福泰製藥 (VRTX) 2012 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to Vertex Pharmaceuticals Incorporated third-quarter 2012 financial results conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. (Operator Instructions). As a reminder, this conference call is being recorded.

各位女士、先生，大家好，歡迎參加 Vertex Pharmaceuticals Incorporated 2012 年第三季財務業績電話會議。此刻，所有與會者皆處於僅收聽模式。稍後我們將進行問答環節，屆時將提供相關指示。（接線員指示）。提醒各位，本次電話會議正在錄音。

I would now like to introduce your host for today's conference, Mr. Michael Partridge. Sir, you may begin.

現在我想介紹今天會議的主持人 Michael Partridge 先生。先生，您可以開始。

Thank you. This call was originally scheduled for Monday night and postponed due to the storm. We know there are many listeners who have been directly affected by the storm, and our thoughts are with them as they try to get things back to normal. So, thank you to everyone for joining us tonight.

謝謝。本次電話會議原定於週一晚上舉行，但因風暴而延期。我們知道有許多聽眾直接受到風暴影響，在他們努力讓生活回復正常之際，我們與他們同在。因此，感謝各位今晚加入我們。

Vertex continued to make progress toward building a global business in the third quarter of 2012. With KALYDECO, our approved medicine for people with cystic fibrosis with the G551D mutation, we achieved sales of $49 million in the quarter.

Vertex 在 2012 年第三季持續朝建立全球性業務的目標取得進展。憑藉 KALYDECO（我們已核准用於帶有 G551D 突變之囊性纖維化患者的藥物），本季銷售額達 4,900 萬美元。

We are now treating the majority of eligible G551D patients in the US. We believe that the near-term inflection point for KALYDECO growth is achieving reimbursement across the major European markets.

我們目前已在美國為大多數符合條件的 G551D 患者提供治療。我們認為，KALYDECO 成長的近期拐點在於於歐洲主要市場取得給付／報銷。

In cystic fibrosis, our goal is to improve the lives of all patients with CF. And we are making progress toward this goal. We refer to KALYDECO as ivacaftor when discussing investigational uses. And ivacaftor monotherapy has the opportunity to address more patients through ongoing label expansion studies.

在囊性纖維化領域，我們的目標是改善所有 CF 患者的生活。我們正朝此目標邁進。在討論研究性用途時，我們將 KALYDECO 稱為 ivacaftor。而 ivacaftor 單藥治療可透過進行中的適應症標籤擴展研究，為更多患者帶來治療機會。

In particular, we have initiated three additional Phase III trials of ivacaftor and, together with other ongoing and planned studies, could expand the treatable population to approximately 15% of CF patients.

特別是，我們已啟動另外三項 ivacaftor 的第三期試驗；連同其他進行中與規劃中的研究，可能將可治療族群擴大至約占 CF 患者的 15%。

Additionally, on the basis of our recent Phase II VX-809 plus ivacaftor data, we are on track to begin pivotal development of this combination in F508del homozygous patients in early 2013. We believe that success with our ivacaftor label expansion studies and success with the VX-809 plus ivacaftor combination would enable us to address the majority of the 70,000 CF patients in the US and Europe.

此外，基於我們近期 VX-809 加 ivacaftor 的第二期數據，我們正按計畫於 2013 年初在 F508del 同型合子患者中啟動此組合的關鍵性開發。我們相信，若 ivacaftor 的標籤擴展研究成功，且 VX-809 加 ivacaftor 組合亦告成功，我們將能涵蓋美國與歐洲 70,000 名 CF 患者中的大多數。

With INCIVEK for the treatment of hepatitis C, we reported sales of $254 million in the third quarter. INCIVEK is the leading DAA in the hepatitis C market and continues to be an important medicine for hepatitis C patients. We reiterated our full-year net revenue guidance for INCIVEK today.

在用於治療 C 型肝炎的 INCIVEK 方面，我們第三季報告銷售額為 2.54 億美元。INCIVEK 是 C 型肝炎市場中領先的 DAA，並持續是 C 肝患者的重要藥物。我們今日重申 INCIVEK 全年淨營收指引。

In hepatitis C, we are advancing our uridine nucleotide analogue VX-135, previously referred to as ALS-2200, which we are developing in collaboration with Alios.

在 C 型肝炎方面，我們正推進尿苷核苷酸類似物 VX-135（先前稱為 ALS-2200），該藥物由我們與 Alios 合作開發。

We are executing on the strategy of developing VX-135 with other promising DAAs in multiple all-oral combinations. We announced agreements this morning with GSK and Janssen to enable us to evaluate VX-135 in multiple 12-week all-oral combination regimens. Our goal is to complete multiple Phase II short-duration all-oral studies within 2013 and be poised to move quickly to pivotal development in 2014.

我們正執行一項策略：將 VX-135 與其他具前景的 DAA 共同開發為多種全口服組合療法。我們今早宣布與 GSK 及 Janssen 達成協議，使我們得以在多種 12 週全口服組合療程中評估 VX-135。我們的目標是在 2013 年內完成多項第二期短療程全口服研究，並準備於 2014 年迅速推進至關鍵性開發。

Joining me on the call tonight to discuss Vertex's strategic and financial outlook and recent progress in our R&D pipeline are Dr. Jeff Leiden, Chairman and CEO; Ian Smith, CFO; and Dr. Peter Mueller, Head of Research and Development and Chief Scientific Officer.

今晚與我一同出席、將討論 Vertex 的策略與財務展望以及我們研發管線近期進展的有：董事長兼執行長 Jeff Leiden 博士；財務長 Ian Smith；以及研發主管兼首席科學官 Peter Mueller 博士。

After the prepared remarks, Stuart Arbuckle, Vertex's recently appointed Chief Commercial Officer; and Dr. Bob Kauffman, Vertex's Chief Medical Officer, will join us for Q&A.

在預先準備的發言之後，Vertex 新近任命的首席商務官 Stuart Arbuckle，以及 Vertex 首席醫療官 Bob Kauffman 博士，將加入問答環節。

We will conclude tonight's call at 6.00 p.m. To help us do that, we would ask that you please limit your question to one with a related follow up.

我們將於今晚 6:00 結束本次電話會議。為協助我們達成此目標，敬請各位將問題限制為一題，並可附帶一個相關追問。

I will note that information discussed on this conference call includes forward-looking statements, which are subject to the risks and uncertainties discussed in detail in our reports, including our 10-K and 10-Q reports, which have been filed with the Securities and Exchange Commission.

我提醒各位，本次電話會議所討論的資訊包含前瞻性陳述，該等陳述受我們報告中所詳述之風險與不確定性影響，包括已向美國證券交易委員會提交的 10-K 與 10-Q 報告。

These statements, including without limitation those regarding the market launch of INCIVEK and KALYDECO, our development plans and expectations, and our guidance are based on management's current assumptions and are subject to risks and uncertainties that could cause actual outcomes and events to differ materially.

這些陳述（包括但不限於關於 INCIVEK 與 KALYDECO 的市場上市、我們的開發計畫與預期，以及我們的指引）係基於管理層目前的假設，並受可能導致實際結果與事件出現重大差異之風險與不確定性影響。

GAAP and non-GAAP financial measures will be discussed on this call. Information regarding our use of these measures and a reconciliation of non-GAAP to GAAP is available in our third-quarter 2012 financial press release, which is on our Website. And I would also refer you to the information on slide 5 of tonight's webcast.

本次電話會議將討論 GAAP 與非 GAAP 財務衡量指標。關於我們使用這些指標的資訊，以及非 GAAP 與 GAAP 的調節表，已載於我們 2012 年第三季財務新聞稿中，並已發布於公司網站。同時也請參考今晚網路直播第 5 張投影片的資訊。

Thank you. And I will now turn the call over to Jeff.

謝謝。接下來我把電話交給 Jeff。

Thanks, Michael. Good evening, everyone. To reiterate what Michael said, our thoughts are with those affected by Hurricane Sandy, including some of you on the phone.

謝謝你，Michael。各位晚上好。重申 Michael 所說，我們的心與受颶風 Sandy 影響的人同在，其中也包括電話線上的部分各位。

I'd like to acknowledge the many Vertex employees who worked through the storm and who are continuing to work hard, with the goal of making sure that patients who need our medicines can continue to get them.

我想向許多在風暴期間仍堅守崗位、並持續努力工作的 Vertex 員工致意；他們的目標是確保需要我們藥物的患者能夠持續取得藥物。

Tonight, I'd like to frame my remarks around Vertex's strategy and our priorities for today, tomorrow, and the future. First, I'll provide a perspective on how we are positioned today in key diseases and also how we are preparing to further improve treatment of these diseases tomorrow and in the future.

今晚，我想以 Vertex 的策略以及我們對今天、明天與未來的優先事項來架構我的發言。首先，我將說明我們目前在關鍵疾病領域的定位，以及我們如何為明天與未來進一步改善這些疾病的治療做準備。

I'll put these strategies in the context of our overall financial strategy and operating philosophy and describe how we're managing our business as we move forward into 2013.

我也會在我們整體財務策略與營運理念的脈絡下說明這些策略，並描述我們在邁向 2013 年的過程中如何管理業務。

After that, Ian will review the details of our third quarter financial performance and discuss the activities we are undertaking to ensure that we are prioritizing our investment in the business.

之後，Ian 將回顧我們第三季財務表現的細節，並討論我們為確保投資優先順序而正在進行的各項工作。

Then Peter will provide you with some specific updates on recent progress in our pipeline and plans for tomorrow and the future and the serious diseases for which we are creating medicines.

接著，Peter 將就我們研發管線近期進展，以及我們對明天與未來的計畫，和我們正在為之研發藥物的嚴重疾病，提供一些具體更新。

I'd like to begin tonight by formally welcoming Stuart Arbuckle, our new Executive Vice President and Chief Commercial Officer. Stuart joined us in early September and has hit the ground running, adding valuable insights and strategic direction from his 25 years experience leading global sales and marketing efforts at biopharmaceutical companies. As Michael said, he will join for the Q&A portion of the call.

今晚我想先正式歡迎我們新任執行副總裁兼首席商務官 Stuart Arbuckle。Stuart 於 9 月初加入我們，並迅速投入工作；他在生物製藥公司領導全球銷售與行銷工作方面擁有 25 年經驗，為我們帶來寶貴洞見與策略方向。如 Michael 所說，他將在問答環節加入。

Let me begin with our approved medicines. We're proud to have two best-in-class therapies on the market, KALYDECO for cystic fibrosis and INCIVEK for hepatitis C.

讓我先從我們已核准的藥物談起。我們很自豪在市場上擁有兩項同類最佳療法：用於囊性纖維化的 KALYDECO，以及用於 C 型肝炎的 INCIVEK。

Beginning with CF, KALYDECO for CF patients with the G551D mutation aged six and older is a transformative medicine that addresses the underlying cause of the disease in these patients.

先從 CF 談起：KALYDECO 用於 6 歲及以上、帶有 G551D 突變的 CF 患者，是一項具變革性的藥物，能針對這些患者的疾病根本原因發揮作用。

Today, only nine months after launch, we are treating the majority of the eligible G551D patients within the US, and we have just initiated our launch in the EU. Over the next year, we expect significant revenue growth from KALYDECO monotherapy as we launch the product in Europe, Canada, and Australia.

今天，距離上市僅九個月，我們已在美國為大多數符合資格的 G551D 患者提供治療，並且剛剛在歐盟啟動上市。在未來一年，我們預期隨著產品在歐洲、加拿大與澳洲上市，KALYDECO 單一療法的營收將顯著成長。

But, this is just the beginning of our efforts in CF. We've talked several times this year about our strategy in CF and how it is to fundamentally change the outlook for as many people with this disease as possible, first by expanding the ivacaftor monotherapy label to address more patients who can benefit from this medicine alone; second, by combining ivacaftor with a corrector compound to address the most common type of CF, which is the delta 508 homozygous population that makes up about half of those with CF; and third, by further enhancing efficacy of our existing treatment regimens and potentially addressing those people with only one copy of the delta 508 mutation, the heterozygotes, using second-generation correctors and dual-corrector regimens.

但是，這只是我們在囊性纖維化（CF）努力的開始。今年我們已多次談到我們在 CF 的策略，以及該策略如何從根本上改變盡可能多患者對此疾病的展望：第一，擴大 ivacaftor 單一療法的適應症標籤，以涵蓋更多可僅靠此藥受益的患者；第二，將 ivacaftor 與校正劑（corrector）化合物合併使用，以治療最常見的 CF 類型，即 delta 508 同型合子族群，約占 CF 患者的一半；第三，進一步提升我們既有治療方案的療效，並可能透過第二代校正劑與雙校正劑方案，涵蓋僅帶有一份 delta 508 突變的患者（異型合子）。

We believe that, collectively, these efforts could enable us to address up to an estimated 90% of all people with CF.

我們相信，綜合而言，這些努力可使我們有能力涵蓋估計高達 90% 的所有 CF 患者。

In the third quarter, we've made significant progress on executing this strategy. We've now initiated four studies, three of which are pivotal Phase III studies, with ivacaftor monotherapy to significantly expand the CF population that we believe we can address with this medicine alone.

