福泰製藥 (VRTX) 2020 Q1 法說會逐字稿

Good evening. Welcome to the Vertex First Quarter 2020 Financial Results Conference Call. This is Michael Partridge, Senior Vice President of Investor Relations for Vertex. Making prepared remarks on the call tonight, we have Dr. Reshma Kewalramani, Vertex's CEO and President; Stuart Arbuckle, Chief Commercial Officer; and Charlie Wagner, Chief Financial Officer. We recommend that you access the webcast slides on our website as you listen to this call. This conference call is being recorded, and a replay will be available on our website.

晚安.歡迎參加Vertex公司2020年第一季財務業績電話會議。我是Vertex公司投資者關係資深副總裁Michael Partridge。今晚在電話會議上發言的有Vertex公司執行長兼總裁Reshma Kewalramani博士、商務長Stuart Arbuckle以及財務長Charlie Wagner。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。本次電話會議將進行錄音，錄音回放將在我們網站上提供。

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 our filings with the Securities and Exchange Commission. These statements, including, without limitation, those regarding Vertex's 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 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。

Thanks, Michael. It is an honor, as Vertex's new CEO and President, to welcome you to this conference call. The COVID-19 pandemic has been a significant challenge for people around the world. These are tough times. We know and we see that the lives of people in every country around the world has been disrupted. We grieve with those who have lost loved ones, and we salute the heroic work being done by those on the frontlines of fighting the pandemic.

謝謝，麥可。身為Vertex的新任執行長兼總裁，我非常榮幸歡迎您參加本次電話會議。新冠肺炎疫情為全世界人民帶來了巨大的挑戰。我們正經歷著艱難時期。我們知道，也看到，世界各國人民的生活都受到了影響。我們與那些失去親人的家庭一同哀悼，並向奮戰在抗疫一線的英雄們致以崇高的敬意。

Acknowledging that this is a difficult time for everyone, I want to begin by telling you why we believe that despite the pandemic, the future of Vertex remains brighter than ever. In many ways, Vertex is a unique company, a company with a proven track record as a serial innovator with 4 approved CF medicines, including TRIKAFTA, a medicine, we believe, can treat up to 90% of CF patients around the world with high efficacy. A company with a broad clinical and late preclinical stage pipeline, using multiple modalities to treat and potentially cure serious diseases outside of CF. A company with current and future top and bottom line growth, and a strong balance sheet. And finally, a company with an extraordinarily talented senior leadership team and a diverse inclusive workforce. In short, exactly the kind of company I want to be a part of going forward.

我深知目前對所有人來說都是一段艱難時期，首先我想談談我們為何相信，即便麵臨疫情挑戰，Vertex 的未來依然一片光明。 Vertex 在許多方面都獨樹一幟，它是一家擁有卓越創新記錄的公司，旗下已有四款獲批的囊性纖維化 (CF) 藥物，其中包括 TRIKAFTA。我們相信，TRIKAFTA 能夠高效治療全球高達 90% 的 CF 患者。 Vertex 擁有廣泛的臨床和後期臨床前研發管線，採用多種療法治療甚至治癒 CF 以外的其他嚴重疾病。 Vertex 擁有持續成長的營收和利潤，以及穩健的資產負債表。此外，Vertex 還擁有一支才華橫溢的高階管理團隊和一支多元化的員工隊伍。簡而言之，Vertex 正是我未來想要加入的公司。

At my core, I'm a physician-scientist driven by a deep passion to advance science and medicine in the interest of patients. Since joining Vertex, I have witnessed the ingenuity and drive that have enabled this company to tackle unprecedented challenges in discovery, development and commercialization of new medicines.

我本質上是一位醫生科學家，對推動科學和醫學發展、造福病人充滿熱情。自從加入Vertex以來，我親眼見證了公司展現出的創造力和進取精神，正是這些特質使公司能夠應對新藥發現、開發和商業化方面前所未有的挑戰。

For example, our rapid advancement of our triple combination program through research and development, and the early approval in the U.S... Today, the majority of eligible patients in the U.S. are already on TRIKAFTA. It's hard to believe, but true, that the original PDUFA date for TRIKAFTA was March 20, 2020.

例如，我們透過研發迅速推進了三聯療法項目，並在美國早期獲得批准……如今，美國大多數符合條件的患者已經在使用TRIKAFTA。令人難以置信的是，TRIKAFTA最初的PDUFA批准日期是2020年3月20日。

Another example is pioneering the use of CRISPR gene editing with our partners at CRISPR Therapeutics to potentially cure diseases like sickle cell and beta thalassemia. I am humbled to have the opportunity to follow Jeff in leading this unique company.

另一個例子是我們與 CRISPR Therapeutics 的合作夥伴共同開創性地使用 CRISPR 基因編輯技術，以期治癒鐮狀細胞貧血症和β地中海貧血症等疾病。能夠有機會接替 Jeff 領導這家獨具特色的公司，我深感榮幸。

Now on to our Q1 performance. Vertex's business, as demonstrated in our record first quarter financial results announced today, is stronger than ever. Our Q1 CF product revenues compared to last year are up 77% and to $1.52 billion, driven by the highly successful launch of TRIKAFTA in the U.S. and the growth of ORKAMBI and SYMKEVI outside the U.S. Our non-GAAP operating income rose 133% to $877 million. Our strategy is working, and we continue to grow our revenues and earnings while also investing significantly in innovation.

現在來看我們第一季的業績。正如我們今天公佈的創紀錄的第一季財務業績所示，Vertex 的業務比以往任何時候都更加強勁。與去年同期相比，我們第一季的 CF 產品收入成長了 77%，達到 15.2 億美元，這主要得益於 TRIKAFTA 在美國的成功上市以及 ORKAMBI 和 SYMKEVI 在美國以外地區的成長。我們的非 GAAP 營業收入成長了 133%，達到 8.77 億美元。我們的策略行之有效，我們將持續提高收入和利潤，同時大力投資創新。

As we look to the future, we are confident in the continued growth of our CF franchise for several reasons. First, our CF medicines are changing the lives of the patient populations they serve. And by addressing the underlying cause of disease, they are an important part of patients' efforts to remain as healthy as possible. Second, our supply chain to manufacture and distribute our medicines is robust, and we remain confident in our ability to continue to supply our medicines uninterrupted to CF patients around the world for the long term.

展望未來，我們對囊性纖維化（CF）業務的持續成長充滿信心，原因有幾點。首先，我們的CF藥物正在改變患者群體的生活。透過解決疾病的根本原因，這些藥物成為患者保持健康的重要保障。其次，我們擁有穩健的藥品生產和分銷供應鏈，我們有信心長期不間斷地為全球CF患者提供藥品。

Finally, while the course of the pandemic is unpredictable, we retain a clear line of sight to securing approval and launching the triple combination regimen in more countries around the world and in younger age groups, and sustaining our CF leadership well into the next decade. Our vision has been for TRIKAFTA to be able to treat 90% of all CF patients, and that vision remains very much intact.

最後，儘管疫情發展難以預測，但我們仍清晰地朝著獲得批准並在更多國家/地區以及更年輕的年齡組人群中推出三聯療法的目標邁進，並保持我們在未來十年內繼續引領囊性纖維化治療領域的領先地位。我們一直以來的願景是讓 TRIKAFTA 能夠治療 90% 的囊性纖維化患者，這個願景仍然堅定不移。

Given the strong performance of our CF products in Q1, we are raising our revenue guidance for the year to a range of $5.3 billion to $5.6 billion. Stuart and Charlie will review the factors underlying our new guidance in a few moments.

鑑於我們CF產品在第一季的強勁表現，我們將全年營收預期上調至53億美元至56億美元。 Stuart和Charlie稍後將詳細解讀我們做出這項新預期的原因。

Let me now turn to our pipeline and discuss how we are taking specific actions to continue to progress our clinical programs while protecting patients and health care providers. As you will see, each program is somewhat unique and different.

現在，我想談談我們的研發管線，以及我們如何採取具體措施，在保障病人和醫護人員安全的同時，繼續推動我們的臨床計畫。正如您將看到的，每個項目都各有特色。

First, our regulatory and development teams have been working diligently to stay on track with our submissions to regulators and to adapt ongoing clinical studies as needed to ensure that they can be completed successfully. We continue to make progress in our ongoing CF trials. For example, our CF regulatory team completed the submission of the sNDA in the U.S. as well as a type 2 variation to the EMA in Europe for KALYDECO, for infants with CF down to 4 months of age.

首先，我們的監管和研發團隊一直努力確保按計劃向監管機構提交申請，並根據需要調整正在進行的臨床研究，以確保研究順利完成。我們正在進行的囊性纖維化（CF）臨床試驗也持續取得進展。例如，我們的CF監管團隊已完成KALYDECO在美國的補充新藥申請（sNDA）提交，以及向歐洲藥品管理局（EMA）提交的針對4個月及以下CF兒童的2型變更申請。

Similarly, we have been able to progress our FSGS program. Our clinical team for our APOL1-mediated kidney diseases program have been able in the past few weeks to initiate our Phase II study of VX-147 in APOL1-mediated FSGS, and we now have 13 sites open. On the other hand, we have recently temporarily paused enrollment or treatment in some ongoing clinical studies, including the Phase II study of VX-814 in our AAT program.

同樣，我們的FSGS專案也取得了進展。過去幾週，我們APOL1介導的腎臟疾病計畫的臨床團隊已啟動了VX-147治療APOL1介導的FSGS的II期臨床試驗，目前已有13個研究中心開放。另一方面，我們近期暫停了部分正在進行的臨床研究的患者招募或治療，包括AAT計畫中的VX-814 II期臨床試驗。

Every program and every clinical study is different, and we have analyzed each situation closely and have made decisions based on the need to keep patients safe and to respect the need to preserve the resources of the health care system for where they are needed most.

每個項目和每項臨床研究都各不相同，我們仔細分析了每種情況，並根據保障患者安全和尊重將醫療保健系統資源用於最需要的地方的需要而做出決定。

In addition to our clinical progress, we are working to maintain momentum in our late-stage preclinical programs so that we can move forward when it is possible to do so into first-in-human studies. Though we have reduced the on-site occupancy at our sites to protect employees and our facilities, our research labs have stayed open. And we have prioritized activities that are IND-enabling for our next medicines centering development. This includes our cell therapy program for type 1 diabetes, where we continue to have a goal of starting clinical development in patients in late 2020 or early 2021.

