福泰製藥 (VRTX) 2024 Q2 法說會逐字稿

Good day, and welcome to the Vertex Pharmaceuticals' second-quarter 2024 earnings call. (Operator Instructions)

美好的一天，歡迎參加 Vertex Pharmaceuticals 的 2024 年第二季財報電話會議。（操作員說明）

Please note this event is being recorded. I would now like to turn the conference over to Ms. Susie Lisa. Pease go ahead.

請注意此事件正在被記錄。現在我想把會議交給蘇西·麗莎女士。皮斯繼續前進。

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 2024 financial results conference call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President, Stuart Arbuckle, Chief Operating Officer; and Charlie Wagner, Chief Financial Officer.

大家晚上好。我叫 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 2024 年第二季財務績效電話會議。在今晚的電話會議上，我們有福泰 (Vertex) 執行長兼總裁 Reshma Kewalramani 博士、營運長 Stuart Arbuckle 發表事先準備好的演講。和財務長查理·瓦格納。

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 be making forward-looking statements on this call that are subject to the risks and uncertainties discussed in today's press release and in our filings with the Securities and Exchange Commission.

我們建議您在收聽本次電話會議時存取網路廣播投影片。通話正在錄音，我們的網站上將提供重播。我們將在本次電話會議中做出前瞻性聲明，這些聲明受到今天的新聞稿以及我們向美國證券交易委員會提交的文件中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, and beta thalassemia; our pipeline, including the potential near-term launches of the vanzacaftor triple in CF and suzetrigine in moderate-to-severe acute pain; and Vertex's future financial performance are based on management's current assumptions. Actual outcomes and events could differ materially.

這些聲明，包括但不限於有關福泰 (Vertex) 上市的囊性纖維化、鐮狀細胞疾病和 β 地中海貧血藥物的聲明；我們的產品線，包括近期可能推出治療 CF 的 vanzacaftor 三聯藥和治療中度至重度急性疼痛的 Suzetrigine；祥峰未來的財務表現是基於管理層目前的假設。實際結果和事件可能存在重大差異。

I would also note that the select financial results and guidance that we will review on the call this evening are presented on a GAAP basis. I will now turn the call over to Reshma.

我還想指出，我們將在今晚的電話會議上審查的選定財務表現和指導是根據公認會計原則（GAAP）提出的。我現在將把電話轉給雷什瑪。

Thanks, Susie. Good evening, all, and thank you for joining us on the call today. We've continued our momentum from Q1 with another quarter of excellent performance across the board, including outstanding commercial execution in both CF and the early launch of CASGEVY, our preparedness for the potential near-term launches of the vanzacaftor in CF and suzetrigine in acute pain, as well as the rapid advancement of our broad and deep pipeline.

謝謝，蘇西。大家晚上好，感謝您今天加入我們的電話會議。我們延續了第一季的勢頭，又一個季度取得了全面的出色表現，包括CF 的出色商業執行力和CASGEVY 的早期推出，我們為近期可能推出CF 中的vanzacaftor 和急性期的Suzetrigine 做好了準備。

In CF, we continue to reach more patients, deliver $2.65 billion in revenue in Q2. And based on this result and our outlook, we are increasing our full year product revenue guidance to $10.65 billion to $10.85 billion, which at point represents 9% growth versus 2023.

在 CF 領域，我們持續覆蓋更多患者，第二季營收達到 26.5 億美元。根據這項結果和我們的展望，我們將全年產品收入指引提高至 106.5 億美元至 108.5 億美元，目前較 2023 年成長 9%。

In sickle cell disease and beta thalassemia, we are pleased with the reception from patients, physicians and payers as we continue the ongoing launch of CASGEVY to bring this potentially transformative medicine to patients across multiple regions.

在鐮狀細胞疾病和β地中海貧血方面，我們對患者、醫生和付款人的反應感到滿意，我們將繼續推出 CASGEVY，將這種潛在的變革性藥物帶給多個地區的患者。

And we are very excited about the multiple near-term opportunities to reach more patients and deliver additional revenue growth from our programs that have completed pivotal development, including the completion and acceptance of two significant regulatory submissions. The vanzacaftor triple-in patients with cystic fibrosis six years and older, which has been given priority review designation and VX-548 or suzetrigine in moderate to severe acute pain, which has also been granted priority review by the FDA.

我們對多個近期機會感到非常興奮，這些機會可以接觸到更多患者，並從我們已完成關鍵開發的專案中帶來額外的收入成長，包括完成並接受兩項重要的監管申請。vanzacaftor適用於六歲以上囊性纖維化患者，已獲得優先審查資格，VX-548或suzetrigine用於治療中度至重度急性疼痛，也已獲得FDA優先審查。

Lastly, on the mid and late-stage pipeline, I am very pleased with our continued rapid progress. I'll call out three specific programs. First, the suzetrigine-LSR Phase II study has significantly accelerated, and we now expect Phase II results by the end of this year.

最後，在中後期管道方面，我對我們持續快速的進展感到非常高興。我將提出三個具體計劃。首先，suzetrigine-LSR II 期研究已顯著加快，我們現在預計 II 期結果將在今年年底獲得。

Second, in the VX-880 Phase I trial in type 1 diabetes, we have completed enrollment and dosing in the original 17-patient study, and we have secured regulatory endorsement to expand the study to 37 patients in total as we advance towards pivotal development. And third, in the povetacicept program, having completed successful Phase II regulatory meetings, we will initiate thes Phase III pivotal trial in IgA Nephropathy later this month.

其次，在針對1 型糖尿病的VX-880 I 期試驗中，我們已經完成了最初17 名患者研究的入組和給藥，並且隨著我們向關鍵開發邁進，我們已獲得監管部門的認可，將研究範圍擴大到總共37 名患者。第三，在 povetacicept 計畫中，在成功完成 II 期監管會議後，我們將於本月稍後啟動 IgA 腎病的 III 期關鍵試驗。

With those highlights, let me now turn to an R&D review, limiting my comments this quarter to the programs with the most significant update cystic fibrosis, pain, type 1 diabetes and IgA Nephropathy.

有了這些重點，現在讓我轉向研發審查，將本季的評論限制在囊性纖維化、疼痛、1 型糖尿病和 IgA 腎病方面最重要更新的項目上。

Starting with CF. We are very pleased with the Phase III results on the vanzacaftor triple program we announced in early February as we continue to drive towards our ultimate of bringing all eligible patients to carrier levels, indeed to normal levels of CFTR function as measured by sweat chloride.

從CF開始。我們對2 月初宣布的vanzacaftor 三重計畫的III 期結果感到非常滿意，因為我們將繼續努力實現最終目標，使所有符合條件的患者達到攜帶者水平，實際上達到透過汗液氯化物測量的CFTR 功能的正常水平。

The vanzacaftor triple demonstrated an even greater reduction in sweat chloride than TRIKAFTA, a very high bar to have crested. And thus sets the stage for the potential to have a new standard in the treatment of CF. The vanzacaftor triple also offers the convenience of once the dosing and a substantially lower royalty burden.

vanzacaftor 三元組比 TRIKAFTA 更能減少汗液氯化物，這是一個非常高的目標。從而為 CF 治療的新標準奠定了基礎。vanzacaftor 三聯還提供一次性給藥的便利性和大幅降低的特許權使用費負擔。

With regard to the Vanza global regulatory submissions, in addition to the US acceptance, our filings have also validated by the EMA in the EU and the MHRA in the UK. With regard to VX-522, our CFTR mRNA therapy in development with our partners at Moderna, it has completed the single ascending dose portion of the Phase I/II study and continues in the multiple ascending dose portion.

關於 Vanza 全球監管申請，除了美國接受外，我們的申請還獲得了歐盟 EMA 和英國 MHRA 的驗證。至於 VX-522，我們與 Moderna 的合作夥伴正在開發 CFTR mRNA 療法，它已經完成了 I/II 期研究的單次劑量遞增部分，並繼續進行多次劑量遞增部分。

As a reminder, VX-522 seeks to provide treatment for the more than 5,000 people with, CF who do not make any CFTR protein and therefore, cannot benefit from CFTR modulators. Based on the pace of enrollment and study dynamics, our current expectation is to complete the study and share both efficacy and safety results from the study in the first half of 2025.

提醒一下，VX-522 旨在為超過 5,000 名 CF 患者提供治療，他們不會產生任何 CFTR 蛋白，因此無法從 CFTR 調節劑中受益。根據入組進度和研究動態，我們目前的預期是在 2025 年上半年完成研究並分享研究的有效性和安全性結果。

Moving now to the pain program and our portfolio of novel, highly selective NaV1.8 and NaV1.7 pain signal inhibitors. In acute pain, a few points to highlight. First, we are very pleased that the suzetrigine submission has been accepted and granted priority review by the FDA with the PDUFA target action date of January 30, 2025.

現在轉向疼痛項目和我們的新型、高選擇性 NaV1.8 和 NaV1.7 疼痛訊號抑制劑產品組合。對於急性疼痛，有幾點需要強調。首先，我們非常高興 Suzetrigine 提交的申請已被 FDA 接受並授予優先審查資格，PDUFA 目標行動日期為 2025 年 1 月 30 日。

Second, our next class NaV1.8 pain signal inhibitor, VX-993 is in the clinic in a Phase I trial with the IV formulation and is currently enrolling and dosing healthy volunteers. Third, VX-993 will soon enter Phase II study with the formulation in acute pain following bunionectomy surgery. This study is on track to begin later this quarter.

其次，我們的下一類 NaV1.8 疼痛訊號抑制劑 VX-993 正在臨床上進行 IV 製劑的 I 期試驗，目前正在招募健康志願者並給予健康。第三，VX-993很快就會進入II期研究，該配方用於治療拇囊炎切除術後的急性疼痛。這項研究預計將於本季晚些時候開始。

And lastly, we continue to make strong progress pre-clinically on NaV1.7 pain signal inhibitor program that may be used alone or in combination with NaV1.8 inhibitors. Just as an again, we have multiple programs moving rapidly development in peripheral neuropathic pain or PNP, starting with painful lumbosacral radiculopathy or LSR, a condition that impacts more than 4 million Americans. There is a high unmet need in LSR. In the US there are no medicines approved specifically for the treatment of pain from LSR.