在第三季，我們在執行此策略方面取得重大進展。我們已啟動四項研究，其中三項為關鍵性第三期（Phase III）研究，使用 ivacaftor 單一療法，以大幅擴大我們認為可僅靠此藥治療的 CF 族群。

If our KALYDECO monotherapy strategy is successful, we could increase the addressable population from the current 4% to perhaps up to approximately 15% of the total CF population. That would bring tomorrow's total population of CF patients in the US and Europe who could benefit from KALYDECO monotherapy to about 10,000.

若我們的 KALYDECO 單一療法策略成功，我們可將可涵蓋族群由目前的 4% 提升至可能約占整體 CF 族群的 15%。這將使明日美國與歐洲可從 KALYDECO 單一療法受益的 CF 患者總數達到約 10,000 人。

We are also on track to initiate pivotal development of the corrector compound VX-809 and ivacaftor in delta 508 homozygous patients in early 2013. We are preparing to meet with the FDA this quarter. Peter will go into more detail on our current pivotal trial plans.

我們也按計畫將於 2013 年初在 delta 508 同型合子患者中，啟動校正劑化合物 VX-809 與 ivacaftor 的關鍵性開發。我們正準備於本季與 FDA 會面。Peter 將更詳細說明我們目前的關鍵性試驗計畫。

We are also advancing our VX-661, another corrector compound, in a proof of concept clinical study with ivacaftor in CF patients who are homozygous for delta 508. We expect to have results from this study in the first half of 2013.

我們也正在推進 VX-661（另一種校正劑化合物），在 delta 508 同型合子的 CF 患者中與 ivacaftor 進行概念驗證（proof of concept）臨床研究。我們預期於 2013 年上半年取得該研究結果。

If in addition to being successful with our monotherapy efforts, we are successful with our combination development efforts targeting delta 508 homozygotes, we could potentially increase the number of CF patients we could address up to 60% or more of the CF population. That's an estimated 40,000 patients in the US and Europe.

若除了單一療法的努力成功之外，我們針對 delta 508 同型合子的合併療法開發也成功，我們可能將可涵蓋的 CF 患者比例提升至 CF 族群的 60% 或更高。這相當於美國與歐洲估計 40,000 名患者。

During the last several months, we've also made progress in identifying second-generation corrector compounds. We've identified second-generation correctors that show significant additive or synergistic activity in vitro when combined with VX-809 plus ivacaftor. We showed some of these results in Orlando a few weeks ago. And we look forward to providing you with more information on these compounds in 2013.

在過去幾個月中，我們也在辨識第二代校正劑化合物方面取得進展。我們已找出第二代校正劑，當與 VX-809 加上 ivacaftor 合併時，在體外（in vitro）呈現顯著的加成或協同作用。幾週前我們在奧蘭多展示了其中部分結果。我們也期待在 2013 年向各位提供更多關於這些化合物的資訊。

Turning now to hepatitis C, today, we are leaders with INCIVEK combination therapy. In the 17 months since launch, more than 50,000 people have been treated with an INCIVEK-based regimen in the US. And many have been cured or on their way to a cure.

接著談丙型肝炎（hepatitis C），目前我們以 INCIVEK 合併療法居於領先地位。自上市以來的 17 個月內，美國已有超過 50,000 人接受以 INCIVEK 為基礎的治療方案。其中許多人已治癒或正走向治癒。

Our market position in hepatitis C is strong. INCIVEK has been and remains the leading direct-acting antiviral or DAA. Approximately three-quarters of genotype 1 hepatitis C patients who initiate therapy with a DAA receive INCIVEK.

我們在丙型肝炎的市場地位穩固。INCIVEK 一直是、且仍然是領先的直接作用抗病毒藥物（DAA）。約四分之三在開始使用 DAA 治療的基因型 1 丙肝患者，會使用 INCIVEK。

Today, there are fewer hepatitis C patients starting treatment as compared to a year ago. Some patients are deferring therapy in anticipation of future treatment regimens. However, there are still many patients that want to be treated or who need to be treated today.

目前，與一年前相比，開始接受丙肝治療的患者較少。部分患者因期待未來的治療方案而延後治療。然而，仍有許多患者希望在今天接受治療，或需要在今天接受治療。

For example, during the third quarter, we estimate that approximately 7,000 patients in the US initiated treatment with INCIVEK.

例如，在第三季，我們估計美國約有 7,000 名患者開始使用 INCIVEK 治療。

Our long-term strategy in hepatitis C is to maintain a significant presence as the treatment of this disease evolves. And we believe we are well positioned to do this with all-oral regimens built around our nucleotide analogue VX-135.

我們在丙型肝炎的長期策略，是在此疾病治療持續演進的過程中維持重要的市場存在。我們相信，透過以我們的核苷酸類似物 VX-135 為核心所建立的全口服療程，我們具備良好條件達成此目標。

Our recently reported seven-day viral kinetic data suggest that VX-135 is highly potent and well tolerated. And we're executing on a strategy of evaluating multiple regimens that combine VX-135 with other promising late-stage DAAs.

我們近期公布的七天病毒動力學（viral kinetic）數據顯示，VX-135 具有高度效力且耐受性良好。我們也正在執行一項策略：評估多種將 VX-135 與其他具前景的後期 DAA 合併的療程。

VX-135 has attracted a lot of interest from other companies in the hepatitis C field. I'm pleased that we're able to share with you some of our progress on this front today.

VX-135 已吸引丙肝領域其他公司的高度興趣。我很高興今天能與各位分享我們在這方面的一些進展。

Specifically, as Michael mentioned, we have established agreements to conduct all-oral 12-week combination studies of our once-daily nucleotide with GSK's once-daily NS5A inhibitor GSK2336805, also known as GSK805, and a separate agreement and study combining VX-135 with the once-daily protease inhibitor TMC435 being developed by Janssen and Medivir.

具體而言，如 Michael 所提到，我們已達成協議，進行為期 12 週的全口服合併研究：將我們每日一次的核苷酸藥物與 GSK 每日一次的 NS5A 抑制劑 GSK2336805（亦稱 GSK805）合併；此外，我們也另行達成協議並進行研究，將 VX-135 與每日一次的蛋白酶抑制劑 TMC435 合併，該藥由 Janssen 與 Medivir 開發。

We expect to initiate these combination studies beginning in early 2013 and to have Phase II data in hand from multiple combinations by the end of 2013. Based on these data, we will plan to pick the best regimens to advance in a pivotal development in 2014.

我們預期自 2013 年初開始啟動這些合併研究，並在 2013 年底前取得多種合併方案的第二期（Phase II）數據。根據這些數據，我們將規劃挑選最佳療程，於 2014 年推進至關鍵性開發。

In addition to cystic fibrosis and HCV, an important part of our R&D strategy has been to continue to bring innovative, potentially transformative drugs forward in other important disease areas. During the third quarter, in addition to CF and HCV, we continued to advance VX-509, VX-787, and several other exciting early-stage programs.

除了囊性纖維化與丙肝之外，我們研發策略的重要一環，是持續在其他重要疾病領域推進具創新性、可能帶來變革的藥物。在第三季，除 CF 與 HCV 外，我們也持續推進 VX-509、VX-787，以及其他數個令人振奮的早期計畫。

In closing, some remarks on our operating philosophy and how we're managing our business today and in the future, today, we have significant annual revenues from multiple sources that allow for reinvestment into a diverse portfolio of discovery and development programs and commercial initiatives, while also creating positive cash flow and earnings.

最後，談談我們的營運理念，以及我們如何在當前與未來管理業務：目前，我們來自多個來源的年度營收相當可觀，使我們得以再投資於多元的探索與開發計畫組合以及商業化倡議，同時也能創造正向的現金流與獲利。

This has enabled us to complete the quarter with approximately $1.3 billion of cash and equivalents while advancing our pipeline in CF, HCV, and autoimmune diseases. We are excited about the product development opportunities we have. But, at the same time, we are being disciplined in our investment in the business.

這使我們在推進 CF、HCV 與自體免疫疾病的產品線之際，於本季結束時擁有約 13 億美元的現金及約當現金。我們對所擁有的產品開發機會感到振奮。但同時，我們在對業務的投資上也保持紀律。

As we enter 2013, we have and we will continue to prioritize our R&D projects, investing in those areas that we believe will create long-term value for patients and for Vertex while exercising strict financial discipline on SG&A spending.

在邁入 2013 年之際，我們已經並將持續優先排序研發專案，投資於我們認為能為患者與 Vertex 創造長期價值的領域，同時對銷售、一般及行政（SG&A）支出採取嚴格的財務紀律。

We remain mindful of our revenues and cash flows and how to most prudently invest these revenues to grow our business.

我們仍密切關注我們的營收與現金流，以及如何以最審慎的方式投資這些營收以推動業務成長。

In summary, we continue to execute on our strategy. Our business is strong with substantial revenues from two marketed medicines, a broad and deep pipeline that is further advanced during the first three quarters of 2012, and we have significant cash on our balance sheet. We are well positioned for growth over the long term.

總結來說，我們持續執行我們的策略。我們的業務穩健，來自兩項已上市藥品的可觀營收、在2012年前三季進一步推進且廣泛而深厚的產品研發管線，以及資產負債表上充裕的現金。我們已為長期成長做好充分布局。

I look forward to updating you as we go.

我期待在推進過程中向各位更新進展。

With that, let me turn it over to Ian.

接下來，我把時間交給Ian。

Thank you, Jeff. And good evening to everyone.

謝謝你，Jeff。也向各位致上晚安。

Financially, Vertex has a diverse revenue base with multiple sources. Our revenue is significant and enables us to fund reinvestment into our pipeline for growth.

在財務面，Vertex擁有多元的營收基礎，來源不只一項。我們的營收規模可觀，使我們得以投入資金再投資於研發管線以推動成長。

As we enter 2013, we're committed to maintaining financial discipline. We're mindful of these revenues and cash flows and will prioritize, as Jeff says, our investments as we seek to grow the future opportunities in cystic fibrosis, hepatitis C, and other priority pipeline areas.

邁入2013年，我們承諾維持財務紀律。我們會審慎看待這些營收與現金流，並如Jeff所說，在尋求擴大囊性纖維化、C型肝炎及其他優先研發領域未來機會的同時，優先排序我們的投資。

Now to our third-quarter financial results, total revenues were $336 million compared to $659 million in the same quarter of last year. Last year's revenues included $200 million in one-time milestone revenues due to the approval and launch of INCIVO in Europe. Without this milestone, our revenues were $454 million last year compared to $336 million this year for this quarter.

接著說明第三季財務結果：總營收為3.36億美元，去年同期為6.59億美元。去年營收包含一次性2億美元的里程碑收入，係因INCIVO在歐洲獲准並上市所致。若不計此里程碑收入，去年本季營收為4.54億美元，而今年本季為3.36億美元。

The key components to the third-quarter revenues are as follows. First, we reported $254 million of INCIVEK net product revenues. As Jeff noted, INCIVEK remains the market-leading DAA with approximately 7,000 patients initiating treatment with INCIVEK during the third quarter.

第三季營收的主要組成如下。第一，我們認列INCIVEK淨產品營收2.54億美元。如Jeff所提，INCIVEK仍是市場領先的DAA，第三季約有7,000名病患開始使用INCIVEK治療。

We continue to see demand for INCIVEK-based therapy, and we are reiterating our INCIVEK net revenue guidance of $1.1 billion to $1.25 billion for 2012.

我們持續看到對以INCIVEK為基礎之療法的需求，並重申2012年INCIVEK淨營收指引為11億至12.5億美元。

Second, we recorded $49 million of net product revenues from KALYDECO in the third quarter. This reflects the majority of eligible patients in the US starting treatment with KALYDECO with only a small number of patients initiating therapy in Europe prior to KALYDECO receiving -- achieving reimbursement in that region.

第二，我們在第三季認列KALYDECO淨產品營收4,900萬美元。這反映美國多數符合資格的病患已開始使用KALYDECO治療；而在歐洲，於KALYDECO在該地區獲得—取得給付（reimbursement）之前，僅有少數病患開始治療。

The number of patients in the US has potential to increase incrementally in the near term as new patients initiate therapy. And as the final patients roll off PERSIST study and onto commercial drug, we anticipate that, in the near term, the most important growth driver for KALYDECO revenue will be in reimbursement acceptance in Europe.

在短期內，隨著新病患開始治療，美國的病患數仍有機會逐步增加。此外，隨著最後一批病患完成PERSIST研究並轉用商業化藥品，我們預期短期內推動KALYDECO營收成長最重要的驅動因素，將是歐洲的給付核准（reimbursement acceptance）。

We received European approval for KALYDECO in G551D patients in July, and we are making progress negotiating reimbursement country by country. We anticipate that, in 2013, each of the four major European countries, which account for 80% of the G551D patients in Europe, will provide reimbursement for KALYDECO.

我們已於7月取得KALYDECO用於G551D病患的歐洲核准，並正逐國推進給付談判。我們預期在2013年，歐洲四個主要國家（占歐洲G551D病患的80%）都將為KALYDECO提供給付。

Third, we recorded $26 million of royalty revenues, including $20 million of INCIVO royalty revenue from J&J. We expect our INCIVO royalties will continue to be an important -- to our financial results during 2012 and 2013 and in the future.

