福泰製藥 (VRTX) 2013 Q3 法說會逐字稿

Good day, ladies and gentlemen. Welcome to the Vertex Pharmaceuticals Incorporated third-quarter 2013 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.

各位女士、先生，大家好。歡迎參加 Vertex Pharmaceuticals Incorporated 2013 年第三季財務業績電話會議。此時所有與會者將以只聽模式參與。稍後我們將進行問答環節，屆時將提供相關指示。

(Operator Instructions)

(接線員指示)

As a reminder this conference call is being recorded.

提醒各位，本次電話會議將被錄音。

I would now like to introduce your host for today's conference, Michael Partridge, Vice President of Investor Relations. You may begin.

現在我想介紹今天會議的主持人：投資人關係副總裁 Michael Partridge。您可以開始了。

Thank you, operator.

謝謝，接線員。

This morning, we announced our third-quarter financial results, and in conjunction with that, the decision to reduce our workforce, and to focus on our investment on future opportunities in cystic fibrosis and other key R&D programs. On the call today, Jeff Leiden, Vertex's Chairman and CEO, will comment on these announcements in the context of Vertex's long term strategy. Then Bob Kauffman, Vertex's Chief Medical Officer, will review Vertex's recent clinical progress in the areas of cystic fibrosis and also review the current status of our hepatitis C and JAK3 development programs. Following that, Ian Smith, Vertex's CFO, will review financial results and provide some perspective on the financial impact of today's announcement on Vertex's profile going forward.

今天上午，我們公布了第三季財務結果，並同時宣布決定縮減人力，將投資重點聚焦於囊性纖維化及其他關鍵研發（R&D）計畫的未來機會。今天的電話會議中，Vertex 董事長兼執行長 Jeff Leiden 將就這些公告在 Vertex 長期策略的脈絡下發表評論。接著，Vertex 首席醫療官 Bob Kauffman 將回顧 Vertex 近期在囊性纖維化領域的臨床進展，並說明我們丙型肝炎與 JAK3 開發計畫的現況。之後，Vertex 財務長 Ian Smith 將回顧財務結果，並就今日公告對 Vertex 未來財務概況的影響提供一些觀點。

Please note that Stuart Arbuckle and Peter Mueller are not available to be on the call this morning. They are communicating with their teams regarding the reduction in workforce announced today. It is our intention to conclude today's call before 9.30 AM. After the call we will be available in our offices for follow-up.

請注意，Stuart Arbuckle 與 Peter Mueller 今天上午無法參與本次電話會議。他們正在就今日宣布的人力縮減與其團隊進行溝通。我們的目標是在上午 9:30 前結束今天的電話會議。會後我們將在辦公室提供後續追蹤。

Before we begin I'll note that information discussed on this conference call includes forward-looking statements, which are subject to risks and uncertainties. These risks and uncertainties are discussed in detail in our 10-K and 10-Q reports filed with the Securities and Exchange Commission, and also in the press release announcing our financial results this morning. These statements, including without limitation, those regarding the commercial performance of INCIVEK and KALYDECO, our development plans and expectations, and our guidance are based on Management's current assumptions. These statements are subject to risks and uncertainties that could cause actual result outcomes and events to differ materially.

在開始之前，我要提醒各位，本次電話會議所討論的資訊包含前瞻性陳述，並受風險與不確定性影響。這些風險與不確定性已在我們向美國證券交易委員會（SEC）提交的 10-K 與 10-Q 報告中詳細說明，亦載於今天上午公布財務結果的新聞稿中。這些陳述（包括但不限於）關於 INCIVEK 與 KALYDECO 的商業表現、我們的開發計畫與預期，以及我們的財測指引，均基於管理層目前的假設。這些陳述受風險與不確定性影響，可能導致實際結果、成果與事件與所述內容出現重大差異。

GAAP and non-GAAP financial measures will be discussed on this call. Information regarding our use of these measures and a reconciliation of GAAP to non-GAAP is available in our third-quarter 2013 financial press release and is described on slide 4 of this morning's website.

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 GAAP 與非 GAAP 之間的調節表，已載於我們 2013 年第三季財務新聞稿中，並於今天上午網站簡報的第 4 頁加以說明。

I'll now turn it over to Jeff.

接下來我把時間交給 Jeff。

Thank you, Michael, and good morning.

謝謝你，Michael，大家早安。

Given the nature of today's announcements, I know we are joined by a significant number of Vertex employees, members of the media, and other interested parties, as well as many investors and analysts. I'd like to thank all of you for joining the call.

鑑於今天公告的性質，我知道有相當多的 Vertex 員工、媒體朋友及其他關注人士，以及許多投資人與分析師一同參與本次電話會議。感謝各位撥冗加入。

Today, we made two announcements. The first was to announce a reduction in workforce related to INCIVEK, and the resulting focus of investment into our opportunities in cystic fibrosis and our research in early development programs, including all oral regimens for hepatitis C. This includes the elimination of 370 positions. We made this decision in response to the continued and rapid decline in hepatitis C treatment rates, which resulted in the reduced use of our marketed therapy, INCIVEK. The overall reduction in hepatitis C treatment has occurred as physicians and patients anticipate the arrival of new treatment regimens.

今天我們發布了兩項公告。第一項是宣布與 INCIVEK 相關的人力縮減，並將投資重點轉向囊性纖維化的機會，以及我們早期研發計畫的研究（包括丙型肝炎的全口服療法方案）。此舉包含裁撤 370 個職位。我們做出此決定，是因為丙型肝炎治療率持續且快速下滑，導致我們已上市療法 INCIVEK 的使用量降低。整體丙型肝炎治療量的下降，源於醫師與病患預期新的治療方案即將到來。

We reached a point where our level of investment and support for INCIVEK was beyond what we believe is necessary to support future physician and patient demand. The groups most impacted by this decision are those related to the promotion and development of INCIVEK. Related G&A infrastructure has also been reduced. This announcement today represents perhaps the most difficult choice for a company to make, and we did not make this decision lightly. Vertex is a very special place, the creativity, passion and dedication of employees define us as a Company. The hepatitis C market, however has changed very rapidly. Reduction in workforce is difficult but it's the right thing for our business, particularly in light of the significant potential we have for future growth.

我們已達到一個程度：對 INCIVEK 的投資與支援水準，超出我們認為支撐未來醫師與病患需求所必需的範圍。受此決定影響最大的是與 INCIVEK 推廣與開發相關的團隊。相關的一般與行政（G&A）基礎架構也已縮減。今天的公告或許是公司最艱難的抉擇之一，我們並非輕率做出此決定。Vertex 是一個非常特別的地方，員工的創意、熱情與投入定義了我們這家公司。然而，丙型肝炎市場變化非常迅速。縮減人力雖然艱難，但對我們的業務而言是正確之舉，尤其考量到我們未來成長的重大潛力。

Going forward our investment in our people are focused on two key areas -- one our CF programs; and two our earlier stage research and development programs, including VX-135 as part of all oral regimens for hepatitis C. INCIVEK was and still is a breakthrough medicine. It transformed the treatment of genotype one hepatitis C patients by doubling cure rates in half the time. Since launch in 2011, more than 100,000 patients have been treated worldwide with this medicine. INCIVEK has transformed our Company as well, bringing in more than $2.8 billion in revenues and royalties since launch and creating a foundation from which we can execute a broad strategy to drive sustained growth. We're continuing to make significant progress against this strategy, which we discussed with you earlier this year, and I'd like to spend the next few minutes reviewing our progress with you.

展望未來，我們對人才的投資將聚焦於兩個關鍵領域——第一是我們的囊性纖維化（CF）計畫；第二是我們較早期的研究與開發計畫，包括將 VX-135 納入丙型肝炎全口服療法方案的一部分。INCIVEK 曾經、且至今仍是一款突破性藥物。它將基因型 1 丙型肝炎患者的治療徹底改變，在一半時間內將治癒率提高一倍。自 2011 年上市以來，全球已有超過 100,000 名患者使用此藥物接受治療。INCIVEK 也改變了我們公司，自上市以來帶來超過 28 億美元的營收與權利金，並奠定基礎，使我們能執行廣泛策略以推動持續成長。我們持續在此策略上取得顯著進展；我們今年稍早已與各位討論過該策略，接下來幾分鐘我想與各位回顧我們的進展。

The first part of the strategy is prioritizing our development investment to advance our cystic fibrosis pipeline. Two weeks ago at the NACF conference we told you about our progress towards expanding the number of CF patients we can treat and maximizing the clinical benefit we can achieve with our transformative CF medicines. We're on track to get key data later in 2013 and throughout 2014.

策略的第一部分，是優先配置我們的開發投資，以推進囊性纖維化產品線。兩週前在 NACF 會議上，我們向各位說明了我們在擴大可治療的 CF 患者人數，以及透過具變革性的 CF 藥物最大化臨床效益方面的進展。我們正按計畫在 2013 年稍晚以及 2014 年全年取得關鍵數據。

The second part of the strategy is to focus our research and early development efforts on innovative medicines for serious diseases. In hepatitis C, we continue to pursue a potential opportunity to participate in the future market of all oral regimens with development of VX-135, our nucleotide polymerase inhibitor. We remain committed to innovation, and I expect you will hear more about some of our emerging early stage programs in 2014. Although it is still early, areas of significant progress include novel approaches in oncology, next generation correctors for CF, and small molecule approaches for progressive multiple sclerosis.

策略的第二部分，是將研究與早期開發的努力聚焦於針對嚴重疾病的創新藥物。在丙型肝炎方面，我們持續透過開發核苷酸類聚合酶抑制劑 VX-135，尋求在未來全口服療法市場中參與的潛在機會。我們仍致力於創新，我預期各位將在 2014 年聽到更多關於我們部分新興早期計畫的消息。雖然仍屬早期，但已有顯著進展的領域包括：腫瘤學的新方法、CF 的下一代校正劑（correctors），以及針對進行性多發性硬化症的小分子策略。

As discussed previously, we also made a decision to seek a partner to advance global development of our JAK3 inhibitor, VX-509. We recently obtained positive 12 week results from a Phase 2b study of VX-509 which will be presented as a late breaker at the ACR conference in San Diego later today. We're committed to pursuing a potential collaboration for further development of VX-509.

