, research and clinical progress remain paramount. And to that end, we continue to rapidly advance the four programs in pivotal development, and are working with urgency to begin our fifth in primary membranous nephropathy.

除了商業化重點之外，研究和臨床進展仍然至關重要。為此，我們繼續快速推進四個關鍵發展項目，並緊急啟動第五個原發性膜性腎病變項目。

Before I cover R&D highlights for the quarter, I would like to acknowledge our CSO, David Altshuler's retirement a year from now and the planned CSO transition to Mark Bunnage, our current SVP and Global Head of Research.

在介紹本季的研發亮點之前，我想先介紹一下我們的首席策略長 David Altshuler 將於一年後退休，併計劃將首席策略官職位移交給我們現任高級副總裁兼全球研究主管 Mark Bunnage。

David will be retiring from Vertex effective August 1, 2026, after an incredible 13 year career with the company. David initially joined Vertex as a member of the Board of Directors in 2012, and became Chief Scientific Officer in 2015.

David 在 Vertex 工作了 13 年，取得了輝煌的成就，他將於 2026 年 8 月 1 日退休。David 最初於 2012 年加入 Vertex 擔任董事會成員，並於 2015 年成為首席科學官。

During David's tenure, multiple CF medicines have advanced from research through commercialization, including ORKAMBI, SYMDEKO, TRIKAFTA and ALYFTREK. Our disease sandbox has broadened, and we successfully advanced the scientific breakthroughs that became CASGEVY and JOURNAVX.

在 David 任職期間，多種 CF 藥物從研究階段走向商業化，包括 ORKAMBI、SYMDEKO、TRIKAFTA 和 ALYFTREK。我們的疾病沙箱已經擴大，我們成功推進了成為 CASGEVY 和 JOURNAVX 的科學突破。

In an industry with notoriously low R&D success rates, David's teams delivered remarkable achievements year after year. David is a world-renowned physician scientist who is known for his creative and critical thinking, penchant for debate and commitment to building teams. On a more personal level, I know him as a deeply passionate Vertexian, dedicated physician and valued member of the executive team.

在研發成功率極低的產業中，David 的團隊年復一年地取得了令人矚目的成就。大衛是一位世界知名的醫師科學家，以其創造性和批判性思維、辯論的熱情和對團隊建立的承諾而聞名。從個人層面來說，我知道他是一位充滿熱情的 Vertexian 醫生、一位敬業的醫生和一位受人尊敬的執行團隊成員。

As mentioned in our earnings release, as part of this planned transition, I am delighted to announce that Mark Bunnage will assume the role of EVP and Chief Scientific Officer effective February 1, 2026, after which David will work with Mark to ensure a smooth transition.

正如我們在收益報告中提到的那樣，作為此次計劃過渡的一部分，我很高興地宣布，Mark Bunnage 將於 2026 年 2 月 1 日起擔任執行副總裁兼首席科學官，之後 David 將與 Mark 合作，確保順利過渡。

Mark joined Vertex and has worked alongside David since 2016. Since that time, Mark has held increasing senior leadership roles across research, starting as SVP Site Head Boston Research and most recently as SVP, Head of Global Research, overseeing all five of Vertex's research sites.

馬克加入 Vertex 並自 2016 年起與大衛一起工作。從那時起，馬克在研究領域擔任了越來越多的高級領導職務，最初擔任波士頓研究高級副總裁，最近擔任全球研究主管高級副總裁，負責監督 Vertex 的所有五個研究站點。

Under Mark's leadership, we advanced many molecules to the clinic, including CASGEVY and JOURNAVX, inaxaplin for AMKD, VX-828 for CF, VX-670 for DM1 and VX-407 for autosomal dominant polycystic kidney disease.

在馬克的領導下，我們將許多分子推進到臨床，包括 CASGEVY 和 JOURNAVX、用於治療 AMKD 的 inaxaplin、用於治療 CF 的 VX-828、用於治療 DM1 的 VX-670 和用於治療常染色體顯性多囊腎病的 VX-407。

Mark was also intimately involved in the diligence that led to the Alpine acquisition, which brought povetacicept to Vertex. I look forward to celebrating David's retirement and welcoming Mark as CSO when the time gets closer.

馬克也密切參與了促成阿爾派收購的盡職調查，此次收購將 povetacicept 帶給了 Vertex。我期待著慶祝大衛退休並在臨近退休時歡迎馬克擔任首席策略長。

Returning then to R&D highlights. I'll limit my comments to the pipeline programs with the most significant new information to share, specifically CF, pain, type 1 diabetes and the renal programs. Starting with CF. As of July, we've gained approval for ALYFTREK in the US, UK, EU and Canada. We've also secured reimbursement for ALYFTREK in England and will add Ireland shortly.

然後回到研發亮點。我的評論將僅限於具有最重要的新資訊可供分享的管道項目，特別是 CF、疼痛、 1 型糖尿病和腎臟項目。從 CF 開始。截至 7 月，我們已獲得美國、英國、歐盟和加拿大對 ALYFTREK 的批准。我們還確保了 ALYFTREK 在英格蘭的報銷，並將很快增加到愛爾蘭。

Patients in Germany and Denmark already have reimbursed access due to existing agreements and provisions. And across other EU member nations and Canada, we're working with reimbursement bodies to secure access for eligible patients as quickly as possible.

根據現有的協議和規定，德國和丹麥的患者已經可以報銷醫療費用。在其他歐盟成員國和加拿大，我們正在與報銷機構合作，以確保符合條件的患者盡快獲得治療。

As we continue to expand our existing CFTR modulator portfolio to younger age groups, we also continue to develop new CFTR regimens with the aim of reaching our long-standing objective of bringing most, if not all, people with CF to normal levels of CFTR function.

隨著我們繼續將現有的 CFTR 調節劑產品組合擴展到更年輕的年齡組，我們還將繼續開發新的 CFTR 方案，旨在實現我們的長期目標，即讓大多數（如果不是全部） CF 患者達到正常的 CFTR 功能水平。

Our Next-Gen 3.0 or NG 3.0 regimen is next on deck. The backbone of the NG 3.0 combination is VX-828, the most efficacious CFTR corrector that we have ever studied in vitro and brought to the clinic. We are nearing completion of the healthy volunteer study, and we remain on track to initiate a cohort of people with CF with the VX-828 regimen before the end of this year.

我們的下一代 3.0 或 NG 3.0 方案即將推出。NG 3.0 組合的核心是 VX-828，這是我們迄今為止在體外研究並應用於臨床的最有效的 CFTR 校正劑。我們即將完成健康志願者研究，我們仍計劃在今年年底前啟動一批 CF 患者使用 VX-828 療法的試驗。

Finally, in CF, on VX-522, I am pleased to note that the Data Safety Monitoring Committee has completed its review and has endorsed restarting the trial. We're now in the process of working to resume dosing in the MAD portion of the Phase 1/2 for the 5,000 or so patients who cannot benefit from our CFTR modulators and expect to do so in the near term.

最後，在 CF 中，關於 VX-522，我很高興地註意到資料安全監測委員會已經完成審查並批准重新開始試驗。目前，我們正在努力恢復 1/2 期 MAD 部分的給藥，為大約 5,000 名無法從我們的 CFTR 調節劑中受益的患者提供服務，並預計在短期內能夠從中受益。

Now shifting to pain. First, in peripheral neuropathic pain or PNP, we had a productive end of Phase 2 meeting with the FDA on our PNP program. While a broad PNP label remains our goal, at this time, the FDA does not see a path to a broad indication. As such, we will not be initiating an LSR trial at present.

現在轉向痛苦。首先，在周邊神經性疼痛或 PNP 方面，我們與 FDA 就 PNP 計畫舉行的第 2 階段會議取得了富有成效的結束。雖然廣泛的 PNP 標籤仍然是我們的目標，但目前，FDA 還沒有找到廣泛適應症的途徑。因此，我們目前不會啟動 LSR 試驗。

Instead, in light of the discussions and clear agreement with the FDA regarding approval requirements for diabetic peripheral neuropathy, or DPN, we will begin a second DPN Phase 3 study shortly in order to secure DPN as our first PNP indication for suzetrigine.

相反，鑑於與 FDA 就糖尿病周圍神經病變 (DPN) 的批准要求進行的討論和明確協議，我們將很快開始第二個 DPN 第 3 階段研究，以確保 DPN 作為 Suzetrigine 的第一個 PNP 適應症。

Recall, we have breakthrough therapy designation for the DPN indication. Also note that our first Phase 3 study of suzetrigine in DPN is already well underway. And with the near-term initiation of the second DPN study, our goal is to complete enrollment of both of these trials by the end of 2026.

回想一下，我們對 DPN 適應症有突破性治療稱號。另外請注意，我們對 DPN 患者使用 Suzetrigine 進行的第一階段 3 期研究已在順利進行中。隨著第二項 DPN 研究的即將啟動，我們的目標是在 2026 年底前完成這兩項試驗的招募。

We look forward to working with the agency to secure DPN as our first PNP indication, to expand the indication over time, and to continue to discuss a potential pathway to a broad PNP label.

我們期待與該機構合作，確保 DPN 作為我們的第一個 PNP 適應症，並隨著時間的推移擴大適應症，並繼續討論獲得廣泛 PNP 標籤的潛在途徑。

Turning now to acute pain and VX-993, another NaV1.8 inhibitor. This afternoon, we shared top line results from the Phase 2 trial of this molecule in the post bunionectomy setting. To recap, as part of our serial innovation strategy, we developed VX-993 with three main goals.

現在轉向急性疼痛和另一種 NaV1.8 抑制劑 VX-993。今天下午，我們分享了該分子在拇囊切除術後進行的第 2 階段試驗的頂線結果。總而言之，作為我們連續創新策略的一部分，我們開發 VX-993 有三個主要目標。

First, to have an IV option. Second, to provide additional NaV1.8 inhibitor candidates for potential use as co-formulation with future NaV1.7 inhibitors. And third, to further refine dose-response relationships, including whether higher clinical exposure might result in greater clinical efficacy.

首先，要有靜脈注射選項。其次，提供額外的 NaV1.8 抑制劑候選物，以便與未來的 NaV1.7 抑制劑共同配製。第三，進一步完善劑量反應關係，包括較高的臨床暴露量是否會帶來更好的臨床療效。

Focusing on this last point of efficacy, based on the predicted clinical potency and exposure of 993, we powered the Phase 2 trial with the goal of detecting a treatment effect higher than previously achieved. This Phase 2 trial included a placebo group, three VX-993 dosage arms and a hydrocodone reference arm. The primary endpoint was SPID48, compared to placebo.

