福泰製藥 (VRTX) 2021 Q2 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Vertex Pharmaceuticals Q2 2021 Conference Call. (Operator Instructions) Please be advised that today's conference call is being recorded. (Operator Instructions)

您好，感謝您的耐心等待。歡迎參加Vertex Pharmaceuticals 2021年第二季業績電話會議。 （操作說明）請注意，本次電話會議正在錄音。 （操作說明）

At this time, I'd like to turn the call over to your host to Mr. Michael Partridge. Sir, you may begin.

現在，我想把電話交給主持人麥可·帕特里奇先生。先生，您可以開始了。

Good evening. This is Michael Partridge. Welcome to the Vertex Second Quarter 2021 Financial Results Conference Call. Making prepared remarks on the call tonight, we have Dr. Reshma Kewalramani, Vertex' CEO and President; Stuart Arbuckle, Chief Commercial and Operations Officer; and Charlie Wagner, Chief Financial Officer.

晚安.我是邁克爾·帕特里奇。歡迎參加Vertex公司2021財年第二季財務業績電話會議。今晚在會議上作發言的有：Vertex公司執行長兼總裁雷什瑪·凱瓦拉馬尼博士；首席商務及營運長斯圖爾特·阿巴克爾；以及首席財務官查理·瓦格納。

We recommend that you access the webcast slides on our website as you listen to this call. This call is being recorded. A replay will be available on our website.

我們建議您在收聽本次電話會議的同時，請造訪我們網站上的網路直播投影片。本次電話會議正在錄音，錄音回放將在我們的網站上提供。

We will make forward-looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission. These statements, including, without limitation, those regarding Vertex' marketed CF medicines, our pipeline and Vertex's future financial performance, are based on management's current assumptions. Actual outcomes and events could differ materially.

我們將在本次電話會議上發表前瞻性聲明，這些聲明受制於今天新聞稿和我們向美國證券交易委員會提交的文件中詳細討論的風險和不確定性。這些聲明，包括但不限於有關Vertex已上市的囊性纖維化藥物、我們的研發管線以及Vertex未來財務業績的聲明，均基於管理層當前的假設。實際結果和事件可能與這些假設有重大差異。

I would also note that select financial results and guidance we will review on the call this evening are non-GAAP.

我還想指出，我們今晚電話會議上將要討論的部分財務表現和指引是非GAAP準則的。

I will now turn the call over to Dr. Reshma Kewalramani.

現在我將把電話轉給雷什瑪·凱瓦拉瑪尼醫生。

Thank you, Michael. As we reach the halfway point in 2021, our business is performing exceptionally well and is very well positioned for the future. Our CF franchise is strong and growing. During the second quarter, we reached a number of new reimbursement agreements for the triple combination as well as other CFTR modulators in our portfolio, including major markets like France and Italy, earlier than expected. These reimbursement agreements are occurring in a time frame that is far quicker than is typical for OUS markets and importantly, we are achieving reimbursements at levels which are robust and reflect the value of our CF medicines.

謝謝邁克爾。 2021年已過半，我們的業務表現非常出色，並為未來發展奠定了堅實的基礎。我們的囊性纖維化（CF）產品線強勁且持續成長。第二季度，我們與多家主要市場（如法國和義大利）達成了新的健保報銷協議，涵蓋了我們產品組合中的三聯療法以及其他CFTR調節劑，且比預期提前完成。這些健保報銷協議的達成速度遠超過美國以外市場的平均水平，更重要的是，我們獲得的報銷金額穩健，充分體現了我們CF藥物的價值。

We also secured regulatory approval for the triple combination in the 6 to 11 age for the U.S. Taken together, these additional reimbursement agreements and regulatory approvals provide thousands of new patients with access to our medicines. As such, we are raising our 2021 guidance range by $500 million to a range of $7.2 billion to $7.4 billion, reflecting 18% year-on-year growth at the midpoint of the range. But our work in CF is not done. There are still more than 30,000 people with CF who are yet to be treated. And by reaching these patients, we see continued significant growth for the CF business.

我們也獲得了美國監管機構對6至11歲兒童三合一療法的批准。這些新增的健保報銷協議和監管批准，將使成千上萬的新患者能夠獲得我們的藥物。因此，我們將2021年的業績預期上調5億美元至72億至74億美元，按預期中位數計算，年增18%。但我們在囊性纖維化領域的工作尚未結束。目前仍有超過3萬名囊性纖維化患者尚未接受治療。我們相信，透過惠及這些患者，囊性纖維化業務將持續保持顯著成長。

With regard to the pipeline, progress is accelerating across the portfolio. We now expect to achieve target enrollment in both CTX001 studies in Q3. We have initiated the VX-548 Phase II program in acute pain. We are on track to begin the Phase III of next-in-class triple combination program in CF shortly. And in the next 6 to 9 months, we expect important data readouts from multiple clinical stage programs, including VX-147 in APOL1-mediated FSGS, VX-548 in acute pain and VX-880 in type 1 diabetes.

在產品線方面，所有專案的進度都在加速。我們預計將在第三季完成兩項CTX001研究的目標入組人數。我們已啟動VX-548治療急性疼痛的II期臨床試驗。我們正按計畫推進，即將啟動針對囊性纖維化的新型三重療法計畫的III期臨床試驗。未來6至9個月內，我們預計將獲得多個臨床階段項目的重要數據，包括VX-147治療APOL1介導的局部節段性腎小球硬化症（FSGS）、VX-548治療急性疼痛以及VX-880治療第1型糖尿病。

I'll now review the key clinical stage programs in more detail. Starting with CF. We are relentless in our efforts to maximize the benefit we can deliver for patients. TRIKAFTA sets the very high bar, and we recognize that any new medicine that aims to treat the 90% of people with CF with at least 1 F508del, including our own medicines, has to show clear potential to improve on TRIKAFTA. We announced earlier this week that the once a day next-in-class triple combination VX-121, tezacaftor, VX-561 is advancing to Phase III. We believe it holds the potential for greater efficacy and convenience for patients. It also has the benefit of enhanced economics for our business based on the fact that the royalty obligation would decrease from low double digits to low single digits.

接下來，我將更詳細地介紹關鍵的臨床階段項目。首先是囊性纖維化（CF）項目。我們始終不懈努力，力求最大化病人。 TRIKAFTA 樹立了極高的標桿，我們認識到，任何旨在治療至少攜帶一個 F508del 突變的 90% CF 患者的新藥，包括我們自己的藥物，都必須展現出超越 TRIKAFTA 的明顯潛力。本週早些時候，我們宣布每日一次的同類三聯療法 VX-121、tezacaftor 和 VX-561 已進入 III 期臨床試驗。我們相信，該療法有望為患者帶來更高的療效和更方便的用藥體驗。此外，由於其特許權使用費將從兩位數低點降至個位數低位，因此也有利於我們業務的經濟效益。

We are also committed to developing therapies for the approximately 10% of patients who cannot benefit from CFTR modulators. Our lead program in partnership with Moderna uses an mRNA-based approach and continues to make progress in late preclinical development.

我們也致力於為約10%無法從CFTR調節劑中獲益的患者開發治療方案。我們與Moderna合作的主要專案採用基於mRNA的方法，並在後期臨床前開發階段持續取得進展。

Let me now turn to our non-CF clinical pipeline which includes 5 mid- to late-stage programs using 3 different therapeutic modalities, including small molecules, cell and genetic therapies. The most advanced program in the pipeline is CTX001, our gene editing therapy, which represents a potential onetime functional cure for patients with beta thalassemia and sickle cell disease. This program continues to have strong momentum and impressive results.

現在，我想談談我們非囊性纖維化（CF）的臨床研發管線，其中包括5個處於中後期階段的項目，採用3種不同的治療模式，包括小分子藥物、細胞療法和基因療法。其中進展最快的項目是CTX001，這是一種基因編輯療法，可望為β地中海貧血和鐮狀細胞貧血患者提供一次性功能性治癒方案。該項目目前發展勢頭強勁，並已取得令人矚目的成果。

We've shared new data at EHA last month involving 22 patients who were treated with CTX001 and had at least 3 months of follow-up. In this data set, all beta thalassemia patients, including beta 0 patients who have the most severe form of the disease were transfusion independent. And all sickle cell patients were free of pain crises following CTX001 therapy. We now have dosed more than 45 patients across the program and are on track to achieve target enrollment in both CTX001 studies in the third quarter. We are working with regulators to finalize the filing package for CTX001 and anticipate filing for approval in the next 18 to 24 months.

上個月，我們在歐洲血液學協會 (EHA) 會議上分享了關於 22 名接受 CTX001 治療且至少追蹤 3 個月的患者的新數據。在該資料集中，所有 β 地中海型貧血患者，包括病情最嚴重的 β0 型患者，均無需輸血。所有鐮狀細胞貧血患者在接受 CTX001 治療後均未出現疼痛危機。目前，我們已在整個計畫中為超過 45 名患者完成了給藥，並預計在第三季度實現兩項 CTX001 研究的目標入組人數。我們正在與監管機構合作，最終確定 CTX001 的申報資料，預計將在未來 18 至 24 個月內提交上市申請。

Moving to VX-147. VX-147 is our lead molecule for the treatment of APOL1-mediated kidney disease, and we anticipate clinical data from our Phase II proof-of-concept study in APOL1-mediated FSGS in the second half of 2021. The VX-147 Phase II study evaluates the safety and the reduction of proteinuria over the course of 13 weeks. The achievement of double digit decreases in proteinuria with this molecule would be a significant risk-lowering milestone for the program as this will establish APOL1 inhibition as a promising new mechanism that can be applied to the approximately 100,000 patients in the U.S. and Europe who have APOL1-mediated nondiabetic proteinuric kidney diseases.

接下來是VX-147。 VX-147是我們治療APOL1介導的腎臟疾病的主導分子，我們預計將於2021年下半年獲得其在APOL1介導的局部節段性腎小球硬化症（FSGS）中開展的II期概念驗證研究的臨床數據。 VX-147 II期研究旨在評估該藥物在13週內的安全性和降低蛋白尿的效果。如果該分子能夠使蛋白尿降低兩位數，這將是該計畫在降低風險方面的一個重要里程碑，因為這將確立APOL1抑制劑作為一種有前景的新機制，可用於治療美國和歐洲約10萬名患有APOL1介導的非糖尿病性蛋白尿性腎臟疾病的患者。

Consistent with the portfolio approach we take with every pipeline program, we have multiple molecules in development behind VX-147 targeting the APOL1 pathway.