如先前所述，我們也決定尋求合作夥伴，以推進我們 JAK3 抑制劑 VX-509 的全球開發。我們近期取得 VX-509 第 2b 期研究的正向 12 週結果，並將於今天稍晚在聖地牙哥舉行的 ACR 會議上以 late breaker 形式發表。我們致力於為 VX-509 的進一步開發尋求潛在合作。

The third part of our strategy is to maintain our financial strength. This will support our continued investment to drive the creation of new medicines. We finished the third quarter with more than $1.4 billion in cash, cash equivalents and marketable securities. In summary, we are focusing our business towards cystic fibrosis and earlier stage pipeline programs. We're well positioned as we move into 2014. Ian will describe the financial implications in more detail during his remarks.

策略的第三部分，是維持我們的財務實力。這將支持我們持續投資，以推動新藥的創製。第三季結束時，我們持有超過 14 億美元的現金、約當現金及有價證券。總結而言，我們正將業務重心聚焦於囊性纖維化以及較早期的產品線計畫。在邁入 2014 年之際，我們已具備良好定位。Ian 將在其發言中更詳細說明財務層面的影響。

I'd like to conclude by thanking and recognizing the many colleagues who have contributed to the success of INCIVEK and the success of Vertex. I will be meeting with Vertex employees today and tomorrow and I'll tell you what I will tell them -- the Management team and I are deeply grateful for everything they have done and continue to do to transform lives. Vertex remains a Company dedicated to the creation of transformative medicines. KALYDECO and INCIVEK have benefited so many patients and there is much more that we can do to bring innovative medicines to the people who need them.

我想在結語時，感謝並表揚許多同仁，他們為 INCIVEK 的成功以及 Vertex 的成功做出了貢獻。我今天和明天將與 Vertex 員工會面，我會告訴他們我也要在此告訴各位的話——管理團隊和我對他們為改變生命所做的一切，以及持續所做的一切，深表感激。Vertex 仍是一家致力於創造具變革性藥物的公司。KALYDECO 與 INCIVEK 已讓許多病患受益，而我們還能做得更多，將創新藥物帶給有需要的人。

Thank you. I'll now turn it over to Bob.

謝謝。我現在把時間交給 Bob。

Thanks, Jeff, and good morning.

謝謝你，Jeff，大家早安。

My remarks will focus on three important clinical areas for the Company. First, I'll recap the updates we gave on our CF development pipeline at the North American Cystic Fibrosis Conference earlier this month. Then, I will review the current status of our nucleotide polymerase inhibitor VX-135. Finally, I will review some of the highlights of the VX-509 RA data that are being presented today at ACR.

我的發言將聚焦於公司三個重要的臨床領域。首先，我會回顧我們本月稍早在北美囊性纖維化大會上所提供的 CF 研發管線更新。接著，我將檢視我們核苷酸聚合酶抑制劑 VX-135 的目前進展狀態。最後，我會回顧今日在 ACR 發表的 VX-509 類風濕性關節炎（RA）數據的一些重點。

Beginning with cystic fibrosis. We presented a comprehensive update in Salt Lake City two weeks ago during the North American Cystic Fibrosis Conference. I will briefly summarize the main points here. First, key clinical data to help understand the full potential of ivacaftor monotherapy is expected to be available in the next eight months. The key studies and anticipated timing of data for ivacaftor monotherapy are shown on slide 6 on the webcast. These include Phase 3 studies in the other gating mutations and R117h populations, as well as a study in children ages two through five with gating mutations, and a proof of concept study in patients with residual function. If successful, we believe ivacaftor monotherapy has the potential to reach more than 7,000 people with CF.

先從囊性纖維化談起。兩週前我們在鹽湖城舉行的北美囊性纖維化大會上，發表了全面性的更新。我將在此簡要總結重點。第一，預期在未來八個月內可取得關鍵臨床數據，以協助了解 ivacaftor 單藥治療的完整潛力。ivacaftor 單藥治療的關鍵研究與預期數據時程，已顯示於網路直播的第 6 張投影片。這些研究包括：其他閘門（gating）突變與 R117h 族群的第 3 期研究、針對 2 至 5 歲且具有閘門突變兒童的研究，以及針對殘餘功能患者的概念驗證研究。若能成功，我們相信 ivacaftor 單藥治療有潛力惠及超過 7,000 名 CF 患者。

Second, we have completed enrollment in our Traffic and Transport Phase 3 studies evaluating fixed dose combinations of lumacaftor, otherwise known as VX-809 and ivacaftor in F508del homozygous patients ages 12 and older. We are evaluating multiple endpoints in Phase 3 including our primary end point of lung function as measured by relative change from baseline in FEV1, and secondary endpoints including change in weight, rate of pulmonary exacerbations and change in quality of life as measured by the CFQR. If successful with the combination of lumacaftor and ivacaftor in F508del homozygous patients, we may expand the treatment population by another 28,000 patients. We expect to have data from these studies in mid 2014.

第二，我們已完成 Traffic 與 Transport 第 3 期研究的收案，該研究評估 lumacaftor（亦稱 VX-809）與 ivacaftor 的固定劑量複方，用於 12 歲以上、F508del 同型合子患者。在第 3 期研究中，我們評估多項終點，包括主要終點：以 FEV1 基線相對變化衡量的肺功能；以及次要終點：體重變化、肺部惡化發生率，以及以 CFQR 衡量的生活品質變化。若 lumacaftor 與 ivacaftor 的組合在 F508del 同型合子患者中成功，我們可能將治療族群再擴大約 28,000 名患者。我們預期在 2014 年年中取得這些研究的數據。

Third, VX-661. For VX-661 we see two principal potential roles. The first role representing our primary strategy is as a first generation corrector as part of a triple combination that includes a next generation corrector and ivacaftor to potentially create a combination medicine for F508del heterozygous patients that may also enhance benefits in the F508del homozygous population. To further this strategy, we plan to advance VX-661 into a 12 week Phase 2b study in combination with ivacaftor in F508del homozygous patients. This study is designed to provide safety and efficacy data for VX-661 and ivacaftor, and we expect to initiate this study in the first quarter of next year following approval of the study protocol by regulatory authorities.

第三，VX-661。對於 VX-661，我們看到兩個主要的潛在角色。第一個角色、也是我們的主要策略，是作為第一代校正劑（corrector），納入三合一組合療法：包含下一代校正劑與 ivacaftor，以期為 F508del 異型合子患者打造一種組合藥物，並可能在 F508del 同型合子族群中提升療效。為推進此策略，我們計畫將 VX-661 推進至一項為期 12 週的第 2b 期研究，與 ivacaftor 併用於 F508del 同型合子患者。此研究旨在提供 VX-661 與 ivacaftor 的安全性與有效性數據；在監管機關核准研究方案後，我們預期於明年第一季啟動該研究。

In addition, VX-661 could serve to enhance efficacy in an F508del heterozygous population that is known to respond to KALYDECO. For example, in patients with G551D on one allele and F508del on the other allele by correcting the F508del CFTR protein produced in these cells which can then be potentiated by KALYDECO. We have now begun enrolling a four week proof of concept study evaluating VX-661 and ivacaftor in patients with both the G551D and F508del mutations. We anticipate data from both of these VX-661 studies in 2014.

此外，VX-661 也可用於提升已知會對 KALYDECO 有反應的 F508del 異型合子族群之療效。例如，在一個等位基因為 G551D、另一個等位基因為 F508del 的患者中，透過校正這些細胞所產生的 F508del CFTR 蛋白，之後可再由 KALYDECO 進一步增效（potentiate）。我們目前已開始收案一項為期四週的概念驗證研究，評估 VX-661 與 ivacaftor 併用於同時具有 G551D 與 F508del 突變的患者。我們預期在 2014 年取得這兩項 VX-661 研究的數據。

Now on to hepatitis C. Our goal is to develop VX-135 as part of a potential all oral 12 week or less pangenotypic regimen with high viral cure rates. We have conducted two studies of VX-135 with Ribavirin, principally to evaluate the safety of VX-135 over the course of 12 weeks. Data from a 20 patient study conducted in Moldova is being presented at ASLD. VX-135 was well tolerated in this study and we are reporting an SVR12 rate of 10% and 50% respectively in the 100 and 200-milligram groups in this study. Additionally, in the US study of 10 patients receiving the 100-milligram dose of VX-135, we are reporting an SVR4 rate of 10%.

接著談丙型肝炎。我們的目標是將 VX-135 開發為一種潛在的全口服、療程 12 週或更短、具泛基因型（pangenotypic）且病毒治癒率高的治療方案之一部分。我們已進行兩項 VX-135 與 Ribavirin 併用的研究，主要用以評估 VX-135 在 12 週療程中的安全性。一項在摩爾多瓦進行、納入 20 名患者的研究數據，正在 ASLD 發表。在該研究中 VX-135 耐受性良好；我們報告在 100 毫克與 200 毫克組別的 SVR12 率分別為 10% 與 50%。此外，在美國一項 10 名患者接受 100 毫克 VX-135 劑量的研究中，我們報告 SVR4 率為 10%。

A 20 patient study of VX-135 and Daclatasvir, an NS5A inhibitor from Bristol Myers Squibb is ongoing in New Zealand. We expect safety and efficacy data from this study in the first quarter of 2014. Our plan is to analyze and discuss the data with regulators and our partner to determine the next steps. We have a complete DDI study of VX-135 and Simeprevir, otherwise known as TMC435, and we are discussing with J&J the design of potential additional studies for this combination. VX-135 is on partial clinical hold in the US. Before finalizing a response to the FDA on the hold, we have decided to include 12 week safety and SVR data from the current VX-135 and Daclatasvir study as part of our submission.

一項納入 20 名患者、評估 VX-135 與 Daclatasvir（百時美施貴寶的 NS5A 抑制劑）併用的研究，正在紐西蘭進行中。我們預期在 2014 年第一季取得該研究的安全性與有效性數據。我們的計畫是分析數據，並與監管機關及合作夥伴討論，以決定下一步。我們已完成 VX-135 與 Simeprevir（亦稱 TMC435）的完整 DDI（藥物交互作用）研究，並正與 J&J 討論此組合可能進一步研究的設計。VX-135 在美國目前處於部分臨床暫停（partial clinical hold）狀態。在向 FDA 最終提交對該暫停措施的回覆之前，我們決定將目前 VX-135 與 Daclatasvir 研究的 12 週安全性與 SVR 數據一併納入提交資料。

Lastly an update on our JAK3 inhibitor VX-509. Later today 12 week data from a 350 patient, 24 week Phase 2b Study of VX-509, dosed once and twice daily in combination with methotrexate in patients with rheumatoid arthritis, is being presented as an oral late breaker at the American College of Rheumatology meeting. We have already summarized the key 12 week results in a press release on October 18 when the abstract was published online. In the study response to therapy was rapid. All VX-509 dose arms had statistically significant ACR20 improvements over placebo by week one.