最後，我們繼續在 NaV1.7 疼痛訊號抑制劑計畫的臨床前取得重大進展，該計畫可單獨使用或與 NaV1.8 抑制劑聯合使用。再說一次，我們有多個治療週邊神經性疼痛 (PNP) 的項目正在快速發展，首先是疼痛性腰骶神經根病變 (LSR)，這種疾病影響了超過 400 萬美國人。LSR 的需求尚未滿足。在美國，沒有專門批准用於治療 LSR 疼痛的藥物。

As mentioned in my opening remarks, the pace of enrollment in this study has been rapid and significantly exceeded our projections. Study enrollment is now complete, and we anticipate sharing Phase II LSR results by the end of this year. Also in peripheral neuropathic pain, we are excited to begin the phase III pivotal program for suzetrigine in painful diabetic peripheral neuropathy, or DPN, later this quarter.

正如我在開場白中提到的，這項研究的招生速度很快，大大超出了我們的預測。研究註冊現已完成，我們預計在今年年底前分享 II 期 LSR 結果。同樣在周邊神經病理性疼痛方面，我們很高興將於本季度晚些時候開始 Suzetrigine 治療疼痛性糖尿病週邊神經病變 (DPN) 的 III 期關鍵計劃。

The DPN pivotal program consists of two identical randomized controlled trials of approximately 1,100 patients each, with suzetrigine at a dose of 70 milligrams once daily and evaluating the change from baseline to week 12 in NPRS pain scores relative to placebo.

DPN 關鍵計畫由兩項相同的隨機對照試驗組成，每項試驗約 1,100 名患者，使用劑量為 70 毫克的 Suzetrigine，每天一次，並評估 NPRS 疼痛評分相對於安慰劑從基線到第 12 週的變化。

The RCTs also include an active comparator arm of pregabalin. A key secondary endpoint is changed from baseline at week 12 in NPRS score, for suzetrigine versus pregabalin assessed for non-inferiority. And if we meet non-inferiority, then we will test for superiority versus pregabalin.

隨機對照試驗也包括普瑞巴林的活性比較組。關鍵的次要終點在第 12 週時 NPRS 評分較基線變化，評估了舒三嗪與普瑞巴林的非劣效性。如果我們滿足非劣效性，那麼我們將測試相對於普瑞巴林的優越性。

Lastly, in PNP, I am pleased to share that we will soon initiate a Phase II study with the oral formulation of VX-993 in diabetic peripheral neuropathy, designed similarly to the suzetrigine Phase II DPN study, this trial is also on track to begin this quarter.

最後，在 PNP，我很高興地告訴大家，我們很快就會啟動一項 VX-993 口服製劑治療糖尿病週邊神經病變的 II 期研究，其設計類似於 Suzetrigine II 期 DPN 研究，該試驗也有望開始本季度。

Turning now to type 1 diabetes. VX-880s are stem cell derived fully differentiated islet cell therapy for people with T1D, an impaired hypoglycemic awareness who experience severe hypoglycemic events despite optimal medical care.

現在轉向第 1 型糖尿病。VX-880 是乾細胞衍生的完全分化胰島細胞療法，適用於1 型糖尿病(T1D) 患者，這種患者的低血糖意識受損，儘管接受了最佳的醫療護理，但仍經歷嚴重的低血糖事件。

At the ADA meeting in June, an oral presentation from the ongoing Phase I/II study included updated data with more patients and longer duration of follow-up and continue to demonstrate the potential of VX-880 as a functional cure for patients with T1D. The data reflected 12 patients from parts B and C of the study who received a full dose of VX-880 as a single infusion and had at least three months of follow-up.

在 6 月的 ADA 會議上，正在進行的 I/II 期研究的口頭報告包括更多患者和更長隨訪時間的更新數據，並繼續證明 VX-880 作為功能性治癒 T1D 患者的潛力。數據反映了該研究 B 部分和 C 部分的 12 名患者，他們單次輸注接受全劑量的 VX-880，並進行了至少三個月的隨訪。

The results are remarkable. Specifically, all patients demonstrated islet cell engraftment and glucose responsive insulin production by day 90. All 12 patients achieved hemoglobin A1c levels less than 7% and all 12 patients also had a time in range for glucose levels of 70% or greater. 11 of the 12 patients greatly reduced or completely eliminated exogenous insulin use.

結果是顯著的。具體來說，所有患者在第 90 天時均表現出胰島細胞移植和葡萄糖反應性胰島素產生。所有 12 名患者的糖化血紅素水平均低於 7%，所有 12 名患者的血糖值也曾一度達到 70% 或更高。 12 名患者中有 11 名大大減少或完全消除了外源性胰島素的使用。

And the three patients with 12 months of follow-up and therefore, evaluable primary end point, each met the primary endpoint of elimination of severe hypoglycemic events, hemoglobin A1c level below 7 as well as the secondary endpoint of insulin independence.

因此，這三名患者經過 12 個月的隨訪，可評估主要終點，均達到了消除嚴重低血糖事件、血紅蛋白 A1c 水平低於 7 的主要終點以及胰島素獨立性的次要終點。

With these results, we are planning forward towards the next phase of development for VX-880. To that end, we are very pleased to have secured regulatory approval to expand the original 17 patient study, which is fully enrolled and dosed to include an additional 20 participants. We look forward to continuing the work with regulators to finalize the requirements for pivotal development and updating you on those discussions.

有了這些結果，我們正在規劃 VX-880 的下一階段開發。為此，我們非常高興獲得監管部門批准擴大最初的 17 名患者研究，該研究已全部入組並增加了 20 名參與者。我們期待繼續與監管機構合作，最終確定關鍵開發的要求，並向您通報這些討論的最新情況。

Beyond VX-880, our cells plus device, or VX-264 program encapsulates the same VX-880 cells in a proprietary device designed to eliminate the need for immunosuppressants. VX-264 is in a Phase I/II multi-part global study.

除了 VX-880 之外，我們的細胞加設備或 VX-264 計畫將相同的 VX-880 細胞封裝在專有設備中，旨在消除對免疫抑制劑的需求。VX-264 正在進行 I/II 期多部分全球研究。

We have completed part A of the study at an initial dose with the stagger between patients. We are currently enrolling and dosing patients in part B, which is at the full target dose, also with the stagger between patients.

我們已經完成了研究的 A 部分，初始劑量是患者之間的錯開劑量。我們目前正在 B 部分中招募患者並對其進行給藥，該部分是完全目標劑量，患者之間也是錯開的。

As a reminder, part C of the trial is at the full target dose with no stagger between patients. The last major R&D update pertains to povetacicept, the lead at from our recently closed acquisition of Alpine Immune Sciences, where our enthusiasm for the acquisition and pove remains high.

提醒一下，試驗的 C 部分是在完全目標劑量下進行的，患者之間沒有交錯。最後的重大研發更新涉及 povetacicept，這是我們最近完成的 Alpine Immune Sciences 收購的領先藥物，我們對收購和 pove 的熱情仍然很高。

As a reminder, pove holds the promise of being a pipeline and a product and has best-in-class potential for the lead indication in IgA nephropathy, given its mechanism of action with dual inhibition of both APRIL and BAF, its pre-clinical profile and the clinical data through Phase II in proteinuria, hematuria and GFR.

提醒一下，pove 有望成為一個管道和產品，並且鑑於其對 APRIL 和 BAF 雙重抑制的作用機制、其臨床前概況，在 IgA 腎病的先導適應症方面具有同類最佳的潛力以及蛋白尿、血尿和GFR的II 期臨床數據。

These attributes plus pove's once-monthly dose frequency and small volume subcutaneous route of administration give us high confidence in its potential to be a transformative medicine for patients with IgAN. I am pleased to share that we are on track to initiate the global Phase III Renier study of povetacicept in patients with IgA nephropathy this month.

這些特性加上 pove 每月一次的給藥頻率和小容量皮下給藥途徑，讓我們對其成為 IgAN 患者變革性藥物的潛力充滿信心。我很高興地告訴大家，我們預計在本月啟動針對 IgA 腎病患者的 povetacicept 全球 III 期 Renier 研究。

To recap, we had successful end of Phase II meetings with the FDA and global regulatory authorities, and we're very pleased to have reached agreement on the following important elements. The pivotal program is designed as a single, global, randomized, double-blind, placebo-controlled trial of approximately 480 patients with biopsy-proven IgAN and proteinuria. Patients will be randomized to receive either pove or placebo on top of standard of care.

回顧一下，我們與 FDA 和全球監管機構的第二階段會議成功結束，我們很高興就以下重要內容達成一致。此關鍵項目被設計為單一、全球、隨機、雙盲、安慰劑對照試驗，受試者為約 480 名經活檢證實患有 IgAN 和蛋白尿的患者。在標準護理的基礎上，患者將被隨機分配接受 POVE 或安慰劑治療。

In the US, the Phase III design affords us the opportunity to submit for an accelerated approval. A pre-planned interim analysis will take place when a number of patients reaches 36 weeks of treatment to evaluate the change in proteinuria from baseline to week 36. For full approval, the study will continue through week 104 and an assessment of GFR.

在美國，第三階段設計為我們提供了提交加速批准的機會。當一些患者的治療達到 36 週時，將進行預先規劃的中期分析，以評估蛋白尿從基線到第 36 週的變化。為了獲得完全批准，該研究將持續到第 104 週並對 GFR 進行評估。

Beyond the Phase III study IgA nephropathy, pove is also being evaluated into two Phase II basket trials, one in renal diseases, termed RUBY-3 and a second in B-cell-mediated cytopenias termed RUBY-4. We look forward to readout from some cohorts in these studies later this year and into next.

除了IgA 腎病的III 期研究之外，pove 還正在接受兩項II 期籃子試驗的評估，一項針對腎臟疾病，稱為RUBY-3，另一項針對B 細胞介導的血細胞減少症，稱為RUBY-4。我們期待在今年稍後和明年公佈這些研究中的一些隊列的結果。

To close the pipeline review, a brief update on VX-634 and VX-668 in alpha-1 antitrypsin deficiency or AATD. Safety was demonstrated in the Phase I studies of both VX-634 and VX-668. However, based on the Phase I biomarker analysis, we have determined that neither VX-634 nor VX-668 would deliver transformative efficacy for people with AATD. And more, we have decided to discontinue development of both molecules. With these learnings, our research efforts in AATD will continue.

為了結束管道審查，我們簡要介紹 VX-634 和 VX-668 治療 alpha-1 抗胰蛋白酶缺乏症或 AATD 的情況。VX-634 和 VX-668 的 I 期研究證明了安全性。然而，根據 I 期生物標記分析，我們確定 VX-634 和 VX-668 都不會為 AATD 患者帶來變革性功效。此外，我們決定停止這兩種分子的開發。有了這些經驗，我們在 AATD 方面的研究工作將持續下去。

I'll turn it over to Stuart for a commercial update.

