福泰製藥 (VRTX) 2012 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to Vertex Pharmaceuticals Incorporated second 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 with instructions following at that time. (Operator Instructions) And as a reminder, this conference is being recorded. Now I'll turn the conference over to Michael Partridge, Vice President of Investor Relations. Please begin.

各位女士、先生，大家好，歡迎參加 Vertex Pharmaceuticals Incorporated 2012 年第二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，屆時會提供相關指示。(接線員指示) 並提醒各位，本次會議正在錄音。現在我將把會議交給投資人關係副總裁 Michael Partridge。請開始。

Good evening and welcome to Vertex's second quarter 2012 conference call. Vertex continued to make progress in the second quarter of 2012 to build our global business. With our approved medicines, in its first full quarter, KALYDECO achieved $46 million in US sales, reflecting increased uptake in people with CF who had the G551D mutation. We also announced on Friday that we have received approval of KALYDECO in the EU.

各位晚安，歡迎參加 Vertex 2012 年第二季電話會議。Vertex 在 2012 年第二季持續推進，打造我們的全球業務。就我們已核准的藥品而言，KALYDECO 在其第一個完整季度於美國達成 4,600 萬美元銷售額，反映出在帶有 G551D 突變的囊性纖維化（CF）患者中的使用量增加。我們也在週五宣布，KALYDECO 已獲得歐盟核准。

INCIVEK, for the treatment of hepatitis C, reported sales of $328 million in the second quarter. We continue to lead the market in hepatitis C. Approximately 70% to 75% of new DAA prescriptions written in the US are for INCIVEK. However, the number of patients initiating treatment for hepatitis C has declined compared to late 2011 and early 2012. Therefore, we have revised our 2012 guidance for total INCIVEK net revenues today. Highlighting our progress in R&D. In cystic fibrosis, which clinical results in study initiation, we advanced our efforts to be able to expand the number of CF patients we may ultimately treat. And in hepatitis C, we today announced promising seven-day viral kinetic data for our first nucleotide analog, ALS-2200, that we licensed from Alios BioPharma.

用於治療 C 型肝炎的 INCIVEK 在第二季報告銷售額為 3.28 億美元。我們持續領先 C 型肝炎市場。美國新開立的 DAA 處方中，約 70% 至 75% 為 INCIVEK。然而，與 2011 年底及 2012 年初相比，開始接受 C 型肝炎治療的患者人數已下降。因此，我們今日修訂了 2012 年 INCIVEK 淨營收總額的財測指引。在研發方面，凸顯我們的進展。在囊性纖維化方面，隨著臨床結果與研究啟動，我們推進相關工作，以期最終能擴大我們可能治療的 CF 患者人數。而在 C 型肝炎方面，我們今日宣布，針對我們自 Alios BioPharma 授權取得的首個核苷酸類似物 ALS-2200，取得令人鼓舞的七天病毒動力學數據。

To discuss these and other developments on the call tonight we have Dr. Jeff Leiden, CEO and Chairman; Ian Smith, CFO; and Dr. Peter Mueller, head of Research and Development and Chief Scientific Officer. After the prepared remarks Bob Kauffman, Vertex's Chief Medical Officer, will join us and we will take your questions. We expect to conclude the call as close to 6.00 PM as we can manage. To help us do that, we would ask that you please limit your questions to one with a related follow-up.

今晚電話會議將由 Jeff Leiden 博士（執行長兼董事長）、Ian Smith（財務長）以及 Peter Mueller 博士（研發主管兼首席科學長）與各位討論上述及其他進展。在預先準備的發言後，Vertex 首席醫療長 Bob Kauffman 將加入，我們將開始回答各位提問。我們預計盡可能在下午 6:00 左右結束本次會議。為協助我們達成此目標，敬請各位將問題限制為一題，並可加上一個相關追問。

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. These statements, including, without limitation, those regarding the market launch of INCIVEK and KALYDECO 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.

我提醒各位，本次電話會議所討論的資訊包含前瞻性陳述，並受我們向美國證券交易委員會提交之報告（包括 10-K 與 10-Q）中所詳述的風險與不確定性影響。這些陳述（包括但不限於關於 INCIVEK 與 KALYDECO 的市場上市以及我們的財測指引）係基於管理層目前的假設，並可能因風險與不確定性而導致實際結果與事件出現重大差異。

GAAP and non-GAAP financial measures will be discussed on this call. Information regarding our use of these measures and a reconciliation of non-GAAP to GAAP is available in our second quarter 2012 financial press release, which is on our website. Thank you. And I will now turn the call over to Jeff.

本次會議將討論 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 年第二季財務新聞稿，並公布於公司網站。謝謝。現在我將把電話會議交給 Jeff。

Thank you, Michael. Good evening, everyone. 2012 has been a very dynamic and productive year for our business. During the last seven months, we have delivered a series of important advancements. For cystic fibrosis the approval and successful launch of KALYDECO in the US. More recently, the approval of KALYDECO in Europe and positive Phase II data for the VX-809 plus KALYDECO combination in delta F508 homozygous payment patients that supports progressing to a pivotal program. And now at hepatitis C, very impressive seven-day viral kinetic data for ALS-2200, our nucleotide analog.

謝謝你，Michael。各位晚安。2012 年對我們的業務而言是非常動態且富有成效的一年。在過去七個月中，我們已交付一系列重要進展。在囊性纖維化方面，KALYDECO 在美國獲准並成功上市。更近期的是，KALYDECO 在歐洲獲准，以及 VX-809 加上 KALYDECO 的第二期正向數據，該組合用於 delta F508 同型合子患者，支持推進至關鍵性試驗計畫。而在 C 型肝炎方面，ALS-2200（我們的核苷酸類似物）展現非常令人印象深刻的七天病毒動力學數據。

With these advancements, all made from the start of this year, we're demonstrating our consistent ability to discover, develop and commercialize multiple transformative medicines. Which in turn, represent the strong foundation for the sustainable long-term growth that we expect to create with our business. During the last few months I've been working closely with the cystic fibrosis and hepatitis C franchise teams at Vertex.

憑藉這些自今年年初以來取得的進展，我們正展現出持續發現、開發並商業化多項具變革性的藥物之能力。而這些能力反過來也構成我們預期可為公司創造可持續長期成長的堅實基礎。在過去幾個月，我一直與 Vertex 的囊性纖維化與 C 型肝炎事業團隊密切合作。

I'll provide a perspective on how we are positioned in these markets and also strategically how we are planning on extending and enhancing our presence in the treatment of these diseases. I'll also highlight for you what I think are the tangible markers for our progress as a business that we will ask you to focus on in the months and years ahead. After that, Ian will review our financial performance, our 2012 guidance, and discuss how we're prioritizing investment in our business. And Peter is going to provide you with a more detailed update on data and recent developments in our pipeline.

我將就我們在這些市場中的定位提供觀點，並從策略面說明我們如何規劃延伸並強化在這些疾病治療領域的布局。我也會為各位重點說明，我認為可作為我們業務進展之具體指標，並希望各位在未來數月與數年持續關注。接著，Ian 將回顧我們的財務表現與 2012 年財測指引，並說明我們如何在業務中優先配置投資。而 Peter 將就我們研發管線的數據與近期進展提供更詳細的更新。

Beginning with cystic fibrosis, Vertex is seeking to fundamentally change the outlook for people with this disease and we have made excellent progress toward the goal this year. KALYDECO, which was approved earlier in the year in the US for G551D CF patients, aged six years and older, has been rapidly adopted in the US as a groundbreaking new medicine that addresses the underlying cause of the disease in these patients. The launch of KALYDECO has exceeded our expectations. We are currently treating a significant number of G551D patients and we expect additional G551D patients to begin treatment in 2012, including patients who are rolling off the PERSIST Phase III extension study.

先從囊性纖維化談起，Vertex 致力於從根本上改變此疾病患者的前景，而我們今年朝此目標已取得極佳進展。KALYDECO 於今年稍早在美國獲准，用於 6 歲及以上、帶有 G551D 突變的 CF 患者；作為一項突破性新藥，能針對這些患者的疾病根本原因發揮作用，因此在美國迅速被採用。KALYDECO 的上市表現超出我們預期。我們目前正在治療相當數量的 G551D 患者，並預期 2012 年將有更多 G551D 患者開始治療，其中包括從 PERSIST 第三期延伸研究結束（rolling off）的患者。

Our field teams have done an excellent job with the launch, working to educate physicians and caregivers about KALYDECO and helping eligible patients and their families get the medicine. Last week we received approval in the EU for KALYDECO for G551D patients, and our team there is working to make KALYDECO available as soon as possible in multiple countries. We also believe that we can significantly expand the CF population that is addressable with KALYDECO alone. And towards that end, we have initiated additional mono therapy studies that Peter will discuss in his remarks. If our strategy is successful these studies could increase the addressable population from the current 4%, to 8% to 10% of the CF population, and potentially more as we consider the applicability of KALYDECO to certain other people with CF.

我們的前線團隊在上市推廣方面表現出色，致力於教育醫師與照護者了解 KALYDECO，並協助符合資格的患者及其家屬取得藥物。上週我們在歐盟獲得 KALYDECO 用於 G551D 患者的核准，而當地團隊正努力使 KALYDECO 盡快在多個國家上市供應。我們也相信，僅使用 KALYDECO 就能顯著擴大可治療的 CF 人群。為此，我們已啟動額外的單藥治療研究，Peter 將在其發言中進一步說明。若我們的策略成功，這些研究可將可涵蓋人群由目前的 4% 提升至 8% 至 10% 的 CF 人群；並且在我們評估 KALYDECO 對某些其他 CF 患者的適用性時，潛在比例可能更高。

During this quarter we also produced clinical data that provided convincing insight into how we may be able to treat a much greater number of people with CF. The Homozygous Delta 508 population. Specifically, we reported Phase II combination data for VX-809 and KALYDECO, which support moving into pivotal development targeting delta 508 homozygous patients early next year. If successful with these development efforts, we could potentially address 60% or more of the cystic fibrosis population with our different medicines. CF is a serious genetic disease and I'm very proud that our team is at the forefront in developing potentially life-changing medicines for patients and their families. We are committed to being a leader in cystic fibrosis and continuing to work closely with the CF Foundation, patient groups, physicians and patients and their families around the world, to develop additional breakthrough medicines and to provide hope.

在本季度，我們也產出臨床數據，提供具說服力的洞見，說明我們可能如何治療更多的 CF 患者。也就是 Delta 508 同型合子族群。具體而言，我們公布了 VX-809 與 KALYDECO 的第二期合併用藥數據，支持於明年初針對 delta 508 同型合子患者推進至關鍵性開發。若這些開發工作成功，我們有機會透過不同藥物，涵蓋 60% 或更多的囊性纖維化患者族群。CF 是一種嚴重的遺傳性疾病，我非常自豪我們的團隊站在最前線，為患者及其家屬開發可能改變生命的藥物。我們承諾成為囊性纖維化領域的領導者，並將持續與 CF 基金會、病友團體、醫師、患者及其家屬在全球各地密切合作，開發更多突破性藥物並帶來希望。

Let me now turn to hepatitis C. We are leaders today in the treatment of this disease and with the portfolio of novel medicines we have in development, we think we are well-positioned to continue to deliver new regimens for the treatment of hepatitis C. I'll make comments on INCIVEK's recent performance and near-term outlook. We've learned a lot about this evolving market in recent months and I want to share our thinking in terms of how we're approaching our commercial efforts. I'll also talk about our ongoing plans to develop all oral treatment regimens for the future, which I think is very promising, based on today's announcement about our new program.

現在讓我轉到 C 型肝炎。我們目前在此疾病的治療方面居於領先地位，且憑藉我們正在開發的新型藥物產品組合，我們認為我們已具備良好條件，能持續推出用於治療 C 型肝炎的新療程。我將就 INCIVEK 近期的表現與短期展望發表評論。過去幾個月，我們對這個不斷演變的市場有了許多了解，我想分享我們在商業推廣工作上採取何種方式的思考。我也會談到我們持續推進未來全口服治療方案的計畫；基於今天關於我們新計畫的公告，我認為這非常有前景。

Let me start with INCIVEK and two things that have not changed in the first half of this year. INCIVEK market share and persistence rates. First, markets position. INCIVEK has been and remains the leading direct acting antiviral, or DAA. 70% to 75% of genotype 1 patients who initiate therapy with a DAA in the United States continue to initiate treatment with INCIVEK. This position, which we have maintained since the launch of the drug, and which we expect to maintain, speaks to strong execution by our commercial team, as well as to the benefit that this treatment provides to those with hepatitis C.