最後更新我們的 JAK3 抑制劑 VX-509。今天稍晚，在美國風濕病學會（American College of Rheumatology）年會上，將以口頭「最新突破」（late breaker）形式發表 VX-509 的 12 週數據；該研究為一項納入 350 名患者、為期 24 週的第 2b 期研究，於類風濕性關節炎患者中，VX-509 每日一次或每日兩次給藥，並與 methotrexate 併用。我們已在 10 月 18 日（摘要於線上公布時）透過新聞稿總結了 12 週的關鍵結果。在該研究中，對治療的反應很快。所有 VX-509 劑量組在第 1 週時，ACR20 的改善相較安慰劑皆達統計顯著。

A further comment I will make on these data is that the ACR50 and 70 rates in patients treated with VX-509 were significantly greater compared to placebo at the 12 week evaluation point and still appear to be increasing. We await the week 24 analysis of these efficacy and safety endpoints. These results further validate JAK3 as a potentially valuable mechanism to treat autoimmune and inflammatory diseases.

我對這些數據還要補充一點：在 12 週評估時間點，接受 VX-509 治療的患者其 ACR50 與 ACR70 比例相較安慰劑顯著更高，而且看起來仍在上升。我們正等待第 24 週對這些有效性與安全性終點的分析。這些結果進一步驗證 JAK3 作為治療自體免疫與發炎性疾病的一種可能有價值的機制。

With that, I'll turn it over to Ian.

接下來，我把時間交給 Ian。

Thank you, Bob.

謝謝你，Bob。

I'll start with today's announcement to reduce our workforce and focus our investment, and how such actions affects the Company financially as we enter 2014. I'll then provide direction on our anticipated financial profile for 2014 and discuss our third-quarter financial results. While there are many strong financial aspects to our business, in particular our current cash position and our growing revenues from KALYDECO, the decline in the hepatitis C treatment rates has occurred at a rapid pace and this has adversely affected our near term revenue outlook. We have therefore chosen to restructure our business. Our developments in commercial investment will be focused on multiple opportunities in cystic fibrosis, which have the potential to drive significant revenue growth in the near term, and also focused our most promising early stage research and development programs, including development of all oral regimens for hepatitis C.

我先從今天宣布將縮減人力並聚焦投資談起，以及在我們邁入2014年之際，這些行動將如何在財務上影響公司。接著我將就我們對2014年預期的財務輪廓提供指引，並討論第三季的財務結果。雖然我們的業務有許多強勁的財務面向，特別是目前的現金部位以及來自KALYDECO日益成長的營收，但丙型肝炎治療率的下滑發生得非常迅速，並已對我們短期的營收展望造成不利影響。因此，我們選擇對業務進行重整。我們在商業化投資上的布局將聚焦於囊性纖維化的多項機會，這些機會有望在短期內帶動顯著的營收成長，同時也將資源集中於最具前景的早期研發計畫，包括開發丙型肝炎的全口服療程。

We've also adjusted our infrastructures for a G&A investment to reflect the updated needs of our business. These actions reduce our headcount by 370 people or approximately 15% of our workforce, and also include a reduction in other spending, principally in those areas that support INCIVEK. We expect to incur a total restructuring charge of approximately $35 million to $45 million in 2013, including a restructuring charge of approximately $11 million in the third quarter of 2013.

我們也已調整一般與行政（G&A）相關的基礎架構投資，以反映業務更新後的需求。這些行動將使我們的人力減少370人，約占員工總數的15%，並且也包含其他支出的縮減，主要是在支援INCIVEK的領域。我們預期2013年將認列約3,500萬至4,500萬美元的重整費用，其中包括2013年第三季約1,100萬美元的重整費用。

Importantly, these actions align our organization and our financial investment with the growth opportunities we see for our future. With clinical success in KALYDECO label expansion studies, success in addressing F508del homozygous patients with a combination therapy, and potential to further expand the number of CF patients we may treat, we have the possibility of emerging in 2015 as a high growth, high operating margin business with significant cash flow and earnings. We intend to continue to manage our business in this way while continuing to invest in product creation for the future.

重要的是，這些行動使我們的組織與財務投資能與我們所看到的未來成長機會一致。若KALYDECO適應症擴增研究取得臨床成功、以合併療法成功涵蓋F508del同型合子患者，並且有機會進一步擴大可治療的CF患者人數，我們有可能在2015年成為一個高成長、高營業利益率的企業，並具備可觀的現金流與獲利。我們打算以此方式持續管理業務，同時也持續投資於未來的產品創新。

I'd now like to provide some specific commentary on our financial profile as we head into 2014. First, from a balance sheet perspective. We finished the third quarter with more than $1.4 billion in cash, cash equivalents and marketable securities and we expect to complete 2013 and enter 2014 with $1.3 billion in cash, cash equivalents and marketable securities. This cash position is a strong starting point for 2014 and along with our growing CF revenues can fund 2014, a period when we receive important clinical data that sets the potential product revenue growth for the future.

接下來我想就我們邁入2014年的財務輪廓提供一些具體說明。首先，從資產負債表的角度。我們在第三季結束時持有超過14億美元的現金、約當現金與有價證券，並預期完成2013年並進入2014年時，將持有13億美元的現金、約當現金與有價證券。這樣的現金部位為2014年提供了強而有力的起點，並可搭配我們成長中的CF營收來支應2014年——在這段期間我們將取得重要的臨床數據，為未來潛在的產品營收成長奠定基礎。

Next, from an operating perspective, we expect 2014 total non-GAAP OpEx to be approximately $150 million to $200 million lower than the forecast of approximately $1.1 billion for 2013. The lower OpEx in 2014 is the result of reductions in our workforce and the realignment of our investment. More specifically, we see one, a $60 million to $70 million reduction in payroll and related costs. Two, a reduction of $30 million to $50 million in commercial and other expenses, primarily those to support hepatitis C sales and marketing. Three, a net reduction in R&D of approximately $35 million to $50 million which reflects INCIVEK, VX-509 and other development costs coming down. This is netted against an expected increased investment in cystic fibrosis. And four, a reduction of $25 million to $30 million in G&A costs and expenses.

其次，從營運角度來看，我們預期2014年非GAAP總營運費用（OpEx）將較2013年約11億美元的預測低約1.5億至2億美元。2014年較低的OpEx來自於人力縮減以及投資重新配置。更具體而言，我們看到：第一，薪資及相關成本將減少6,000萬至7,000萬美元。第二，商業化及其他費用將減少3,000萬至5,000萬美元，主要是支援丙型肝炎銷售與行銷的費用。第三，研發（R&D）淨減少約3,500萬至5,000萬美元，反映INCIVEK、VX-509及其他開發成本下降。此數字已與我們預期在囊性纖維化方面增加的投資相互抵銷後計算。第四，一般與行政（G&A）成本與費用將減少2,500萬至3,000萬美元。

We continue to analyze and plan our business and will provide a further update in early 2014. I will just make a quick comment that we expect research investment to remain relatively consistent between 2013 and 2014. We believe this level of ongoing operating expense provides financial leverage in our business as we move beyond 2014 with the potential revenue growth in cystic fibrosis.

我們將持續分析與規劃業務，並會在2014年初提供進一步更新。我只快速補充一點：我們預期2013年與2014年的研究投資將大致維持相對一致。我們相信，這樣的持續營運費用水準，將在我們跨越2014年後、隨著囊性纖維化潛在營收成長而為業務帶來財務槓桿。

Now turning to the third-quarter 2013 results. Total revenues were $222 million. Our non-GAAP operating expenses, which exclude cost of product revenues and other charges, were $276 million for a non-GAAP loss of $74 million or $0.32 per share.

現在轉到2013年第三季的結果。總營收為2.22億美元。我們的非GAAP營運費用（不含產品營收成本及其他費用）為2.76億美元，因此非GAAP虧損為7,400萬美元，或每股0.32美元。

Now for the more detailed results. In the third quarter, total KALYDECO revenues were $101 million, reflecting the fact that we are treating nearly all G551D patients in the US and the EU. With the sale to date in 2013 and the visibility we have into the fourth-quarter revenues, we have increased our 2013 KALYDECO net revenue guidance to between $360 million and $365 million from a previous range of $345 million to $360 million. As we have stated previously, we see the potential for KALYDECO growth in 2014 based on the following. Achieving reimbursement for G551D patients in Australia and Canada. And two, expansion of KALYDECO label into additional populations.

接著說明更詳細的結果。第三季KALYDECO總營收為1.01億美元，反映我們在美國與歐盟幾乎已治療所有G551D患者。基於2013年至今的銷售情況以及我們對第四季營收的能見度，我們已將2013年KALYDECO淨營收指引由先前的3.45億至3.60億美元，上調至3.60億至3.65億美元。如同先前所述，我們認為KALYDECO在2014年仍有成長潛力，基於以下因素。取得澳洲與加拿大G551D患者的給付核准。第二，將KALYDECO適應症標籤擴展至更多族群。

INCIVEK revenues in the third quarter were $86 million. This decrease in INCIVEK revenues compared to the second quarter stems from a smaller number of patients entering treatment as the next wave of treatment regimens is anticipated, as well as a reduction in channel inventory and lower realized revenue per unit sold as the mix shifts to government payers. INCIVEK royalties were $21 million compared to $44 million in the second quarter, driven by both patient warehousing and seasonal treatments -- seasonal changes in treatments. Finally, collaborative and other revenues in the third quarter were $14 million. Based on the sharper than anticipated decline in hepatitis C product and royalty revenues, we are revising our total 2013 revenue guidance down by approximately $100 million to $1 billion to $1.05 billion.

第三季INCIVEK營收為8,600萬美元。與第二季相比，INCIVEK營收下滑的原因在於：隨著市場預期下一波治療方案到來，進入治療的患者人數減少；同時通路庫存下降；以及因銷售組合轉向政府給付方，導致每單位實現的營收降低。INCIVEK權利金為2,100萬美元，較第二季的4,400萬美元下降，主要受患者延後治療（patient warehousing）以及季節性治療——治療的季節性變化——所影響。最後，第三季合作及其他營收為1,400萬美元。由於丙型肝炎產品與權利金營收的下滑幅度較預期更為劇烈，我們將2013年總營收指引下修約1億美元，至10億至10.5億美元。

Now to our non-GAAP operating expenses of $276 million, which excludes cost of product revenues and other charges. This was lower than the prior quarter and was made up of approximately $202 million in R&D investments and $74 million in SG&A expenses. We expect 2013 non-GAAP operating expense to be approximately $1.1 billion, which is at the low end of the guidance range of $1.09 billion to $1.15 billion that we provided in February of 2013.