我會將其交給斯圖爾特進行商業更新。

Thanks, Reshma. I'll first discuss CF, then provide some highlights of the ongoing CASGEVY launch and the outlook for suzetrigine in acute pain. As Reshma noted, we once again delivered strong results in CF as we grew the number of eligible patients taking our CFTR modulators, and we continue to expect sustained growth in CF over the near, medium, and long term.

謝謝，瑞詩瑪。我將首先討論 CF，然後提供正在進行的 CASGEVY 上市的一些要點以及 Suzetrigine 在急性疼痛方面的前景。正如 Reshma 所指出的那樣，隨著服用 CFTR 調節劑的合格患者數量的增加，我們在 CF 方面再次取得了強勁的成果，並且我們繼續預計 CF 在近期、中期和長期內持續增長。

In the near term, we continue to focus on reaching more eligible patients, including younger age groups as with the ongoing KAFTRIO launches in the 2 to 5 age group in Europe, with anticipated global approvals for additional rare mutations later this year and through additional geographies such as Brazil, where we now have national reimbursement for TRIKAFTA for patients ages 6 and above.

短期內，我們將繼續專注於覆蓋更多符合條件的患者，包括較年輕的年齡組，正如正在歐洲2 至5 歲年齡組中推出的KAFTRIO 一樣，預計今年晚些時候以及更多地區將批准更多罕見突變藥物例如巴西，我們現在為 6 歲及以上患者提供 TRIKAFTA 國家報銷。

We were also pleased to have announced in June an extended long-term reimbursement agreement with NHS England, which ensures access to our CFTR modulators for all existing and future eligible CF patients in England. Comparable arrangements have subsequently been entered into in Scotland, Wales, and Northern Ireland. The agreements are a result of positive recommendation for NICE and SMC for our CFTR modulators.

我們也很高興在 6 月宣布與英格蘭 NHS 達成一項延長的長期報銷協議，確保英格蘭所有現有和未來符合條件的 CF 患者能夠使用我們的 CFTR 調節器。隨後蘇格蘭、威爾斯和北愛爾蘭也簽訂了類似的安排。這些協定是 NICE 和 SMC 對我們的 CFTR 調製器積極推薦的結果。

In the medium, we anticipate growth driven by the launch of our fifth CFTR modulator therapy, the vanzacaftor triple combination. We believe many existing TRIKAFTA patients may seek to achieve even greater levels of CFTR function and the added convenience of once-daily dosing. And there are also more than 6,000 patients who have discontinued one of our current CFTR modulators who at may be interested in a new treatment option.

在中期，我們預計我們的第五種 CFTR 調節劑療法 vanzacaftor 三聯療法的推出將推動成長。我們相信，許多現有的 TRIKAFTA 患者可能會尋求實現更高水平的 CFTR 功能以及每日一次給藥的額外便利。還有超過 6,000 名患者已停用我們目前的一種 CFTR 調節劑，他們可能對新的治療選擇感興趣。

We continue to execute our Vanza pre-launch activities including pre-approval informational exchange with payers are encouraged by the outlook. And longer term, we expect continued growth in CF from developing medicines to more than 5,000 people with CF who do not respond to CFTR modulators, which is the focus of our mRNA program, VX-522.

我們繼續執行 Vanza 啟動前活動，包括與付款人進行預先批准資訊交流，這對前景感到鼓舞。從長遠來看，我們預計，透過開發藥物，治療 5,000 多名對 CFTR 調節劑沒有反應的 CF 患者，CF 患者數量將持續成長，這是我們 mRNA 計畫 VX-522 的重點。

Now turning to CASGEVY, our launches in sickle cell disease and beta thalassemia. We continue to make strong progress with ATC activation as well as physician, patient and payer engagement as we work to bring this potentially curative therapy to patients around the globe.

現在轉向 CASGEVY，我們針對鐮狀細胞疾病和 β 地中海貧血推出的產品。我們繼續在 ATC 活化以及醫生、患者和付款人參與方面取得重大進展，努力將這種潛在的治癒療法帶給全球患者。

CASGEVY represents enormous advancement for the estimated 35,000 people living with severe sickle cell disease and transfusion-dependent beta-thalassemia in the US and Europe, as well as the estimated 23,000 eligible patients in the Kingdom of Saudi Arabia and Bahrain. To update you on the two key metrics we are sharing externally as important markers of our early launch progress.

CASGEVY 代表了美國和歐洲約 35,000 名嚴重鐮狀細胞疾病和輸血依賴性 β-地中海貧血患者以及沙烏地阿拉伯王國和巴林約 23,000 名符合資格的患者的巨大進步。為了向您介紹我們向外部分享的兩個關鍵指標的最新情況，作為我們早期發布進度的重要指標。

Firstly, ATC activation. We're pleased with our progress as we now have more than 35 activated centers, up from 25 last quarter and 9 at launch. We continue to expect to activate approximately 75 total ATCs globally. Secondly, patient cell collections. We continue to see a growing number of patients beginning the treatment journey, approximately 20 patients have already had cells collected.

首先，ATC 啟動。我們對我們的進展感到滿意，因為我們現在擁有超過 35 個激活中心，高於上季度的 25 個和啟動時的 9 個。我們仍然預計全球將啟動約 75 個 ATC。其次，收集患者細胞。我們繼續看到越來越多的患者開始治療之旅，大約 20 名患者已經收集了細胞。

As mentioned last quarter, patients are initiating the treatment journey in every region where CASGEVY is approved, the US, Europe, and the Middle East. And we are pleased to report growth in patient cell collections across all of these regions this quarter. We also continue to make strong progress with payers in all regions who recognize the transitive clinical benefits of CASGEVY and are moving quickly rapid and equitable access.

正如上季度所提到的，患者正在 CASGEVY 批准的每個地區（美國、歐洲和中東）開始治療之旅。我們很高興地報告本季所有這些地區的患者細胞收集量都有所增長。我們也繼續與所有地區的付款人取得強勁進展，他們認識到 CASGEVY 的可傳遞臨床效益，並正在快速、公平地採取行動。

Outside the US, we are building upon our early successes, such as the early access program in France for TDT, and we now have an early access program approved there for sickle cell disease as well as reimbursement in Austria, Bahrain, and KSA.

在美國以外，我們正在以早期成功為基礎，例如在法國的 TDT 早期獲取計劃，現在我們在法國批准了鐮狀細胞疾病的早期獲取計劃，並在奧地利、巴林和沙烏地阿拉伯進行了報銷。

In the US, given payer support across all market segments, commercial, Medicaid and Medicare, I'm pleased to report that we do not see coverage as a significant obstacle to patient access. We have always known that CASGEVY offers an enormous advancement for patients. We've also consistently communicated that the patient journey, that is the process to go from patient interest all the way to infusion of edited cells is long and complex.

在美國，考慮到所有細分市場（商業、醫療補助和醫療保險）的付款人支持，我很高興地報告說，我們不認為保險範圍是患者獲得醫療服務的重大障礙。我們一直知道 CASGEVY 為患者帶來了巨大的進步。我們也一直強調，患者的旅程，即從患者興趣一直到輸注編輯細胞的過程是漫長而複雜的。

Whilst it's still early in the launch, we have gained many learnings. Interest level is high among patients, physicians, governments and other stakeholders. The value of CASGEVY has been widely recognized, leading to broad access and reimbursement by payers.

雖然還處於發布初期，但我們已經學到了很多。患者、醫生、政府和其他利害關係人對此興趣濃厚。CASGEVY 的價值已被廣泛認可，導致付款人獲得廣泛的使用和報銷。

The patient opportunity in the Middle East is particularly significant given the high prevalence of these hemoglobinopathies and government's clear focus on elevating the health of their citizens. And lastly, the treatment process does take time, but we are now even more confident in our view that CASGEVY will help large numbers of patients around the world and represents a multibillion-dollar opportunity.

鑑於這些血紅蛋白疾病的高盛行率以及政府明確關注提高公民健康的目標，中東地區的病患機會尤其重要。最後，治療過程確實需要時間，但我們現在更加相信 CASGEVY 將幫助世界各地大量患者，並代表著一個數十億美元的機會。

Shifting now to suzetrigine. We believe this novel, highly selective NaV1.8 pain signal inhibitor has the potential to provide a transformative treatment option for the 90 million patients suffering from acute and peripheral neuropathic pain in the US. This quarter, I'll limit my commercial comments to the opportunity in acute pain.

現在轉向suzetrigine。我們相信，這種新型、高選擇性 NaV1.8 疼痛訊號抑制劑有潛力為美國 9,000 萬名患有急性和周邊神經性疼痛的患者提供變革性的治療選擇。本季度，我將把我的商業評論限制在急性疼痛中的機會。

We have continued to make significant progress building out our commercial team. We've now completed hiring of our strategic account leads who will primarily focus on the leadership and formulary decision makers at IDNs, as well our pain territory account managers who post approval, will call on hospitals and other large treatment sites such as ambulatory surgical centers.

我們在商業團隊建立方面持續取得重大進展。我們現已完成對策略客戶主管的聘用，他們將主要關注 IDN 的領導層和處方決策者，以及我們的疼痛領域客戶經理，他們將在獲得批准後拜訪醫院和其他大型治療場所，例如門診手術中心。

Recall that approximately 80 million patients are prescribed to medicine for moderate to severe acute pain each year in the US, with approximately two-thirds of patients treated in the institutional setting. As a result, our field force will primarily focus on this institutional setting. We have begun engaging in pre-approval information exchanges in those institutional settings, with IDN leadership and formulary decision makers who have responsibility for formularies that enable use in both the inpatient and discharge settings.

回想一下，美國每年約有 8,000 萬名患者接受治療中度至重度急性疼痛的藥物，其中約三分之二的患者在機構環境中接受治療。因此，我們的現場工作人員將主要關注此機構設置。我們已經開始在這些機構環境中與負責處方集的 IDN 領導層和處方決策者進行預先批准資訊交流，這些決策者負責在住院和出院環境中使用處方集。

We've encountered high levels of enthusiasm for a new class of treatment for pain, specifically for an effective and well-tolerated pain medication that does possess addictive properties by way of its mechanism of action.

我們遇到了對新型疼痛治療方法的高度熱情，特別是對一種有效且耐受性良好的止痛藥，該藥物透過其作用機制確實具有成癮性。

Hospital formulary and payer processes are well defined, and we are engaging appropriately to encourage and support swift reviews by the relevant bodies like P&T committees, including by providing key clinical and economic information. Depending on the institution or organization, it can take up to 12 months post approval for hospital formulary and payer decisions to be finalized, but we are working to accelerate these timelines.