第三，我們認列權利金收入2,600萬美元，其中包含來自J&J的INCIVO權利金收入2,000萬美元。我們預期INCIVO權利金在2012年與2013年，以及未來，將持續成為—對我們財務結果的重要貢獻。

The GAAP net loss attributable to Vertex was $58 million in the third quarter of 2012 or approximately $0.27 per share. The non-GAAP net income was $27 million or $0.13 per diluted share.

2012年第三季歸屬於Vertex的GAAP淨損為5,800萬美元，約每股0.27美元。非GAAP淨利為2,700萬美元，稀釋後每股0.13美元。

The non-GAAP income principally excludes two charges, $27 million in stock compensation and $58 million related to the increasing fair value of expected future payments under our Alios collaboration.

非GAAP獲利主要排除兩項費用：2,700萬美元的股票酬勞費用，以及與我們Alios合作案下預期未來付款之公允價值上升相關的5,800萬美元費用。

Now to our operating expenses, beginning in the second quarter, we increased and accelerated our R&D investment on the base of clinical data into high-priority programs in the areas of cystic fibrosis and hepatitis C.

接著談營業費用：自第二季起，我們基於臨床數據，在囊性纖維化與C型肝炎等高優先計畫上，提高並加速了研發投資。

Despite the increased investment in these programs, we are reiterating our non-GAAP operating expense guidance for 2012 of $1.03 billion to $1.13 billion that we originally provided on our February 2nd call earlier this year.

儘管對這些計畫的投資增加，我們仍重申先前於今年2月2日電話會議所提供的2012年非GAAP營業費用指引：10.3億至11.3億美元。

We accomplished this by prioritizing and reducing expenses, specifically in the areas of reductions in G&A spend, aligning our commercial spend to follow future demand in markets in which we operate, and reprioritizing investment in R&D towards key programs.

我們透過優先排序並降低費用來達成此目標，具體包括：降低一般及行政（G&A）支出、使商業化支出與我們所營運市場的未來需求相匹配，以及將研發投資重新聚焦於關鍵計畫。

This expense reduction and investment allocation is visible in our third-quarter results. Our R&D spend is essentially flat compared to second quarter, despite the progress of our clinical pipeline. And our SG&A spend in the third quarter is significantly reduced compared to the second quarter. As we move into 2013, we plan to continue these initiatives.

這些費用削減與投資配置在第三季結果中清楚可見。儘管臨床研發管線持續推進，我們的研發支出相較第二季基本持平。而第三季的銷售、一般及行政（SG&A）支出則較第二季顯著下降。邁入2013年，我們計畫持續推動這些措施。

In summary, we continue to derive significant revenue and cash flow from INCIVEK sales and INCIVO royalties. KALYDECO is positioned to provide growth in the near term, and with the execution of our hepatitis C and CF strategies, we anticipate expanding our presence and the number of people we can treat over the long term. We are balancing this with our financial position and prioritizing our investments.

總結來說，我們持續從INCIVEK銷售與INCIVO權利金取得可觀的營收與現金流。KALYDECO在短期內具備成長動能；隨著我們執行C型肝炎與囊性纖維化（CF）策略，我們預期長期將擴大我們的市場布局以及可治療的人數。同時，我們也會兼顧財務狀況並優先排序投資。

I'll now turn it over to Peter.

接下來我把時間交給Peter。

Thank you, Ian, and good evening, everybody.

謝謝你，Ian，也向各位致上晚安。

Tonight, my remarks will focus on the progression of our pipeline, mainly in the areas of CF and hepatitis C. Two weeks ago, we reviewed our R&D strategy in cystic fibrosis at the North American CF Conference in Orlando. And I want to briefly summarize and reiterate that strategy.

今晚我的發言將聚焦於我們研發管線的進展，主要在囊性纖維化（CF）與C型肝炎領域。兩週前，我們在奧蘭多舉行的北美CF大會上回顧了我們在囊性纖維化的研發策略。我想簡要總結並重申該策略。

We have demonstrated our commitment to discover new treatments for cystic fibrosis by working closing with the medical community and the CF Foundation for about 14 years now.

我們透過與醫療界及CF基金會密切合作約14年，展現了我們致力於發現囊性纖維化新療法的承諾。

Through our work, we have developed a proprietary research platform that enables us to uniquely target the underlying cause of that disease, the defective CFTR proteins. From this platform, we developed KALYDECO, an important breakthrough that is available today for G551D patients ages six and older.

透過這些工作，我們建立了專有的研究平台，使我們能以獨特方式鎖定該疾病的根本原因：缺陷的CFTR蛋白。基於此平台，我們開發出KALYDECO，這是一項重要突破，目前已可供6歲以上的G551D病患使用。

If you look to how we can further advance therapy in the near future, we have three studies underway to expand the label for ivacaftor monotherapy. These studies are a six-month Phase III study in patients with the R117H mutation, representing an additional 3% of the population; a crossover Phase III study in patients with non-G551D gating mutations, representing an additional 1% of the population; and the pediatric Phase III study in patients aged two to five years with gating mutations, where we expect to begin enrollment by the end of the year.

若看我們如何在不久的將來進一步推進治療，我們正在進行三項研究，以擴大ivacaftor單藥治療的適應症標籤。這些研究包括：針對R117H突變病患、為期六個月的第三期研究（約占族群額外3%）；針對非G551D閘門（gating）突變病患的交叉設計第三期研究（約占族群額外1%）；以及針對2至5歲、具有閘門突變之兒科第三期研究，我們預期在年底前開始收案。

We have also initiated a proof of concept study in patients with residual CFTR functions. We anticipate receiving the first data from these studies next year. If we are successful with these and other planned studies, we could treat many more patients with ivacaftor alone than we do today, up to approximately 15% of the CF population.

我們也已在具有殘餘CFTR功能的病患中啟動概念驗證（proof of concept）研究。我們預期明年可取得這些研究的第一批數據。若這些及其他規劃中的研究成功，我們可望讓單用ivacaftor治療的病患人數遠多於目前，最多可達約占CF病患族群的15%。

Also, in the relatively near term, we have the potential to expand therapy to the largest group of CF patients, those homozygous for the delta 508 mutation that make up an additional approximately 50% of the CF population.

此外，在相對較近的期間內，我們有機會將治療擴展至最大的囊性纖維化（CF）患者族群，也就是帶有 delta 508 突變純合子的患者，這一族群約占 CF 總人口的另外約 50%。

We presented Phase II results at the North American Cystic Fibrosis Conference a few weeks ago. And on the basis of this positive data, we are planning to initiate a pivotal program of VX-809 plus ivacaftor in the early part of 2013.

我們在幾週前的北美囊性纖維化會議上發表了第二期（Phase II）結果。基於這些正面的數據，我們計畫在 2013 年初啟動 VX-809 與 ivacaftor 併用的關鍵性（pivotal）計畫。

While details of the pivotal program design will depend on the outcomes of regulatory discussions, we can provide some of what we think the important aspects of the pivotal program will be.

雖然關鍵性計畫設計的細節將取決於與監管機構討論的結果，但我們可以提供一些我們認為該關鍵性計畫的重要面向。

Firstly, we will seek to confirm the safety and activity of 600-milligram VX-809 QD in combination with 250 milligram of ivacaftor twice a day in patients homozygous for delta 508, 12 years of age and older. This was the regimen that demonstrated the greatest improvement in FEV1 compared to patients' baseline and also to placebo in the Phase II study.

首先，我們將尋求在 12 歲及以上、delta 508 純合子患者中，確認每日一次（QD）600 毫克 VX-809 與每日兩次 250 毫克 ivacaftor 併用的安全性與活性。這是在第二期研究中，相較於患者基線以及相較於安慰劑，顯示 FEV1 改善幅度最大的給藥方案。

Based on our experience with KALYDECO, we anticipate the pivotal study to be anything between six and 12 months duration, pending our discussions with regulatory authorities.

根據我們使用 KALYDECO 的經驗，在與監管機構討論後，我們預期關鍵性研究的期間可能介於 6 到 12 個月。

We expect that the primary endpoint will be change in FEV1 and that we will evaluate a number of other endpoints as well, including weight gain, reduction in primary exacerbations and CFQR.

我們預期主要終點將是 FEV1 的變化，同時也會評估多項其他終點，包括體重增加、主要急性惡化事件的降低，以及 CFQR。

Finally, we may include a higher dose of VX-809. We're evaluating 400 milligram BID of VX-809 in an additional cohort of patients called Cohort 3. Safety and PK data from Cohort 3 will inform the potential inclusion of a 400-milligram BID VX-809 dose as part of the pivotal program. Cohort 3 is fully enrolled. And we expect to have the data in time for the start of the pivotal program.

最後，我們可能會納入更高劑量的 VX-809。我們正在一個稱為第 3 隊列（Cohort 3）的額外患者隊列中評估每日兩次（BID）400 毫克 VX-809。第 3 隊列的安全性與藥物動力學（PK）數據，將為是否在關鍵性計畫中納入每日兩次 400 毫克 VX-809 劑量提供依據。第 3 隊列已完成收案。我們預期能在關鍵性計畫開始前及時取得數據。

The VX-809 and ivacaftor combination represents our first opportunity to create a significant treatment benefit for the most common group of CF patients, the 508 delta homozygous group.

VX-809 與 ivacaftor 的併用，代表我們首次有機會為最常見的 CF 患者族群——508 delta 純合子族群——帶來顯著的治療效益。

But, it is not the only program we have to address this population. We are working on strategies to further optimize therapy for these and additional patients, including delta 508 heterozygotes.

但這並不是我們針對此族群的唯一計畫。我們正在研擬策略，以進一步最佳化這些患者以及其他患者（包括 delta 508 雜合子）的治療。

In this context, we are developing an additional novel corrector compound VX-661 in combination with ivacaftor in a Phase II study. This study's designed as a dose-escalation, placebo-controlled study. The design is very different than the Phase II VX-809 study and is our first trial of VX-661 in patients.

在此背景下，我們正在第二期研究中開發另一個新型校正劑（corrector）化合物 VX-661，並與 ivacaftor 併用。此研究設計為劑量遞增、安慰劑對照研究。其設計與 VX-809 的第二期研究非常不同，並且是 VX-661 首次在患者中進行的試驗。

Part A of the study, which we initiated earlier this year, is evaluating different doses of VX-661 alone for 28 days in approximately 50 patients and in combination with ivacaftor for 28 days in an additional 50 patients. The monotherapy doses escalate ahead of the combination doses.

本研究的 A 部分（Part A）我們於今年稍早啟動，將在約 50 名患者中評估不同劑量的 VX-661 單藥治療 28 天，並在另外 50 名患者中評估 VX-661 與 ivacaftor 併用 28 天。單藥治療的劑量遞增將先於併用治療的劑量遞增。

All arms are 28 days, and each new dose enrolls a completely new set of patients. We will be evaluating safety and efficacy of these ascending doses. And this will inform our next steps for this combination therapy. We expect results from this study will be available in the first half of 2013.

所有組別皆為 28 天，且每一個新劑量都會招募一批完全新的患者。我們將評估這些遞增劑量的安全性與療效。這將為我們此併用療法的下一步提供依據。我們預期此研究結果將於 2013 年上半年出爐。

Beyond VX-809 and VX-661, we are very exciting -- we have very exciting efforts underway to further expand and optimize therapy in CF. We have now identified novel correctors that, in vitro, have additive or synergistic activity with VX-809 and ivacaftor.

除了 VX-809 與 VX-661 之外，我們也非常振奮——我們正進行多項非常令人振奮的工作，以進一步擴展並最佳化 CF 的治療。我們目前已鑑定出新的校正劑，在體外（in vitro）與 VX-809 及 ivacaftor 併用時具有加成或協同作用。

This work is based on recent advancements in the understanding of the folding pathway of the CFTR protein. We look forward to updating you on our progress with second-generation correctors and further combination approaches as we move ahead in 2013.

這項工作是基於近期對 CFTR 蛋白摺疊途徑理解的進展。隨著我們在 2013 年持續推進，我們期待向各位更新第二代校正劑以及更多併用策略的進展。

In summary, in CF, we believe we are well positioned to bring innovation and clinical advancement to this area today, tomorrow, and in the future.

總結而言，在 CF 領域，我們相信我們已具備良好條件，能在今天、明天以及未來為此領域帶來創新與臨床進展。

Now turning to hepatitis C, we have a range of development activities underway. But, I would like to focus my comments on our nucleotide VX-135.

接著談到 C 型肝炎，我們正在進行一系列的開發活動。但我想將我的評論重點放在我們的核苷酸類藥物 VX-135。

Based on our seven-day viral kinetics study, VX-135 appears to be a highly potent nuke with an excellent early clinical profile. We are excited to present some preclinical and viral kinetic data for this compound at the upcoming AASLD a week from now.

根據我們為期 7 天的病毒動力學研究，VX-135 似乎是一種效力極高的核苷（nuke），且早期臨床特徵非常優異。我們很期待在一週後即將舉行的 AASLD 會議上，發表此化合物的一些臨床前與病毒動力學數據。

Since receiving the viral kinetic results in July, we have articulated our strategy for how we think we can position VX-135 as an important backbone in future short-duration all-oral regimens for hepatitis C.

自 7 月取得病毒動力學結果以來，我們已闡述我們的策略：我們認為可如何將 VX-135 定位為未來短療程、全口服 C 型肝炎治療方案中的重要骨幹藥物。

Today, we shared our significant progress with that strategy with the announcement of two agreements for Phase II combination studies. These collaborations will enable us to evaluate VX-135 in combination with two highly promising compounds, each of them representing complementary direct antiviral mechanisms.

