福泰製藥 (VRTX) 2012 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Vertex Pharmaceuticals Incorporated fourth quarter 2012 earnings and financial results conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will be given at that time.

各位女士、先生，大家好，歡迎參加 Vertex Pharmaceuticals Incorporated 2012 年第四季盈餘與財務結果電話會議。此刻，所有與會者將以僅聆聽模式參與。稍後我們將進行問答環節，屆時會提供相關指示。

(Operator Instructions)

(接線員指示)

As a reminder, this call may be recorded.

提醒各位，本次電話會議可能會被錄音。

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

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

Thank you, Operator; and good evening, everyone. Joining me on tonight's call are Dr. Jeff Leiden, Chairman and CEO; Dr. Peter Mueller, Head of Research and Development and Chief Scientific Officer; Stuart Arbuckle, Chief Commercial Officer; and Ian Smith, Chief Financial Officer.

謝謝，接線員；各位晚安。今晚與我一同參與電話會議的有：董事長兼執行長 Jeff Leiden 博士；研發主管兼首席科學長 Peter Mueller 博士；首席商務長 Stuart Arbuckle；以及財務長 Ian Smith。

Our agenda tonight is as follows. Jeff will begin with Vertex's strategy and key business priorities heading into 2013. After that, Peter will update our progress with our clinical development programs. Then, Stuart will discuss INCIVEK and hepatitis C market trends and provide some commentary on the outlook for KALYDECO in the US and Europe. To close, Ian will review the fourth quarter and full year 2012 results and our 2013 financial guidance.

今晚的議程如下。Jeff 將先談 Vertex 在邁入 2013 年時的策略與主要業務優先事項。接著，Peter 將更新我們臨床開發計畫的進展。然後，Stuart 將討論 INCIVEK 與丙型肝炎市場趨勢，並就 KALYDECO 在美國與歐洲的展望提供一些評論。最後，Ian 將回顧 2012 年第四季與全年業績，以及我們 2013 年的財務指引。

After the prepared remarks, Dr. Bob Kauffman, Vertex's Chief Medical Officer, will join us for Q&A. We'd like to conclude tonight's call at 6 PM. We want every analyst who has a question to be able to ask it, so please be considerate and limit your questions to one with a related follow up.

在準備好的發言之後，Vertex 首席醫療長 Bob Kauffman 博士將加入我們進行問答。我們希望在晚上 6 點結束今晚的電話會議。我們希望每位有問題的分析師都能提問，因此請大家體諒並將問題限制為一題，並可加上一個相關的追問。

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, our development plans and expectations, and our guidance are based on management's current assumptions and are subject to risks and uncertainties that could cause actual outcomes and events to differ materially.

我提醒各位，本次電話會議所討論的資訊包含前瞻性陳述，並受我們報告中所詳述之風險與不確定性影響，包括已向美國證券交易委員會提交的 10-K 與 10-Q 報告。這些陳述包括但不限於關於 INCIVEK 與 KALYDECO 的市場上市、我們的開發計畫與預期，以及我們的指引，均基於管理層目前的假設，並受可能導致實際結果與事件出現重大差異之風險與不確定性影響。

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

本次電話會議將討論 GAAP 與非 GAAP 財務衡量指標。關於我們使用這些衡量指標的資訊，以及 GAAP 與非 GAAP 的調節表，已載於我們 2012 年第四季財務新聞稿中，並已公布於我們的網站。此外，也請參考今晚網路直播第 5 張投影片上的資訊。

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

謝謝。現在我把電話交給 Jeff。

Thank you, Michael.

謝謝你，Michael。

Good evening. I had the opportunity to speak with many investors at the JPMorgan conference earlier this month. What I spoke about then, and what I'd like to reiterate now, is that during the last two years Vertex has undergone a rapid and profound evolution. We launched two transformative medicines in that time -- one for people with hepatitis C and one for patients with cystic fibrosis. The successful launches of these two medicines allowed us to significantly strengthen our financial position over this period. We finished 2012 with approximately $1.3 billion in cash and equivalents.