醫院處方和付款人流程都有明確的定義，我們正在適當地參與鼓勵和支持 P&T 委員會等相關機構的快速審查，包括提供關鍵的臨床和經濟資訊。根據機構或組織的不同，醫院處方和付款人決定在獲得批准後可能需要長達 12 個月的時間才能最終確定，但我們正在努力加快這些時間表。

We anticipate engaging in contracting discussions in the latter half of 2024 with the goal of building formulary and payer coverage during 2025. We also continue to be engaged with federal and state policymakers, including state governors who have expressed strong interest in a novel, highly effective and well tolerated for pain without the addictive potential of opioids.

我們預計將在 2024 年下半年進行合約討論，目標是在 2025 年建立處方和付款人覆蓋範圍。我們也繼續與聯邦和州政策制定者接觸，包括州長，他們對一種新型、高效且耐受性良好的鴉片類藥物表達了濃厚的興趣，用於治療疼痛且沒有成癮潛力。

Federally, in December 2022, Congress passed the No Pain Act, in which non-opioid therapies are eligible for separate payment for Medicare patients in the outpatient and ACS settings beginning in January 2025. It is promising to see CMS continuing the process of implementation as the annual outpatient prospective payment system or OPPS, proposed rule was released for public comment last month.

在聯邦方面，國會於 2022 年 12 月通過了《無痛法案》，其中從 2025 年 1 月開始，非阿片類藥物療法有資格在門診和 ACS 環境中為醫療保險患者單獨付款。預計 CMS 將繼續實施年度門診預期支付系統（OPPS），擬議規則於上個月發布以徵求公眾意見。

Because suzetrigine is still investigational, it is not currently included in the list of seven drugs in the proposed rule, but we fully expect suzetrigine will be eligible for separate payment once it is FDA approved. We view the No Pain Act as an important indication of the broad range of supportive policy initiatives, both at the federal and state level that can provide a meaningful tailwind to suzetrigine adoption.

由於 Suzetrigine 仍處於研究階段，目前尚未包含在擬議規則的七種藥物清單中，但我們完全預計 Suzetrigine 一旦獲得 FDA 批准將有資格獲得單獨付款。我們認為《無痛法案》是聯邦和州層級廣泛支持性政策舉措的重要標誌，可以為 Suzetrigine 的採用提供有意義的推動力。

We are also encouraged by the progress of the alternatives to Pain Act, which aims to level the playing field for access to non-opioids for Medicare part D patients.

我們也對《疼痛法》替代方案的進展感到鼓舞，該法案旨在為 Medicare D 部分患者獲得非阿片類藥物提供公平的競爭環境。

In the discharge or outpatient pharmacy setting, it's important to understand that patients who receive a prescription, must be able to access their acute pain medication immediately. Unlike patients with asymptomatic or chronic conditions, patients in acute pain cannot wait for another day or another week to have their prescription filled. We are, therefore, working with key pharmacy retail organizations to ensure broad availability of suzetrigine nationally.

在出院或門診藥局環境中，重要的是要了解收到處方的患者必須能夠立即獲得其急性止痛藥物。與無症狀或慢性疾病的患者不同，急性疼痛患者不能再等一天或一週才能配藥。因此，我們正在與主要藥房零售組織合作，以確保舒三嗪在全國範圍內的廣泛供應。

In addition, we are planning a range of initiatives for the first year of launch, including co-pay assistance and other financial assistance programs to enable patients at the pharmacy to access their prescribed suzetrigine to payer coverage decisions. We are very enthusiastic about the potential launch of suzetrigine for patients with moderate to severe acute pain and the impact we believe it will have on society.

此外，我們還計劃在推出的第一年採取一系列舉措，包括共同支付援助和其他財務援助計劃，以使藥房的患者能夠獲得其處方的蘇三三嗪，以做出付款人承保決定。我們對可能推出用於中度至重度急性疼痛患者的舒三嗪以及我們相信它將對社會產生的影響感到非常興奮。

We recognize that even in the case of significant unmet need, it can take time some components of our health care system to adopt new technologies, and we are working to accelerate these processes. Ultimately, our goal is to fundamentally and forever change the way pain is treated, and we look forward to delivering on the first of this vision for patients with moderate to severe acute pain in early 2025.

我們認識到，即使在需求未滿足的情況下，我們的醫療保健系統的某些組成部分也需要時間來採用新技術，我們正在努力加快這些進程。最終，我們的目標是從根本上永久改變疼痛的治療方式，我們期待在 2025 年初為中度至重度急性疼痛患者實現這一願景。

In conclusion, it's an exciting time to be at Vertex. We continue to treat more CF patients around the world and are well advanced in planning for the launch of the Vanzacaftor triple combination. We are entering a new era of commercial diversification with the launch of CASGEVY in the US, Europe, and the Middle East, and our launch preparations for suzetrigine in acute pain are well underway. As we seek to redefine the treatment of pain and drive further diversified revenue growth.

總之，在 Vertex 是一個激動人心的時刻。我們繼續在世界各地治療更多的囊性纖維化患者，並在計劃推出 Vanzacaftor 三重療法方面取得了進展。隨著 CASGEVY 在美國、歐洲和中東的上市，我們正在進入商業多元化的新時代，而用於治療急性疼痛的舒三嗪的上市準備工作也在順利進行中。我們尋求重新定義疼痛治療並推動進一步的多元化收入成長。

I will now turn the call over to Charlie to review the financials.

我現在將把電話轉給查理審查財務狀況。

Thanks, Stuart. Vertex's excellent Q2 results demonstrate once again our consistent strong performance and attractive growth profile.

謝謝，斯圖爾特。Vertex 出色的第二季業績再次證明了我們一貫的強勁業績和有吸引力的成長前景。

Second-quarter 2024 revenue increased 6% year over year to $2.65 billion with solid growth of 7% in the US and 5% outside the US. The drivers of this strong quarter were in line with our expectations, including an anticipated reduction in channel inventories in select international markets.

2024 年第二季營收年增 6%，達到 26.5 億美元，其中美國穩定成長 7%，美國以外成長 5%。這一強勁季度的推動因素符合我們的預期，包括部分國際市場通路庫存的預期減少。

Second-quarter US growth was driven by continued strong patient demand for TRIKAFTA. Outside the US, growth was also driven by strong demand with continued uptake from the KAFTRIO launches in children's ages 2 to 5, partially offset by the reversal of the first-quarter channel inventory build.

美國第二季度的成長是由患者對 TRIKAFTA 持續強勁的需求推動的。美國以外地區的成長也受到強勁需求的推動，KAFTRIO 面向 2 至 5 歲兒童推出的產品持續受到歡迎，但部分被第一季通路庫存建設的逆轉所抵消。

On the expense front, Q2 '24 combined non-GAAP R&D, acquired IP R&D, and SG&A expenses were $5.43 billion compared to $1.04 billion in the second quarter of 2023. Q2 '24 operating expenses include over $4.4 billion in AIP R&D charges, primarily as a result of the Alpine acquisition, which we previously disclosed is being accounted for as an asset acquisition.

在費用方面，2024 年第二季的非 GAAP 研發、收購的智慧財產權研發和 SG&A 費用合計為 54.3 億美元，而 2023 年第二季為 10.4 億美元。2024 年第二季的營運支出包括超過 44 億美元的 AIP 研發費用，這主要是由於收購 Alpine 造成的，我們先前揭露的這項收購被視為資產收購。

This compares to just $111 million of AIP R&D charges in Q2 of '23. Q2 '24 non-GAAP R&D expenses of $697 million were roughly flat year over year, reflecting ongoing investment in the advancement of our broad R&D portfolio, offset by reduced costs from the recently completed clinical trials as well as the associated transition of certain costs from R&D to COGS and inventory.

相較之下，23 年第二季 AIP 研發費用僅 1.11 億美元。24 年第二季非GAAP 研發費用為6.97 億美元，與去年同期大致持平，反映出我們對廣泛研發組合的持續投資，但被最近完成的臨床試驗的成本降低以及某些成本的相關轉變所抵消。

Q2 '24 non-GAAP SG&A expenses of $280 million increased 28% versus prior year primarily as a result of investments in the commercial organization, including launch activities for CASGEVY and pre-launch activities for suzetrigine acute pain.

2024 年第 2 季非 GAAP SG&A 費用為 2.8 億美元，較去年同期成長 28%，這主要是由於對商業組織的投資，包括 CASGEVY 的上市活動和 Suzetrigine 急性疼痛的上市前活動。

We anticipate that quarterly non-GAAP R&D and SG&A expenses will increase over the remainder of 2024 within our guidance as we advance multiple studies, including suzetrigine, pove, and inaxaplin in Phase III programs VX-993 in acute and peripheral neuropathic pain studies and the expansion of the VX-880 trial in T1D. In addition, we continue to invest in preparation for upcoming potential new launches, including the further build-out of our commercial capabilities in acute pain.

我們預計，隨著我們推進多項研究，包括急性和周圍神經性疼痛研究的III 期項目VX-993 中的Suzetrigine、pove 和inaxaplin，以及2024 年剩餘時間內的季度非GAAP 研發和SG&A 費用將在我們的指導範圍內增加。此外，我們繼續投資為即將推出的潛在新產品做好準備，包括進一步增強我們在急性疼痛方面的商業能力。

Q2 '24 results reflected strong revenue and underlying operating results, though due to the $4.4 billion AIP R&D charge from Alpine transaction accounting, we reported a second-quarter 2024 non-GAAP operating loss of $3.1 billion.

24 年第二季的業績反映了強勁的收入和基本營運業績，儘管由於 Alpine 交易會計產生的 44 億美元 AIP 研發費用，我們報告 2024 年第二季非 GAAP 營運虧損為 31 億美元。

In the second quarter of 2023, we reported $1.15 billion in non-GAAP operating income. Our tax rate for the quarter was also impacted by the onetime non-deductible Alpine AIP R&D charge leading to a reported non-GAAP tax rate for the second quarter of 2024 of negative 10% compared to a tax rate of 21% in Q2 of '23. Aside from the effects of the non-deductible Alpine charge, there were no material changes in Vertex's non-GAAP tax rate for the quarter, which would have been approximately 21%.