專注於最後一點療效，基於 993 的預測臨床效力和暴露量，我們進行了第 2 階段試驗，目的是檢測出比以前更高的治療效果。此 2 期試驗包括安慰劑組、三個 VX-993 劑量組和一個氫可酮參考組。與安慰劑相比，主要終點是 SPID48。

The results showed that VX-993 was safe and well tolerated with no related SAEs and an overall profile consistent with the placebo arm. The placebo effect was well controlled, and desired 993 exposures were achieved, with adequate separation between doses.

結果顯示，VX-993 安全且耐受性良好，沒有相關的 SAE，整體情況與安慰劑組一致。安慰劑效應得到了很好的控制，達到了預期的 993 次暴露，並且劑量之間有足夠的間隔。

On efficacy, VX-993 did not meet the primary endpoint and did not show statistical significance at the 0.05 level. This SPID48 treatment effect was similar at both the mid and high doses and both were numerically better versus placebo.

在療效方面，VX-993 未達到主要終點，且未在 0.05 水準上表現出統計學意義。SPID48 的治療效果在中劑量和高劑量下相似，並且與安慰劑相比在數值上均較好。

The outcome of this study, combined with the totality of evidence from our preclinical models and previous NaV1.8 inhibitor clinical studies in acute pain suggest we are at the high end of the NaV1.8 dose response curve for acute pain in the post bunionectomy setting.

這項研究的結果，結合我們臨床前模型和先前 NaV1.8 抑制劑在急性疼痛方面的臨床研究的全部證據，表明我們處於拇囊切除術後急性疼痛的 NaV1.8 劑量反應曲線的高端。

As such, we do not plan to advance VX-993 as monotherapy in acute pain because we do not expect that it will be superior to our NaV1.8 inhibitors. We do plan to complete the ongoing VX-993 study of DPN to further define the exposure response, relationship and maximal efficacy of NaV1.8 inhibitors in this chronic pain indication.

因此，我們不打算將 VX-993 作為急性疼痛的單一療法，因為我們不認為它會優於我們的 NaV1.8 抑制劑。我們確實計劃完成正在進行的 DPN VX-993 研究，以進一步確定 NaV1.8 抑制劑在這種慢性疼痛適應症中的暴露反應、關係和最大療效。

To close out on pain, a quick word on our NaV1.7 inhibitor program. We're very encouraged by our strong preclinical progress in this program and look forward to advancing candidates for use alone or in combination with NaV1.8 inhibitors.

為了結束痛苦，我們來簡單介紹一下我們的 NaV1.7 抑制劑計劃。我們對該計畫在臨床前階段取得的強勁進展感到非常鼓舞，並期待推進單獨使用或與 NaV1.8 抑制劑聯合使用的候選藥物。

Transitioning now to type 1 diabetes. Zimislecel will soon complete enrollment in dosing of its pivotal study, positioning us for global regulatory submissions in 2026 if the data are supportive. Recall, we expect about 60,000 severe type 1 diabetic patients may potentially benefit from this first zimislecel submission.

現在正在轉變為第 1 型糖尿病。Zimislecel 很快就會完成其關鍵研究的劑量招募，如果數據支持，我們將在 2026 年提交全球監管申請。回想一下，我們預計大約 60,000 名嚴重 1 型糖尿病患者可能會從首次提交的 zimislecel 中受益。

In June at the ADA meeting and concurrently in the New England Journal of Medicine, positive data for zimislecel in type 1 diabetes were presented that continue to demonstrate this cell therapy's transformative potential.

今年 6 月，在 ADA 會議和同期的《新英格蘭醫學雜誌》上，研究人員公佈了 zimislecel 治療 1 型糖尿病的積極數據，繼續證明了這種細胞療法的轉化潛力。

All 12 patients with at least one year follow-up who received a full dose of zimislecel as a single infusion achieved ADA recommended target hemoglobin A1C levels less than 7%, freedom from severe hypoglycemic events during the evaluation period and greater than 70% time in range.

所有 12 名接受單次輸注全劑量 zimislecel 的患者均接受了至少一年的隨訪，均達到了 ADA 推薦的目標血紅蛋白 A1C 水平（低於 7%），在評估期間沒有發生嚴重的低血糖事件，並且範圍內的時間超過 70%。

Remarkably, 10 of the 12 patients at 12 months were insulin free, a testament to the potential transformative benefit and durability of this therapy. We also continue to make preclinical progress on our approaches to cloak the same VX-880 cells from the immune system, including improved immunosuppressive regimens, gene editing to produce hyperimmune islet cells and novel immuno protection to encapsulate these cells. We look forward to updating you as these programs advance.

值得注意的是，12 個月後，12 名患者中有 10 名不再使用胰島素，證明了這種療法的潛在轉化益處和持久性。我們也繼續在將相同的 VX-880 細胞從免疫系統中隱藏起來的方法上取得臨床前進展，包括改進的免疫抑制方案、基因編輯以產生高免疫胰島細胞和新型免疫保護以包裹這些細胞。我們期待隨著這些計劃的進展向您通報最新情況。

Finally, a few updates on our kidney portfolio, which now has clinical stage programs in four diseases; IgA nephropathy, AMKD, membranous nephropathy and ADPKD, or autosomal dominant kidney disease.

最後，對我們的腎臟產品組合進行一些更新，目前已有四種疾病的臨床階段項目：IgA 腎病變、AMKD、膜性腎病變和 ADPKD，即常染色體顯性腎病變。

Starting with povetacicept, a number of autoimmune diseases are driven by uncontrolled B cells. By controlling B cells, pove is designed to restore immune balance for patients and hold the potential to have transformative benefit across multiple disease states.

從 povetacicept 開始，許多自體免疫疾病都是由不受控制的 B 細胞引起的。透過控制 B 細胞，pove 旨在恢復患者的免疫平衡，並有可能在多種疾病狀態下帶來變革性益處。

Pove was specifically engineered for better tissue penetration and to deliver optimized targeted dual inhibition of the BAFF and APRIL cytokines, which both play a key role in the pathogenesis of B cell mediated autoimmune diseases.

Pove 經過專門設計，具有更好的組織滲透性，並對 BAFF 和 APRIL 細胞因子提供優化的靶向雙重抑制，這兩者在 B 細胞介導的自身免疫性疾病的發病機制中都發揮著關鍵作用。

First up for pove is IgAN. We disclosed previously that we completed enrollment of the interim analysis cohort in the RAINIER Phase 3 trial. Today, we are pleased to share that we are on track to complete enrollment of the full RAINIER study by the end of this year.

首先要考慮的是 IgAN。我們先前揭露，我們已經完成了 RAINIER 第 3 階段試驗中期分析隊列的招募。今天，我們很高興地告訴大家，我們將在今年年底前完成 RAINIER 研究的全面招募。

With regard to the interim analysis cohort, once this group completes 36 weeks of treatment, we will conduct the interim analysis, and if positive, we'll file for potential accelerated approval in the US in the first half of 2026.

對於中期分析隊列，一旦該組完成 36 週的治療，我們將進行中期分析，如果結果呈陽性，我們將在 2026 年上半年在美國申請潛在的加速批准。

To close out on IgAN, studies to support the launch of pove for at-home self-administration with a subcutaneous auto injector are also well underway. Next and consistent with this pipeline and our product potential, the second disease state where we believe pove can provide B-cell control is primary membranous nephropathy.

為了結束對 IgAN 的研究，支持推出使用皮下自動注射器進行家庭自我給藥的方法的研究也在順利進行中。接下來，與該管道和我們的產品潛力一致的是，我們認為 pove 可以提供 B 細胞控制的第二種疾病狀態是原發性膜性腎病變。

Based on strong emerging data from the RUBY-3 study, we completed our end of Phase 2 meeting with the FDA and reached agreement on a Phase 2/3 adaptive study for traditional approval of pove versus standard of care, with the primary endpoint of complete remission at 72 weeks. This Phase 2/3 study will begin later this year.

基於 RUBY-3 研究的強大新數據，我們完成了與 FDA 的第 2 階段會議，並就第 2/3 階段適應性研究達成一致，以批准傳統的 pove 與標準治療，主要終點為 72 週的完全緩解。該 2/3 期研究將於今年稍後開始。

And third, we have prioritized additional diseases in which we believe pove also holds best-in-class promise. Based on emerging data, potential patient impact, the treatment landscape and commercial opportunity, the next two autoimmune diseases in focus for us are generalized myasthenia gravis and warm autoimmune hemolytic anemia, or wAIHA.

第三，我們優先考慮了我們認為 pove 也具有一流前景的其他疾病。根據新興數據、潛在患者影響、治療前景和商業機會，我們接下來關注的兩種自體免疫疾病是全身性重症肌無力和溫自體免疫溶血性貧血（wAIHA）。

So to summarize, our current priority disease areas are IgAN, membranous nephropathy, generalized myasthenia gravis and wAIHA, and we are deprioritizing other indications at this time.

總而言之，我們目前的優先疾病領域是 IgAN、膜性腎病變、全身性重症肌無力和 wAIHA，我們目前正在降低其他適應症的優先順序。

Next on inaxaplin for APOL1-mediated kidney disease, we remain on track to complete enrollment in the interim analysis cohort of the AMPLITUDE pivotal trial in primary AMKD this year. Of note, while we are able to enroll more adolescent patients, we've hit an important milestone in this study, where the target number of 10 to 17 year old AMKD patients has now been achieved.

接下來，我們將使用 inaxaplin 治療 APOL1 介導的腎臟疾病，並在今年完成 AMPLITUDE 原發性 AMKD 關鍵試驗的中期分析隊列的招募。值得注意的是，雖然我們能夠招募更多的青少年患者，但我們在這項研究中已經達到了一個重要的里程碑，即 10 至 17 歲 AMKD 患者的目標數量已經實現。

After completing enrollment in the IA cohort, these patients will be followed for 48 weeks of treatment, at which point we will conduct the interim analysis. And if positive, we'll be poised to file for potential accelerated approval in the US. The AMPLIFIED study, a Phase 2 proof-of-concept study in patients with AMKD and comorbidities, including type 2 diabetes, is also underway, and this trial is on track to complete enrollment by the end of 2025.