今天，我們透過宣布兩項用於第二期併用研究的協議，分享了我們在該策略上的重大進展。這些合作將使我們能評估 VX-135 與兩種極具前景的化合物併用；這兩種化合物各自代表互補的直接抗病毒作用機制。

We intend to move as rapidly as possible. Specifically, we will begin a series of Phase II 12-week studies with VX-135 in combination with these oral DAAs with and without ribavirin. The goal of these studies will be to evaluate safety, PK, and SVR in Genotype 1 noncirrhotic naive patients.

我們打算以最快速度推進。具體而言，我們將啟動一系列為期 12 週的第二期研究，評估 VX-135 與這些口服直接抗病毒藥物（DAAs）併用，並分別在有或無 ribavirin 的情況下進行。這些研究的目標是評估在基因型 1、無肝硬化且未治療（naive）患者中的安全性、PK 與 SVR。

We are planning additional Phase II proof of concept studies with VX-135, including a study of VX-135 in combination with ribavirin by the end of 2012 and a study of VX-135 in combination with INCIVEK planned for 2013.

我們也規劃其他 VX-135 的第二期概念驗證（proof of concept）研究，包括在 2012 年底前進行 VX-135 與 ribavirin 併用的研究，以及規劃於 2013 年進行 VX-135 與 INCIVEK 併用的研究。

We are aiming to identify the best regimens to treat hepatitis C patients. And our goal is to complete Phase II evaluation of multiple regimens in 2013 so that we can choose regimens for pivotal development in 2014.

我們的目標是找出治療 C 型肝炎患者的最佳療程組合。我們的目標是在 2013 年完成多種療程的第二期評估，以便在 2014 年選定用於關鍵性開發的療程。

I will just quickly note, during the third quarter, we also advanced Phase II development of VX-509 for inflammatory diseases, including rheumatoid arthritis and VX-787 for influenza.

我也簡要提一下，在第三季期間，我們也推進了 VX-509（用於發炎性疾病，包括類風濕性關節炎）的第二期開發，以及 VX-787（用於流感）的開發。

In summary, our efforts in cystic fibrosis reflect a commitment to leverage our R&D expertise, scientific knowledge, and capabilities to make a big difference in the lives of thousands of CF patients. And our ongoing efforts in hepatitis C demonstrate our commitment to continued innovation in this area.

總結而言，我們在囊性纖維化方面的努力，反映出我們致力於運用我們的研發專長、科學知識與能力，為數千名 CF 患者的生活帶來重大改變。而我們在 C 型肝炎方面的持續努力，則展現我們對此領域持續創新的承諾。

I look forward to reporting on our progress in these and other areas in upcoming quarters. I will now turn back it over and back and over to Michael.

我期待在接下來的季度中，向各位報告我們在這些以及其他領域的進展。我現在把時間交回給 Michael。

Thank you, Peter. That concludes our prepared remarks. We would now like to open the call to Q&A.

謝謝你，Peter。以上為我們事先準備的發言。接下來我們想開放電話會議進入問答（Q&A）環節。

(Operator Instructions). Our first line -- question comes from the line of Geoff Porges with Bernstein Research. Your line is open.

（接線員指示）。我們的第一個問題來自 Bernstein Research 的 Geoff Porges。您的線路已開通。

Thanks very much for taking the question. Peter, I just wanted to follow up on some of the comments about 135 since it seems to be a focus inside and outside the Company.

非常感謝讓我提問。Peter，我想就你剛才關於 135 的一些評論再追問一下，因為看起來它在公司內外都是關注焦點。

First, it's sort of an obvious question, which is this is a rapidly changing landscape. And can you tell us what sort of differences there are between this molecule and the other nukes that have failed recently and over time? And why should investors ascribe any real value to this at this stage? What gives you the conviction?

首先，這算是一個很明顯的問題，也就是這是一個快速變動的環境。你能否告訴我們，這個分子與其他近期及過去一段時間內失敗的核苷類藥物（nukes）之間有哪些差異？以及為什麼投資人在這個階段應該賦予它任何實質價值？你們的信心來自哪裡？

Secondly, related to 135, conspicuously, you're not mentioning VX-222. Is there any drug-drug interaction thing that you're concerned about there? Why wouldn't you want to combine this with 222 rather than combining it with ribavirin?

第二個問題，與135相關的是，很明顯你們沒有提到VX-222。你們是否擔心任何藥物—藥物交互作用？為什麼你們不想把它與222併用，而是選擇與利巴韋林（ribavirin）併用？

And then lastly, could you tell us when we'll see the 787 influenza data? Thanks.

最後，你能否告訴我們何時會看到787流感數據？謝謝。

So, Geoff, this is Bob Kauffman. I'll take the first question. And yes, we recognize the rapidly changing landscape. We certainly recognize the issues that have occurred with a couple of other nukes in this space in the past few months.

Geoff，我是Bob Kauffman。我先回答第一個問題。是的，我們認知到這個快速變動的環境。我們也確實注意到在過去幾個月裡，這個領域中其他幾個核苷類藥物所發生的一些問題。

All I can say is that VX-135 has a very strong preclinical profile and, in our early clinical studies, really was extremely well tolerated and produced a very impressive antiviral activity. And therefore, we have very great confidence going in.

我能說的是，VX-135在臨床前具有非常強的特徵；而且在我們早期的臨床研究中，它的耐受性確實非常好，並且展現出非常令人印象深刻的抗病毒活性。因此，我們對接下來的推進非常有信心。

As we've noted, it's a uridine analogue, unlike some of the other compounds that have not done so well lately. And it just gives us more confidence that we'll have a very good outcome in the next set of studies.

如同我們先前提到的，它是一種尿苷類似物（uridine analogue），不同於近期表現不佳的一些其他化合物。這也讓我們更有信心，在下一組研究中會得到非常好的結果。

Obviously, we recognize the limitations of the data we have. We have only seven-day safety data. Clearly, 12-week data will give us even more confidence. And that's why we're moving as rapidly as we can to obtain those data.

當然，我們也了解目前數據的限制。我們只有七天的安全性數據。很明顯，12週的數據會讓我們更有信心。這也是為什麼我們正盡可能快速地推進以取得那些數據。

So, Geoff, that's Peter speaking. I think good questions. So, I want to just confirm on the one hand what Bob said about 135. And I think the good thing for 135 is it has a metabolic profile that allows us to basically combine it with many different molecules.

Geoff，我是Peter。我認為這些問題問得很好。我想先確認Bob對135所說的內容。我認為135的一個優點是，它的代謝特徵使我們基本上可以把它與許多不同分子進行併用。

And that leads me to your second question about what is about 222 and other molecules that we have in our portfolio. So, obviously, we are currently looking deeply into what the best regimens are. And we will have in mind in our different concepts where 222 is part of it. And we will come later when we prioritize whatever we can do. So, 222 is a viable asset, a highly viable asset in our regimen and I think should not be forgotten.

這也引出你第二個問題：關於222以及我們產品組合中的其他分子。很明顯，我們目前正在深入評估最佳的治療方案（regimens）。在我們不同的方案構想中，會把222納入考量。等到我們釐清並排定可優先推進的事項後，會再回來更新。因此，222是我們治療方案中一項可行、而且高度可行的資產，我認為不應被忽視。

So, and the last question was when do we hear something about 661? And I turn it over to Ian because that's a disclosure question, the flu, the 787, yes.

那麼，最後一個問題是：我們何時會聽到關於661的消息？我把問題交給Ian，因為那是資訊揭露的問題，流感、787，是的。

787, yes.

787，是的。

Yes, topical in flu season. Thanks, Geoff. So, as we've communicated earlier in the year, we anticipate giving you top line results from that study before the end of this year. And we're still on track for that.

是的，正值流感季。謝謝你，Geoff。如同我們今年稍早所溝通的，我們預期會在今年年底前提供該研究的主要結果（top line results）。我們目前仍按計畫進行。

Okay. Thanks very much for the questions.

好的。非常感謝你們的提問。

Thank you. Our next question comes from the line of Rachel McMinn with Bank of America. Your line is open.

謝謝。下一個問題來自美國銀行（Bank of America）的Rachel McMinn。請發問。

Yes, thanks very much. Two totally separate questions, one just on -- congratulations on the collaborations for 135. But, I'm just wondering why you would bother running the INCIVEK combination studies. Is that really just for safety, or is there really a point since you have this partnership now with a low-dose once-a-day protease inhibitor with a very well-established safety profile?

是的，非常感謝。兩個完全不相關的問題。第一個是——恭喜你們在135方面的合作。不過我想知道，你們為什麼還要費心進行INCIVEK的併用研究？那真的只是為了安全性，還是其實有其必要性？因為你們現在已經與一個低劑量、每日一次、且安全性特徵非常成熟的蛋白酶抑制劑建立合作夥伴關係了。

And then secondly, Ian, I think you've talked a number of times of not wanting to be cash flow negative in 2013 or 2014. But, at the same time, you're talking about putting more money into R&D from SG&A. So, I'm just wondering how you can manage that. Can we be sure that R&D overall will be down annually in 2013 versus 2012? Thank you.

第二個問題，Ian，我想你多次提到不希望在2013或2014年出現現金流為負。但同時你又談到要把更多SG&A的資金投入到研發（R&D）。所以我想知道你們要如何做到這點。我們能否確定2013年的研發總支出會比2012年按年下降？謝謝。

Rachel, given there's a number of questions, given the collaboration comment, I mean, we share your thanks on the collaborations. Jeff's going to take the first piece, and then I'll take the financial question.

Rachel，因為你問了好幾個問題，也提到合作的評論——我們也同樣感謝這些合作。第一部分由Jeff回答，財務問題由我來回答。

Hi, Rachel. It's Jeff. And thanks for your questions.

嗨，Rachel。我是Jeff。謝謝你的提問。

The first question really had to do with how we're thinking about prioritizing these different regimens. And I know you're familiar with this. But, let me just take a step back and briefly rearticulate the strategy that we talked about in July, which was we do feel that VX-135 has a profile as a nuke that makes it potentially a very valuable piece of multiple combination regimens.

第一個問題主要是關於我們如何思考並排定這些不同治療方案的優先順序。我知道你對此很熟悉。不過我先退一步，簡要重申我們在7月談到的策略：我們確實認為VX-135作為一個核苷類藥物（nuke），其特徵使它可能成為多種併用治療方案中非常有價值的一個組成部分。

We also feel that it may be the case that there will be several regimens, one optimal regimen, for example, for easy-to-treat patients and a separate one or separate duration for longer-to-treat patients.

我們也認為，可能會存在多個治療方案：例如，對於容易治療的病人有一個最佳方案；而對於較難治療的病人，則可能需要另一個方案或不同的治療期間。

So, our strategy was to combine 135, both with different combinations of our own medicines, 222, INCIVEK, et cetera, but also to be open to collaborations with others. And obviously, you heard today about how we're executing on that strategy.

因此，我們的策略是將135與我們自有藥物的不同組合進行併用測試，例如222、INCIVEK等等，同時也對與其他公司合作保持開放。而且很明顯，你們今天也聽到我們正在如何執行這項策略。

If you look at where we are today, we feel really good about what we have in hand, right, because we have now a very potent and tolerable members of each of the major classes that we think are going to be important, nukes, nonnukes, PIs, and 58s.

如果你看我們目前的狀況，我們對手上的資產感到非常滿意，對吧，因為我們現在在我們認為重要的主要類別中，各自都有非常強效且耐受性良好的成員：核苷類（nukes）、非核苷類（nonnukes）、蛋白酶抑制劑（PIs）以及58類。

And so, we're in a very nice position to begin to combine them in different combinations and learn pretty quickly in 12-week studies what the best or winning combinations are going to be.

因此，我們處於一個非常有利的位置，可以開始把它們以不同方式進行組合，並在12週研究中相當快速地了解哪些會是最佳或勝出的組合。

We're obviously in the process right now of prioritizing those studies. So, we've told you that we're going to do VX-135 plus ribavirin. We certainly are going to do VX-135 plus 435 as well as the GSK5A. And then we're trying to understand where INCIVEK and 222 are really going to fit into that. And we'll be able to give you a lot more details as we move forward.

我們目前顯然正在進行這些研究的優先順序排序。因此，我們已告訴各位我們會做VX-135加利巴韋林（ribavirin）。我們也確實會做VX-135加435，以及GSK5A。接著我們正試圖釐清INCIVEK與222在其中究竟會如何定位與融入。隨著我們持續推進，我們將能提供更多細節。

But, the strategy remains the same. We're going to test multiple combinations, find the best ones for patients in 2013 so that we're in a position to pick those and move into pivotal studies in 2014. And I'm just really pleased now that we have all the pieces in hand do to that.

但策略仍然相同。我們會在2013年測試多種併用組合，找出對病人最好的方案，讓我們能在2014年選定並推進到關鍵性研究（pivotal studies）。我也非常高興我們現在已經具備所有必要的拼圖來完成這件事。

And, Rachel, to your question about financial profile in '13, I'm hoping that you did hear the comments that Jeff made in his prepared remarks and then also echoed by my own.