我先從 INCIVEK 談起，以及今年上半年有兩件事並未改變。INCIVEK 的市占率與治療持續率。第一，市場地位。INCIVEK 一直是、且仍然是領先的直接作用型抗病毒藥物（DAA）。在美國，開始使用 DAA 治療的第 1 型基因型患者中，有 70% 至 75% 仍然選擇以 INCIVEK 作為起始治療。我們自藥物上市以來一直維持、且預期將持續維持的這一地位，反映了我們商業團隊的強力執行力，也反映了此治療為 C 型肝炎患者帶來的效益。

Second, persistence rates. That is the number of patients completing 12 weeks of treatment with INCIVEK. Persistence rates for INCIVEK remain strong and this has been consistent since launch, which once again speaks to the benefit of INCIVEK and the execution of our commercial for team. What has changed in this market is the number of hepatitis C patients initiating treatment, which I'll refer to as the treatment rate. This treatment rate is changing faster than we expected compared to earlier this year, and this is the reason for our revised guidance that Ian will talk about during his remarks.

第二，治療持續率。也就是完成 12 週 INCIVEK 治療的患者人數。INCIVEK 的治療持續率仍然強勁，且自上市以來一直如此，這再次說明 INCIVEK 的效益以及我們商業團隊的執行力。這個市場改變的是開始接受 C 型肝炎治療的患者人數，我將其稱為治療率。與今年稍早相比，治療率的變化速度比我們預期更快，這也是我們修訂指引的原因，Ian 將在他的發言中談到。

I'd like to describe the pattern we've observed to provide some perspective for you on the 13 months since INCIVEK was approved. Soon after launch in the fall of 2011, the annualized treatment rate for all genotype 1 patients had increased to approximately 90,000 to 105,000 patients per year, due in large part to the influx of warehouse patients seeking treatment with the newly approved DAA. During the first four months of 2012 this treatment rate stabilized at approximately 70,000 to 75,000 genotype 1 patients per year. The guidance range that we set in February and reiterated in April was based upon this relatively stable treatment rate adjusted downward for anticipated seasonality and potential for fewer patients to start treatment as the year progressed, as well as on our stable share of this market and our persistence rates. However, in May and June the number of people with hepatitis C initiating any type of therapy substantially decreased by 20% to 25% when compared to the first four months of this year.

我想描述我們觀察到的模式，為各位提供一些視角，回顧 INCIVEK 獲准後的 13 個月。在 2011 年秋季上市後不久，由於大量「囤積等待」的患者湧入、尋求使用新核准的 DAA 治療，所有第 1 型基因型患者的年化治療率上升至約每年 90,000 至 105,000 人。在 2012 年前四個月，該治療率穩定在約每年 70,000 至 75,000 名第 1 型基因型患者。我們在 2 月設定並於 4 月重申的指引區間，是以這個相對穩定的治療率為基礎，並因預期的季節性因素及隨著年度推進可能有較少患者開始治療而向下調整，同時也考量我們在此市場的穩定市占率與治療持續率。然而，在 5 月與 6 月，與今年前四個月相比，開始接受任何類型治療的 C 型肝炎患者人數大幅下降 20% 至 25%。

We attribute this decrease in the overall hepatitis market to two main factors. First, physicians deferring treatment of patients, especially those with less advanced liver disease, following the presentation of multiple sets of mid-stage results for oral combination therapies at this year's EASL conference in April. And second, an increase in the number of ongoing and planned clinical trials in hepatitis C, which has drawn in increasing numbers of patients. The timing and impact of these factors has been difficult to predict and forecast, especially the deferral of treatment in some patients.

我們將整體 C 型肝炎市場的下滑歸因於兩個主要因素。第一，在今年 4 月的 EASL 會議上發表多組口服聯合療法的中期結果後，醫師延後對患者治療，尤其是肝病進展較不嚴重者。第二，C 型肝炎正在進行及規劃中的臨床試驗數量增加，吸引了越來越多患者參與。這些因素的發生時點與影響難以預測與推估，尤其是部分患者的延後治療。

Based on this change in treatment patterns, we are adapting our marketing efforts for INCIVEK and we have also revised our 2012 INCIVEK revenue guidance. As I mentioned, we believe that expectations of future all oral regimens are an important factor in the decreased treatment rates we're seeing over the last few months. Therefore, I would also like to provide some perspective on Vertex's potential to participate in the evolution of these all oral therapies. Based on the Alios data we reported today, we are moving quickly to develop all oral regimens for hepatitis C that we believe could make a major difference for patients and be highly competitive as hepatitis C treatment continues to evolve. We're very encouraged by the clinical potency of ALS-2200 and the compound has shown excellent tolerability to date. Therefore, we believe ALS-2200 could be a central component for future all oral combination regimens.

基於治療模式的改變，我們正在調整 INCIVEK 的行銷推廣工作，並且也修訂了 2012 年 INCIVEK 的營收指引。如我所提，我們認為對未來全口服療程的期待，是我們在過去幾個月看到治療率下降的重要因素。因此，我也想就 Vertex 參與全口服療法演進的潛力提供一些觀點。根據我們今天公布的 Alios 數據，我們正快速推進 C 型肝炎全口服療程的開發；我們相信這將為患者帶來重大改變，並在 C 型肝炎治療持續演進之際具備高度競爭力。我們對 ALS-2200 的臨床效力深受鼓舞，且迄今該化合物顯示出極佳的耐受性。因此，我們相信 ALS-2200 可能成為未來全口服聯合療程的核心組成。

Our guiding principle in the development of all oral regimens is that we want to do what's best for patients. Our new Alios data, coupled with the evolving regulatory pathways, opens the field for us to pursue multiple options. Our key imperatives with our all oral development program are first, evaluate combination regimens with our own DAA's, and consider combination regimens with other company's DAA's. And second, gather as much Phase II data as quickly as possible and in parallel, to enable us to pick the best regimen or regimens to take forward into a pivotal program next year.

我們在開發全口服療程時的指導原則，是希望做對患者最有利的事。我們新的 Alios 數據，加上不斷演進的監管途徑，為我們開啟了追求多種選項的空間。我們全口服開發計畫的關鍵要務，第一是評估與我們自有 DAA 的聯合療程，並考量與其他公司 DAA 的聯合療程。第二是盡可能快速且並行地蒐集更多第二期（Phase II）數據，使我們能在明年選出最佳的一種或多種療程，推進至關鍵性（pivotal）計畫。

More specifically, our approach will be to initiate smaller Phase II studies of ALS-2200 plus multiple other therapies this year to design -- to guide the design of a pivotal trial. Given the many unknowns concerning different all oral combinations, we believe it will be important to design our pivotal program based upon efficacy and safety data from these Phase II studies. With this Phase II data in hand in the first half of next year, we will then target the initiation of a pivotal program starting in late 2013, which we believe represents the best and shortest duration regimen or regimens for people with hepatitis C. Peter will talk more about our data and our plans in a moment.

更具體而言，我們的方法是在今年啟動較小規模的第二期研究，評估 ALS-2200 與多種其他療法的組合，以指導關鍵性試驗的設計。鑑於不同全口服組合存在許多未知數，我們認為根據這些第二期研究的療效與安全性數據來設計關鍵性計畫將非常重要。在明年上半年取得這些第二期數據後，我們將以於 2013 年下半年啟動關鍵性計畫為目標；我們相信這將代表對 C 型肝炎患者而言最佳且療程最短的一種或多種方案。Peter 稍後會進一步談我們的數據與計畫。

In summary, during the last year we have seen a significant evolution in our business at Vertex. Our teams have produced a series of major clinical and commercial achievements that have markedly enhanced the foundation of the business going forward. These achievements, which speak to Vertex's ability to consistently discover develop and commercialize multiple breakthrough medicines, are the foundation upon which we will build a sustainable growing global business over the years to come. I look forward to updating you as we go. I'll now turn it over to Ian.

總結而言，在過去一年中，我們看到 Vertex 的業務出現顯著演進。我們的團隊達成了一系列重大的臨床與商業里程碑，明顯強化了公司未來發展的基礎。這些成就展現了 Vertex 持續發現、開發並商業化多項突破性藥物的能力，並將成為我們在未來多年打造可持續、成長中的全球業務的基石。我期待在推進過程中向各位更新進展。現在我把時間交給 Ian。

Thank you, Jeff. Good evening to everyone. Financially, 2012 is demonstrating that we have a diverse revenue base with multiple sources. These revenues remained significant and are important to enable reinvestment in our pipeline for future growth and value creation in multiple diseases. Now to the results.

謝謝你，Jeff。各位晚安。在財務方面，2012 年顯示我們擁有多元的營收基礎與多個來源。這些營收仍然可觀，並且對於我們再投資於研發管線、以在多種疾病領域實現未來成長與價值創造至關重要。接下來看業績結果。

In second quarter 2012, total revenues were approximately $418 million, compared to approximately $114 million in the same quarter of last year. The key components of these second-quarter revenues are as follow. First, we reported approximately $328 million of INCIVEK net product revenues. This reflects a strong April and then a decrease in a number of new patients initiating treatment, most notably in May and June, as Jeff has already described.

2012 年第二季，總營收約為 4.18 億美元，相較於去年同期約 1.14 億美元。第二季營收的主要組成如下。第一，我們認列約 3.28 億美元的 INCIVEK 產品淨營收。這反映 4 月表現強勁，隨後新患者開始治療的人數下降，尤其在 5 月與 6 月最為明顯，如 Jeff 先前所述。

Second, we recorded $46 million of net product revenues from KALYDECO, which reflects the first full quarter of sales since launch in February earlier this year. This reflects strong patient demand, the connectivity of the CF community, and the broad awareness of the importance of KALYDECO. We expect this revenue stream to grow as more people start and maintain treatment with KALYDECO. We have now received approval in Europe to add to this revenue base and provide further growth. We foresee a sustainable long-term and growing revenue base from KALYDECO.

第二，我們認列 KALYDECO 產品淨營收 4,600 萬美元，反映該產品於今年 2 月上市後的第一個完整銷售季度。這反映了患者需求強勁、囊性纖維化（CF）社群的緊密連結，以及市場對 KALYDECO 重要性的廣泛認知。隨著更多人開始並持續使用 KALYDECO 治療，我們預期此營收來源將成長。我們現已在歐洲取得核准，可進一步擴大此營收基礎並帶來更多成長。我們預期 KALYDECO 將帶來可持續、長期且成長中的營收基礎。

Third, we received $33 million of royalty revenues, including $28 million of INCIVO royalty revenue from J&J. We expect our INCIVO royalties will continue to contribute positively to our financial results during 2012, given that INCIVO is now available in more than 25 countries. And finally we received collaborative revenues of $12 million. These revenues primarily fund R&D activities where we have relationships in the areas of hepatitis C and cystic fibrosis.

第三，我們收到3,300萬美元的權利金收入，其中包括來自J&J的2,800萬美元INCIVO權利金收入。鑑於INCIVO目前已在超過25個國家上市，我們預期INCIVO權利金在2012年將持續對我們的財務結果帶來正面貢獻。最後，我們收到1,200萬美元的合作收入。這些收入主要用於資助研發活動，我們在丙型肝炎與囊性纖維化領域有合作關係。

The GAAP net loss attributable to Vertex was $65 million in the second quarter of 2012, or approximately $0.31 per share. The net -- the non-GAAP net income was approximately $100 million, or $0.46 per diluted share. The non-GAAP income includes three charges, $31 million excludes three charges -- my apologies -- $31 million in stock compensation, $56 million related to increasing the fair value of the expected future payments under our Alios collaboration following the positive viral kinetic data announced today, and a $78 million charge in the cost of product revenues to reserve against the potential excess INCIVEK inventory.

2012年第二季歸屬於Vertex的GAAP淨損為6,500萬美元，約每股0.31美元。非GAAP淨利約為1億美元，稀釋後每股0.46美元。非GAAP淨利包含三項費用，3,100萬美元不含三項費用——抱歉——3,100萬美元的股票薪酬費用、因今日公布的正向病毒動力學數據而提高我們與Alios合作下預期未來付款公允價值所致的5,600萬美元，以及在產品收入成本中提列7,800萬美元費用，用以針對可能過剩的INCIVEK庫存進行備抵。

And now 2012 financial guidance. Based on the recent decline in the number of hepatitis C patients initiating treatment, we have revised our 2012 forecast for a total annual INCIVEK revenues to $1.1 billion to $1.25 billion. This range reflects recent decline in patients initiating treatment, which Jeff noted.

