福泰製藥 (VRTX) 2011 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Vertex Pharmaceuticals Inc. fourth quarter 2011 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) As a reminder, this conference call is being recorded. Now I'll turn the conference over to Michael Partridge. Please begin.

各位女士、先生，大家好，歡迎參加 Vertex Pharmaceuticals Inc.2011 年第四季財務業績電話會議。此刻，所有與會者將以僅收聽模式參與。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) 提醒各位，本次電話會議正在錄音。現在我將把會議交給 Michael Partridge。請開始。

Good evening, and welcome to Vertex's 2011 financial results conference call. 2011 began a fulfillment of Vertex's vision of improving patients lives with breakthrough medicines. As we look to 2012, we are focused on balancing the revenues we are generating with the breadth of investment required to drive continued innovation in our pipeline and generating significant earnings and cash flows. With me today to review our 2011 accomplishments and outlook for 2012 are Dr. Jeff Leiden, who will kick off the call with an overview of our business focus for 2012; and Ian Smith, who will comment on selected year-end and fourth quarter 2011 financial results and 2012 financial guidance.

各位晚安，歡迎參加 Vertex 的 2011 年財務業績電話會議。2011 年是 Vertex 願景開始落實的一年：以突破性藥物改善病患生活。展望 2012 年，我們專注於在我們所創造的營收與推動研發管線持續創新所需的投資廣度之間取得平衡，同時創造可觀的獲利與現金流。今天與我一同回顧 2011 年成果並展望 2012 年的有 Dr.Jeff Leiden，他將以 2012 年業務重點概述為本次會議開場；以及 Ian Smith，他將就部分年終與 2011 年第四季財務結果及 2012 年財務指引發表評論。

A press release announcing our fourth quarter and 2011 financial results and 2012 financial guidance has been issued. Please refer to this release for the primary line items within our income statement. After our prepared remarks, we will be joined by Dr. Peter Mueller, Nancy Wysenski and Dr. Bob Kauffman and will be happy to take your questions. We will ask you to please limit your questions to one with a related follow-up. We're stopping tonight's call promptly at 6.00 PM and for any questions after that we will be in our offices to take your call.

我們已發布新聞稿，公告第四季與 2011 年財務結果以及 2012 年財務指引。請參閱該新聞稿，以了解損益表中的主要項目。在我們的準備發言之後，Dr.Peter Mueller、Nancy Wysenski 與 Dr.Bob Kauffman 也將加入，我們很樂意回答各位的問題。我們請各位將問題限制為一題，並可附帶一個相關追問。今晚的電話會議將準時於下午 6:00 結束；若在此之後仍有問題，我們會在辦公室接聽您的來電。

Finally, let me 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 filed with the Securities and Exchange Commission, including our 10-K. GAAP and non-GAAP financial measures will be discussed on this call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our full-year 2011 financial results press release which is on our website.

最後提醒，本次電話會議所討論的資訊包含前瞻性陳述，可能受到我們向美國證券交易委員會（SEC）提交之報告（包括 10-K）中詳述的風險與不確定性影響。本次會議將討論 GAAP 與非 GAAP 財務衡量指標。關於我們使用非 GAAP 財務衡量指標的資訊，以及這些指標與 GAAP 之間的調節表，已載於我們網站上的 2011 全年財務結果新聞稿。

All 2010 and 2011 expenses discussed in this call exclude stock-based compensation expense, restructuring expense, and any intangible asset impairment charges net of tax, any revenues and expenses related to certain September 2009 financial transactions, commercial milestone payments and items related to Vertex's collaboration with Alios. Thank you, and I will now turn the call over to Jeff.

本次電話會議所討論之 2010 年與 2011 年所有費用，均不包含以股份為基礎之薪酬費用、重組費用，以及任何無形資產減損費用（扣除稅後），亦不包含與 2009 年 9 月特定金融交易相關的任何收入與費用、商業里程碑付款，以及與 Vertex 與 Alios 合作相關的項目。謝謝，現在我把電話交給 Jeff。

Thanks, Michael. I joined Vertex just six weeks ago and I am extremely pleased with the execution we are demonstrating across the business. On today's call, I want to reiterate for you again what I said at the beginning of the year at the annual JPMorgan Healthcare Conference and what I said two days ago when we announced the approval of KALYDECO, and that is that Vertex is well-positioned to be a global business, to help many more patients with serious diseases, and to continue to generate significant cash flows. In less than a year, Vertex received approvals and launched two breakthrough medicines in different life-threatening diseases, INCIVEK for the treatment of hepatitis C and KALYDECO for the treatment of cystic fibrosis.

謝謝你，Michael。我加入 Vertex 才六週，我對我們在整體業務上的執行力表現感到非常滿意。在今天的電話會議上，我想再次重申我在年初 JPMorgan 醫療保健年會上所說的，以及兩天前我們宣布 KALYDECO 獲准時所說的：Vertex 已具備成為全球性企業的良好定位，能協助更多嚴重疾病患者，並持續創造可觀的現金流。在不到一年的時間內，Vertex 在兩種不同的致命疾病領域取得核准並上市兩款突破性藥物：用於治療 C 型肝炎的 INCIVEK，以及用於治療囊性纖維化的 KALYDECO。

Looking ahead, we have a pipeline of eight other potential medicines and expect to generate proof-of-concept data for many of these programs throughout 2012. This is a very exciting and deep pipeline that gives us the opportunity to launch additional new medicines over the next few years that could deliver significant benefits to patients and their families and significant value to Vertex and our shareholders. Launching INCIVEK last year was a crucial turning point for Vertex and enabled us to demonstrate not only our research and development expertise, but also our ability to build a commercial team that flawlessly executed one of the most successful drug launches in the industry.

展望未來，我們的研發管線中還有另外八項潛在藥物，並預期在 2012 年期間為其中多個計畫取得概念驗證（proof-of-concept）數據。這是一條非常令人振奮且深厚的研發管線，讓我們有機會在未來幾年推出更多新藥，為患者及其家人帶來重大效益，並為 Vertex 及股東創造顯著價值。去年推出 INCIVEK 是 Vertex 的關鍵轉捩點，使我們不僅展現研發專業，也展現建立商業團隊的能力，並以無懈可擊的執行完成業界最成功的藥物上市之一。

Prior to launch, we anticipated strong demand for this medicine from people living with hepatitis C and the healthcare providers who treat them. But INCIVEK's performance in the first seven months exceeded even those expectations. INCIVEK is now available in multiple countries including the US, Canada and nine countries in Europe. We believe this reflects the clinical benefits of the drug and the outstanding work of our commercial organization. Our fourth quarter and year-end 2011 results reflect the very rapid launch of INCIVEK and have created strong cash flow to enable investment in our late stage pipeline of medicines while also returning value to shareholders.

在上市前，我們預期 C 型肝炎患者以及治療他們的醫療照護提供者對此藥物會有強勁需求。但 INCIVEK 在前七個月的表現甚至超出這些預期。INCIVEK 目前已在多個國家上市，包括美國、加拿大以及歐洲九個國家。我們相信這反映了該藥物的臨床效益，以及我們商業組織的卓越工作。我們 2011 年第四季與年終結果反映了 INCIVEK 極為迅速的上市推進，並帶來強勁現金流，使我們得以投資於後期研發管線，同時也回饋股東價值。

Ian will review our financial results with you momentarily. As our hepatitis C commercial group remains keenly focused on INCIVEK's launch we are progressing efforts to sustain our leadership in hepatitis C for the long term. We have a number of future opportunities in this disease including an all-oral regimen in Phase 2 and two novel nucleotide medicines which are now in Phase 1. These nucleotide compounds are pan-genotypic in vitro and we expect to obtain viral kinetic data this year, not only genotype-1 but also in multiple HCV genotypes. In the area cystic fibrosis, the team's execution on the development and regulatory submissions of KALYDECO for the treatment of a subset of patients was absolutely extraordinary.

Ian 稍後將為各位檢視我們的財務結果。在我們的 C 型肝炎商業團隊仍高度專注於 INCIVEK 上市推進之際，我們也在推動各項工作，以長期維持我們在 C 型肝炎領域的領導地位。我們在此疾病領域有多項未來機會，包括一項處於第 2 期的全口服療法，以及兩項新型核苷酸藥物，目前均在第 1 期。這些核苷酸化合物在體外呈現泛基因型（pan-genotypic）活性，我們預期今年可取得病毒動力學數據，不僅涵蓋第 1 型，也涵蓋多種 HCV 基因型。在囊性纖維化領域，團隊在 KALYDECO（用於治療特定患者子群）的開發與法規申請上的執行力可說是極為卓越。

As a result of these efforts, we launched our second breakthrough medicine within nine months after the launch of our first, and only three months after the submission of the NDA. Nancy and her team are working together to bring KALYDECO to CF patients aged 6 and older with a G551D mutation. And I'm pleased to announce that just two days after approval, KALYDECO has begun to arrive at the network of specialty pharmacies. Through our disease education initiative we're providing doctors and nurses with specific resources to understand the science behind CFTR modulation and the importance of knowing a patient's genotype.

因此，我們在推出第一款突破性藥物後九個月內就推出第二款，而且距離 NDA 提交僅三個月。Nancy 與她的團隊正共同努力，將 KALYDECO 帶給年滿 6 歲且帶有 G551D 突變的囊性纖維化（CF）患者。我也很高興宣布，在獲准僅兩天後，KALYDECO 已開始送達專科藥局網絡。透過我們的疾病教育計畫，我們正為醫師與護理人員提供特定資源，以理解 CFTR 調節背後的科學，以及了解患者基因型的重要性。

We're also educating the community on KALYDECO's label and the patients who can benefit from this medicine to enable the successful outcomes that patients, providers and payers all want. And we're equally excited about ways to improve the treatment for other people living with cystic fibrosis. KALYDECO is part of a long-standing and ongoing program, our work is not done. We have a portfolio of medicines and we're committed to doing everything we can to help as many CF patients as possible. Specifically, we are now getting ready to start three additional studies of KALYDECO as monotherapy, which may help to expand the addressable population. With positive results from these studies, we believe we could submit data to begin to expand KALYDECO's label as early as 2013.