接著談我們2.76億美元的非GAAP營運費用（不含產品營收成本及其他費用）。此數字低於前一季，其中約2.02億美元為研發投資，7,400萬美元為銷售、一般與行政（SG&A）費用。我們預期2013年非GAAP營運費用約為11億美元，位於我們在2013年2月提供之10.9億至11.5億美元指引區間的低端。

In summary, I hope the financial results reported today and the actions we have taken are understood in the context of how we're seeking to advance our business. In particular, I have provided some clarity around the opportunity for revenues and earnings growth that we see ahead of us and how we are managing our investment and aligning our business with our financial growth opportunity.

總結來說，我希望今天公布的財務結果以及我們採取的行動，能在我們推動業務前進的脈絡下被理解。特別是，我已就我們所看到的未來營收與獲利成長機會提供更清楚的說明，以及我們如何管理投資並使業務與財務成長機會對齊。

I'd now like to open the call for questions.

接下來我想開放提問。

(Operator Instructions)

(接線生指示)

Geoff Meacham of JPMorgan.

摩根大通（JPMorgan）的Geoff Meacham。

Good morning guys. Thanks for taking the question. Just in light of the INCIVEK decision. Does this change the internal hurdle rate for you guys for VX-135 moving forward? I want to get a sense for how you're thinking about hepatitis C as we go forward.

各位早安。謝謝讓我提問。就INCIVEK的決策而言。這是否會改變你們未來推進VX-135時的內部門檻報酬率（hurdle rate）？我想了解你們接下來如何看待丙型肝炎。

So Geoff, thanks for the question. I'll actually take it. I think you said internal hurdle rate can I just clarify?

Geoff，謝謝你的問題。我來回答。我想你提到的是內部門檻報酬率——我可以先確認一下嗎？

Yes, that's right.

是的，沒錯。

So it is an early stage program, proof of concept study in terms of combination therapy that we're running VX-135 with Daclatasvir. As we look at that study, we need to get the data which we with anticipate will be in the first quarter of 2014 and at that point we'll decide on how we progress our business. We're very, [in fall] HCV oral therapies, and very aware of the external environment. It's progressing fast. It's highly competitive and we're going to be taking that into account when we get our data from this combination study that's being run down in New Zealand and I will advise you at that point in early 2014.

因此這是一個早期階段的計畫，就合併療法而言，我們正在進行 VX-135 與 Daclatasvir 的概念驗證研究。在檢視該研究時，我們需要取得數據；我們預期數據將在 2014 年第一季出爐，屆時我們將決定如何推進我們的業務。我們非常關注 HCV 口服療法的發展，也非常了解外部環境。進展很快。競爭非常激烈；當我們取得這項在紐西蘭進行的合併研究數據時，我們會將這些因素納入考量，我也會在 2014 年初向您說明。

That's good. And then just one follow-up if I could on CF. For 661 plus ivacaftor, when you're looking at the G551D and the delta F hetero patients, how fast do you think when you get the proof of concept data, what could be the next steps there? Do you feel like you'd have to do a full on Phase 2b that's a 12 week study or do you feel like you could get into a faster population at the Phase 3 setting?

很好。然後如果可以的話，我還想就 CF 再追問一個問題。針對 661 加上 ivacaftor，當你們觀察 G551D 與 delta F 異合子患者時，你們認為在取得概念驗證數據後，接下來可能的步驟會有多快？你們覺得需要做一個完整的 2b 期、為期 12 週的研究，還是覺得可以在 3 期的設定下進入一個更快的族群？

This is Bob. I'll take that question. Obviously, depending on the results we think we could move really fairly quickly into a more advanced program. Obviously, this would take some discussion with the regulatory agencies once we have the results of the study to decide on the next steps. But given the track record of ivacaftor and what we're developing in knowledge about 661, we could probably move into a Phase 2 study fairly quickly.

我是 Bob。我來回答這個問題。顯然，取決於結果，我們認為可以相當快地推進到更進階的計畫。當然，一旦我們拿到研究結果，仍需要與監管機構進行一些討論，以決定下一步。但考量到 ivacaftor 的既有紀錄，以及我們對 661 的開發與累積的認知，我們可能可以相當快地進入 2 期研究。

Okay, thank you.

好的，謝謝。

Geoff Porges of Sanford Bernstein.

Sanford Bernstein 的 Geoff Porges。

Thanks very much for taking the question, and I suppose congratulations on taking the tough decisions at the Company's P&L. A couple of questions. First, on VX-135, you haven't disclosed anything about genotype two and three and it would be helpful to know whether you've contemplated or are planning any studies in the other genotypes with the Ribavirin combination because certainly it appears as though it's reasonably well tolerated.

非常感謝讓我提問，我想也要恭喜公司在損益表（P&L）上做出了艱難的決策。有幾個問題。第一個，關於 VX-135，你們尚未披露任何關於第二型與第三型基因型的資訊；若能了解你們是否已考慮或計畫在其他基因型中，進行與 Ribavirin 聯合的研究，會很有幫助，因為看起來它的耐受性相當不錯。

And secondly, just to follow-up on the question of hurdle, if you do not go ahead with VX-135, is there additional savings to your P&L if you abandon virology, and would that be the decision if VX-135 didn't go ahead? Thanks.

第二個問題，延續門檻（hurdle）的提問：如果你們不繼續推進 VX-135，那麼若你們放棄病毒學（virology），在損益表上是否還能有額外節省？如果 VX-135 不再推進，是否就會做出那樣的決定？謝謝。

Geoff, I'll take the first part and then I'll turn it over to Ian. For genotype two, three, we did develop some data as you know in our virokinetic study, seven day data to show very good activity in both of those other genotypes. And we do plan to carry that forward into more advanced studies once we have the initial data in genotype one from the 135 and Daclatasvir study.

Geoff，我先回答第一部分，然後再交給 Ian。就第二型、第三型而言，如你所知，我們在病毒動力學（virokinetic）研究中取得了一些數據，7 天的數據顯示在這兩種其他基因型上都有非常好的活性。而且我們確實計畫在取得 135 與 Daclatasvir 研究於第一型基因型的初步數據後，將其推進到更進階的研究。

Whether we would pursue the Ribavirin and 135 combination I think is unlikely given the efficacy results that others have generated. And obviously, our work going forward would be likely with Daclatasvir in combination in those other genotypes.

至於是否會推進 Ribavirin 與 135 的組合，我認為可能性不大，考量到其他人已產生的療效結果。而且很明顯，我們後續在那些其他基因型上的工作，較可能會是與 Daclatasvir 的合併。

Okay, thanks, Bob.

好的，謝謝，Bob。

Geoff, thanks for the question. It gives me the opportunity to say that we're still in our planning phase as we look at 2014 and maybe I could expand on that which is the planning phase means we're still trying to gain an assessment of the revenue picture in 2014 as well. We've got some important data coming up, most proximal data is actually coming out of an R117H label expansion study. So again that will drive potential expectations on revenue in 2014 as well.

Geoff，謝謝你的問題。這也讓我有機會說明：我們在看 2014 年時仍處於規劃階段；我可以再多補充一點，所謂規劃階段，表示我們也仍在嘗試評估 2014 年的營收樣貌。我們有一些重要數據即將出爐，最近期的數據其實來自一項 R117H 標籤擴增研究。因此，這也會影響我們對 2014 年營收的潛在預期。

And then as far as the cost structure of the business is concerned, we are communicating $150 million to $175 million of savings off what we anticipate will be a $1.1 billion operating expense in 2013. We're pretty tight on those costs. We have good visibility on those costs and as I explained where they come from on the call.

至於業務的成本結構，我們對外溝通的是：相較於我們預期 2013 年 11 億美元的營運費用，可節省 1.5 億至 1.75 億美元。我們對這些成本控管得相當緊。我們對這些成本有很好的可視性，而且我也在電話會議中說明了它們的來源。

As far as additional savings, if in terms of if decisions are made to pursue certain programs or not, and you referred to VX-135, those haven't yet been taken into account. So yes, there would be probably further savings beyond the $150 million to $175 million. We're planning for success at this point. That's how we run our business at this point in time. That's how we plan financially, frankly how we built the balance sheet to assume how we need to invest in the business. So we look forward to finding out what those results are out of New Zealand and probably late January, early February when we're on our year-end call, we'll give you the more precise GAAP financial guidance for 2014.

至於額外節省，如果就是否追求某些計畫的決策而言，而你提到 VX-135，這些尚未被納入考量。所以是的，可能會有超過 1.5 億至 1.75 億美元的進一步節省。我們目前是以成功為前提在做規劃。這就是我們此刻經營業務的方式。坦白說，這也是我們做財務規劃、以及建立資產負債表的方式，以便假設我們需要如何投資於業務。因此，我們期待看到紐西蘭那邊的結果；大概在 1 月下旬、2 月上旬我們的年終電話會議時，我們會提供更精確的 2014 年 GAAP 財務指引。

Okay, thanks very much, Ian.

好的，非常感謝，Ian。

Michael Yee of RBC Capital Markets.

RBC Capital Markets 的 Michael Yee。

Hi, thanks. Congrats as well. Two questions. One is on the expense structure, Ian maybe you could give us a little bit more specifics on the size of the R&D programs. In other words, what is, how much is early stage versus CF versus Hep C and same with SG&A. Maybe you could break that down a little bit so we know the size of the moving parts.

嗨，謝謝。也恭喜你們。兩個問題。第一個是關於費用結構，Ian，也許你可以更具體說明一下研發（R&D）計畫的規模。換句話說，早期階段相對於 CF 相對於 C 肝（Hep C）各占多少？SG&A 也是一樣。也許你可以稍微拆解一下，讓我們了解各個變動項的規模。

And the second question is on 661. You said you were starting a homozygous study, 12 week study. That data probably comes out some time after the 809 study, so maybe you could explain what the point of that study is and what we do with that once that data comes out, thanks.