完成 IA 隊列的招募後，這些患者將接受 48 週的治療隨訪，屆時我們將進行中期分析。如果結果為陽性，我們將準備向美國申請加速批准。AMPLIFIED 研究是一項針對 AMKD 和包括 2 型糖尿病在內的合併症患者進行的 2 期概念驗證研究，該研究正在進行中，該試驗預計在 2025 年底完成招募。

To close on our kidney pipeline is VX-407 for ADPKD, a first-in-class molecule protein folding corrector that is designed to treat the underlying cause of ADPKD by restoring PC1 protein function, thereby reducing total kidney volume and preventing progression to kidney failure. As a reminder, there are approximately 300,000 patients with ADPKD, and there are no approved therapies that treat the underlying cause of this disease.

我們腎臟治療管道的最後一項是用於治療 ADPKD 的 VX-407，這是一種一流的分子蛋白折疊校正劑，旨在透過恢復 PC1 蛋白功能來治療 ADPKD 的根本原因，從而減少腎臟總體積並防止發展為腎衰竭。提醒一下，大約有 30 萬名 ADPKD 患者，目前尚無批准的療法可以治療該疾病的根本病因。

We believe about 10% of patients with ADPKD may be eligible for treatment with VX-407. This quarter, we'll begin the VX-407 proof-of-concept trial, which is a 52 week single-arm study in 24 patients that will evaluate the efficacy of VX-407 as measured by height-adjusted total kidney volume.

我們相信大約 10% 的 ADPKD 患者可能適合接受 VX-407 治療。本季度，我們將開始 VX-407 概念驗證試驗，這是一項針對 24 名患者進行的為期 52 週的單組研究，旨在透過身高調整後的總腎臟體積來評估 VX-407 的療效。

In closing, Vertex has multiple Phase 3 programs well underway that are poised for accelerated or traditional approval. These trials have either already completed enrollment or are on track to do so in 2025. They each serve a disease with high unmet need, and they've secured multiple regulatory designations, including Fast Track, Breakthrough, Regenerative Medicine or RMAT, Prime, amongst others, all of which positions us for multiple regulatory submissions in 2026 and early 2027, with potential approvals and launches to follow.

最後，Vertex 有多個 3 期專案正在順利進行中，準備獲得加速或傳統批准。這些試驗要么已經完成招募，要么預計在 2025 年完成招募。它們各自針對一種具有高度未滿足需求的疾病，並且已獲得多項監管認證，包括快速通道認證、突破認證、再生醫學或 RMAT、Prime 等，所有這些都使我們能夠在 2026 年和 2027 年初提交多項監管申請，並有可能獲得批准和上市。

Accordingly, as we drive to achieve our R&D milestones, we're executing on the concurrent work of preparing for commercialization of these potential launches. With that, I'll now turn over the call to Duncan for a commercial update.

因此，在我們努力實現研發里程碑的同時，我們也同時進行這些潛在產品商業化的準備。說完這些，我現在將電話轉給鄧肯，讓他講講商業更新狀況。

Thanks very much, Reshma. I will focus my comments tonight on the CF franchise, including the launch of ALYFTREK in the US, the continuing global launch of CASGEVY, and the US launch of JOURNAVX in moderate to severe acute pain.

非常感謝，Reshma。今晚我將重點介紹 CF 系列產品，包括在美國推出 ALYFTREK、在全球繼續推出 CASGEVY 以及在美國推出治療中度至重度急性疼痛的 JOURNAVX。

Starting with CF. Our CF franchise continues to deliver strong results as we grow the number of eligible patients taking our CFTR modulators. We continue to make progress with younger patients, patients with rare mutations and patients in new geographies. The overall market outlook is also supported by the fact that patients are living longer.

從 CF 開始。隨著使用我們的 CFTR 調節劑的合格患者數量的增加，我們的 CF 特許經營權繼續取得強勁業績。我們在治療年輕患者、攜帶罕見突變的患者以及新地區的患者方面不斷取得進展。病患壽命延長的事實也支持了整體市場前景。

Now turning to the US launch of ALYFTREK, our fifth therapy approved to treat the underlying cause of CF. We believe ALYFTREK is the best CFTR modulator available for eligible patients. As we've discussed on prior calls, versus TRIKAFTA, ALYFTREK provides further improvements in CFTR function as measured by sweat chloride is indicated for additional mutations not covered by the TRIKAFTA label and offers the convenience of once-daily dosing.

現在談談美國推出的 ALYFTREK，這是我們第五種獲準治療 CF 根本病因的療法。我們相信 ALYFTREK 是適合符合條件的患者的最佳 CFTR 調節劑。正如我們在先前的電話會議中討論過的，與 TRIKAFTA 相比，ALYFTREK 可以進一步改善 CFTR 功能（以汗液氯化物測量），適用於 TRIKAFTA 標籤未涵蓋的其他突變，並提供每日一次給藥的便利。

In the US, the early 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 thus newly eligible for ALYFTREK, as well as those who previously discontinued one of our other CFTR modulators.

在美國，ALYFTREK 的早期推出在所有患者群體中進展順利。我們發現，那些對 CFTR 調節劑尚無經驗、因此新近有資格使用 ALYFTREK 的患者以及先前已停止使用我們的其他 CFTR 調節劑的患者對 ALYFTREK 的吸收尤其迅速。

For patients currently on TRIKAFTA, many have been on therapy for multiple years, have experienced incredible clinical benefit, and therefore, have considerable brand loyalty. In this context, the pace of transitions is steady as these patients continue their conversations with physicians and make decisions that balance the short-term logistics of augmented liver monitoring with ALYFTREK against a lifetime of potential benefits, including greater CFTR protein function and once-daily dosing.

對於目前接受 TRIKAFTA 治療的患者來說，許多患者已經接受治療多年，獲得了令人難以置信的臨床益處，因此具有相當的品牌忠誠度。在此背景下，隨著這些患者繼續與醫生交談並做出決定，轉變的步伐是穩定的，這些決定平衡了使用 ALYFTREK 進行增強肝臟監測的短期後勤與一生的潛在益處，包括更強的 CFTR 蛋白功能和每日一次的給藥。

Overall, we're very pleased with the reports of ALYFTREK's clinical success that physicians and patients are sharing whether they were naive to a CFTR modulator, are returning to therapy or have recently transitioned from TRIKAFTA.

總體而言，我們對 ALYFTREK 臨床成功的報告感到非常滿意，醫生和患者都在分享這些報告，無論他們是否對 CFTR 調節劑不熟悉，正在恢復治療，還是最近從 TRIKAFTA 過渡。

We continue to expect the majority of patients who are currently on CFTR modulator therapy will transition to ALYFTREK over time given its multiple benefits. We're also now in the process of launching ALYFTREK in England following our recent reimbursement agreement with NHS England as well as in Germany and Denmark.

鑑於 ALYFTREK 的多種益處，我們繼續預期目前正在接受 CFTR 調節劑治療的大多數患者將隨著時間的推移轉向 ALYFTREK。繼我們最近與英國國家醫療服務體系 (NHS England) 達成報銷協議之後，我們現在也正在英國、德國和丹麥推出 ALYFTREK。

Transitioning to CASGEVY, our transformative one-time treatment for patients with sickle cell disease and beta thalassemia. The CASGEVY launch is building momentum, and we're pleased with the progress we're making in 2025 as well as the growth it positions us for in 2026.

轉向 CASGEVY，這是我們針對鐮狀細胞疾病和β地中海貧血患者的變革性一次性治療方法。CASGEVY 的推出正在積聚勢頭，我們對 2025 年取得的進展以及它為我們在 2026 年帶來的成長感到滿意。

In quarter two, we've seen an acceleration across the board in patient initiations, cell collections and infusions. This progress is a reflection of the foundational work initiated in 2024 to build our ATC network, expand our geographic footprint to include the Middle East and secure reimbursement for CASGEVY worldwide.

在第二季度，我們看到患者入院、細胞採集和輸注全面加速。這項進展反映了我們於 2024 年啟動的基礎工作，旨在建立我們的空中交通管制網絡、擴大我們的地理覆蓋範圍以涵蓋中東地區並確保在全球範圍內獲得 CASGEVY 的報銷。

Regarding reimbursement, 10 countries now provide access to CASGEVY, including the US and several European and Middle Eastern countries. In terms of our CASGEVY launch metrics, I'm pleased to report that since launch and through the end of quarter two, 2025, firstly, we have met our authorized treatment center goal with more than 75 ATCs now activated globally. We are now dosing patients with sickle cell disease or TDT in multiple regions, including the Middle East, Europe and the US.

關於報銷，目前已有 10 個國家提供 CASGEVY 服務，其中包括美國和幾個歐洲和中東國家。就我們的 CASGEVY 發布指標而言，我很高興地報告，自發布以來到 2025 年第二季度末，首先，我們已經實現了授權治療中心的目標，目前全球已激活超過 75 個 ATC。我們目前正在為中東、歐洲和美國等多個地區的鐮狀細胞疾病或 TDT 患者提供藥物。

And secondly, nearly 250 patients have been referred by their physicians to an ATC to initiate the treatment process. Approximately 115 patients have had their first cell collections, including 35 first cell collections in quarter two, 2025. And finally, a total of 29 patients have completed their treatment journey and received their infusions of CASGEVY edited cells, including 16 patients in the second quarter of 2025.

其次，近 250 名患者已被醫師轉診至 ATC 開始治療。約有 115 名患者進行了首次細胞採集，其中包括 2025 年第二季的 35 名患者進行了首次細胞採集。最後，共有 29 名患者完成了治療並接受了 CASGEVY 編輯細胞的輸入，其中包括 2025 年第二季的 16 名患者。

Now shifting to the launch of JOURNAVX in moderate to severe acute pain. JOURNAVX received FDA approval on January 30 and has been available in channel since March. We continue to see a very positive reaction to this novel non-opioid option for the treatment of moderate to severe acute pain.

現在轉向推出針對中度至重度急性疼痛的 JOURNAVX。JOURNAVX 於 1 月 30 日獲得 FDA 批准，並於 3 月起在各大渠道上架。我們繼續看到人們對這種用於治療中度至重度急性疼痛的新型非鴉片類藥物的非常積極的反應。

We're pleased with the rapid pace of payer coverage, P&T committee reviews, formulary adoption, breadth of usage and hospital uptake. We're also very encouraged by the broad range of positive JOURNAVX experiences reported by both physicians and patients.