除了臨床進展之外，我們也在努力維持後期臨床前計畫的勢頭，以便在條件允許的情況下盡快進行首次人體試驗。儘管我們已減少了各試驗點的現場人員數量以保護員工和設施，但我們的研究實驗室仍然保持開放。我們優先進行了與新藥研發相關的IND申報活動，其中包括我們針對第1型糖尿病的細胞療法項目，我們仍然計劃在2020年底或2021年初啟動該項目的臨床開發。

We are also continuing to progress our business development strategy and investing in external innovation. This week, we announced a new collaboration with Affinia Therapeutics. This collaboration supports the discovery and development of novel AAV capsids for in-vivo delivery of genetic therapies in a number of disease areas. We are pleased to bring this capability into the cell and gene therapy toolbox that we are building.

我們也持續推動業務發展策略，並加大對外部創新的投入。本週，我們宣布與Affinia Therapeutics公司建立新的合作關係。此次合作將支持新型AAV衣殼的發現與開發，用於在多種疾病領域進行體內基因治療。我們很高興能將這項技術融入我們正在建構的細胞和基因療法工具箱中。

Finally, despite the pandemic, we continue to grow our senior leadership team with several important new hires and promotions in Q1 the first is Dr. Carmen Bozic, who was promoted to Chief Medical Officer earlier this month. Carmen now has responsibility for clinical development, medical affairs, drug safety, global clinical operations, biometrics and other related functions. Carmen has extensive experience in clinical drug development and joined Vertex in 2019 from Biogen, where she oversaw the development and regulatory approval of 9 important medicines, including TECFIDERA and SPINRAZA.

最後，儘管受到疫情影響，我們仍在第一季透過幾項重要的人事任命和晉升繼續壯大我們的高階領導團隊。首先是卡門·博齊克博士，她於本月初晉升為首席醫療官。卡門現在負責臨床開發、醫學事務、藥物安全、全球臨床營運、生物統計及其他相關職能。卡門在臨床藥物開發方面擁有豐富的經驗，她於2019年加入Vertex，此前曾在百健公司工作，負責監督包括TECFIDERA和SPINRAZA在內的9種重要藥物的開發和監管審批。

The second is Dr. Bastiano Sanna who joined Vertex when we acquired Semma in 2019, where he was CEO. We have expanded Bastiano's role, and he is Chief of Cell and Genetic Therapies at Vertex. In this new role, he now leads all of our gene editing, gene therapy and cell therapy programs as well as related technologies for sickle cell disease, beta thalassemia, DMD, type 1 diabetes and others. Bastiano has extensive experience and expertise in cell and genetic therapies from prior roles at Magenta and Novartis. And I am confident that his skill set will enable us to build capabilities at Vertex that are second to none. I am absolutely delighted to have Carmen and Bastiano on the team.

第二位是巴斯蒂亞諾桑納博士，他於2019年Vertex收購Semma時加入公司，此前他擔任Semma的執行長。我們擴大了巴斯蒂亞諾的職責範圍，他現在擔任Vertex細胞和基因療法主管。在這個新職位上，他負責領導我們所有的基因編輯、基因療法和細胞療法項目，以及鐮狀細胞貧血症、β地中海貧血、杜氏肌肉營養不良症（DMD）、第1型糖尿病等相關技術。巴斯蒂亞諾曾在Magenta和諾華公司擔任要職，在細胞和基因療法領域擁有豐富的經驗和專業知識。我相信，他的技能將使我們能夠在Vertex上打造首屈一指的實力。我非常高興卡門和巴斯蒂亞諾加入我們的團隊。

In summary, this extraordinary moment in time in which we find ourselves right now will pass. We will all get through this together. Despite these unusual circumstances, Vertex is well positioned to continue to serve our CF patients, grow revenues and earnings and advance our pipeline of transformative medicines in disease areas beyond CF.

總之，我們目前所處的這個特殊時期終將過去。我們所有人都會攜手共渡難關。儘管面臨這些特殊情況，Vertex 仍具備充分的實力，繼續為囊性纖維化患者提供服務，實現營收和利潤增長，並推進我們在囊性纖維化以外疾病領域的變革性藥物研發。

Let me turn it over to Stuart.

讓我把麥克風交給史都華。

Thanks, Reshma. I am pleased to review with you this evening our continued strong commercial performance in the first quarter of 2020. I am very proud of our commercial supply, market access, patient support, marketing and field teams who were fully prepared for the early approval of TRIKAFTA in the U.S. and we also want to recognize the remarkable job that CF centers and health care professionals have done to respond to both the approval and the high level of payment interest in starting the medicine.

謝謝，雷什瑪。今晚很高興能與您一起回顧我們在2020年第一季持續強勁的商業表現。我為我們的商業供應、市場准入、患者支援、行銷和現場團隊感到非常自豪，他們為TRIKAFTA在美國的提前獲批做好了充分準備。我們也要感謝囊性纖維化中心和醫療保健專業人員為響應藥物獲批和各方對該藥物的高度關注所做出的卓越貢獻。

Our teams have executed what is by every measure a very rapid and successful U.S. launch of TRIKAFTA for CF patients 12 years and older with at least one F508del mutation. Approved in October 2019, 5 months ahead of its PDUFA date, TRIKAFTA has been widely adopted. We have seen strong demand across all groups of patients eligible for TRIKAFTA. And it is now being taken by the majority of the 18,000 eligible patients in the U.S.

我們的團隊在美國成功快速地推出了TRIKAFTA，適用於12歲及以上且至少攜帶一個F508del突變的囊性纖維化（CF）患者。 TRIKAFTA於2019年10月獲批，比原定的PDUFA日期提前了5個月，並已被廣泛採用。我們看到所有符合TRIKAFTA使用條件的患者群體都對它有強烈的需求。目前，美國18,000名符合條件的患者中，大多數都在服用該藥。

Total CF product revenues for Q1 2020 were $1.52 billion. And in its first full quarter, TRIKAFTA accounted for $895 million of those revenues. This was due in large part to more rapid-than-expected adoption of TRIKAFTA in all eligible patient groups in the U.S. Geographically for our CF product portfolio, we recorded approximately $1.19 billion in revenues in the U.S. and $328 million outside the U.S. Growth outside the U.S. was driven by strong patient uptake of ORKAMBI and SYMKEVI, following the completion of multiple reimbursement agreements in late 2019. In most countries outside the U.S. where our medicines are reimbursed, the majority of eligible patients have now initiated treatment.

2020年第一季度，囊性纖維化（CF）產品總收入為15.2億美元。其中，TRIKAFTA在其首個完整季度貢獻了8.95億美元的收入。這主要歸功於TRIKAFTA在美國所有符合條件的患者群體中比預期更快被接受。從地理來看，我們的CF產品組合在美國的收入約為11.9億美元，在美國以外地區的收入約為3.28億美元。美國以外地區的成長主要得益於ORKAMBI和SYMKEVI在2019年底完成多項健保報銷協議後，病患接受度的大幅提升。在我們藥物獲得健保報銷的大多數美國以外國家，目前大多數符合條件的患者已經開始接受治療。

Based on our strong Q1 revenue performance, we have raised our revenue guidance for the year, as Reshma mentioned. The new guidance and range takes into account both the rapid uptake of TRIKAFTA we have seen since October 2019 as well as additional dynamics that we either saw during Q1 or that we anticipate as we move through the year. First, we did see some benefit in Q1 from early prescription refills by patients, both in the U.S. and outside the U.S., as well as advanced buying from some government payers outside the U.S.

正如Reshma所提到的，鑑於我們第一季強勁的營收表現，我們提高了全年營收預期。新的預期和範圍不僅考慮了自2019年10月以來TRIKAFTA的快速成長，還考慮了我們在第一季度觀察到的其他因素以及我們預計在今年後續階段將出現的其他因素。首先，我們確實在第一季受益於美國及美國以外患者提前續訂處方，以及美國以外一些政府健保機構的提前採購。

Second, while there are still new patients starting TRIKAFTA treatment, the pace of initiation has slowed. A high percentage of currently eligible patients are already on TRIKAFTA in the U.S. and so we have reached the flatter part of the uptake curve. Additionally, COVID-19 has resulted in some CF centers limiting their nonemergency interactions, and this could impact the rate of future initiations.

其次，雖然仍有新患者開始接受 TRIKAFTA 治療，但啟動速度已放緩。目前美國符合條件的患者中，已有相當一部分人正在接受 TRIKAFTA 治療，因此我們已經進入了成長曲線的平緩期。此外，COVID-19 疫情導致一些囊性纖維化中心減少了非緊急就診，可能會影響未來的啟動率。

Third, given that we have only just completed the first full quarter of the TRIKAFTA launch, we know that we have yet to see the full impact of persistence and compliance rates on the ongoing utilization of this medicine. As with all of our medicines, the revenue impact of persistence and compliance does not become fully reflected until several quarters after launch.

第三，鑑於TRIKAFTA上市至今僅完成了第一個完整季度，我們知道，持續用藥率和依從性對該藥物持續使用的全面影響尚未顯現。與我們所有藥物一樣，持續用藥率和依從性對收入的影響，在上市幾季後才能完全體現。

Looking ahead, the focus of our efforts to serve patients is twofold. First, ensuring that we can continue to meet the strong demand for our medicines with uninterrupted supply. Our team has closely analyzed our existing supply chain and has worked during the emergence of the pandemic to ensure that there was no change in our ability to provide medicines to patients. Our manufacturing facilities have remained fully operational, and we have continued to produce new supply of our CF medicines. We are confident that this will remain the case moving forward.

展望未來，我們服務患者的工作重點有兩個面向。首先，確保我們能夠持續滿足市場對我們藥品的強勁需求，並確保藥品供應不間斷。我們的團隊對現有供應鏈進行了深入分析，並在疫情爆發初期積極採取措施，確保我們為患者提供藥物的能力不受影響。我們的生產設施一直保持正常運轉，我們持續生產新的囊性纖維化（CF）藥物。我們相信，這種情況將持續下去。

Second, we are progressing with urgency to expand the number of patients eligible for and able to access our CF medicines. We anticipate several important milestones in the coming 12 months, which are expected to drive access to our CF product portfolio for even more patients.

其次，我們正加緊推動擴大符合條件並獲得我們囊性纖維化藥物的患者群體。我們預計未來12個月內將取得幾個重要里程碑，這些里程碑有望使更多患者能夠獲得我們的囊性纖維化產品組合。

The MAA for the elexacaftor triple combination is filed and under review with the European Medicines Agency. Approval by EMA would significantly increase the number of patients eligible for triple combination and enable us to begin reimbursement decisions across many European countries, as well as provide rapid access in some countries where we have a portfolio agreement. We have also now submitted the elexacaftor triple combination for approval in Switzerland and Australia.