而且，Rachel，關於你對於『13年財務概況』的問題，我希望你確實有聽到 Jeff 在其事先準備的發言中所做的評論，並且我也在我的發言中再次呼應。

You can see with just the results we've disclosed at the third quarter that we're working very hard towards prioritizing our R&D investment, as you can see that the R&D investment remains consistent with how we guided at the beginning of the year and then also from Q2 to Q3, despite the increased investments in CF and HCV.

從我們在第三季所揭露的結果，你可以看到我們正非常努力地朝著優先排序我們的研發投資前進；你也可以看到，儘管在 CF 與 HCV 上增加了投資，研發投資仍與我們在年初所給出的指引一致，且從 Q2 到 Q3 也保持一致。

So, you can see that we're reprioritizing throughout our portfolio there. And we'll continue that effort into 2013 for the high-value programs. On the SG&A side, again, we can continue probably more dramatically if you see the reduction in SG&A spend between Q2 and Q3.

所以，你可以看到我們正在整個產品組合中重新排序優先順序。而且我們會在 2013 年持續把這項努力聚焦在高價值的計畫上。在 SG&A 方面，同樣地，如果你看到 Q2 到 Q3 之間 SG&A 支出的下降，我們可能還能更明顯地持續下去。

Again, that's active management of SG&A. We're following where the demand is in the markets. We're looking at programs. We're looking at our infrastructure. And we've made decisions there as well.

同樣地，這是對 SG&A 的主動管理。我們會跟隨市場中的需求走向。我們在檢視各項計畫。我們在檢視我們的基礎設施。而且我們也在那裡做出了決策。

So, we're working very hard. These efforts will continue into 2013. And I'll just close by we are in our planning process. We're taking a look at what we believe our revenues may be for '13, 2013, both the growth on KALYDECO side and what the potential is there and specifically looking to how we think we may go into Europe and penetrate that patient population for KALYDECO, and on INCIVEK acknowledging that INCIVEK, it is a challenge. We acknowledge that.

所以，我們正非常努力。這些努力將延續到 2013 年。最後我想補充的是，我們正處於規劃流程中。我們正在檢視我們認為『13 年、2013 年』的營收可能會是多少，包括 KALYDECO 端的成長以及其潛力，並特別評估我們可能如何進入歐洲並滲透 KALYDECO 的患者族群；同時在 INCIVEK 方面，我們也承認 INCIVEK 確實是一項挑戰。我們承認這一點。

And so, we're taking those revenues and being mindful of our cash flows for reinvestment. And we'll give you more of an update specifically as we go into 2013 with our call early on in that year. But, we're in the middle of that process. But, I hope you can hear the themes that are coming strongly on this call.

因此，我們在考量這些營收的同時，也會留意我們用於再投資的現金流。而當我們進入 2013 年、在該年初的電話會議時，我們會就此提供更具體的更新。但我們目前正在這個流程的中段。不過，我希望你能聽到本次電話會議中強烈傳達的主題。

But, you still agree cash flow neutral or positive next year.

但是，你仍然同意明年現金流量持平或為正嗎？

As I say, we're going through our planning processes. We need to understand what our revenues will be at this point in time. And as we go into '13, we'll provide you more specific direction for our business at that time.

如我所說，我們正在進行規劃流程。我們需要在此時點了解我們的營收會是多少。而當我們進入『13 年』時，我們會在那個時候為你提供更具體的業務方向。

Thank you.

謝謝。

Thank you. Our next question comes from the line of Gloria Wu with Citi. Your line is open.

謝謝。我們的下一個問題來自 Citi 的 Gloria Wu。你的線路已開通。

Hi. Thanks for taking my question. I first had a question on CF and then one on your HCV. We wanted to know how should we anticipate (inaudible) picking up KALYDECO and whether you actually need formal NICE or (inaudible) reimbursement for the UK and how many patients you think that are in the UK and Scotland?

嗨。謝謝讓我提問。我先有一個關於 CF 的問題，然後一個關於你們 HCV 的問題。我們想了解應該如何預期（聽不清）開始使用 KALYDECO，以及在英國你是否實際上需要正式的 NICE 或（聽不清）給付，另外你認為英國與蘇格蘭各有多少名患者？

And then moving on to HCV, could you just give us an idea of GSK's NS5A inhibitor, the potency? You mentioned it's going to be a once-a-day pill. But, can you give us a little bit more information on the resistance profile and how much data there is on that drug already, just based on safety in animals and in humans? Thanks.

接著談到 HCV，你能否給我們一個關於 GSK 的 NS5A 抑制劑效力的概念？你提到它會是每日一次的藥丸。但你能否再提供一些關於抗藥性特徵，以及目前對該藥物已有多少資料的資訊，特別是基於動物與人體的安全性？謝謝。

Yes, I'm sorry, Gloria, but with your questions, I'm not sure whether you're in the office or maybe you're out, given weather conditions of this week, but your question really didn't come through very clearly. I'm not sure whether you can pick up the phone or whether there's something else. But, it really didn't come through very clearly. If you could try repeating it and -- .

是的，抱歉，Gloria，但就你的問題而言，我不確定你是在辦公室還是在外面，考量到本週的天候狀況，你的問題其實沒有很清楚地傳過來。我不確定你是否可以拿起話筒，或是否有其他方式。但確實聽得不太清楚。如果你可以試著再重複一次，然後——。

Sure.

當然。

We will try our best to answer it.

我們會盡力回答。

Sure. I'll try again. Sorry. We're out of the office right now. Just first, on KALYDECO, just if you need formal NICE reimbursement in the UK before you can have broad use in Scotland and the UK and how many patients you think are in the UK and Scotland?

好的。我再試一次。抱歉。我們現在不在辦公室。首先，關於 KALYDECO，在英國你是否需要正式的 NICE 給付，才能在蘇格蘭與英國廣泛使用？以及你認為英國與蘇格蘭各有多少名患者？

And for HCV, can you give us some information on GSK's NS5A inhibitor, the potency, the resistance profile, and any safety data that may be in animals and in human? Did that come through?

另外，關於 HCV，你能否提供一些關於 GSK 的 NS5A 抑制劑的資訊，包括效力、抗藥性特徵，以及在動物與人體中可能已有的任何安全性資料？這樣有傳過來嗎？

Yes, it did. Thank you, Gloria. Maybe we'll just start with the HCV question with GSK's NS5A inhibitor. And maybe Bob can give you a quick profile of that compound.

有的。謝謝你，Gloria。也許我們先從 HCV 的問題、也就是 GSK 的 NS5A 抑制劑開始。也許 Bob 可以快速介紹一下該化合物的概況。

I would also offer that, following the call, Michael Partridge can send you a package on that. And so, therefore, you'll have specific details of what's been discussed on that compound at previous medical conferences. But, maybe Bob can give you a top line at this moment.

我也想補充，會後 Michael Partridge 可以寄給你一份資料包。因此，你將會拿到先前在醫學會議上對該化合物所討論內容的具體細節。不過，也許 Bob 現在可以先給你一個高層次的重點。

Yes, so, this is a very -- we believe is a very promising NS5A inhibitor. It's been evaluated in short-term viral kinetic studies, single dose studies, and shows approximately a 3-log drop at the dose that's being chosen for further development, which is 60 milligrams.

好的，所以，這是一個非常——我們認為非常有前景的 NS5A 抑制劑。它已在短期病毒動力學研究、單次劑量研究中進行評估，並在選定用於進一步開發的劑量（60 毫克）下，顯示約 3-log 的下降。

That 3-log drop is really comparable to the other NS5A inhibitors that are in development now, including one from BMS and one from Gilead. It is a once-a-day medication, once-a-day pill.

這個 3-log 的下降，確實可與目前正在開發的其他 NS5A 抑制劑相當，包括 BMS 的一個以及 Gilead 的一個。它是每日一次用藥，每日一次的藥丸。

And in terms of its other profile, it has a very good preclinical profile. And its resistance profile has not been fully discussed. They are in the midst of a 12-week study with -- in combination with PEG and riba at the present time. It looks as though it has a resistance profile which is similar to the other NS5A inhibitors that are in development but really has very good properties, and we're really looking forward to the combination studies that we're about to start.

至於其他特性，它有非常好的臨床前特徵。而其抗藥性特徵尚未被完整討論。他們目前正在進行一項為期 12 週的研究，與——以 PEG 與 riba 的合併治療。看起來它的抗藥性特徵與其他正在開發的 NS5A 抑制劑相似，但確實具有非常好的特性，我們也非常期待即將開始的合併研究。

And then to the question on KALYDECO, welcoming Stuart Arbuckle, our newly appointed Chief Commercial Officer.

接著回到 KALYDECO 的問題，我們也歡迎新任命的首席商務長 Stuart Arbuckle。

Yes, thanks, Ian. This is Stuart Arbuckle, so just addressing your questions on KALYDECO reimbursement in the UK. It -- as an orphan drug doesn't actually currently go through NICE, but it is going through an official reimbursement process in England and Scotland and the other countries in the UK and the Republic of Ireland.

好的，謝謝，Ian。我是 Stuart Arbuckle，針對你關於英國 KALYDECO 給付的問題做回應。它——作為孤兒藥，目前其實不會走 NICE 流程，但它正在英格蘭、蘇格蘭以及英國其他地區與愛爾蘭共和國進行正式的給付流程。

We are in the middle of that process. It's going well. It's difficult to predict, though, exactly when that process will conclude.

我們正處於該流程的中段。進展良好。不過，很難精確預測該流程何時會結束。

And in terms of patient numbers, across Europe, we think there's about the same number of G551D patients in Europe as there are in the United States. And approximately half of them are in the UK and the Republic of Ireland.

就患者人數而言，在整個歐洲，我們認為歐洲的 G551D 患者人數大約與美國相同。其中約有一半在英國與愛爾蘭共和國。

Next question, please?

下一個問題，請？

Thank you.

謝謝。

Thank you. Our next question comes from the line of Geoff Meacham with J.P. Morgan. Your line is open.

謝謝。我們的下一個問題來自摩根大通（J.P. Morgan）的 Geoff Meacham。您的線路已開通。

Hey, guys. Thanks for taking the question. Got a couple on the CF combo. You guys mentioned you're meeting with FDA this quarter. So, I guess I appreciate the urgency on starting the Phase III. But my first question is, should we read into this that you guys ultimately expect 661 to look less robust? In other words, why wouldn't you at least wait for that data?

嗨，各位。謝謝讓我提問。我有幾個關於 CF 聯合療法的問題。你們提到本季會與 FDA 會面。所以，我想我理解你們急於啟動第三期試驗。但我的第一個問題是，我們是否應該從中解讀為你們最終預期 661 的效果可能沒那麼強？換句話說，為什麼你們不至少等到那份數據出來？

And then the second question is, if the 800-milligram 809 does look stronger than the -- than 400 or 600, do you think you go into -- right into Phase III, or do you think another FDA meeting to tweak the protocol would be required? And I have one follow up.

第二個問題是，如果 800 毫克的 809 看起來確實比——比 400 或 600 更強，你們會認為可以——直接進入第三期嗎？還是你們覺得需要再跟 FDA 開一次會來微調試驗方案？我還有一個追問。

Yes, so, thanks, Geoff. Peter will take that question.

是的，謝謝你，Geoff。Peter 會回答這個問題。

Hi, Geoff. That's Peter speaking. I think I start with the second questions first about -- that is the BID 400-milligram question. And do we need to do another study to go in Phase III or go directly into Phase III? So, the answer is we have enough data in our Phase I and II packages gathered to basically do molecular modeling that gets to an insight about how you might conduct a Phase III study in different dose regimens.

嗨，Geoff。我是 Peter。我想我先從第二個問題開始——也就是 BID 每日兩次 400 毫克的問題。我們是否需要再做另一項研究才能進入第三期，或是可以直接進入第三期？答案是：我們在第一期與第二期的資料包中已累積足夠數據，基本上可以進行分子建模，從而洞察在不同劑量方案下第三期試驗應如何設計。

One is obviously the 600 milligram that we have to confirm that is sort of standard approach. You have to confirm the data in what you have to have had in Phase II. And the other one is go with a higher dose. And I think the twice 400 is from a modeling point what it is.

其中一個方案顯然是 600 毫克，我們需要確認這算是某種標準做法。你必須在第二期所得到的數據上加以確認。另一個方案則是採用更高劑量。而我認為每日兩次 400 毫克，從建模角度來看就是這樣得出的。

That's the reason why we also do Cohort 3 to confirm that we have a chance to go with a higher dose in that study. We do not need at this current point in time -- and that's our strong belief -- another study to add a higher dose of VX-809 into our Phase III regimen.

這也是我們進行第 3 隊列（Cohort 3）的原因，用以確認在該研究中我們有機會採用更高劑量。在目前這個時間點——而且這是我們堅定的看法——我們不需要再做另一項研究，來把更高劑量的 VX-809 納入我們的第三期方案。

Now, the question will be with the agency what the right dose is and what the higher dose is. It might not necessarily be twice 400. It could be something else. But, that is the reason why we did this study.

接下來要與主管機關討論的問題是：正確的劑量是多少，以及所謂更高劑量應該是多少。它不一定是每日兩次 400 毫克。也可能是其他劑量。但這就是我們做這項研究的原因。

So, I think the answer is, no, we go directly into pivotal trials with 600 milligram as the confirmatory arm of it and then with another higher dose. And that might be twice 400, or it might be something else. So, that's the first question.