接下來是2012年財務指引。基於近期開始接受治療的丙型肝炎患者人數下降，我們已將2012年全年INCIVEK總收入預測修正為11億至12.5億美元。此區間反映了Jeff所提到的近期開始治療患者人數下滑。

Now to our operating expenses. Based upon the achievements of multiple successful proof of concept studies in cystic fibrosis, ACD, and RA respectively, being VX-809 and KALYDECO combination results reported in the second quarter, the viral kinetic results in ALS-2200, announced today, and the results of VX-509 in rheumatoid arthritis last year, we have increased and accelerated our investment into these high-priority programs. These monies were significant. Despite its increased investment, we have maintained our operating expense guidance for 2012 of $1.03 billion to $1.13 billion, which we provided on our February 2 call. We accomplished this by prioritizing and reducing expenses, specifically with significant reductions in G&A spend and aligning our commercial spend to follow future demand in the markets we are in. These expense reductions have enabled us to reallocate resources towards and within R&D to support the acceleration of these programs, yet maintain our operating expense guidance.

接著談我們的營運費用。基於在囊性纖維化、ACD與RA等領域分別完成多項成功的概念驗證研究之成果，包括第二季公布的VX-809與KALYDECO合併用藥結果、今日公布的ALIS-2200病毒動力學結果，以及去年VX-509在類風濕性關節炎的結果，我們已提高並加速對這些高優先級計畫的投資。這些資金投入相當可觀。儘管投資增加，我們仍維持2012年營運費用指引為10.3億至11.3億美元，該指引已於2月2日電話會議中提供。我們透過設定優先順序並降低費用來達成此目標，具體而言，大幅削減一般及行政（G&A）支出，並使商業化支出與我們所處市場的未來需求相匹配。這些費用削減使我們得以將資源重新配置至研發（R&D）並在研發內部調整，以支持這些計畫加速推進，同時仍維持我們的營運費用指引。

In summary, we continue to derive a significant revenue and cash flow from INCIVEK sales and INCIVO royalties. KALYDECO continues to exceed our expeditions, and with the clinical results in hepatitis C and CF, we hope to expand our presence and the number of people we can treat over the long-term. Now with viral kinetic data announced today for ALS-2200, our nucleotide analog for hepatitis C, we have the potential to participate in the high-value HCV market with all oral combinations. We accomplished all of this while generating earnings and cash flow to end the quarter with approximately $1.2 billion of cash and equivalents. I will now turn the call over to Peter.

總結而言，我們仍持續從INCIVEK銷售與INCIVO權利金中取得可觀的收入與現金流。KALYDECO持續超出我們的預期，並且隨著丙型肝炎與囊性纖維化（CF）的臨床結果，我們希望長期擴大我們的布局以及可治療的人數。此外，隨著今日公布ALS-2200（我們用於丙型肝炎的核苷酸類似物）的病毒動力學數據，我們有機會以全口服合併療法參與高價值的HCV市場。我們在達成上述成果的同時，也創造了獲利與現金流，使本季末現金及約當現金約為12億美元。接下來我將把電話會議交給Peter。

Thank you, Ian, and good evening, everybody. My remarks will cover some of the pipeline advances that we have made in recent months, most notably in the areas of CF and hepatitis C.

謝謝你，Ian，各位晚安。我的發言將涵蓋我們近幾個月在研發管線上的一些進展，尤其是在囊性纖維化與丙型肝炎領域。

In cystic fibrosis, during the second quarter we announced resource from a Phase II study of the correct VX-809 in combination with KALYDECO. We are very pleased with the resource we have found and data support to start of a pivotal to the program early next year. To briefly summarize the key data again, the top dose of VX-809, 600 milligrams once daily, showed a mean absolute improvement in FEV1 of 3.4% over the 56 day course of the study compared to base line, and a 6.7% improvement in FEV1 over the placebo arm for the same time period. Both of these were statistically significant with P values of 0.03 and 0.002 respectively.

在囊性纖維化方面，我們在第二季公布了一項第二期研究的結果，該研究評估校正劑VX-809與KALYDECO合併使用。我們對所獲得的結果非常滿意，相關數據支持我們於明年初啟動該計畫的關鍵性試驗。簡要再次總結關鍵數據：VX-809最高劑量組為每日一次600毫克，在56天研究期間，相較基線FEV1平均絕對改善3.4%，且在相同期間相較安慰劑組FEV1改善6.7%。兩者皆達統計顯著，P值分別為0.03與0.002。

To ask the most important data comes from the period between day 28 and day 56, which was when the patients were actually receiving VX-809 and KALYDECO in combination. A distinct pattern emerged between day 28 and day 56. All the dose arms involving VX-809 and KALYDECO in combination improved over this time period, while the placebo arm declined. The 600 milligram dose showed the best response of -- within subject mean absolute improvement in FEV1 of 6.1% over this time period, with a P value of less than 0.001 and a mean absolute improvement in FEV1 compared to placebo of 8.6%, also with a P value of less than 0.001. More than half of the patients in the 600 milligram once daily arm experienced a greater than 5% absolute improvement in FEV1 during this period.

我們認為最重要的數據來自第28天到第56天這段期間，因為患者在此期間實際上是接受VX-809與KALYDECO的合併治療。在第28天到第56天之間出現了明顯的趨勢。所有包含VX-809與KALYDECO合併用藥的劑量組在此期間皆有所改善，而安慰劑組則下降。600毫克劑量組反應最佳：受試者內FEV1平均絕對改善為6.1%，P值小於0.001；相較安慰劑的FEV1平均絕對改善為8.6%，P值亦小於0.001。在此期間，每日一次600毫克組超過一半的患者FEV1絕對改善幅度大於5%。

VX-809 was well tolerated as a single agent and in combination with KALYDECO. Adverse events and severe adverse events were similar between VX-809 and placebo groups. We have analyzed the data many different ways, by dose versus placebo versus baseline, and on an individual patient basis. All of this analysis support the conclusion that VX-809 in combination with KALYDECO was well tolerated and associated with significant clinical activity. We expect that investigators will present additional Phase II combination data at the medical conference this fall. We continue to make progress in designing a pivotal program in the delta 508 homozygous patients 12 years and older and are on track to initiate a global pivotal program in the early part of 2013, pending discussions with regulatory authorities. Our goal is to confirm the results of cohort two of the Phase II study by evaluating 600 milligram once daily of VX-809 and potentially other doses in combination with KALYDECO twice a day.

VX-809無論單獨使用或與KALYDECO合併使用，耐受性皆良好。VX-809組與安慰劑組之不良事件與嚴重不良事件相近。我們以多種方式分析數據，包括依劑量對照安慰劑與基線，以及以個別患者為基礎的分析。所有分析均支持以下結論：VX-809與KALYDECO合併使用耐受性良好，且與顯著的臨床活性相關。我們預期研究者將於今年秋季的醫學會議上發表更多第二期合併治療數據。我們持續在設計針對Δ508純合子、12歲以上患者的關鍵性計畫方面取得進展，並按計畫在2013年初啟動全球關鍵性計畫，惟仍需與監管機關討論後確定。我們的目標是透過評估每日一次600毫克VX-809以及可能的其他劑量，並與每日兩次KALYDECO合併使用，以確認第二期研究第二隊列的結果。

We have also initiated two important new Phase III studies of KALYDECO mono therapy. The first is a 40 patient study in patients with at least one copy of the R117H mutation, and the second is a 20 patient crossover study of patients with a non-G551D [gating] mutation. These are both six-month studies with primary endpoints of FEV1 and safety. We anticipate having results of both studies next year, with the goal of generating data that will support an expansion of KALYDECO's label to address these populations. Just last week, we received approval of KALYDECO in EU for G551D patients aged six and older. I'm proud of the efforts of our team to achieve this first European approval for a Vertex medicine.

我們也已啟動兩項重要的KALYDECO單藥治療第三期新研究。第一項為40名患者研究，對象為至少帶有一份R117H突變拷貝的患者；第二項為20名患者的交叉試驗，對象為具有非G551D［gating］突變的患者。兩項研究皆為期六個月，主要終點為FEV1與安全性。我們預期明年取得兩項研究結果，目標是產生可支持擴大KALYDECO適應症標籤、以涵蓋這些族群的數據。就在上週，我們獲得KALYDECO在歐盟核准，用於6歲以上G551D患者。我為我們團隊的努力感到自豪，成功達成Vertex藥品在歐洲的首次核准。

I would also like to comment on our second CFTR corrector, VX-661. The Phase II study is ongoing, it's lowering the corrector VX-661 in combination with KALYDECO in CF patients who are homozygous with delta 508. This study is designed as a dose escalation placebo-controlled study. Part A of the study, which we initiated earlier this year, is evaluating different doses of VX-661 alone or in combination with KALYDECO for 28 days in approximately 100 patients in total. The design is different than the Phase II VX-809 study, reflecting the earlier stage of development for VX-661. This is our first trial of VX-661 in patients. We expect to conclude all dosing and follow-up in part A of the VX-661 study before we discuss results publicly. And we anticipate that this will take place in 2013.

我也想就我們的第二個 CFTR 校正劑 VX-661 做一些評論。第二期研究正在進行中，該研究是在帶有 delta 508 同型合子之囊性纖維化（CF）患者中，評估校正劑 VX-661 與 KALYDECO 併用。本研究設計為劑量遞增、安慰劑對照研究。研究的 A 部分我們在今年稍早啟動，將在約 100 名患者中，評估 VX-661 單獨使用或與 KALYDECO 併用、為期 28 天的不同劑量。此設計不同於 VX-809 的第二期研究，反映 VX-661 仍處於較早期的開發階段。這是我們首次在患者中進行 VX-661 的試驗。我們預期在對外公開討論結果之前，會先完成 VX-661 研究 A 部分的所有給藥與追蹤。我們預期這將在 2013 年發生。

Now, turning to hepatitis C. Today, we announced seven-day viral kinetic results for ALS-2200, a nucleotide analog that was licensed from Alios last year. These are very encouraging results that allow us to move rapidly into Phase II all oral studies later this year. We achieved a median reduction of 4.54 [blocks in ACD RNA] from baseline, into seven-day trial with a 200 milligram once a day dose. The activity was consistent among patients with a range of 3.81 to 5.08 blocks after seven days of treatment. The initial drop in viral load in this dose group was steep. 3.85 blocks after three days and ALS-2200 was also well tolerated. There were no SAE's or dropouts.

接著談丙型肝炎。今天，我們公布了 ALS-2200 的七天病毒動力學結果；ALS-2200 是一種核苷酸類似物，去年自 Alios 取得授權。這些結果非常令人鼓舞，使我們能在今年稍晚迅速推進至第二期全口服研究。在七天試驗中，以每日一次 200 毫克劑量，我們達到相較基線的中位數下降 4.54 [blocks in ACD RNA]。在治療七天後，不同患者的活性表現一致，範圍為 3.81 至 5.08 blocks。在此劑量組中，病毒量的初始下降幅度很陡峭。三天後下降 3.85 blocks，且 ALS-2200 的耐受性也良好。未出現任何嚴重不良事件（SAE），也沒有退出試驗的情況。

From here, we are advancing rapidly to all oral interferon-free combination studies. We expect to begin two clinical studies with compounds within our own portfolio in the second half of this year. First, a Phase II 12 week study of ALS-2200 in combination with INCIVEK in genotype 1 patients. And second, also a Phase II study, 12 weeks of ALS-2200 in combination with ribavirin in genotype 1 patients. These studies will evaluate safety and efficacy as measured by SVR 4 and SVR 12 and should enable us to move into advanced studies. As Jeff mentioned, we will consider regimens with our own compounds, as well as the merits of combining ALS-2200 with other leading direct antivirals currently in development. We will work towards the best target regimens for the different patient populations in hepatitis C.

接下來，我們將快速推進至全口服、無干擾素的聯合治療研究。我們預期在今年下半年啟動兩項使用我們自有產品組合中化合物的臨床研究。第一項為第二期、為期 12 週的研究：ALS-2200 與 INCIVEK 併用，對象為基因型 1 患者。第二項同樣為第二期研究：ALS-2200 與利巴韋林（ribavirin）併用 12 週，對象亦為基因型 1 患者。這些研究將評估安全性與療效，並以 SVR 4 與 SVR 12 作為衡量指標，應可使我們進入更後期的研究。如 Jeff 所提，我們將考量使用自有化合物的療程，也會評估將 ALS-2200 與目前開發中的其他領先直接抗病毒藥物併用的優點。我們將致力於為丙型肝炎不同患者族群制定最佳目標療程。

In summary, our efforts in cystic fibrosis reflect the conviction that we can leverage our R&D experience, scientific knowledge and capabilities, to make a big difference in the lives of many patients with cystic fibrosis. In our ongoing efforts in hepatitis C demonstrate our commitment to continued innovation in this area. I would like to thank our development teams who have executed extremely well to advance and broaden our pipeline in the last 12 months.