我們對付款人覆蓋範圍、P&T 委員會審查、處方集採用、使用範圍和醫院採用的快速進展感到滿意。我們也對醫生和患者報告的大量積極的 JOURNAVX 體驗感到非常鼓舞。

I'll detail several key elements of our ongoing launch. One, we continue to make great progress with payers, which is a testament to their appreciation for the JOURNAVX clinical profile and the importance of offering a novel non-opioid option in the treatment of acute pain.

我將詳細介紹我們正在進行的發布的幾個關鍵要素。首先，我們與付款人的關係繼續取得巨大進展，這證明了他們對 JOURNAVX 臨床概況的讚賞以及在治療急性疼痛方面提供新型非阿片類藥物選擇的重要性。

As of mid-July, across commercial and government payers, approximately 150 million lives or roughly half of all lives covered in the US have reimbursed access to JOURNAVX. With commercial payers, our negotiations continue to progress very favorably.

截至 7 月中旬，在商業和政府付款人中，約有 1.5 億人（約占美國所有受保人的一半）已報銷 JOURNAVX 的使用費用。我們與商業付款人的談判繼續取得非常有利的進展。

We recently reached a formal coverage agreement with a second large national pharmacy benefit manager to make JOURNAVX available to their customers, representing an incremental 22 million commercial lives. As a result, we now have formal coverage from two of the three large national PBMs and anticipate adding the third before year-end.

我們最近與第二家大型國家藥品福利管理公司達成了正式的覆蓋協議，向其客戶提供 JOURNAVX，這意味著商業生命將增加 2,200 萬人。因此，我們現在已經獲得了三大全國性 PBM 中的兩家的正式報道，並預計在年底前增加第三家。

In addition, we now have national agreements in place with the two largest hospital group purchasing organizations to make JOURNAVX available to acute pain patients in their network member hospitals.

此外，我們現在已經與兩家最大的醫院集團採購組織達成了全國協議，讓其網路成員醫院的急性疼痛患者可以使用 JOURNAVX。

In Medicare, we continue to engage with plans to secure coverage. And for Medicaid patients, through mid-July, we added 6 state plans since our quarter one earnings call for a total of 16 states with legislation that ensures access is available without prior authorization or step edit requirements. We continue to expect the coverage across commercial, Medicare and Medicaid payers will continue to expand through 2025.

在醫療保險方面，我們繼續參與計劃以確保覆蓋範圍。對於醫療補助患者，截至 7 月中旬，自第一季度收益電話會議以來，我們增加了 6 個州的計劃，總共 16 個州制定了立法，確保患者無需事先授權或分步編輯要求即可獲得醫療補助。我們繼續預計，到 2025 年，商業、醫療保險和醫療補助支付者的覆蓋範圍將繼續擴大。

Two, we are prioritizing the P&T committees at approximately 150 healthcare systems and roughly 2,000 hospitals. The majority of these 2,000 hospitals ladder up to 1 of the 150 health care systems. Last quarter, we disclosed that more than a third of these target health care systems had taken steps to initiate the P&T review of JOURNAVX.

二是，我們優先考慮大約 150 個醫療系統和大約 2,000 家醫院的 P&T 委員會。這 2,000 家醫院中的大多數都隸屬於 150 個醫療保健系統之一。上個季度，我們揭露，超過三分之一的目標醫療保健系統已採取措施啟動對 JOURNAVX 的 P&T 審查。

I'm very happy to report that over a third of these priority target health care systems have now added JOURNAVX to formularies, protocols or order sets, and many more have JOURNAVX under active consideration. In addition, at the hospital level, about 500 of the 2,000 hospitals we're targeting have also added JOURNAVX to their formularies, protocols or order sets.

我很高興地報告，超過三分之一的優先目標醫療保健系統現在已將 JOURNAVX 添加到處方集、協議或醫囑集中，還有更多的系統正在積極考慮使用 JOURNAVX。此外，在醫院層面，我們所針對的 2,000 家醫院中約有 500 家也將 JOURNAVX 加入其處方集、方案或醫囑集中。

Three, prescribing patterns are encouraging for the near and long-term outlook for JOURNAVX with excellent breadth of usage to date across a wide range of inpatient and outpatient settings, pain conditions and physician specialties, in line with the broad label.

第三，處方模式對 JOURNAVX 的近期和長期前景來說是令人鼓舞的，迄今為止，其在廣泛的住院和門診環境、疼痛狀況和醫生專業領域中的使用範圍非常廣泛，符合廣泛的標籤。

Lastly, more than 110,000 prescriptions were successfully filled for JOURNAVX across the retail and hospital settings as of mid-July. We remain tremendously excited about our opportunity to transform the treatment of pain, and we'll continue to invest as we see warranted.

最後，截至 7 月中旬，JOURNAVX 在零售和醫院環境中已成功配發了超過 11 萬份處方。我們對改變疼痛治療方法的機會仍然感到非常興奮，我們將繼續進行我們認為有必要的投資。

Given the rapid contracting and formulary progress we have made as well as the prescriber and patient feedback, we believe now is the time to make additional investments in our commercial activities behind JOURNAVX.

鑑於我們在合約和處方方面取得的快速進展以及處方醫生和患者的反饋，我們認為現在是時候對 JOURNAVX 背後的商業活動進行額外投資了。

This includes additional marketing activities in Q3, as well as field support as we continue to secure more access and hospital formulary wins over the coming months. We have high confidence that we are in the early days of creating another multibillion-dollar franchise for Vertex.

這包括第三季的額外行銷活動以及現場支持，因為我們將在未來幾個月繼續獲得更多的訪問權和醫院處方集勝利。我們非常有信心，我們正處於為 Vertex 打造另一個價值數十億美元的特許經營權的早期階段。

To conclude, we are well on our way to establishing a new era of commercial diversification at Vertex as we execute on multiple launches in CF, sickle cell disease, TDT and acute pain and begin the build-out for the next wave of launches in a number of disease areas with high unmet need.

總而言之，隨著我們在 CF、鐮狀細胞疾病、TDT 和急性疼痛領域實施多項產品發布，並開始在大量未滿足需求的疾病領域開展下一波產品發布，Vertex 正在順利開啟商業多元化的新紀元。

We look forward to bringing our transformative therapies to millions more patients and to keeping you updated on our progress. I'll now turn the call over to Charlie to review the financials.

我們期待為數百萬患者帶來變革性的療法，並隨時向您通報我們的進展。我現在將電話轉給查理審查財務狀況。

Thanks, Duncan. Vertex's Q2 2025 revenue growth accelerated as expected, and our results demonstrate our consistent strong performance and attractive growth profile. Second quarter 2025 total revenue increased 12% year-over-year to $2.96 billion.

謝謝，鄧肯。Vertex 2025 年第二季的營收成長如預期加速，我們的業績證明了我們持續強勁的業績和誘人的成長前景。2025 年第二季總營收年增 12%，達到 29.6 億美元。

US revenue growth of 14% year-over-year was driven in CF by ongoing patient demand and favorable gross to net versus prior year and also included contributions from CASGEVY, JOURNAVX and collaboration revenue.

我們營收年增 14%，這得益於 CF 的持續患者需求以及與上年相比有利的毛利與淨利增長，同時也包括來自 CASGEVY、JOURNAVX 和合作收入的貢獻。

As expected, revenue outside the US rebounded this quarter and was up 8% year-on-year, including healthy CF growth and a contribution from CASGEVY. Included in total revenue and the regional growth rates was $30 million of CASGEVY revenue, $12 million from JOURNAVX, and $21 million of collaboration revenue.

正如預期的那樣，本季度美國以外地區的收入出現反彈，年增 8%，其中包括健康的 CF 成長和 CASGEVY 的貢獻。總收入和區域成長率包括 3,000 萬美元的 CASGEVY 收入、1,200 萬美元的 JOURNAVX 收入以及 2,100 萬美元的合作收入。

Second quarter 2025 combined non-GAAP R&D, acquired IPR&D and SG&A expenses were $1.24 billion compared to $5.43 billion in the second quarter of 2024. Excluding Alpine related acquired IPR&D, non-GAAP operating expenses increased 24% year-on-year, driven primarily by the continued advancement of our broad pipeline, including clinical trials for IgAN, pain and type 1 diabetes as well as the build-out of commercial capabilities in pain.

2025 年第二季非 GAAP 研發、收購智慧財產權與開發及銷售、一般及行政費用合計為 12.4 億美元，而 2024 年第二季為 54.3 億美元。不包括與阿爾派相關的收購知識產權與研發費用，非公認會計準則營運費用年增 24%，主要得益於我們廣泛產品線的持續推進，包括針對 IgAN、疼痛和 1 型糖尿病的臨床試驗以及疼痛商業能力的建設。

Second quarter 2025 acquired IPR&D expenses were $2 million compared to $4.4 billion in the second quarter of 2024, which included the acquisition of Alpine Immune Sciences. Second quarter 2025 non-GAAP operating income was $1.33 billion compared to a non-GAAP operating loss of $3.15 billion in the second quarter of 2024.

2025 年第二季收購的 IPR&D 費用為 200 萬美元，而 2024 年第二季為 44 億美元，其中包括收購 Alpine Immune Sciences。2025 年第二季非 GAAP 營業收入為 13.3 億美元，而 2024 年第二季非 GAAP 營業虧損為 31.5 億美元。

Second quarter 2025 non-GAAP effective tax rate was 19.4%. Second quarter 2025 net income was $1.2 billion compared to a net loss of $3.3 billion in Q2 of '24. Second quarter 2025 non-GAAP earnings per share were $4.52 compared to a loss per share of $12.83 in the second quarter of 2024, primarily due to higher revenue and disciplined operating spend as well as the impact of the Alpine AIPR&D expense in the second quarter of 2024.

2025 年第二季非公認會計準則有效稅率為 19.4%。2025 年第二季淨收入為 12 億美元，而 2024 年第二季淨虧損為 33 億美元。2025 年第二季非 GAAP 每股盈餘為 4.52 美元，而 2024 年第二季每股虧損為 12.83 美元，主要歸因於 2024 年第二季營收增加、營運支出嚴謹以及 Alpine AIPR&D 費用的影響。

We ended the quarter with $12 billion in cash and investments after deploying approximately $395 million to repurchase more than 865,000 shares in the second quarter. In May, we announced a new $4 billion share repurchase program, building upon our existing $3 billion share repurchase program which was authorized in 2023, and had $570 million remaining as of June 30. Our priorities for cash deployment remain unchanged, innovation and growth fueled by investment, both internal and external, followed by share repurchases.