所以，我想答案是：不，我們會直接進入關鍵性試驗（pivotal trials），以 600 毫克作為確認性組別，然後再加上一個更高劑量。那可能是每日兩次 400 毫克，也可能是其他劑量。這是第一個問題的回答。

So, the second question is, why do we not wait for 661 data and all these type of things. I think we have basically concluded a Phase II study. And we go as fast as we can with the regimen for the patient population that responded well over the finish line.

第二個問題是，為什麼我們不等 661 的數據以及諸如此類的事情。我想我們基本上已完成一項第二期研究。我們會以最快速度，讓對該方案反應良好的患者族群，盡快跨過終點線。

And so, if we would wait for 661, we would delay basically substantially the entire development and the outcome. And we have a commitment to basically reach out to those patients as fast as we can. This is our commitment as a company. And I think the 809/770 combination is a very viable regimen that really will have big impact in a big population. And I think we want to not slow down by two years waiting for 661.

因此，如果我們等待 661，我們基本上會大幅延後整個開發進程與結果。我們承諾要盡快把治療帶給那些患者。這是我們公司的一項承諾。而我認為 809/770 的組合是一個非常可行的方案，確實會對龐大的患者族群產生重大影響。我想我們不希望因為等待 661 而放慢腳步兩年。

Gotcha. And then the follow up, just a quick one on the dual-corrector strategy, is the assumption that you guys would include 809 and KALYDECO as part of the combo, or I guess I want to get a better sense for whether you think two new agents that are correctors may be needed or if it's sort of an add on to 809 KALYDECO. And what have you seen thus far in some of your preclinical work? Thanks a lot.

了解。那追問一下，關於雙校正劑（dual-corrector）策略，是否假設你們會把 809 和 KALYDECO 納入組合的一部分？或者我想更清楚了解，你們認為是否需要兩個新的校正劑，還是說這更像是在 809 + KALYDECO 的基礎上加成。到目前為止，你們在一些臨床前工作中看到了什麼？非常感謝。

Yes, all right. I think what we -- so, there's two questions. What we have seen so far is basically addition of a second-generation corrector to our existing correctors in KALYDECO. And so, there is an 809 ivacaftor or KALYDECO type of regimen as a base, and we add in new correctors. And when you add in one of these, you basically get nice synergistic efforts.

好的。我想我們——這裡有兩個問題。到目前為止我們看到的是：在既有的校正劑與 KALYDECO 的基礎上，再加入第二代校正劑。因此，以 809 + ivacaftor（或 KALYDECO）這類方案作為基底，再加入新的校正劑。當你加入其中一個時，基本上會看到不錯的協同效應。

There is also what we have seen the combination of two new ones that will bring you to very high levels of CFTR expression, which is I think a good one. And at the end of the day, it will be probably a mix and match out of different type of things, where you have in one case maybe 770 and 809 and one of those correctors, in other cases maybe the two correctors.

我們也看到兩個新的校正劑的組合，能把 CFTR 表現量提升到非常高的水準，我認為這是很好的。而最終，可能會是不同方案的混搭：某些情況下可能是 770、809 再加上一個校正劑；其他情況下可能是兩個校正劑的組合。

And that is driven by the patient population that segregate in the CF world because you have heterozygotes. You have homozygotes. You have pancreatically sufficient ones. And they might respond differently to different regimens.

而這取決於 CF 領域中不同的患者族群分層，因為有異合子（heterozygotes）。也有同合子（homozygotes）。也有胰臟功能足夠者（pancreatically sufficient）。他們對不同方案的反應可能不同。

So, it is basically not a one-size-fits-all solution. It is a patient-tailored personalized medicine approach to treat those populations the best we can.

所以，這基本上不是一種「一體適用」的解決方案。而是一種以患者為中心、量身打造的個人化醫療方法，盡我們所能最佳地治療這些族群。

Okay. Thanks.

好的。謝謝。

Thank you. Our next question comes from the line of Mark Schoenebaum with ISI Group. Your line is open.

謝謝。我們的下一個問題來自 ISI Group 的 Mark Schoenebaum。您的線路已開通。

Hey, guys. Thanks. This is Omar filling in for Mark. I had a couple of questions, both on CF. Number one, on disclosure plans, so will -- should we expect a press release with FEV1 data after part A of 661 trial finishes?

嗨，各位。謝謝。我是 Omar，代替 Mark。我有幾個問題，都與 CF 有關。第一，關於資訊揭露計畫——當 661 試驗的 A 部分結束後，我們是否應該預期會發布包含 FEV1 數據的新聞稿？

And also, when the third cohort in the 809 combination trials for the 400-mg BID dose finishes, should we expect FEV1 data and a press release for that?

另外，當 809 聯合試驗中每日兩次 400 毫克劑量的第三隊列結束時，我們是否應該預期會有 FEV1 數據以及一份新聞稿？

And secondly, are there any plans for an extension phase of the 400-mg BID arm beyond the two months? Thank you.

第二，對於每日兩次 400 毫克組別，是否有任何計畫把延伸期（extension phase）拉長到兩個月以上？謝謝。

Thanks, Omar. I'll take the disclosure questions, and then maybe Peter can take the -- whether there's a plan for any extension.

謝謝你，Omar。我先回答資訊揭露方面的問題，接著也許 Peter 可以回答——是否有任何延長計畫。

I'm first going to go to the 400 BID. And I appreciate as to the question there's been a number of questions regarding disclosure of this data. I refer you back to Peter's commentary just a moment ago, which is the purpose of that study, which effectively is to support the data we'd already gathered from Phase I and Phase II with our combination therapy. And it's a PK/PD modeling exercise. And that data in Cohort 3 will supplement the data we've already collected.

我先談 400 BID。我也理解這個問題，因為關於這些數據的揭露已經有不少提問。我請你回顧 Peter 剛才的評論，也就是那項研究的目的：實質上是用來支持我們在第一期與第二期、以聯合療法所蒐集到的數據。而這是一個 PK/PD 建模的工作。第三隊列（Cohort 3）的數據將補充我們已經收集的數據。

I think the key for us is the Phase III study design, which we'll be shortly discussing with regulatory authorities. And when we have a better understanding of what the protocol and design is and all the various arms and the duration of that study, we'll provide you a disclosure around the design for the Phase III.

我認為對我們而言，關鍵在於第三期研究的設計，我們很快就會與監管機關討論。當我們更清楚了解該研究的試驗計畫書與設計、所有不同的治療組別以及研究期間後，我們會就第三期的設計提供資訊揭露。

And at that point in time, in disclosing the Phase III data, we'll give you a basis for that protocol design. So, that's the answer for the Cohort 3. And I'd just point out that it is only 15 patients, and it is not powered to measure FEV.

而在那個時間點，在揭露第三期數據時，我們也會提供該試驗計畫設計的依據。所以，以上是對第三隊列的回答。我也要指出，這只有 15 位病人，且其統計設計並不足以衡量 FEV。

As far as VX-661 is concerned, that's in a combination study at this point. Bob described -- sorry, Peter described that study in his prepared remarks. It is a dose-escalating study, a monotherapy which goes to combination therapy and then escalating doses. We are in the process of running that study. And it will run into 2013. And at the point that we have completed the whole study, so it will be final data, we'll provide you a top line press release. And that would include FEV. But, it's effectively a safety and efficacy top line press release. And that will be in the first half of 2013.

至於 VX-661，目前是在一項聯合用藥研究中。Bob 描述——抱歉，是 Peter 在他事先準備的發言中描述了那項研究。這是一項劑量遞增研究，先做單藥治療，接著進入聯合療法，然後再進行劑量遞增。我們正在進行該研究。而它會持續到 2013 年。當我們完成整個研究、也就是取得最終數據時，我們會發布一則重點新聞稿。其中會包含 FEV。但基本上那會是一則安全性與有效性的重點新聞稿。時間會在 2013 年上半年。

And as to your third question, I'm going to turn it back to Peter. And that was regarding the extension.

至於你的第三個問題，我把問題交回給 Peter。那是關於延長（extension）的問題。

Yes, and with respect to the extension for the twice 400 BID, we have no intention to basically have an extension for that particular small population at this given point in time.

是的，關於 400 BID 每日兩次的延長試驗，就目前這個時間點而言，我們沒有打算針對那個特定的小族群做延長。

Okay. Great. Thank you very much.

好的。很好。非常感謝。

Our next question comes from the line of Michael Yee with RBC Capital Markets. Your line is open.

下一個問題來自 RBC Capital Markets 的 Michael Yee。請發問。

Okay, thanks. On your plan to start combination studies with 135 with the new GSK and the J&J compounds, what data do you actually need to have or present to FDA or anything to actually start dosing patients? What actually goes on in that discussion?

好的，謝謝。關於你們計畫以 135 與新的 GSK 以及 J&J 化合物啟動聯合研究，你們實際上需要具備或向 FDA 提交哪些數據，才能開始對病人給藥？那個討論實際上會進行哪些內容？

And related to that, I noticed that you said you actually need to have a drug-drug interaction with the J&J drug. But, that wasn't really mentioned with the GSK drug, so just want to understand what logistically do you need to do to actually start dosing patients and what are the steps?

另外相關地，我注意到你們提到確實需要針對 J&J 的藥物做藥物—藥物交互作用研究。但對 GSK 的藥物似乎沒有特別提到，所以我想了解，從執行面來看，要開始對病人給藥你們需要做哪些事、步驟是什麼？

So, maybe Bob will take the first question. Peter can talk about the J&J compound.

所以，也許 Bob 先回答第一個問題。Peter 可以談談 J&J 的化合物。

The drug-drug interaction stuff.

也就是藥物—藥物交互作用（DDI）的部分。

So, in terms of going forward, we have an open IND in the US. And so, it is a matter of submitting a protocol to the FDA for their review. And oftentimes, comments may come either in writing or on a brief telecom. But, we have already had some discussions with them regarding our ribavirin study and the telaprevir study. And we certainly understand what's required in order to move forward, and we're planning on doing that with the ribavirin study, which we'll be starting imminently.

就後續推進而言，我們在美國有一個開放中的 IND。因此，基本上就是向 FDA 提交一份試驗計畫書供其審查。而通常他們可能會以書面或透過簡短的電話會議提出意見。不過，我們先前已就我們的 ribavirin 研究與 telaprevir 研究與他們進行過一些討論。我們也很清楚推進所需的要求，並且計畫以 ribavirin 研究來執行，我們將在近期內啟動。

Process is really very much the same with the other two compounds. Both are under review with the FDA. There are INDs obviously for both other compounds. And so, it's a rather straightforward matter to just get the FDA to cross reference the INDs, review the data, and then have a discussion about the protocol, nothing complicated.

其他兩個化合物的流程基本上也非常相同。兩者都在 FDA 審查中。而且顯然這兩個化合物各自都有 IND。因此，這相當直接：讓 FDA 交叉引用這些 IND、審查數據，然後就試驗計畫書進行討論，沒有什麼複雜的。

Yes, so, what is going on? Maybe I just say I think there is absolutely fair discussion going on in the FDA. And it is a compound-by-compound discussion. And it's not a one-size-fits-all type of approach. I think you have to provide data. And then basically, you get treated dependent on your data and not necessarily dependent on other people's data.

是的，所以目前在進行什麼？我想我可以說，FDA 內部確實正在進行相當合理的討論。而且是逐一化合物（compound-by-compound）的討論。並不是一種一體適用（one-size-fits-all）的做法。我認為你必須提供數據。然後基本上，你會依據你的數據來被對待，而不一定是依據別人的數據。

So, I want to just say that. And then that goes with the DDI study. So, I think every compound has a different metabolism. And dependent on what the metabolism is and what the potential interaction could be in combination of two compounds, you might consider or not to do a DDI study.

我想先強調這一點。接著回到 DDI 研究。我認為每個化合物的代謝途徑都不同。而依據其代謝方式，以及兩個化合物併用時可能產生的交互作用，你可能會考慮要做或不做 DDI 研究。

And there is a difference between PIs and NS5As in general about how they get metabolized. And so, there's not the same size and the same type of approach for each and every compound. And that's the reason why we basically opted for the Janssen compound, the TMC435 to do a DDI study upfront to get the better dosage.

而一般而言，蛋白酶抑制劑（PI）與 NS5A 在代謝方式上是有差異的。因此，並不存在對每一個化合物都採用相同規模、相同類型的方法。這也是為什麼我們針對 Janssen 的化合物 TMC435，選擇先做一個 DDI 研究，以取得更合適的劑量。

Okay. Thank you. I appreciate that.

好的。謝謝。我很感謝這個說明。

Our next question comes from the line of Liisa Bayko with JMP Securities. Your line is open.

下一個問題來自 JMP Securities 的 Liisa Bayko。請發問。

Hi. I wanted to change topics to your influenza program. And I'm just looking at clinicaltrials.gov. And it says that you're going to inoculate healthy adult volunteers. First question is, who actually would enroll in the study?

嗨。我想把話題轉到你們的流感計畫。我正在看 clinicaltrials.gov。上面寫你們將對健康成人志願者進行接種（inoculate）。第一個問題是，實際上會是哪些人來參加這項研究？

And number two, actually, the more important question is, what data are you looking for to really get excited about the program? And what's the sort of the hurdle for going -- taking this program forward? Thanks.