我們也在向社群說明 KALYDECO 的標籤內容，以及哪些患者可從此藥物受益，以促成患者、醫療提供者與支付方都期望達成的成功治療結果。同時，我們也同樣期待能改善其他囊性纖維化患者的治療方式。KALYDECO 是一項長期且持續進行的計畫的一部分，我們的工作尚未完成。我們擁有一系列藥物組合，並承諾竭盡所能協助盡可能多的 CF 患者。具體而言，我們目前正準備啟動三項 KALYDECO 單藥治療（monotherapy）的額外研究，這可能有助於擴大可治療族群。若這些研究結果正面，我們相信最早可於 2013 年提交數據，以開始擴大 KALYDECO 的適應症標籤。

We're also exploring combining KALYDECO with VX-809 and VX-661, two potential medicines known as correctors, which target the most common CF mutation called Delta F508. We have exploratory studies ongoing in parallel with these medicines and expect to get clinical data from these studies later this year. Beyond our hepatitis C and cystic fibrosis areas, we're advancing our pipeline of other medicines. We're initiating Phase 2b studies of VX-509, our selective JAK3 inhibitor for rheumatoid arthritis and other autoimmune diseases, and VX-765 for epilepsy. Also this year, we're planning to initiate a proof-of-concept study for VX-787, a novel medicine for influenza.

我們也在探索將 KALYDECO 與 VX-809 及 VX-661 併用；這兩項潛在藥物被稱為校正劑（correctors），其標的為最常見的 CF 突變 Delta F508。我們正同步進行這些藥物的探索性研究，並預期在今年稍晚取得臨床數據。除 C 型肝炎與囊性纖維化之外，我們也在推進其他藥物的研發管線。我們正啟動 VX-509（用於類風濕性關節炎及其他自體免疫疾病的選擇性 JAK3 抑制劑）的第 2b 期研究，以及 VX-765（用於癲癇）的研究。此外，今年我們也計畫啟動 VX-787（一種用於流感的新型藥物）的概念驗證研究。

These opportunities in our drug pipeline are both diverse and global, and could build upon the revenue base of INCIVEK and KALYDECO to provide substantial growth for Vertex in the next three to five years. We fundamentally believe that the value of our business will be driven by innovations in our pipeline, while we maintain a financial return from our marketed drugs. In summary, only a few biotech companies are fortunate enough to go from being a drug development Company to a successful commercial organization with multiple approved medicines. And fewer have done so with a broad and diverse pipeline in serious diseases like we have developed at Vertex.

我們藥物研發管線中的這些機會兼具多元性與全球性，並可在 INCIVEK 與 KALYDECO 的營收基礎上再接再厲，於未來三到五年為 Vertex 帶來可觀成長。我們從根本上相信，我們業務的價值將由研發管線中的創新所驅動，同時我們也將從已上市藥品中維持財務回報。總結而言，只有少數生技公司有幸能從藥物研發公司，轉型為擁有多項核准藥品的成功商業化組織。而能像 Vertex 一樣，在嚴重疾病領域建立廣泛且多元研發管線並做到這一點的公司更是少之又少。

As we look ahead, we see 2012 as the year that underscores to many our capability to consistently discover, develop and bring breakthrough medicines to patients. Thank you, and I'll now turn the call over to Ian.

展望未來，我們認為 2012 年將向許多人凸顯我們持續發現、開發並將突破性藥物帶給病患的能力。謝謝各位，接下來我把電話交給 Ian。

Thanks, Jeff, and evening to everyone. Financially, 2011 was a turning point for the Company. It marked Vertex's first full year of profitability and reflected the success in treating a significant number of hepatitis C patients with INCIVEK. We've now transitioned to a business generating significant revenues and as we enter 2012 we have a financial objective to balance our investments into R&D, required for innovation and growth opportunities, while still generating significant earnings and cash flows.

謝謝你，Jeff，各位晚安。就財務面而言，2011 年是公司的一個轉捩點。這是 Vertex 首次達成全年獲利的一年，也反映出 INCIVEK 成功治療大量 C 型肝炎病患的成果。我們如今已轉型為能創造可觀營收的企業；進入 2012 年，我們的財務目標是在持續產生可觀獲利與現金流的同時，平衡對研發（R&D）的投資，以支持創新與成長機會。

Tonight I'm going to report on our GAAP and non-GAAP income for the full year 2011, and then focus my remarks on how we're financially managing 2012. I will, of course, be happy to address any questions during the question-and-answer session. First, to our 2011 financial results. The GAAP net income attributable to Vertex in 2011 was approximately $30 million, or $0.14 per diluted share. This compares to a $755 million 2010 GAAP net loss.

今晚我將報告我們 2011 全年的 GAAP 與非 GAAP 獲利情況，接著把重點放在我們如何進行 2012 年的財務管理。當然，我也很樂意在問答環節回答任何問題。首先，談 2011 年的財務結果。2011 年歸屬於 Vertex 的 GAAP 淨利約為 3,000 萬美元，稀釋後每股盈餘為 0.14 美元。相較之下，2010 年 GAAP 淨損為 7.55 億美元。

For the full year 2011, our non-GAAP net income was approximately $16 million, or $0.08 per diluted share which compares to a $606 million of 2010 non-GAAP loss. We achieved these results, and specifically the full-year profitability, due to the successful launch of INCIVEK in the US coupled with a focus on financial discipline that balances the investment necessary for continued innovation. Before I turn to the guidance we're providing for 2012, I'd like to remind everyone that at the end of 2011 we had NOLs, that is net operating losses, of approximately $3 billion. Utilization of these NOLs contributed to the cash position in 2011 and will continue to reduce our tax obligations going forward.

2011 全年，我們的非 GAAP 淨利約為 1,600 萬美元，稀釋後每股盈餘為 0.08 美元；相較之下，2010 年非 GAAP 虧損為 6.06 億美元。我們能達成這些成果，特別是全年獲利，主要歸功於 INCIVEK 在美國成功上市，同時我們也專注於財務紀律，在持續創新所需的投資之間取得平衡。在我談到我們對 2012 年提供的財測指引之前，我想提醒各位：截至 2011 年底，我們的 NOL（即營運淨損結轉扣抵）約為 30 億美元。這些 NOL 的運用在 2011 年有助於我們的現金部位，並將在未來持續降低我們的稅負義務。

Now turning to the financial guidance for 2012. The components of the guidance we're providing are as follows. INCIVEK net product revenues and non-GAAP total operating expenses excluding cost of revenues stock-based compensation and the expenses related to accounting treatment of the Alios collaboration. These are important financial measures of cash inflows and reinvestment back into our business. We may provide further financial guidance in 2012 as we gain more understanding of the revenues generated from the recently approved and now launched KALYDECO, and also the royalty revenues from the recent approval of INCIVO, which is marketed in Europe by J&J. Both may provide substantial revenues and contribute to earnings and cash flow.

接著談 2012 年的財務指引。我們提供的指引包含以下組成項目。INCIVEK 的產品淨營收，以及非 GAAP 的總營業費用（不含銷貨成本、以股份為基礎的薪酬，以及與 Alios 合作案會計處理相關的費用）。這些是衡量現金流入以及再投資回公司業務的重要財務指標。隨著我們對近期獲准並已上市的 KALYDECO 所帶來的營收有更多了解，以及對近期獲准、由嬌生（J&J）在歐洲銷售的 INCIVO 所帶來的權利金收入有更清楚掌握，我們可能在 2012 年提供進一步的財務指引。兩者皆可能帶來可觀營收，並對獲利與現金流做出貢獻。

We believe our 2012 guidance reflects our ability to build value by creating earnings while we continue to prudently invest in our pipeline of medicines to drive further innovation. It's a careful balance of priorities. First, we expect US INCIVEK net product revenues to be within a range of $1.5 billion to $1.7 billion for the full year of 2012. This compared to 2011 net product revenues for INCIVEK of approximately $951 million, which represents the first seven months of sales for INCIVEK. Additionally, this compares to our fourth quarter INCIVEK revenues of approximately $457 million.

我們相信，2012 年的指引反映出我們在持續審慎投資藥物研發管線、推動進一步創新的同時，也能透過創造獲利來累積價值的能力。這是一種優先順序之間的謹慎平衡。首先，我們預期 2012 全年美國 INCIVEK 產品淨營收將落在 15 億至 17 億美元之間。相較之下，2011 年 INCIVEK 的產品淨營收約為 9.51 億美元，這代表 INCIVEK 上市後前七個月的銷售額。此外，這也可與 2011 年第四季 INCIVEK 約 4.57 億美元的營收相比。

The 2012 projected INCIVEK revenues are based on our assessment of the genotype-1 hepatitis C market, our understanding of the underlying demand, trend in physician treatment decision-making and our general market knowledge. It also takes into account the anticipated increases in the gross to net adjustments from our weighted average cost or list price based on contractual terms with commercial and government payers.

2012 年預估的 INCIVEK 營收係基於我們對基因型 1 型 C 型肝炎市場的評估、對潛在需求的理解、醫師治療決策趨勢，以及我們對整體市場的認知。其中亦考量到，依據與商業及政府付款方的合約條款，從加權平均成本或牌價所推導的「毛額轉淨額」（gross-to-net）調整預期將增加。

Next, projected 2012 non-GAAP total operating expenses, specifically those of R&D and SG&A expenses, we expect these expenses to be in the range of $1.03 billion to $1.13 billion compared to $981 million for 2011. This is an increase of approximately 10% using the midpoint of our 2012 expense guidance. This also compares to approximately $276 million for the fourth quarter of 2011.

接下來，2012 年預估的非 GAAP 總營業費用，特別是研發（R&D）與銷售、一般及行政（SG&A）費用，我們預期將落在 10.3 億至 11.3 億美元之間，相較 2011 年為 9.81 億美元。以 2012 年費用指引的中位數計算，約增加 10%。此外，這也可與 2011 年第四季約 2.76 億美元相比。

Now looking at the individual components of the non-GAAP R&D and SG&A expenses. First, our R&D expenses are anticipated to be in the range of $690 million to $760 million. This compares to approximately $627 million in 2011, and approximately $166 million for the fourth quarter of 2011. This spend will be focused on the advancement and the initiation of multiple clinical trials planned in several different serious diseases including our lead programs in hepatitis C and cystic fibrosis, as well as clinical programs in rheumatoid arthritis, influenza and epilepsy.

現在來看非 GAAP 研發與 SG&A 費用的各個組成。首先，我們預期研發費用將落在 6.9 億至 7.6 億美元之間。相較之下，2011 年約為 6.27 億美元，2011 年第四季約為 1.66 億美元。這些支出將聚焦於推進並啟動多項臨床試驗，規劃涵蓋多種不同的重大疾病領域，包括我們在 C 型肝炎與囊性纖維化的主力計畫，以及類風濕性關節炎、流感與癲癇的臨床計畫。

On the commercial side of our business, we will continue to support the launch of INCIVEK and the recent US launch of KALYDECO for cystic fibrosis patients. We will also incur costs associated with the initial preparation for and the potential launch of KALYDECO in the EU later this year. To support these important areas of our business, we anticipate SG&A expenses to be in the range of $340 million to $370 million. This compares to $354 million for the year ended 2011, and approximately $110 million for the fourth quarter of 2011. In summary, we believe the approval of our first two medicines has demonstrated our capability to develop breakthrough medicines in serious diseases. But we would not be where we are today without shareholder support in making significant investments in the pipeline to advance these innovations.