在第二季投入約 3.95 億美元回購超過 865,000 股股票後，本季末我們擁有 120 億美元的現金和投資。5 月份，我們宣布了一項新的 40 億美元股票回購計劃，該計劃以我們現有的 30 億美元股票回購計劃為基礎，該計劃於 2023 年獲得授權，截至 6 月 30 日還剩餘 5.7 億美元。我們的現金部署重點保持不變，即透過內部和外部投資推動創新和成長，然後是股票回購。

Now switching to guidance. We are reiterating all elements of our financial guidance, including our 2025 total revenue guidance range of $11.85 billion to $12 billion, representing growth of approximately 8% at the midpoint at current exchange rates.

現在轉向指導。我們重申財務指引的所有要素，包括 2025 年總收入指引範圍 118.5 億美元至 120 億美元，以當前匯率中間價計算，成長率約 8%。

This outlook reflects our expectation for continued growth from our portfolio of CF medicines, including the ongoing launch of ALYFTREK in the US, followed by other regions later this year. Recall that ALYFTREK carries a meaningfully lower royalty burden than TRIKAFTA and extends our composition of matter patent protection to 2039.

這一前景反映了我們對 CF 藥物組合持續成長的預期，包括正在美國推出的 ALYFTREK，以及今年稍後在其他地區推出的 ALYFTREK。回想一下，ALYFTREK 的專利費負擔比 TRIKAFTA 低得多，並將我們的物質成分專利保護延長至 2039 年。

Revenue guidance also includes CASGEVY revenue as we treat more patients in geographies where we have secured regulatory approval and reimbursement. Given the duration of the patient journey, we have high visibility into CASGEVY revenue.

收入指引還包括 CASGEVY 收入，因為我們在獲得監管部門批准和報銷的地區治療了更多的患者。考慮到患者就診時間的長短，我們對 CASGEVY 的收入有很高的可預見性。

As patient initiations and cell collections continue to ramp, we expect commensurate increases in infusions. But note that because the timing of infusions is predicated on patient scheduling choices, there may be revenue variability from quarter-to-quarter.

隨著患者入院和細胞採集的不斷增加，我們預計輸注量也會相應增加。但請注意，由於輸液時間取決於患者的安排選擇，因此每季的收入可能會有所不同。

In addition, guidance reflects additional revenue contribution from JOURNAVX in the second half due to gains in sustainable payer coverage. Recently announced positive coverage decisions are included in our revenue guidance. Overall, we are confident in our ability to deliver another strong year of revenue growth for Vertex in 2025.

此外，由於可持續付款人覆蓋範圍的擴大，該指引也反映了 JOURNAVX 在下半年的額外收入貢獻。最近宣布的積極報道決定已包含在我們的收入指導中。總體而言，我們有信心在 2025 年為 Vertex 帶來另一個強勁的營收成長。

We are also reiterating guidance for combined non-GAAP R&D acquired IPR&D and SG&A expenses in a range of $4.9 billion to $5 billion for the full year 2025, though we expect to be at the high end of this guidance range.

我們也重申，2025 年全年非 GAAP 研發獲得的智慧財產權與開發費用和銷售、一般及行政費用總額將在 49 億美元至 50 億美元之間，但我們預計該數字將處於此指導範圍的高端。

Consistent with prior commentary, this range includes approximately $100 million in projected IPR&D charges. We will continue to invest the majority of our operating expenses into R&D given the momentum in our multiple mid and late-stage clinical development programs, with four and soon to be five Phase 3 studies ongoing and multiple Phase 2s.

與先前的評論一致，該範圍包括預計約 1 億美元的 IPR&D 費用。鑑於我們多個中後期臨床開發項目的勢頭，我們將繼續將大部分營運費用投入到研發中，目前正在進行四個、即將有五個 3 期研究和多個 2 期研究。

In addition, given progress with respect to reimbursement and access and the size of the opportunity for JOURNAVX, as Duncan mentioned, we are increasing our investment in marketing and commercial initiatives to support the launch in the second half of this year.

此外，鑑於報銷和訪問方面的進展以及 JOURNAVX 的機會規模，正如 Duncan 所提到的，我們正在增加對行銷和商業計劃的投資，以支持今年下半年的推出。

We 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.

由於我們在美國的業務規模龐大且供應鏈遍布全球，根據目前掌握的情況，我們預期 2025 年關稅對成本的影響不會太大。當然，鑑於關稅情勢的動態性，包括特定行業關稅的可能性，這種前景可能會改變。

And finally, on guidance, there is no change to our expected full year 2025 non-GAAP effective tax rate in the range of 20.5% to 21.5%, which implies a higher effective tax rate in the second half of the year. We do not anticipate recent tax legislation to have a material impact on our expected effective tax rate in 2025.

最後，根據指引，我們預期 2025 年全年非 GAAP 有效稅率在 20.5% 至 21.5% 之間，沒有變化，這意味著下半年的有效稅率會更高。我們預計最近的稅收立法不會對我們 2025 年預期的有效稅率產生重大影響。

In closing, Vertex yet again delivered strong results in Q2 '25, growing and diversifying our revenue with the launch of two new products in the US, ALYFTREK and JOURNAVX, continuing the global launch of CASGEVY and making significant pipeline progress across the portfolio.

最後，Vertex 在 2025 年第二季度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，繼續在全球推出 CASGEVY，並在整個產品組合中取得了重大的管道進展，實現了營收的成長和多樣化。

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

投影片 17 詳細介紹了這些以及多個疾病領域持續進展的其他預期里程碑。我們期待在未來的電話會議上向您通報我們的進展。現在我請蘇西開始問答環節。

(Operator Instructions) Jessica Fye, JPMorgan.

（操作員指示） Jessica Fye，摩根大通。

Hey guys, good afternoon, thanks for taking my questions. I had a couple on pain. So for the additional commercial efforts behind JOURNAVX, was that increase always planned as coverage came into place? Or is that a reaction to what you're seeing as you kind of continue to launch so far?

大家好，下午好，謝謝你們回答我的問題。我有一些疼痛。那麼，對於 JOURNAVX 背後的額外商業努力，這種增加是否在報導開始後就一直計劃著？或者這是對您迄今為止繼續推出的產品所見情況的反應？

And then for suzetrigine in DPN, I think you said you'd complete enrollment in both Phase 3s by the end of 2026. I'm just curious, can we expect enrollment completion for the first Phase 3 trial much sooner than that? Thank you.

然後對於 DPN 中的 Suzetrigine，我想您說過您將在 2026 年底之前完成兩個 3 期臨床試驗的招募。我只是好奇，我們是否可以預期第一階段 3 試驗的招募能更快完成？謝謝。

Hey Jess, this is Reshma. Let me split that into two parts. I'll take the second part first, and then I'll ask Duncan to comment. Yes, I think that the first DPN might well enroll ahead of the second DPN because it started ahead of time, and the enrollment is going very well.

嘿，傑西，我是雷什瑪。讓我將其分為兩部分。我先講第二部分，然後請鄧肯發表評論。是的，我認為第一個 DPN 很可能會先於第二個 DPN 入學，因為它提前開始，並且入學進展順利。

I will ask Duncan to comment on JOURNAVX. As you know, it's really important to secure payer coverage as we ramp commercial efforts behind that. Duncan, any more comments on how you're thinking about commercialization?

我會請鄧肯對 JOURNAVX 進行評論。如您所知，在我們加大商業努力的同時，確保付款人覆蓋非常重要。鄧肯，你對商業化有什麼看法嗎？

Sure, and thank you for the question, Jess. So obviously, we're now about five months or so into the launch. And I'd say there's sort of three factors that are really driving our thinking. Firstly, as Reshma just alluded to, we're very pleased with the progress we're making with payer coverage and hospital formularies, particularly considering how lengthy P&T processes can be.

當然，謝謝你的提問，傑西。顯然，我們現在距離發布已經過去了大約五個月的時間。我想說有三個因素真正推動我們的思考。首先，正如 Reshma 剛才提到的，我們對付款人覆蓋和醫院處方集方面取得的進展感到非常滿意，特別是考慮到 P&T 流程的冗長。

Secondly, we're receiving incredibly positive feedback from physicians and patients on how well JOURNAVX is working for them clinically. And thirdly, we've seen both in the face-to-face arena with our sales organization as well as in the digital arena, we've seen JOURNAVX to be incredibly promotionally responsive.

其次，我們收到了醫生和患者的非常正面的回饋，他們稱讚 JOURNAVX 在臨床上為他們提供了良好的治療效果。第三，無論是在與我們的銷售組織面對面的交流中，還是在數位領域，我們都看到 JOURNAVX 對促銷的反應非常迅速。

So based on those 3 factors, yes, we are thinking that now is the right time to augment our spend in marketing and field support. I would add the last comment that we do anticipate that field support would still sit within the specialty model.

因此，基於這三個因素，是的，我們認為現在是增加行銷和現場支援支出的最佳時機。我想補充最後一條評論，我們確實預計現場支援仍將屬於專業模型。

Thank you.

謝謝。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Good afternoon. Thanks for taking my question. So with regard to the strategy in pain here, can you help us understand now that you won't be moving forward with a broad PNP label today, maybe what your plan is around running these DPN trials, and then whether it's taking next-generation drugs or so forth to move into LSR or any of the other smaller indications like small fiber neuropathy or some of the others?

午安.感謝您回答我的問題。因此，關於這裡的疼痛策略，您能否幫助我們理解，現在您不會繼續推進廣泛的 PNP 標籤，也許您的計劃是圍繞運行這些 DPN 試驗，然後是否採取下一代藥物等進入 LSR 或任何其他較小的適應症，如小纖維神經病變或其他一些？

And then secondly, in light of the JOURNAVX launch that's progressing here, maybe help us understand how to think about gross to net over the balance of the year and beyond? Thank you.