第二個、其實更重要的問題是，你們希望看到哪些數據，才會對這個計畫真正感到興奮？以及把這個計畫往前推進的門檻大概是什麼？謝謝。

You want to do it, or we can do it like this.

你要回答嗎？或者我們可以這樣回答。

This is Bob. People volunteer for studies is all I can say. Obviously, there's some remuneration that goes on for these volunteers. But, that is just the way things work.

我是 Bob。我只能說，人們會自願參加研究。顯然，這些志願者會有一些報酬。但事情就是這樣運作的。

That was kind of a joke question. You don't really have to answer it. I just can't believe it. But, I really was more interested in sort of like the -- when we think about the endpoints, what you're looking at and what is really going to be compelling to take the program forward.

那有點像是開玩笑的問題。你其實不用真的回答。我只是覺得很難相信。但我真正更感興趣的是，例如——當我們思考終點（endpoints）時，你們在看什麼，以及什麼才會真正具有說服力、足以把這個計畫往前推進。

Right. So, what we look for is, obviously, we're looking for evidence of antiviral activity. And that's really measured by viral shedding in nasal secretions. And that can be measured either by looking for live virus or by various PCR technologies. So, we're looking first of all for antiviral activity. We're obviously looking for the safety of the compound. And we're also looking for change in -- reduction in symptomatology.

沒錯。所以，我們要找的很明顯是抗病毒活性的證據。而這主要是透過鼻腔分泌物中的病毒排出量來衡量。這可以透過檢測活病毒，或透過各種 PCR 技術來測量。因此，我們首先要看的是抗病毒活性。我們當然也在看該化合物的安全性。另外也在看症狀表現是否改變——也就是症狀是否減輕。

This is an attenuated strain of influenza. The subjects don't get that sick. But, we do -- we are able to measure shortening of the clinical illness. And so, it's really a combination of antiviral and clinical symptomatology measures that are the way one describes efficacy in these kinds of studies. And that's really what we're looking for.

這是一株減毒的流感病毒株。受試者不會病得那麼嚴重。但是，我們確實——我們能夠測量臨床病程縮短的情況。因此，在這類研究中，用來描述療效的方式，實際上是抗病毒指標與臨床症狀指標的綜合衡量。這也正是我們要看的。

Yes, Liisa, I want to just add one thing to the enrollment because you might have sort of questions whether people want to get sort of infected. There is a flu camp in the UK that's called Flu Camp. And we are basically having the study completely enrolled in those. Okay. So, I think we're basically sort of currently in the data-collecting phase. And that's the reason why we basically hope by end of year we're happy now that we can sort of analyze and then tell you sort of early next year what it is.

是的，Liisa，我想就招募再補充一點，因為你可能會有疑問：人們是否願意被「感染」。英國有一個流感營，叫做 Flu Camp。而我們基本上就是在那裡把這項研究完整招募完成。好的。所以，我認為我們目前基本上是在資料收集階段。也因此我們希望在今年年底前能夠完成分析，然後在明年年初左右告訴你結果是什麼。

And can you get a little bit more specific, like, quantitatively what kind of threshold antiviral effect, like how it will be measured and what levels you're going to be looking for, what range would be sufficient to move forward? And the same thing -- I don't know if there's a way to talk about symptomatology or shedding, nasal shedding, et cetera.

你們能不能再更具體一點，例如用量化方式說明：你們要看的抗病毒效果門檻是什麼？例如會如何測量、會看哪些水準、什麼範圍足以支持往下推進？同樣地——我不知道是否能談談症狀表現或病毒排出、鼻腔排毒等。

I mean, the purpose of this study really, first of all, is to look at safety of the compound. It's our first real longer-duration trial. And so, we're looking for safety. We're also looking for dose response because one of the goals of this trial is to help narrow down the dose range when we would ultimately conduct the study in natural influenza.

我的意思是，這項研究的目的其實首先是看該化合物的安全性。這是我們第一次真正較長期間的試驗。所以，我們在看安全性。我們也在看劑量反應，因為這個試驗的目標之一，是協助縮小劑量範圍，以便我們最終在自然感染的流感研究中進行試驗。

And I would say that, given that it's attenuated, given the characteristics of the way these studies are run, that's really kind of what we're looking for is a dose response. We're looking for as complete an antiviral response as we can get. And then we go on and do further trials.

我會說，考量到它是減毒株、以及這類研究的執行特性，我們真正要找的就是劑量反應。我們希望看到盡可能完整的抗病毒反應。然後我們再進一步做後續試驗。

All right. That's helpful. Thanks a lot.

好的。這很有幫助。非常感謝。

Thank you. Our next question comes from the line of Robin Karnauskas with Deutsche Bank. Your line is open.

謝謝。下一個問題來自德意志銀行（Deutsche Bank）的 Robin Karnauskas。您的線路已開通。

Yes, this is [Lethia] for Robin. Just a quick question. Your guidance for Q -- in the -- for INCIVEK seems to imply kind of a wide range of outcomes in Q4. But, just wondering if you could give us some color in what you're seeing around trends and Q4 in the hep C market in a little bit more detail.

是的，我是代替 Robin 的 [Lethia]。簡單問一個問題。你們對 INCIVEK 的第四季指引——在——似乎暗示第四季的結果可能有相當大的區間。但想請你們多補充一些：你們看到的趨勢是什麼？以及第四季丙肝市場的情況能否更詳細說明？

Sure. So, I'll just first of all reiterate our guidance and why we're reiterating guidance, which is, at any point through the year, we've recorded net revenues for INCIVEK of around $940 million. And our guidance that we're updating tonight or reiterating tonight is $1.1 billion to $1.25 billion.

當然。我先重申我們的指引，以及我們為什麼要重申指引：截至今年任何時間點，我們已記錄的 INCIVEK 淨營收約為 9.4 億美元。而我們今晚更新或重申的指引是 11 億到 12.5 億美元。

And when we see the current demand of our product, we are also heading into November now. We're very comfortable in reiterating that guidance. And we'll be providing you more information on trends as we go into 2013.

以我們目前看到的產品需求來看，而且我們現在也即將進入 11 月。我們非常有信心重申該指引。隨著我們進入 2013 年，我們也會提供你們更多關於趨勢的資訊。

Obviously, we're watching it closely because it impacts how we think about our business for 2013.

很明顯地，我們會密切關注，因為這會影響我們對 2013 年業務的看法。

And also, on the TMC435 trial, is that a US trial or a global trial?

另外，關於 TMC435 的試驗，那是美國試驗還是全球試驗？

It's likely that sites in the US -- a substantial number of sites in the US will be involved in that trial. The planning is still ongoing with Janssen, who are going to be running that study.

很可能會有美國的試驗中心——相當多的美國中心會參與該試驗。目前仍在與 Janssen 進行規劃，他們將負責執行這項研究。

Great. Thanks.

很好。謝謝。

Thank you. Our next question comes from the line of Brian Abrahams with Wells Fargo Securities. Your line is open.

謝謝。下一個問題來自富國證券（Wells Fargo Securities）的 Brian Abrahams。您的線路已開通。

Hi. Thanks very much for taking my question. With respect to the ongoing 661 study, I'm just wondering, what are you looking for to conclude dose escalation? Is that going to be driven more by safety or by efficacy?

嗨。非常感謝讓我提問。關於正在進行的 661 研究，我想問的是：你們要看什麼來決定結束劑量遞增？這會比較由安全性驅動，還是由療效驅動？

And should we take the official narrowing of guidance for results to come in the first half of next year to mean that you're at or near doses that you're expecting will have activity or at least exposure similar to 600 mgs of VX-809?

另外，我們是否可以把你們把結果指引正式縮小到明年上半年，解讀為你們已經到達或接近你們預期會有活性、或至少暴露量與 600 毫克 VX-809 類似的劑量？

I'll take the first part of that in terms of guidance of disclosure, Brian. Frankly, I don't know whether it's a narrowing of guidance. We anticipate the data coming in the first half of 661, as I commented earlier. It is a dose-escalation study. And maybe I'll turn it over to Bob in terms of what we're looking at as we go up in each of the doses. So, Bob, do you -- ?

Brian，我先回答你前半段，關於揭露時點的指引。坦白說，我不確定這是否算是縮小指引。如我先前評論的，我們預期 661 的資料會在明年上半年出來。這是一項劑量遞增研究。至於我們在每個劑量往上走時要看什麼，也許我把問題交給 Bob。所以，Bob，你要不要——？

Yes, I mean, normally, we're looking for a dose response for the endpoints that we're looking at, which includes sweat chloride and other measures. And the hope is that we can define the large part of the dose response curve so that we can pick doses for the next set of studies. And that's really -- that's what we do.

是的，我的意思是，一般而言，我們會針對我們關注的終點指標去看劑量反應，其中包括汗氯（sweat chloride）以及其他量測。我們希望能界定劑量反應曲線的大部分區段，這樣就能為下一階段研究選定劑量。基本上——我們就是做這件事。

I think the interesting piece here is that 661 has a different biodistribution. And so, you cannot basically collect data from 809 and basically sort of refer to it. So, you have to do your own study. The changes are here that you can come with substantially lower doses. And that is basically what we are trying to do, to have basically a low pill burden, a low dose burden. And that allows us to do better combination studies in the future with many different second generation correctors or KALYDECO or anything in the mix.

我認為這裡有趣的一點是，661 的生體分布不同。因此，你不能只是收集 809 的資料然後拿來直接類推。所以，你必須做你自己的研究。這裡的改變在於，你可以用顯著更低的劑量達成。而這基本上就是我們想做的：讓藥丸負擔低、劑量負擔低。這也讓我們未來能做更好的合併療法研究，搭配許多不同的第二代校正劑（correctors）或 KALYDECO，或任何組合中的其他藥物。

That's very helpful. Thanks. Just a quick follow up. Following the Phase II studies for the VX-135 combos, just wondering broadly speaking what types of options you might envision. Would your preference be to pursue further studies with those compounds, perhaps bring in other assets within the same classes? Where do you sort of foresee the next steps fast forwarding beyond next year?

這非常有幫助。謝謝。再快速追問一下。在 VX-135 聯合療法的第二期研究之後，想請教整體而言你們可能會設想哪些選項？你們會偏好用這些化合物繼續做後續研究，或是可能引入同一類別中的其他資產？你們如何看待明年之後、加速推進的下一步？

Yes, this is Jeff. Let me answer at a high level and then Peter and Bob can add additional color. So, as I said before, we're really pleased with where we are today because we now have high-potency and competitive assets in each of the major classes. So, obviously, our nuke, which you've seen the data on, TMC, which you've also seen a lot of data on, and the protease inhibitor class we feel is an excellent next-generation protease inhibitor.

是的，我是 Jeff。我先從較高層次回答，接著 Peter 和 Bob 可以再補充更多細節。所以，如我先前所說，我們對目前的進展非常滿意，因為我們現在在各主要類別中都擁有高效力且具競爭力的資產。因此，顯然，我們的核苷類（nuke），你們已看過其數據；TMC，你們也看過很多數據；以及蛋白酶抑制劑類別，我們認為這是一款優秀的下一代蛋白酶抑制劑。

222, our nonnuke, which also is highly potent, you've seen some already all-oral. And then the GSK NS5A, which both NS5As, as you know, look like they're going to be important components of regimens, and it's a once-a-day highly potent NS5A that's already been in humans and shown very nice viral log drops.

222，我們的非核苷類（nonnuke），同樣具有很高效力，你們也已經看過一些全口服的數據。接著是 GSK 的 NS5A，兩個 NS5A 如你們所知，看起來都將成為療程方案中的重要組成部分；而這是一款每日一次、效力很高的 NS5A，已在人體中使用並顯示出非常好的病毒量對數下降。

And so, I think we have the pieces in hand. The question now is, which regimens for which patients? We're going to try some two-drug regimens, particularly for the easy-to-treat patients. We may try some three-drug regimens. But, our strategy is to collect that data next year and, based on that data, pick regimens to go forward into pivotal trials in 2014.

因此，我認為我們已經具備了所有組件。現在的問題是：哪些病人適用哪些療程方案？我們將嘗試一些雙藥療法，特別是針對較容易治療的病人。我們也可能嘗試一些三藥療法。但我們的策略是明年蒐集這些數據，並根據數據選定要在 2014 年推進至關鍵性試驗（pivotal trials）的療程方案。

Now, each of the collaborations we signed today are nonexclusive. And so, we do have the opportunity as we go forward, if we see compounds that would have benefit to patients to do additional collaborations. But, we're pretty pleased with where we are today in terms of having all the pieces in hand to begin these studies.

另外，我們今天簽署的每一項合作都是非排他性的。因此，隨著我們往前推進，如果看到某些化合物能為病人帶來益處，我們仍有機會進行更多合作。不過，就目前而言，我們對已具備所有組件以開始這些研究感到相當滿意。

Thanks.

謝謝。

Our next question comes from the line of Matt Roden with UBS. Your line is open.

下一個問題來自 UBS 的 Matt Roden。請發問。

Hi, guys. Thanks very much for taking the questions. Thanks for letting the call to go a little bit long. I wanted to get into the KALYDECO commercial trends a little bit. The experts tell us that KALYDECO is well penetrated in the big academic centers. But, just trying to get a sense for where we are on a broader basis so we can understand what the -- where we are with the eligible segment that's not yet penetrated, what it'll take and over what timeframe do you expect to capture those patients?