2023 年第二季度，我們報告的非 GAAP 營業收入為 11.5 億美元。我們本季的稅率也受到一次性不可扣除的阿爾派 AIP 研發費用的影響，導致 2024 年第二季的非公認會計準則稅率為負 10%，而 2024 年第二季的稅率為 21%。 .除了不可扣除的 Alpine 費用的影響外，Vertex 本季的非 GAAP 稅率沒有重大變化，約為 21%。

The $4.4 billion AIP R&D charge for the Alpine acquisition equates to an impact of approximately $17 per share on Q2 GAAP and non-GAAP results and drove a non-GAAP loss per share of $12.83 in Q2 '24 compared to non-GAAP earnings per share of $3.89 in the second quarter of 2023.

收購Alpine 的44 億美元AIP 研發費用相當於對第二季GAAP 和非GAAP 業績產生每股約17 美元的影響，與非GAAP 每股收益相比，2024 年第二季非GAAP 每股虧損為12.83美元2023 年第二季為 3.89 美元。

We ended the quarter with $10.2 billion in cash and investments after paying approximately $5 billion to fund the acquisition of Alpine Immune Sciences. Additionally, we deployed over $300 million of cash in the second quarter to repurchase more than 700,000 shares.

在支付約 50 億美元收購 Alpine Immune Sciences 的資金後，我們在本季結束時擁有 102 億美元的現金和投資。此外，我們在第二季部署了超過 3 億美元的現金，回購了超過 70 萬股股票。

Now switching to guidance. We are raising our 2024 total product revenue guidance to a range of $10.65 billion to $10.85 billion, representing 9% revenue growth at the midpoint at current exchange rates. We continue to have high visibility revenue outlook as we expect continued growth in CF as we reach more patients, including younger ones in core markets and select other countries. Guidance also continues to include a contribution in the second half of the year from the commercial launch of CASGEVY.

現在切換到指導。我們將 2024 年產品總收入指引上調至 106.5 億美元至 108.5 億美元，以目前匯率計算，營收成長中位數為 9%。我們的收入前景仍然具有較高的可見性，因為我們預計，隨著我們接觸到更多患者，包括核心市場和其他國家的年輕患者，CF 業務將持續成長。指導意見也繼續包括下半年 CASGEVY 商業發布的貢獻。

For Vertex operating expenses, our non-GAAP guidance continues to include a $4.2 billion to $4.3 billion in combined R&D and SG&A expenses, which is unchanged from the guidance provided on our last earnings call. As previously communicated, we are absorbing Alpine's projected non-GAAP operating expenses for the remainder of 2024 within our guidance range for R&D and SG&A.

對於 Vertex 營運費用，我們的非 GAAP 指引繼續包括 42 億至 43 億美元的研發和 SG&A 合併費用，這與我們上次財報電話會議上提供的指導沒有變化。如同先前所傳達的，我們將阿爾派在 2024 年剩餘時間內預期的非 GAAP 營運費用納入我們的研發和銷售、一般管理費用指導範圍內。

For acquired [IP] R&D, we now expect approximately $4.6 billion for the year, including the Alpine asset acquisition charge recorded in the second quarter. Given that the Alpine IP R&D charge is not deductible for tax purposes, we expect a non-GAAP full-year 2024 tax rate of approximately 100%. Note that, the anticipated percentage tax rate is highly sensitive to projected pre-tax income.

對於收購的 [IP] 研發，我們現在預計今年約為 46 億美元，其中包括第二季記錄的 Alpine 資產收購費用。鑑於 Alpine 智慧財產權研發費用不可扣除稅收，我們預期 2024 年非 GAAP 全年稅率約為 100%。請注意，預期百分比稅率對預計稅前收入高度敏感。

Aside from the impact of the non-deductible Alpine AIP R&D charge, our underlying full year 2024 non-GAAP effective tax rate would have remained in the range of 20% to 21%. In closing, Vertex posted excellent results yet again as we delivered strong revenue growth, advanced our CASGEVY launch and secured important regulatory approvals.

除了不可扣除的阿爾派 AIP 研發費用的影響外，我們的 2024 年全年非 GAAP 基本有效稅率將保持在 20% 至 21% 的範圍內。最後，Vertex 再次取得了優異的業績，我們實現了強勁的營收成長，推進了 CASGEVY 的推出並獲得了重要的監管批准。

We also strengthened our capabilities in preparation for additional near-term launches progressed our pipeline and made rapid progress closing and integrating Alpine. A compelling fit with Vertex's R&D strategy with significant potential as a pipeline in a product.

我們也加強了為近期推出更多產品做準備的能力，推進了我們的產品線，並在關閉和整合 Alpine 方面取得了快速進展。與 Vertex 的研發策略完美契合，具有作為產品管道的巨大潛力。

We are already leveraging Vertex's clinical, regulatory and commercial capabilities to accelerate development in IgAN with Phase III set to begin this month. we are targeting US accelerated approval in IgAN in late 2027 and a contribution to Vertex's revenue growth and diversification beginning in 2028.

我們已經在利用 Vertex 的臨床、監管和商業能力來加速 IgAN 的開發，第三階段將在本月開始。我們的目標是在 2027 年底 IgAN 在美國加速獲得批准，並從 2028 年開始為 Vertex 的收入成長和多元化做出貢獻。

In addition, as we move through 2024, we anticipate further important achievements, including multiple milestones in our pain portfolio, such as a Phase II data readout with suzetrigine in LSR Phase II initiation of VX-993 studies in acute pain and in diabetic peripheral neuropathy as well as progress towards pivotal development in T1D. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17.

此外，隨著2024 年的到來，我們預計將取得進一步的重要成就，包括我們的疼痛產品組合中的多個里程碑，例如LSR 中使用Suzetrigine 的II 期數據讀出，以及針對急性疼痛和糖尿病週邊神經病變的VX-993 研究的II 期啟動以及 T1D 關鍵發展的進展。這些以及多個疾病領域持續進展的其他預期里程碑詳見幻燈片 17。

We look forward to updating you on our progress on future calls, and I'll ask Susie to begin the Q&A period.

我們期待在未來的通話中向您通報我們的最新進展，我將請 Susie 開始問答環節。

(Operator Instructions) Salveen Richter, Goldman Sachs.

（操作員指令）Salveen Richter，高盛。

Good afternoon. Thanks for taking my question. Noting that around 6,000 patients continued CFTR modulators as we think about uptake for vanzacaftor triple, can you help us understand what the early launch dynamics could look like and whether they could be a significant bolus of early adopters? And then just a second question, if I may. What is the relative contribution of CASGEVY to the updated product revenue guidance?

午安.感謝您提出我的問題。當我們考慮使用 vanzacaftor 三聯療法時，注意到大約 6,000 名患者繼續使用 CFTR 調節劑，您能否幫助我們了解早期推出動態可能是什麼樣子，以及它們是否可能成為早期採用者的重要推注？如果可以的話，還有第二個問題。CASGEVY 對更新後的產品收入指引的相對貢獻為何？

Thanks, Salveen. We will be breaking down the revenue for the CF franchise versus CASGEVY. And I'll turn it over to Stuart to tell you a little bit more about the vanzacaftor launch dynamics.

謝謝，薩爾文。我們將細分 CF 特許經營權與 CASGEVY 的收入。我將把它交給斯圖爾特，告訴你更多關於 vanzacaftor 發射動態的資訊。

Yes, Salveen, thanks for the question. I don't think there's going to be a single bolus of patients based on our research with physicians that they are considering for the vanzacaftor triple combination. I'd say that they are excited about the prospects for vanzacaftor both for their existing patients who are honestly, CFTR modulator, many of whom I think are going to be very interested in a treatment option, which promises the potential for increased CFTR function.

是的，薩爾文，謝謝你的提問。根據我們與醫生的研究，我認為患者不會考慮使用 vanzacaftor 三重療法。我想說，他們對 vanzacaftor 的前景感到興奮，他們現有的患者都是 CFTR 調節劑，我認為他們中的許多人會對治療方案非常感興趣，這有望增加 CFTR 功能。

And also being the fact that it's once a day. And then as you say, there are also patients who are not currently on a CFTR modulator, who I think are going to welcome the opportunity for a new treatment option. So I don't think it's going to be one or the other. I think there's going to be broad interest in the vanzacaftor triple across both patients who are persistent today and those who've discontinued previously.

而且事實上它是每天一次。正如你所說，還有一些患者目前沒有使用 CFTR 調節劑，我認為他們會歡迎新治療選擇的機會。所以我認為不會是其中之一。我認為現在堅持使用 vanzacaftor 三聯療法的患者和先前已經停藥的患者都會對它產生廣泛的興趣。

David Risinger, Leerink Partners.

大衛‧瑞辛格 (David Risinger)，Leerink 合夥人。

Congrats on the strong execution. I have two questions. First, could you just discuss the potential to develop VX-548 ex-US for neuropathic pain? And second, could you provide latest on your pre-clinical development efforts for NaV1.7 inhibitors?

祝賀強大的執行力。我有兩個問題。首先，您能否討論一下在美國以外開發 VX-548 治療神經性疼痛的潛力？其次，您能否提供 NaV1.7 抑制劑臨床前開發工作的最新資訊？

Sure thing. Hey Dave, this is Reshma. Let me break that into two parts, and let me take the pre-clinical NaV1.7 first, turn it over to Stuart to talk about our goals ex-US. So we are making really strong progress on the NaV1.7 inhibitors. They are still in pre-clinical development. But I would characterize it, Dave, as it's in late pre-clinical development.

當然可以。嘿戴夫，這是瑞詩瑪。讓我把它分成兩部分，首先讓我看看臨床前 NaV1.7，把它交給 Stuart 來談談我們在美國以外的目標。因此，我們在 NaV1.7 抑制劑方面取得了巨大進展。它們仍處於臨床前開發階段。但我會描述它，戴夫，因為它處於臨床前開發的後期。

And to contextualize this a little bit more for everybody else, we expect that the NaV1.7s could be used alone in acute pain or neuropathic pain or they could be used in combination with our NaV1.8 inhibitors, be it 548 or 993 or any in our portfolio. With that, I'll turn it over to Stuart for a little bit on ex-US ambitions.

為了讓其他人更了解這一點，我們預計NaV1.7 可以單獨用於治療急性疼痛或神經性疼痛，或者可以與我們的NaV1.8 抑制劑（無論是548 或993 或任何其他抑制劑）聯合使用。說到這裡，我將把它交給斯圖爾特，讓他了解一些關於前美國的野心。

Yeah. Hi David, thanks for the question. So I would say that the clinical landscape and by that, I mean the kind of the treatment options and the way that they're used is very similar outside the US as it is here in the U. with things like ANCA to acetaminophen in neuropathic pain, things like pregabalin, gabapentin, and then obviously opioids. And that's true in both acute pain and neuropathic pain.