與我們對每個研發管線專案採取的組合策略一致，除了 VX-147 之外，我們還有多個針對 APOL1 路徑的分子正在研發中。

Turning to the NaV1.8 program. As announced last week, the Phase II trial in acute pain following bunionectomy surgery with our selective NaV1.8 inhibitor, VX-548, is underway, and data are expected by early 2022. NaV1.8 is both generally and pharmacologically validated with our previous molecule VX-150, demonstrating positive proof-of-concept in acute neuroplastic and musculoskeletal pain. VX-548 is more potent than our prior molecules, which allows us to use lower doses and also more fully explore the dose response curve.

接下來談談NaV1.8計畫。正如上周宣布的那樣，我們選擇性NaV1.8抑制劑VX-548治療拇外翻切除術後急性疼痛的II期臨床試驗正在進行中，預計將於2022年初獲得數據。 NaV1.8已通過我們先前的分子VX-150進行了普遍驗證和藥理學驗證，在急性神經可塑性和肌肉骨骼疼痛方面展現出積極的概念驗證。 VX-548比我們之前的分子效力更強，這使我們能夠使用更低的劑量，並更全面地探索劑量反應曲線。

We expect to move faster with VX-548 by conducting multiple clinical studies in parallel. Indeed, we are starting a second Phase II acute pain study following abdominoplasty in the coming weeks. The potential to serve patients suffering from acute pain is substantial, and Stuart will share additional perspective on the market opportunity in his remarks.

我們計劃透過並行進行多項臨床研究來加快VX-548的研發進程。事實上，我們將在未來幾週內啟動第二項針對腹部整形術後急性疼痛的第二期臨床研究。該藥物在治療急性疼痛方面具有巨大的潛力，Stuart將在演講中分享他對市場機會的更多見解。

Moving on to type 1 diabetes, the Phase I/II study with VX-880, our islet cells-alone approach is underway, and the first patient has been dosed. Ours is the only approach to use stem cell-derived fully differentiated insulin-producing islet cells, distinguishing it from all other therapies in clinical development today. Similar to CTX001, we anticipate that proof of concept for VX-880 may be established with relatively small numbers of patients over a reasonably efficient time frame. We expect initial data from the study in 2022.

接下來談談第1型糖尿病，我們針對1型糖尿病開發的VX-880（一種僅使用胰島細胞的療法）的I/II期臨床試驗正在進行中，首例患者已接受給藥。我們的療法是唯一使用幹細胞衍生的完全分化的胰島素分泌胰島細胞的療法，這使其區別於目前所有其他正在臨床開發的療法。與CTX001類似，我們預期VX-880的概念驗證可以在相對較少的患者中，在合理的時間範圍內完成。我們預計將於2022年獲得該研究的初步數據。

Our optimism for this program and for the ability of VX-880 to demonstrate clinical benefit comes from the cadaveric islet cell transplantation experience, which has already provided a precedent for transformational outcome. Beyond VX-880, our cell plus device program is continuing to progress in late preclinical development.

我們對此計畫以及VX-880展現臨床療效的能力充滿信心，這源自於我們以往的屍體胰島細胞移植經驗，這已為變革性療效提供了先例。除了VX-880之外，我們的細胞聯合裝置計畫也持續推進，目前正處於臨床前開發的後期階段。

Finally, in AATD. As we shared with you in June, the VX-864 Phase II clinical data showed clear evidence of biological activity, though the magnitude of clinical effect did not support its progression to pivotal studies. Based on these data, we remain confident in and committed to AATD and to our small molecule corrector approach. This is the only approach that targets the underlying cause of AATD and therefore, holds the potential to treat both the lung and liver manifestations of disease. We expect that our next wave of molecules will advance into the clinic in 2022, and that we will be a more rapidly through clinical development with the insights we have gained from the VX-864 trial.

最後，我們來談談AATD。正如我們在6月與您分享的，VX-864的II期臨床數據顯示其具有明顯的生物活性，但臨床療效的程度尚不足以支持其進入關鍵性研究階段。基於這些數據，我們仍然對AATD以及我們的小分子矯正劑療法充滿信心並致力於此。這是目前唯一針對AATD根本病因的療法，因此有望同時治療肺部和肝臟的疾病表現。我們預計下一批分子將於2022年進入臨床試驗階段，並且憑藉從VX-864試驗中獲得的經驗，我們將更快地推進臨床開發。

I'll now hand it off to Stuart.

現在我把它交給史都華。

Thank you, Reshma. I'll begin by reviewing the Q2 revenue performance of our CF medicines. Our Q2 global revenues reached nearly $1.8 billion, driven by increasing revenues outside the U.S. as a result of the launch of KAFTRIO and continued strong performance in the U.S. In the U.S., the launch of TRIKAFTA in ages 12-plus has been highly successful. And just under 2 years since regulatory approval, the vast majority of eligible patients have initiated treatment.

謝謝Reshma。我首先回顧我們囊性纖維化藥物第二季度的營收表現。第二季全球營收接近18億美元，主要得益於KAFTRIO上市後美國以外地區營收的成長，以及美國市場持續強勁的業績。在美國，TRIKAFTA針對12歲及以上族群的上市取得了巨大成功。自從獲得監管部門批准以來，不到兩年時間，絕大多數符合條件的患者已經開始接受治療。

We have continued to see very high persistence and compliance levels, and we're now focused on the ongoing launch of TRIKAFTA in children ages 6 to 11 in the U.S., following the approval in June. Outside the U.S., we have made significant progress with reimbursement for our medicines. We now have reimbursed access for KAFTRIO in more than 15 countries outside the U.S., less than 1 year following EMA approval. This compares favorably to the industry standard, both in terms of the time line in individual countries and the total number of markets to reimbursement agreements.

我們持續觀察到極高的患者依從性和堅持度，目前正專注於TRIKAFTA在美國6至11歲兒童中的持續上市，該藥物已於6月獲得批准。在美國以外，我們在藥品報銷方面取得了顯著進展。在獲得EMA批准不到一年後，KAFTRIO已在美國以外的15個以上國家/地區獲得報銷。無論從單一國家/地區的報銷時間或獲得報銷協議的市場總數來看，這都優於行業標準。

Our rapid reimbursement progress can be attributed to multiple factors: the transformative clinical benefits of the triple combination, the support and collaboration of governments and the CF community and the expertise of our commercial team, built over the course of a decade.

我們快速獲得報銷的進展可歸因於多種因素：三合一療法的變革性臨床益處、政府和囊性纖維化社群的支持與合作，以及我們商業團隊在過去十年中累積的專業知識。

Importantly, as Reshma mentioned earlier, we are achieving reimbursement for our medicines at levels that recognize their considerable clinical value. The pivotal clinical trial data for TRIKAFTA were unprecedented. And as with all of our prior medicines, we are continuing to track the long-term performance of the triple combination in extension studies of our pivotal trials and in the real world, to be able to fully understand and communicate the long-term benefits of CFTR modulator therapy to all key stakeholders.

正如Reshma之前提到的，我們藥物的報銷水平已達到與其顯著臨床價值相符的水平，這一點至關重要。 TRIKAFTA的關鍵性臨床試驗數據前所未有。與我們以往的所有藥物一樣，我們正在關鍵性試驗的擴展研究和真實世界中持續追蹤三聯療法的長期療效，以便能夠充分了解CFTR調節劑療法的長期益處，並將其傳達給所有關鍵利益相關者。

We have previously shown powerful evidence that treatment with KALYDECO, ORKAMBI and SYMDEKO slows lung function decline, results in multisystem benefits and transforms the course of the disease in CF patients. Earlier this month, we have obtained our first long-term follow-up data with the triple combination. In the FF and FMF patient populations treated for at least 96 weeks with TRIKAFTA in the open-label extension of the pivotal clinical trials, we do not see any decline in mean lung function over time. This is a first for any of our CFTR modulators. We look forward to sharing these data in a forthcoming medical forum.

我們先前已提供強有力的證據，顯示使用 KALYDECO、ORKAMBI 和 SYMDEKO 治療可延緩囊性纖維化 (CF) 患者的肺功能下降，帶來多系統獲益，並改變疾病進程。本月初，我們獲得了該三聯療法的首個長期追蹤數據。在關鍵性臨床試驗的開放標籤擴展研究中，接受 TRIKAFTA 治療至少 96 週的家族性地中海熱 (FMF) 和家族性纖維化纖維化 (FF) 患者群體中，我們未觀察到平均肺功能隨時間推移而下降。這是我們所有 CFTR 調節劑中首次觀察到這種情況。我們期待在即將舉行的醫學論壇上分享這些數據。

Although we are pleased with what we have achieved so far, we still have a long way to go to reach all CF patients. As we have previously communicated, we estimate there are 83,000 people living with CF in the U.S., Canada, Europe and Australia, and approximately 90% of these are likely to benefit from a CFTR modulator. We estimate that there are more than 30,000 patients who could benefit from our current CF medicines who are not yet being treated.

儘管我們對目前所取得的成就感到欣慰，但要惠及所有囊性纖維化（CF）患者，我們還有很長的路要走。正如我們之前所溝通的，我們估計美國、加拿大、歐洲和澳洲共有83,000名CF患者，其中約90%的人可能受益於CFTR調節劑。我們估計，還有超過30,000名患者可能受益於我們現有的CF藥物，但尚未接受治療。

Reaching these patients, which will drive significant additional revenue growth, will be achieved by successfully launching our medicines where we have reimbursement, securing additional new reimbursement agreements and label expansions to younger age groups, and we remain confident we will be able to reach the vast majority of these patients.