第二個問題是關於 661。你說你們正在啟動一項同型合子研究，為期 12 週。那個數據可能會在 809 研究之後一段時間才出來，所以也許你可以解釋一下該研究的目的，以及當數據出來後我們會如何運用，謝謝。

Good morning, Michael. Thanks for the question. I'll first of all start by commenting on 2013 and kind of the trajectory for the R&D and SG&A. So as we look into the fourth quarter, so how you understand how we may finish the year, you should anticipate that our operating expense is very similar to actually the third quarter. You may see some slight reductions in the SG&A specifically because it's easier to adapt that cost structure with the decisions we've made in R&D. We still have a full program that's going ahead in many areas in R&D. So you'll see a slight decline in the fourth quarter of SG&A. But overall, relatively similar to the Q3 results.

早安，Michael。謝謝你的問題。我先評論一下 2013 年，以及研發（R&D）與 SG&A 的走勢。因此，當我們看第四季、也就是你要如何理解我們可能如何結束今年時，你應該預期我們的營運費用其實與第三季非常相近。你可能會看到 SG&A 有些微下降，特別是因為在我們對研發做出決策後，SG&A 的成本結構更容易調整。我們在研發的許多領域仍有完整的計畫在推進。因此你會看到第四季 SG&A 略為下降。但整體而言，與第三季結果相對接近。

I think more importantly as we look at 2014, and again I'll reiterate we are in our planning phase but I can give you an idea of the trajectory again, which is that when you look at the R&D expense in 2014, you should see a slight reduction. That's principally due to a reduction in development of areas that I mentioned in my prepared remarks which was VX-509 and INCIVEK-based therapies. We were actually still studying those in 2013.

我認為更重要的是，當我們看 2014 年時——我再次重申我們仍在規劃階段——但我可以再給你一個走勢概念：也就是當你看 2014 年的研發費用時，你應該會看到小幅下降。這主要是因為我在事先準備的發言中提到的領域之開發縮減，也就是 VX-509 與以 INCIVEK 為基礎的療法。我們在 2013 年其實仍在研究那些項目。

The big reduction, and by the way we expect the research investment to stay relatively similar in 2014. The big reduction that you would expect to see when you look at the GAAP financials is in the SG&A area. That's where we have been able to reduce the costs around INCIVEK marketing and sales support. So you should see that decline in 2014.

大幅度的削減；另外，我們預期 2014 年的研發投資將維持在相對相近的水準。當你查看 GAAP 財報時，你會預期看到的最大降幅會出現在 SG&A（銷售、一般及行政費用）這一塊。那是因為我們已能降低與 INCIVEK 行銷與銷售支援相關的成本。因此你應該會在 2014 年看到那樣的下降。

And sometimes, even though I provide you some numbers, sometimes there are some missing features that are kind of buried within the numbers because we still are continuing to invest in cystic fibrosis, so we do actually anticipate an increase in the investment in development in cystic fibrosis, and also to support the launch and label expansion in 2014. So even though you're seeing these declines, we continue to invest in the area of cystic fibrosis to drive that growth opportunity.

而且有時候，即使我提供了一些數字，仍可能有一些細項被埋在數字裡而不易看出來，因為我們仍持續投資囊性纖維化（CF），所以我們確實預期在 CF 的開發投資會增加，同時也會支援 2014 年的上市以及適應症標籤擴增。因此即便你看到這些下降，我們仍會持續投資 CF 領域，以推動那個成長機會。

But if I were to just ask a little more, what percent of your R&D is early stage versus CF, the clinical trials, CF clinical trials versus say early stage?

但如果我再多問一點，你們的研發（R&D）中，早期階段相對於 CF 的占比是多少？也就是說，CF 的臨床試驗相對於例如早期階段的占比是多少？

Back in February 2013 we gave that break out when we gave the guidance for the full year. I can't commit that we'll do that again at this point but that would be a better point in time that we would be able to help you understand the full profile for 2014. It's just a little early. We are only at Q3 2013.

早在 2013 年 2 月，我們在提供全年指引時就給過那樣的拆分。我現在無法承諾我們會再做一次，但那會是更合適的時間點，讓我們能協助你理解 2014 年的完整輪廓。現在只是有點太早。我們目前才在 2013 年第三季（Q3 2013）。

Okay.

好的。

This is Bob. I'll take the second part of your question related to 661. So this is a study in homozygous patients. The reason for that obviously is that we want to be able to assess PKPD and efficacy and dose response as part of that study, the 12 week duration is really to get a much better handle on safety as sort of a second molecule coming through, the bar is fairly high compared to VX-809, we want to characterize it well. And we would then have an opportunity to further develop 661.

我是 Bob。我來回答你問題中與 661 相關的第二部分。這是一項在同型合子患者中的研究。原因很明顯：我們希望在該研究中評估 PK/PD（藥物動力學/藥效學）、療效以及劑量反應；12 週的期間主要是為了更好地掌握安全性。作為第二個進入開發流程的分子，相較於 VX-809，門檻相當高，我們希望把它特性描述得更完整。接著我們就會有機會進一步開發 661。

As to when the data would come out from those two studies I really can't speculate at this point. The ivacaftor 809 combination study and this one, we haven't started this one yet, so we don't really have that much visibility on the exact timing, but we will do that once we get the study enrolled.

至於那兩項研究的數據何時會出來，我目前真的無法推測。ivacaftor 與 809 的合併研究以及這一項（我們尚未開始），因此對確切時程的能見度不高；但在完成收案後，我們會再提供更新。

Thanks.

謝謝。

Mark Schoenebaum of ISI Group.

ISI Group 的 Mark Schoenebaum。

Hi guys, thank you very much for taking the question. Thanks for all of the clarity. I had a longer term question. I know you aren't giving any kind of long term guidance, but this is qualitative I guess question. Am I thinking about this the right way, now that you're effectively reducing or eliminating or greatly reducing the hepatitis C infrastructure on the SG&A side you should be left basically with a CF infrastructure? And obviously if things play out the revenue growth for CF should be pretty dramatic. So my question is, as we look at the SG&A line over the very long term, and if we make then the assumption that Vertex stays focused commercially on cystic fibrosis, would it be reasonable to assume that that SG&A line really shouldn't grow all that much over the long term as revenue potentially grows, obviously a heck of a lot of things work out?

嗨，各位，謝謝你們回答問題。也謝謝你們提供這麼清楚的說明。我有一個較長期的問題。我知道你們不提供任何形式的長期指引，但我想這算是定性問題。我這樣理解對嗎：既然你們在 SG&A 端實質上正在縮減、取消或大幅縮減 C 肝的基礎建設，那你們基本上就會剩下一個 CF 的商業基礎建設？而且很顯然，如果事情如預期發展，CF 的營收成長應該會相當顯著。所以我的問題是：從非常長期來看，若我們假設 Vertex 在商業上仍聚焦於囊性纖維化，那麼隨著營收可能成長（當然前提是很多事情都順利），是否可以合理假設 SG&A 這條線長期其實不需要成長太多？

And then I had one more question, more on the clinical development side if I may. Could you just remind us of the powering on FEV in the KALYDECO plus 809 ongoing Phase 3 Traffic and Transport? And then also remind us what you deem to be a clinically meaningful improvement in FEV please.

另外如果可以，我還有一個偏臨床開發面的問題。你們能否提醒我們，KALYDECO 加 809 目前進行中的第三期 Traffic 與 Transport 試驗，在 FEV1 的統計檢定力（powering）設定是什麼？也請再提醒我們，你們認為 FEV1 改善多少才算具有臨床意義。

And then just housekeeping. Do you happen to know how many INCIVEK patients were treated in the quarter in the US, if you happen to have that?

最後是一些例行問題。你們是否剛好知道本季在美國治療了多少名 INCIVEK 病人？如果你們手上剛好有這個數字的話。

So Mark thanks for the list of questions and good morning.

Mark，謝謝你這一串問題，早安。

Good morning.

早安。

Yes, so I think you're thinking about the business financially in the right way. We are consolidating down around cystic fibrosis at this point. That's where the growth opportunity is for us. We still have a research investment for product creation and we're still investing in that early stage all oral program for hepatitis C.

是的，我認為你在財務面對這個業務的理解方向是對的。我們目前正在把重心整合到囊性纖維化上。那是我們的成長機會所在。我們仍有用於產品創造的研發投資，同時也仍在投資 C 肝的早期全口服方案。

But in terms of earnings capability and cash flow if successful in the area of CF, we don't anticipate a significant expansion in SG&A. There will be some because you have got a launch of products, you're getting to a broader audience and there's a geographic, it's more of a US, Europe or North America and Europe type expansion, so there will be some growth. But the financial leverage in the area is important to us frankly, and that's why we're managing the business in this way.

但就獲利能力與現金流而言，若 CF 領域成功，我們不預期 SG&A 會有顯著擴張。會有一些增加，因為你會有產品上市、觸及更廣泛的受眾，以及地理擴張——更像是從美國擴展到北美與歐洲——因此會有一些成長。但坦白說，這個領域的財務槓桿對我們很重要，這也是我們以這種方式管理業務的原因。

This is Bob. I'll take the other part of the question in terms of the powering of this study. This study is powered based on a 5% relative improvement in FEV1. I won't really talk much about what we think is a clinically meaningful FEV1 change because I think you have to see the study endpoints in their totality, and particularly some of the non-pulmonary endpoints that we saw with ivacaftor actually are clinically quite meaningful to patients, the weight gain, reduction in exacerbations. So I think we should take a little bit more broad look at the way this study is being conducted. It is the case that the FEV1 change however is the primary end point and that's how the study was powered.

我是 Bob。我來回答關於這項研究統計檢定力設定的部分。這項研究的設計是以 FEV1 相對改善 5% 作為檢定力基礎。我不太想多談我們認為多大的 FEV1 變化才算臨床上有意義，因為我認為你必須把研究終點整體一起看，特別是我們在 ivacaftor 看到的一些非肺部終點，對病人其實相當有臨床意義，例如體重增加、急性惡化（exacerbations）減少。所以我認為我們應該用更廣的角度來看這項研究的執行方式。不過確實，FEV1 的變化是主要終點，而研究的檢定力也是依此設定。

Mark this is Jeff. Just one minor addition really to elaborate a bit on what Bob said. You probably said the recent results from the GOAL study at NACF, which looked at a variety of other endpoints in patients treated with KALYDECO, including mucociliary appearance and digestive function, pseudomonas colonization. I think we really do think about these therapies as being systemic and one of the things that we will focus on as we move forward is measuring a number of these other endpoints because they really reflect patient outcomes very accurately.