各位晚安。本月稍早我有機會在摩根大通（JPMorgan）會議上與許多投資人交流。我當時談到的，以及我現在想再次強調的是，在過去兩年中，Vertex 經歷了快速且深刻的演變。我們在這段期間推出了兩款具變革性的藥物——一款用於丙型肝炎患者，另一款用於囊性纖維化患者。這兩款藥物的成功上市，使我們在此期間得以大幅強化財務狀況。我們在 2012 年結束時，現金及約當現金約為 13 億美元。

During the same period we also progressed multiple potential transformative medicines into late-stage development, and we are now poised to expand our presence in the important disease areas of hepatitis C and CF. Our evolution has positioned us for the future with a clear focus -- using innovative science to develop new transformative medicines for people with serious diseases in specialty markets.

在同一期間，我們也推進多項可能具變革性的藥物進入後期開發階段，而我們目前已蓄勢待發，準備在丙型肝炎與囊性纖維化（CF）等重要疾病領域擴大布局。這樣的演變使我們以清晰的聚焦為未來做好定位——運用創新科學，為專科市場中罹患嚴重疾病的人們開發新的變革性藥物。

Let me, now, take a moment to discuss the four strategic priorities that we believe will enable us to achieve this goal. Priority one -- we are focusing investment on key development programs in cystic fibrosis, hepatitis C, and autoimmune diseases. In cystic fibrosis, Vertex's long-term strategy is to provide benefit to as many CF patients as possible and to maximize the benefit for these patients with our approved and investigational medicines. KALYDECO is already approved for people with a G551D mutation in the CFTR gene. There are approximately 2,000 such patients worldwide, age six and older, that we hope to treat.

現在讓我花點時間談談我們認為能協助達成此目標的四項策略優先事項。第一項優先事項——我們將投資聚焦於囊性纖維化、丙型肝炎與自體免疫疾病的關鍵開發計畫。在囊性纖維化方面，Vertex 的長期策略是讓盡可能多的 CF 患者受益，並透過我們已核准及研發中的藥物，將患者的受益最大化。KALYDECO 已獲核准用於 CFTR 基因帶有 G551D 突變的患者。全球約有 2,000 名符合條件、年滿 6 歲以上的患者，我們希望能為其提供治療。

In 2013, we are conducting multiple Phase 3 and other proof-of-concept label expansion studies of ivacaftor monotherapy. Ivacaftor is the generic name for KALYDECO. If successful, these studies would allow us to treat up to 7,000 patients worldwide with ivacaftor. We also expect to initiate a pivotal Phase 3 development program, this quarter, for a combination regimen of VX-809 and ivacaftor in people with CF who have two copies of the Delta-508 mutation. These patients represent approximately 50% of the worldwide CF population, or about 35,000 people.

在 2013 年，我們將進行多項第 3 期及其他概念驗證的適應症擴展研究，評估 ivacaftor 單藥治療。Ivacaftor 是 KALYDECO 的學名。若研究成功，將使我們得以在全球以 ivacaftor 治療多達 7,000 名患者。我們也預期在本季啟動一項關鍵性第 3 期開發計畫，針對帶有兩個 Delta-508 突變拷貝的 CF 患者，評估 VX-809 與 ivacaftor 的合併療法。這些患者約占全球 CF 人口的 50%，約為 35,000 人。

In hepatitis C, our long-term strategy is to develop simple, all-oral regimens with durations of 12 weeks or less that provide a high viral cure rate. In 2013, we plan to conduct multiple Phase 2 studies of 12-week, all-oral treatment regimens that include our nucleotide analogue VX-135. Our goal is to generate both safety and viral cure data in the second half of 2013 to support the start of pivotal development of one or more all-oral regimens in 2014.

在丙型肝炎方面，我們的長期策略是開發簡單、全口服、療程 12 週或更短，且能提供高病毒治癒率的治療方案。在 2013 年，我們計畫進行多項第 2 期研究，評估包含我們的核苷酸類似物 VX-135 的 12 週全口服治療方案。我們的目標是在 2013 年下半年產出安全性與病毒治癒資料，以支持在 2014 年啟動一種或多種全口服方案的關鍵性開發。

In autoimmune diseases, our strategy is to maximize the value of our JAK3 inhibitor, VX-509, across multiple autoimmune diseases globally. We continue to progress our Phase 2b study of VX-509 in people with rheumatoid arthritis, and we've initiated a small Phase 2 MRI study in RA, as well, and we expect data later this year. To broaden and accelerate the global development of VX-509, we will evaluate collaborative opportunities that could provide both funding and capabilities.