我們已向歐洲藥品管理局 (EMA) 提交了 elexacaftor 三聯療法的上市許可申請 (MAA)，目前正在審核中。 EMA 的批准將顯著增加符合三聯療法適應症的患者人數，使我們能夠在許多歐洲國家開始進行醫保報銷決策，並在我們已簽署產品組合協議的部分國家/地區提供快速用藥途徑。此外，我們已向瑞士和澳洲提交了 elexacaftor 三重療法的上市申請。

Also in Switzerland, we have just entered a portfolio reimbursement agreement for both SYMDEKO and ORKAMBI, and we look forward to treating more CF patients there. The Swiss agreement is also designed to include the triple combination in the future. And with label expansion efforts, we are on track to submit the sNDA in the U.S. for TRIKAFTA for the treatment of CF patients, aged 6 to 11, with at least one F508del mutation in the second half of 2020.

此外，我們在瑞士也剛簽署了SYMDEKO和ORKAMBI的藥品報銷協議，我們期待在那裡治療更多囊性纖維化患者。該瑞士協議還旨在未來將三聯療法納入其中。隨著適應症擴展工作的推進，我們正按計畫於2020年下半年在美國提交TRIKAFTA的補充新藥申請（sNDA），用於治療6至11歲且至少攜帶一個F508del突變的囊性纖維化患者。

We are pleased with the rate of uptake that we have seen for TRIKAFTA in the U.S., and for ORKAMBI and SYMKEVI outside the U.S. We continue to see the potential to reach 90% of CF patients worldwide with TRIKAFTA, and we believe that this will continue to drive revenue growth for Vertex in the future.

我們對 TRIKAFTA 在美國的市場接受度以及 ORKAMBI 和 SYMKEVI 在美國以外地區的市場接受度感到滿意。我們仍然認為 TRIKAFTA 有潛力覆蓋全球 90% 的囊性纖維化患者，我們相信這將繼續推動 Vertex 未來的收入成長。

I will now turn the call over to Charlie.

現在我將把通話轉給查理。

Thanks, Stuart. I will provide additional comments this evening regarding our Q1 2020 financial results and will also discuss our revised 2020 financial guidance. All of the results and guidance I will discuss are non-GAAP.

謝謝，斯圖爾特。今晚我將就我們2020年第一季的財務業績提供更多評論，並討論我們修訂後的2020年財務預期。我將要討論的所有業績和預期均基於非GAAP準則。

First quarter total CF product revenues were $1.52 billion, a 77% increase compared to 2019. TRIKAFTA sales in the first full quarter after launch were $895 million, and remarkably, TRIKAFTA now generates more revenue than all of our other CF medicines combined. The growth of TRIKAFTA reflects rapid uptake among newly eligible patients as well as among patients switching from other medicines.

第一季囊性纖維化（CF）產品總收入達15.2億美元，較2019年同期成長77%。 TRIKAFTA上市後首個完整季度的銷售額為8.95億美元，值得一提的是，TRIKAFTA目前的收入已超過我們所有其他CF藥物的總和。 TRIKAFTA的成長反映了新符合條件的患者以及從其他藥物轉換而來的患者對該藥物的快速接受。

Importantly, ORKAMBI and SYMKEVI continue to grow outside the U.S.-based on rapid uptake in key markets where we achieved reimbursement agreements in late 2019. In the first quarter of 2020, CF product revenues were $328 million outside the U.S., an increase of 51% over the prior year. Our first quarter 2020 combined R&D SG&A expenses were $477 million compared to $388 million for the first quarter of 2019.

值得注意的是，ORKAMBI 和 SYMKEVI 在美國以外的市場持續成長，這得益於我們在 2019 年底達成健保報銷協議的關鍵市場迅速接受這兩款產品。 2020 年第一季度，囊性纖維化產品在美國以外的營收為 3.28 億美元，較上年同期成長 51%。 2020 年第一季度，我們的研發、銷售、管理及行政費用總額為 4.77 億美元，而 2019 年第一季為 3.88 億美元。

Overall, the combination of significant growth in revenues and more moderate growth in spending in the first quarter resulted in an operating margin of 58% and operating income of $877 million, an increase of 133% compared to the first quarter of 2019. Net income for the first quarter of 2020 was $674 million compared to $296 million in the first quarter of 2019.

總體而言，第一季營收的大幅成長和支出的較為溫和的成長相結合，使得營業利潤率達到 58%，營業收入達到 8.77 億美元，比 2019 年第一季度增長了 133%。 2020 年第一季的淨收入為 6.74 億美元，而 2019 年第一季為 2.96 億美元。

Now I'll review 2020 guidance. Today, we are revising upward our 2020 financial guidance for total CF product revenues to a range of $5.3 billion to $5.6 billion, which at the midpoint reflects 36% growth over 2019. This range reflects both the very strong TRIKAFTA uptake that Stuart described in his prepared remarks as well as the moderating factors he described for the remainder of 2020. We are leaving our OpEx and tax guidance unchanged.

現在我將回顧2020年的業績指引。今天，我們將2020年CF產品總收入的財務指引上調至53億美元至56億美元，其中數值較2019年成長36%。這一區間既反映了Stuart在事先準備好的發言稿中提到的TRIKAFTA的強勁增長，也反映了他所描述的2020年剩餘時間可能出現的抑制因素。我們的營運支出和稅務指引保持不變。

Now turning to capital allocation. We finished Q1 2020 with $4.2 billion in cash, and our top priority for capital allocation remains to reinvest in both internal and external innovation to create future medicines, and our thinking and strategy in business development have not changed. We are focused on programs and technologies that can accelerate the creation of transformational medicines for the diseases in which we are interested.

現在談談資本配置。截至2020年第一季末，我們擁有42億美元的現金儲備。我們資本配置的首要任務仍然是投資內部和外部創新，以研發未來的藥物。我們在業務發展方面的思路和策略並沒有改變。我們專注於能夠加速研發針對我們所關注疾病的變革性藥物的專案和技術。

For example, this week, we announced a new collaboration with Affinia Therapeutics. This collaboration gives us access to Affinia's innovative and novel AAV capsids and allows us to leverage their AAV expertise to advance the multiple gene editing and genetic therapy programs in development at Vertex. Finally, as we look ahead through 2020, we expect our strong cash flow to continue to support additional investments to fuel our long-term growth.

例如，本週我們宣布與Affinia Therapeutics達成新的合作。此次合作使我們能夠獲得Affinia創新且新型的AAV衣殼，並藉助其在AAV領域的專業知識，推進Vertex正在開發的多個基因編輯和基因治療計畫。展望2020年，我們預期強勁的現金流將持續支持更多投資，進而推動我們的長期成長。

Now back to Reshma for a few concluding remarks.

現在請雷什瑪做幾句總結性發言。

In closing, it's obviously a difficult time for people and for businesses around the world. You have heard tonight that Vertex is operating according to a set of clear principles and that we are committed to protecting the health and safety of our people and meeting the needs of the patients we serve.

最後，顯然，對於世界各地的人們和企業來說，這都是一段艱難的時期。今晚大家也聽到了，Vertex 始終遵循一套明確的原則運營，我們致力於保護員工的健康和安全，並滿足我們所服務患者的需求。

I am proud of the many Vertex employees who are going above and beyond, adapting to new circumstances and continuing to advance our R&D programs and helping our business outperform expectations. I am also proud of our many recently announced philanthropic programs to help support the people and communities in which we live and work.

我為Vertex眾多兢兢業、積極適應新環境、不斷推進研發專案並幫助公司業績超越預期的員工感到自豪。我也為我們近期宣布的眾多慈善項目感到驕傲，這些項目旨在幫助我們生活和工作所在的社區和人民。

The Vertex Foundation has made a number of donations, including to the Boston Resiliency Fund and organizations around the globe, providing health supplies to frontline workers and to support vulnerable populations through food, care and education. I look forward to sharing further news of our progress in the months ahead.

Vertex基金會已向包括波士頓復原基金在內的多個組織以及全球其他機構捐贈物資，為第一線工作人員提供醫療用品，並透過食物、護理和教育等方式支持弱勢群體。我期待在未來幾個月與大家分享我們取得的更多進展。

Thank you, and we'll now open the call to questions.

謝謝，現在開始接受提問。

(Operator Instructions) And our first question comes from Phil Nadeau with Cowen and Company.

（操作說明）我們的第一個問題來自 Cowen and Company 的 Phil Nadeau。

Congrats on all progress. Just a 2-part question from me. First, you talked about the supply chain and manufacturing continuing at pace. Are there any pinch points that you can identify in your distribution networks that could hinder the patients' access to your therapies, anything from not being able to get their deliveries at home to lack of ability to have telemedicine reauthorizations for prescriptions that have already been written? That's part one. And then second question is just on the pipeline. I think we're all focused on the AAT program. Do you have a sense when you'll be able to provide guidance on when the data from the Phase II study could be available?

祝賀你們取得的所有進展。我有兩個問題。首先，您提到供應鏈和生產都在快速推進。在經銷網路中，是否有任何可能阻礙患者獲得治療的瓶頸，例如無法送貨上門，或無法對已開立的處方進行遠距醫療續約？這是第一個問題。第二個問題是關於研發管線的。我想我們目前都在關注AAT專案。您預計何時能夠公佈二期臨床試驗的數據？

Phil, it's Stuart, I'll take the first question on supply chain and patients being able to get our medicines, and then Reshma will cover AAT. So in terms of the supply chain and manufacturing, we don't see any pinch points really that are not anything that can be overcome. So far, as I've mentioned in our prepared remarks, our manufacturing facilities have remained fully operational.

菲爾，我是斯圖爾特，我先回答關於供應鏈和患者能否獲得我們藥品的問題，然後雷什瑪會談到AAT的情況。就供應鏈和生產而言，我們目前沒有發現任何無法克服的瓶頸。正如我在事先準備好的演講稿中提到的，到目前為止，我們的生產設施一直保持正常運作。

Our ability to supply medicines around the world has continued. Clearly, with things like commercial flights being reduced, there have been some challenges. But it's really delays of a number of days and things like that, and certainly nothing that is disrupting patients' ability to get their medicines when they need them. And so we continue to feel very confident that we're going to be able to continue to supply both patients who are currently are our medicines and be able to supply launches if we get subsequent approvals.

我們向全球供應藥品的能力一直保持正常。誠然，由於商業航班減少等原因，我們面臨一些挑戰。但這僅僅造成幾天左右的延誤，絕不會妨礙患者在需要時獲得所需藥物。因此，我們仍然非常有信心能夠繼續為目前正在服用我們藥品的患者提供藥品，並在後續藥品獲得批准後，能夠及時供應新上市的藥品。

And with that, I'll hand it over to Reshma to handle the AAT question.