我們將透過在已獲得報銷的地區成功推出我們的藥物、爭取更多新的報銷協議以及將適應症擴大到更年輕的年齡組，來接觸到這些患者，這將推動顯著的額外收入增長。我們仍然有信心能夠接觸到絕大多數這類患者。

I would now like to provide some perspective on the market opportunities for some of the other medicines in our mid- and late-stage pipeline. Starting with CTX001. With the amendment of our collaboration agreement with CRISPR Therapeutics, Vertex now has taken global leadership for all aspects of the CTX001 program. As a result, we are in a position to leverage Vertex's demonstrate the ability to develop and secure access and reimbursement for transformative medicines.

現在我想就我們中後期研發管線中其他一些藥物的市場機會提供一些見解。首先是CTX001。隨著我們與CRISPR Therapeutics合作協議的修訂，Vertex目前已在全球全面主導CTX001計畫的各個面向。因此，我們能夠充分發揮Vertex在開發、確保變革性藥物的可近性和健保報銷方面的能力。

We see tremendous potential for CTX001. We estimate that there are more than 150,000 patients in the U.S. and Europe who have beta thalassemia or sickle cell disease, approximately 32,000 of whom have severe disease. 25,000 are severe sickle cell disease patients, and the vast majority of these are in the U.S.

我們看到了CTX001的巨大潛力。據估計，美國和歐洲有超過15萬名β地中海貧血或鐮狀細胞疾病患者，其中約3.2萬名患者病情嚴重。 2.5萬名患者是重症鐮狀細胞疾病患者，而絕大多數患者都在美國。

We believe that a gene-editing approach, which holds the potential for a onetime curative treatment will be highly valued by patients, physicians and payers. Consistent with our own internal market research, published physician surveys in the U.S. consistently indicate that they expect 1/4 to 3/4 of the sickle cell disease patients would be good candidates for a onetime curative approach using the current conditioning regimen, which is in line with the estimates of the numbers of severe patients. And with gentler conditioning regimens in the future, we expect CTX001 to be an attractive option for a much larger proportion of the 150,000 beta thalassemia and sickle cell disease patients.

我們相信，基因編輯療法有望實現一次性治愈，因此將受到患者、醫生和支付方的高度重視。與我們內部市場調查結果一致，美國已發表的醫生調查也一致表明，他們預計有四分之一到四分之三的鐮狀細胞病患者適合採用目前的預處理方案進行一次性治愈，這與重症患者數量的估計相符。隨著未來更溫和的預處理方案的出現，我們預期CTX001將成為15萬β地中海貧血和鐮狀細胞疾病患者中更大比例族群的理想選擇。

Our pre-commercial efforts are well underway. There are a number of notable features that are guiding our approach to this market, including: one, patients with severe beta thalassemia and sickle cell disease are symptomatic and have a lifelong history of hospitalizations and other significant cost burdens. We are developing health economic models to demonstrate the cost effectiveness of a functional cure for these patients. Two, new and flexible payment models will be needed for a functional cure for these diseases. We are engaged with payers to understand what models work best for them and for patients. And three, patients are geographically concentrated. For instance, 75% of eligible sickle cell patients in the U.S. live in 15 states.

我們的商業化前期工作進展順利。我們針對這一市場採取的策略主要基於以下幾個顯著特徵：第一，重度β地中海貧血和鐮狀細胞疾病患者症狀明顯，且終生需要住院治療，並承受著其他沉重的經濟負擔。我們正在開發衛生經濟學模型，以證明針對這些患者進行功能性治癒的成本效益。第二，針對這些疾病的功能性治癒需要新的、靈活的支付模式。我們正在與支付方溝通，以了解哪些模式對他們和患者最有利。第三，患者在地理分佈上高度集中。例如，美國75%符合條件的鐮狀細胞疾病患者居住在15個州。

We will use these and other insights to establish a commercial operation that is both lean and highly effective as we have in CF today.

我們將利用這些以及其他見解，建立一個像我們今天在CF中那樣精簡且有效率的商業營運模式。

Let me now turn to pain and share our perspective on the market opportunity for a novel medicine in this area. Acute pain therapies represent 1.8 billion treatment days a year in the U.S. Despite more than 90% of prescriptions being generic, acute pain still represents a $4 billion market, underscoring the opportunity for a novel transformative agent. A new medicine that even takes a portion of the current treatment days has multibillion dollar potential.

現在，我想談談疼痛，並分享我們對該領域新型藥物市場機會的看法。在美國，急性疼痛治療​​每年需要18億個治療日。儘管超過90%的處方藥是仿製藥，但急性疼痛市場仍高達40億美元，凸顯了新型變革性藥物的巨大潛力。即使新藥只能減少部分現有治療日，但也具有數十億美元的市場潛力。

In acute pain, a significant component of the market is opioids. A medicine with high efficacy and without the limitations of opioids, particularly their addictive potential, would be transformative for patients and the health care system.

在急性疼痛治療​​領域，阿片類藥物佔據了相當大的市場。如果有一種藥物既高效又沒有阿片類藥物的局限性，尤其是成癮性，那麼它將對患者和醫療保健系統產生變革性的影響。

With regards to commercialization, treatment is highly concentrated within hospital and postoperative settings. 25% of U.S. hospitals account for 80% of all opioid prescriptions. Given this concentration, successful commercialization will be possible with a small specialist focused commercial model, again, consistent with our lean SG&A approach.

就商業化而言，治療高度集中在醫院和術後環境。美國25%的醫院開出了80%的鴉片類藥物處方。鑑於這種集中度，採用小型專業化的商業模式即可成功實現商業化，這與我們精簡的銷售、管理及行政費用（SG&A）策略相一致。

Finally, type 1 diabetes. VX-880 has advanced to patient studies. And relatively soon, we will begin to have a view of its clinical profile. We estimate that 60,000 patients in the U.S. and Europe with severe type 1 diabetes or type 1 diabetes with prior kidney transplant would be potential candidates for VX-880. In and of itself, the islet cells alone program is a significant market opportunity, and existing transplant approaches establish a basis for the high value of a transformative therapy. Beyond VX-880, the cells and device program could address the broader type 1 diabetes population, 2.6 million patients in the U.S. and Europe.

最後，我們來看看第1型糖尿病。 VX-880已進入患者研究階段。不久之後，我們將開始了解其臨床概況。我們估計，美國和歐洲約有6萬名重度第1型糖尿病患者或先前接受過腎臟移植的第一型糖尿病患者可能適合接受VX-880治療。光是胰島細胞療法本身就蘊含著巨大的市場機遇，而現有的移植方法也為這種變革性療法的高價值奠定了基礎。除了VX-880之外，細胞和器械療法計畫還可以惠及更廣泛的第1型糖尿病族群，即美國和歐洲的260萬名患者。

In conclusion, it's an exciting time to be at Vertex as we continue to bring our CF medicine to more patients, and we still have significant growth ahead in CF with new reimbursement agreements and label expansions to younger age groups. And beyond CF, mid and late-stage pipeline is rapidly advancing with each program, having both the potential to transform lives and presenting a significant commercial opportunity.

總之，對Vertex而言，這是一個令人振奮的時刻。我們正持續將囊性纖維化（CF）藥物帶給更多患者，隨著新的醫保報銷協議的簽署以及適應症擴展至更年輕的患者群體，我們在CF領域仍擁有巨大的成長潛力。此外，除CF領域外，我們的中後期研發管線也正在快速推進，每個專案都具有改變病患生活的潛力，並蘊藏著巨大的商業機會。

And with that, I'll hand it over to Charlie.

然後，我就把它交給查理了。

Thanks, Stuart. In the second quarter of 2021, Vertex, again continued its record of outstanding financial performance. In fact, we're in the midst of our eighth consecutive year of at least double-digit revenue growth. Second quarter total product revenues were $1.79 billion, an 18% increase compared to the second quarter of 2020. This growth was primarily driven by strong international uptake of KAFTRIO and continued performance of TRIKAFTA in the U.S.

謝謝，斯圖爾特。 2021年第二季度，Vertex再次延續了其卓越的財務表現。事實上，我們已連續第八年實現至少兩位數的營收成長。第二季產品總營收為17.9億美元，較2020年第二季成長18%。這一成長主要得益於KAFTRIO在國際市場的強勁表現以及TRIKAFTA在美國市場的持續成功。

Our second quarter revenues included $1.26 billion in the U.S. and $536 million outside the U.S. Ex U.S. revenues for the quarter grew 71% over the prior year, reflecting the full quarter effect of prior initiations in Europe as well as any new patient initiations in countries where patients have access to KAFTRIO.

我們第二季的營收包括美國 12.6 億美元和美國以外 5.36 億美元。本季度美國以外地區的收入比上年增長了 71%，反映了先前在歐洲啟動的全部季度影響，以及在患者可以獲得 KAFTRIO 的國家/地區啟動的任何新患者。

Our second quarter combined R&D and SG&A expenses were $537 million compared to $467 million for the second quarter of 2020, driven largely by investment in our clinical stage programs and our research pipeline. As our pipeline continues to expand and mature, we expect our R&D investments will continue to be substantial while we drive toward proof-of-concept data and further clinical and regulatory progress across the pipeline.

我們第二季的研發和銷售、管理及行政費用合計為5.37億美元，而2020年第二季為4.67億美元，主要得益於對臨床階段專案和研發管線的投資。隨著研發管線的不斷擴展和成熟，我們預計研發投入將繼續保持強勁勢頭，同時我們將努力獲得概念驗證數據，並在臨床和監管方面取得進一步進展。

Our continued growth in revenues, combined with carefully managed growth in spending translates to a second quarter operating margin of 57%. With our strong revenue and profitability, we ended the quarter with $6.7 billion in cash, following the onetime $900 million payment to CRISPR Therapeutics for the amended collaboration.

我們持續成長的收入，加上對支出成長的謹慎控制，使得第二季營業利潤率達到 57%。憑藉強勁的收入和盈利能力，在向 CRISPR Therapeutics 支付了 9 億美元的一次性款項以用於修訂合作協議後，我們本季末持有 67 億美元的現金。

Our strong financial performance to date, the future growth profile in CF and the tremendous potential of our broad and deep pipeline made this the right time for the $1.5 billion stock repurchase authorization that we announced in June. This authorization gives us the opportunity to repurchase stock at very attractive prices as we seek to offset future dilution from equity programs.