是的。嗨大衛，謝謝你的提問。所以我想說的是，臨床情況，我的意思是，治療方案的種類和使用方式在美國以外與在美國非常相似，例如 ANCA 和對乙醯氨基酚等治療神經病的藥物。加巴噴丁等藥物，當然還有鴉片類藥物。對於急性疼痛和神經性疼痛都是如此。

And I know you're asking specifically about neuropathic there are differences. I think it's fair to say that the level of abuse and misuse of opioids is less. It's not zero, but it's less outside of the US. But in addition, the pricing dynamics and the value recognition of health care and innovation by health care systems outside the US is very different.

我知道你具體問的是神經病，兩者之間有差異。我認為可以公平地說，阿片類藥物的濫用和誤用程度較低。它不是零，但在美國以外的地區更少。但除此之外，美國以外的醫療保健系統的定價動態以及醫療保健和創新的價值認知也非常不同。

And as such, our focus at this time is very much on the unmet need and opportunity to serve patients here in the US first. And ex-US is something that we will consider later on.

因此，我們目前的重點主要是首先為美國患者提供服務的未滿足的需求和機會。美國以外的地區是我們稍後會考慮的。

Jessica Fye, JPMorgan.

潔西卡法耶，摩根大通。

Hey, there. Thanks for taking my question. I wanted to ask about your type 1 diabetes effort. How do you envision the regulatory path for VX-880? And for VX-264, the encapsulated cells product, I believe you've completed part A with the low-dose patients. Is there anything you can share with respect to kind of what you're seeing so far with that one?

嘿。感謝您提出我的問題。我想問一下您在治療第 1 型糖尿病方面所做的努力。您如何看待 VX-880 的監管路徑？對於 VX-264（封裝細胞產品），我相信您已經與低劑量患者完成了 A 部分。關於您迄今為止所看到的情況，您有什麼可以分享的嗎？

Yes. Jess, it's Reshma. Let me take those two questions. Maybe we'll go with 264 first, and then we'll go to VX-880. So on VX-264, this is the calls plus device program.

是的。傑西，我是瑞詩瑪。讓我回答這兩個問題。也許我們會先選擇 264，然後再選擇 VX-880。所以在VX-264上，這是呼叫加設備程式。

You're exactly right about the stage of the program. We're in part B, which is the full dose. It's a full dose with the stagger period between patients. I would say that results are a 2025 time frame. We're making progress, and I'm really happy to be in the clinic with both 264 and 880.

你對節目階段的看法完全正確。我們處於 B 部分，即完整劑量。這是一個完整的劑量，患者之間的間隔期是錯開的。我想說的是，結果是 2025 年的時間框架。我們正在取得進展，我很高興能在診所與 264 和 880 一起工作。

On VX-880, this is the naked cell program, so cells alone. This is the one that has now completed, which is obviously a big milestone enrollment and dosing in the original 17 patient study. We are in the phase of development where we're in full dose with patients who don't have a stagger.

在 VX-880 上，這是裸細胞程序，因此只有細胞。這是目前已經完成的一項研究，這顯然是最初的 17 名患者研究中的一個重大里程碑。我們正處於開發階段，我們正在全力治療沒有搖晃的患者。

I'm really happy with the regulatory discussions to date and their endorsement for us to expand the study to a total of 37 patients, so an additional 20 patients. And with regard to your direct question on how should we think about the path forward with regard to regulatory expectations.

我對迄今為止的監管討論以及他們對我們將研究範圍擴大到總共 37 名患者（即額外的 20 名患者）的認可感到非常滿意。至於你直接提出的問題，即我們應該如何思考監管期望的前進道路。

I don't have an answer for you today because that's exactly the conversations that we're going to compete in the coming months. But I would think about the type 1 diabetes program more like a CASGEVY program than a small model program. You'll remember that CASGEVY program in either TDT or in a sickle cell was a very efficient sample size.

我今天沒有給你答案，因為這正是我們在未來幾個月內將要進行的對話。但我認為第 1 型糖尿病項目更像是 CASGEVY 項目，而不是小型模型項目。您會記得，無論是 TDT 還是鐮狀細胞中的 CASGEVY 程序都是非常有效的樣本量。

And what we did in the case of CASGEVY is converted from a Phase I/II to a Phase I/II/III trial. Exactly look like for VX-880. I look forward to keeping you updated as we complete the discussions with regulators.

我們在 CASGEVY 案例中所做的工作是從 I/II 期試驗轉為 I/II/III 期試驗。與 VX-880 完全相同。我期待在我們完成與監管機構的討論後向您通報最新情況。

Evan Seigerman, BMO Capital Markets.

Evan Seigerman，BMO 資本市場。

Hi, guys. Thank you so much for taking my question. I think, Stuart, in your prepared remarks, you suggested that the launch of suzetrigine might be more gradual than some other launches -- maybe once approved, can you walk me through some of the gating factors to really get to the hands of patients to have a maximum impact on the health care system, kind of what you have to do once approved to really get it to these patients.

嗨，大家好。非常感謝您回答我的問題。我想，Stuart，在您準備好的發言中，您建議 Suzetrigine 的推出可能比其他一些產品的推出更加漸進——也許一旦獲得批准，您能否引導我了解一些真正到達患者手中的控制因素？醫療保健系統產生最大的影響，這就是一旦獲得批准才能真正將其提供給這些患者所必須要做的事情。

Sure, Evan. Thanks for the question. And just to be absolutely crystal clear, our enthusiasm for suzetrigine is growing as we get closer to the launch, not diminishing. And that's due to the benefit we've got from market research and also our interactions and discussions with physicians post the Phase III data and the filing. But there are practical realities that we are going to have to face and they are things like. Obviously, the majority of patients with acute pain are treated in the institutional setting.

當然，埃文。謝謝你的提問。需要明確的是，隨著上市時間的臨近，我們對 Suzetrigine 的熱情正在增長，而不是減弱。這是由於我們從市場研究以及我們與醫生的互動和討論中獲得的好處，發布了 III 期數據和備案。但我們必須面對一些實際的現實，就像這樣。顯然，大多數急性疼痛患者在機構環境中接受治療。

That means we're going to have to go through formulary and P&T processes with those institutions. We're going to have to work with payers and work through their formulary and other policy adoption processes. And so whilst those policies are very well defined, they do take time. And obviously, work everything we can to accelerate those timelines. And that's why we're already engaging for instance, with GPOs and IDN leadership to support institutional use.

這意味著我們將必須與這些機構一起完成處方和 P&T 流程。我們將不得不與付款人合作，並完成他們的處方和其他政策採用流程。因此，儘管這些政策的定義非常明確，但它們確實需要時間。顯然，我們會盡一切努力加快這些時間表。這就是為什麼我們已經與 GPO 和 IDN 領導層合作來支持機構使用。

We're talking with payers and PBMs to support rapid policy adoption. In addition, we are going to want suzetrigine to be broadly available at retail pharmacies across America. And so we're also reaching with the major retail the organizations as well.

我們正在與付款人和 PBM 進行討論，以支持政策的快速採用。此外，我們希望 Suzetrigine 在美國各地的零售藥局廣泛銷售。因此，我們也正在與主要零售組織進行接觸。

And lastly, because we know that these processes can take time despite the fact we're going to do everything we can to accelerate them. We are also looking at deploying a range of initiatives, including things like co-pay assistance and financial assistance program so that if a physician and patient decide that suzetrigine is right for them, that patient can access the product without delay and isn't forced to kind of abandon the prescription because their particular plan or payer has not finalized their medical policy yet.

最後，因為我們知道這些過程可能需要時間，儘管我們將盡一切努力加速它們。我們也正在考慮部署一系列舉措，包括共同支付援助和財務援助計劃等，這樣，如果醫生和患者認為舒三嗪適合他們，患者就可以立即使用該產品，而不會被迫使用該產品因為他們的特定計劃或付款人尚未最終確定他們的醫療政策而放棄處方。

So those are some of the challenges we're going to be facing. They're not unique to Vertex. They are relatively well defined, and we're going to do everything we can to accelerate them to suzetrigine, can become the multibillion-dollar drug. We know it's going to become.

這些是我們將面臨的一些挑戰。它們並不是 Vertex 獨有的。它們的定義相對明確，我們將盡一切努力加速它們成為 Suzetrigine，使其成為價值數十億美元的藥物。我們知道它會變成這樣。

Chris Raymond, Piper Sandler.

克里斯·雷蒙德，派珀·桑德勒。

Hey. Thanks. Just maybe two questions. First, maybe on pove. Just a competitive question as IgAN seems to be getting a little bit more crowded. Biogen just got access to [gosuranemab] which I think had a pretty interesting Phase II data. Just maybe talk a little bit about how you view the sort of match up to that?

嘿。謝謝。也許只是兩個問題。首先，也許是在 pove 上。這只是一個競爭性問題，因為 IgAN 似乎變得更加擁擠了。百健（Biogen）剛剛獲得了 [gosuranemab]，我認為它有一個非常有趣的 II 期數據。也許可以談談您如何看待迄今為止的比賽？

And maybe how does anti-CD38 compared to BAF APRIL inhibition? And then maybe a CASGEVY commercial question. Just on the HHS suit around fertility treatments for patients getting CASGEVY. Can you maybe talk about the overall timelines there with that case? And maybe also talk about how much of an impact it is to not have this reimbursement for fertility in place during the early stage of the launch.

也許抗 CD38 與 BAF APRIL 抑制相比如何？然後可能是一個 CASGEVY 商業問題。就在 HHS 針對接受 CASGEVY 的患者進行生育治療的訴訟中。您能否談談該案例的總體時間表？也許還可以談談在啟動的早期階段沒有生育補償的影響有多大。

Sure. This is Reshma. Let me take the first question first, and then I'll turn it over to Stuart to talk about CASGEVY and how that's going. So important things to know about IgA nephropathy. It is a rare disease, but it is one of the more common rare disease.

當然。這是瑞詩瑪。讓我先回答第一個問題，然後我將把它交給 Stuart 來談談 CASGEVY 以及情況如何。有關 IgA 腎病的重要知識。它是一種罕見疾病，但卻是較常見的罕見疾病之一。

There's more than 130,000 with IgA nephropathy in the US alone. It's actually the most common primary glomerulonephritis. So there are lots of patients that are waiting to be served. To date, there is no specific therapy that treats the underlying cause of this disease. And the reason for our enthusiasm and after a IgA nephropathy has been in our sandbox as it were a disease area of interest for a long time.