總結而言，我們在囊性纖維化上的努力，反映我們堅信能運用研發經驗、科學知識與能力，為許多囊性纖維化患者的生活帶來重大改變。我們在丙型肝炎方面持續的努力，展現了我們對此領域持續創新的承諾。我要感謝我們的開發團隊，在過去 12 個月中執行得非常出色，推動並擴大了我們的產品線。

Before I finish, I will just highlight one more high-priority program, our JAK3 inhibitor, VX-509. We established proof of concept in rheumatoid arthritis last year and advanced this program now into Phase IIb to study VX-509 on a background of methotrexate. We are enrolling now and we expect to initiate studies in auto-immune mediated inflammatory diseases beginning in 2013. Beyond hepatitis C, CF and RA, we have important programs in development, targeting flu, epilepsy and other diseases. I look forward to reporting on our progress in those areas in upcoming quarters. I will now turn it back over to Michael.

在結束之前，我再強調一個高優先級計畫：我們的 JAK3 抑制劑 VX-509。我們去年在類風濕性關節炎中建立了概念驗證，並已將此計畫推進至第二期 b，研究在甲氨蝶呤（methotrexate）背景治療下的 VX-509。我們目前正在收案，並預期自 2013 年起啟動針對自體免疫介導之發炎性疾病的研究。除了丙型肝炎、囊性纖維化與類風濕性關節炎之外，我們還有多項重要開發計畫，目標涵蓋流感、癲癇及其他疾病。我期待在接下來的季度中，向各位報告我們在這些領域的進展。現在我把時間交回給 Michael。

Thank you, Peter. That now concludes our prepared remarks. Tyrone, we'd like to open up the call to questions.

謝謝你，Peter。以上為我們事先準備的發言內容。Tyrone，我們想開放電話會議進入提問。

(Operator Instructions) Geoffrey Porges, Bernstein.

（接線員指示）Bernstein 的 Geoffrey Porges。

Congratulations on another important discovery or at least development program. Well done. Just a few questions. On the Alios nucs, the first is -- Bill, sort of technical questions is the first we learned much about them. Peter, can you tell us whether there are -- whether there is any C3 or 4A metabolism there or likely interactions?

恭喜你們又有一項重要的發現，或至少是一個開發計畫。做得很好。我有幾個問題。關於 Alios 的核苷酸類藥物（nucs），第一個問題——Bill，算是技術性問題，也是我們第一次對它們有較多了解。Peter，你能否說明是否存在任何 C3 或 4A 代謝，或可能的交互作用？

Secondly, if you were to cast a wide net, what would be your preference for combination with the nucs, given the profile you've seen so far? You conspicuously didn't mention 222 and I wonder if we should read anything into that? And lastly, is there any dose response worth pursuing to a higher dose than the 200? Thanks and I'll get back in the queue.

第二，如果你們要廣泛地考量，基於目前看到的特性，你們偏好核苷酸類藥物與哪些藥物併用？你們很明顯沒有提到 222，我想知道我們是否需要從中解讀出什麼？最後，是否有任何值得追求的劑量反應關係，讓劑量高於 200？謝謝，我回到隊列中。

Not exactly in the order that you gave them, but let's say for 222, it was not knowingly omitted, for sure. We're certainly looking at ways of folding that into our development. We've mentioned the two potential Phase 2 studies that we're planning. They may well be other Phase 2 studies in more difficult to treat populations where a somewhat larger number of compounds combined together might be useful. And that's likely where you'll see 222 come in. We also could combine it with one of the nucs and there would be no reason not to do that. It's just that we've chosen INCIVEK as the initial one that we're going to pursue.

我不完全按照你提問的順序回答；先談 222，它絕對不是刻意省略。我們當然正在思考如何把它納入我們的開發計畫。我們已提到正在規劃的兩項潛在第二期研究。也可能會有其他第二期研究，針對較難治療的族群，在那種情況下，將較多化合物一起併用可能會有幫助。而那很可能就是你會看到 222 介入的地方。我們也可以把它與其中一個核苷酸類藥物併用，沒有理由不這麼做。只是我們選擇 INCIVEK 作為最初要推進的組合。

In terms of dose response, yes, we're going to be exploring that more with some PK/PD analyses to try to figure out if it makes any sense to go higher. And we certainly could do that if we choose to do so. In terms of SIP metabolism, at this point, we don't know that much about these compounds. They just obviously have been in very short term studies. But in general, nucs have not really had major drug interactions with other compounds and we would expect these to be similar. Obviously, we'll see what we get in future studies.

就劑量反應而言，是的，我們會透過一些 PK/PD 分析進一步探索，試著判斷提高劑量是否有意義。如果我們選擇這麼做，當然也可以提高劑量。至於 SIP 代謝，目前我們對這些化合物了解還不多。它們顯然只在非常短期的研究中使用過。但一般而言，核苷酸類藥物與其他化合物之間並沒有顯著的藥物交互作用，我們預期這些也會類似。當然，我們會在後續研究中看看結果如何。

Thanks very much. I'll jump back in the queue.

非常感謝。我回到隊列中。

Rachel McMinn, Bank of America Merrill Lynch.

美國銀行美林（Bank of America Merrill Lynch）的 Rachel McMinn。

I also had a couple of LIS questions. I wanted to better understand why you're interested in doing separate studies, one with telaprevir and one with the ribavirin, but not looking to do triple? And just make sure that the ribavirin study is going to be in genotype 1 and understand that rationale?

我也有幾個關於 LIS 的問題。我想更了解你們為什麼有興趣做分開的研究，一個與 telaprevir 併用、另一個與利巴韋林併用，但不打算做三聯療法？另外也想確認：利巴韋林研究將在基因型 1 中進行，並了解其理由？

And is this nuc the adenosine? Can you tell us which -- what the base is? And should we presume that because you've made the decision to go forward that if you -- are there any inferences to make on the other Alios nucs? So if the data looks just as strong, are you planning on -- how would that influence your clinical decisions going forward? Thanks.

另外，這個核苷酸類藥物是腺苷（adenosine）嗎？你能告訴我們是哪一種——其鹼基（base）是什麼嗎？以及我們是否應該推定，既然你們已決定推進，對其他 Alios 的核苷酸類藥物是否有任何可推論之處？所以如果數據同樣強勁，你們是否打算——這將如何影響你們接下來的臨床決策？謝謝。

Maybe I'll take the last one first. And just say that clearly we have the data for ALS-2200 in our hand right now, and our plan is to move as quickly as we can with that compound. If all goes well with 2158 and we have another compound, obviously we'll fold that into development when it comes along. And that could be in the setting of either new nuc combinations or combinations of each one with other compounds. I wouldn't otherwise read anything into it except just that two studies are just not running completely in parallel with each other.

也許我先從最後一個問題回答。我只想清楚地說，我們現在手上已經有 ALS-2200 的數據，而我們的計畫是盡可能快速推進這個化合物。如果 2158 一切順利，而且我們還有另一個化合物，顯然等它出來時我們也會把它納入開發。而那可能是在新的 nuc 組合，或是各自與其他化合物搭配的組合情境下進行。除此之外我不會做其他解讀，只是兩項研究並不是完全彼此同步、平行地進行。

In terms of the structure, we haven't revealed that so I won't say much more about that. In terms of the ribavirin study, yes, we do plan to do all of our work in genotype 1. We see that as where the biggest unmet medical need is at that point. And so we would pursue that.

就結構而言，我們尚未揭露，所以我不會再多說。至於利巴韋林（ribavirin）研究，是的，我們確實計畫把所有工作都放在基因型 1。我們認為那是當時最大的未被滿足醫療需求所在。因此我們會朝那個方向推進。

And one of the reasons to do the ribavirin plus 2200 study is obviously part of the goal of Phase 2 is to gather some additional, well-needed safety data on the compounds in longer durations. And we just want as clean system as we can to be able to tease out the safety profile of 2200 from the other compounds. The reason for separate studies is convenience rather than folding everything into one humongous thing. It is easier to manage separate studies.

而進行利巴韋林加 2200 研究的原因之一，顯然是因為第二期（Phase 2）的部分目標，是在較長療程下蒐集一些額外且非常需要的化合物安全性資料。我們也希望系統盡可能乾淨，好把 2200 的安全性特徵從其他化合物中釐清出來。分開做研究的原因是便利性，而不是把所有東西都塞進一個龐然大物。分開的研究比較容易管理。

I'm still unclear why you wouldn't just run triple. If you have an arm without the PI, one with the PI, why wouldn't you run all three together?

我還是不太明白為什麼你們不直接做三聯。如果你們有一組不含 PI 的組別、一組含 PI 的組別，為什麼不把三個一起跑？

Just our preference to do it this way.

這只是我們偏好用這種方式來做。

Obviously, we just deceived this data and we're thinking through it. It gives us a lot of optionality, as you point out with respect to our own compounds. As we said, we'll consider combining 2200 with other folks' compounds as well. I want to be clear as part of what you're hearing is an evolution of our thinking as we understand what the true optionality here is. And I think the important thing to take away from this is that our plan is to do multiple Phase 2 studies quickly in order to pick the best combination that we can take forward into Phase 3 based on actual efficacy and safety data.

顯然，我們才剛拿到這些數據，正在消化並思考。如你所指出的，這讓我們在自家化合物方面有很多選擇彈性。正如我們所說，我們也會考慮把 2200 與其他公司的化合物做組合。我想要說清楚，你們聽到的部分內容，是我們在理解這裡真正的選擇彈性後，思維正在演進。我認為最重要的重點是：我們的計畫是快速進行多項第二期研究，根據實際的療效與安全性數據，挑選我們能帶入第三期（Phase 3）的最佳組合。

Great. Thank you very much.

很好。非常感謝。

Mark Schoenebaum, ISI Group.

Mark Schoenebaum，ISI Group。

Quick one. Do you guys have the data in-house for 2158? I don't know if -- you may have mentioned and I may have missed it. And maybe on CF, on the 661 trial can you be really clear, is there an interim or is there not an interim in that trial? And what changed that caused you guys to move the timelines out from this year to next year? And also on that, can you remind us of the design? Also on the combo, can you give us an update on when you're actually going to meet with the FDA to talk about a Phase 3 design? Thanks.

快速問一個。你們有 2158 的內部數據嗎？我不知道——你們可能提過但我可能漏聽了。另外關於 CF、關於 661 試驗，你們能不能講得很清楚：那個試驗到底有沒有期中分析（interim）？以及是什麼改變，導致你們把時程從今年延到明年？也請提醒我們一下試驗設計。另外關於組合療法，你們能否更新一下你們實際上何時會與 FDA 會面，討論第三期設計？謝謝。

I'll take the 2158 question. And that is the study is ongoing and still blinded so there's nothing really much that I can say about it.

我來回答 2158 的問題。那項研究仍在進行中，而且仍是盲態，所以我其實沒有太多可以說的。

So with respect to 661, Mark, it's a complicated study. It's adaptive trial design so we will have some data as we go along and we want to see the entirety of the data before we basically make any statement to the outer world, obviously. And that takes a while. So it's not a linear type of design. It's an adaptive trial designed to make sure we look at the compound from different angles and get a good feeling about dosing and compatibility with 809. So we hope that if everything goes well we can provide you data in 2013. So that's -- for this piece in terms of -- what was the other question?

至於 661，Mark，這是一個很複雜的研究。它是適應性試驗設計（adaptive trial design），所以我們會在進行過程中取得一些數據，但顯然我們希望在基本上對外發表任何說法之前，先看到完整的數據。而那需要一些時間。所以它不是線性式的設計。這是一個適應性試驗，目的是確保我們從不同角度評估該化合物，並對劑量以及與 809 的相容性有良好掌握。因此我們希望如果一切順利，能在 2013 年提供數據。所以——就這部分而言——另一個問題是什麼？

The Phase 3 on the combo. When you may meet with the FDA?

關於組合療法的第三期。你們可能何時會與 FDA 會面？

Towards the fourth quarter of this year we will have a meeting and then talk about how we go forward that is needed to initiate the trial the beginning of 2013.

今年第四季左右我們會開會，然後討論接下來需要怎麼做，才能在 2013 年初啟動該試驗。

Can I slip one in for Ian? Ian, if revenues decline -- I know you're not giving 2013 guidance but a general philosophical question -- if revenues continue to decline into 2013, how should we be thinking about our 2013 expense modeling?