在商業營運方面，我們將持續支持 INCIVEK 的上市推廣，以及近期在美國針對囊性纖維化病患推出的 KALYDECO。我們也將承擔與今年稍晚在歐盟為 KALYDECO 進行初期準備及潛在上市相關的成本。為支持這些重要業務領域，我們預期 SG&A 費用將落在 3.4 億至 3.7 億美元之間。相較之下，2011 年度為 3.54 億美元，2011 年第四季約為 1.10 億美元。總結而言，我們相信前兩項藥品的核准已證明我們有能力在重大疾病領域開發突破性藥物。但若沒有股東支持我們對研發管線進行重大投資、推進這些創新，我們不可能走到今天。

We are now fortunate to have a strong capital structure, and significant cash inflows from product revenues that we believe will enable us to deliver significant return back to our shareholders while maintaining investments in our business. Thank you for your support, and, Michael, back to you.

我們如今很幸運擁有穩健的資本結構，以及來自產品營收的可觀現金流入；我們相信這將使我們在維持對業務投資的同時，也能為股東帶來可觀回報。感謝各位的支持，Michael，交回給你。

Thank you. Tyrone, we'd now like to open up the call to questions.

謝謝。Tyrone，我們現在想開放電話會議進入提問。

Thank you. (Operator Instructions) Our first question is from Geoffrey Porges of Bernstein. Your line is open.

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

Thanks very much for taking the questions. Congratulations on the first year of profitability. Ian, a couple of questions on your philosophy in giving us this guidance. First of all, you seem to be guiding that INCIVEK is expected to be down modestly versus the fourth quarter. And can you tell us what you thought about that? And secondly, as you think about expenses, presuming there may be some revenue opportunities emerging from either KALYDECO or else coming from royalties, do you expect expenses would be fixed at those levels or would they ramp up if there was incremental revenue? And lastly, could you just give us a sense of whether you think this gross margin is sustainable at this level given the portfolio? Thanks.

非常感謝讓我提問。恭喜你們第一年達成獲利。Ian，關於你們提供這份指引的理念，我有幾個問題。首先，你們的指引似乎暗示 INCIVEK 相較第四季預期會小幅下滑。你能談談你們對此的看法嗎？第二，談到費用方面，假設未來可能出現一些營收機會，無論是來自 KALYDECO 或權利金收入，你們預期費用會固定在這些水準，還是若有額外營收就會隨之增加？最後，你能否讓我們了解一下，考量到產品組合，你們認為目前這個毛利率水準是否可持續？謝謝。

Okay, Jeff, how you doing? I think I got all five of those questions. (laughter) So let's start, and if I missed any, please take me back. First of all, why guidance? Well, as I'd said in my prepared remarks, we do think it's important to give the investors and analysts a good understanding of the cash inflows that are coming into our business and then how we choose to reinvest them versus allowing them to drop to the bottom line. The key line items in terms of those coming into our business are in the INCIVEK net revenues.

好的，Jeff，你最近怎麼樣？我想我把那五個問題都回答到了。（笑聲）所以我們開始吧，如果我漏了任何一個，請你再提醒我。首先，為什麼要提供財測指引？嗯，正如我在事先準備的發言中所說，我們確實認為，讓投資人與分析師充分了解流入我們業務的現金，以及我們如何選擇再投資這些現金、而不是讓它直接落到淨利（bottom line），是很重要的。就流入我們業務的關鍵科目而言，主要是 INCIVEK 的淨營收。

We feel as though we have a good understanding of the hepatitis C market, and the range that we gave up $1.5 billion to $1.7 billion is a range that we're confident of achieving in 2012. Other line items on the revenue, though, it's a little more difficult because we're at the earlier stages of launches of products. So the KALYDECO revenue stream for 2012, we have to see how that goes, and then also the same with INCIVO which is, of course, INCIVEK in Europe. But that is also at its early stage of the launch. As we go through the year, we get a better understanding, we may provide further guidance. Those are two line items that could provide significant cash inflow to the business.

我們覺得自己對 C 型肝炎市場有相當好的掌握，而我們給出的 15 億到 17 億美元區間，是我們有信心在 2012 年達成的範圍。不過，營收的其他科目就比較困難一些，因為我們的產品仍處於上市初期階段。因此，2012 年 KALYDECO 的營收走勢，我們必須觀察實際進展；同樣地，INCIVO（也就是歐洲的 INCIVEK）也是如此。但它也仍在上市初期。隨著年度推進、我們掌握度提高，我們可能會提供進一步的指引。這兩個科目都可能為公司帶來顯著的現金流入。

And as we go through the year, then we may give further guidance on those line items. But at this stage, it just feels too early. From an expense base, clearly, the trajectories in our business of R&D, which have been questioned a number of times, we want to give the guidance on how are managing the business financially on the investment side. And as you see, the total operating expense guidance that we're giving, it is a 10% increase on the prior year, but from an SG&A perspective, it is being held fairly constant to 2011. There is slight growth in the R&D side, but that's because of the progression and advancement of development programs.

而隨著年度推進，我們也可能就這些科目提供進一步指引。但在目前這個階段，感覺還太早。在費用基礎方面，很明顯，我們業務中的研發（R&D）費用走勢已被多次提問；我們希望透過指引，說明我們在投資端如何進行財務管理。如你所見，我們給出的總營運費用指引，相較前一年增加 10%，但從銷售、一般及行政（SG&A）角度來看，基本上維持在與 2011 年相當的水準。研發端有些微成長，但那是因為開發計畫的推進與進展。

So we wanted to give that kind of financial structure to the business and that's the reason to give the guidance and we have the confidence to give that guidance. To your other questions, you asked about the INCIVEK trajectory, I assume you are comparing it to a Q4 number. We were fortunate in Q4 to benefit from this rapid uptake following launch where there was a high volume of patients flowing into the system, which we, clearly, benefit from a revenue perspective as we went to the fourth quarter.

因此，我們希望為業務提供這樣的財務架構，這就是提供指引的原因，而且我們也有信心給出這樣的指引。至於你其他的問題，你問到 INCIVEK 的走勢，我猜你是在拿它和第四季的數字比較。我們在第四季很幸運，受惠於上市後的快速採用，當時有大量病患進入治療體系；很明顯，從營收角度來看，這讓我們在第四季受益。

As we go into 2012, we're establishing where we believe the run rate of the patients are flowing through the system and that's reflected in our guidance of $1.5 billion to $1.7 billion. I would point out, we did benefit early on by patients that were waiting for therapy, then came our approval and they came into the system. We do feel as we give guidance of $1.5 billion to $1.7 billion that we have a confidence of achieving that. As far as the other revenues, I mentioned those. Those are the INCIVO royalty revenues and also the KALYDECO revenues.

進入 2012 年後，我們正在建立我們所認為的、病患在體系中流動的常態化速度（run rate），這也反映在我們 15 億到 17 億美元的指引中。我要指出的是，我們在初期確實受惠於那些原本在等待治療的病患；在我們獲准後，他們就進入了體系。我們在給出 15 億到 17 億美元指引時，確實有信心能達成。至於其他營收，我剛才也提到了。那包括 INCIVO 的權利金（royalty）收入，以及 KALYDECO 的營收。

Expenses in terms of how the business performs through the year, we're holding ourselves accountable internally to the numbers that we've provided to you, so we do not see those flexing and we have a number of programs internally ongoing in the Company that maintain those expenses and in some parts of our business, actually, take the expense away. As far as the gross margin on the products, we see it remaining fairly similar to 2011. We've always mentioned that the gross margins for the products we sell should be above 90% including the royalties that are attached to some of those products. So we're still in good shape as we go into 2012 on the gross margins of the two products that are now in the market.

就費用而言、以及公司在全年中的表現方式，我們在內部會對你們所收到的這些數字負責，因此我們不預期它們會有彈性變動；公司內部也有多項持續進行的計畫來維持這些費用水準，而在我們業務的某些部分，實際上還會把費用降下來。至於產品毛利率，我們預期會與 2011 年大致相近。我們一向提到，我們所銷售產品的毛利率應該高於 90%，其中也包含附帶於部分產品的權利金。因此，展望 2012 年，我們目前已在市場上的兩項產品，其毛利率狀況仍然良好。

Thank you very much. Appreciate that.

非常感謝。感謝你的說明。

Thank. The next question is from Terence Flynn of Goldman Sachs. Your line is open.

謝謝。下一個問題來自高盛（Goldman Sachs）的 Terence Flynn。你的線路已開通。

Hi, thanks for taking my question. Congrats on the progress. I just had a question on the ongoing KALYDECO 809 trial. I was wondering, first, if you can give us any update on enrollment? And then, two, maybe you could help us frame what you guys would view as a go/no go decision for taking that combination forward into a larger Phase 3 program?

嗨，謝謝讓我提問。恭喜你們的進展。我想問一下正在進行中的 KALYDECO 809 試驗。首先，想請問你們能否更新一下收案（enrollment）情況？第二，或許你們可以幫我們界定一下，你們會如何看待是否推進這個組合、進入更大型第三期（Phase 3）計畫的 go/no go 決策？

Hi, Terence. That's Peter speaking, and Bob will also maybe say a couple words to that. So first of all, Cohort 2 enrollment is going as expected, no delays or anything. We are expecting mid-year to have data that might be available for broader communication. Everything so far is on track and there are no stoplights that I can see at this given point in time. So what was the other question?

嗨，Terence。我是 Peter，Bob 也可能會補充幾句。首先，第 2 組（Cohort 2）的收案進度如預期進行，沒有延遲或任何問題。我們預期在年中會有一些資料，可能可以對外做更廣泛的溝通。到目前為止一切都在軌道上，就目前這個時間點，我看不到任何需要亮紅燈的地方。那你另一個問題是什麼？

This is Bob. Your second point is sort of our benchmarks for going forward into Phase 3. We've been asked this many times and it's very hard to put an exact number on it. I think a lot will depend on what we see in the trial. Obviously, looking at (inaudible) results and lung function results and it's just pretty hard to really pin ourselves down to something.