在自體免疫疾病方面，我們的策略是在全球多種自體免疫疾病中，將我們的 JAK3 抑制劑 VX-509 的價值最大化。我們持續推進 VX-509 用於類風濕性關節炎（RA）患者的第 2b 期研究；同時也已在 RA 中啟動一項小型第 2 期 MRI 研究，並預期在今年稍晚取得資料。為了擴大並加速 VX-509 的全球開發，我們將評估合作機會，以取得資金與能力的雙重支持。

Priority number two -- we will continue to invest in innovative research programs to support development of new specialty medicines for serious diseases. Vertex's research efforts are concentrated on additional advancements in CF and other genetic diseases such as Huntington's disease, as well as serious diseases in specialty markets, such as progressive multiple sclerosis and cancer. Innovative research is what creates our transformative medicines, and we will continue to support these productive efforts.

第二項優先事項——我們將持續投資於創新研究計畫，以支持針對嚴重疾病開發新的專科藥物。Vertex 的研究工作聚焦於推動 CF 的進一步突破，以及亨丁頓舞蹈症等其他遺傳性疾病；同時也涵蓋專科市場中的嚴重疾病，例如進行性多發性硬化症與癌症。創新研究是我們打造變革性藥物的根本，我們將持續支持這些富有成效的努力。

Priority three -- we plan to maximize revenues and cash flow from our marketed products, INCIVEK and KALYDECO. In particular, we see the potential for increased uptake of KALYDECO for patients in Europe and other countries outside the US.

第三項優先事項——我們計畫將已上市產品 INCIVEK 與 KALYDECO 的營收與現金流最大化。尤其是，我們看見 KALYDECO 在歐洲及美國以外其他國家，患者使用量有提升的潛力。

Finally, priority four -- maintaining our financial strength to support future long-term growth and shareholder returns. Ian will discuss this in a few moments.

最後，第四項優先事項——維持我們的財務實力，以支持未來的長期成長與股東報酬。Ian 將在稍後進一步說明。

There are important milestones in 2013 that will allow both you and us to measure our business progress. We described these milestones to you on January 7, and they're shown here again on slide 7. In many ways, these milestones position us to provide more certainty around the market opportunities for our clinical stage medicines throughout 2013.

2013 年有一些重要的里程碑，能讓各位與我們一同衡量業務進展。我們已在 1 月 7 日向各位說明這些里程碑，並在此於第 7 張投影片再次呈現。從許多方面來看，這些里程碑使我們能在 2013 年期間，對我們臨床階段藥物的市場機會提供更高的確定性。

In summary, as we enter 2013, we are executing on a clear strategy and set of goals, and we look forward to keeping you informed of our progress throughout the year.

總結而言，隨著我們邁入2013年，我們正依循明確的策略與目標執行，並期待在全年持續向各位通報我們的進展。

I will now turn it over to Peter.

我現在把時間交給Peter。

Thank you, Jeff; and good evening, everyone. My comments this evening will focus on the priority development areas that we have identified for investment in 2013, those of cystic fibrosis, all-oral hepatitis C therapies, and autoimmune diseases.

謝謝你，Jeff；各位晚安。我今晚的評論將聚焦於我們已辨識、並計畫在2013年投入資源的優先開發領域，包括囊性纖維化、全口服丙型肝炎療法，以及自體免疫疾病。

Beginning with cystic fibrosis, we are pleased that both KALYDECO and the VX-809 plus ivacaftor combination regimen received breakthrough therapy designation from the FDA. While the specific implications of this new designation are not yet clear, we are committed to working with regulators to explore novel and potentially more rapid development strategies for both the KALYDECO label expansion and VX-809 plus ivacaftor combination regimens.

先從囊性纖維化談起，我們很高興KALYDECO以及VX-809加ivacaftor的合併療法方案，皆獲得FDA授予突破性療法認定。雖然這項新認定的具體影響目前仍不明確，但我們承諾將與主管機關合作，探索針對KALYDECO適應症標籤擴增，以及VX-809加ivacaftor合併療法方案之新穎且可能更快速的開發策略。

Pending the outcome of our discussions, we hope that this will enable us to reach more patients as soon as possible. Currently, we are working toward agreement with regulators on Phase 3 trial designs for our combination regimen to treat CF patients homozygous for the Delta-508 CFTR mutation. We expect to complete these discussions and initiate a Phase 3 program this quarter.