接下來，我將把AAT問題交給Reshma來解答。

Yes. So this is Reshma. Just to remind everyone, the study that you're talking about is the VX-814 study in the AATD disease area. This is a Phase II dose-ranging study, proof-of-concept study. It's about 50 people, 3 doses plus placebo. It's 28 days of treatment with another 1 month of follow-up. So that's the study we're talking about. And you're right, we had temporarily paused screening and enrollment, and where we are today is that we are in the process of reinitiating screening and enrollment on a site-by-site, country-by-country, region-by-region basis in those areas that are opening and are now able to resume clinical trial activity.

是的。我是Reshma。提醒大家一下，你們提到的研究是針對AATD疾病領域的VX-814研究。這是一項II期劑量探索性概念驗證研究。研究對象約50人，分為3個劑量組，另設安慰劑組。治療期為28天，之後進行1個月的追蹤。這就是我們討論的研究。你說得對，我們之前暫停了篩選和入組工作。目前，我們正在逐步重啟篩選和入組工作，具體在那些已經開放並能夠恢復臨床試驗活動的地區，逐個研究中心、逐個國家、逐個地區地進行。

With regard to when will the results be available, so this now depends on the dynamics around enrollment. And we'll only know that when we have a little bit more time under our belt because, as I said, it's site by site, region by region, country by country. We are in the process of reinitiating screening enrollment, but we need a little bit more time to determine what those enrollment dynamics will be. We will know what that is, it's just going to take a little bit of time. And when we know, I will certainly update you. That day is not today.

至於何時公佈結果，這取決於招募情況的動態。我們需要更多時間才能確定，因為正如我所說，這要視具體地點、地區和國家而定。我們正在重新啟動篩檢招募工作，但需要更多時間來確定招募情況。我們會知道結果的，只是需要一些時間。一旦確定，我一定會通知大家。但今天還不是公佈結果的日子。

Our next question comes from Michael Yee with Jefferies.

下一個問題來自傑富瑞集團的麥可葉。

And congrats on the progress as well. A great quarter. I guess, 2 questions. Forward looking, you have a European approval potentially coming. Can you just talk about how the dynamics of your existing portfolio deals were -- remind me which countries have that and the pace and adoption of some of your recent other deals for the doublets could help accelerate the timing of uptake and launch in some of those other countries for TRIKAFTA? Maybe just talk about how you think about that versus prior history of your other CF drugs in Europe this year.

也祝賀你們的進展。這個季度表現出色。我想問兩個問題。展望未來，你們的藥物可能即將獲得歐洲批准。能否談談你們現有產品組合交易的動態－提醒我哪些國家已經批准了該藥物，以及你們近期其他一些雙聯療法交易的進展速度和市場接受度是否能夠加快TRIKAFTA在這些國家的上市進程？能否談談您如何看待TRIKAFTA與今年其他囊性纖維化藥物在歐洲市場的發展有何不同？

And then the second question relates -- going back to AAT. Appreciate the comments. I see that you didn't mention VX-864. Was there anything to say about that? Was that study completed? Maybe just make a comment about that. I thought that was finishing Phase I.

第二個問題是關於AAT的。感謝您的評論。我注意到您沒有提到VX-864。關於它有什麼要說的嗎？那項研究完成了嗎？或許可以簡單談談。我以為它已經完成第一階段了。

Okay. Mike, it's Stuart here.

好的。麥克，我是史都華。

Stuart, why don't you do this?

斯圖爾特，你為什麼不做這件事？

Yes, I'll take the question on reimbursement, Mike. Firstly, thanks for the congratulations on the quarter. We feel thrilled with how well the business has performed in this first quarter 2020. In terms of the EU approval for the triple combination and reimbursement, as you know, we filed and the file was accepted in October of last year and is currently under review.

好的，麥克，關於報銷的問題我來回答。首先，感謝您對本季業績的祝賀。我們對2020年第一季的業務表現感到非常滿意。關於三聯療法的歐盟審批和報銷問題，如您所知，我們已於去年10月提交了申請，申請已被接受，目前正在審核中。

I really think of the access to patients outside of the U.S. really being in kind of 3 categories. There's obviously a country like Germany, which provides immediate access while you then negotiate the price that they will pay you on a prospective basis. Then as you say, there's a number of countries where we have portfolio reimbursement agreements. That's countries like Ireland, Denmark, also we recently concluded a similar agreement in Switzerland.

我認為在美國以外地區獲得患者治療的機會大致可以分為三類。首先是像德國這樣的國家，它們提供即時治療，然後你可以與他們協商未來的付款價格。其次，正如你所說，我們與一些國家簽訂了藥品報銷協議，例如愛爾蘭、丹麥，最近我們也與瑞士達成了類似的協議。

All the portfolio agreements are all slightly different. Some of them include just the currently approved patient populations. Some of them, like in Ireland for instance, also include the FMF population as well. But we would imagine that soon after getting regulatory approval, we would be working with those countries to get, hopefully, access very, very quickly after the regulatory approval. And then there's the remaining countries where we don't have portfolio agreements where the regulatory approval really is the beginning of that reimbursement process.

所有產品組合協議都略有不同。有些協議僅涵蓋目前已核准的患者族群。有些協議，例如在愛爾蘭，也涵蓋了家族性地中海熱（FMF）患者群體。但我們預計，在獲得監管部門批准後，我們將盡快與這些國家合作，爭取在監管部門批准後迅速實現藥物的可及性。此外，還有一些國家我們尚未簽署產品組合協議，在這些國家，監管部門的批准只是報銷流程的開始。

I do hope that our reimbursement processes can move more quickly. And I think there are some reasons to be optimistic about that, Mike, not least because we have reimbursement agreements in the vast majority of countries now. And that sets 2 things, it sets a price in the marketplace and it also sets a profile of benefit risk in the marketplace. And as you know, we feel very good about the benefit risk profile of the triple combination compared to even our own transformative medicines. And so I'm hopeful that, that will provide a tailwind.

我真心希望我們的報銷流程能夠加快。麥克，我認為有理由對此保持樂觀，尤其因為我們現在與絕大多數國家都簽訂了報銷協議。這決定了兩件事：一是確定了市場價格，二是確定了市場上的獲益風險比。如你所知，我們對三聯療法的獲益風險比非常滿意，甚至超過了我們自身俱有變革意義的藥物。因此，我希望這能帶來利好。

Obviously, from a payer perspective, label dependent, the triple combination could increase the number of eligible patients, which would be an increase in budget impact. I'm sure that's something we're going to have to negotiate with them. But that's how we see the reimbursement landscape playing out subsequent to regulatory approval. And on AAT, I'll throw it over to Reshma.

顯然，從支付方的角度來看，根據藥品標籤，三重療法可能會增加符合條件的患者數量，從而增加預算負擔。我相信我們需要就此與他們進行協商。但這就是我們預計在獲得監管機構批准後，報銷格局將如何變化。關於AAT，我把這個問題交給Reshma來回答。

Yes. So Mike, thanks for the question on VX-864. So VX-814 is the one we just went through, where we had temporarily paused screening and further enrollment. That's the one where we're in the process of reinitiating both screening and enrollment. And that's the one that's already in Phase II dose-ranging. VX-864 is the next molecule in our AATD program. That one has completed its Phase I study. We've had a chance to look at the safety and the PK. That one is going to be ready to go into its Phase II proof-of-concept dose-ranging study, and I anticipate that that's going to happen in this year, the second half of this year.

是的。麥克，謝謝你問關於VX-864的問題。 VX-814是我們之前暫停篩選和招募的那個項目，現在我們正在重新啟動篩選和招募工作。 VX-814已經進入II期劑量探索階段。 VX-864是我們AATD計畫中的下一個分子，它已經完成了I期研究。我們已經評估了它的安全性和藥物動力學。 VX-864即將進入II期概念驗證劑量探索研究，我預計在今年下半年進行。

Our next question comes from Salveen Richter with Goldman Sachs.

下一個問題來自高盛的薩爾文·里希特。

Congratulations on the launch as well. When you talked about guidance, you mentioned a couple of buckets here. And would it be possible to quantify on how to think about the early prescription refills and the buying patterns from other countries that will push forward? And then secondly, with persistence and patient compliance, where do you see that level typically level off based on historically what's been seen with this franchise? And then thirdly, I guess, on the pipeline, should we expect 147 data in APOL1-mediated kidney disease to be on track for the year? And maybe you could just frame for us what the clinical bar is here.

也恭喜你們成功推出新產品。在談到指導方針時，您提到了幾個方面。能否量化如何看待早期處方續藥以及其他國家的購買模式，這些因素將推動產品上市？其次，關於堅持治療和患者依從性，根據該系列產品的歷史數據，您認為其通常會在什麼水平趨於穩定？第三，關於研發管線，我們是否可以預期今年能按計畫取得147項關於APOL1介導的腎臟病的數據？您能否簡要說明一下該系列產品的臨床標準是什麼？

Yes. Salveen, let me ask Charlie to tackle the question around guidance, and then I'll come back and talk to you about 147. Charlie?

好的。薩爾文，我先請查理解答指導方面的問題，然後再回來跟你談147號問題。查理？

Yes. Thanks, Salveen. As you noted, we've increased guidance for the year to the range of $5.3 billion to $5.6 billion. And really, the primary driver behind that is the success of the launch and the significant patient uptake, and you see that reflected in Q1. With that, we're always mindful that folks not look at a single quarter performance and extrapolate from there.

是的，謝謝，薩爾文。正如您所說，我們已將全年業績預期上調至53億至56億美元。這主要得益於產品上市的成功和患者數量的顯著增長，而這一點在第一季也得到了體現。儘管如此，我們始終提醒大家，不要只憑一個季度的業績就妄下斷言。

So I think it's important, as Stuart outlined in the call, we did see some patients refilling prescriptions early in the first quarter as well as some countries OUS accelerating their purchases, which resulted in a little bit earlier revenue recognition for us. We're not going to dollarize that specifically, but I think you can conclude since we mentioned it, it was significant enough that we thought it was worth calling out. And then Stuart talked about the fact where we are in terms of the ramp-up on patients. There are still some patients to get on drug of course, but the rate of new initiations is slowing and could see some delays in future quarters as a result of changes in policies at CF centers in response to COVID.

所以我認為這一點很重要，正如斯圖爾特在電話會議中提到的，我們確實看到一些患者在第一季初就續訂了處方，一些美國境外國家也加快了採購速度，這使得我們提前確認了部分收入。我們不會具體說明具體金額，但既然我們提到了這一點，我想大家應該可以明白，這非常重要，值得特別說明。之後，史都華也談到了我們目前在患者用藥方面的進展。當然，還有一些患者需要開始用藥，但新患者啟動治療的速度正在放緩，並且由於囊性纖維化治療中心為應對新冠疫情而調整了政策，未來幾個季度可能會出現一些延遲。

And then lastly, around persistence and compliance, I think that the way to think about it is when patients first initiate on a medicine, their persistence and compliance rates are essentially at 100%, and that number only goes down from there over subsequent quarters until it's -- until it levels out at more of a steady state. And so we've talked about it in the past, persistence and compliance, the combination of those 2 factors, even if you're at 90-plus percent on both, you do the math on that, you can see that we have to come down from 100%.