鑑於我們迄今為止強勁的財務表現、CF業務的未來成長前景以及我們廣泛而深厚的產品線所蘊含的巨大潛力，現在正是我們6月份宣布的15億美元股票回購計劃的恰當時間。這項授權使我們能夠以極具吸引力的價格回購股票，從而抵消未來股權激勵計畫可能帶來的稀釋效應。

Now to guidance. We are making a significant upward revision to our previously issued 2021 guidance for total product revenues to a range of $7.2 billion to $7.4 billion. This $500 million increase in our revenue guidance range reflects year-to-date business outperformance as well as the rapid progress we have made in reaching new reimbursement agreements. Year-over-year, this guidance represents nearly 18% growth at the midpoint. As is our practice, the guidance only includes revenue for countries that are currently reimbursed. Future new reimbursements are not included.

現在來說說業績指引。我們大幅調高了先前發布的2021年產品總收入指引，目標區間為72億美元至74億美元。此次調漲5億美元，反映了年初至今的業務表現優異，以及我們在達成新的健保報銷協議方面取得的快速進展。與去年同期相比，該指引的中位數成長近18%。依照慣例，指引僅包含目前已納入健保報銷範圍的國家的收入，未來新增的健保報銷不包括在內。

We are maintaining our non-GAAP OpEx guidance for the full year 2021 at $2.25 billion to $2.3 billion. Driven by R&D investment, we anticipate that our OpEx in the second half of 2021 will be sequentially greater than in the first half of the year. Specific drivers include the new economic split under the amended CTX001 collaboration, advancement of VX-548 to multiple studies in pain and investment to support type 1 diabetes clinical development.

我們維持2021年全年非GAAP營運支出預期為22.5億美元至23億美元。受研發投入的推動，我們預計2021年下半年的營運支出將較上月高於上半年。具體驅動因素包括：根據修訂後的CTX001合作協議，新的經濟分成比例；VX-548在疼痛治療領域推進至多項研究；以及對第1型糖尿病臨床開發的支持性投資。

For our non-GAAP tax rate, we continue to guide to a range of 21% to 22% this year.

對於我們的非GAAP稅率，我們預計今年的稅率區間為21%至22%。

Looking to the future, the financial profile of our business is exceptional in many ways. First, we expect to see continued significant top and bottom line growth from our CF franchise into the middle of the decade as we continue to reach more and more patients. Second, our CF revenues are well protected by the triple combinations strong IP, which extends to the late 2030s and which could be further extended with the new next-in-class triple now entering pivotal trials. Third, our differentiated business model and lean SG&A lead to high margins and strong cash flow, which allows for sustained levels of investment into internal and external R&D and continued strong earnings growth.

展望未來，我們公司的財務狀況在許多方面都堪稱卓越。首先，隨著我們持續拓展服務對象，預計到本世紀中期，囊性纖維化（CF）業務的營收和利潤將持續顯著成長。其次，我們強大的三聯療法智慧財產權為CF業務的收入提供了強有力的保障，該知識產權的有效期至2030年代末，並且隨著新一代三聯療法進入關鍵性試驗階段，其有效期有望進一步延長。第三，我們差異化的商業模式和精簡的銷售、管理及行政費用（SG&A）帶來了高利潤率和強勁的現金流，從而能夠持續加大對內部和外部研發的投入，並保持強勁的盈利增長。

And finally, we have a number of multibillion-dollar opportunities advancing in the pipeline, many with near-term milestones, including those in beta thal, sickle cell disease, APOL1-mediated kidney disease, pain, type 1 diabetes and AAT, each of which have the potential to drive significant growth beyond CF into the 2030s.

最後，我們還有多個價值數十億美元的項目正在推進中，其中許多項目近期都有里程碑式的進展，包括β地中海貧血、鐮狀細胞病、APOL1介導的腎病、疼痛、1型糖尿病和AAT，每一項都有可能在2030年代推動囊性纖維化以外的顯著增長。

With that, I'll turn it back to Reshma to close.

這樣，我就把麥克風交還給雷什瑪，讓她來收尾。

Why don't we go directly to questions and open the phone lines now.

不如我們直接進入問答環節，現在就開通電話熱線吧。

(Operator Instructions) I show our first question comes from the line of Michael Yee from Jefferies.

（操作說明）我展示的第一個問題來自 Jefferies 的 Michael Yee 的演講。

Reshma, I know that there's an important Phase II readout for FSGS later this year, and you've talked about that, and I know you've talked about what you're looking for in terms of reduction proteinuria. I guess my question was twofold. One, are there scenarios where reductions are more modest and you have to think about what that would mean for going forward?

雷什瑪，我知道今年稍後會有一項重要的FSGS II期臨床試驗結果公佈，你也談到過這一點，也知道你談到過你在蛋白尿減少方面所關注的指標。我的問題有兩個面向。第一，是否有蛋白尿減少幅度較小的情況，你需要考慮這對未來的研究意味著什麼？

And second, if it was really good reduction proteinuria is a surrogate. So when you still need to run a much longer study. I appreciate, it's a genetic mutation patient population. So maybe you could talk to those scenarios and how you think about the robustness of data?

其次，如果蛋白尿減少效果確實很好，那它就只是一個替代指標。所以，你仍然需要進行更長時間的研究。我知道，這是基因突變患者群。那麼，您能否談談這些情況，以及您如何看待數據的可靠性？

Yes. Mike, the question you asked is about the VX-147 program. For the others on the phone, this is the APOL1-mediated FSGS program that is currently in Phase II, and we are on track to read out the Phase II results in the second half of this year. The way I see this program, Mike, and what we're really looking for is safety for sure. It's a Phase II program. And on the efficacy side, you're right, it is about percent reduction in proteinuria. And we are looking for a double-digit reduction in proteinuria because at those levels, it's meaningful and it is correlated with improvements in GFR and the hard endpoints of time to ESRD.

是的。麥克，你問的問題是關於VX-147專案的。對於其他電話裡的朋友，這是針對APOL1介導的FSGS的II期臨床試驗項目，我們計劃在今年下半年公佈II期臨床試驗結果。麥克，在我看來，這個項目，我們真正關注的當然是安全性。這是一個II期臨床試驗計畫。至於療效方面，你說得對，我們關注的是蛋白尿的降低百分比。我們希望蛋白尿降低達到兩位數，因為達到這個水平才有意義，而且與腎小球濾過率（GFR）的改善以及進展至終末期腎病（ESRD）的時間等硬終點指標相關。

As with all of our programs, Mike, we have a portfolio approach here. I am excited to see these results. The community physicians as well as patient groups and the regulators, particularly in the U.S., have had multiple workshops and conferences over the last several years. And the regulators have expressed openness for proteinuria to be the regulatory enabling endpoint. Now whether that's an accelerated approval, whether that's a full approval, all of that obviously will need to be discussed as we progressed the program and have those discussions with the regulators. But I've been really pleased with how the regulators have thought about it and the fact that this is indeed a genetically defined renal disease. And what the regulators have often talked about is a homogeneous proteinuric kidney disease and that is what this is. So I feel optimism for proteinuria to be the regulatory enabling end point. And obviously, that makes a more efficient trial.

麥克，和我們所有的專案一樣，我們在這裡也採用了組合式策略。我很高興看到這些結果。在過去幾年裡，社區醫生、病患團體以及監管機構，尤其是在美國的監管機構，已經舉辦了許多研討會和會議。監管機構表示，他們願意將蛋白尿作為監管審批的終點指標。至於這究竟是加速審批還是全面審批，顯然都需要在我們推進專案並與監管機構進行討論的過程中加以探討。但我對監管機構的思考方式以及這確實是一種基因定義的腎臟疾病感到非常滿意。監管機構經常提到的是一種同質性蛋白尿腎病，而這正是我們所研究的疾病。因此，我對蛋白尿作為監管審批的終點指標持樂觀態度。顯然，這將使試驗更加有效率。

I show our next question comes from the line of Phil Nadeau from Cowen and Company.

我接下來要問的問題來自 Cowen and Company 的 Phil Nadeau。

Kind of a 2-part regulatory question from us. You recently announced the design of the CF Phase III trial, and it's notable because as a noninferiority primary endpoint. We're curious to know whether simple noninferiority is sufficient to support FDA approval? Or if the FDA asked for superiority or something else from the secondary end points?

我們有一個包含兩部分的監管問題。您最近公佈了囊性纖維化（CF）III期臨床試驗的設計，值得注意的是，該試驗的主要終點是非劣效性。我們想知道，僅憑非劣效性是否足以獲得FDA批准？還是FDA要求在次要終點證明療效優於現有療法或其他療效？

And then second part of the question is, when will we get similar details on what's necessary to file CTX001. And I think you've been guiding for FDA and FDA update sometime this year, we're kind of curious is that going to come sooner rather than later? And if you have any preliminary idea of what will be necessary for filing that candidate?

問題的第二部分是，我們何時才能獲得關於提交CTX001申請所需資料的詳細資訊？您之前提到過FDA的審批流程，並表示會在今年稍後發布更新，我們很想知道這些資訊是否會盡快公佈？您是否對提交該候選藥物申請所需的材料有任何初步了解？

Sure. Let me take the CTX001 question first. As I mentioned in my prepared remarks, we are now looking to achieve completion of target enrollment in Q3. So that's really a very near-term completion of the target enrollment. So what we're looking at now and I've described it before as we've had these conversations with regulators and we do have the benefit of really virtually every regulatory designation one can image. So we've had the opportunity to have productive discussions with the agency. It's about the size of the filing package, it's about the duration of follow-up and the CMC manufacturing controls, I'd like to say. Achievement enrollment is really short term, so it's about the duration of follow-up in CMC manufacturing.

當然。我先回答關於CTX001的問題。正如我在準備好的發言稿中提到的，我們目前的目標是在第三季完成目標受試者招募。所以，目標受試者招募的完成指日可待。我們目前正在關注的是，正如我之前與監管機構溝通時所描述的那樣，我們幾乎擁有所有你能想到的監管資格。因此，我們有機會與監管機構進行富有成效的討論。關鍵在於申報資料的規模、後續追蹤的持續時間、CMC生產控制。我想說的是，完成目標受試者招募是短期目標，所以關鍵在於CMC生產後續追蹤的持續時間。

I do expect that we're going to bring those discussions to a conclusion in the next coming months. And I do anticipate filing to be possible in the next, let's call it, 18 to 24 months. So that's really what it looks like on CTX001.