我是 Bob。你第二點是關於我們推進到第三期的基準（benchmarks）。這個問題我們被問過很多次，而要給出一個精確數字其實很難。我想很大程度會取決於我們在試驗中看到什麼。顯然會看（聽不清）結果以及肺功能結果，但要把自己完全釘在某個明確門檻上，確實很難。

The other comment I want to add, the decision is not solely on 809. We have two correctors, the other one is 661. It is not a binary yes or no, it is choosing the best regimen as we go forward. And we will get data in the course of the next couple of months to get a better insight, as Bob said, what there is. So don't see it as just an 809 type of event, see it as a broader approach to identify a viable regimen that treats this broader population.

我還想補充一點：這個決策不會只看 809。我們有兩個校正劑（correctors），另一個是 661。這不是二元的是或否，而是要在往前推進時選擇最佳的治療方案（regimen）。而在接下來幾個月的過程中，我們會取得資料，以便更深入了解情況；正如 Bob 所說，要看實際呈現的是什麼。所以不要把它只視為一個 809 的單一事件；應把它視為一個更廣泛的方法，用來找出可行的治療方案，以治療這個更廣泛的族群。

Okay, and can I just ask one follow-up on the design of the KALYDECO 809 study? I was wondering, I know you're enrolling both patients, homozygous and heterozygous, for F508 Delta. Is that a pre-specified stratification criteria, and are there set numbers of patients for each of those you're going to enroll?

好的，那我可以再追問一個關於 KALYDECO 809 研究設計的問題嗎？我想確認一下，我知道你們同時收納 F508 Delta 的同型合子（homozygous）與異型合子（heterozygous）病患。這是否是預先指定的分層（stratification）標準？另外，你們是否對各組要收納的病患人數有設定固定數量？

Yes. There's specific subgroups. The majority of the trial is the homozygous patients and there's one cohort of heterozygous patients and enrollment is, obviously, separately into those groups.

是的。有特定的子群（subgroups）。試驗的大多數是同型合子病患，另外有一個隊列（cohort）是異型合子病患；而收案當然是分別在這些組別中進行。

Okay, thanks a lot.

好的，非常感謝。

Thank you. Our next question is from Rachel McMinn of Bank of America-Merrill Lynch. Your line is open.

謝謝。我們下一個問題來自美國銀行美林（Bank of America-Merrill Lynch）的 Rachel McMinn。你的線路已開通。

Yes, two questions, one very specific, a broader one. On the specific one, I'm wondering, even though you can give us guidance for INCIVO, can you give us a sense of what INCIVO royalties really were in the quarter, whether there were one-time stocking effects in 4Q? Just want to make sure we don't overestimate the run rate going into 2012. And then the broader question on capital allocation, the exiting CEO had kind of previously articulated that R&D investment would kind of be first into the pipeline, second into kind of small M&A and deals, and then third, a distant third would be share repurchases. Jeff, I was wondering if you could, if I could take your temperature on your view of that capital allocation strategy? Thanks.

是的，有兩個問題，一個非常具體，另一個比較宏觀。先就具體的問題，我想請教，雖然你們可以提供 INCIVO 的指引，但能否讓我們了解一下本季 INCIVO 權利金實際是多少？第四季是否有一次性的鋪貨（備貨）效應？只是想確認，我們在進入 2012 年時不會高估其持續性營運水準。接著是關於資本配置的更廣泛問題：先前卸任的執行長曾表達，資金配置的優先順序大致是：第一投入研發以推進產品線；第二投入小型併購與交易；第三，而且是遠遠排在第三的，才是庫藏股回購。Jeff，我想請問你對這樣的資本配置策略的看法如何？我能否了解一下你的態度與傾向？謝謝。

Hi, Rachel it's Ian. So the royalties from INCIVO in the fourth quarter were approximately $16 million. There is a little bit of stocking in there, but it's also right at the beginning of the approvals and launches of INCIVO in the various European countries. It has been approved in the major European countries now. We would anticipate that the run rate of that royalty to pick up significantly, frankly, as we go into 2012.

嗨，Rachel，我是 Ian。第四季來自 INCIVO 的權利金約為 1,600 萬美元。其中確實有一點鋪貨（備貨），但同時也正值 INCIVO 在歐洲各國剛開始獲批並上市的初期。目前已在主要歐洲國家獲得核准。坦白說，我們預期進入 2012 年後，該權利金的常態化水準會顯著提升。

And, Rachel, this is Jeff on your question on capital allocation. I think Matt and I were and are in complete agreement about that. As you know, I've told you before we're quite excited about a number of opportunities in our current pipeline, including our Alios nukes, triple oral in HCV, our KALYDECO label expansion in CV, and then, of course, the combination studies. And behind that, the flu, the epilepsy and the JAK compounds. So there are a lot of exciting things to invest in. We plan invest in them because not to do so would be to starve the future growth of our business.

Rachel，關於你資本配置的問題，我是 Jeff。我想 Matt 和我對此完全一致，過去如此，現在也一樣。如你所知，我之前也提過，我們對目前產品線中的多個機會感到相當興奮，包括 Alios 的核苷類（nukes）、HCV 的三藥全口服方案、KALYDECO 在 CV 的適應症標籤擴展，當然還有各項聯合用藥研究。此外還有流感、癲癇以及 JAK 化合物。因此有很多令人振奮、值得投資的項目。我們計畫投入資源，因為若不投入，就等於扼殺公司未來的成長。

With respect to M&A activities, I think like most companies, we keep a careful eye on what is going on on the outside. We're in the fortunate position of not having to do deals because of our pipeline. On the other hand, we're always looking for interesting things that can complement what we have internally and we will continue to do so.

至於併購活動，我想和多數公司一樣，我們會密切關注外部正在發生的事情。我們很幸運，因為憑藉我們的產品線，我們並不需要為了填補產品線而被迫做交易。但另一方面，我們也一直在尋找能與內部資產互補的有趣機會，並且會持續這麼做。

And I'm sorry, just a quick follow-up to that. Anything specific on HCV, or do you feel comfortable your HCV portfolio?

抱歉，我再快速追問一下。在 HCV 方面有沒有任何具體的考量？或者你們對自己的 HCV 產品組合感到安心嗎？

We feel very comfortable with our HCV portfolio. In fact, I would say as I look at it, and I've been looking at it for a while now, it's the broadest and deepest portfolio that allows us the most swings at the ball, Rachel. And I think, again, I've talked with you about this before, I don't think anybody knows exactly what the winning combinations are going to be yet for the different patient sub-populations, and what I like about our pipeline is we have many different swings at the ball. With the two Alios nukes, which can be combined with each other, ribavirin, obviously, our non-nuke, VX-222, and INCIVEK. So I think when I look at our pipeline, we have the component parts to create a number of winning regimens and we plan to pursue several of those to understand how they are going to work and how it's going to play out in these different patient sub-populations.

我們對自己的 HCV 產品組合非常有信心。事實上，就我目前的觀察——而且我已經研究一段時間了——這是最廣、也最深的產品組合，讓我們有最多次「揮棒」的機會，Rachel。而且我想我之前也跟你談過，沒有人能完全確定，針對不同病患亞族群，最終勝出的聯合療法會是哪些；我喜歡我們產品線的一點是，我們有很多不同的揮棒機會。我們有兩個 Alios 的核苷類（可彼此搭配），再加上利巴韋林（ribavirin），當然還有我們的非核苷類 VX-222，以及 INCIVEK。所以當我看我們的產品線時，我認為我們具備組成多種勝出療程的零組件；我們也計畫推進其中數個方案，以了解它們將如何運作，以及在不同病患亞族群中會如何發展。

Perfect, thanks very much.

太好了，非常感謝。

Thank you. Our next question is from Geoff Meacham of JPMorgan. Your line is open.

謝謝。下一個問題來自摩根大通（JPMorgan）的 Geoff Meacham。您的線路已開通。

Hi, thanks for taking the question. This is actually Mike in for Jeff. Just wondering if you can maybe break out for us INCIVEK patient numbers in terms of the dynamic between those that are naive and experienced, and maybe sort of what you're seeing and how that is sort of changing over time? Thanks.

嗨，謝謝讓我提問。其實我是 Mike，代 Jeff 提問。想請問你們是否能拆分一下 INCIVEK 的病患人數，特別是初治（naive）與經治（experienced）病患之間的動態比例，以及你們觀察到的情況、以及這種情況隨時間如何變化？謝謝。

Sure, Mike, this is Nancy. Actually, when we first launched the drug we saw a slight tip toward the naive patient group at about a 60/40 split, and to date but really hasn't changed. And I think that's an indication of the fact that there are a good number of patients who are out there, who are still coming into offices, that are seeking treatment from all types of backgrounds, and contributes to some of the facts that Ian mentioned in our guidance for this year.

當然可以，Mike，我是 Nancy。其實在我們剛上市時，初治病患略多一些，大約是 60/40 的比例；到目前為止基本沒有改變。我認為這顯示仍有相當多不同背景的病患持續走進診間尋求治療，也呼應了 Ian 在今年指引中提到的一些因素。

Great, thanks.

很好，謝謝。

Thank you. Our next question is from Mark Schoenebaum of ISI. Your line is open.

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

Hi, this is Wes sitting in for Mark. I actually had a question about the SG&A guidance. I noticed that the fourth quarter SG&A expense annualized is larger than the 2012 guidance. So I was wondering if you could just talk about how the split of SG&A expense will occur over the quarter? And also, over the year, excuse me, and also if you could explain the variance of that annualized 4Q SG&A number? Thanks.

嗨，我是 Wes，代 Mark 提問。我其實想問的是關於 SG&A（銷售、一般及行政）費用指引。我注意到第四季的 SG&A 費用若年化後，會高於 2012 年的指引。所以想請你們談談 SG&A 費用在各季之間會如何分配，以及在全年（抱歉，我是指全年）層面，也請解釋一下第四季 SG&A 年化數字與指引之間的差異原因。謝謝。

Sure, appreciate the question, actually appreciate you pointing it out, something financially we're actually very proud of. So we have a number of initiatives, as I mentioned in answer to another question, within our business where we're looking at processes and efficiencies and we've set ourselves some objectives, and we're going to be going about some things different this year than we have in the past. And we expect those to result in expense savings. There have also been a few costs that have been of a one-time nature in 2011 that we will no longer be incurring. But we're at that stage of our business where we have gone through our business, how we operate, look at processes, and we're trying to find out how we can operate our business efficiently while maintaining our priority and key focus on investment in R&D that will drive the future of the Company. And I appreciate you asking the question because it's coming through in the SG&A line.