Mark，我是 Jeff。我只補充一點，稍微延伸 Bob 的說法。你可能在 NACF 看到 GOAL 研究的近期結果；該研究在接受 KALYDECO 治療的病人中，檢視了多種其他終點，包括黏液纖毛外觀、消化功能、以及綠膿桿菌（pseudomonas）定植。我想我們確實把這些療法視為全身性的治療；而我們接下來會聚焦的一件事，就是衡量更多這類其他終點，因為它們非常能準確反映病人的結果。

Thanks Mark. Next question please?

謝謝你，Mark。請下一題？

Rachel McMinn of Bank of America.

美國銀行（Bank of America）的 Rachel McMinn。

Thanks very much. I'll try to keep my list a little bit shorter but I do have a couple of questions as well. Jeff, for you I guess I'm wondering why you chose not to make any changes to your research infrastructure. I think I recall that number being around $200 million annually.

非常感謝。我會盡量把問題清單縮短一些，但我也有幾個問題。Jeff，我想問的是，你們為什麼選擇不對研發基礎建設做任何調整？我記得那個數字大約是每年 2 億美元。

And as a corollary, when do we as investors get more visibility into your efforts there, just in terms of value creation? On 135 can you confirm that 200 migs is being studied in the Daclatasvir study? And then what do you do if 135, just big picture question, if you can actually get this through the FDA and you get a profile that's worth reinvesting in, is this something that you plan to just partner off to multiple companies, keep, look to in license something to bring in with it? I just want to better understand your strategic outlook there, thank you.

另外延伸問一下，作為投資人，我們何時能對你們在那方面的努力有更多能見度，就價值創造的角度而言？關於 135，你能否確認在 Daclatasvir 研究中正在評估的是 200 mg？再來從大方向來看，如果 135 真的能推進到 FDA 並且得到一個值得再投資的產品特性，你們打算怎麼做：把它授權/合作給多家公司、自己保留，或是尋求引進授權（in-license）某些產品來搭配？我想更了解你們在那方面的策略展望，謝謝。

Thanks, Rachel. I'll answer the first part of the question and thanks for it. This concerns our investment in research, and as Ian said, as we move into next year, we expect the investment in research to be approximately equivalent to what we invested this year. And the reason for that is straightforward, we believe that our research engine is really the current and future engine for the growth of the Company, actually with what I would consider a very modest spend in research.

謝謝，Rachel。我會先回答問題的第一部分，也謝謝你的提問。這涉及我們在研發上的投資；正如Ian所說，隨著我們進入明年，我們預期研發投資將大致與今年的投入相當。原因很直接：我們相信研發引擎確實是公司當前與未來的成長引擎，而且我認為我們在研發上的支出其實相當克制。

This organization has produced a series of transformative drugs from INCIVEK to KALYDECO to now 809, 661, the JAK inhibitor et cetera. And certainly as we look to the future, we are relying on this engine to continue to do so. So we have a short-term financial issue that we're addressing in 2014 as Ian described, but it just doesn't make sense to cut the long term engine of growth for a short-term financial issue. We think we have a pretty good strategy for managing it otherwise.

這個組織已經產出一系列具變革性的藥物，從INCIVEK到KALYDECO，再到現在的809、661、JAK抑制劑等等。而且，當我們展望未來時，我們也仰賴這個引擎持續做到這一點。因此，我們確實有一個短期的財務議題要在2014年如Ian所描述地加以處理，但為了短期財務問題而削減長期成長引擎並不合理。我們認為我們有一個相當不錯的策略，可以用其他方式來管理。

Just, this is Bob. Just a quick comment on 135. We are studying 100 and 200 milligrams in combination with Daclatasvir.

補充一下，我是Bob。針對135簡短說明一下。我們正在研究100毫克與200毫克劑量，並與Daclatasvir合併使用。

And then Rachel to your point about in licensing, out licensing, and let's say a cooperative overall business strategy around hepatitis C broadly. To me, it's about the results we achieve in the combination study that's ongoing, and pending let's say the quality of the those results I think it sets a path. High quality results obviously means that Vertex is in the game of all oral therapies for hepatitis C. Something that's not high quality, then we have to understand how VX-135 may play a role in hepatitis C, whether that's with Vertex or with another company that has a combination approach.

然後，Rachel，回到你提到的引進授權、對外授權，以及更廣泛的丙型肝炎整體合作商業策略。對我而言，關鍵在於我們正在進行的聯合用藥研究所取得的結果；視結果品質而定，我認為它會指引後續路徑。高品質的結果顯然意味著Vertex將參與丙肝全口服療法的競局；若結果不夠理想，那我們就必須理解VX-135在丙肝治療中可能扮演的角色——不論是與Vertex一起，或是與另一家擁有聯合方案的公司合作。

And so I'd like to think that we're looking at our position in hepatitis C at this point by looking at the external landscape, understanding the commitment we have as a company but we've got to make a decision as we go into 2014 based on data.

因此，我希望大家理解：我們目前是透過檢視外部競爭態勢來看待我們在丙肝領域的位置，同時也了解公司所做的承諾；但我們必須在進入2014年時，依據數據做出決策。

I'm sorry your early stage pipeline, when do we get visibility outside of CF? Thanks.

不好意思，關於你們早期研發管線，除了CF之外，我們何時能看到更多能見度？謝謝。

Yes, as Ian mentioned we hope to begin to give you visibility to some of that next year, as you know traditionally, we do provide visibility once we begin to see human proof of concept data and we hope for some of the programs that will be beginning next year.

是的，如Ian提到的，我們希望明年開始讓你們看到其中一些項目的進展。正如你所知，傳統上我們會在開始看到人體概念驗證（proof of concept）數據後提供能見度；我們希望明年啟動的部分專案能做到這點。

Ying Huang of Barclays.

Barclays的Ying Huang。

Good morning. Thanks for taking my questions as well. So my first question has to do with the Australian Canadian patients with G551D mutations, so because it sounds like those are the two major markets where you not have tapped on KALYDECO. Can you give us a little bit of clarity in terms of patients number with that G551D mutation? Should we also assume 4% of CF patients and those who cultured having G551D?

早安。也謝謝你們回答我的問題。我第一個問題是關於澳洲與加拿大帶有G551D突變的患者；因為聽起來這兩個市場是你們尚未在KALYDECO上充分觸及的兩個主要市場。你們能否更清楚說明一下具有G551D突變的患者人數？我們是否也應假設CF患者中約4%（以及培養檢出者）具有G551D？

And then secondly, the R117H trial success here. I've got a lot of questions from investors about the trial because we know now you're going to put out the top line data by the end of this year. I guess when we talk to physicians, there are many mild patients there. That's why some investors were concerned about the trial success for R117H, so I would like to have any thoughts from you guys.

第二，關於R117H試驗的成功。投資人對這個試驗有很多問題，因為我們知道你們會在今年底前公布主要（top line）數據。我想當我們與醫師交流時，裡面有很多是病情較輕的患者。因此一些投資人擔心R117H試驗是否能成功，我想聽聽你們的看法。

And then lastly, given the I guess HCV strategic direction here in your Company, are you thinking differently about let's say the flu program as well or are you still going to out license that program and find a partner? Thank you.

最後，考量到你們公司在HCV策略方向上的調整，你們是否也會用不同方式看待例如流感（flu）專案？還是你們仍會將該專案對外授權並尋找合作夥伴？謝謝。

So, Ying, thanks for the list of questions again. I'll take the first and last question and Bob can talk about 117H heterogeneity of population.

Ying，再次謝謝你這一串問題。我先回答第一個與最後一個問題，Bob會談117H族群的異質性。

So first, Canada or Australia it's approximately 300 G551D patients, and that will be important once we gain reimbursement approval in those two countries to add to growth. And just staying on the KALYDECO growth path as you're aware, we do have a filing that's currently under review for other gating non-G551 patients, and that's currently being reviewed by the FDA and Europe.

首先，加拿大或澳洲大約有300名G551D患者；一旦我們在這兩個國家取得給付核准，這將對成長很重要。另外，延續KALYDECO的成長路徑，如你所知，我們也已針對其他閘控（gating）但非G551的患者提出申請，目前正由FDA與歐洲審查中。

As to the third question you asked which is our commitment to the flu program, the flu program is actually one of those molecules that we are seeking a partnership to advance forward. Given our focus in consolidation and let's say financial direction of the Company earlier this year we communicated that we would be along with VX-509 looking for a potential partner to advance the flu program, and we continue to seek that partner. Bob?

至於你問的第三個問題，也就是我們對流感專案的承諾：流感專案其實是我們正在尋求合作夥伴以推進的一個分子。鑑於我們今年稍早聚焦於整併以及公司財務方向，我們曾對外溝通，除了VX-509之外，我們也會為流感專案尋找潛在合作夥伴以推進；我們仍在持續尋找該合作夥伴。Bob？

Yes, this is Bob. So on the R117H population, we estimate the total R117H population at around 1,100 patients worldwide. It is true that it's a heterogeneous group from really quite mild disease to almost no disease, all the way up to more significant disease with declines in FEV1 and exacerbations just like other patients with significant cystic fibrosis. So it is heterogeneous. The way we've tried to deal with that is to narrow the population that we evaluated in our study.

是的，我是Bob。關於R117H族群，我們估計全球R117H總患者數約為1,100人。確實，這是一個高度異質的族群，從相當輕微的疾病到幾乎沒有疾病，一直到更嚴重的疾病，出現FEV1下降與急性惡化，與其他嚴重囊性纖維化患者相似。所以它是異質的。我們嘗試處理這點的方法，是縮小我們在研究中評估的族群範圍。

That population has a percent predicted FEV1 to baseline of between 40% and 90%, which for R117H clearly puts you into a more severe and more significant group. That is a way of kind of dealing with the heterogeneities to basically homogenize the population a little bit, and obviously, we'll see how the results come out when we have them at the end of this year. From a clinical point of view, how -- should this study be successful how the uptake will be I think we'll have to see. It likely will not be as rapid as what we have seen for KALYDECO and G551D.

該族群的基線預測值百分比FEV1介於40%到90%之間；對R117H而言，這明確把你放在較嚴重、較具臨床意義的一群。這是一種處理異質性的方式，基本上是讓族群稍微同質化一些；當然，我們會在今年底拿到結果時看看表現如何。從臨床角度來看，如果這項研究成功，市場採用速度會如何，我想還需要觀察。它很可能不會像我們在KALYDECO與G551D上看到的那樣快速。

Thank you.