其次，鑑於 JOURNAVX 的發布進展，也許可以幫助我們了解如何考慮今年及以後的總額與淨額？謝謝。

Sure thing. Salveen, let me take those questions. With regard to our plans in PNP, it remains our goal to get a broad PNP indication. Our conversations with the FDA at this recent meeting were very productive. They were open-minded, they were very open to ongoing discussions. But it was equally clear that at this time, they do not see a path to PNP. That's just not where they are.

當然可以。薩爾文，請容許我回答這些問題。關於我們在 PNP 方面的計劃，我們的目標仍然是獲得廣泛的 PNP 指示。我們在最近的會議上與 FDA 的對話非常有成效。他們思想開放，非常樂意進行持續的討論。但同樣明顯的是，目前他們還沒有看到通往 PNP 的道路。他們現在的處境並非如此。

However, we have a clear agreement on DPN. So the first order of business for us is to secure the DPN indication, and hence the start of the second DPN study. We can broaden that indication and we had really good conversations on how that could occur.

但是，我們對 DPN 有明確的共識。因此，我們的首要任務是確保 DPN 指示，從而開始第二項 DPN 研究。我們可以擴大這項指示，並且我們就如何實現這一目標進行了非常好的討論。

As you point out, small fiber neuropathy, that could be one -- a broadening of the label. It could be by way of mono or polyneuropathies. It could be by way of distal or proximal. And there are certainly ways in which we can augment that label.

正如您所指出的，小纖維神經病變可能是一種—標籤的擴大。這可能是由於單神經病或多神經病變引起的。它可以通過遠端或近端。當然，我們可以透過一些方法來增強這個標籤。

The real big price for us remains broad PNP. And we think that the way to get there might well be with ongoing conversations with the agency and with our NaV1.7 plus NaV1.8 portfolio.

對我們來說，真正巨大的代價仍然是廣泛的 PNP。我們認為，實現這一目標的方法可能是與該機構進行持續對話，並利用我們的 NaV1.7 和 NaV1.8 產品組合。

So what I would say is here and now, secure DPN, work to broaden the indication and might be one step at a time. SFN is one example of a next indication. And then broaden all the way to PNP as we are able to have more conversations with the agency. Any comments that you want to add to gross to net, Charlie?

所以我現在想說的是，保護 DPN，努力擴大適應症，一步一腳印。SFN 是下一個指示的一個例子。然後擴展到 PNP，因為我們能夠與該機構進行更多對話。查理，你想對總收入與淨收入進行什麼補充嗎？

Yeah, I mean, on gross to net, obviously, it's elevated in the early months of the launch. We had said all along that volume would ramp up ahead of revenue, with the most significant revenue contribution in the second half of the year.

是的，我的意思是，總收入與淨收入之比顯然在推出後的頭幾個月有所上升。我們一直說銷售量的成長會快於營收的成長，其中下半年的營收貢獻最為顯著。

Again, the elevated gross to net in the early days is a result of our patient support programs. As we continue to expand our coverage, those programs will start to fall away, gross to net will normalize over the course of the year. But beyond that, I'm not going to provide further detail.

再次強調，早期總收入與淨收入的上升是我們病患支持計畫的結果。隨著我們繼續擴大覆蓋範圍，這些計劃將開始消失，總額與淨額的比率將在一年內恢復正常。但除此之外，我不會提供更多細節。

Geoff Meacham, Citibank.

花旗銀行的傑夫‧米查姆。

Good afternoon, guys. Thanks for the question. Just have a couple, also on pain. Reshma, I want to ask you about the implications of the FDA feedback and the 993 data. I guess the first question is, could the strategy in chronic pain involve to now include broader indications, such as joint pain, et cetera, in other words, like outside of PNP?

大家下午好。謝謝你的提問。剛吃幾口，也痛。Reshma，我想問您有關 FDA 回饋和 993 數據的含義。我想第一個問題是，慢性疼痛的策略是否可以包括更廣泛的適應症，例如關節痛等，換句話說，就像 PNP 之外的？

And then on 993, do you think it makes sense to look at more of a pan -- 1.8, 1.7 mechanism, at least involving maybe multiple isoforms just to try to maximize the treatment effect? I wasn't sure kind of what the strategy is there from a pipeline perspective. Thank you.

然後對於 993，您是否認為更全面地研究 1.8、1.7 機制是有意義的，至少可能涉及多種亞型以嘗試最大化治療效果？我不確定從管道角度來看那裡的策略是什麼。謝謝。

Sure thing. Let me do chronic pain first, and then we'll come back to 993. Just on chronic pain, I think the approach is, as we just described for the previous question, DPN first, then add on single indications but work with the agency to get to broad PNP. They have -- we've had these discussions. They've left us with some questions we need to talk with each other some more.

當然可以。我先處理慢性疼痛，然後我們再回到 993。就慢性疼痛而言，我認為方法就像我們剛才針對上一個問題所描述的那樣，首先是 DPN，然後添加單一適應症，但與機構合作以獲得廣泛的 PNP。他們——我們已經進行了這些討論。他們給我們留下了一些問題，我們需要進一步討論。

On musculoskeletal, which is, I think, the point you were raising, I do think that this class of compounds can work based on the data that we saw, for example, with VX-150 and osteoarthritic pain, but we're still very focused, first and foremost, on acute and then neuropathic. We will get to the musculoskeletal, but I don't see that in the highest priorities.

關於肌肉骨骼，我想這就是您提出的觀點，根據我們看到的數據，我確實認為這類化合物可以發揮作用，例如 VX-150 和骨關節炎疼痛，但我們仍然非常關注，首先是急性疼痛，然後是神經性疼痛。我們將討論肌肉骨骼問題，但我並不認為這是最優先考慮的事情。

On 993 and what the plan is with regard to acute pain, the big next step for us on acute pain, obviously, launch JOURNAVX. We have our IV formulation with the 993 version, and we now have two potential molecules that could be used with the NaV1.7 molecule that's making very good progress on the bench.

關於 993 以及針對急性疼痛的計劃，我們在急性疼痛方面的下一步重大舉措顯然是推出 JOURNAVX。我們有 993 年版本的 IV 配方，現在我們有兩種潛在分子可以與 NaV1.7 分子一起使用，該分子在實驗室中取得了非常好的進展。

But I would say the big next thing to look for us to do in acute pain is combination NaV1.7, 1.8. Remember, preclinically, what we see is a synergistic, not additive effect. And so that's going to be really important. I hope that helps.

但我想說，我們在急性疼痛治療方面下一步的重點是合併使用NaV1.7和1.8。記住，在臨床前研究中，我們看到的是綜效，而不是疊加效應。所以這真的非常重要。我希望這能有所幫助。

Yeah, thank you.

是的，謝謝。

Sure. Thanks.

當然。謝謝。

Eliana Merle, UBS.

瑞銀的 Eliana Merle。

Hey guys, thanks so much for taking the question. Just two on JOURNAVX me. So just first, can you comment a little bit more on how the progress in the real-world evidence generation is going at some of these key health systems and how you expect that to impact the cadence of P&T formulary placement?

嘿夥計們，非常感謝你們回答這個問題。JOURNAVX 上只有兩個。首先，您能否進一步評論一下這些關鍵醫療系統中真實世界證據生成的進展情況，以及您預計這將如何影響 P&T 處方集的投放節奏？

And then just second, on gross to net. I know you mentioned that there's been use of patient support programs initially in the launch, just what we should expect going forward in terms of the use of the patient support programs as we think about gross to net from here? Thanks.

然後在總淨值比上排名第二。我知道您提到在啟動之初就已經使用了患者支持計劃，那麼當我們考慮從現在開始的總額到淨額時，我們應該對患者支持計劃的使用有何期待？謝謝。

You bet. Ellie, let me take the first half of your question, and I'll ask Duncan to talk to you a little bit about the PSP patient support programs. So formulary coverage, Ellie, is going really well with the hospitals and with the integrated delivery networks. Some extremely -- some very large prominent programs with lots of procedures have added JOURNAVX, frankly, faster than I would have expected, given how long P&T committees normally take.

當然。艾莉，讓我來回答你問題的前半部分，然後我會請鄧肯跟你簡單談談 PSP 患者支援計畫。因此，艾莉，處方集覆蓋範圍與醫院和綜合配送網絡的配合非常好。一些極其——一些擁有大量程序的非常大的著名程序已經添加了 JOURNAVX，坦率地說，考慮到 P&T 委員會通常需要多長時間，添加的速度比我預期的要快。

With regard to evidence generation, I'll speak to a couple of studies that we're running in terms of life cycle management. We have a Phase 4 trial in a variety of let's call it, plastic surgery indications and another one in a variety of orthopedic conditions.

關於證據生成，我將談談我們在生命週期管理方面正在進行的幾項研究。我們對各種整形外科適應症進行了第 4 階段試驗，並針對各種骨科疾病進行了另一項試驗。

And the emerging data look really good not only in terms of pain control, but also in terms of reducing opioid use and having patients go through an opioid free journey, and I expect that you're going to see us presenting those papers in upcoming conferences. Duncan, can I ask you to make a couple of comments on the PSP program?

新出現的數據不僅在疼痛控制方面看起來非常好，而且在減少阿片類藥物的使用和讓患者經歷無阿片類藥物的旅程方面也非常好，我希望你會在即將召開的會議上看到我們發表這些論文。鄧肯，我可以請你對 PSP 計劃發表一些評論嗎？

Yeah, sure. So just to step back, we put in the PSP program in place in order to provide a seamless experience for patients in advance of payer coverage. And as we noted in our prepared remarks and what Charlie commented on a couple of minutes ago, as we see our coverage with payers increasing over the course of this year, that program becomes unnecessary.

是的，當然。因此，退一步來說，我們實施 PSP 計劃是為了在付款人承保之前為患者提供無縫體驗。正如我們在準備好的發言中以及查理幾分鐘前所評論的那樣，隨著我們看到今年我們的付款覆蓋範圍不斷擴大，該計劃變得不再必要。

And essentially, we will retire that program as we see national coverage. Obviously, we're not quite at that point yet. But that is the plan by the end of the year is to conclude that program. And as Charlie alluded to earlier, I don't think we're providing specific growth to that guidance with regard to that program.

從本質上講，當我們看到全國覆蓋後，我們就會停止該計劃。顯然，我們還沒有到達那個地步。但計劃是在年底前完成該計劃。正如查理之前提到的，我認為我們並沒有針對該計劃提供具體的成長指導。

Got it. Thanks.