當然，謝謝你的問題，也謝謝你指出這點；從財務角度來看，我們其實對此非常自豪。如同我在回答另一個問題時提到的，我們在業務中推動了多項計畫，著眼於流程與效率；我們設定了一些目標，今年會以不同於過去的方式來做一些事情。我們預期這些將帶來費用節省。另外，2011 年也有少數一次性成本，之後我們將不再發生。我們正處於這樣的階段：全面檢視我們的業務與營運方式、檢視流程，並嘗試找出如何在維持效率的同時，仍把重點與優先順序放在研發投資上，因為研發將驅動公司未來。也謝謝你提出這個問題，因為這確實反映在 SG&A 這一行。

Great, thank you.

很好，謝謝你。

Thank you. Our next question is from Yaron Werber of Citi. Your line is open.

謝謝。下一個問題來自花旗（Citi）的 Yaron Werber。您的線路已開通。

Hi, this is Gloria on for Yaron. He wanted to know whether or not you would consider buying back CF royalties from the CF Foundation? And also, if I could ask a second question, for Q4 '11 it seemed that you had a tax rate of 10.7%. We were wondering if you can sustain that through 2012?

嗨，我是 Gloria，代 Yaron 提問。他想知道你們是否會考慮向 CF Foundation 買回 CF 權利金？另外我可以再問第二個問題嗎？2011 年第四季看起來你們的稅率是 10.7%。我們想了解你們是否能在 2012 年維持這個水準？

Yes, thanks for the question, a couple questions there. First of all, we don't comment on potential business development type transactions. I would say that if there is something that is interesting for our business and makes financial sense we'll give it consideration. As far as the tax rate concern, I understand your question, it is a little confusing, the number that you're referring to is actually the tax line that we have to consolidate from Alios and it's actually not our taxes. The accounting for Alios is that we actually have to consolidate Alios into our financial statements. We then remove them on the bottom line. So it's actually not our tax line item.

好的，謝謝你的提問，裡面有兩個問題。首先，我們不評論潛在的商務開發類交易。我會說，如果有任何對我們業務有吸引力且在財務上合理的事情，我們會加以考量。至於你對稅率的疑問，我理解你的問題，這確實有點容易混淆；你所指的數字其實是我們因合併 Alios 而必須在稅項行列中納入的項目，實際上並不是我們自己的稅負。Alios 的會計處理方式是：我們必須將 Alios 併入我們的財務報表。然後在最終淨利（bottom line）再把它們剔除。所以那其實不是我們的稅項科目。

As I mentioned in the prepared remarks, we actually have NOLs that allow us to offset the income that we make and our tax obligations are actually minimal. So cash tax obligations are minimal, we do have some small state taxes but it really is minimal. If you look to the non-GAAP financials that we disclosed in our press release, you'll see that the true -- kind of the true tax cash rate.

如同我在事先準備的發言中提到的，我們其實有可用的淨營業虧損（NOLs），讓我們能夠抵減我們所產生的所得，因此我們的稅負義務其實非常低。所以現金稅負義務很低，我們確實有一些小額的州稅，但真的很少。如果你看我們在新聞稿中揭露的非 GAAP 財務數據，你會看到真正的——算是真正的現金稅率。

Thank you, next question, please?

謝謝，請下一題？

Thank you. Our next question is from Howard Liang of Leerink Swann. Your line is open.

謝謝。我們的下一個問題來自 Leerink Swann 的 Howard Liang。您的線路已開通。

(Inaudible) did you say anything about the contribution from inventory changes to the sales in the fourth quarter and whether there were any sales to a third party for clinical supply?

（聽不清楚）你們是否有提到第四季銷售中，庫存變動的貢獻，以及是否有向第三方銷售臨床供應用藥？

Could you say that again? It didn't come through quite clearly, please?

可以再說一次嗎？剛剛聽得不是很清楚，麻煩您？

Inventory change and any sales for clinical trials.

庫存變動，以及任何臨床試驗用的銷售。

Okay. In terms of, if you measure from September 30 through to December 31 and look at the level of inventory it was negligible change, Howard. I don't have an impact on the revenue recognition.

好的。就庫存而言，如果你以 9 月 30 日到 12 月 31 日來衡量並看庫存水位，變動可以忽略不計，Howard。我看不出對收入認列有任何影響。

Any contribution from sales to third party for clinical supply and whether that may continue in 2012?

臨床供應用藥向第三方銷售是否有任何貢獻？以及 2012 年是否可能延續？

There have been pieces within our revenue line where third parties have been buying INCIVEK for their own clinical trials, but as you might expect, it's the majority of sales are to patients.

我們的營收項目中確實有一些部分是第三方為了他們自己的臨床試驗而購買 INCIVEK，但如你所預期，絕大多數的銷售仍是給病患。

Okay. If I could just follow up a separate question, you're interferon-free regimen, how you make the determination to move forward, what would it take for you to move to Phase 3 for the 222 INCIVEK ribavirin combination? When would you consider trial-specific for subgroups for genotype-1 patients, 1a or 1b?

好的。如果我可以再追問一個不同的問題：關於你們的無干擾素（interferon-free）療程，你們如何決定要往前推進？要達到什麼條件你們才會把 222 的 INCIVEK 與利巴韋林（ribavirin）組合推進到第三期？你們何時會考慮針對基因型 1 病患的亞群（1a 或 1b）做特定試驗？

Yes, this is Bob, we are awaiting the results of the SVR 4 data from the ribavirin triple, and, clearly, that will be the most important piece of information that we get in order to decide whether to go forward. Obviously, the bar is set really quite high in the field for, certainly, for expectations for what SVR rates are, and, obviously, we'll be looking to see that we have a competitive regimen based on the data that we obtain. We have multiple potential non-interferon-based regimens and we will have to spend some time thinking about sort of allocating resources to those various options, including the ribavirin triple, and then coming a little later in the year the possibility of combinations with the Alios compounds. And there's a lot of mixing and matching within our own portfolio that we believe can occur. So it's going to be a bit of a complex equation but it will surely be data driven.

是的，我是 Bob。我們正在等待利巴韋林三聯療法的 SVR4 數據結果，而很明顯，這將是我們用來決定是否繼續推進最重要的一項資訊。顯然，在這個領域的門檻設得相當高，尤其是對 SVR 率的期待；我們也會觀察我們取得的數據是否能支持一個具競爭力的療程。我們有多個潛在的非干擾素基礎療程，必須花一些時間思考如何在各種選項之間配置資源，包括利巴韋林三聯療法，以及在今年稍晚與 Alios 化合物進行組合的可能性。而且我們相信，在我們自有產品組合內也有很多可以進行的混搭組合。所以這會是一個有點複雜的方程式，但肯定會以數據為驅動。

Thank you.

謝謝。

Thank you. Our next question is from Jason Kantor of RBC Capital Markets. Your line is open.

謝謝。我們的下一個問題來自 RBC Capital Markets 的 Jason Kantor。您的線路已開通。

Yes, a couple of questions. First of all, congratulations, again, on KALYDECO. In terms of the launch, I know that awareness for this drug was really high and genotyping was also something that has been done a lot, and there's a lot of interest in those trials, so I'm wondering, should we be thinking about this as a real bolus of patients that come on very quickly following the approval? And also on the HCV market, if you could give us some sense of what you think the market dynamics are right now in terms of capacity, warehousing, and any kind of seasonality that we can expect in Q1? Thanks.

是的，兩個問題。首先，再次恭喜 KALYDECO。就上市推廣而言，我知道這個藥的知名度非常高，基因分型也已經做了很多，而且大家對那些試驗很有興趣，所以我想問，我們是否應該把它視為在核准後會有一波病患非常快速地開始用藥？另外在 HCV 市場方面，你們能否讓我們了解一下你們認為目前市場動態如何，包含產能、囤藥（warehousing），以及第一季可能出現的任何季節性？謝謝。

Great, Jason. Let me see if I can hit all that. So first of all, on cystic fibrosis and KALYDECO, this is a very well-known patient community, and as you know the majority of them are children and they are in routine care at a predictable number around, just slightly more than 110 CF centers across the United States. What that means is that they all show up for care at least once quarterly. And since the vast majority of them have already been genotyped, either the patient, their caregiver or the physician is clearly aware of which patients KALYDECO will be used in.

好的，Jason。我看看能不能把這些都回答到。首先談囊性纖維化與 KALYDECO，這是一個非常熟悉彼此的病患社群；如你所知，多數病患是兒童，他們會在美國大約、略多於 110 家 CF 中心接受例行照護。這代表他們至少每季都會回診一次。而且由於絕大多數病患都已完成基因分型，不論是病患、照護者或醫師，都很清楚哪些病患會使用 KALYDECO。

We've heard a few early rumors that in some cases they're actually canceling their routine clinic appointments in order to open up days just to be dedicated to bringing in these patients. But I think from those comments you can probably begin to think through what that uptake is going to look like. Switching over to HCV, capacity and warehousing. Well, first of all, to the talk about the market in general as it relates to capacity, last year as we launched, we saw a really huge spike in treatment because prior to the launch of the PIs, there really weren't any medications that were nearly as efficacious.

我們聽到一些早期傳聞，在某些情況下，他們甚至取消例行門診，以便騰出日子專門用來安排這些病患就診。不過我想，從這些評論你大概可以開始推想其採用速度會是什麼樣子。再切換到 HCV，談產能與囤藥。首先，談到整體市場與產能的關係，去年我們上市時，治療量出現非常大的尖峰，因為在蛋白酶抑制劑（PI）上市之前，幾乎沒有任何藥物有那麼好的療效。

So what that meant was that we really had to jump and some of the offices realized that stretched them a little too far and the general capacity has calmed down a little. Following that, we saw the holiday effect. We talked about that holiday in advance, I think what we saw was consistent with what we expected and what the historical use, even with the pegylated interferon showed. And then typically, what happens is in January you see a restabilization, and we believe that restabilization will -- well, it's already beginning to occur, it will continue. And that the slope of that curve for next year is going to, again, be consistent with what we've seen with the pegylated interferon in being a pretty steady sort of state.

這代表我們必須迅速應對，而有些診所也發現這讓他們的負荷有點超出，因此整體產能後來稍微冷卻下來。之後我們看到假期效應。我們事前就談過這個假期效應，我認為我們看到的情況與我們的預期一致，也與歷史用藥情形一致，即便是在聚乙二醇化干擾素（pegylated interferon）時期也是如此。接著通常在一月會看到重新穩定，我們相信這種重新穩定——其實已經開始發生——會持續下去。而且明年那條曲線的斜率也將再次與我們在聚乙二醇化干擾素上看到的情況一致，呈現相當穩定的狀態。

In terms of warehousing, we're not quite certain that we've burned through all the warehousing that occurred prior to the launch of the PIs. We see those patients continuing to come in. And although every physician makes some unique determinations in a patient's first call, kind of a patient's first visit, they tend to put a patient aside here or there. We don't think that there is any significant impact from their thoughts about future therapies, and really, there's not that much information out there yet. So it's too early to even begin to think about quantifying an impact like that. But we'll be watching it through the year and keeping you apprised as we see things develop differently.