光在美國就有超過 13 萬名 IgA 腎病患者。它實際上是最常見的原發性腎絲球腎炎。所以有很多病人在等待服務。到目前為止，還沒有特定的療法可以治療這種疾病的根本原因。我們熱情的原因是 IgA 腎病一直在我們的沙盒中，因為它是長期以來我們感興趣的疾病領域。

And after there has been some activity in this space and a full analysis by us of everything available out there our enthusiasm for Alpine and their povetacicept, which is a dual-APRIL BAF inhibitor comes from the fact that it is the agent that works directly on the underlying cause of the disease to put it in a short way, the disease is caused by B cells. It is the activation of these B cells.

在這個領域進行了一些活動並對現有的一切進行了全面分析後，我們對 Alpine 及其 povetacicept（一種雙 APRIL BAF 抑製劑）的熱情來自於它是直接作用於疾病的根本原因簡單來說，就是B細胞引起的疾病。這是這些 B 細胞的活化。

It is about auto antibodies. And this drug APRIL BAF directly inhibits B-cell proliferation, maturation and proliferation. And what we have seen by way of mechanism of action, this dual-APRIL BAF inhibition all of the pre-clinical data potency affinity as well as the clinical data, it is through its Phase II development. So we're talking about proteinuria, hematuria, GFR and also the biomarker of what's called GVA IgA, that's the advertently glycosylated IgA, which is the underlying problem.

這是關於自身抗體的。而這個藥物APRIL BAF直接抑制B細胞的增生、成熟和增生。我們透過作用機制看到，這種雙重 APRIL BAF 抑制所有臨床前數據、效力親和力以及臨床數據，它是透過其 II 期開發進行的。所以我們談論的是蛋白尿、血尿、GFR 以及所謂的 GVA IgA 的生物標記物，即無意中糖基化的 IgA，這是根本問題。

Not to mention two monthly dosing, it's subcutaneous and small volume. You put that all together, pove has the most transformational profile and holds the potential to be best-in-class for IgAN, but also holds the potential to have effect -- transformative effect in a whole host of other cell-mediated kidney diseases like lupus nephritis, membranous, ANCA associated and a host of B-cell-mediated heme diseases like ITP, cold agglutinin disease, warm hemolytic anemia.

更不用說每月兩次給藥，而且是皮下注射，劑量小。綜上所述，pove 具有最具變革性的特徵，並且有可能成為 IgAN 同類最佳藥物，也有可能對許多其他細胞介導的腎臟疾病（如狼瘡性腎炎、膜性、ANCA 相關性和許多B 細胞介導的血紅素疾病，如ITP、冷凝集素病、溫溶血性貧血。

So I couldn't be more excited about this molecule getting to its first Phase III program, which is IgA Nephropathy.

因此，我對這種分子進入第一個 III 期計畫（即 IgA 腎病變）感到非常興奮。

Yes, let me just take a step back before I talk specifically about fertility preservation. So because of the treatment early to get CASGEVY, which requires multiple trips to the activated and authorized treatment centers. And because there's only a certain number of sites in the United States, and in addition, because of the b-cell fan conditioning regimens is where the fertility risk comes in, we have sought to try and provide support to patients in two particular areas.

是的，在具體談論生育力保存之前，讓我先退後一步。因此，由於治療早期要獲得CASGEVY，這需要多次前往激活和授權的治療中心。由於美國祇有一定數量的站點，而且由於 B 細胞風扇調理方案存在生育風險，因此我們試圖嘗試為兩個特定領域的患者提供支援。

One, travel and lodging and the other one is in fertility preservation, and we want to provide those support services to patients equitably no matter what the payer. We are able to buy both of those services to commercially insured patients. And we are able to provide travel and lodging support to government-insured patients because that has previously been ruled on by the OIG.

一是旅行和住宿，二是生育力保存，我們希望公平地向病人提供這些支援服務，無論付款人是誰。我們能夠向商業保險患者購買這兩項服務。我們能夠為政府投保的患者提供旅行和住宿支持，因為監察長辦公室此前曾對此做出裁決。

What they have not met decision on is on fertility preservation, and that's why we've launched our suit to try and get fertility preservation approved for government-insured patients as well.

他們還沒有就生育力保存做出決定，這就是為什麼我們發起訴訟，試圖讓政府保險患者的生育力保存獲得批准。

It's impossible that exactly on the timing of when that suit will be heard and resolved. In the short term, I don't see it as being rate-limiting to a successful launch of CASGEVY, and I think we're already seeing that in the number of patients who are beginning the treatment journey and in the number of collections. Having said that, we are completely committed to the sickle cell and TET communities, and we are going to fight for their rights to cable access, whatever their payer.

確切的時間不可能確定該訴訟的審理和解決時間。短期內，我不認為這會限制 CASGEVY 的成功上市，而且我認為我們已經在開始治療之旅的患者數量和收集的數量中看到了這一點。話雖如此，我們完全致力於鐮狀細胞和 TET 社區，我們將爭取他們使用有線電視的權利，無論他們的付款人是誰。

Terence Flynn, Morgan Stanley.

特倫斯‧弗林，摩根士丹利。

Hi. Thanks for taking my question. Maybe two for me. Stuart, you discussed at a high level your confidence in vanzacaftor pricing. Maybe just -- I know you're not going to comment directly on the price, but just what are some of the inputs you're considering as you think about making that decision on next year? And then any update on where we might see the full Phase III data for VX-548 this fall?

你好。感謝您提出我的問題。也許對我來說有兩個。Stuart，您在高層討論了您對 vanzacaftor 定價的信心。也許只是——我知道你不會直接評論價格，但當你考慮明年做出決定時，你會考慮哪些因素？那麼今年秋天我們可能會在哪裡看到 VX-548 的完整 III 期數據？

Terence, let me take the second question first. I think it's now been released. The VX-548 suzetrigine data have been accepted at the ASA fall conference, and it has been accepted in the best abstract category. So you can expect to see it there. I'm sure the teams are also going to be working on full manuscripts probably in the fall/winter time frame, but the Congress acceptance of suzetrigine as best-in-class abstracts has already been announced. Stuart, over to you.

特倫斯，讓我先回答第二個問題。我想現在已經被釋放了。VX-548 Suzetrigine資料已在ASA秋季會議上被接受，並且已被接受為最佳摘要類別。所以你可以期待在那裡看到它。我確信這些團隊也可能會在秋季/冬季的時間範圍內完成完整的手稿，但國會已經宣布接受 Suzetrigine 作為一流的摘要。斯圖爾特，交給你了。

Yes. Terence, on vanzacaftor, we're going to approach the pricing of vanzacaftor as we have with all of our medicines, which is we're going to base it on the clinical benefits and the value it provides to patients. And as you know, we're very positive about the vanzacaftor profile.

是的。Terence，關於 vanzacaftor，我們將按照我們對所有藥物的定價方式來定價 vanzacaftor，即我們將根據臨床益處及其為患者提供的價值來定價。如您所知，我們對 vanzacaftor 的概況非常看好。

It performed brilliantly in the Phase III program, noninferior as anticipated to TRIKAFTA on FEV1, but demonstrated superior restoration of CFTR function as measured by sweat chloride. And of course, it has the convenience of being once daily. So we're going to take all of those factors into consideration when thinking of the pricing, which is obviously a decision we'll make much closer to the launch.

它在 III 期項目中表現出色，在 FEV1 方面不遜色於 TRIKAFTA，但透過汗液氯化物測量，顯示出 CFTR 功能的卓越恢復。當然，它還有每天一次的便利。因此，在考慮定價時，我們將考慮所有這些因素，這顯然是我們在接近發佈時所做的決定。

Mohit Bansal, Wells Fargo.

莫希特·班薩爾，富國銀行。

Great. Thanks very much for taking my question. Maybe one question on LSR trial. If you could help set some expectations there. It's a placebo-controlled trial. So should we think a two-point improvement just like a DPN trial would be good enough here? The other one is that, are you expecting any AdCom for the acute pain program at this point?

偉大的。非常感謝您提出我的問題。也許是關於 LSR 試驗的問題。如果您能幫助在那裡設定一些期望。這是一項安慰劑對照試驗。那麼我們是否應該認為像 DPN 試驗那樣的兩點改進就足夠了？另一個問題是，您目前是否期待針對急性疼痛計畫的 AdCom？

Mohit, let me take the second question first. As I said in my prepared remarks, we are thrilled that suzetrigine, the submission was not only accepted but granted priority review. The agency has let us know that they do not plan to hold an Adcom as it stands today. But also, as you know, the agency can let us know that they wish to have one at any time between the acceptance of the filing and the actual approval.

莫希特，我先回答第二個問題。正如我在準備好的演講中所說，我們很高興 Suzetrigine 提交的資料不僅被接受，而且還獲得了優先審查。該機構已告知我們，他們不打算按目前的情況舉辦 Adcom。而且，正如您所知，該機構可以讓我們知道他們希望在接受申請和實際批准之間的任何時間擁有一個。

On the LSR, so that's also a VX-548 trial. That has significantly honestly, far significantly exceeded our projections in terms of enrollment and study, and we're now expecting that study this year and for us to be able to share results this year.

在 LSR 上，這也是 VX-548 試用版。老實說，就入學率和學習而言，這遠遠超出了我們的預測，我們現在期待今年的研究，並讓我們能夠在今年分享結果。

So with regard to this study and how you can think about it, it uses the high dose. So the 69 milligrams from the Phase II study of DPN. The big difference between DPN and LSR is that LSR has no specific therapy approved for the treatment of this kind of radiculopathy pain.

所以關於這項研究以及你如何看待它，它使用了高劑量。69 毫克來自 DPN II 期研究。DPN 和 LSR 之間的最大區別在於，LSR 沒有批准用於治療這種神經根病變疼痛的特異性療法。

And so our Phase II trial in LSR is a within group. So it's within arm change of the NPRS for the LSR -- sorry, for the VX-548 group. And equally, we'll have the placebo group change. And the goal for the LSR study, which frankly was goal as the DPN study to get a magnitude of the treatment effect so that we can appropriately power the Phase III study.

因此，我們的 LSR II 期試驗是在組別內進行的。因此，對於 LSR 來說，NPRS 的變化是在手臂之內的——抱歉，對於 VX-548 組來說。同樣，我們將改變安慰劑組。LSR 研究的目標，坦白說，與 DPN 研究一樣，目標是獲得一定程度的治療效果，以便我們能夠適當地為 III 期研究提供動力。

And the reason the DPN study had a pregabalin arm was because pregabalin is an available therapy for the treatment of DPN. This study, LSR, as a placebo arm because there is no specifically approved therapy for the treatment of LSR. I hope that helps.