我預計我們將在未來幾個月內結束這些討論。我也預計在未來18到24個月內可以提交申請。這就是CTX001專案目前的進度。

On the Phase III next-in-class CF program, we've gone through our discussions with the regulators. We've had our end of Phase II meetings, and this trial design that you see reflects those considerations in those discussions.

關於第三期同類新型囊性纖維化治療項目，我們已經與監管機構進行了討論。我們完成了二期臨床試驗的總結會議，您看到的這項試驗設計正是基於這些討論中的考量。

I will point out that as I look at the VX-121 data, there are 3 really important elements that stand out to me. The first is that in our HBE assays, and you know that our HBE assays translates very well into the clinic, not only qualitatively but quantitatively, singularly or in combination. So 121 alone or in combination with TRIKAFTA 561, the results are -- in our HBEs that 121 is more efficacious, more efficacious than even TRIKAFTA. That's really saying something.

我想指出的是，在分析VX-121的數據時，有三個非常重要的方面引起了我的注意。首先，在我們的HBE檢測中——您也知道，我們的HBE檢測結果與臨床結果的轉化性非常好，不僅在定性方面，而且在定量方面，無論是單獨使用還是聯合使用——VX-121單獨使用或與TRIKAFTA 561聯合使用，結果都表明——在我們的HBE檢測中，VX-121的療效更佳，TRIKAFTA。這確實意義非凡。

And in the Phase II results, you can look at the sweat chloride, which is the real direct translation of chloride transport in vitro. And you can see that we're looking at numbers that are more like 45 to 45 millimolar with the 121 regimen versus 33 to 39. That's what we saw in Phase II with the TRIKAFTA regimen. And then, of course, ppFEV1, which is more variable, but even that has indications for being better than TRIKAFTA. So while the primary endpoint is noninferiority, I see a lot of optimism in these data to even have the potential to be better than TRIKAFTA.

在第二期臨床試驗結果中，我們可以觀察到汗液氯化物濃度，這才是體外氯離子轉運的真實直接反映。可以看到，121方案組的汗液氯化物濃度約為45至45毫摩爾/公升，而TRIKAFTA方案組則為33至39毫摩爾/公升。這與我們在二期臨床試驗中觀察到的結果一致。當然，ppFEV1（第一秒用力呼氣容積百分比）的波動性更大，但即便如此，也顯示出優於TRIKAFTA的跡象。因此，儘管主要終點是非劣效性，但我認為這些數據非常樂觀，甚至有可能優於TRIKAFTA。

I show our next question from Geoff Meacham from Bank of America.

接下來，我將展示來自美國銀行的傑夫·米查姆提出的問題。

Just a couple for you guys. So on the pipeline, I know there's been a lot of emphasis on BD. But for what you have today in the pipeline, are there investments that you can accelerate to get into registration trials faster, for example, like in pain?

給你們提幾個問題。我知道你們一直很重視業務拓展，但就目前的產品線而言，有沒有哪些投資可以加快推進，以便更快地進入註冊試驗階段，例如針對疼痛的藥物？

And then when you look in CF, beyond rolling out across the EU and maybe adding younger patients across the board, what do you think -- I know you're not going to give long-term guidance, but what is the normalization of the market look like in terms of the maybe the incidence rate? What are you guys assuming? I'm just trying to get a sense for when CF is more moderate growth, is that the time frame where -- will you think that you're going to have more of a P&L impact from sickle cell and beta thal from 001 or other elements of the pipeline? I'm just trying to get a sense to put all the pieces together for kind of the long-term growth picture.

然後，當我們審視囊性纖維化（CF）領域時，除了在歐盟範圍內推廣並可能全面擴大年輕患者群體之外，您認為——我知道您不會給出長期預測——市場正常化後的情況會是怎樣的？例如發病率方面？你們的假設是什麼？我只是想了解一下，當囊性纖維化市場成長趨於溫和時，您是否認為鐮狀細胞貧血症和β-地中海貧血症（來自001或其他在研產品）會對您的損益表產生更大的影響？我只是想了解所有因素，以便更好地掌握長期成長前景。

Yes. It's a great question, Geoff. And let me set it up for you, and then I'm going to ask Stuart to comment on market dynamics, and then I'll come back and address your question about the pipeline and how we see that going. What I'll say to start with is I really see continued significant growth for many years to come in our CF franchise. And I'm going to ask Stuart to outline those dynamics for why I say that.

是的，傑夫，你問得好。我先給你鋪墊一下，然後我會請史都華談談市場動態，之後我再回來回答你關於產品線以及我們對此的看法的問題。首先我想說的是，我非常看好我們CF業務在未來很多年持續顯著成長。接下來我會請史都華詳細闡述我做出這個判斷的原因。

Yes, Geoff. So as you know, we updated our estimates of the epidemiology for people living with CF in the U.S., Canada, Europe and Australia earlier this year, it's approximately 83,000 patients. And we're probably treating about half of those patients today. And as you know, we updated our guidance today to a range of $7.2 billion to $7.4 billion. What that means is and I don't want to gloss over this is that there is more than 30,000 patients remain eligible for our CFTR modulators, they are likely to benefit from our existing CFTR modulators. And those 30,000 patients really pull into 3 categories. The first one is people who live in countries where we have regulatory approval and we've secured reimbursement and we are beginning the launches in those markets. And as you know, the launches of our CF medicines tend to be a very rapid.

是的，傑夫。如你所知，今年早些時候，我們更新了美國、加拿大、歐洲和澳洲囊性纖維化（CF）患者的流行病學估計，大約有83,000名患者。目前，我們可能正在治療其中大約一半的患者。你也知道，今天我們更新了指導意見，將目標範圍擴大到72億至74億美元。這意味著，我不想迴避這一點，那就是仍有超過30,000名患者符合我們CFTR調節劑的治療條件，他們很可能從我們現有的CFTR調節劑中獲益。這30,000名患者大致可分為三類。第一類是居住在我們已獲得監管部門批准並獲得報銷的國家/地區的患者，我們正在這些市場開始推出我們的產品。你也知道，我們的CF藥物上市速度通常非常快。

The second group of patients are those who live in countries where we have regulatory approval, but don't yet have reimbursement. Obviously we've had a great year securing reimbursement for KAFTRIO just a year -- just under a year from EMA approval, and I have full confidence that we're going to continue that run and secure additional reimbursement agreements in countries where we don't have it today.

第二類患者是居住在我們已獲得監管部門批准但尚未獲得醫療保險報銷的國家的患者。顯然，我們今年取得了巨大的成功，僅用了不到一年的時間（從獲得EMA批准到獲得醫療保險報銷）就為KAFTRIO爭取到了醫保報銷。我完全有信心，我們將繼續保持這一勢頭，並在目前尚未獲得健保報銷的國家達成更多健保協議。

And then we have to get down into the younger patients. And as you know, we've done that with KALYDECO and ORKAMBI. And given the benefit risk profile of TRIKAFTA, we fully expect we'll be able to get down to younger age groups. So over the next several years, we see multibillion dollar revenue growth potential through getting to those more than 30,000 patients.

接下來，我們需要拓展到更年輕的患者族群。如您所知，我們已經透過 KALYDECO 和 ORKAMBI 實現了這一點。鑑於 TRIKAFTA 的獲益風險比，我們完全有信心能拓展到更年輕的年齡層。因此，在未來幾年，我們預計透過覆蓋超過 3 萬名患者，將實現數十億美元的收入成長潛力。

Additionally, we are also working on the 7% to 10% of patients who aren't going to be eligible for our CFTR modulators, using genetic approaches through our collaborations with amongst others at Moderna. So we do see continued growth of our CF franchise for several years to come based on continuing to execute in the way that we have done over the last few years.

此外，我們也與 Moderna 等公司合作，利用基因療法，為 7% 到 10% 不適合使用 CFTR 調節劑的患者提供治療方案。因此，我們預計，在未來幾年裡，只要我們繼續保持過去幾年的良好勢頭，我們的囊性纖維化產品線將持續成長。

And then to tell you how the pipeline is going to layer on top of that, I'll hand it back to Reshma.

然後，為了告訴你們管道將如何在此基礎上進行疊加，我把這個主題交還給雷什瑪。

The pipeline is progressing nicely. And I actually would say it's accelerating. And let me tell you why I say that. The pain program is now in Phase II for the bunionectomy study. And in parallel, very shortly, we're going to start up the abdominoplasty study. The CTX001 program, as I said in my prepared remarks, that one is going to achieve target enrollment in Q3 now.

研發管線進展順利，實際上，我認為它的進展速度正在加快。讓我解釋一下原因。目前，拇外翻切除術的疼痛治療計畫已進入第二期臨床試驗。同時，我們很快也將啟動腹部整形術的研究。正如我在準備的發言稿中提到的，CTX001專案預計將在第三季達到預期的入組目標。

And when I think about 147, that is absolutely on track to have results in the second half of this year. And when I put all of that together, it looks like a really important next 6 to 9 months in terms of not only data readouts but the opportunity to advance to stones in each of these programs. And that's not even talking about the programs that are in late preclinical development or in Phase I.

就147號項目而言，它絕對有望在今年下半年取得成果。綜合所有因素來看，未來6到9個月至關重要，不僅因為數據解讀，更因為每個計畫都有機會推進到臨床試驗階段。這還不包括那些處於臨床前後期或I期臨床試驗階段的項目。

So we are investing heavily in our pipeline. It is because the pipeline is accelerating, and there are many opportunities for us to get to the next important milestones in clinical development. I would be remiss if I didn't say a word about VX-880. This is the naked cells-only approach. This one is a Phase I/II trial. And I would think about this one as similar to CTX001 in that a reasonably small number of patients, in a reasonably efficient time frame, will really tell us what we have. And so that was another one that I think is going to be important to keep our eyes on and to invest behind.