就囤藥而言，我們不太確定在 PI 上市前所發生的囤藥是否已經完全消化完畢。我們看到那些病患仍持續進來。雖然每位醫師在病患第一次來診、也就是病患的首次就診時，都會做一些獨特的判斷，可能會把某些病患先暫緩一下。我們不認為他們對未來療法的想法會造成任何顯著影響，因為目前外界其實也還沒有那麼多資訊。所以現在就要開始量化這類影響還太早。但我們會在今年持續觀察，若看到情況有不同發展，也會隨時向各位更新。

Thank you.

謝謝。

Thank you. Our next question is from Matt Roden of UBS. Your line is open.

謝謝。我們的下一個問題來自 UBS 的 Matt Roden。您的線路已開通。

Hi, guys. This is actually Andrew in for Matt, and congratulations on the quarter. I was wondering if I could ask, I guess, your general interest on partnering, specifically for 509 and 787? Those are pretty sizable markets and I think the clinical requirements for a trial in flu, as well is in RA are pretty significant. So what are your thoughts on how you would manage those kind of Phase 3s on your own as opposed to kind of getting a partner to help manage some of those costs? Thanks.

嗨，各位。我其實是 Andrew，代替 Matt 發問，恭喜本季表現。我想請問你們對合作夥伴（partnering）的整體意願，特別是針對 509 和 787？這些都是相當大的市場，而且我認為無論是流感或類風濕性關節炎（RA），其臨床試驗的要求都相當高。所以你們對於如何自行管理這類第三期試驗有什麼想法？相較之下，是否會考慮找合作夥伴來協助分攤並管理部分成本？謝謝。

Thanks for the question. I'll start by saying that if we have the opportunity to run a Phase 3 with these drugs and these diseases, I think that's a rare opportunity for a company. So you can see where we're leaning as business. The hardest thing to do is actually get the molecule all the way through, ready to start of Phase 3 in these diseases. So if we're successful with the next stages of these two compounds that you refer to, we'd look forward to running a Phase 3. We think we have the capacity in our business both from resources and financial resources to run those to Phase 3 and they are a big opportunity for us. And as we look into the future, if we have the ability to run those to Phase 3 what it says is we actually have that opportunity for continued revenue growth in the middle and latter parts of this decade. As far as considering the compounds going outside the Company, we don't comment on those kind of transactions. We're running the studies, as Peter has mentioned, and Jeff has mentioned, and we look forward to getting the results from them.

感謝提問。我先說，如果我們有機會用這些藥物在這些疾病上進行第三期試驗（Phase 3），我認為對一家公司而言那是難得的機會。所以你可以看出我們在商業面上的傾向。最困難的其實是把分子一路推進到位，準備好在這些疾病上啟動第三期試驗。因此，如果我們在你提到的這兩個化合物的下一階段取得成功，我們會期待進行第三期試驗。我們認為，無論在人力資源或財務資源方面，我們的業務都有能力把它們推進到第三期試驗，這對我們是很大的機會。而展望未來，如果我們有能力把它們推進到第三期試驗，這代表我們在本十年中後段將有持續營收成長的機會。至於是否考慮將這些化合物移出公司之外，我們不評論這類交易。我們正在進行研究，如 Peter 與 Jeff 所提到的，我們也期待取得研究結果。

Okay, thanks.

好的，謝謝。

Thank you. Our next question is from Ted Tenthoff of Piper Jaffray. Your line is open.

謝謝。下一個問題來自 Piper Jaffray 的 Ted Tenthoff。您的線路已開通。

Thank you very much. I have to say, looking into 2012 I'm very excited about where the Company is and congratulations on launch and approval of KALYDECO. I actually had two quick kind of housekeeping questions. Ian, you said about the tax rate, that it would be -- remain kind of low. Will it be -- can you give us any guidance on what that actually might be? Because I know there's a lot of different parts to that. And also, and I had to -- you'll have to excuse me if I missed this, but I recall that you got the EU milestones for payment for approval of INCIVO last quarter, but I didn't see where that came out in this quarter. I just wanted to see if you have any comment on that?

非常感謝。我必須說，展望 2012 年，我對公司目前的狀況感到非常振奮，也恭喜 KALYDECO 的上市與核准。我其實有兩個簡短的例行問題。Ian，你提到稅率會——維持在相對偏低。能否——給我們一些指引，實際上大概會是多少？因為我知道這裡面有很多不同的組成部分。另外，而且——如果我漏聽了請見諒，我記得你們上季收到了 INCIVO 在歐盟核准的里程碑款，但我沒有看到這一季反映在哪裡。我想確認一下你們是否能對此做些評論？

Sure. So, have a little patience on this and we don't get through it, Ted, then I'll certainly catch up with you offline on the taxes. But I'd just ask you to refer to the reconciliation of GAAP to non-GAAP and what you'll see on the left-hand side where you've got the GAAP numbers you will see a provision for income taxes. And as somebody mentioned earlier, that is up around [10%-ish] but that actually is a somebody else's tax line that we're consolidating, unfortunately. When we do our reversals for the Alios transaction and other kind of deferred type tax assets we end up with minimal taxes. That is the tax position and the cash tax position of the business and it's because of the NOLs.

當然。Ted，這部分請稍微有點耐心，如果我們在這裡沒能完整說清楚稅務，我之後一定會私下再跟你補充。不過我想請你參考 GAAP 與非 GAAP 的調節表，你會在左側看到 GAAP 數字中有一項所得稅費用提列。如同先前有人提到的，那大約在 [10%-左右]，但不幸的是，那其實是我們合併報表中「別人」的稅務項目。當我們針對 Alios 交易以及其他類型的遞延稅資產做回轉後，最終的稅負就會非常少。這就是本業的稅務狀況與現金稅負狀況，原因在於我們有 NOL（淨營運虧損結轉扣抵）。

The NOLs aren't just federal NOLS, we have state NOLS, as well, so we take advantage of those. As you think about a cash tax for our business, certainly, as we work through the $3 billion with NOLs they will continue, the cash taxes will continue to be minimal in our business. So I'd just ask you to take a look at that GAAP to non-GAAP reconciliation, as I say, I can do it offline. As far as the INCIVO milestones are concerned, we did have milestones that were recorded earlier in the year and we actually reversed those out in the non-GAAP and I think those were recorded, if I remember correctly, in Q3. And that's why they do not show up in Q4 -- yes -- the milestone that came in in Q4 was the Mitsubishi milestone and you'll see that, that's $65 million.

這些 NOL 不僅是聯邦層級的 NOL，我們也有州層級的 NOL，因此也會加以運用。就我們業務的現金稅負而言，當我們逐步使用這約 30 億美元的 NOL 時，現金稅負在我們的業務中將會持續維持在很低的水準。所以我仍建議你看一下那份 GAAP 對非 GAAP 的調節表；如我所說，我也可以私下再說明。至於 INCIVO 的里程碑款，我們確實在今年稍早認列過里程碑收入，而在非 GAAP 中我們其實把那些回轉掉了；如果我沒記錯，那是在第三季（Q3）認列的。因此它們不會出現在第四季（Q4）——是的——第四季進來的里程碑款是三菱（Mitsubishi）的里程碑，你會看到那筆是 6,500 萬美元。

Yes. Okay, perfect, I appreciate the comments there. I'm looking forward to a good launch for KALYDECO.

是的。好的，完美，我很感謝這些說明。我也期待 KALYDECO 有個好的上市表現。

Thank you.

謝謝。

Thank you. The next question is from Brian Abrahams of Wells Fargo. Your line is open.

謝謝。下一個問題來自 Wells Fargo 的 Brian Abrahams。您的線路已開通。

Good evening, this is Matthew Andrews calling in for Brian. Thank you for taking the question. On Tuesday you noted that there were 190 patients in the persist long-term follow-up KALYDECO study with about 100 of those being in the US. Can you discuss the EAP, how many patients are in that? How many are enrolled in the US and Europe? And how quickly the ones that are in the United States could transition over to commercial therapy? Thank you.

晚安，我是 Matthew Andrews，代替 Brian 來提問。謝謝讓我提問。你們週二提到，在 KALYDECO 的 persist 長期追蹤研究中有 190 位病患，其中約 100 位在美國。能否談談 EAP（擴大使用計畫），其中有多少病患？在美國與歐洲各有多少人納入？以及在美國的那些病患能多快轉換到商業化治療？謝謝。

So I think it currently, so that's Peter speaking, Matthew, in the US, that's correct, that's currently about 100 patients on that will trickle off in the next -- start in Q2 and lasting all into first quarter of 2013. And in Europe, it is set up for now sort of as an inpatient program with about 100 patients overall, but there's not 100 on right now, it's about 30 or so. That's about what we have right now. But we are in negotiations with different countries to see whether we can reach out there and launch the program.

我想目前——我是 Peter，Matthew——在美國，你說得沒錯，目前大約有 100 位病患在那個計畫中，接下來會在第二季（Q2）開始逐步退出，並一路延續到 2013 年第一季。而在歐洲，目前的設計比較像是住院（inpatient）方案，整體約 100 位病患的規模，但現在並沒有 100 位正在參與，大約是 30 位左右。這就是我們目前的狀況。不過我們正在與不同國家洽談，看看是否能在那邊擴大並啟動該計畫。

Okay, thank you.

好的，謝謝。

Thank you. The next question is from Ying Huang of Barclays. Your line is open.

謝謝。下一個問題來自 Barclays 的 Ying Huang。您的線路已開通。

Thank you for taking the question and congratulations on the quarter. First question, you commented on your still burning to the warehouse patients from the (inaudible) interferon days, but are you guys actually seeing actually warehousing of these patients again for the next wave of interferon [R] regimen? And if, yes, do you actually figure in that when you provide the guidance for $1.5 billion to $1.7 billion this year? And secondly, I have a follow-up on the financials.

謝謝讓我提問，也恭喜本季表現。第一個問題，你提到仍有一些從（聽不清）干擾素時代就被「囤積到倉庫」的病患，但你們是否真的又看到這些病患為了下一波干擾素 [R] 療程而再次被「囤積／延後治療」？如果是，你們在提供今年 15 億到 17 億美元的指引時，是否已把這點納入考量？第二，我有一個關於財務數字的追問。

Okay, let me take the first part of that, Ying, that's a great question. So you're right, there are two different issues around warehousing. And the comment that I made earlier, what I was trying to explain is that when a patient comes in and a physician decides to treat they always sort of triage them in their own mind, and as they believe that there are new therapies that may come down the road, they begin to add those into their thinking. However, at this point in time, it's really too early for us to think about any quantitative impact from what we're seeing in the market and we believe that if there is any warehousing like that that has occurred it's really very minimal. So we're not very concerned about that at this point and our current view is baked into our guidance of $1.5 billion to $1.7 billion.