我可以替 Ian 插問一題嗎？Ian，如果營收下滑——我知道你不提供 2013 年指引，但這是一個比較哲學性的問題——如果營收持續下滑到 2013 年，我們在做 2013 年費用模型時應該怎麼思考？

Actually, to the expense question, Mark, I think you can expect us to look at it the same way that we have this year. What we're trying to communicate on this call is a very active program, specifically in our G&A area this year, as well as being nimble as we see markets change and adapt our marketing programs as well. That's allowed us to maintain the guidance that we have this year despite the increased investments in the priority programs.

其實就費用問題而言，Mark，我想你可以預期我們會用和今年相同的方式來看待。我們在這通電話中想傳達的是：今年我們有一個非常積極的計畫，特別是在一般及行政（G&A）領域，同時也會在看到市場變化時保持靈活，並相應調整我們的行銷計畫。這讓我們即使在優先項目投資增加的情況下，仍能維持今年的指引。

As we go into 2013, we have to have a good understanding, we'll get more data and more understanding of the market. But in terms of philosophical question, we're trying to minimize the G&A, the SG&A in our business to the extent we can to prioritize that investment into R&D into these high-value programs.

進入 2013 年時，我們必須有良好的掌握；我們會取得更多數據，對市場也會有更多理解。但就哲學性問題而言，我們會盡可能把業務中的 G&A、以及銷售、一般及行政（SG&A）降到最低，以便把投資優先放到研發（R&D）這些高價值計畫上。

Thank you.

謝謝。

Mark, this is Jeff. Maybe just to add even a bit higher-level view, because Ian reviewed the pure financial considerations, I think our vision and our strategy has been quite consistent, which is that we're trying to build a global multi-product business that can produce long-term growth. And obviously we've made some important and impressive progress this year on our late-stage pipeline.

Mark，我是 Jeff。也許補充一個更高層次的觀點：因為 Ian 已經回顧了純粹的財務考量，我認為我們的願景與策略一直相當一致，也就是我們正努力打造一個全球性的多產品業務，能夠帶來長期成長。而且顯然今年我們在後期研發管線上取得了一些重要且令人印象深刻的進展。

As we go into 2013, I think we want to continue to invest in that pipeline to maximize value. And we'll do so. But we've also said we're going to be financially very disciplined, both in terms of prioritizing programs and in terms of controlling our expenses. And that's our plan. And we'll give you more insight on that as all the pieces of the puzzle from both revenue and expense side come together later this year.

進入 2013 年，我想我們希望持續投資該管線以最大化價值。我們會這麼做。但我們也說過，我們在財務上會非常自律，無論是在計畫優先順序的取捨上，或是在費用控管上。這就是我們的計畫。等到今年稍晚，營收端與費用端的各個拼圖逐步到位後，我們會提供你們更多洞見。

Thank you.

謝謝。

Yaron Werber, Citi.

Yaron Werber，花旗（Citi）。

A few questions if you don't mind on the Alios nucs. One, any sense you can give us what was the breakdown between 1A and 1B in that study? Second question, did you see any breakthrough at all on therapy and then three, what's the metabolism of the nucs? Are they metabolized by the liver at all? Just give us a little sense on what are you seeing in animals?

如果你們不介意，我有幾個關於 Alios nucs 的問題。第一，你們能否告訴我們該研究中 1A 與 1B 的分布大概是怎樣？第二個問題，治療期間你們有看到任何突破（breakthrough）嗎？第三，這些 nucs 的代謝如何？它們會在肝臟代謝嗎？請稍微讓我們了解一下你們在動物身上看到什麼。

As you saw in our release, the patient population was primarily genotype 1B. That's likely just geographically based. The study was conducted primarily in Eastern and Western Europe. In terms of breakthroughs, there were none on therapy. And metabolism we haven't really talked about very much, so there's not much to say about those. These are nucleotide pro-drugs and so they are metabolized as they get into the liver through first-pass metabolism into the active compounds.

如同你們在我們的新聞稿中看到的，受試者族群主要是基因型 1B。那很可能只是地理因素所致。該研究主要在東歐與西歐進行。就突破而言，治療期間沒有出現。至於代謝，我們其實沒有談很多，所以也沒有太多可以說。這些是核苷酸前驅藥（nucleotide pro-drugs），因此它們進入肝臟後會經由首渡代謝（first-pass metabolism）轉化為活性化合物。

Just in terms of the 1A/1B breakdown I'll just say that in general for the nucs, there really hasn't been any real difference in activity between genotype 1A and 1B clinically. In vitro for these compounds, there's no real difference between them. And when you look at the data in the trial, even though there were just a couple of people with genotype 1A, the viral declines were really indistinguishable from the genotype 1B patients. So we don't really anticipate there being any big difference there.

就 1A/1B 的拆分而言，我只想說，一般來說，對於這些核苷（nucs），在臨床上基因型 1A 與 1B 之間其實並沒有任何真正的活性差異。在體外試驗中，這些化合物之間也沒有真正的差異。而當你看試驗數據時，即使基因型 1A 的受試者只有少數幾位，其病毒下降幅度也確實與基因型 1B 病患幾乎無法區分。因此我們並不預期那裡會有任何重大差異。

And maybe a last question, how do you -- give us a little bit of a sense, you have a lot of work to do. This data is fantastic, but you have data on eight patients at seven days. At this point, you need to do drug/drug interactions, you need to have several hundred patients on drug before you can move into a pivotal -- just trying to understand how is it possible that you can start a pivotal study within 16 months or so?

也許最後一個問題，你們能不能——讓我們稍微了解一下，你們還有很多工作要做。這些數據非常棒，但你們只有 8 位病患、7 天的數據。在這個時間點，你們需要做藥物/藥物交互作用研究，而且在進入關鍵性試驗之前，你們需要讓數百位病患用藥——我只是想了解，為什麼你們有可能在大約 16 個月內就啟動一項關鍵性研究？

The way we do it is to move as quickly as we can into a broad Phase 2 program that will give us the safety database that we need. And we don't disagree with the numbers. It will be hundreds of patients required, and we anticipate gaining those in various combinations in a series of Phase 2 studies, perhaps in different patient populations to basically try to define the right regimens for the right patients. And that is how we will go forward.

我們的做法是，盡可能快速地推進到一個廣泛的第二期（Phase 2）計畫，來建立我們所需要的安全性資料庫。而且我們不否認你提到的數字。確實需要數百位病患，我們預期會透過一系列第二期研究、在各種不同的組合中取得這些數據，或許也會在不同的病患族群中進行，基本上是要為合適的病患界定合適的治療方案。這就是我們將如何往前推進。

And we anticipate being able to move quickly. There's a great demand for patients to enter trials with nucs because of their potential advantages. We don't expect any difficulties with recruitment. And so we will be moving it along quickly.

我們也預期能夠快速推進。由於核苷（nucs）具有潛在優勢，病患對於參與核苷試驗的需求非常高。我們不預期招募會有任何困難。因此我們會很快把進度往前推。

Yes. And as we go forward, when you really look into how those trials normally proceed, we have really an option here by end of next year to basically enter into a pivotal program. The nice thing, as Jeff alluded to, is we will have numerous evaluations of differing combinations in different patient populations that gives us a good sense what is the best direction and for a particular patient population that we want to move forward. I think our decision will be data-driven and safety-data-driven. And so we go forward by end of next year with as a solid program. And I think that gives us an option to be a player in the field.

是的。而且隨著我們往前推進，當你真正去看那些試驗通常如何進行時，我們其實有一個選項：在明年年底之前，基本上就能進入一個關鍵性計畫。如 Jeff 所提到的，好處在於我們將在不同病患族群中評估多種不同的組合，這能讓我們對最佳方向有很好的掌握，並針對我們想要推進的特定病患族群做出選擇。我認為我們的決策將以數據為依據，並以安全性數據為依據。因此到明年年底，我們會以一個扎實的計畫向前推進。我認為這讓我們有機會成為這個領域的參與者。

Geoff Meacham, JPMorgan.

Geoff Meacham，摩根大通（JPMorgan）。

For KALYDECO and the R117H pivotal, it looks to be a six-month study. I'm curious if there's an interim at, say, three months and then if you guys are thinking initially that your delta F homozygous study will also be six months or have you had any preliminary discussions with FDA that it still will have to be a 12-month pivotal? And I have one follow-up.

關於 KALYDECO 以及 R117H 的關鍵性試驗，看起來會是一項為期六個月的研究。我想知道是否會在例如三個月時做期中分析（interim），另外你們是否一開始就認為你們的 delta F 純合子研究也會是六個月，還是你們已經和 FDA 做過初步討論，認為仍然必須做 12 個月的關鍵性試驗？我還有一個追問。

With respect to the mono therapy in KALYDECO label extension studies, 117 and the gating, the non-551D gating, both of them will be six-month studies without interims. So we are not doing interims here. It's a small patient population. You don't want to disturb the integrity of the drug by doing interims. So we are not doing this. So the data will be available at the course of next year. And then we will basically file an SNDA to get a label extension so that's for this part.

就 KALYDECO 標籤延伸研究中的單藥治療而言，117 以及 gating（非 551D gating）這兩項都會是六個月的研究，且不做期中分析。所以我們不做期中分析。這是一個小型病患族群。你不希望透過期中分析去干擾藥物試驗的完整性。因此我們不會這麼做。所以數據會在明年期間取得。接著我們基本上會提交 SNDA 以取得標籤延伸，這部分就是如此。

In terms of the combo 809 for 12 years and older, we are currently planning a study that has, from a global point of view, the ability to produce one-year safety and one-year efficacy data and we might, depending on discussions with regulatory agencies, have an option in the US maybe to start an earlier rolling submission as we did with KALYDECO. And that could be on the basis of half a year data point. But I think that needs to be discussed with regulatory agencies.

至於 809 的聯合療法、適用於 12 歲及以上族群，我們目前規劃的研究，從全球角度來看，能夠產出一年期的安全性與一年期的療效數據；並且我們可能會——視與監管機構的討論而定——在美國有一個選項，像我們對 KALYDECO 所做的那樣，較早開始滾動式送件（rolling submission）。而那可能會以半年數據為基礎。但我認為這需要與監管機構討論。

Got you. And just the follow-up is on the hepatitis C franchise. I'm curious if you guys have some ROI target for hep C? I'm trying to get a sense many maybe at a higher level what magnitude of investment are you willing to make given the current dynamics of the market and the landscape? Thanks.

了解。我的追問是關於 C 型肝炎產品線。我想知道你們對 C 肝是否有一些 ROI 目標？我想從更高層次了解，在目前市場動態與競爭版圖之下，你們願意投入的投資規模大概會是多大？謝謝。

Yes. It's a good question. Obviously this is a very dynamic, very competitive market. And rather than go into ROI details I would say what we said before, which is that we need to be convinced that we have winning regimens that will allow us to address large parts or large portions of this market going forward.

是的。這是個好問題。顯然這是一個非常動態、競爭非常激烈的市場。與其深入談 ROI 的細節，我會重申我們之前說過的：我們必須確信我們擁有能勝出的治療方案（regimens），使我們未來能夠涵蓋這個市場的很大一部分或很大區塊。

I think as you probably remember, we said that our new data needs to be competitive with anything out there in order to move forward. We feel it is which is why we're going to move forward. And we'll make the same kinds of decisions as we go and collect our Phase 2 data prior to moving into Phase 3 to make sure, again, that we're not chasing the market with a second-rate or a non-competitive regimen. But we think that the new data we provided today is a good start.

我想你可能記得，我們說過，我們的新數據必須在競爭力上能與市面上任何方案相比，才能繼續往前推進。我們認為它做到了，這也是為什麼我們要往前推。而且在我們持續推進、並在進入第三期（Phase 3）之前收集第二期數據的過程中，我們也會做出同樣類型的決策，以再次確保我們不是用一個次等或缺乏競爭力的方案去追逐市場。但我們認為今天提供的新數據是一個良好的開始。

Okay. Thanks.

好的。謝謝。

Matt Roden, UBS.

Matt Roden，瑞銀（UBS）。

Congrats on the Alios data here. So on the hepatitis C program, a couple questions here. Can you talk about the baseline characteristics a little bit, maybe the IL28 genotype, BMI, things like that just so we can maybe help assess the degree of difficulty, if you will, on this study? Secondly, if you can speak to any treatment-emergent adverse events in the study?