DPN 研究之所以有普瑞巴林組，是因為普瑞巴林是治療 DPN 的可用療法。這項研究將LSR作為安慰劑組，因為沒有專門批准的治療LSR的療法。我希望這有幫助。

Chuck, we'll take two more questions, please.

Chuck，我們再問兩個問題。

Liisa Bayko, Evercore ISI.

莉莎·貝科，Evercore ISI。

Hi. Thanks for taking my question. Just a follow-up on vanzacaftor. Maybe you can talk about how you're expecting the rollout there in terms of patient uptake. It's not quite as much as at least as some of your other therapies are, but nevertheless, like the value there is obvious. Do you expect like quite quick conversion? Will it happen solely over time? Do you think the vast majority of patients will switch over? Just curious about what the feedback has been there?

你好。感謝您提出我的問題。只是 vanzacaftor 的後續行動。也許您可以談談您對在患者接受方面的推廣有何期望。它至少不如其他一些療法那麼多，但儘管如此，它的價值是顯而易見的。您期望如此快速的轉換嗎？它會隨著時間的推移而發生嗎？您認為絕大多數患者會轉行嗎？只是好奇那裡的回饋是什麼？

Stuart, any additional comments to make?

Stuart，還有什麼補充意見嗎？

Yes, just that we're as excited about the vanzacaftor launches of any of our other CFTR modulators for the reasons I think it's got a great benefit risk profile. And I think it is going to -- as I said earlier, I think it's going to be equally of interest to patients who are on a CFTR modulator today, but would like increased CFTR function as demonstrated by sweat chloride because these patients know that, that is important for their kind of health and well-being, but I think it's also going to be of value to those who continued.

是的，我們對 vanzacaftor 推出的任何其他 CFTR 調節劑感到興奮，因為我認為它具有巨大的效益風險。我認為，正如我之前所說，我認為今天使用 CFTR 調節劑的患者也會同樣感興趣，但希望透過汗液氯化物來增強 CFTR 功能，因為這些患者知道，這對他們的健康和福祉很重要，但我認為這對那些繼續堅持的人也很有價值。

So as I said earlier on, I really don't think there's kind of one group or another who are going to be more interested than others. I do think it's something that's going to be broadly of appeal to people. And as I also mentioned, not to forget the fact that it has the benefit of being once daily, which again, is an attractive part of a chronic medication. So as I said, we're as excited about the launch of vanza as we have been about any of our other CFTR modulators.

因此，正如我之前所說，我真的不認為某個群體會比其他群體更感興趣。我確實認為這會對人們產生廣泛的吸引力。正如我還提到的，不要忘記這樣一個事實，即它具有每天一次的好處，這又是慢性藥物的一個有吸引力的部分。正如我所說，我們對 vanza 的推出感到興奮，就像我們對任何其他 CFTR 調節劑一樣興奮。

I was just trying to get a sense of the -- like how quickly people might convert over your thinking? Do you think it will be kind of slow and steady or pretty rapid.

我只是想了解一下——例如人們會以多快的速度轉變你的想法？你認為它會是緩慢而穩定的還是相當快的？

Yes. I mean certainly, the reaction with physicians and patients, the profile has been very enthusiastic. I'm not going to speculate exactly on how much -- how rapidly we're going to get the transitions and people restarted, Liisa.

是的。我的意思當然是，醫生和患者的反應非常熱情。我不會準確推測我們將以多快的速度進行過渡和人員重新啟動，莉薩。

Liisa, maybe I'll just add one thing if you want to think through it. Patients with CF usually visit their doctors once a quarter. As Stuart said, the patients are very aware of drug development and vanzacaftor, in particular, as are their physicians and patients have consistently expressed interest in thinking about medicines that may bring them the potential for higher efficacy. I think that's as far as we can go with regard to timing. But maybe those are pieces of information that are helpful to you.

莉莎，如果你想仔細考慮的話，也許我可以添加一件事。囊性纖維化患者通常每季去看一次醫生。正如史都華所說，患者非常了解藥物開發和 vanzacaftor，尤其是他們的醫生和患者一直表示有興趣考慮可能為他們帶來更高療效的藥物。我認為這就是我們在時間安排方面所能做到的。但也許這些資訊對您有幫助。

Michael Yee, Jefferies.

麥可葉，杰弗里斯。

Hey, guys. Thank you. Two questions for us. On the Alpine product, can you just remind me, I know you guys think it's best-in-class, but how to think about greater reduction in proteinuria versus, say, a [beta] program that will have data in first half '25? And is it your idea that you have greater reductions and therefore, better stabilization of 3GFR or that it also will just be shining through in lupus and other autoimmune diseases for which we will have to wait for RUBY-3 data.

大家好。謝謝。有兩個問題想問我們。關於 Alpine 產品，您能提醒我一下嗎？您是否認為您的 3GFR 下降幅度更大，因此 3GFR 更穩定，或者它也將在狼瘡和其他自體免疫疾病中發揮作用，我們將不得不等待 RUBY-3 數據。

So just maybe talk about and remind us how you think the benefits will be seen on that product? And then really quickly on the Acute Pain launch, can you just remind me on the comments on the No Pain Act, you believe you'll eventually get reimbursement there, but that's more of a CMS exposure population to take that in considering. And for commercial, that's more about blocking and tackling on formularies and commercial plans?

那麼也許可以談談並提醒我們您認為該產品的好處如何？然後很快就推出了“急性疼痛”，您能提醒我有關《無痛法案》的評論嗎？對於商業而言，更多的是阻止和解決處方集和商業計劃？

Yes. Mike, I'm going to ask Stuart to comment on no pain first. I think it was a little hard to hear you might. But I think Stuart Mike's question is there's the No Pain Act pertain to government-paid patients and how are you thinking about commercial? And then I'll come back for pove.

是的。麥克，我要先請史都華對沒有疼痛發表評論。我認為聽到你的聲音有點困難。但我認為史都華麥克的問題是《無痛法案》適用於政府付費的患者，您如何看待商業？然後我會回來吃點東西。

Yes. So No Pain, Mike, is looking at the add-on payment to patients who are treated in the out-patient ambulatory surgical center setting. As you said, we were not listed as one of the products, but that is because we're not approved. And so yes, we do anticipate being added to that list -- suzetrigine is approved.

是的。因此，麥克，No Pain 正在考慮向在門診門診手術中心接受治療的患者提供附加付款。正如您所說，我們沒有被列為產品之一，但那是因為我們沒有獲得批准。所以，是的，我們確實預計會被添加到該清單中——suzetrigine 已獲得批准。

In terms of in the Medicare area, maybe you're also thinking of the alternatives to No Pain Act, which is looking at the level the playing field in terms of things like step therapy and not allowing things like that and utilization management in part D and also making sure that there is parity in terms of the co-pay for patients between opioids and non-opioids. In terms of commercial, as you said, these are less relevant to that. This is really the sort of, as you said, blocking and tackling is what we'll be doing in talking to commercial plans

就醫療保險領域而言，也許您也在考慮《無痛法案》的替代方案，該法案正在考慮階梯治療等方面的公平競爭環境，並且不允許此類事情以及 D 部分中的利用管理並確保阿片類藥物和非鴉片類藥物之間患者的自付額相同。就商業而言，正如您所說，這些與此不太相關。正如您所說，這確實是我們在討論商業計劃時要做的阻止和處理

And Mike, on the question on pove, I think the question was how should we think about pove in IgA nephropathy? And then how should we think about it in the other studies all about proteinuria. So the way I would think about it is underlying cause of disease and B-cell diseases. We have two Phase II studies going on. It was a very clever design by Alpine scientists.

麥克，關於 pove 的問題，我認為問題是我們應該如何看待 IgA 腎病中的 pove？那麼在其他有關蛋白尿的研究中我們該如何思考它。所以我的想法是疾病和 B 細胞疾病的根本原因。我們正在進行兩項二期研究。這是阿爾卑斯科學家的一個非常聰明的設計。

There's a RUBY-3, which is a basket of B-cell mediated renal diseases, IgA nephropathy, which is now going to Phase III this month. It has lupus nephritis in there, ANCA-associated nephritis as well as membranes.

RUBY-3 是一籃子 B 細胞介導的腎臟疾病、IgA 腎病，本月將進入 III 期臨床。它有狼瘡性腎炎、ANCA 相關性腎炎和膜性腎炎。

All of these diseases are B-cell-mediated diseases. In many of these diseases, proteinuria is important. But I'll tell you, for example, in membranes, PLA2R is a very important biomarker. And in some of the Nephritis, as you may know, hematuria is very, very important.

所有這些疾病都是 B 細胞介導的疾病。在許多此類疾病中，蛋白尿很重要。但我會告訴你，例如，在膜中，PLA2R 是一個非常重要的生物標記。如您所知，在某些腎炎中，血尿是非常非常重要的。

So I think protein is -- proteinuria is clearly very important in IgA nephropathy and its prominence is elevated because of the FDA's acceptance of proteinuria in IgA nephropathy as an accelerated approval endpoint. But hematuria is important in some looking at biomarkers like PLA2R is important in others.

因此，我認為蛋白尿在 IgA 腎病變中顯然非常重要，並且由於 FDA 接受 IgA 腎病變中的蛋白尿作為加速核准終點，因此其重要性得到了提升。但血尿對某些人來說很重要，而 PLA2R 對其他人來說也很重要。

And in the RUBY-4 basket, these are B-cell-mediated heme diseases, it's really not about proteinuria. It's about other markers of interest like it could be something like hemoglobin or in the case of ITP, it would be platelets. But the way I would look at it and my enthusiasm for povetacicept is because it is such a good B-cell -- such a good medicine to tamp down the B cells because it's dual inhibition and impacts maturation, proliferation and differentiation of B cells. And that's where my optimism for B-cell mediated diseases comes from.

在 RUBY-4 籃子中，這些是 B 細胞介導的血紅素疾病，實際上與蛋白尿無關。它與其他感興趣的標記物有關，例如血紅蛋白等，或者就 ITP 而言，可能是血小板。但我看待它的方式以及我對povetacicept 的熱情是因為它是一種非常好的B 細胞——一種抑制B 細胞的好藥，因為它具有雙重抑製作用並影響B 細胞的成熟、增殖和分化。這就是我對 B 細胞介導的疾病持樂觀態度的來源。

This concludes our question-and-answer session as well as our conference call for today. Thank you for presentation. A replay of today's event will be available shortly after the call concludes by dialing 1 (877) 344-7529 or 1 (412) 317-0088 using replay access code 10186971. Thank you for your participation, and you may now disconnect.

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