最後，關於堅持用藥和依從性，我認為可以這樣理解：當患者最初開始服用某種藥物時，他們的堅持用藥率和依從性幾乎是100%，之後這個數字會隨著時間推移而逐漸下降，直到趨於穩定。我們之前也討論過，堅持用藥和依從性這兩個因素的結合，即使這兩個因素都達到了90%以上，你稍微計算一下就會發現，我們最終還是要從100%下降的。

So those will have an increasing impact over the balance of the second half of the year and is part of what we considered as we put the guidance together. But importantly, the midpoint of the guidance implies 36% growth year-over-year. It's an acceleration over last year's 32%. And so we are shaping up for another great year, and it really highlights just how differentiated this business is, particularly at this very uncertain time.

因此，這些因素將在下半年剩餘時間內產生越來越大的影響，這也是我們在製定業績指引時所考慮的因素之一。但重要的是，業績指引的中位數意味著年增36%，高於去年的32%。因此，我們有望迎來另一個輝煌的年份，這也充分凸顯了我們業務的差異化優勢，尤其是在當前充滿不確定性的時期。

Salveen, this is Reshma. With regard to your question around 147, just to remind everyone, this is our program in APOL1-mediated FSGS, and FSGS is a -- APOL1-mediated FSGS, I should say, the homogeneous kidney disease that is characterized by heavy proteinuria. And unfortunately, for these patients, it's sort of a relentless course of a decline in kidney function with one of only 2 outcomes. One is going on to dialysis or transplantation, and the other one unfortunately is death. Clearly, a disease with high unmet need.

Salveen，我是Reshma。關於你提到的147號問題，我再提醒大家一下，這是我們關於APOL1介導的局部節段性腎絲球硬化症（FSGS）的計畫。 FSGS是一種——更準確地說，是APOL1介導的FSGS——同質性腎臟疾病，其特徵是大量蛋白尿。不幸的是，對於這些患者來說，腎功能會持續下降，最終只有兩種結局：一是需要透析或腎臟移植，二是死亡。顯然，這是一種亟待解決的疾病。

This program, the key endpoint that we're looking for in terms of efficacy is proteinuria, and we are looking for a decrease in proteinuria. The renal community, regulators in the U.S., the FDA and academics and those involved in research in kidney disease have had many conferences around the topic of endpoints. And I think it would be very fair to say that proteinuria, which is the endpoint we are measuring in this Phase II proof-of-concept study that I just described that we are now up and running in, that would be the endpoint of importance in Phase III and in terms of patients. That's what we are looking for, and that's what we're monitoring for.

在本計畫中，我們評估療效的關鍵終點是蛋白尿，我們希望看到蛋白尿水平下降。腎臟病領域、美國監管機構（包括FDA）、學術界以及腎臟疾病研究人員已經就終點指標這個主題召開了多次會議。我認為可以肯定地說，蛋白尿——也就是我們剛才提到的這項正在進行中的II期概念驗證研究的終點指標——在III期臨床試驗中，對於患者而言，也將是至關重要的終點指標。這正是我們所關注和監測的。

Our next question comes from Geoff Meacham with Bank of America.

下一個問題來自美國銀行的傑夫‧米查姆。

Big congrats on the quarter. Just had a couple. Stuart, when I look at the guidance, the run rate is higher than your guidance. Is the delta primarily from the expected decline from SYMDEKO and ORKAMBI just switching to TRIKAFTA? Or is it that you guys are being conservative? And then beyond the 10% of CF patients that you can't address today, are there any updates to the commercial efforts to expand the TRIKAFTA CF patient base, for example, in Latin America, South Africa or other regions beyond the ones that you're expected to go in?

恭喜你們本季業績出色！我剛喝了幾杯。 Stuart，我看了一下你們的業績指引，實際銷量比你們的預期要高。這個差額主要是因為SYMDEKO和ORKAMBI的銷售預期下降，然後轉而使用TRIKAFTA嗎？還是你們的預測比較保守？另外，除了目前你們無法涵蓋的10%的囊性纖維化患者群體之外，在拓展TRIKAFTA囊性纖維化患者群體方面，例如在拉丁美洲、南非或其他你們計劃之外的地區，你們的商業計劃是否有任何更新？

And just for Reshma, real quick on the pipeline. You guys have been pretty active on the BD front. And have a ton of different assets and indications. But the question is, does the acceleration in the uptick in CF really change urgency or the size of future BD deals?

雷什瑪，關於你們的研發管線，我只想簡單問一下。你們在業務拓展方面一直非常活躍，擁有大量不同的資產和適應症。但問題是，CF（臨床預測）成長加速是否真的會改變未來業務拓展交易的迫切性或規模？

Sure, Geoff. Let me ask Stuart to go first and talk a little bit about the launch and some launch dynamics. I'll just make a quick comment. We have seen uptake of TRIKAFTA in the U.S. in all eligible populations. And we've just been so pleased to be able to serve all patients who are eligible. Stuart?

當然，傑夫。我先請史都華談談產品上市的情況和一些進展。我先簡單說幾句。我們看到，TRIKAFTA 在美國所有符合資格的人群中都得到了推廣。我們非常高興能夠為所有符合條件的患者提供服務。史都華？

Yes. Geoff, as Reshma said, the uptake of TRIKAFTA has been very strong across all eligible patients, and that includes transitioning from our existing medicines where the indications are overlapping. So KALYDECO, ORKAMBI and SYMDEKO patients have been moving over from those medicines to TRIKAFTA. In our results, that's obviously balanced by the growth we've seen outside the U.S. with ORKAMBI and SYMKEVI, as it's called outside of the U.S., following the new reimbursement agreements. So we've really got that kind of -- those 2 different dynamics going on, some cannibalization in the U.S. and continued growth outside of the U.S.

是的。正如雷什瑪所說，傑夫，TRIKAFTA 在所有符合條件的患者中的接受度都非常高，這其中也包括那些從我們現有藥物過渡而來，且適應症與 TRIKAFTA 重疊的患者。因此，KALYDECO、ORKAMBI 和 SYMDEKO 的患者已經開始從這些藥物轉而使用 TRIKAFTA。從我們的業績來看，這顯然與我們在美國以外地區（在美國以外地區稱為 SYMKEVI）的增長相平衡，這得益於新的醫保報銷協議。因此，我們確實看到了這兩種不同的動態：在美國存在一些市場蠶食，而在美國以外地區則持續成長。

As Charlie referenced earlier, we did see in the first quarter some early refills by patients and also some advanced purchasing by some governments outside the U.S., presumably in response to the early days of the pandemic that essentially is something that we would expect to sort of even out over the course of this year. In terms of the dynamics, which we are anticipating could potentially play out for the balance of the year, as Charlie said, the biggest single factor really is going to be persistence and compliance. As he said, a patient when they initiate therapy, they're 100% persistence -- persistent and compliant. And as we know, those numbers are only going to drift downwards from there.

正如查理之前提到的，我們在第一季確實看到一些患者提前續購藥品，以及一些美國以外國家的政府提前採購藥品，這大概是為了應對疫情初期的情況。我們預計這種情況會在今年逐漸趨於平衡。至於我們預期今年剩餘時間可能出現的市場動態，正如查理所說，最重要的因素將是病患的堅持度和依從性。正如他所說，患者在開始治療時，堅持度是100%——既堅持治療又依從性高。但我們都知道，這些數字只會從此開始下降。

Now we expect them to be high with TRIKAFTA because of the benefit risk profile. But those will have an impact on our future revenues, and that is incorporated as a slowing of initiations into our revised guidance. And as Charlie said, at $5.3 billion to $5.6 billion, that still represents, at the midpoint, 36% growth over 2019, which is actually an acceleration of the revenues we delivered in 2019. So we're pleased to be able to increase our guidance at this uncertain time.

由於TRIKAFTA的收益風險較高，我們預期其成本也會較高。但這將對我們的未來收入產生影響，我們已將此因素反映在修訂後的業績預期中，即新用戶數量將有所放緩。正如查理所說，53億美元至56億美元的預期收入，以中間值計算，仍比2019年增長36%，實際上比2019年的收入增長更快。因此，我們很高興能夠在當前充滿不確定性的時期提高業績預期。

And then on the kind of capital allocation and BD question, I think I'll hand that one over to Reshma.

至於資本配置和業務拓展的問題，我想我會把這個問題交給雷什瑪來回答。

Sure. So with regard to our strategy around BD, the truth of the matter is that the strategy is exactly the same and nothing has changed. And for those of you who haven't heard me say it or haven't heard us say it, let me just say it very simply, we have 3 pillars in our BD strategy. The first is we look at anything that moves in CF regardless of modality, regardless of stage of development.

當然。關於我們的BD策略，事實上，策略完全一樣，沒有任何改變。對於那些之前沒聽我說過或沒聽我們說過的人，我簡單概括一下：我們的BD策略有三大支柱。第一，我們會關注CF中任何活動的部位，無論其模式或發展階段為何。

The second is we look for early-stage assets that fit into our corporate and R&D strategy, and that fit into our sandbox. And I say early stage because up until recently, the assets in later stages of development have been fully priced, if not overpriced, and our ability to bring value is in our research development, regulatory and commercialization engine.

第二點是，我們會尋找符合公司和研發策略，以及我們既定發展方向的早期資產。之所以強調早期階段，是因為直到最近，處於後期研發階段的資產定價過高，甚至已經充分定價，而我們創造價值的能力在於我們的研發、監管和商業化體系。

And the third is to add tools to our toolbox. And you've seen us be very active in this area, including today's announcement with Affinia. We've done deals in small molecules. We've done deals with AAV manufacturing. We've done deals with CRISPR as well as in cell and other genetic therapies. And so those 3 pillars are going to stay exactly the same.

第三點是豐富我們的工具箱。你們已經看到我們在這一領域非常活躍，包括今天與Affinia的合作公告。我們在小分子藥物領域、AAV生產領域、CRISPR技術以及細胞和其他基因療法領域都達成了合作。因此，這三大支柱將保持不變。

Maybe what's changed for where we find ourselves in terms of time is what we bring to the table is probably even stronger today than at any previous time. What I mean by that is we know exactly what we want. As I described, our strategy is really very clear, and it's been there for some time. So we're very clear on what we are looking for. The second is our capacity to do deals and our ability to consummate deals is, I think, very strong. And you see that we were able to do the Affinia deal despite this COVID situation that is upon us. And the third is our balance sheet is strong and growing, and I think that is an important element in this moment in time.