好的，Ying，我先回答第一部分，這個問題問得很好。你說得對，所謂「囤積／延後治療（warehousing）」其實有兩個不同面向。我先前的評論想要說明的是：當病患就診、醫師決定是否治療時，通常會在心中對病患做某種分級排序；而當他們認為未來可能會有新療法推出時，也會把這些因素納入考量。不過就目前而言，我們認為現在要從市場觀察推估任何量化影響仍為時過早；而且我們相信，即便有發生這樣的囤積／延後治療，其程度也非常有限。因此我們目前並不太擔心，而我們目前的看法也已反映在 15 億到 17 億美元的指引之中。

Great, thanks. And then, Ian, I just calculated your cost of goods sold for 4Q, it is only 5%. If you look at the whole year 2011 it's about 6.7%. When you commented on that for 2012 your costs will be consistent to '11. Did you specifically mention that it was closer to the whole year average of 2.7%, or it's actually going to be consistent to the 5% you recorded in 4Q here? Thanks.

很好，謝謝。接著，Ian，我剛計算你們第四季（4Q）的銷貨成本（COGS），只有 5%。如果看 2011 全年，大約是 6.7%。你提到 2012 年的成本會與 2011 年一致。你具體是指更接近全年平均的 6.7%，還是會更接近你們在第四季記錄的 5%？謝謝。

Ying, I always appreciate your accuracy of comparing 5% to 6%. Certainly, we're very focused on that but I'm not going to go beyond the comments that I made earlier. I think the past cost of goods line is a pretty good indicator of how of 2012 will go, as well.

Ying，我一向很欣賞你把 5% 與 6% 做比較時的精準度。當然，我們非常專注於此，但我不會超出我先前所做的評論。我認為過去的銷貨成本（COGS）項目也相當能指示 2012 年的走向。

Great, thank you.

很好，謝謝你。

Thank you. Our next question is from Liisa Bayko of JMP Securities. Your line is open.

謝謝。下一個問題來自 JMP Securities 的 Liisa Bayko。請開線。

Hi, thanks for taking the question, and congratulations on a great quarter, as well. Can you maybe just talk about -- I'm just trying to figure out the gross to net adjustment for KALYDECO. And then, maybe a follow-up question in the same regard is just on changes in stocking that occurred for INCIVEK in the US? Thanks.

嗨，謝謝讓我提問，也恭喜你們本季表現很棒。你們能否談談——我正在試著釐清 KALYDECO 的毛額到淨額（gross-to-net）調整。另外，同一脈絡的追問是：美國 INCIVEK 的備貨（stocking）在本季是否有任何變化？謝謝。

Sure. I'll take the latter first, Liisa, thanks, which is the stocking between September 30 and December 31 there was minimal change. So there wasn't a change in the levels of inventory at the wholesalers so it didn't really have an impact on the revenues that we recorded in the fourth quarter. As far as the gross to net adjustment is concerned on KALYDECO, we explained this on the call the other day which is that this is primarily driven by the split in patients which are either on commercial insurance or supported through the government.

當然。Liisa，謝謝，我先回答後者：在 9 月 30 日到 12 月 31 日之間，備貨變化很小。因此，批發商端的庫存水位沒有變動，所以對我們第四季認列的營收並沒有實質影響。至於 KALYDECO 的毛額到淨額調整，我們前幾天的電話會議已說明，主要是由病患結構所驅動，也就是病患是商業保險或由政府支持。

We anticipate this market is split 60/40, 60% being commercial insurance and 40% being government, and there is minimal discounting, minimal discounting on the commercial side. And on the government side, there is a statutory or mandatory discounting that ranges between 15% and 25% which will give you an idea of, if you blend those patient flows, it will give you an idea of the gross to net adjustment.

我們預期市場結構為 60/40，60% 為商業保險、40% 為政府，商業端折扣很少、折扣幅度很小。政府端則有法定或強制折扣，約介於 15% 到 25%；把這些病患流量加權後，就能大致推估毛額到淨額的調整幅度。

And then how do we think about for KALYDECO where any payment for free drug or co-pay assistance runs through and what -- how do we think about that as a percentage of the cost?

那麼對 KALYDECO 而言，免費用藥或自付額補助（co-pay assistance）的支付會如何反映？——我們應該如何把它視為成本的百分比？

It's very small.

非常小。

Okay.

好的。

Really doesn't impact the gross to net.

真的不會影響毛額到淨額。

And just one follow-up, if I may. Were there -- was there any change in patient discontinuations for INCIVEK in the quarter from past? I'm just trying to reconcile what the demand looks like from the prescription audit versus what you actually reported?

如果可以的話再追問一個。本季 INCIVEK 的病患停藥（discontinuations）相較過去是否有任何變化？我只是想把處方稽核（prescription audit）看到的需求，和你們實際揭露的數字對起來？

We are not aware of any changes at this point in time, Liisa.

Liisa，就目前而言，我們沒有注意到任何變化。

Okay, great. Thanks a lot.

好的，很好。非常感謝。

Thank you. OUr next question is from David Friedman of Morgan Stanley. Your line is open.

謝謝。下一個問題來自 Morgan Stanley 的 David Friedman。請開線。

Hi, thanks for taking the question. Just two quick ones. The first is can you let us know gross sales for INCIVEK for the quarter? And then the other is, in the combination CF study that you ran in the past with 809 and 770, could you just describe any PK-related drug interactions between the two drugs?

嗨，謝謝讓我提問。兩個很快的問題。第一個是：能否告訴我們本季 INCIVEK 的毛銷售額（gross sales）？第二個是：你們先前做過 809 與 770 的囊性纖維化（CF）合併用藥研究，能否描述兩個藥物之間任何與藥物動力學（PK）相關的交互作用？

So I actually don't have the gross sales number available, David, but if the question is referring to what was the gross net discount in the fourth quarter?

David，我手邊其實沒有毛銷售額的數字；但如果你的問題是指第四季的毛到淨折扣（gross-to-net discount）是多少？

Yes.

是的。

It was slightly above that of the third quarter. It approximated 13%, approximated. The reason why I give that number is it gives you an indication of how we go into 2012. I did mention in my prepared remarks that we anticipate a widening of the gross to net margin, that's because we have more covered lives with our insurers these days. And we're also maybe seeing more flow through the government channel, as well. So I give you as a marker and those we go into 2012, the gross to net adjustment is built into the guidance we gave of $1.5 billion to $1.7 billion.

它略高於第三季。大約是 13%，大約。我之所以提供這個數字，是因為它能讓你了解我們進入 2012 年時的狀況。我在事先準備的發言中提到，我們預期毛到淨的差距會擴大，原因是我們目前與保險公司涵蓋的受保人（covered lives）更多。此外，我們也可能看到更多經由政府通路的流量。因此我提供這個作為進入 2012 年的參考；毛到淨調整已納入我們給出的 15 億至 17 億美元指引之中。

Thanks.

謝謝。

And I might, this is Peter speaking, Mark. So with respect to your question of the earlier 778/809 study, I think we didn't release any data around PK in any specificity, however, I want to say, just remind you that it was a viable regimen, it was safe, it was a safety study. And it basically has proven the concept, at least the mechanism, to the point that we saw action on the channel which is basically proof that the target basically gets to the surface and does something. And the chosen dose at those phase was maybe not high enough to see a therapeutically relevant outcome, it was sort of borderline. But we learned that is the part of the Cohort 2 study, investigate different, those regimens, in different concentrations and then basically have maybe a better inroad into that patient population.

我補充一下，我是 Peter，Mark。關於你提到先前的 778/809 研究，我想我們並沒有針對 PK 發布任何具體細節的數據；不過我想提醒你，那是一個可行的療程，且是安全的——那是一項安全性研究。它基本上已驗證概念，至少在機制層面：我們看到通道（channel）有作用，這基本上證明標的確實到達細胞表面並產生作用。而當時階段所選的劑量可能不足以看到具治療意義的結果，算是介於臨界之間。但我們學到的是：在 Cohort 2 研究中，我們會以不同濃度去探索不同療程，進而可能更好地切入那個病患族群。

Okay, but you can't say whether there's any drug/drug interaction or PK change from 809?

好的，但你們無法說明是否存在任何藥物/藥物交互作用，或 809 的 PK 是否有變化嗎？

There's nothing out of the extraordinary, so, and we will study that as we go forward.

沒有任何異常之處；而且我們會在後續推進時持續研究。

Okay. Great, thank you.

好的。非常感謝。

Thank you. Our next question is from Marko Kozul of ThinkEquity. Your line is open.

謝謝。下一個問題來自 ThinkEquity 的 Marko Kozul。請開線。

Hi, good afternoon, and thanks for taking the question, and I also echo my congratulations. A few quick cystic fibrosis questions, part A is if we were to assume encouraging data from Cohort 2, mid-2012 for the combo KALYDECO with 809 what might Phase 3 designs look like? And part B, you announced, I think, today the start of the VX-661/KALYDECO study. I was wondering if you could outline its design? Thanks.

嗨，午安，謝謝讓我提問，我也同樣要恭喜你們。幾個關於囊性纖維化的快速問題：A 部分是，若我們假設 2012 年年中 KALYDECO 與 809 的合併療法在 Cohort 2 得到令人鼓舞的數據，第三期試驗設計可能會長什麼樣子？B 部分是，你們今天似乎宣布啟動 VX-661/KALYDECO 研究。我想請你們概述其試驗設計？謝謝。

So let's assume that data comes positive, that is always a good optimistic view. I think we cannot really 100% speculate what the design finally is because it needs regulatory authorities to approve that. We have to have a type C meeting to go into that and those discussions are basically partly ongoing and we will go from there. It is still to be determined how long those studies have to be, and how much and how big the safety -- the patient populations have to be to require basically a safety database that is wanted. So I can't really speculate on that because you have to have on a case-by-case basis a regulatory interaction. You have to have that not just in the US, but also globally, this is a global program, and I think we have to align sort of regulatory views in the world and we're currently doing that.