恭喜你們這次的 Alios 數據。關於 C 型肝炎計畫，我有幾個問題。你們能談談基線特徵嗎？例如 IL28 基因型、BMI 之類的，讓我們可以協助評估這項研究的難度程度（如果可以這麼說的話）？第二，你們能否說明研究中任何治療期間出現的不良事件（treatment-emergent adverse events）？

And then for planning purposes, as you move into a pivotal study, is it your assumption that if there is a new standard of care established by that time in the overall space whether or not you would actually have to run up against an active control or whether or not you could take advantage of the progressiveness that the FDA is taking forward in the current hep C studies?

另外就規劃而言，當你們進入關鍵性試驗時，你們是否假設到那時整體領域會建立新的照護標準（standard of care），因此你們是否必須與一個有效對照（active control）正面比較，或是你們能否利用 FDA 在目前 C 肝研究中所展現的更具彈性的推進方式？

In terms of baseline characteristics, there's nothing particularly notable about them. The IL28 B genotype distribution was as you would expect, but we have not yet analyzed the study by IL28 B individual subjects, so I can't say too much about that nor by any of the baseline factors. So that will be coming as we look at the data. Obviously it's very fresh so we don't have a whole lot of additional analyses. In terms of adverse events, they were typical for a Phase I study. That's all I can say. And obviously we'll provide more information when these data are presented at a medical conference.

就基線特徵而言，沒有什麼特別值得注意的地方。IL28 B 基因型的分布如你所預期，但我們尚未按 IL28 B 的個別受試者來分析這項研究，因此我無法就此或任何基線因素多說什麼。所以等我們進一步檢視數據時，這些分析會再出來。顯然這些數據非常新鮮，所以我們目前沒有太多額外分析。至於不良事件，它們符合第一期（Phase I）研究的典型情況。我能說的就這些。而且很明顯地，當這些數據在醫學會議上發表時，我們會提供更多資訊。

In terms of the regulatory strategy, I think it's just a little bit early to say at this point. The FDA, as they have done publicly in a number of settings, has indicated a great deal of flexibility in the development of all orals. We hope to take advantage of that. It may help us to speed up our program, but it's really premature to think about the comparators and all that part of it. Obviously we'll gain more information as we go along.

就監管策略而言，我認為現在說還稍微早了一點。FDA 如同他們在多個場合公開表示的那樣，對於全口服（all orals）開發展現了相當大的彈性。我們希望能善用這一點。這可能有助於我們加速計畫，但現在去思考對照組（comparators）以及那一部分的細節，確實還言之過早。顯然我們會在推進過程中獲得更多資訊。

And then I just want to add two comments to that. First of all, from a baseline point of view, viral [RNA] is pretty high. It's six-point something. That means it's hard to bring patients in general, so that means we really picked hard-to-treat people. That's number one. And on top of that, I want to just make sure that we are all understand that there were no severe adverse events in this entire study, which is actually an important outcome too.

然後我還想再補充兩點評論。首先，從基線的角度來看，病毒 [RNA] 相當高。大約是 6 點多。這代表一般而言很難讓病人達到（理想結果），也就是說我們確實挑選了難治的族群。這是第一點。此外，我也想確保大家都理解：在整個研究中沒有出現任何嚴重不良事件，這其實也是一個重要的結果。

Okay. Great. And related, as a follow-up on the last question, and that is it safe to assume or should we infer that since you are continuing to invest in hepatitis C with an early stage asset here, that it's your view that the commercial market will be more sustainable under all oral standards of care as opposed to the rapid rise and rapid decline of the treatment rate, both 10 years ago and then again in your experience with pegylated and telaprevir?

好的。很好。另外，延續上一個問題作為追問：是否可以合理假設或推論，既然你們仍持續在丙型肝炎領域投入、而且這裡有一個早期資產，代表你們認為在全口服標準治療之下，商業市場會更具可持續性，而不是像 10 年前以及你們在聚乙二醇化干擾素與 telaprevir 經驗中所見到的那樣，治療率快速上升又快速下滑？

Our view is that this is a large market that will likely evolve into multiple segments, some of which will be large. And that once all orals come, there's a very nice commercial opportunity. There is also a great opportunity to treat more patients, which is very, very important. And so as we look at it, as I said, once we see our Phase 2 data I think we'll be in a good position to conclude whether we have what's called winning or first-rate regimens that can address some of these large patient populations. And if we do, that's a worthwhile investment for us and a worthwhile investment for patients.

我們的看法是，這是一個龐大的市場，未來很可能會演變成多個區隔，其中有些區隔會很大。而一旦全口服療法到來，將會有非常好的商業機會。同時也有很大的機會能治療更多病人，這點非常、非常重要。因此就我們的評估而言，如我所說，等我們看到第二期數據後，我認為我們將處於一個良好位置，去判斷我們是否擁有所謂的致勝或一流療程，能夠涵蓋其中一些龐大的病人族群。如果有，那對我們而言是值得的投資，對病人而言也同樣值得。

Thanks very much.

非常感謝。

Liisa Bayko, JMP Securities.

JMP Securities 的 Liisa Bayko。

When we think about the combination with INCIVEK and the Alios nuc, can you talk about the type of regimen or dosing you're thinking about for INCIVEK? Are you going to be considering daily dosing and lower doses than currently available? How should we think about that?

談到與 INCIVEK 以及 Alios 的核苷（nuc）合併時，你能談談你們對 INCIVEK 所考慮的療程型態或給藥劑量嗎？你們會考慮每日一次給藥，或比目前核准的劑量更低的劑量嗎？我們應該如何看待這件事？

We'll likely be dosing INCIVEK twice a day dosing in the combination studies. In general, principals of antiviral therapy are that you don't generally lower levels doses of each of the agents. You obviously need them to cover the variance for the other, so I would not anticipate any different dosing of INCIVEK than we are currently using.

在合併研究中，我們很可能會讓 INCIVEK 採每日兩次給藥。一般而言，抗病毒治療的原則是，你通常不會把每一個藥物的劑量都降低。你顯然需要它們彼此覆蓋（互補）對方的變異，因此我不預期 INCIVEK 的給藥會與我們目前使用的方式有任何不同。

And along with timing wise -- 12 weeks -- just trying to think about if there's a way to make the safety or tolerability a little more tolerable in the combination?

另外在時間上——12 週——我只是想了解，是否有方法能在合併治療中讓安全性或耐受性更好一些？

Yes. So just a quick word on that, obviously we had a little bit of a window into the safety profile of INCIVEK without peg interferon in the [Zena] study dual arms and it was actually quite a bit more favorable as you'd expect than what we saw with the triple therapy. And it gives us some amount of confidence that we'll be able to design tolerable regimens, and clearly will confirm that when we combine them with the nucs but that is one of the goals, of course, of Phase 2 is to get that information. And we are looking at 12 weeks as our primary development there.

是的。簡單說一下，顯然我們在 [Zena] 研究的雙臂中，已經稍微看到 INCIVEK 在沒有聚乙二醇干擾素情況下的安全性概況；如你所預期，這比我們在三聯療法中看到的要好得多。這讓我們對於能設計出耐受性良好的療程有一定信心；當然，當我們與核苷類（nucs）合併時會再加以確認，而這也是第二期研究的目標之一：取得這些資訊。而我們在那裡的主要開發目標是 12 週。

Okay. Thanks. And a question on the CF program, are you considering higher doses of 809 currently? Are you exploring any? And then I wanted to understand the launch plan in Europe. In what sequence will you be rolling out in countries, timing and how should we think about price? Thanks.

好的。謝謝。另外關於 CF 計畫的問題，你們目前是否在考慮更高劑量的 809？有在探索任何方案嗎？然後我也想了解歐洲的上市計畫。你們會以什麼順序在各國推出、時程如何，以及我們應該如何看待價格？謝謝。

The first thing with the dosing. So as we said, I think there are two aspects of the people trials, number one is you have to confirm what you have to see or what you have seen in cohort two in Phase 2, which is the 600-milligram once a day and KALYDECO 250 twice a day. And we actually planned, because we see from the response that we might not have maxed out yet, we will try several other does regimens that are higher on the VX-809 and one of them as we always said could be a BID 400. So that gives you a higher exposure and hopefully then a better translation into the correction, but that's what we are trying to do.

先談劑量。如我們所說，我認為人體試驗有兩個面向：第一，你必須確認你在第二期第二隊列看到的結果，也就是 VX-809 每日一次 600 毫克，搭配 KALYDECO 每日兩次 250 毫克。而我們其實已經規劃，因為從反應來看我們可能還沒有達到最大效果，我們會嘗試幾個 VX-809 更高劑量的其他給藥方案，其中之一如我們一直說的，可能是每日兩次 400（BID 400）。這樣可以提高暴露量，並希望能帶來更好的校正效果轉譯，這就是我們正在嘗試的方向。

First, as I think we mentioned before, we've been planning for this launch so the entire commercial organization is in place in Europe. We're focusing on the four major countries with most of the G551D patients, which is Germany, France, UK and Ireland initially, although we may roll it out in additional countries over time as we identify these patients or they are identified to us.

首先，如我想我們之前提過的，我們一直在為這次上市做準備，因此歐洲的整個商業組織都已到位。我們初期會聚焦於擁有最多 G551D 病人的四個主要國家：德國、法國、英國與愛爾蘭；不過隨著我們辨識出這些病人、或他們被辨識並回報給我們，我們也可能會隨時間在更多國家推出。

As I'm sure you know, the way reimbursement works in Europe is a little different. It's negotiated country by country. And we are just beginning those discussions now with each of the countries. Therefore, it's early to talk about price and we'll keep you informed as we go. But as I said before, we view the value -- the pricing of our medicines with respect to their value to patients and we think that based on the data this is a very valuable medicine for G551D patients.

如你所知，歐洲的給付方式有些不同。它是逐國談判。而我們現在才剛開始與各國展開這些討論。因此現在談價格還太早，我們會在進展過程中持續向各位更新。但如我之前所說，我們看待藥品定價是以其對病人的價值為基礎；而我們認為根據這些數據，這對 G551D 病人是一個非常有價值的藥物。

Terence Flynn, Goldman Sachs.

Goldman Sachs 的 Terence Flynn。

Just was wondering if you can give us any update on how many of the patients have rolled over from persist onto commercial KALYDECO? And if all of them have rolled over and then any details on the gross to net this quarter for KALYDECO? And then I have one follow-up.

想請問你們能否更新一下，有多少病人已經從 persist 轉入商業化的 KALYDECO？以及是否全部都已轉入？另外，這一季 KALYDECO 的 gross-to-net（毛額到淨額）有沒有任何細節可以分享？然後我還有一個追問。

With respect to the rollover, we are not providing detailed information on the patient numbers. They started rolling over in May and they will continue to rollover, most of them actually in the first third in the fourth quarter. So far the rollovers are going well, Terence, with a sense it's been a fairly easy process to move patients over.

關於轉入（rollover），我們不會提供病人人數的詳細資訊。他們在 5 月開始轉入，並會持續轉入；其中大多數其實會在第四季的前三分之一期間完成轉入。到目前為止，Terence，轉入進行得很順利，整體感覺是把病人轉過來的流程相當容易。

Your other question was on the gross to net for KALYDECO. And again, we haven't disclosed a number. The gross to net for KALYDECO is really based mostly on payer mix. And the payer mix is about 70% commercial, 20% government and 10% other. That may change a little bit over time as we get more government funded patients on the drug. But we don't anticipate it will be a major change.

你另一個問題是關於 KALYDECO 的 gross-to-net。同樣地，我們尚未揭露一個數字。KALYDECO 的 gross-to-net 主要取決於付款方組合（payer mix）。目前付款方組合大約是 70% 商業保險、20% 政府、以及 10% 其他。隨著時間推進，當我們讓更多由政府資助的病人使用該藥時，這個組合可能會有些微變化。但我們不預期會有重大改變。

Okay. And then have you guys looked at any of the PK/PD data yet from the KALYDECO 809 Phase 2 trial? And where are you on that front?

好的。那你們是否已經看過 KALYDECO 809 第二期試驗的任何 PK/PD 數據？在這方面你們目前進度如何？

We're looking at those data constantly. We will basically present some of them most likely in a conference later this year.

我們一直在持續檢視那些數據。我們基本上很可能會在今年稍晚的一個會議上發表其中一部分。

Any details you can share with us?

您能與我們分享任何細節嗎？

No. Not at this given point in time. I think what I indicated is that we go for higher does regimens, which gives you an indication that we have a confidence that we reach exposure levers that are covered by our safety ranges, and that's, I think, the most we can say at this given point in time.