或許，我們所處的時間節點發生了變化，那就是我們如今所擁有的實力可能比以往任何時候都更強。我的意思是，我們非常清楚自己想要什麼。正如我之前所說，我們的策略非常清晰，而且已經實施了一段時間。所以我們非常清楚自己在尋找什麼。其次，我認為我們達成交易的能力非常強。您可以看到，儘管面臨新冠疫情的挑戰，我們仍然成功完成了對Affinia的收購。第三，我們的資產負債表穩健且持續成長，我認為這在當前情況下至關重要。

And we have a call -- a question from Paul Matteis with Stifel.

我們接到一個電話——來自 Stifel 的 Paul Matteis 提問。

Great. I wanted to ask one commercial question and one pipeline question. On the TRIKAFTA launch, I was wondering if you could comment on physician-patient dynamics in the pandemic as it relates to prescribing. Do physicians need to see their patients in person to prescribe this medicine? And how might that vary in the U.S. and Europe? And then second, on the AAT program, I was wondering if you've had any evolving thoughts on what might constitute a great outcome in that study. What AAT level threshold do you think is kind of a home run and almost unequivocal in its implications of clinical benefit versus what level range might be a little bit harder to kind of extrapolate as we think about future outcomes?

好的。我想問一個商業方面的問題和一個研發管線的問題。關於TRIKAFTA的上市，我想請您談談疫情期間醫病關係對處方的影響。醫師是否需要親自接診患者才能開立這種藥物？這種情況在美國和歐洲會有哪些不同？其次，關於AAT項目，我想請您思考一下，對於這項研究中怎樣的結果才算「理想結果」？您認為AAT達到什麼水平的閾值才能算作“成功”，並且幾乎可以肯定地表明其臨床獲益？而哪個水平範圍可能更難預測未來的療效？

Paul, it's Stuart here. On the physician-patient dynamic, for sure, that physician-patient dynamic has been disrupted by the pandemic for the reasons that you can imagine. Many of these positions are actually on the frontline, certainly the adult pulmonary physicians dealing with the pandemic. And as you well know, CF patients do fall into that category of patients who would potentially be vulnerable were they to become infected. And so it certainly has disrupted the dynamic.

保羅，我是史都華。關於醫病關係，毫無疑問，疫情已經擾亂了這種關係，原因你也能想像。許多醫護人員其實都處於抗疫一線，尤其是那些奮戰在抗疫第一線的成人肺科醫生。你也知道，囊性纖維化患者屬於易感族群，一旦感染病毒，他們就容易受到感染。因此，疫情無疑地擾亂了醫病關係。

What we do know, though, is that physicians and patients have managed to maintain very, very active dialogue. Many of them moving to more remote digital ways of interacting, and those interaction levels are very high. Although, obviously, face-to-face interactions have been reduced in many places for all but emergency situations.

不過，我們確實知道，醫生和病人一直保持著非常正面的溝通。他們中的許多人轉向了更遠端的數位化互動方式，而且互動頻率非常高。當然，除了緊急情況外，許多地方的面對面交流都減少了。

That doesn't seem to have interrupted initiations too much in the first quarter, given the strength that we saw in the first quarter. But it is something that we are certainly conscious of and are aware may have an impact on the rate of future initiations. And it's one of the factors we've tried to take into account when establishing our revised guidance range.

鑑於第一季強勁的成長勢頭，這似乎並未對第一季的業務拓展造成太大影響。但我們當然意識到這一點，並明白這可能會對未來的業務拓展速度產生影響。這也是我們在調整績效指引範圍時力求考慮的因素之一。

And AAT, I'll hand over to Reshma.

至於AAT，我將交給Reshma。

Sure. So what I can tell you is, what are we looking for, how will we know that we've had success with our proof-of-concept study in AAT. So there are a few important parameters that we're monitoring as we think about the Phase II dose-ranging study. The first is safety. Obviously, this is the first use of the correctors of the AAT protein in a population of people who have this disease. So safety is critical, and it's right up there.

當然。我可以告訴您，我們正在關注什麼，以及我們如何判斷我們在AAT概念驗證研究中是否取得了成功。在考慮進行II期劑量範圍研究時，我們會監測幾個重要的參數。首先是安全性。顯然，這是首次在AAT蛋白矯正劑應用於患有這種疾病的人。因此，安全性至關重要，而且是我們關注的重點。

The second is PK and exposure. We're looking to ensure that we have the right exposure, that we have the right dosing in tool and that we are seeing the kinds of impact that we are projecting based on our first-in-human study. And then lastly, and probably what you are alluding to is the AAT levels, and that's really important. What I'm looking for here with our studies is that the levels go up, not only in terms of antigenic levels but in terms of the functional AAT levels.

第二點是藥物動力學和暴露量。我們希望確保藥物暴露量合適，給藥劑量正確，並且能夠觀察到我們基於首次人體試驗預測的療效。最後，也是您可能提到的，是AAT水平，這一點非常重要。我希望透過我們的研究觀察到AAT水平的升高，不僅包括抗原水平，還包括功能性AAT水平。

And the reason I say that it's -- I'm looking for the levels to go up -- and I'm not really focused on any particular number, is this, you know when we think about drug development here at Vertex, we really divide it into cracking the biology and then pouring on the chemistry. In this disease area, unlike in CF, the stage that we're really at and the part that's very, very difficult is cracking the biology. And our ability to look at safety, exposure and note that the levels of both antigenic and functional are going up tells us that we've cracked the biology. And then it's a matter of pouring on the chemistry. And that is, amongst the 2, will be easier. And I certainly don't mean to imply that the chemistry is easier, but it is the easier part of that equation.

我之所以說——我期待這些指標上升——而不是特別關注某個具體數值，是因為，你知道，在Vertex，我們思考藥物研發時，通常會將其分為破解生物學和推進化學兩個階段。在這個疾病領域，與囊性纖維化不同，我們目前所處的階段，也是最非常困難的部分，就是破解生物學。我們能夠觀察安全性、暴露情況，並注意到抗原性和功能性指標都在上升，這表明我們已經破解了生物學。接下來就是推進化學。在這兩個階段中，化學部分會比較容易。我當然不是說化學部分比較容易，但它確實是整個過程中比較容易的部分。

Our next question comes from Alethia Young with Cantor Fitzgerald.

下一個問題來自 Cantor Fitzgerald 的 Alethia Young。

Congrats on a very good quarter. One, I guess, just philosophically, with what's going on with COVID. I mean do you prioritize kind of the near-term pipeline the same way? I mean some of this ties into what we've been talking about with AAT and getting that trial back up and running versus an FSGS, certainly people with lung may be a little bit more prone to these challenges. And then my second question just is I wonder if you'd talk a little bit about the Affinia deal today and what you think that adds in your capacity in DMD and CF?

恭喜你們本季表現出色。首先，我想從哲學角度談談新冠疫情的影響。我的意思是，你們是否會像對待其他疾病一樣，優先考慮近期研發管線？這與我們先前討論的AAT療法以及如何重啟臨床試驗有關，尤其是針對FSGS（局部節段性腎小球硬化症）患者，肺部疾病患者可能更容易面臨這些挑戰。其次，我想請您談談今天與Affinia的合作，以及您認為這筆交易將如何提升你們在DMD（杜氏肌肉營養不良症）和CF（囊性纖維化）領域的研發能力？

I think the -- you cut out just a little bit, but I think that the first question was around COVID and clinical trials. And your second question was...

我覺得——你稍微省略了一點，但我認為第一個問題是關於新冠疫​​情和臨床試驗的。你的第二個問題是…

Well, just I wanted to understand, like, if this changes the prioritization of your pipeline itself, like in light of what disruption you have with your clinical studies, some of them.

我只是想了解一下，鑑於你們的臨床研究受到一些幹擾，這是否會改變你們研發管線本身的優先順序。

Sure. Sure. So with regard to the COVID-19 situation and our clinical trials, our priorities remain very much the same. Our trials in CF are progressing, and we've been able to continue that quite well. We've moved to telephonic visits. We've moved more to remote monitoring and such. But obviously, the safety of our patients is our top priority. We're making sure that the integrity of our trials remain, but we have been able to continue our work in CF quite well.

當然。當然。關於新冠疫​​情和我們的臨床試驗，我們的工作重點仍然基本不變。我們在囊性纖維化（CF）方面的試驗正在順利進行，並且進展良好。我們已經轉向電話隨訪，更多地採用遠端監測等方式。但顯然，病人的安全始終是我們的首要任務。我們正在確保試驗的完整性，並且我們能夠在囊性纖維化領域繼續工作。

And the remainder of our pipeline outside of CF, as I said, the AATD program, we have already reinitiated our activities to have screening and enrollment restart in the 814 program. The FSGS program is actually exactly on time with the sites getting started up in April. And huge credit, I am so proud of our Vertex team that have just stepped up and gone above and beyond to get this work done.

至於囊性纖維化以外的其他項目，正如我之前提到的，AATD項目已經重啟，814項目的篩檢和入組工作也已重新啟動。 FSGS計畫也進展順利，各研究中心已於四月正式啟動。在此，我要特別感謝Vertex團隊，他們挺身而出，竭盡全力完成了這項工作，我為此感到無比自豪。

And if you think about clinical trials as a whole, as I said in my prepared remarks, each disease area, each study is quite different. It depends on the phase of the study. It depends on whether there is established benefit risk. And it even depends on some more nuanced factors around whether the study sites are hospital affiliated, i.e., in the hospital itself or separate institution, separate buildings. Of course, the disease area matters because physicians in certain subspecialties are more pulled into the pandemic than in others.

正如我在準備的演講稿中所說，從整體來看臨床試驗，每個疾病領域、每項研究都截然不同。這取決於研究的階段，取決於是否存在已確定的獲益風險，甚至取決於一些更細緻的因素，例如研究中心是否隸屬於醫院（即在醫院內）或位於獨立的機構或建築物內。當然，疾病領域也很重要，因為某些亞專科的醫生比其他亞專科的醫生更容易受到疫情的影響。

With regard to Affinia, what this really is, is another tool in our toolbox. And you've seen us methodically, carefully and very deliberately go around and assemble what I think is really one of the best, if not the best, toolboxes in the industry. This particular strategic partnership has to do with research activities to develop -- engineer capsids that have greater affinity and tropism for certain tissues like muscle for DMD and DM1, as well as for some of our other disease areas of interest. And given the presence and our great interest in genetic therapies, this is a key tool in our toolbox.