嗨，各位。非常感謝讓我提問。也謝謝你們讓電話會議稍微延長一些。我想更深入了解一下 KALYDECO 的商業化趨勢。專家告訴我們，KALYDECO 在大型學術中心的滲透率很高。但我想更廣泛地了解我們目前的狀況，以便理解——也就是說，對於尚未滲透的符合資格族群，我們目前處於什麼位置、需要做什麼，以及你們預期在多長時間內能涵蓋到那些病人？

I heard you mention at the top of the call that a majority of those eligible in the US are being treated. But, can you actually give us more specific in terms of where we are and penetration into that market and how you expect to convert those patients?

我聽到你們在電話會議一開始提到，在美國符合資格者中多數已在接受治療。但你們能否更具體說明我們目前的進度、市場滲透情況，以及你們預期如何轉換那些病人？

Yes, hi. This is Stuart. I'll take that one. So, yes, you heard correctly. The vast majority of patients in the US who are eligible are already taking the product. And so, in the US, while we're expecting a handful more of products to be added into the mix, we really are at the vast majority of patients right now. And we're very pleased with that.

是的，嗨。我是 Stuart。我來回答這題。所以，是的，你聽得沒錯。在美國，符合資格的病人中絕大多數已經在使用這項產品。因此，在美國，雖然我們預期還會有少數病人陸續加入，但目前我們確實已涵蓋了絕大多數病人。我們對此非常滿意。

As Jeff said, the uptake of KALYDECO has been astonishingly quick. In my experience, it's been an incredibly impressive launch and really reflects what a great breakthrough medicine KALYDECO is.

如 Jeff 所說，KALYDECO 的採用速度快得驚人。以我的經驗來看，這是一個極其令人印象深刻的上市表現，也真正反映了 KALYDECO 作為突破性藥物的價值。

And again, as Jeff said, in the future, what we're expecting is the major inflection for KALYDECO in 2013 to come from uptake in the EU.

同樣地，如 Jeff 所說，未來我們預期 KALYDECO 在 2013 年的主要拐點將來自歐盟的採用提升。

Okay. Can you comment on gross to net? Was there any change this quarter? Just trying to get a sense for whether or not -- I mean, is 50 million really the peak run rate with the current label that you have right now in the US?

好的。你們能評論一下 gross-to-net（毛額到淨額）嗎？本季是否有任何變化？我只是想了解——我的意思是，在美國以你們目前的適應症標籤來看，5,000 萬美元是否真的是最高的穩態營收水準（peak run rate）？

Matt, thanks. I'll take that question. And I would say the gross to net is -- the discount has slightly increased through the year. As we launched, it was -- it tended to be around 8% to 9%. And right now, as we enter the fourth quarter, it's around 9% to 10%. That's really just a reflection of the patients that we're treating. And we'd anticipate that to continue into the future.

Matt，謝謝。我來回答這題。我會說 gross-to-net——折扣率在今年略有上升。剛上市時，大約在 8% 到 9% 左右。而目前進入第四季時，大約在 9% 到 10%。這其實只是我們正在治療的病人組成所反映出的結果。我們預期未來也會持續維持這樣的水準。

Yes, thanks very much.

好的，非常感謝。

Thank you. Our next question comes from the line of Terence Flynn with Goldman Sachs. Your line is open.

謝謝。下一個問題來自 Goldman Sachs 的 Terence Flynn。請發問。

Hi. Thanks for taking the question. Was just wondering if you can tell us on the KALYDECO 661 Phase II trial if there is an interim analysis. I understand you guys are going to release final data to us. But, is there an interim analysis built into that trial?

嗨。謝謝讓我提問。我想請問在 KALYDECO 661 的第二期試驗中，是否有期中分析（interim analysis）？我了解你們會向我們公布最終數據。但該試驗是否設計了期中分析？

And then the second question is, thinking about the disconnect between, I guess, FEV and sweat chloride, seeing the KALYDECO 809 trial, is there rationale to think that you'd see a similar disconnect in the KALYDECO 661 trial? Thanks.

第二個問題是，考量到我想是 FEV 與汗氯（sweat chloride）之間的脫鉤現象，在 KALYDECO 809 試驗中看到這點後，有沒有理由認為在 KALYDECO 661 試驗中也會看到類似的脫鉤？謝謝。

Terence, I'll take the disclosure question. We'd like to complete the study, VX-661 in combination with KALYDECO. That means going through the monotherapy and then the combination period for each of the escalating doses. We'd like to complete all of those ascending doses. And at that point, with final and complete data, we'll provide a top line press release. And that's why we're guiding to first half of 2013 in terms of a top line release.

Terence，我來回答資訊揭露的問題。我們希望完成 VX-661 與 KALYDECO 併用的研究。這表示要完成單藥期，然後對每個遞增劑量完成併用期。我們希望完成所有這些遞增劑量。屆時，在取得最終且完整的數據後，我們會發布一份重點摘要的新聞稿（top line press release）。因此，我們才會指引在 2013 年上半年發布 top line 結果。

So, the second question that you had -- that's Peter speaking -- is about do we anticipate a similar disconnect between sweat chloride and FEV? The answer is I don't know because that's why we're doing the study. And we will see at the end of the day what the relationship is because they have very different molecules here that penetrate differently into the body and into the tissue. So, I can't really answer that at this given point in time. That's one of the reasons why we're doing the study.

至於你第二個問題——我是 Peter——是關於我們是否預期汗氯與 FEV 之間會出現類似的脫鉤。答案是我不知道，因為這正是我們進行此研究的原因。我們會在研究結束時看到兩者之間的關係，因為這裡的分子不同，在體內與組織中的滲透方式也不同。所以在目前這個時間點，我無法真正回答。這也是我們進行此研究的原因之一。

Operator, we're now five minutes past 6.00. We'd have time for two more questions.

接線員，我們現在已經超過 6 點 5 分鐘了。我們還有時間再回答兩個問題。

Okay. Our next question comes from the line of Ying Huang with Barclays. Your line is open.

好的。下一個問題來自 Barclays 的 Ying Huang。請發問。

Hey, guys. Thanks for taking my questions as well. So, can you elaborate a little more on your position to collaborate on VX-135 with GSK's NS5A inhibitor? We know that there's a scarcity of all the nukes in the development. That's why VX-135 is very precious. But, there's no shortage of NS5A in the development right now. So, what attracts you guys in terms of the GSK's 5A program compared to, let's say, a more advanced drug like the Bristol's Daclatasvir?

各位好。也謝謝讓我提問。那麼，能否再多談一點你們對於與 GSK 的 NS5A 抑制劑在 VX-135 上合作的立場？我們知道目前在研發中的所有核苷（nukes）相當稀缺。因此 VX-135 非常珍貴。但目前在研發中的 NS5A 並不缺。所以，相較於例如更先進的藥物像是百時美施貴寶的 Daclatasvir，GSK 的 5A 計畫有哪些地方吸引你們？

And then second question is, do you guys think, between your internal studies, for example, combination with INCIVEK and ribavirin and then the TMC435 and then the GSK studies, you will have sufficient database in terms of safety to move onto a pivotal study in 2014? Thanks.

第二個問題是，你們認為在你們內部研究（例如與 INCIVEK 和利巴韋林的合併）以及 TMC435、再加上 GSK 的研究之間，你們是否會有足夠的安全性資料庫，能在 2014 年推進到關鍵性試驗？謝謝。

So, the first is about our excitement about the Glaxo 5A inhibitor. I must say, what I have seen from a preclinical package, it's really impressive what I have seen. And the clinic is really impressive. And the log drop is basically in a range that all the other 5As have. The interesting piece, though, is the metabolic profile that allows it to really be easily combined with our own molecules, which is a key criteria when you basically do combination regimens. And so, I'm really excited about that molecule.

好，第一個是關於我們為何對葛蘭素史克（Glaxo）的 5A 抑制劑感到興奮。我必須說，我從臨床前資料包看到的內容非常令人印象深刻。而臨床表現也非常令人印象深刻。其 log 降幅基本上落在其他所有 5A 類藥物相同的範圍內。不過，有趣之處在於它的代謝特性，使其能很容易與我們自家的分子併用；在設計聯合療法時，這是一項關鍵標準。因此，我對那個分子非常興奮。

And then I think it is far enough advanced. And it is a once a day. That is the other piece. It offers the opportunity at the end of the day to come out with a once-a-day regimen.

另外，我認為它的研發進度也已經足夠成熟。而且它是每日一次。這是另一個重點。最終它提供了推出每日一次療程方案的機會。

And given the 60-milligram dose that you basically have seen in the regimen, what it also allows is -- and that's why I'm really excited about it -- to do coformulation studies and have maybe a once-a-day pill with whatever regimen that we have at the end of the day in mind.

再者，考量你們在該療程中看到的 60 毫克劑量，它也讓我們——這也是我非常興奮的原因——能進行共製劑（coformulation）研究，或許最終能做出一顆每日一次的藥丸，搭配我們最後所構想的任何療程組合。

This is really fantastic. And so, this is the excitement about this. And the other question was about do we have enough data by doing all those Phase II studies to enter into Phase III in 2014. And the answer is absolutely yes because we will have a [polling] concept from a safety point of view with everybody that has received 135. And then for the regimen that we pick, we have enough data to move forward in 2014 from an efficacy point of view.

這真的非常棒。所以，這就是我們興奮的原因。另一個問題是：做完所有這些第二期研究後，我們是否有足夠資料在 2014 年進入第三期。答案絕對是肯定的，因為從安全性的角度，我們會把所有接受過 135 的受試者資料彙整成一個整體的安全性概念（[polling]）。然後，就我們選定的療程而言，從療效角度我們也有足夠資料在 2014 年往前推進。

Thank you.

謝謝。

And our -- I'm sorry?

還有我們——抱歉？

And our last question, please?

請問我們最後一個問題？

Our final question comes from the line of David Friedman with Morgan Stanley. Your line is open.

我們最後一個問題來自摩根士丹利（Morgan Stanley）的 David Friedman。請開麥。

Hi. Thanks. Just two quick questions. The first is, in the ivacaftor, the minimal [zero moderate] CFTR residual function, how are you defining residual exocrine pancreatic function?

你好。謝謝。兩個很快的問題。第一個是，在 ivacaftor 的研究中，針對 CFTR 殘餘功能最低（[zero moderate]）的族群，你們如何定義殘餘的胰臟外分泌功能？

And then just the second quickly is, do you have a sense as to how well efficacy in an experimental flu model correlates with the efficacy in a real sort of real-life flu situation? Thanks.

第二個很快的問題是，你們是否了解在實驗性流感模型中的療效，與真實生活情境下流感療效之間的相關性有多高？謝謝。

Right. So, just for the second question, yes, it's an artificial system. And the goal is really to get some preliminary read on antiviral activity and more importantly to narrow the dose range. One can get a sense of the dose range to be studied in subsequent natural influenza. And that really is the goal of the study.

好的。先回答第二個問題：是的，那是一個人工系統。其目標主要是先初步讀取抗病毒活性，更重要的是縮小劑量範圍。我們可以藉此掌握在後續自然感染流感研究中應該評估的劑量範圍。這就是該研究真正的目的。

I can add maybe one thing to that. That is maybe different for 787 compared to Tamiflu, there was a possibility to study viral clearance because that's the mechanism of action I think that Tamiflu doesn't provide. And so, we will also look into that.

我可以再補充一點。也許相較於克流感（Tamiflu），787 有一個不同之處：我們有機會研究病毒清除（viral clearance），因為我認為這是 Tamiflu 的作用機轉所無法提供的。因此，我們也會去看這一點。

And that is basically the time factor to -- we do know with the challenge study what day you have infected. And you can basically go stepwards back and say what is the clearance after one day, two days, three days, which is a really important line to basically add value to the molecule. So, that's the other piece that we have to sort of look into.

而這基本上涉及時間因素——在挑戰試驗（challenge study）中，我們知道你是哪一天被感染的。你就可以逐步回推並說明：一天後、兩天後、三天後的清除情況如何；這是一條非常重要的資訊線索，可用來為該分子增加價值。所以，這也是我們需要進一步檢視的另一部分。

And in terms of the ivacaftor question, it's really primarily based on functional results. Those people who are dependent on pancreatic enzyme replacement are considered to be insufficient. And those who can manage without them are like -- are generally pancreatic sufficient. And that's how we define it.

至於 ivacaftor 的問題，我們主要是依功能性結果來判定。需要依賴胰臟酵素替代治療的人，被視為胰臟功能不全。而不需要使用、也能自行管理的人——一般被視為胰臟功能充足。我們就是這樣定義的。

Okay. Thank you.

好的。謝謝。

Okay. Thanks, everybody, for joining us tonight. We are in our offices if you didn't get to ask a question or if you have a further follow up. And with that, we look forward to seeing many of you at the AASLD Conference, which starts in Boston at the end of next week. Thank you.

好的。謝謝各位今晚加入我們。如果你沒有來得及提問，或是還有後續追問，我們都在辦公室。此外，我們也期待在下週末於波士頓開始的 AASLD 會議上見到各位。謝謝。

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a wonderful day.

各位女士先生，感謝參與今天的會議。本次議程到此結束，您可以掛線離開。祝各位有美好的一天。