不。在目前這個時間點還不行。我想我所指出的是，我們會採用更高劑量的給藥方案，這表示我們有信心能達到在我們安全範圍所涵蓋的暴露水準，而這大概就是我們在目前這個時間點所能說的最多了。

Okay. Thanks a lot.

好的。非常感謝。

Tom Russo, Baird.

Tom Russo，Baird。

Congrats on the great results for the nuc. First question and then a follow-up, wanted to get a little more granular thoughts on cross-company collaborations. Maybe the appetite that you have, mechanisms that you'd favor, how advanced any conversations you've already had are and whether one or more of the Phase 2 trials that you're talking about could be adapted to accommodate outside compounds?

恭喜這個 nuc 的優異結果。第一個問題，接著一個追問，我想更細緻地了解你們對跨公司合作的看法。例如你們的意願、偏好的機制、目前已進行的對話有多深入，以及你們提到的一個或多個第二期試驗是否可能調整設計以納入外部化合物？

We're not going to comment on any specific discussions or strategies there. I would really go back to what I said originally, which is our goal is to find the best regimen or regimens for patients. We think there's still a fair amount unknown about what those regimens are. And our goal is to learn more about that. And I think the classes of molecules one would combine with the nuc are pretty obvious at this point, so they don't bear reiterating. But it is our plan to go forward with our own drugs in combination with the nucs. As I said, we would consider combining them with the drugs of other companies as well.

我們不會就任何特定討論或策略發表評論。我會回到我一開始說的：我們的目標是為病患找到最佳的療程組合。我們認為對於那些療程組合究竟是什麼，目前仍有相當多未知之處。而我們的目標是進一步了解。我想此時此刻，會與 nuc 搭配的分子類別其實相當明顯，因此不需要再重複。但我們的計畫是以我們自家的藥物與 nuc 進行聯合治療向前推進。如我所說，我們也會考慮與其他公司的藥物進行組合。

Okay. And then other question, I don't think we've really seen or heard much on the pre clinical for the nucs yet. Is there anything that you can say on the dose limiting talks or how close -- how much coverage you have in terms of the therapeutic window versus the 200 milligrams that we're seeing today?

好的。另外一個問題，我想我們目前還沒有真正看到或聽到太多關於 nuc 的臨床前資料。你能否談談限制劑量的因素，或是——相對於我們今天看到的 200 毫克，在治療窗方面你們有多少安全覆蓋範圍？

I think there will be data in the upcoming conference that basically describes the pre-clinical profile. We have spoken a little bit about that in the earlier days and I want to repeat that. So we did a careful evaluation of this before we made a decision to pursue Alios nucs. And on that basis, safety was an important component. And as I said then, I say now, it was from a pre-clinical point of view, one of the safest if not the safest nucs that we have seen in the landscape out there. And I think it was part of the decision to go forward.

我想在即將到來的會議上會有資料，基本上會描述臨床前特徵。我們在更早的時候已稍微談過，我想再重申一次。在我們決定推進 Alios 的 nuc 之前，我們做了審慎的評估。在此基礎上，安全性是重要的組成部分。正如我當時所說、現在也同樣：從臨床前的角度來看，它是我們在外部版圖中所見過最安全、或至少是最安全之一的 nuc。我想這也是我們決定繼續推進的原因之一。

Okay. Thanks, Peter.

好的。謝謝你，Peter。

Ying Huang, Barclays.

Ying Huang，Barclays。

Congratulations also on the nuc data. My first question is for Bob. Can you confirm that in the Phase I trial for the placebo-treated patients there also predominantly genotype 1B? And then question for Ian, the excess inventory at $78 million, is that all accumulated from 2Q of this year? Thanks.

也恭喜 nuc 的數據。我的第一個問題是問 Bob。你能否確認在第一期試驗中，接受安慰劑治療的病患也主要是 1B 基因型？接著問 Ian，7,800 萬美元的超額庫存，是不是全部都在今年第二季累積的？謝謝。

So just a quick answer. Yes, the placebo subjects were predominantly 1B.

簡短回答一下。是的，安慰劑受試者主要是 1B。

And to your question on inventory, it's actually the inventory we've built over quite a long period based on our expectations of the market. And consistent with how we've communicated on this call, we have seen a change in that market and declining treatment rates, which has resulted with reserving against potential for excess inventory.

至於你問的庫存問題，這其實是我們基於對市場的預期，在相當長一段時間內建立的庫存。並且如同我們在本次電話會議中所溝通的，我們看到市場出現變化且治療率下降，因此我們針對可能出現的超額庫存提列了備抵。

Thanks. And then if I can squeeze one more in for Peter, do you guys have sufficient toxicology data to support 12-week study in human now?

謝謝。如果我可以再追問 Peter 一個問題，你們目前是否已有足夠的毒理資料來支持在人類進行 12 週的研究？

Yes, we do. 12-week is all basically ready to go. And as we go forward, we will provide actually six-month tox data to have longer treatment regimens possibilities if we decide so.

是的，我們有。12 週的部分基本上都已準備就緒。而隨著我們往前推進，如果我們決定要更長的治療療程，我們也會提供 6 個月的毒理資料，以支持更長療程的可能性。

Great. Thanks.

很好。謝謝。

Brian Abrahams, Wells Fargo Securities.

Brian Abrahams，Wells Fargo Securities。

My congrats as well on the Alios nuc data. Question on the KALYDECO 809 combo, recognizing that the design is still evolving I was wondering if you could talk about how you might be thinking about inclusion criteria for a Phase 3 versus a Phase 2? I'm just wondering if there's anything you're seeing as you continue to look at the Phase 2 data that might be suggestive of ways you might further enrich the population?

我也恭喜 Alios nuc 的數據。關於 KALYDECO 809 聯合療法的問題，理解設計仍在演進中，我想請你談談你們對第三期相較於第二期的納入標準可能會如何思考？我只是想知道，隨著你們持續檢視第二期資料，是否看到任何跡象顯示可以用某些方式進一步富集受試族群？

And then on KALYDECO pricing, can you confirm that the ultra-orphan status whether or not with the ultra-orphan status KALYDECO you still need to go through the value assessment process as in Germany and the UK? Thanks.

另外關於 KALYDECO 的定價，你能否確認：即使具有超罕見疾病（ultra-orphan）身分，KALYDECO 是否仍需要像在德國與英國那樣走價值評估流程？謝謝。

So, Brian, in terms of inclusion and learning something from a Phase 2 towards Phase 3, I think there was a broad population that we will include that's obviously, as we said, first homozygotes and we will not have any particular exclusions as for probably all homozygotes, the 508 patients in a certain age group. That's what drives the selection of the patients. We have to go with 12 years and older to grow on a fast-track because that's what we have tested in Phase 2.

Brian，關於納入標準，以及如何從第二期學到東西以走向第三期，我想我們會納入一個廣泛的族群；如同我們所說，首先是同型合子（homozygotes），而我們不會設定任何特別的排除條件，基本上會涵蓋某個年齡層的所有同型合子，也就是 508 病患。這就是驅動病患選擇的因素。我們必須從 12 歲以上開始，才能走快速通道，因為這是我們在第二期所測試的族群。

That's the only marker in a way that we have and then there's the usual selection of people that have sometimes contraindication in terms of the co-medication, which they can't go, that's normal. But I think broad population for almost everybody in the age group for 12 years and older. That's sort of what I can say to this.

某種程度上，這是我們唯一的標記；另外就是一般常見的受試者篩選，例如有時在併用藥物方面存在禁忌而無法納入，這是正常的。但我想會是相當廣泛的族群，幾乎涵蓋 12 歲以上這個年齡層的所有人。我大概只能就此說到這裡。

Brian, in terms of KALYDECO reimbursement in Europe again, as you know, whether it's orphan or not, it does need to go through the German value process. And you may have seen recently the UK has been changing its rules around the value process. And we're just talking with the UK about whether we will come under the new rules or the old rules since they are literally changing over the last couple weeks. I can't give you a final answer on that yet.

Brian，關於 KALYDECO 在歐洲的給付，如你所知，不論是否為孤兒藥，都需要走德國的價值評估流程。而你可能也看到，英國最近正在調整其價值評估流程的規則。我們正在與英國方面討論，因為他們在過去幾週內正處於規則切換期，我們會適用新規則還是舊規則。我目前還無法給你最終答案。

Thanks very much.

非常感謝。

David Friedman, Morgan Stanley.

David Friedman，Morgan Stanley。

Thanks for taking my question. It's actually just around the R&D. Is there any way that you guys could discuss or in general buckets, what the R&D breakdown is in terms of hep C, CF, basic, research, and other?

謝謝讓我提問。其實是關於研發。你們是否能以一般分類的方式討論研發費用的拆分，例如 C 肝、囊性纖維化（CF）、基礎研究以及其他？

No. We haven't actually broken it down that way. I think what we said today is that our philosophy, our strategy if you will, is to reinvest in the most promising late-stage programs and we consider CF, HCV and JAK to be promising programs. We clearly need to continue to invest in research, otherwise we won't have future late-stage programs. And then we take a very careful look as we get proof of concept with the earlier development compounds to make sure we have transformative medicines that we are bringing to late stage pipeline's.

不行。我們其實沒有用那種方式做拆分。我想我們今天所說的是，我們的理念、或者說策略，是把資金再投入到最有前景的後期計畫中，而我們認為 CF、HCV 以及 JAK 都是有前景的計畫。我們顯然也需要持續投資研究，否則未來就不會有後期計畫。接著，當我們在較早期開發化合物上取得概念驗證時，我們會非常審慎地檢視，以確保我們帶入後期研發管線的是具變革性的藥物。

All right. Thanks.

好的。謝謝。

Katherine Xu, William Blair.

Katherine Xu，William Blair。

If you look at the hep C competitive space, you have Gilead already having a co-formulated double combo going to Phase 3 in the end of this year. So if you are going to Phase 3 a year later, are you targeting a profile of a pan-genotypic combo or do you think you can still go with genotype 1 only combo that your analyses can still be successful?

如果你看丙肝（hep C）的競爭態勢，Gilead 已經有一個共同配方的雙藥組合，預計在今年年底進入第三期。所以如果你們晚一年才進第三期，你們是要鎖定泛基因型（pan-genotypic）組合的產品特性，還是你們認為只做基因型 1 的組合也仍然可行、你們的分析仍能成功？

Obviously, we don't comment on what Gilead is doing so I can just tell you what our strategy is. And as I said, we plan to test multiple all-oral regimens in Phase 2 between now and the first half of next year in multiple small studies. And based on both safety and efficacy results, we think that's going to allow us to design a single or multiple pivotal trial which will go in parallel with a high probability of success. We can do that by the end of next year.

顯然，我們不評論 Gilead 在做什麼，所以我只能告訴你我們的策略。如我所說，我們計畫在現在到明年上半年之間，在第二期以多個小型研究測試多種全口服療法。並且基於安全性與療效結果，我們認為這將使我們能設計一個或多個關鍵性試驗，並行推進且成功機率很高。我們可以在明年年底前做到。

Do you think that will be a pan-genotypic combo or is that a target profile you're going with or you're just genotype 1 only is okay as well?

你認為那會是泛基因型組合嗎？或者那是你們採用的目標產品特性？還是只做基因型 1 也可以？

Our initial strategy really is genotype 1-specific. That we still believe is the major unmet need. I think if you look around the world at all the markets and all the various genotype distributions, it still comes out that genotype 1 is the most valuable proposition.

我們最初的策略確實是針對基因型 1。我們仍然相信那是主要未被滿足的需求。我想如果你放眼全球所有市場與各種基因型分布，結論仍是基因型 1 具有最高的價值主張。

Got it. And follow-up if I may, for 2518, the other nuc. What is taking so long? Just curious. I thought both studies were started around the same time. And what is taking longer for the other one?

了解。如果可以的話再追問一下，關於 2518，也就是另一個 nuc。為什麼進度拖這麼久？只是好奇。我以為兩個研究差不多同時開始。那另一個為什麼比較久？

It's not so long. Basically, the studies -- the 2158 study started about a month later than the 2200 study. Obviously, running one program on time is hard. Running two programs exactly in parallel is almost impossible. And recruitment's been a little bit slower than we expected in the countries where it's being run, so we do expect the data sometime in the next couple of months.

其實不算久。基本上，這些研究——2158 的研究比 2200 的研究晚大約一個月開始。顯然，把一個計畫按時推進就很難。要讓兩個計畫完全同步幾乎不可能。而且在執行的國家中，招募速度比我們預期稍慢，所以我們預期在接下來幾個月內會有數據。

Thank you.

謝謝。

Howard Liang, Leerink Swann.