關於Affinia，它實際上是我們工具箱中的另一個利器。您已經看到，我們一步一步地、謹慎周密地建立了我認為業內最佳（如果不是最佳）的工具箱。這項策略合作旨在進行研究活動，開發——改造對特定組織（例如肌肉）具有更高親和力和趨向性的衣殼，用於治療DMD和DM1，以及我們關注的其他一些疾病領域。鑑於我們對基因療法的濃厚興趣，這無疑是我們工具箱中的關鍵工具。

Our next question comes from Evan Seigerman with Credit Suisse.

下一個問題來自瑞士信貸的埃文·塞格曼。

Congrats on the progress. So looking towards potential reimbursement negotiations outside of the United States for TRIKAFTA, assuming approval, do you see any risk of access delays or issues if government budgets are impacted due to the economic decline as a result of the ongoing pandemic? And how flexible would you be to open up access for patients with these -- given these potential economic issues?

恭喜取得進展。假設TRIKAFTA獲得批准，展望未來在美國以外地區的潛在報銷談判，您認為如果由於持續的疫情導致經濟衰退，政府預算受到影響，是否會造成准入延遲或出現問題？考慮到這些潛在的經濟問題，您在為患者開放用藥方面會有多大的彈性？

Yes. Thanks for the question, Evan. Clearly, the COVID-19 pandemic and government's responses around the world has put a significant strain on finances and none more so than in their various health services. And we'll have to see how that situation plays out. Obviously, we're not actually in those reimbursement negotiations in the vast majority of countries yet because those really only commenced at the point of regulatory approval. So we'll really have to see what approach they take at that point in time.

是的，謝謝你的提問，埃文。顯然，新冠疫情以及世界各國政府的應對措施給財政帶來了巨大壓力，尤其對各種醫療服務而言更是如此。我們拭目以待，看看事態將如何發展。顯然，目前絕大多數國家尚未真正進入報銷談判階段，因為這些談判實際上只在獲得監管機構批准後才開始。所以，我們還需要觀察他們屆時會採取什麼措施。

As Reshma said though, in her prepared remarks, this is a situation that will pass over time, and we're really going to be negotiating reimbursement agreements, which are hopefully going to be long-lasting because this is a terrific medicine, one that we feel very strongly has an incredible benefit risk profile, and therefore, we believe deserves to be rewarded with a premium price that is reflective of the value that it brings to patients. And so there's really not much more we can say about those discussions because we really haven't got into them with the various government authorities involved.

正如雷什瑪在事先準備好的發言稿中所說，這種情況會隨著時間推移而過去，我們真正要談的是報銷協議，希望這些協議能夠長期有效，因為這是一種非常有效的藥物，我們堅信它具有極高的獲益風險比，因此，我們認為它應該獲得與其為患者帶來的價值相符的高價。所以，關於這些討論，我們真的沒什麼好說的了，因為我們還沒有真正與相關政府部門進行深入探討。

Our next question comes from Robyn Karnauskas with SunTrust.

下一個問題來自 SunTrust 的 Robyn Karnauskas。

And I think you've done a great job sort of outlining a lot of the questions that we have. So great job on the call. Great job in the quarter. Just a follow up a couple of things. So Reshma, I know you said that your business development, it hasn't really changed as far as strategy. But you did highlight that you have more capacity to deals, you have more cash and your balance sheet is strong. So what does that mean? Does that mean we could see bigger deals over time?

我認為你做得很好，基本上概括了我們提出的許多問題。電話會議做得非常棒，季度業績也很出色。還有幾個後續問題。 Reshma，我知道你說過，你們的業務拓展策略並沒有太大變化。但你也強調了你們現在有更大的交易能力，現金流更充裕，資產負債表也很穩健。這意味著什麼？這是否意味著我們未來可能會看到更大的交易？

And second question is, people believe Vertex is very protected given so many of your patients are government reimbursed. What are you seeing in the United States as far as any signals that there could be a disruption to reimbursement of your drug in the coming quarters as COVID moves forward and people may have challenges with obtaining employment?

第二個問題是，鑑於貴公司許多病患都享有政府報銷，人們普遍認為Vertex公司受到的保護非常周全。隨著新冠疫情的持續蔓延，人們可能面臨就業困難，您在美國觀察到的任何跡象表明，未來幾季貴公司藥物的報銷可能會受到影響嗎？

Yes. Thanks for those questions, Robyn. With regard to BD, what can you expect from us. You can expect us to continue to be disciplined. Our strategy is really clear to us, and we're very, very disciplined about executing on the strategy, as I laid it out. You're right about the fact that our balance sheet is strong and getting stronger by the day.

是的，謝謝你的提問，Robyn。關於業務拓展，你們對我們有什麼期待？你們可以期待我們繼續保持嚴謹的作風。我們的戰略非常清晰，而且我們會嚴格地按照我之前闡述的戰略執行。你說得對，我們的資產負債表非常穩健，而且還在日益增強。

And you've seen us transact on a number of deals, be it partnerships in the research arena or, as you saw us towards the tail end of 2019, 2 acquisitions, one with Exonics and one with Semma. And let me just tell you, I am absolutely delighted with both of those acquisitions and very excited about the integration that has happened. And the more we get into it, the sweeter it gets. And so those have been very, very positive for us.

您已經看到我們完成了一系列交易，無論是研發領域的合作，還是像您在2019年底看到的，我們完成的兩項收購——分別收購了Exonics和Semma。我可以告訴您，我對這兩項收購都非常滿意，也對目前的整合情況感到非常興奮。我們越深入了解，就越覺得一切都很順利。所以，這些交易對我們來說都非常積極。

The capacity that we've built here is increased to do deals. I'm very pleased with how the integrations have gone, and Charlie has been running those. So our ability to do acquisitions and integrate is also advanced. And the fact that we have done this, have been recognized to be able to do it, I think, is something that will do well by us as we go forward. So can you expect us to do more deals? Yes. Will they be greater in number? We're going to have to let some time pass, but that wouldn't surprise me. Are they going to be deals that are huge? Are we going to buy revenues? No. Though that's not part of our strategy, and that's not what you're going to see us do.

我們在這裡建立起來的交易能力已經提升。我對整合工作的進展非常滿意，查理一直在負責這些工作。因此，我們的收購和整合能力也得到了提升。而且，我們已經做到了這一點，並且得到了認可，我認為這對我們未來的發展大有裨益。那麼，你們可以期待我們達成更多交易嗎？是的。交易數量會更多嗎？我們需要一些時間來觀察，但這不會讓我感到驚訝。這些交易會是規模龐大的嗎？我們會收購營收嗎？不會。雖然這不是我們的策略，你們也不會看到我們這樣做。

And Robyn, on the question of coverage here in the U.S., actually, the majority of our payer mix is actually commercial rather than government. During the course of the quarter, we really haven't seen any change in our payer mix. Obviously, that's something that we are monitoring closely, sensitive to the increase in unemployment that there has been. And those uncertainties were one of the reasons why we widened our guidance range. Whilst at the same time increasing our guidance, we also widened our guidance range because there are a number of uncertainties that we are going to have to see how they play out over time. But certainly, in the first quarter, we didn't see any change in our payer mix and/or signals of disruptions to coverage for patients.

羅賓，關於美國這邊的健保覆蓋範圍，實際上，我們的大部分支付方是商業保險而非政府保險。本季度，我們的支付方構成基本沒有變化。當然，我們會密切關注這一情況，尤其關注失業率上升的影響。這些不確定性也是我們擴大業績預期範圍的原因之一。在提高業績預期的同時，我們也擴大了預期範圍，因為存在一些不確定因素，我們需要觀察它們最終會如何發展。但可以肯定的是，在第一季度，我們沒有看到支付方組成發生任何變化，也沒有發現任何病患健保覆蓋範圍中斷的跡象。

Our next question comes from Mohit Bansal with Citi.

下一個問題來自花旗銀行的莫希特·班薩爾。

Congrats on the progress. Just moving a little bit on the pipeline side, regarding your diabetes program, it seems like your approach uses a fully differentiated beta cell, while there are other approaches, including progenitor cells. So could you please help us understand how these differences could ultimately impact the end result? And why one could be better than other approach here?

恭喜你們的進展。關於你們的糖尿病項目，我想稍微探討一下研發流程的問題。你們似乎採用了完全分化的β細胞，而其他方法，例如使用祖細胞，也存在。能否請你們解釋一下這些差異最終會如何影響結果？以及為什麼一種方法可能優於另一種方法？

Mohit, I think you're asking about how our approach to type 1 diabetes and the cell program may be different from other approaches. And let me just tell you a little bit about our approach, and then I can do a little bit of a compare and contrast for you. So our program that came into us with our acquisition of Semma is really a program that is based on 20-plus years of work done by Doug Melton, who is the preeminent beta cell physician-scientist in the world. And what Semma was successful in doing, and the reason that we were so excited about the acquisition, is they have found a process and a methodology to not only develop, grow and, in an industrial manner, make pancreatic islet cells.

莫希特，我想你是想問我們治療第1型糖尿病和進行細胞療法的計畫與其他療法有何不同。讓我先簡單介紹一下我們的方法，然後再做一些比較分析。我們收購Semma公司後獲得的這個項目，實際上是基於道格·梅爾頓（Doug Melton）二十多年的研究成果。梅爾頓是世界頂尖的β細胞醫學科學家。 Semma公司之所以成功，也是我們如此興奮的原因，在於他們找到了一種能夠以工業化方式開發、培養和生產胰島細胞的工藝和方法。

These islet cells are fully differentiated. And they have also come up with a technology that allows for a device in which these cells can be placed that can be put into patients with type 1 diabetes. And with the device, the big idea would be no immunosuppression would be needed. Obviously, immunosuppression is going to be required for the naked cells.

這些胰島細胞已經完全分化。他們也研發出一種技術，可以將這些細胞植入一種裝置，然後移植到第一型糖尿病患者體內。這種裝置的核心概念是無需使用免疫抑制劑。顯然，對於裸露的細胞，免疫抑制是必要的。

I would say that there are a few differences compared to other approaches, but the highlights are the following. The approach that we are pursuing pertains to fully differentiated islet cells. And two, that we have an approach here that has been tested in large animal models with the device that has shown itself to be a device that can be placed over time without the troubles that many others have seen.

我認為與其他方法相比，我們的方法有一些不同之處，但主要特徵如下。首先，我們採用的方法是針對完全分化的胰島細胞。其次，我們的方法已經在大型動物模型中進行了測試，所用裝置已證明可以長期植入，而不會出現許多其他方法遇到的問題。

And we have a question from Cory Kasimov with JPMorgan.