那我們就假設數據是正面的——這當然是很樂觀的看法。我認為我們無法 100% 推測最終設計會是什麼，因為需要監管機關核准。我們必須召開一次 Type C 會議來進行討論，而這些討論部分已在進行中，之後我們會再往下推進。目前仍待確定這些研究需要做多久，以及安全性——病患族群需要多大，才能建立監管所要求的安全性資料庫。所以我無法在此推測，因為你必須依個案與監管單位互動。而且不只是在美國，還包括全球；這是一個全球性計畫，我們必須在全球範圍內對齊監管觀點，我們目前正在做這件事。

So in terms of, just one last comment is, obviously, the endpoints, of course, are likely to be the same as the ones we did for the 770 program. Those are the standard endpoints. In terms of 661, obviously, that program is at an earlier stage and so the study is really looking at 661 individually in homozygous Delta F patients, and then 661 in combination with KALYDECO in the same patient population. And so we're kind of working our way through the monotherapy part of it and then we'll be doing some of the combination work.

至於——最後補充一點：顯然，終點指標很可能會與我們在 770 計畫中使用的相同。那些是標準終點。就 661 而言，該計畫仍處於較早期階段，因此此研究主要是觀察 661 單藥在同型合子 Delta F 病患中的表現，接著是在同一病患族群中評估 661 與 KALYDECO 的合併使用。因此我們會先完成單藥治療部分，之後再進行一些合併治療的工作。

Right. And the data you might expect in sort of the [first] quarter for 661 study in combination or alone with 770.

好的。以及你們可能預期在（大約）第一季看到的 661 研究數據，無論是與 770 聯合或單獨使用。

And maybe just a quick follow-up, the 661 dose, is that dose escalated as 809 is in the current ongoing combo, as well? Thanks.

另外也許快速追問一下，661 的劑量是否也會像目前正在進行的聯合療法中 809 一樣做劑量遞增？謝謝。

Yes, we'll be looking at multiple dose levels of 661 in that study.

是的，我們會在那項研究中評估 661 的多個劑量水準。

Thanks again for taking the questions.

再次感謝讓我們提問。

Operator, we have time we think for two more questions.

接線員，我們認為時間還夠再回答兩個問題。

Thank you. Our next question is from Brian Skorney of Brean Murray. Your line is open.

謝謝。下一個問題來自 Brean Murray 的 Brian Skorney。您的線路已開通。

Hi, yes, this is actually Dan Brims in for Brian today. I have one quick question, I think I might have missed it. Did you mention what the gross to net was going to be for KALYDECO as well as what your gross to net is for INCIVEK right now?

嗨，是的，我今天其實是代替 Brian 的 Dan Brims。我有一個簡短問題，我想我可能漏聽了。你們有提到 KALYDECO 的毛轉淨（gross-to-net）會是多少，以及目前 INCIVEK 的毛轉淨是多少嗎？

Well, Dan, I'll start with INCIVEK. We give guidance of $1.5 billion to $1.7 billion for 2012 and that incorporates a gross to net adjustment, that is the net INCIVEK revenues. In the fourth quarter, we were at a gross to net adjustment of around 13%. It may widen slightly from there into 2012, not significantly. As far as KALYDECO is concerned, the gross to net adjustment is made up of the mix of patients, whether their commercially insured or supported by the government. On the commercial side, which we anticipate is maybe 60% of the cystic fibrosis patients, the discounting is minimal, really minimal. And then on the government side, there is a -- which would be 40% of the patients -- there is mandated and statutory discounts and support that is between 15% to 25%. So I'm sure you can do the triangulation from there.

Dan，我先從 INCIVEK 開始。我們對 2012 年提供的指引是 15 億到 17 億美元，這已包含毛轉淨調整，也就是 INCIVEK 的淨營收。在第四季，我們的毛轉淨調整約為 13%。2012 年可能會從那個水準略為擴大，但不會顯著。至於 KALYDECO，毛轉淨調整取決於病患組合，也就是他們是商業保險承保或由政府支持。在商業端，我們預期約占囊性纖維化病患的 60%，折扣很少，真的非常少。而在政府端——約占 40% 的病患——有法定與強制性的折扣與支持，介於 15% 到 25%。所以我相信你可以由此推算出來。

Okay. And one other quick question, with Japan, I guess, you're getting milestones in place of royalties there. What would be triggering those royalties and when would -- when might you be seeing some of those? Or those milestones, excuse me?

好的。另外一個簡短問題，關於日本，我想你們在那邊是以里程碑款取代權利金。那會是什麼觸發那些權利金、以及你們何時——何時可能會看到其中一些？或是那些里程碑款，不好意思？

So while ago, in fact, years ago, the collaboration we struck with Mitsubishi Pharma was actually, we did not have royalties once the drug was on the market. It was actually a sales milestone. We received that sales milestone in the fourth quarter of 2011, it was $65 million, and that was recorded in the financial statements of this fourth quarter 2011.

其實很久以前，甚至是多年前，我們與 Mitsubishi Pharma 達成的合作是：藥品上市後我們不收取權利金。而是採用銷售里程碑款。我們在 2011 年第四季收到了該銷售里程碑款，金額為 6,500 萬美元，並已記錄在 2011 年第四季的財務報表中。

And that's all you're going to be getting from that collaboration then?

那麼這項合作你們之後就只會拿到這些了嗎？

Yes.

是的。

Okay. Thank you.

好的。謝謝。

Thank you. Our next question is from George Farmer of Canaccord. Your line is open.

謝謝。下一個問題來自 Canaccord 的 George Farmer。您的線路已開通。

Great, thanks for squeezing me in, I really appreciated. I was wondering if you could give us any feel for the duration of activity you're seeing with KALYDECO, at least without going into too much detail in the persist trial? And do you think that duration can continue on based on what you know now? And also, when do you think you'll be able to disclose more about the Alios nukes and the Phase 1 trial design?

太好了，謝謝把我加進來，我非常感激。我想請問，你們能否在不透露 persist 試驗太多細節的前提下，談談你們在 KALYDECO 看到的活性持續時間大概如何？以及就你們目前所知，你們認為那樣的持續時間是否能延續下去？另外，你們何時會能夠披露更多關於 Alios 核苷類（nukes）以及第一期試驗設計的資訊？

So, George, that's Peter speaking. The first is about duration and the longevity of KALYDECO activity and efficacy in patients. As you know, we have patients on trial which is sort of about 60 weeks to 90 weeks. And those are all basically still performing the same way as they did sort of when they kicked in the benefit of the regimen, which is sort of after two weeks. So it's a long-lasting type of thing. Anecdotally, we also have patients that we know on KALYDECO now for up to three years, and I think they are still performing well. And actually, you also have to look at the other way around, some of those patients anecdotally had to basically, because of some other circumstances, let out KALYDECO for a couple weeks in the regimen because of antibiotic situations and other things. And they deteriorated quickly down to, from [FAV] 90 down to 40 or so, or even less. And then when they came back on KALYDECO, they basically reaching the high levels again that they had seen sort of beforehand. So what that tells you this there is a true, long-lasting efficacy of that. I cannot say more than three years but that's, for a stage when you launch a product, quite an amazing timeframe.

George，我是 Peter。第一個問題是關於 KALYDECO 在病患中的作用與療效持續時間與長期性。如你所知，我們有病患在試驗中已經大約 60 週到 90 週。而這些病患基本上仍維持與他們開始出現療程效益時相同的表現，也就是大約在兩週後開始見效。所以這是一種持久的效果。另外就我們所知的個案而言，也有病患目前使用 KALYDECO 長達三年，我認為他們仍表現良好。其實你也可以從反面來看：有些病患因為其他情況，在療程中必須停用 KALYDECO 幾週，例如抗生素治療等因素。他們的狀況很快惡化，從（[FAV]）90 掉到 40 左右，甚至更低。而當他們恢復使用 KALYDECO 後，基本上又回到先前看到的高水準。因此這告訴你，它確實具有真正、長期且持久的療效。我無法說超過三年，但以產品剛上市的階段來看，這是相當驚人的時間跨度。

Yes, it's wonderful.

是的，這很棒。

And I must say there is a high hope that it will last even longer. So that's to that point, so it's not like a one-day (inaudible) when everything is out, so it's long lasting, at least in my view. Now the other thing is that Alios compounds. Basically, as Jeff said, we will do a couple of different studies with them, so there is an G1 population, obviously, there's a genotype-1, a and b, which is sort of the first cohort that we basically look into. Those data you will see in the course of the second quarter, towards sort of mid-year.

我必須說，我們非常希望它能維持更久。所以就這點而言，它不是那種一天（聽不清）就結束、然後一切都沒了的情況；至少在我看來，它是長期持續的。接著談到 Alios 的化合物。基本上，如 Jeff 所說，我們會用它們做幾項不同的研究；因此會有一個 G1 族群，顯然是基因型 1，包括 1a 與 1b，這是我們首先會評估的第一個隊列。你們會在第二季期間、接近年中時看到那些數據。

We also are about to initiate another arm which has pan-genotypic regimens in there. So we will basically evaluate genotype-2, -3, -4, -5, -6 and all those, so that we have real data and not just speculations. And then basically, we also will look into, let's say, a combination of each of them with ribavirin and see what that does. And this will all come in the course of this year, and you will see an (inaudible) maybe start in the first set of data from our other oral regimen, which is basically INCIVEK 222 and ribavirin. We might come at that point in time with some data, we will try, at least, as we record data. And then, as I said, mid-year you will see what Alios does.

我們也即將啟動另一個分支，納入泛基因型（pan-genotypic）的療程。因此我們會評估基因型 2、3、4、5、6 等所有這些，以便取得真實數據，而不只是推測。另外，我們也會研究把它們各自與 ribavirin 聯合使用，看看效果如何。這些都會在今年內陸續進行；而你們也會看到一個（聽不清）可能從我們另一個口服療程的第一批數據開始，也就是 INCIVEK 222 與 ribavirin。到那個時間點我們可能會提供一些數據，我們至少會在數據整理出來時努力提供。然後，如我所說，年中你們會看到 Alios 的表現。

I'm really convinced it will be exciting and then (inaudible) ASoD you have a bunch of other data that help you to make a good judgment about that program. I'm really excited, those molecules are behaving very well so far, and I'm looking forward for a good outcome.

我非常確信這會很令人興奮，然後（聽不清）ASoD 你還會有一大堆其他數據，幫助你對該計畫做出良好判斷。我真的很期待；到目前為止這些分子表現得非常好，我也期待能有好的結果。

Great, thanks very much.

太好了，非常感謝。

Well, thank you very much. We appreciate your participating tonight. We'll be happy to take additional questions in our offices. Thank you, and look forward to seeing you soon.

好的，非常感謝。感謝各位今晚的參與。我們也很樂意在辦公室接受更多問題。謝謝，也期待很快再見到各位。

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，感謝您參與今天的電話會議。本次議程到此結束。您現在可以掛線。祝您有美好的一天。