知道了。謝謝。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

Hi guys. Maybe to switch the subjects up a little bit. Can I ask a couple on pove? Is it your plan to launch with the auto-injector when you go live on IgAN?

嗨，大家好。也許可以稍微轉換一下話題。我可以問一對夫婦關於 pove 的問題嗎？當您在 IgAN 上線時，您是否計劃使用自動注射器？

And then in terms of the indications that you're prioritizing on a go-forward basis, you've included GMG. I'm just curious about where you think you could particularly differentiate given that it seems like that's a pretty credit market already? Thanks.

然後，就您在前進的道路上優先考慮的跡象而言，您已經將 GMG 納入其中。我只是好奇，鑑於這似乎已經是一個信貸市場，您認為您可以特別在哪裡實現差異化？謝謝。

Yeah. Tazeen, on pove, you have it exactly right. We plan to launch in the IgAN indication, which, of course, is the first indication with the autoinjector. And just to confirm, GMG, you mean myasthenia, not membranous?

是的。Tazeen，關於 pove，你說得完全正確。我們計劃推出 IgAN 適應症，當然是自動注射器的第一個適應症。只是為了確認一下，GMG，你的意思是重症肌無力，而不是膜性肌無力？

Yeah, that's correct.

是的，沒錯。

Yeah. The myasthenia indication is very exciting for us, and it is one of the ones that we've prioritized. Maybe four lines of reasoning to share with you. The first is there remains a very high unmet need in this area. We don't have any medicines that target the underlying cause of disease.

是的。重症肌無力的適應症對我們來說非常令人興奮，它是我們優先考慮的適應症之一。也許有四個理由可以與你們分享。首先，該領域仍有大量未滿足的需求。我們沒有任何針對疾病根本原因的藥物。

And as you know, some of the medicines being used need to be cycled on and cycled off. And in the off period, that gives the opportunity for the auto antibodies to redevelop and call -- continue to cause damage at the junction.

如您所知，某些正在使用的藥物需要循環使用和停用。在關閉期間，這為自身抗體的重新開發和調用提供了機會——繼續在連接處造成損害。

The pove mechanism is a dual APRIL BAFF inhibition, i.e., it dampens down the B cells, both the earlier B cells and the plasma cells, which is, of course, the underlying cause of myasthenia.

可能的機制是雙重 APRIL BAFF 抑制，即抑制 B 細胞（早期 B 細胞和漿細胞），這當然是重症肌無力的根本原因。

The second is emerging data in this class is a very appealing and a point to a strong treatment effect. The third is that I expect that the regulatory pathway is going to be an efficient development pathway.

第二，此類新興數據非常有吸引力，並且具有強烈的治療效果。第三，我預期監理路徑將會是一條高效率的發展路徑。

And the last is, as you put all of this together and you think about the underlying cause of disease, high unmet need, the emerging data from others in this class and then you think about the fact that pove was specifically engineered to have best-in-class properties in terms of potency, binding affinity as well as tissue distribution. This is why we're so excited about myasthenia.

最後，當你把所有這些放在一起，思考疾病的根本原因、未滿足的巨大需求、來自同類其他人的新數據，然後思考這樣一個事實：pove 是經過特殊設計的，在效力、結合親和力以及組織分佈方面具有一流的特性。這就是我們對重症肌無力如此興奮的原因。

Evan Seigerman, BMO Capital Markets.

埃文·塞格曼 (Evan Seigerman)，BMO 資本市場。

Hi guys. Thank you so much for taking my question. Another follow-up kind of on the pipeline and the product for pove. Can you kind of walk me through the rationale for prioritizing the indications such as GMG, warm -- autoimmune hemolytic anemia, of course, IgAN. Was it clinical data? Early data, kind of preclinically or commercial considerations that drove these decisions?

嗨，大家好。非常感謝您回答我的問題。關於 pove 的管道和產品的另一個後續行動。您能否向我解釋一下優先考慮 GMG、溫 - 自體免疫溶血性貧血以及 IgAN 等適應症的理由。是臨床數據嗎？早期數據、臨床前或商業考慮促使了這些決定？

Yeah, Evan, this is Reshma. Let me take that one for you. All of the above. So as you know, RUBY-3 and RUBY-4 give us good insight into a basket of renal indications and the basket of heme indications. And we have emerging data, for example, in membraneous, which points us to best-in-class potential in that disease, which has no other treatment and it gives us an indication of best-in-class potential for wAIHA or warm autoimmune hemolytic anemia.

是的，艾文，這是雷什瑪。讓我幫你拿那個。上述所有的。如你所知，RUBY-3 和 RUBY-4 讓我們對一籃子腎臟適應症和一籃血紅素適應症有了很好的了解。例如，在膜性貧血方面，我們擁有新興數據，這些數據表明該藥物在該疾病方面具有最佳潛力，目前尚無其他治療方法，並且表明該藥物在 wAIHA 或溫自身免疫性溶血性貧血方面具有最佳潛力。

So it is indeed emerging data from our own data sets. Sometimes as in the case with myasthenia, it's emerging data from the class, taking into account that pove has this benefit of being engineered to be best-in-class. So there's the emerging data.

所以它確實是來自我們自己的數據集的新興數據。有時就像重症肌無力的情況一樣，它是來自該類別的新數據，考慮到 pove 具有被設計為同類最佳的優勢。這就是新出現的數據。

There is also consideration given what exists in the marketplace and whether it treats the underlying cause of disease and whether we have a transformative medicine and certainly takes into account our ability to be successful commercially.

我們也要考慮市面上現有的產品，以及它是否能夠治療疾病的根本原因，以及我們是否擁有變革性的藥物，當然也要考慮我們在商業上取得成功的能力。

All of those have gotten into us prioritizing IgAN membranes, myasthenia and wAIHA. And just to close out on that, prioritizing from for myasthenia means we are ready to go to the agency to have our discussion on what the pivotal program looks like and prioritizing for wAIHA means we are awaiting a final data set we expect towards the end of this year. I hope that helps.

所有這些都促使我們優先考慮 IgAN 膜、重症肌無力和 wAIHA。最後，對重症肌無力進行優先排序意味著我們已準備好與機構討論關鍵項目的具體內容，而對 wAIHA 進行優先排序意味著我們正在等待預計在今年年底前獲得的最終數據集。我希望這能有所幫助。

Great, thank you.

太好了，謝謝。

You bet.

當然。

Divya Rao, Cowen and Company.

Divya Rao，Cowen and Company。

Hi, this is Divya on for Phil. I just had two questions on JOURNAVX. One is just got a little bit technical, but I was curious for patients that are getting free samples, if they are to show up at a retail pharmacy, I was curious if you could walk me through the protocol for how they actually are able to secure the free drug?

大家好，我是 Divya，為 Phil 服務。我剛剛對 JOURNAVX 有兩個疑問。其中一個問題有點技術性，但我很好奇，對於那些獲得免費樣品的患者，如果他們出現在零售藥店，您是否可以向我介紹他們如何實際獲得免費藥物的協議？

And then second is, I was curious if you could comment on the split of JOURNAVX scripts and how much are coming from maybe retail pharmacies versus hospitals? And any insights into the type of physicians prescribing JOURNAVX? Thank you.

第二，我很好奇您是否可以評論一下 JOURNAVX 處方的分配情況，以及有多少來自零售藥局，有多少來自醫院？對開出 JOURNAVX 處方的醫生類型有什麼見解嗎？謝謝。

You bet. Duncan, can I ask you to comment first, maybe quickly on how free samples work? And then a little bit more detail on physician types and split between hospital and retail.

當然。鄧肯，我可以請你先快速評論一下免費樣品的工作原理嗎？然後更詳細地介紹醫生類型以及醫院和零售店之間的劃分。

Absolutely. Thank you for the question. So in terms of the free samples, these are provided through the patient's physician, they're supplied to the patient by the physician, and they do not show up in the retail data.

絕對地。謝謝你的提問。因此，就免費樣品而言，這些都是透過患者的醫生提供的，由醫生提供給患者，並且不會出現在零售數據中。

In terms of the split of retail versus hospital prescriptions, about 65% of the prescriptions in the weekly IQVIA data that you see for retail prescriptions, the remainder are in the hospital space. And in terms of the types of physicians using JOURNAVX, it is a broad range. It's about 15,000 physicians are now prescribing JOURNAVX.

就零售處方和醫院處方的劃分而言，每週 IQVIA 數據中約 65% 的處方來自零售處方，其餘的則來自醫院。而就使用 JOURNAVX 的醫師類型而言，範圍很廣。目前約有 15,000 名醫生正在開立 JOURNAVX 處方。

We're seeing many more patients -- sorry, physicians, hundreds of physicians come on each week. And the types of physicians are general surgeons, plastic surgeons, orthopedic surgeons, dentists and anesthesiologists. And they are prescribing for a broad range of treatments consistent with the label, everything from sprains and strains through reconstructive surgery to total knee replacements.

我們接待了越來越多的病人——對不起，是醫生，每周有數百名醫生來就診。醫生的類型包括一般外科醫生、整形外科醫生、骨科醫生、牙醫和麻醉師。他們開出的處方符合標籤上的各種治療方案，從扭傷和拉傷到重建手術，再到全膝關節置換術。

David Risinger, Leerink Partners.

Leerink Partners 的 David Risinger。

Yes, thanks very much. So I have two questions, please. First, on JOURNAVX, I was wondering if you could comment on the number of commercial lives with unrestricted access?

是的，非常感謝。我有兩個問題。首先，關於 JOURNAVX，我想知道您是否可以評論一下不受限制訪問的商業生活的數量？

And then second, with respect to VX-828, could you please provide a little bit more color on your expectations for the profile of this candidate? Thanks very much.

其次，關於 VX-828，您能否更詳細地說明您對這位候選人的期望？非常感謝。

First thing, Dave, let me take the 828 question, and then I'll ask Duncan to comment on JOURNAVX. So 828, as said in my prepared remarks, it is the most efficacious CFTR corrector that we've ever studied in vitro that we've advanced into the clinic.

首先，戴夫，讓我來回答第 828 個問題，然後我會請鄧肯對 JOURNAVX 進行評論。因此，正如我在準備好的演講中所說，828 是我們迄今為止在體外研究並已進入臨床的最有效的 CFTR 校正劑。

I expect that it is going to have most, if not all, patients get to carrier levels of sweat chloride. I expect a good safety profile. I expect a good DDI profile based on the preclinical data. To wrap up on 828, we do continue to track towards initiating the CF cohort before the end of this year. Duncan, JOURNAVX?