謝謝。

Terence Flynn of Goldman Sachs.

Goldman Sachs的Terence Flynn。

Thank you for the question. Just maybe one point of clarification. Is there any sales force still left to market INCIVEK or is that completely restructured today?

謝謝讓我提問。我想先釐清一點。目前是否還有任何銷售團隊在推廣INCIVEK，還是今天已經完全重整了？

And then was just looking back at your guidance you gave for peak KALYDECO sales, gave at NACFC, and if I do some simple math here it seems to me that I get about $180,000 per year on average for pricing for the drug on a worldwide basis. Just wondering if that's a good ballpark for net pricing or if there's other assumptions like a discontinuation rate that I might be missing that goes into that number. Thanks a lot.

另外，我回頭看你們在NACFC給的KALYDECO銷售峰值指引；如果我做一些簡單計算，看起來全球平均每年藥價約為18萬美元。想請問這是否是淨價格（net pricing）的合理概算，或是其中還包含其他假設，例如停藥率，是我在這個數字裡漏掉的。非常感謝。

Terence, thanks for the question. Can you just remind me of the first question? Oh, yes sorry, no we have completely restructured the marketing and sales support behind INCIVEK.

Terence，謝謝你的問題。你可以提醒我第一個問題是什麼嗎？喔，對，抱歉；不，我們已經完全重整了INCIVEK背後的行銷與銷售支援。

And then as to the realized price we don't comment on the realized price. We provide you guidance on total revenues for the full year of $360 million to $365 million.

至於實現價格（realized price），我們不評論實現價格。我們提供你們的指引是全年總營收3.60億至3.65億美元。

Matt Roden of UBS.

UBS 的 Matt Roden。

Great, thanks very much for taking my question as well. First on 509, on efficacy it looks pretty potent here. Just wondering, Bob if there's anything mechanistic behind the two cardiovascular events that you've seen across the two studies and your relative comfort with the safety profile of the molecule overall?

很好，非常感謝也讓我提問。首先談 509，就療效而言，看起來相當強勁。想請問 Bob，針對你們在兩項研究中看到的兩起心血管事件，背後是否有任何機轉上的原因？以及你們對這個分子整體安全性概況的相對信心如何？

And then how do you extract maximal value from 509? Has there been significant interest from other parties? I don't know to what extent you can comment on that, but when do you think would be the right time to look to partner?

另外，你們要如何從 509 中萃取最大價值？是否有其他方表達了相當程度的興趣？我不確定你能評論到什麼程度，但你認為何時會是尋求合作夥伴的適當時機？

And just lastly just wanted to follow-up on the earlier question on the R117H study. With considering the heterogeneity of this population, Bob, can you specifically speak to any steps that you took to control for that heterogeneity in terms of minimizing risk of baseline balances? Thanks a lot.

最後想追問先前關於 R117H 研究的問題。考量到這個族群的異質性，Bob，你能否具體說明你們採取了哪些步驟來控制這種異質性，以降低基線不平衡的風險？非常感謝。

So several questions. First of all with 509, we agree with you the efficacy we think is really very good.

有幾個問題。首先關於 509，我們同意你的看法，我們認為其療效確實非常好。

In terms of the safety profile we're actually quite pleased both in the safety profile, both without methotrexate in our prior study as well as this one. As you're well aware, cardiovascular disease is very common in this population, in fact it's the most common cause of death in patients with RA. So it's not unexpected in a study of these durations to see outcomes such as that. So looking over the program overall, we actually are pretty comfortable with the cardiovascular safety profile that we generated.

就安全性概況而言，無論是在我們先前未合併 methotrexate 的研究，或是這次的研究，我們其實都相當滿意。如你非常清楚，心血管疾病在這個族群非常常見，事實上它是 RA 患者最常見的死因。因此，在這種研究期間長度的試驗中看到這類結果並不意外。所以綜觀整個計畫，我們對所建立的心血管安全性概況其實相當放心。

And I'll add to how to extract maximum value for the VX-509. For us it's a fascinating area but it's also a competitive area in terms of the all oral creation of these types of molecules. To get full success from the opportunity, you need to run multiple, let's say multiple studies in multiple diseases to get the full benefit as most companies are doing.

我再補充一下如何為 VX-509 萃取最大價值。對我們而言，這是一個很迷人的領域，但就這類全口服分子的開發而言，也是競爭激烈的領域。要讓這個機會獲得完全成功，你需要在多種疾病上進行多項、可以說多個研究，才能取得完整效益，正如多數公司正在做的那樣。

Given our focus at this point in time, we look for somebody else to do that so we continue to explore partnerships, it's nice to have such good data in our hands which will enhance those discussions with potential partners, and it may be even better to have our week 24 data as well, depending on how that comes out. And we'll continue that discussion with partners to do the right kind of partnership to extract the value. But our focus right now is around cystic fibrosis and all oral therapies for hepatitis C and also continue to invest in research.

鑑於我們目前的聚焦方向，我們會尋找其他人來做這件事，因此我們持續探索合作夥伴關係；手上有這麼好的數據很不錯，這將強化我們與潛在合作夥伴的討論，而且若第 24 週數據也同樣出色，可能會更好，這取決於結果如何。我們會持續與合作夥伴討論，做出合適的合作安排以萃取價值。但我們目前的重點是在囊性纖維化、以及丙肝的全口服療法，同時也會持續投入研發。

And then this is Bob again. On R117H, I think the primary way that we try to manage variability was really by as I've said before, limiting the population to those with baseline FEV1 of 40% to 90%. Otherwise we relied on randomization as we usually do to create the balance between the treatment groups.

接著又是 Bob。關於 R117H，我認為我們管理變異性的主要方式，正如我之前說過的，是將族群限制在基線 FEV1 為 40% 到 90% 的受試者。除此之外，我們如同往常依賴隨機分派來在治療組之間建立平衡。

Bob there wasn't any specific stratification of any of the parameters that would speak to the severity of the population?

Bob，你們沒有針對任何能反映族群嚴重程度的參數做特定分層嗎？

Honestly I don't remember that but I don't think there's anything major. I think it really was just the baseline FEV1 to define the population.

老實說我不記得了，但我不認為有什麼重大的分層。我想主要就是用基線 FEV1 來界定族群。

Great. Thanks very much for all of the clarity.

很好。非常感謝你們說明得這麼清楚。

Yes.

是的。

Brian Abrahams of Wells Fargo Securities.

Wells Fargo Securities 的 Brian Abrahams。

Hi, thanks very much for taking my questions. At the NACFC conference you outlined a relatively large population with residual function mutations. Can you give us the latest views of how you think the NF1 study would be interpreted by regulators just given the growing positive safety experience with the drug? And what the process would be for getting these groups on the label?

嗨，非常感謝讓我提問。在 NACFC 會議上，你們概述了一個相對龐大的、具有殘餘功能突變的族群。鑑於該藥物累積了越來越多正面的安全性經驗，你們能否分享最新看法：監管機構可能會如何解讀 NF1 研究？以及要讓這些族群被納入適應症標籤的流程會是什麼？

And then Bob maybe you could just remind us about the pre clinical assays you've looked at over time with 809 and KALYDECO and how the time frame and cell lines might be similar or different to some of the studies we saw from investigators at the conference last week, thanks.

另外 Bob，你能否提醒我們，過去一段時間你們針對 809 與 KALYDECO 做過哪些臨床前測試？以及其時間範圍與細胞株，與我們上週在會議上看到研究者所做的一些研究相比，可能有哪些相同或不同？謝謝。

Yes, so just in terms of the NF1 study, this is a proof of concept study. Obviously, we need to learn more about the efficacy of ivacaftor in this population. Obviously, depending on how this study comes out, of course we'll talk about it with the regulatory agencies. However, at this point, we are considering that we may need to run another study in order to get an approval, but obviously, much depends on what we actually see in terms of the results.

好的，先就 NF1 研究而言，這是一項概念驗證研究。顯然，我們需要進一步了解 ivacaftor 在這個族群的療效。當然，視這項研究結果而定，我們會與監管機構討論。不過，就目前而言，我們認為可能需要再進行另一項研究才能取得核准，但顯然很大程度取決於我們實際看到的結果。

In terms of pre clinical assays, I think I know which paper you're referring to from the CF meeting, we've had some questions about that. Obviously, they have their data, we've done similar studies in cell lines for perhaps a somewhat longer duration. This is a combination of ivacaftor and VX-809. We don't see the same diminution of the activity of CFTR that we've seen in those studies. And I think from our viewpoint, the clinical data that we have really kind of trumps the non-clinical data in that we, both for 661 and for 809, have seen really well maintained clinical benefit over at least a 28 day period.

至於臨床前測試，我想我知道你指的是 CF 會議上的哪篇論文，我們也收到一些相關問題。顯然他們有他們的數據；我們也在細胞株中做過類似研究，可能持續時間稍長一些。這是 ivacaftor 與 VX-809 的合併。我們沒有看到那些研究中所見的 CFTR 活性下降。而且從我們的角度來看，我們的臨床數據在某種程度上確實勝過非臨床數據，因為無論是 661 或 809，我們都看到至少在 28 天期間內臨床效益維持得很好。

That's very helpful, thank you.

這非常有幫助，謝謝。

Yaron Werber of Citi.

Citi 的 Yaron Werber。

Great, Thanks for taking my questions and I know it's a tough day over there, but I think you're doing the right thing. I have a couple questions on CF and if you don't mind a quick question on hep C. Just on, the residual function mutation, the KALYDECO proof of concept Phase 2 which is taking R117H plus a broader set of residual patients, what's your sense on the variability in phenotypically in the non-R117H population?

很好，謝謝讓我提問。我知道你們那邊今天很艱難，但我認為你們做的是正確的事。我有幾個關於 CF 的問題，如果可以的話也想快速問一個丙肝的問題。先談殘餘功能突變：KALYDECO 的概念驗證第二期研究納入 R117H 以及更廣泛的一組殘餘功能患者，你們對非 R117H 族群在表型上的變異性有何看法？

And then just on CF, a second question on R117H, is there -- can you correlate at all what the residual CFTR function is to the actual phenotype, the predicted FEV1? I'm trying to get a sense can you control for that variability by any way or no? And then I just have a follow-up on hep C.