因此，我們正在大力投資我們的研發管線。這是因為管線正在加速推進，我們有很多機會在臨床開發中達到下一個重要里程碑。如果我不提一下VX-880，那就太失職了。這是一種僅使用裸細胞的方法。目前正處於I/II期臨床試驗階段。我認為它與CTX001類似，都是透過招募數量適中、時間合理的患者，就能真正了解我們研發的藥物的療效。因此，我認為VX-880也是我們需要密切關注並持續投資的藥物之一。

I show our next question comes from the line Salveen Richter from Goldman Sachs.

我指出，我們的下一個問題來自高盛的薩爾文·里希特。

For CTX001, on manufacturing, do you have an understanding of the assays required or how differences could play out regulatory-wise versus gene therapy, given this is a new technology? And then with your work with Moderna on mRNA and gene editing, maybe you could just help us understand how that's progressing and when those might enter the clinic?

關於CTX001的生產製造，您是否了解所需的檢測方法，或者考慮到這是一項新技術，它在監管方面與基因療法可能有哪些差異？另外，您在Moderna公司從事mRNA和基因編輯方面的工作，能否幫助我們了解這方面的進展以及何時可能進入臨床試驗階段？

Sure. Salveen, with regard to CTX001, we really have had the opportunity to have multiple discussions with the regulators, not just on what the potential filing package could look like in terms of the clinical data, sample size, et cetera, but also on CMC and manufacturing. And we have a very good understanding of what the agency, both here and outside the U.S., would like to see in terms of potency assays and release assays, and that work is going very well.

當然。 Salveen，關於CTX001，我們確實有機會與監管機構進行了多次討論，不僅討論了潛在的申報資料包（包括臨床數據、樣本量等），還討論了CMC和生產過程。我們非常清楚美國國內外監管機構希望看到哪些效力測定和放行測定方面的數據，而且這方面的工作進展非常順利。

In terms of the mRNA program, you know that we have multiple programs for the last 10% of our CF patients, the most advanced of which is the mRNA program in partnership with Moderna. There's really 2 components here. It's the mRNA construct itself and it's also delivery. We have made solid progress on both of those. And I would say the important one is on delivery. A little too early for me to give you timing for when that would enter the clinic. But I will say that the progress has been very good. And I'm feeling very optimistic about our ability to get to that last 10% of patients, maybe even compared to 6 months ago.

關於mRNA項目，您知道我們針對最後10%的囊性纖維化患者開展了多個項目，其中最先進的是與Moderna合作的mRNA項目。這個項目其實包含兩個部分：mRNA構建體本身和遞送系統。我們在這兩方面都取得了顯著進展。我認為遞送系統尤其重要。現在給出具體的臨床應用時間還為時過早，但我可以肯定的是，進展非常順利。我對我們能夠惠及最後10%的患者感到非常樂觀，甚至可能比6個月前更快。

I show our next question comes from the line of Robyn Karnauskas from Truist Securities.

下一個問題來自 Truist Securities 的 Robyn Karnauskas。

Starting first a little bit on -- I have to ask this question. I did not want to be the person who asked this question on the call, Reshma, but I have to. Your thoughts on the Galapagos headwind as people are focusing on their data coming up. I know they're behind you, but can you just give any more additional color on the biology, perhaps, even though, on how you view their drugs? And second, on pain, you mentioned like time lines, you could get some clarity on your pipeline over the next 6 to 9 months. When could we actually see data from pain? Those trials enrolled really quickly. Maybe give us some sense of what your expectations are or your next dataset and what the bar might be?

首先，我必須問一個問題。雷什瑪，我本來不想在電話會議上問這個問題，但我不得不問。你對加拉巴哥群島計畫目前面臨的不利影響有什麼看法？我知道他們落後於你們，但你能否再詳細解釋一下生物學方面的內容，或者說說你對他們藥物的看法？其次，關於疼痛治療，你提到了時間表，你們的研發管線可能會在未來6到9個月內更加清晰。我們什麼時候才能看到疼痛治療的實際數據？這些試驗的入組速度非常快。能否讓我們了解一下你們的預期，或是你們的下一個資料集是什麼，以及你們的目標是什麼？

Yes. Sure thing, Robyn. Let me start with pain. I'm really excited about our pain program. You know that we have a program in NaV1.8, that's the one that's furthest ahead. In our discovery and preclinical research, we also have programs in NaV1.7. The reason I'm particularly excited about NaV1.8 is it's a genetically validated target for sure, but it's also pharmacologically validated by our very own VX-150. The molecule that's in the clinic now, VX-548, really is all the attributes we were looking for in terms of potency as well as in drug like properties, DDIs, manufacturability, et cetera.

好的，當然可以，羅賓。我先來說說疼痛治療。我對我們的疼痛治療計畫感到非常興奮。你知道，我們有一個針對NaV1.8的項目，這是目前進展最快的項目。在我們的藥物發現和臨床前研究中，我們也有針對NaV1.7的計畫。我之所以對NaV1.8特別興奮，是因為它不僅是一個經過基因驗證的靶點，而且也透過我們自己的VX-150進行了藥理學驗證。目前正在進行臨床試驗的分子VX-548，在效力、類藥特性、藥物交互作用、可生產性等方面，都真正具備了我們所尋找的所有特性。

So this one really looks very exciting to us. It's already in the bunionectomy study that is up and running as a Phase II proof-of-concept study. The abdominoplasty is right behind it, and that should start-up very shortly. We are also interested in pursuing peripheral neuropathic pain in the NaV1.8 area. And the reason for that is because, again, our VX-150 molecule had proof of -- positive proof-of-concept data, not only in acute pain, but also in neuropathic pain. So that one is another study that's coming.

所以，這個項目看起來真的非常令人興奮。目前，我們正在進行一項針對拇外翻切除術的II期概念驗證研究。腹部整形手術的研究也緊跟著，應該很快就會啟動。我們也對NaV1.8區域的周邊神經性疼痛研究很感興趣。原因在於，我們的VX-150分子已經獲得了積極的概念驗證數據，不僅在急性疼痛方面有效，在神經性疼痛方面也有效。因此，這方面的研究也即將展開。

With regard to acute pain, the studies are very short in duration because it's a procedure like a bunionectomy, you have treatment that is over a couple of days. And so the results can be obtained in a reasonably efficient time frame. I expect that the bunionectomy results will be ready by, let's say, the tail end of this year, beginning part of next year, abdominoplasty results thereafter. So that's really how I would encapsulate the pain program.

關於急性疼痛，由於像拇外翻切除術這樣的手術，治療通常只需幾天時間，因此研究週期很短。所以可以在相當短的時間內獲得結果。我預計拇趾外翻切除術的結果將在今年年底或明年年初公佈，腹部整形術的結果則隨後公佈。這就是我對疼痛治療方案的概括。

With regard to the Galapagos data, maybe Galapagos AbbVie data, Robyn, I'd rather focus on our portfolio and tell you about how I see our portfolio. And maybe the best way to summarize it is VX-121, 561 tezacaftor holds the potential to bring greater patient benefit than even TRIKAFTA a once daily dosing, which I think adds a level of convenience for our patients. And in all honesty, the greatest threat to TRIKAFTA, the greatest competitor to TRIKAFTA in terms of the most advanced is our very owned VX-121,561 tezacaftor.

關於 Galapagos 的數據，或許是 Galapagos AbbVie 的數據，Robyn，我更願意專注於我們自身的產品組合，並談論我對我們產品組合的看法。或許最好的概括方式是，VX-121,561 tezacaftor 具有比 TRIKAFTA 更大的潛力，能夠為患者帶來更多益處，而且每日一次的給藥方式也為患者帶來了便利。坦白說，TRIKAFTA 最大的威脅，或者說，就目前最先進的技術而言，TRIKAFTA 最強勁的競爭對手正是我們自主研發的 VX-121,561 tezacaftor。

Our next question comes from the line of Cory Kasimov from JPMorgan.

我們的下一個問題來自摩根大通的科里·卡西莫夫。

Actually want to follow up, Reshma, on what you were just talking about, I'm talking about Phil's earlier question on the qd CF study, but from a slightly different point of view. So recognize it's designed to demonstrate statistical noninferiority from a regulatory standpoint. But what do you think you need to show for this to actually displace a product as good as TRIKAFTA in the market? I'm assuming once versus twice a day isn't enough on its own.

雷什瑪，我其實想就你剛才說的話題再追問一下。我指的是菲爾之前問的關於qd CF研究的問題，不過我想從一個略微不同的角度來談。我知道這項研究旨在從監管角度證明其統計上的非劣效性。但是，你認為要證明它能夠真正取代市場上像TRIKAFTA這樣優秀的產品，需要證明哪些面向呢？我猜想，僅僅一天服用一次和兩次的差別是不夠的。

And did you say in the prepared remarks -- I just want to make sure we have this right, that the royalty on the qd goes to low single digit from low double digit? Do we get that right?

您在準備好的發言稿中是否提到—我只是想確認一下我們理解得是否正確，即量子衍生性商品的版稅從兩位數低點降至個位數低點？我們理解對嗎？

Yes, yes. Cory, with regard to the study, you're right. For the regulatory enabling end point, it is a noninferiority study, and that noninferiority is on ppFEV1.

是的，是的。 Cory，關於這項研究，你說得對。就監理審批終點而言，這是一項非劣效性研究，而該非劣效性指標為ppFEV1。

You're also correct that the royalties go from low double digits with TRIKAFTA, KAFTRIO to low single digits.

你說的也對，版稅從 TRIKAFTA、KAFTRIO 的兩位數低點逐漸降至個位數低點。

Let me just take a step back, though, and help maybe everyone on the phone line to understand our perspective on the 121 program and why we're really doing this. So our long-standing goals in CF have been threefold. First, bring forward a medicine that can treat up to 90% of patients with cystic fibrosis. Give that a check, that's TRIKAFTA, KAFTRIO.