Howard Liang，Leerink Swann。

The INCIVO royalty is down quarter over quarter. Can you give some color where your partner is in European launch and whether we should expect that line to increase over time?

INCIVO 的權利金（royalty）較上一季下滑。你能否補充一下你們合作夥伴在歐洲上市推進到哪個階段，以及我們是否應預期這一項目會隨時間增加？

As I mentioned in my remarks, we've been -- INCIVO has now been approved in over 25 countries, most of the major European countries and certainly in the major countries. So they are at the earlier stage of launch, a lot of those approvals have been this year, so we'll look to see how they perform in those markets.

如我在發言中提到的，我們——INCIVO 現在已在超過 25 個國家獲准，包括多數主要歐洲國家，當然也包含主要市場。因此他們仍處於上市初期階段，許多核准是在今年取得的，所以我們會觀察他們在這些市場的表現。

Great. And I think you said that you're interested in combining 2200 with other nucs. Would that be with 2158 or other experimental nucs?

很好。我想你提到你們有興趣把 2200 與其他 nuc 結合。那會是與 2158 結合，還是其他實驗性 nuc？

Our goal would be potentially to combine 2158 and 2200 together. We haven't really thought about other nucs at this point. And obviously, we won't know the feasibility of that until we have 2158 data.

我們的目標可能是把 2158 和 2200 結合在一起。目前我們還沒有真正考慮其他 nuc。而且顯然，在我們拿到 2158 的數據之前，我們也無法知道這是否可行。

Thank you.

謝謝。

Michael Yee, RBC Capital Markets.

Michael Yee，RBC Capital Markets。

On 661, I don't think the answer was fully clear. Can you better describe the adaptive design? I've got a lot of questions on that and trying to understand what actually triggers a readout. Is it safety? Is it an efficacy time point? Maybe explain that a little bit better because I thought as -- it was dose escalation. So the longer it goes the higher doses you're going at?

關於 661，我覺得答案還不夠清楚。你能更清楚描述一下適應性設計（adaptive design）嗎？我對此有很多問題，想了解究竟是什麼觸發讀出（readout）。是安全性嗎？是某個療效時間點嗎？也許可以再解釋清楚一點，因為我以為——它是劑量遞增。所以時間越久，你們就會用到越高的劑量？

I'll point out that there is a slide on the webcast that has a bit of a graphic that describes how the doses escalate a little bit and other features in the design, but I'll let Peter -- Peter says the slide describes it pretty well.

我想指出，網路直播的投影片中有一張用圖示稍微描述了劑量如何逐步遞增，以及設計中的其他特點；不過我讓 Peter——Peter 說那張投影片已經描述得很清楚。

Okay. And let me ask one last question now. On the 809 combo on Phase 3, you said you could look at higher doses. What data do you have to support higher doses? They were never tested in Phase 2, so wondering how that's possible in Phase 3.

好的。那我再問最後一個問題。關於 809 組合進入第三期，你說你們可以考慮更高劑量。你們有哪些數據支持更高劑量？第二期從未測試過更高劑量，所以想知道第三期怎麼可能這樣做。

We have obviously Phase I data that basically measured the exposure levels. And that is linked to safety in humans, but also in animals. And that gives us basically using PK/PD modeling the opportunity to feel like different doses that are within that safety range.

我們顯然有第一期數據，基本上量測了暴露量（exposure levels）。而這與人體的安全性相關，也與動物的安全性相關。這讓我們能透過 PK/PD 建模，評估在該安全範圍內的不同劑量。

Okay. That's helpful. Thanks.

好的。這很有幫助。謝謝。

Michael, we'll give you a call and walk you through the slide and describe how 661 works. We find most of the questions regarding the 661 study is when data is available and the design will help you understand the final data will be available in 2013.

Michael，我們會打電話給你，帶你看那張投影片並說明 661 的運作方式。我們發現多數關於 661 研究的問題在於何時會有數據，而該設計會幫助你理解最終數據將在 2013 年出爐。

That's why I asked. Thanks.

所以我才問。謝謝。

Ted Tenthoff, Piper Jaffray.

Ted Tenthoff，Piper Jaffray。

In first quarter of KALYDECO launch, you said that estimated roughly 60% of patients were of G551D patients in the US were on drug. How has that changed in the second quarter? Has that increased, and can you provide what that level is?

在 KALYDECO 上市的第一季，你們說估計美國約有 60% 的 G551D 病患已在用藥。第二季有什麼變化？是否有增加？你能提供目前的比例嗎？

As we said on our first-quarter call, we are not going to provide numbers of patients going forward. To clarify what we said, we said 600 patients in the US at the end of the first quarter. And as I said today, the number has increased and we anticipate it will continue to increase, both as we identify new G551D patients and as G551D patients rollover from persist.

如我們在第一季電話會議中所說，往後我們不會提供病患人數。澄清一下我們當時說的是：第一季末美國有 600 名病患。而如我今天所說，這個數字已經增加，我們也預期會持續增加，無論是因為我們辨識出新的 G551D 病患，或是因為 G551D 病患從 persist 計畫轉入。

Great. Thanks. And then for Ian real quickly, with the focus of more on R&D, does that change the breakdown in R&D in that $690 million to $760 million guidance that you've given?

很好。謝謝。接著很快問 Ian 一個問題，既然更聚焦在研發（R&D），這會改變你們所給的 6.9 億到 7.6 億美元指引中，研發的拆分比重嗎？

The relative weighting of those two remains similar.

這兩者的相對比重仍然相近。

Okay. Thanks.

好的。謝謝。

Phil Nadeau, Cowen & Company.

Phil Nadeau，Cowen & Company。

At the risk of asking something you just said you're not going to answer, as you've launched in the US, have you found -- is there anything that's changed your mind on the number of G551D patients in the US? Do you still think that's about 1,100 patients? Similar question about the four countries you mentioned earlier, you said 1,000 to 1,100 patients approximately the right number of G551D patients in those four countries?

冒著問到你剛說不會回答的風險，隨著你們在美國上市，你們是否發現——有任何事情改變了你們對美國 G551D 病患人數的看法？你們仍然認為大約是 1,100 名病患嗎？對你先前提到的四個國家也有類似問題：你說那四個國家的 G551D 病患大約是 1,000 到 1,100 名，這個數字仍然大致正確嗎？

A good question, Phil. In the US nothing has changed our estimate of 1,000 to 1,100. Our best estimate in Europe is also around 1,000 to 1,100, although I always put the caveat on this, Phil, that as you know, the genotyping in Europe is not as advanced as it is here. And so the precision of the 1,000 to 1,100 in Europe is a little bit less than what we know in the US.

問得好，Phil。在美國，沒有任何事情改變我們對1,000到1,100的估計。我們在歐洲的最佳估計也大約是1,000到1,100，不過我一向會加上一個但書，Phil，如你所知，歐洲的基因分型不像我們這裡這麼先進。因此，歐洲1,000到1,100這個數字的精確度，比我們在美國所掌握的要稍微低一些。

And did you have any compassionate-use program in Europe that has enrolled patients? Are there any patients on drug today?

那你們在歐洲是否有任何同情用藥計畫已經納入病患？目前是否有任何病患正在用藥？

Yes. There are. We have a program in France that's enrolled some patients as part of a APU program. And we anticipate those patients will roll over to commercial drug now that it's approved.

有。有的。我們在法國有一個計畫，作為APU計畫的一部分，已經納入了一些病患。而且我們預期，現在既然已獲核准，這些病患將會轉換到商業用藥。

Okay. Would you care to tell us how many patients that is?

好的。你願意告訴我們那是多少位病患嗎？

No. We haven't disclosed how many patients that is. It's a small number.

不。我們尚未披露那是多少位病患。數量不多。

Okay. Thanks for taking my questions.

好的。謝謝回答我的問題。

Brian Skorney, Brean Murray.

Brian Skorney，Brean Murray。

Congrats on the data from the Alios nuc. Just digging a little bit more on the molecule with the understanding you're not ready to talk about the structure, but just in terms of a little bit of a comparison to the resistance of this drug compared to the other nucs, which I think all have the two methyl nucleotide background, I'm just wondering is it a totally different structure than that? And in pre-clinical studies have you've been able to select for resistance and what sort of mutations would confer resistance to this drug? Thanks.

恭喜Alios核苷（nuc）的數據。我想再深入一點了解這個分子；我知道你們還沒準備好談結構，但就與其他核苷類藥物的抗藥性做個比較而言，我認為其他核苷類藥物都有「雙甲基核苷酸」的背景，我想請問：它的結構是否與那完全不同？另外，在臨床前研究中，你們是否能夠篩選出抗藥性？哪些類型的突變會賦予對這個藥物的抗藥性？謝謝。

I really can't talk at all about the structures. I will just say that these compounds have a very high barrier to resistance. And, therefore, are excellent combinations for other drugs, much like the other nucs that have been described.

我真的完全不能談結構。我只能說，這些化合物具有非常高的抗藥性屏障。因此，它們是與其他藥物併用的極佳組合，就像先前描述的其他核苷類藥物一樣。

Thanks.

謝謝。

There will be a bit more detail coming out at a medical conference later on some of these issues.

稍後在某個醫學會議上，針對其中一些議題會有更多細節公布。

Okay. I'll wait for them.

好的。那我就等你們公布。

Okay.

好的。

Operator, this is Michael. We are now about 10 minutes past our planned stop time for the call so the interest of everybody's time we'll take just two more questions. Thanks.

接線員，我是Michael。我們現在已經比原定的電話會議結束時間晚了大約10分鐘，為了大家的時間，我們只再接受兩個問題。謝謝。

[Ravi Mehrotra], Credit Suisse.

[Ravi Mehrotra]，瑞士信貸（Credit Suisse）。

Congrats on the data. This is actually Kuhn calling on behalf of Ravi. I had a question regarding one of the trials for the Alios nucs with ribavirin. I just wanted to know if there was anything in the data that you've seen that would suggest that your nuc with ribavirin might give you better results than what we've seen so far. Thanks.

恭喜這些數據。其實我是Kuhn，代表Ravi來電。我有一個問題，關於Alios核苷類藥物與利巴韋林（ribavirin）併用的其中一項試驗。我想了解的是，你們在數據中是否看到任何跡象，顯示你們的核苷類藥物搭配利巴韋林，可能會比我們目前看到的結果更好？謝謝。

That's obviously why we're going to do the study is to find out. Clearly the properties that we've seen so far, very high level of antiviral activity would make it potentially a good companion with ribavirin. And as I said both efficacy wise and safety wise, we think it's a good trial to you.

這顯然就是我們要做這項研究的原因：找出答案。很明顯，我們目前看到的特性——非常高水準的抗病毒活性——使它有潛力成為與利巴韋林併用的良好搭檔。而且如我所說，無論在療效或安全性方面，我們都認為這是一項對你們而言很好的試驗。

Okay. Thanks.

好的。謝謝。

The other thing that is impressive what we said in the call is we had a very steep decline from the viral kinetic point of view of 3.85 drop in three days, which is a good indicator that you might have a good chance for combination and good viral outcome at the end of the day.

另外一個令人印象深刻、我們在電話會議中提到的點是：從病毒動力學的角度來看，我們看到非常陡峭的下降——三天內下降3.85個log——這是一個很好的指標，顯示你可能有很好的機會進行併用治療，並在最後獲得良好的病毒學結果。

Alan Carr, Needham and Company.

Alan Carr，Needham and Company。

Any sense of off label use other genotypes patients using KALYDECO? Thanks.

對於其他基因型病患使用KALYDECO的適應症外用藥（off-label use），你們有任何了解嗎？謝謝。

As you know, Alan, we only promote KALYDECO for the labeled indication, which is G551D greater than six, and we don't track or keep track of any off- label use, so I don't have any data of off-label use.

如你所知，Alan，我們只針對KALYDECO核准標示的適應症進行推廣，也就是6歲以上的G551D，我們不追蹤或記錄任何適應症外用藥，因此我沒有任何適應症外用藥的數據。

Thanks.

謝謝。

Thanks very much, everybody, for joining us tonight. I think everybody got to ask at least one question. If you didn't get your follow-up or you have additional questions for any of us, happy to talk further tonight. Thanks very much for tuning in.

非常感謝各位今晚加入我們。我想大家至少都問到了一個問題。如果你沒有問到追問問題，或對我們任何一位還有其他問題，我們也很樂意今晚再進一步交流。非常感謝收聽。

Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may now disconnect. Have a wonderful day.

各位女士、先生，感謝您參與今天的會議。本節目到此結束。您現在可以掛線。祝您有美好的一天。