接著第二個 CF 問題仍是關於 R117H：你們是否能將殘餘 CFTR 功能與實際表型（預測的 FEV1）做任何相關性連結？我想了解的是：你們能否用任何方式控制這種變異性，還是無法？然後我還有一個關於丙肝的追問。

So this is Bob. I'll try to answer those questions. In terms of the residual function, obviously we're, I think in the big picture, the residual function sort of part of the program starts to shift over from a genetically based program to a phenotypically based program. That's really where the end of one study fits in, is our first look as to whether it's feasible to do that, see how much variability we have and try to get a handle on what a path forward would be for that population.

我是 Bob。我會嘗試回答這些問題。就殘餘功能而言，從大方向來看，我認為殘餘功能這部分的計畫開始從以基因為基礎的計畫，轉向以表型為基礎的計畫。這正是這項研究的定位：我們首次檢視這樣做是否可行、我們會有多大的變異性，並嘗試掌握該族群未來前進路徑會是什麼。

And I think until we see those data it's going to be pretty hard to speculate. Obviously these are people that have sweat chlorides that tend to be lower than those with severe disease. They tend to have more mild disease, most of them are pancreatic sufficient as compared to insufficient and so there are many differences. I think that's why we're running an exploratory Phase 2 study.

我認為在看到那些數據之前，很難做太多推測。顯然，這些人的汗氯值往往比重症患者更低。他們的疾病通常較輕，多數人胰臟功能是足夠的（pancreatic sufficient），相較之下不是不足（insufficient），因此存在許多差異。我想這也是我們要進行探索性第二期研究的原因。

One additional comment, this is Jeff, I'll remind you if you look back at the KALYDECO G551D studies, the responses that we saw really didn't correlate with the baseline FEV1 so we had patients with very high baseline FEV1 who actually responded very nicely. So I think until we get the data what we are really doing in the NF1 is we're studying, as Bob said, a spectrum of patients with different mutations and different severities to try to understand exactly the answer to your question. Until we see the data in a representative population, it's a little difficult to speculate.

再補充一點意見，我是 Jeff。我提醒你，如果你回頭看 KALYDECO G551D 的研究，我們看到的反應其實與基線 FEV1 並沒有相關性，所以有些患者的基線 FEV1 非常高，但實際上反應也非常好。所以我認為，在我們拿到數據之前，我們在 NF1 方面真正做的是——如 Bob 所說——研究一個涵蓋不同突變與不同嚴重程度的患者光譜，以便精確理解你問題的答案。在我們看到具代表性族群的數據之前，現在要推測有點困難。

Okay. And just, thank you for that and just a follow-up on hep C. At the 200, and maybe I'm asking to dive into some of your very early data on monotherapy with 135, at the 200-milligram dose, do you have enough potency do you think that with another DA, like Daclatasvir, you can really get to a high enough potency, or do you really think that you might need a third agent?

好的。另外，謝謝你的說明，我想再追問一下 C 型肝炎。在 200（毫克）——也許我是在深入你們非常早期的 135 單藥數據——在 200 毫克劑量下，你們認為效力是否足夠，能夠搭配另一個 DA（直接作用抗病毒藥），例如 Daclatasvir，真正達到足夠高的效力？還是你們認為可能需要第三個藥物？

So the data we have is in our virokinetic studies where we have seen very good activity, comparable to that sofosbuvir, and that obviously kind of factored into our choice of doses that we're studying going forward. And obviously for the Daclatasvir study we'll see the results when they come out.

我們目前掌握的數據來自病毒動力學（virokinetic）研究，我們看到非常好的活性，與 sofosbuvir 相當，而這也顯然影響了我們選擇後續研究劑量的決策。至於 Daclatasvir 的研究，我們會在結果出來時再看。

Thank you.

謝謝。

Operator, we're close to 9.30 so we have time for just two more quick questions, thank you.

接線員，我們快到 9:30 了，所以只剩下兩個簡短問題的時間，謝謝。

Liisa Bayko of JMP Securities.

JMP Securities 的 Liisa Bayko。

Hi. Thanks for the question. Actually most of mine have been answered but maybe just to drill down on Rachel's earlier question. Can you maybe, I know we'll hear about early stage pipeline development when it comes, but can you just maybe review the core areas that you're investing in? Obviously CF, virology with hep C and flu as a focus and then inflam. Is there anything else that we might expect something to come from, what are the core areas of investment? Thanks.

嗨。謝謝讓我提問。其實我的大多數問題都已經被回答了，但也許我想更深入追問 Rachel 先前的問題。你能否——我知道等到早期管線進展時我們會聽到更多——但你能否先回顧一下你們正在投入的核心領域？顯然有 CF、以 C 肝與流感為重點的病毒學，然後還有發炎（inflammation）。還有其他我們可能期待會有成果的領域嗎？核心投資領域有哪些？謝謝。

Yes, this is Jeff. So I think you've got it right. In the mid to later stage obviously CF, and then the all oral program in HCV which we've been talking about today. Flu is not a program that we're going to invest in further, just to be clear about that, nor do we plan to invest in 509 further.

是的，我是 Jeff。我想你說得沒錯。在中後期階段，顯然是 CF，然後是我們今天一直在談的 HCV 全口服方案。需要澄清的是，流感不是我們會再進一步投資的項目，我們也不打算再對 509 進一步投資。

But as you move back into the earlier stage pipeline we do have programs as we've said in cancer, in progressive MS, in Huntington's disease and others. And as well as the early stage CF programs and the second gen correctors. And it's those programs that I was referring to when I said we'll begin to get some data beginning next year and certainly into 2015 and as we get the human proof of concept data that's usually when we start really talking about these programs.

但回到更早期的研發管線，如我們所說，我們在癌症、進行性 MS（多發性硬化症）、亨丁頓氏症等方面都有項目。另外也包括早期的 CF 項目以及第二代校正劑（second gen correctors）。我先前提到的就是這些項目：我們將從明年開始取得一些數據，並且在 2015 年及之後持續取得；而當我們拿到人體概念驗證（proof of concept）數據時，通常就是我們開始真正深入談論這些項目的時點。

Thanks.

謝謝。

Robyn Karnauskas of Deutsche Bank.

Deutsche Bank 的 Robyn Karnauskas。

Hi, thanks for taking my question. So I guess two things. Number one, what is the genotype composition for the 135 studies you reported today? And then the second question is, now that you have longer term data with KALYDECO, you mentioned outcomes, some outcomes measures. When you think about how pairs might look at an 809 KALYDECO combination, do you think that pairs will take into account the durability you see with KALYDECO and view it as a class of drugs or view the combination as completely independent? Thanks.

嗨，謝謝讓我提問。我想有兩點。第一，你們今天報告的 135 研究，其基因型組成是什麼？第二，既然你們現在有 KALYDECO 的較長期數據，你提到一些結局（outcomes）與結局衡量指標。當你思考保險支付方（payors）可能如何看待 809 與 KALYDECO 的合併療法時，你認為支付方會把 KALYDECO 所呈現的持久性納入考量，並把它視為同一類藥物的效果，還是會把該合併療法視為完全獨立？謝謝。

So this is Bob. The composition of the population is genotype 1 in the study that we were discussing today, the study that was conducted in Moldova. Most of the patients were genotype, in fact all of the patients were genotype 1b, which reflects the composition of the patients in that country.

我是 Bob。我們今天討論的那項研究——在摩爾多瓦進行的研究——其受試者族群組成是基因型 1。大多數患者是 1b，事實上所有患者都是 1b，這反映了該國患者的組成。

And what about CC --

那 CC 呢——

Pardon me?

不好意思？

What about subtype?

亞型呢？

Yes, there was a mix of subtypes, it was relatively a little low on the CC patients but I think you'll see the full data when the poster is presented next week.

是的，亞型有混合；CC 患者的比例相對偏低一些，但我想你會在下週海報發表時看到完整數據。

In terms of durability, without kind of getting beyond the data we currently have, I would say that based on the data from the Persist study, CFTR modulation appears to be a long term effect. There was really no diminution in the activity over a three year period with KALYDECO monotherapy. While obviously I can't speculate, because we don't have such long term data for the combination of 809 and ivacaftor, I would generalize it a little bit and just say that this mechanism appears to be one that produces a longer lasting effect. And obviously we'll see as we get further data over the next couple of years how that turns out. I think the payors obviously, if I can speak for them, I think they obviously will be interested in, and I think obviously very happy to see that this effect is long lasting, and for the patients clearly, very important.

至於持久性，在不超出我們目前掌握的數據範圍下，我會說，根據 Persist 研究的數據，CFTR 調節看起來是一種長期效果。在 KALYDECO 單藥治療的三年期間，活性並沒有真正減弱。當然我無法推測，因為我們沒有 809 與 ivacaftor 合併療法那麼長期的數據；但我可以稍微概括地說，這個機轉似乎會產生較持久的效果。而且很明顯，接下來幾年隨著我們取得更多數據，我們會看到結果如何。我想支付方顯然——如果我可以代他們說——會對此感興趣，而且我想他們也會很高興看到這個效果是長期持續的；對患者而言，這也非常重要。

Thank you, I'm going to turn it over to Jeff for some final remarks.

謝謝。接下來我把時間交給 Jeff 做最後結語。

Yes, first of all thank you for your questions today. I just want to finish with a very clear acknowledgment of our employees. This is obviously a difficult day for all of us here at Vertex and I want to make sure to acknowledge the incredible work that our employees did to develop and commercialize INCIVEK. We've treated more than 100,000 patients worldwide with very high cure rates. This was and is truly a breakthrough drug, and we have a lot more to do, but I want to make sure to acknowledge what's been done by our employees because that really formed foundation of our Company going forward. Thanks very much for your questions and for joining the call today.

是的，首先感謝大家今天的提問。我想最後以非常明確的方式向我們的員工致謝。對我們 Vertex 的所有人來說，今天顯然是艱難的一天；我想特別肯定我們員工在開發並商業化 INCIVEK 上所做的卓越工作。我們已在全球治療超過 100,000 名患者，治癒率非常高。這曾經、也仍然是一款真正的突破性藥物；我們還有很多工作要做，但我想確保肯定員工已完成的成果，因為那確實奠定了公司未來發展的基礎。非常感謝各位的提問，也謝謝大家今天參與電話會議。

Thank you.

謝謝。

Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program. You may all disconnect. Have a great day, everyone.

各位女士、先生，感謝您參與今天的會議。今天的議程到此結束。各位可以掛線。祝各位今天愉快。