不過，讓我先退一步，或許可以幫助電話線上的各位理解我們對121項目的看法，以及我們開展這項計畫的真正原因。我們在囊性纖維化領域的長期目標有三點。首先，研發一種能夠治療高達90%囊性纖維化患者的藥物。沒錯，那就是TRIKAFTA，KAFTRIO。

Second, get patients who can benefit from CFTR modulators with the highest levels of efficacy. And the way we've discussed that is to bring patients to carrier levels of sweat chloride. And that's really important because as those levels, when you look at carriers of cystic fibrosis, they really have no manifestation of disease. And when you look at our own data, other published data, it is absolutely true that the better the sweat chloride results, which is a reflection of CFTR function, the better the outcomes for our patients.

其次，要找到那些能從療效最高的CFTR調節劑中獲益的患者。我們之前討論過，要讓患者的汗液氯化物水平達到囊性纖維化攜帶者的水平。這一點至關重要，因為當汗液氯化物水平達到這個水平時，囊性纖維化攜帶者通常不會出現任何疾病症狀。而我們自身的數據以及其他已發表的數據都表明，汗液氯化物水平越好（這反映了CFTR的功能），患者的治療效果就越好。

And the third big goal has been to get to the last 10% of patients. The 121, 561 tezacaftor program is all about that big goal number 2, get patients to carrier levels of sweat chloride. And certainly, it is the case that some patients on TRIKAFTA can get there. But we are looking to get many, many more patients to those levels, if not all patients, and that is 121, 561 teza.

第三個重要目標是涵蓋最後10%的患者。 121,561 tezacaftor 計畫的核心在於實現第二個重要目標，即讓患者的汗液氯化物水平達到載體水平。當然，服用 TRIKAFTA 的部分患者確實可以達到這個水平。但我們希望讓更多患者達到這個水平，甚至讓所有患者都達到，這就是 121,561 tezacaftor 計畫的目標。

And as I reviewed from what we see in the HPE cells, in terms of chloride transport, sweat chloride from the Phase II studies and even ppFEV1, all these measures point us in the direction that this is possible with 121, 561. And of course, we're busy in the labs working on even more efficacious molecules.

正如我從 HPE 細胞中觀察到的，就氯離子轉運、II 期研究中的汗液氯離子以及 ppFEV1 而言，所有這些指標都指向一個方向，即使用 121,561 是有可能實現這一目標的。當然，我們正在實驗室裡忙於研究更有效的分子。

I show our next question comes from the line of Liisa Bayko from Evercore ISI.

我發現我們的下一個問題來自 Evercore ISI 的 Liisa Bayko。

I want to ask a little bit more about the FSGS study design. Can you talk about sort of the background therapies that patients will be on? And will they be on steady background meds headed into the study? Or will there be any changes ahead of the study? Will you allow for the use of steroids? Just curious about some of the other factors.

我想再問一些關於FSGS研究設計的問題。能談談患者在研究開始前會接受哪些基礎治療嗎？他們會一直服用這些藥物嗎？還是會在研究開始前進行調整？你們允許使用類固醇嗎？我只是對其他一些因素比較感興趣。

Yes. Sure thing. Liisa, in our Phase II study, we are looking at patients who have APOL1-mediated FSGS with 2 APOL1 allele. And we are looking for patients with heavy amounts of proteinuria. We are allowing patients to be on background therapy and we are looking for the double-digit percent reduction of proteinuria that I was talking about earlier on top of whatever background therapy our patients may be coming into our trial with.

是的，當然可以。莉薩，在我們的第二期研究中，我們正在尋找攜帶兩個APOL1等位基因的APOL1介導的局部節段性腎小球硬化症（FSGS）患者。我們尤其關注那些伴隨大量蛋白尿的患者。我們允許患者在接受基礎治療的同時進行試驗，並希望在患者入組時已接受的基礎治療基礎上，進一步降低蛋白尿水平，達到我之前提到的兩位數百分比。

Okay. Great. Helpful. And then...

好的。太好了。很有幫助。然後…

Our next question comes from the line of Brian Abrams from RBC Capital Markets.

下一個問題來自加拿大皇家銀行資本市場的布萊恩‧艾布拉姆斯。

So 2 questions on 121. Can you talk about where you're planning to conduct the Phase III triple combo study? And is that going to be in the U.S. or outside the U.S., would you expect any medium-term impact to TRIKAFTA or KAFTRIO revenues?

關於121號表格，我有兩個問題。您能否談談您計劃在哪裡進行第三期三重療法研究？這項研究是在美國境內還是境外？您預計這會對TRIKAFTA或KAFTRIO的收入產生任何中期影響嗎？

And then it looks like the sweat chloride that you observed, at least in the [regimen], was dose dependent. I'm wondering, do you feel you fully explored the dosing curve here? Any safety or PD reason not to further dose escalate just given the high bar set by TRIKAFTA?

然後，看起來您觀察到的汗液氯化物水平，至少在[該方案]中，與劑量相關。我想知道，您是否覺得已經充分探索了這裡的劑量曲線？鑑於TRIKAFTA設定的高標準，是否有任何安全或藥效學方面的原因，導致不應進一步增加劑量？

Sure thing. Brian, we are going to be conducting the study in the usual countries, U.S., European countries, the standard. Remember, this study, both the studies in the 121 program, are compared to TRIKAFTA or KAFTRIO. So this is not placebo-controlled. So patients are going to be on active therapy in either arm. That obviously makes it a lot easier for patients to enroll into this study.

當然可以。布萊恩，我們將在通常的國家，例如美國和歐洲國家，進行這項研究。記住，這項研究，以及121項目中的兩項研究，都是與TRIKAFTA或KAFTRIO進行比較的。所以這不是安慰劑對照研究。也就是說，無論選擇哪一組，患者都將接受活性藥物治療。這顯然會大大方便患者參與這項研究。

With regard to impact on revenues for TRIKAFTA, no, we don't see any impact on revenues to TRIKAFTA.

至於對 TRIKAFTA 收入的影響，不，我們認為不會對 TRIKAFTA 的收入產生任何影響。

And with regard to how did we select the dose, how did we think about this program. We shared with you the results from the Phase II study. And as is the case with all of our programs, we take all of that data. We do quite a bit of modeling and simulation to settle on the best dose that maximizes efficacy and has the greatest benefit risk profile.

至於劑量選擇，以及我們是如何構思這個計畫的，我們已經和大家分享了第二期臨床試驗的結果。就像我們所有的項目一樣，我們會綜合考慮所有數據，進行大量的建模和模擬，最終確定能夠最大限度提高療效並兼顧最佳獲益風險比的劑量。

I think that's exactly what we've done with regimen that we've selected. And as I mentioned on my response to one of the other questions, what I see in these data with the regimen that we're selecting is in vitro chloride transport that is even better than TRIKAFTA. Sweat chloride levels, which is the most approximate translation of chloride transport, so the sweat chloride levels in our Phase II trial that are higher than what we saw with TRIKAFTA, and ppFEV1 which, you know has greater variability, that is also showing us particular potential to be better than TRIKAFTA.

我認為這正是我們所選擇的治療方案所體現的。正如我在回答另一個問題時所提到的，從這些數據來看，我們選擇的治療方案在體外氯離子轉運方面甚至優於 TRIKAFTA。汗液氯離子水平是氯離子轉運最近似的指標，因此，在我們 II 期試驗中，此方案的汗液氯離子水平高於 TRIKAFTA 組。此外，ppFEV1（其變異性較大）也顯示出該方案優於 TRIKAFTA 的潛力。

I have to say what is obvious. TRIKAFTA is a great medicine. What we saw in the clinical trials has been recapitulated in the real world. You heard Stuart talk about the longer-term data with TRIKAFTA that just continues to look excellent. But we think we have something that might be even better than that with 121, 561 tezacaftor, and I'm really looking forward to the Phase III results.

我必須說，TRIKAFTA 是一種非常優秀的藥物。我們在臨床試驗中觀察到的結果在現實世界中也得到了驗證。你們也聽到了 Stuart 談到的 TRIKAFTA 的長期數據，這些數據持續表現優異。但我們認為，121,561 tezacaftor 可能比它更好，我非常期待 III 期臨床試驗的結果。

I show our next question comes from the line of Paul Matteis from Stifel.

我接下來要問的問題來自 Stifel 的 Paul Matteis 系列。

Congrats on the quarter. I just had a couple of other APOL1 questions, if you don't mind. One was just on finding these patients. I know the study or at least per clinical trials that's been going on for a little over a year, and the implied sample size is estimated to end up at around 10. Has it been difficult to find patients? Is genetic testing a headwind?

恭喜你本季取得好成績。我還有幾個關於APOL1的問題，如果你不介意的話。其中一個是關於尋找這些患者的。我知道這項研究，或至少臨床試驗，已經進行了一年多了，預計樣本量最終會在10人左右。尋找患者是否困難？基因檢測是否會成為阻礙？

And then second, Reshma, I know you talked about this is obviously a first study, double-digit proteinuria is the goal. Can you just kind of contextualize that in terms of what thresholds of change in proteinuria have predicted clinical benefit in the past? Is there some sort of minimum change that has been relevant to get FDA comfortable with accelerated approval?

其次，Reshma，我知道你提到這顯然是一項初步研究，兩位數蛋白尿是研究目標。你能否解釋一下，過去哪些蛋白尿變化閾值可以預測臨床效益？是否存在某種最低變化值，能夠讓FDA認可並加速核准？

Yes, yes. All great questions about the APOL1-mediated FSGS program.

是的，是的。這些都是關於APOL1介導的FSGS程式的很好的問題。

Let me start with the clinical trials and the enrollment and such. First and foremost, we are on track to have results in this calendar year, in the second half of the year. It has been a study that has taken some time to enroll, and I'm not surprised about that. The factors that we need to think about are, remember, this study started right in the midst of the pandemic, actually right when the pandemic was hitting a real high point in terms of case numbers here in the U.S.

讓我先談談臨床試驗和受試者招募等情況。首先，我們預計在今年下半年獲得結果。這項研究的招募工作耗時較長，對此我並不感到驚訝。我們需要考慮的因素是，這項研究啟動於疫情高峰期，確切地說，是在美國疫情達到高峰的時候。

The second is that this is a disease that for which we don't routinely employ genetic testing in renal medicine. So it takes a little bit of time to find the patients, genetically test them and have them enroll in our studies.