我們現在收到摩根大通的科里·卡西莫夫提出的問題。

Just have one left for you on the topic of reimbursement. I wanted to ask about the ICER report on the cost effectiveness of TRIKAFTA that was published earlier this week. We'd just love to get your thoughts on the current pricing versus their much-lower recommendation. Why do you think there's such a big discrepancy? And do you foresee or think there's a risk of any pushback from payers as a result of this?

關於報銷問題，我還有一個問題想請教您。我想問ICER本週稍早發布的關於TRIKAFTA成本效益的報告。我們很想聽聽您對當前定價與他們建議的較低價格之間的區別。您認為造成如此大差異的原因是什麼？您是否預見或認為這可能會導致支付方的抵制？

Cory, thanks for the question. As you know, we have and others have some significant methodological concerns with ICER and the way -- approaches and assessment of a medicine's value, both the methods, some of the rather arbitrary thresholds that are chosen, and really its inability to fully capture the benefits of transformative medicines with lifelong benefits like ours. So we do have concerns with the methodologies and thresholds, and I won't go into them in my new detail.

科里，謝謝你的提問。如你所知，我們和其他一些人對ICER（增量成本效益比）及其評估藥物價值的方法存在一些重大的方法論上的擔憂，包括一些相當武斷的閾值設定，以及它無法充分體現像我們這種具有終身療效的變革性藥物的益處。因此，我們確實對ICER的方法論和閾值設定有所顧慮，但我不會在新報告中詳細闡述這些內容。

In terms of the statistics, the most important statistic to me is that 99% plus of the patients who are eligible for TRIKAFTA are covered by either government or commercial plans which are reimbursing the medicine. And to me, that's the most important statistic because it demonstrates that payers recognize the value of TRIKAFTA and want to provide immediate access to it consistent with our label. And if they haven't done that, we wouldn't have been able to deliver the great quarter that we've had. And so we feel that's a much better mark of whether payers recognize the value of TRIKAFTA. And we are certainly going to be doing everything we can to ensure that the ICER report doesn't lead them to restricting coverage, which I think would be a tragic day for CF patients.

就統計數據而言，對我來說最重要的數據是，超過99%符合TRIKAFTA用藥條件的患者都享有政府或商業保險的報銷。我認為這是最重要的數據，因為它表明支付方認可TRIKAFTA的價值，並希望根據藥品說明書提供即時用藥途徑。如果他們沒有這樣做，我們就無法取得如此出色的季度業績。因此，我們認為這更能反映支付方是否認可TRIKAFTA的價值。我們一定會盡一切努力，確保ICER報告不會導致他們限制TRIKAFTA的報銷範圍，因為我認為這對囊性纖維化患者來說將是悲劇性的一天。

Okay. Very helpful.

好的，很有幫助。

If I could add a comment, Cory, this is Reshma. TRIKAFTA is a medicine with absolutely unprecedented efficacy. The benefit risk is 100% clear. It is something that is recognized by physicians and patients around the globe. I do not expect any change in pricing or our approach in the U.S. or outside the U.S. You know that we have a long tradition of pricing our drugs for the value that they bring. And there is just no doubt about the value that this particular medicine, TRIKAFTA, brings to patients.

科里，如果我可以補充一點，我是雷什瑪。 TRIKAFTA 是一種療效前所未有的藥物。其獲益風險比非常明確，這一點已獲得全球醫生和患者的認可。我預計在美國或美國以外地區，我們的定價或策略都不會有任何改變。您也知道，我們一直以來都堅持根據藥物的實際價值來定價。而 TRIKAFTA 這種藥物為患者帶來的價值毋庸置疑。

We have a question from Brian Abrahams with RBC Capital Markets.

我們收到來自加拿大皇家銀行資本市場的布萊恩亞伯拉罕的提問。

Congratulations on the strong quarter. A commercial question and a pipeline question. On the commercial side, any surprises in gross to net? Any additional inventory build, given the rapidity of TRIKAFTA uptake? And might you expect any benefits on persistence and compliance due to COVID-19, such that it may -- those may drift down less than would have otherwise been expected? And then on the pipeline side, with the PK/PD characterized for 864, just curious if there's any additional insights that you guys have on similarities and differences versus 814.

恭喜貴公司本季業績強勁。我有一個關於商業和產品線的問題。在商業方面，毛利潤和淨利潤方面是否有任何意外變化？鑑於TRIKAFTA的快速普及，是否需要增加庫存？您是否預期新冠疫情會對患者的用藥依從性和持續用藥率產生正面影響，例如，這些指標的下降幅度是否會小於預期？在產品線方面，鑑於864的藥物動力學/藥效學特徵已經完成，我想了解你們對它與814的異同點有何見解。

Why don't I ask Stuart to just comment on persistence and compliance, and then I'll ask Charlie to comment on the rest of your question. Stuart?

不如我先請史都華談談堅持和服從，然後再請查理回答你問題的其他部分。史都華？

Yes, Brian. On persistence and compliance, as we said in our prepared remarks, we did see patients refill early in the quarter, both here in the U.S. and ex U.S. And so mathematically, that is an increase in compliance. However, we do expect that, that is going to play out over the course of the year. And I don't expect that COVID-19 will really have a substantial impact on persistence and compliance of TRIKAFTA. I think the thing that's going to drive the levels of persistence and compliance are the exceptional benefit risk profile that Reshma just mentioned.

是的，布萊恩。關於用藥持續性和依從性，正如我們在事先準備好的發言稿中提到的，我們確實看到患者在本季度初就續訂了處方，無論是在美國還是美國以外的地區。因此，從數學角度來看，這確實提高了依從性。然而，我們預計這種情況將在今年持續一段時間。而我認為新冠疫情不會對TRIKAFTA的用藥持續性和依從性產生實質影響。我認為真正推動用藥持續性和依從性水平的因素是雷什瑪剛才提到的卓越的收益風險比。

And then on the gross to net and inventory changes, I'll hand that over to Charlie.

至於毛利淨利和庫存變動，我會交給查理處理。

Yes, Brian, on gross to net, nothing noteworthy in the quarter. The gross to net moves around a little bit from quarter-to-quarter depending on when we true-up invoices that come in, but nothing noteworthy in the quarter here. And then around inventory, I guess I would distinguish, you'll recall that in the fourth quarter we talked about a launch-related inventory build, that was more of a channel inventory build. And what we're talking about here as we're giving color on the first quarter results and on guidance is more of a patient-driven or government-driven inventory build, which is different from the channel build that we talked about in fourth quarter. There's no incremental color in the first quarter on the channel inventory that has not changed significantly and it's not part of the color that we're giving on the first quarter.

是的，布萊恩，就毛利和淨利而言，本季沒有什麼特別值得注意的地方。毛利和淨利會根據我們何時結算收到的發票而略有波動，但本季沒有什麼特別之處。至於庫存，我想澄清一下，你可能還記得，我們​​在第四季度討論過與產品上市相關的庫存增加，那更多的是渠道庫存增加。而我們現在在分析第一季業績和展望時，討論的是更多由患者或政府需求驅動的庫存增加，這與我們第四季度討論的通路庫存增加不同。第一季通路庫存沒有顯著變化，因此不屬於我們分析的第一季業績的範疇。

Operator, now that we're past 6:00 p.m., we have time for just one more question.

接線員，現在已經過了下午6點，我們還有時間再回答一個問題。

We have a question from Matthew Harrison with Morgan Stanley.

我們收到摩根士丹利的馬修·哈里森提出的問題。

Great. I was -- Stuart, I was just hoping maybe you could help us think about phasing of revenues broadly as we think about pushing into the younger patients as well as Europe. Just maybe remind us about the sizes of those populations relative to the population that you've currently penetrated with TRIKAFTA.

太好了。我是——斯圖爾特，我只是希望您能幫我們大致考慮一下收入分階段增長的問題，因為我們正計劃拓展年輕患者群體以及歐洲市場。您能否提醒我們一下，這些人群的規模相對於您目前透過 TRIKAFTA 滲透的人群而言如何？

Yes. Thanks for the question. Obviously, from a long-term perspective, we believe TRIKAFTA has the potential to treat up to 90% of CF patients because of the levels of efficacy we are able to deliver. And clearly, to do that, we need to do a couple of things. One, we need to get it approved outside of the U.S. for the 12-plus population. And then obviously, we need to increase the label there to expand it down into lower-age populations. We have submitted the -- in the back end of last year in Europe for TRIKAFTA or the triple combination, I should say, for the 12-plus population. No -- the label we're going to get there yet, so it's really impossible to tell you exactly how big the size of the eligible patient population is there. We have more recently also submitted in Australia and Switzerland, again for 12-plus.

是的，謝謝你的提問。顯然，從長遠來看，我們相信TRIKAFTA有潛力治療高達90%的囊性纖維化患者，因為我們能夠達到如此高的療效。顯然，為了實現這一目標，我們需要做兩件事。首先，我們需要在美國以外地區獲得TRIKAFTA的批准，用於12歲及以上。其次，我們顯然需要擴大其適應症範圍，使其適用於較低年齡層的族群。去年年底，我們已向歐洲提交了TRIKAFTA（或更準確地說是三重療法）的申請，用於12歲及以上人群。目前，我們尚未獲得歐洲地區的批准，因此無法準確告知符合條件的患者群體規模。最近，我們也向澳洲和瑞士提交了申請，同樣是用於12歲以上人口。

In terms of the label expansions, in terms of taking the age range down, the 6 to 11 TRIKAFTA sNDA here in the U.S., we anticipate submitting in the second half of this year. So really, the primary drivers of our guidance and the increase in our guidance are really TRIKAFTA in the 12-plus population here in the U.S. And the growth that we've seen in ORKAMBI and SYMKEVI outside the U.S. as a result largely of the reimbursement agreements that we put in place in the second half of 2019.

就標籤擴展而言，就降低適用年齡範圍而言，我們預計將於今年下半年在美國提交針對6至11歲人群的TRIKAFTA補充新藥申請（sNDA）。因此，我們業績指引及其成長的主要驅動因素實際上是TRIKAFTA在美國12歲及以上人群中的市場表現，以及ORKAMBI和SYMKEVI在美國以外地區的增長，這主要得益於我們在2019年下半年達成的醫保報銷協議。

Okay, operator. Thanks, everybody, for joining the call tonight. The Investor Relations team is either in the office or remote, and we'll be following up with analysts who didn't get a chance to ask a question, as well as any other questions you may have tonight. Really appreciate you dialing in and stay safe.

好的，接線生。感謝各位今晚參加電話會議。投資人關係團隊的成員有的在辦公室，有的遠距辦公，我們會跟進那些今晚沒機會提問的分析師，也會解答各位的其他問題。非常感謝大家撥入，祝大家平安健康。

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.

女士們、先生們，今天的電話會議到此結束。感謝各位的參與。現在可以掛斷電話了。祝大家今天過得愉快。