我預計，即使不是全部，大多數患者的汗液氯化物也能達到載體水平。我期望有良好的安全性。我希望根據臨床前數據獲得良好的 DDI 概況。為了完成 828 計劃，我們將繼續努力在今年年底前啟動 CF 隊列。鄧肯，JOURNAVX？

Yeah, thank you for the question, David. So obviously, we are extremely pleased with the 150 million lives covered in just a few months. To get to the answer to your question, that 84 million of those lives are unrestricted.

是的，謝謝你的提問，大衛。顯然，我們對短短幾個月內覆蓋 1.5 億人的生命感到非常高興。回答你的問題，其中 8400 萬人的生活不受限制。

I can tell you that for every single contract we have negotiated to date, every single one of those is for unrestricted access, which we define, as you know, as no prior authorization or step edit. So what that means, of course, is that based on high demand for JOURNAVX, there are, of course, some plans that have put in place coverage of JOURNAVX in advance of any agreement with us.

我可以告訴你，迄今為止我們談判的每一份合約都是無限制訪問的，正如你所知，我們將其定義為無需事先授權或步驟編輯。所以，這當然意味著，基於對 JOURNAVX 的高需求，當然有一些計劃在與我們達成任何協議之前就已經對 JOURNAVX 進行了覆蓋。

And in those situations, there can be a prior authorization or step edit. Obviously, we'll be working to reduce that ratio over the balance of the year. But at this point, 150 million lives covered, two out of the three PBMs are covering, and we're working with the third, as you'd expect. And every single agreement we have done is for unrestricted access.

在這些情況下，可以進行事先授權或逐步編輯。顯然，我們將努力在今年內降低這一比例。但目前，我們已經涵蓋了 1.5 億人的生命，三個 PBM 中有兩個正在覆蓋，而且正如您所期望的那樣，我們正在與第三個 PBM 合作。我們達成的每一項協議都是為了不受限制的訪問。

William Pickering, Bernstein.

威廉‧皮克林，伯恩斯坦。

Hi, thank you very much for taking my question. Just a couple from me. One was on the NOPAIN Act. I was a little bit surprised to see that JOURNAVX was not included in the draft rule that was published. I guess, was it about a month ago? And any kind of concerns or kind of process to get that on the list for 2026?

您好，非常感謝您回答我的問題。距離我只有幾對。其中一項是關於 NOPAIN 法案。我有點驚訝地看到 JOURNAVX 並未被列入已發布的規則草案中。我猜，大概就是一個月前吧？為了將其列入 2026 年名單，有哪些顧慮或流程？

And then second was with CASGEVY, just -- what are you seeing in terms of the cycle time from cell collection to infusion? And do you see potential for that to accelerate going forward? Thank you.

其次是 CASGEVY，您看到從細胞收集到輸注的週期時間是怎麼樣的？您是否認為這趨勢未來有加速發展的潛力？謝謝。

Sure thing. Well, let's do CASGEVY first. As you heard Duncan talk to his prepared remarks, we are seeing an acceleration in the momentum. And part of that is simply having patients at various points in their journey. So there are a lot more patients who now had self-collected and ready to be infused, and that's what we're looking forward to in the back half of this year.

當然可以。好吧，我們先做 CASGEVY。正如你們聽到鄧肯發表他準備好的演講時所說，我們看到了這種勢頭的加速。其中一部分就是簡單地在患者旅程的各個階段接待他們。因此，現在有更多的患者已經自行採集血液並準備輸注，這就是我們在今年下半年所期待的。

With regard to cycle time, yes, I do think that there is opportunity for improvement. I'd say -- I think we said it was going to be somewhere around four to five months for the full process. And that's kind of where we see it.

關於週期時間，是的，我確實認為還有改進的機會。我想說──我想我們說過整個過程大約需要四到五個月的時間。這就是我們所看到的。

Of course, it makes a difference if the patient is a TDT patient or if the patient is a sickle cell disease patient, easier for cell collection with our TDT patients. We have plans in place to ensure that the cycle time comes down as we make progress overall.

當然，如果患者是 TDT 患者或鐮狀細胞疾病患者，情況會有所不同，我們的 TDT 患者更容易收集細胞。我們已製定計劃，以確保在整體取得進展的同時縮短週期時間。

On the NOPAIN Act, so you know that the draft proposal included some language that says that because JOURNAVX is not specifically indicated for postsurgical pain, it was not included on the draft list. Clearly, JOURNAVX is indicated for postsurgical pain.

關於 NOPAIN 法案，您知道提案草案中包含一些語言，其中指出由於 JOURNAVX 並非專門用於治療術後疼痛，因此未列入草案名單。顯然，JOURNAVX 適用於治療術後疼痛。

Indeed, both Phase 3 RCTs were in postsurgical pain, one in abdominoplasty, one in bunionectomy. I think we're going to be able to get this confusion resolved. And I do expect that JOURNAVX will be on the final list, which is due this fall.

事實上，兩項 3 期 RCT 均涉及術後疼痛，一項涉及腹部整形術，另一項涉及拇囊切除術。我認為我們能夠解決這個困惑。我確實希望 JOURNAVX 能夠出現在今年秋季公佈的最終名單上。

Terence Flynn, Morgan Stanley.

摩根士丹利的特倫斯弗林。

Great. Thanks so much for taking the question. Just wondering -- two questions. The first is on JOURNAVX. If you can just confirm if there's any inventory in the second quarter that we need to think about as we do the math on a dollar per script basis?

偉大的。非常感謝您回答這個問題。只是想知道——兩個問題。第一個是在 JOURNAVX 上。當我們按每部劇本的美元金額進行計算時，您是否可以確認第二季是否有任何庫存需要我們考慮？

And then on the 993 Phase 2 data. Just wondering if you think you need to make any tweaks to the preclinical models at all here, given that data and particularly as you think about the NaV1.7 assets that you're developing? Thank you.

然後是 993 第二階段的數據。只是想知道，考慮到這些數據，特別是考慮到您正在開發的 NaV1.7 資產，您是否認為需要對這裡的臨床前模型進行任何調整？謝謝。

Terence, could you just maybe rephrase the first part of your question? We didn't quite get it here.

特倫斯，您能否重新表達問題的第一部分？我們還沒完全明白。

Yeah. Sorry. Was there any inventory in 2Q for JOURNAVX?

是的。對不起。JOURNAVX 第二季有庫存嗎？

Terence, on JOURNAVX, you know the buying patterns for hospitals are variable. So we see the normal variability for buying patterns in hospital, but no inventory to speak of. On 993, this is a really important question you asked about how did our preclinical models perform.

特倫斯，在 JOURNAVX 上，您知道醫院的購買模式是多樣化的。因此，我們看到醫院的購買模式正常變化，但沒有庫存可言。在 993 上，您問的一個非常重要的問題是我們臨床前模型的表現如何。

So the reason it was really important for us to do the 993 study and go up to the dose levels we did and to ensure that in this study, we saw good dose separation between the low, medium and high dose is exactly to do what you were referencing to make sure that our models are properly trained.

因此，對於我們來說，進行 993 研究並提高劑量水平，並確保在這項研究中看到低、中、高劑量之間良好的劑量分離，這一點非常重要，這正是您所提到的，以確保我們的模型得到適當的訓練。

And what we saw with 993 coming into the Phase 2 study is a molecule that was predicted to be more potent, a molecule that we could dose higher, and the exposures are very, very high. So our models would predict this is at the 99.999% to the EC50.

我們看到，進入第 2 階段研究的 993 分子被預測會更有效，我們可以使用其更高的劑量，而且暴露量非常非常高。因此我們的模型預測這是 EC50 的 99.999%。

So multi, multifold, the EC50 levels. And what we learned from this is we do indeed get very high exposures. And we do indeed get separation of exposures of the mid and high dose. Nonetheless, the efficacy for the medium and high dose, as you can see in the press release, is about the same. Different than low dose, but the same to each other.

EC50 水準有多種多樣。我們從中了解到，我們確實獲得了非常高的曝光率。我們確實將中劑量和高劑量的暴露分開了。儘管如此，正如您在新聞稿中所看到的，中劑量和高劑量的療效大致相同。與低劑量不同，但彼此相同。

And this is what lets us know that now we are at the very high end of the dose response curve. And we know that our this medicine is not likely to be superior to our existing molecules. So this is a very important Phase 2 result, and that's why we are pleased to have completed the study and to have gained this information. We are now able to be at the leading edge with our models.

這讓我們知道，現在我們正處於劑量反應曲線的最高端。我們知道，我們的這種藥物不太可能優於我們現有的分子。所以這是非常重要的第二階段結果，這就是我們很高興完成這項研究並獲得這些資訊的原因。現在，我們的模型已經能夠處於領先地位。

Nick, we'll take one more question. Please.

尼克，我們再回答一個問題。請。

Mohit Bansal, Wells Fargo.

富國銀行的 Mohit Bansal。

Great, thank you very much for taking my question. Just wanted to check in on the most [severed nation] and the latter government has sent out here. Given that your exposure to Medicaid, do you see any risk there? I mean you could be protected because of the orphan disease, but just wanted to make sure it is not on the cards. Thank you.

太好了，非常感謝您回答我的問題。只是想檢查一下受災最嚴重的國家以及後者政府派人來這裡的情況。鑑於您接觸醫療補助，您認為其中有任何風險嗎？我的意思是，你可以因為孤兒病而受到保護，但我只是想確保它不會發生。謝謝。

Mohit, we have not received a letter. The lines of communication are open. We are able to have good dialogue with DC, and we're paying close attention and digesting the latest news. But I can confirm that we did not receive a letter.

Mohit，我們還沒收到信。溝通管道是暢通的。我們能夠與 DC 進行良好的對話，並且我們正在密切關注和消化最新消息。但我可以確認我們沒有收到信。

Got it. Thank you.

知道了。謝謝。

This will conclude our question-and-answer session as well as conference call. Thank you all 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 the replay code 741-7417. Thank you.

我們的問答環節和電話會議將結束。感謝大家參加今天的演講。通話結束後不久，撥打 1-877-344-7529 或 1-412-317-0088（重播代碼 741-7417）即可收聽今天活動的重播。謝謝。