第二點是，這種疾病在腎臟病學中並不常規採用基因檢測。因此，我們需要一些時間來尋找患者，進行基因檢測，並讓他們參與我們的研究。

And the third thing is APOL1-mediated FSGS is the smaller of the spectrum of APOL1-mediated kidney disease. And the APOL1-mediated FSGS patients, because it's a smaller component, they are spread across the U.S., and they don't necessarily live close to a testing center. And so that was particularly difficult in the pandemic.

第三點是，APOL1介導的局部節段性腎小球硬化症（FSGS）是APOL1介導的腎臟疾病譜中較小的一種。由於APOL1介導的FSGS患者數量較少，因此分散在美國各地，而且不一定居住在檢測中心附近。因此，在疫情期間，這尤其困難。

With regard to what we are looking for, we are looking for percent decreases in proteinuria, and I think double-digit decreases in proteinuria, in this Phase II study, which is a first-in-class molecule for this genetically validated target, would be just excellent.

至於我們想要達到的效果，我們想要看到蛋白尿的百分比下降，我認為在這項針對這一基因驗證靶點的首創分子的 II 期研究中，如果蛋白尿能夠下降兩位數，那就非常出色了。

And the question around what is the agency looking for and such. It really depends on the kidney disease of interest. We are looking at a homogeneous kidney disease. It is all genetically defined. And I think that, that falls into a category in and of itself. And as I said, there is no precedent for this. We are the first to bring a targeted therapy for APOL1-mediated kidney disease. But I do think a percent reduction in the double digits would be very meaningful.

至於該機構究竟在尋找什麼等等問題，這實際上取決於他們關注的腎臟疾病類型。我們研究的是一種同質性腎臟疾病，它完全由基因決定。我認為這本身就屬於一個獨特的類別。正如我所說，這方面尚無先例。我們是首個推出針對APOL1介導的腎臟疾病的標靶療法的團隊。但我認為，如果能實現兩位數的百分比降低，那將意義非凡。

I show our next question comes from the line of Brian Skorney from Baird.

我接下來要問的問題來自 Baird 公司的 Brian Skorney。

Mine is just really on the diabetes program. Just strictly thinking about the opportunity in patients who are going to require lifetime immunosuppression. How do you kind of think about differentiation from your cell line from sort of the cell trans donor cells, which I think should probably get approved in the next month? Is there a supply constraint there due to sourcing that you think you overcome with the sort of the stem cell line? Or are there other characteristics of differentiation that you think can make your technology work better?

我的研究主要集中在糖尿病項目。我主要考慮的是那些需要終身服用免疫抑制劑的患者。您認為您的細胞系與細胞移植供體細胞（我認為下個月應該就能獲批）有何不同？是否有因來源限製而導致的供應不足，而您認為幹細胞係可以克服這個問題？或者，您認為分化的其他特性是否能讓您的技術發揮更大的作用？

And then in terms of -- I know you're working on a sort of encapsulation for protecting the differentiated islet cells to reduce immunoreactactivity. But are you exploring other ways such as the induction of immune tolerance or cell editing to get around the need for immunosuppression as well? And any thoughts on sort of those pathways?

另外，我知道您正在研究一種用於保護分化胰島細胞以降低免疫反應性的封裝技術。但您是否也在探索其他方法，例如誘導免疫耐受性或細胞編輯，以避免使用免疫抑制劑？您對這些途徑有什麼想法嗎？

Yes. Really, really great questions, Brian. And thank you for those. I'm really happy to talk about the Type 1 diabetes programs. I'm sure you can hear from the enthusiasm in my voice, it's one of the ones that is -- really holds enormous potential for patients.

是的，布萊恩，你問的問題真的非常好，謝謝你。我很高興能和大家聊聊1型糖尿病計畫。我相信你從我的語氣中也能感受到我的熱情，這個計畫對病人來說真的很有潛力。

So let's just start at the very top of the funnel. There are more than 2 million patients, 2 million patients with Type 1 diabetes in the U.S. and Europe. So the potential to help patients is enormous when you look at it from that perspective.

那麼，我們就從最底層開始說起。美國和歐洲有超過200萬1型糖尿病患者。從這個角度來看，幫助患者的潛力是巨大的。

I'll take your second question first about encapsulation. I do think that it will be important to have the cells being capsulated in a device or in some way, be immune-evasive so that you don't require immunosuppressives to be able to get to all of those patients.

我先回答你關於細胞封裝的第二個問題。我認為將細胞封裝在某種裝置中，或以某種方式使其具有免疫逃脫能力，這一點非常重要，這樣就不需要使用免疫抑制劑就能治療所有患者。

I think that the device approach is elegant because it has the benefit of simplicity. That's not to say that it's a simple device, but it is to say that the cells encapsulated with this device then don't require any further manipulation, which is elegant.

我認為這種裝置方案的巧妙之處在於它的簡潔性。這並不是說裝置本身很簡單，而是指封裝在該裝置中的細胞無需任何後續處理，這一點非常巧妙。

That all being said, we are very interested in all other approaches, and we are pursuing other approaches to immunoevasion. The lead approach is with the cells encapsulated in the device.

儘管如此，我們對所有其他方法都非常感興趣，並且正在探索其他免疫逃脫方法。目前的主要方法是將細胞封裝在裝置中。

With regard to the cadaveric cells and the cells that are available currently, the big differentiator, and this is really important to understand because it's fundamental. Those cells are cadaveric cells. And those cadaveric cells have all of the limitations that have made the procedure difficult for patients to undergo. That is to say quality and quantity of cells are limited. Our approach are as a stem cell-derived, full-differentiated, insulin-producing islet cells. And that makes quantity not an issue and quality not an issue. And so that's really the foundational difference between our approach and the other.

關於目前可用的屍體細胞和其他細胞，最大的區別在於——這一點至關重要，因為它關乎根本——這些細胞是屍體細胞。而屍體細胞有許多局限性，使得患者難以接受手術。也就是說，細胞的品質和數量都有限。我們採用的是幹細胞衍生的、完全分化的、能產生胰島素的胰島細胞。因此，數量和品質都不是問題。這正是我們方法與其他方法之間的根本差異。

Operator, we have time for one more question.

操作員，我們還有時間再問一個問題。

Our last question comes from the line of Alethia Young from Cantor Fitzgerald.

我們的最後一個問題來自坎托·菲茨杰拉德的阿萊西亞·楊的詩句。

Just a quick question on how you're kind of thinking about maybe kind of external deals. Maybe is there an interest in kind of proof of concept? Or are you still kind of focused on kind of earlier-stage deals?

我有一個關於您如何考慮外部合作的問題想問一下。您是否對概念驗證之類的項目感興趣？還是您仍專注於早期階段的合作？

I'm sorry, Alethia, I didn't -- we couldn't hear your question in the room. Could you repeat your question?

對不起，阿萊西亞，我們沒聽清楚你的問題。你能再說一次嗎？

Yes. My question was on external deals kind of in the early stage or in the late stage. I guess I've just been thinking about the time lines with the alpha-1 antitrypsin program being a little bit more delayed than we thought.

是的。我的問題是關於早期或後期階段的外部交易。我一直在思考α-1抗胰蛋白酶計畫的進度安排，它比我們預想的要晚一些。

I think the question is about deals, external deals we're looking at, what phase might we be looking at.

我認為問題在於我們正在考慮的外部交易，以及我們可能處於哪個階段。

We're interpreting your question in the room about...

我們正在翻譯您提出的關於…的問題。

Can you hear me now? Can you hear me now?

現在你聽得到我說話嗎？現在你聽得到我說話嗎？

We can hear you.

我們能聽到你的聲音。

Yes. Basically, I'm just asking about kind of external time lines of external development, kind of aspirations, like whether you're looking at more proof of concept still? Or are you looking at kind of earlier-stage development programs that you kind of have gone with in light of what's been going on with alpha-1 antitrypsin?

是的。我主要是想問一些關於外部研發時間表和目標方面的問題，例如你們是否還在進行概念驗證？或者你們是否已經著手進行一些早期研發項目，並根據α-1抗胰蛋白酶的進展做出了相應的調整？

Sure thing. I think you're asking about business development and how we are doing -- yes, okay, and external innovation.

當然可以。我想您問的是業務發展以及我們做得怎麼樣——是的，還可以，還有外部創新。

Alethia, we are -- we have been and we remain today, very focused on innovation, both internal and external. And we've talked in the past about our areas of interest and how we view this, namely in CF, in tools to augment our toolbox and assets that fit our sandbox diseases, all of those exactly the same. Our R&D strategy encompasses both internal and external innovation. You have never seen us invest more in our internal innovation. Our pipeline has both sources of assets from our own pipeline and what we brought in from acquisitions like Semma and Exonics and partnerships like CRISPR and Moderna, and you should expect us to continue in the same way.

Alethia，我們一直以來都非常注重創新，包括內部創新和外部創新。過去我們也曾談到我們的關注領域以及我們對這些領域的理解，尤其是在囊性纖維化領域，包括增強我們現有工具箱的工具以及適用於我們現有疾病的研發資產，所有這些都是相同的。我們的研發策略涵蓋了內部和外部創新。您從未見過我們對內部創新投入如此之多。我們的研發管線既包含我們自身研發管線的資產，也包含我們透過收購（例如Semma和Exonics）以及與CRISPR和Moderna等合作夥伴取得的資產，您可以期待我們繼續保持這種發展勢頭。

Thank you. This concludes our Q&A session. At this time, I'd like to turn the call back over to Mr. Partridge for closing remarks.

謝謝。問答環節到此結束。現在，我想把電話交還給帕特里奇先生，請他作總結發言。

Thanks, operator. Thanks, everybody, for tuning into tonight's call. The Investor Relations team is in the office and we look forward to any additional questions that you have. Have a good night.

謝謝接線生。感謝各位收聽今晚的電話會議。投資者關係團隊已在辦公室，期待您提出任何其他問題。祝您晚安。

This concludes today's conference call. Thank you for participating. You may now disconnect. Good day.

今天的電話會議到此結束。感謝您的參與。您可以斷開連線了。祝您今天愉快。