視我們討論結果而定，我們希望這能使我們盡快觸及更多病患。目前，我們正與主管機關就用於治療Delta-508 CFTR突變同型合子之CF病患的合併療法方案第三期試驗設計，朝達成共識努力。我們預期將在本季完成這些討論並啟動第三期計畫。

As for the KALYDECO label expansion studies, all of these trials are currently ongoing and we anticipate having the first data from these trials in the second half of 2013. Vertex expects to discuss with the US FDA and European regulatory authorities any potential implications of breakthrough therapy designation on the timing and content of regulatory submissions in the US and EMA to support expansion of the KALYDECO label. Also in CF, we are on track to report data from the VX-661 plus ivacaftor Phase 2 combination study in 508 homozygous patients. We plan to report safety and efficacy data from this trial, including FEV1 and sweat chloride, on each of four cohorts in the first half of this year.

至於KALYDECO標籤擴增研究，這些試驗目前皆在進行中，我們預期在2013年下半年取得這些試驗的首批數據。Vertex預期將與美國FDA及歐洲監管機關討論，突破性療法認定對於在美國與EMA提交支持KALYDECO標籤擴增之法規申請的時程與內容，可能帶來的任何影響。在CF方面，我們也按計畫將報告VX-661加ivacaftor於508同型合子病患之第二期合併研究數據。我們計畫在今年上半年，針對四個隊列分別報告本試驗的安全性與療效數據，包括FEV1與汗氯。

Turning now to hepatitis C. In the first half of 2013, we expect to get three 12-week Phase 2 studies under way -- VX-135 in combination with ribavirin; VX-135 in combination with GSK's NS5A inhibitor, GSK805; and VX-135 in combination with the protease inhibitor, TMC435. We expect to have 12-week safety and first [SBR] data from these regiments in the second half of 2013, and our goal is to choose one or more regimens to move into pivotal development in 2014.

接著談丙型肝炎。在2013年上半年，我們預期將啟動三項為期12週的第二期研究——VX-135合併ribavirin；VX-135合併GSK的NS5A抑制劑GSK805；以及VX-135合併蛋白酶抑制劑TMC435。我們預期在2013年下半年取得這些方案的12週安全性與首批[SBR]數據，我們的目標是在2014年選定一項或多項方案推進至關鍵性開發。

Now, moving to autoimmune diseases and our selective JAK3 inhibitor, VX-509. We expect to have data from the Phase 2b study in rheumatoid arthritis in the second half of 2013. Additionally, we recently initiated a 40-patient MRI study to evaluate the potential for VX-509 to improve joint health and structure in rheumatoid arthritis patients. We also expect results from this trial in the second half of 2013.

現在轉到自體免疫疾病，以及我們的選擇性JAK3抑制劑VX-509。我們預期在2013年下半年取得類風濕性關節炎第二期b試驗數據。此外，我們近期啟動了一項40名病患的MRI研究，以評估VX-509改善類風濕性關節炎病患關節健康與結構的潛力。我們也預期在2013年下半年取得此試驗結果。

Finally, I'll note that we are in the process of analyzing and reviewing the VX-787 data from our Phase 2 challenge study in influenza, and we expect to report the results in the coming weeks.

最後我要提到，我們正在分析並審閱VX-787於流感第二期挑戰試驗的數據，並預期在未來幾週公布結果。

In summary, our clinical pipeline is advancing as planned, and I really look forward to updating you as we progress.

總結而言，我們的臨床研發管線正按計畫推進，我也非常期待在我們持續進展時向各位更新。

I will now turn it over to Stuart.

我現在把時間交給Stuart。

Good evening, everyone. Tonight, I'd like to give you some background on our performance with INCIVEK and KALYDECO in 2012 and what we foresee as we head into 2013.

各位晚安。今晚我想向各位說明我們在2012年INCIVEK與KALYDECO的表現背景，以及我們在邁入2013年時的展望。

In hepatitis C, we remain the market leader, with approximately three out of four new patients in the US initiating therapy with INCIVEK -- a measure unchanged since launch. As we have said previously, in 2012, we saw treatment rates change in anticipation of the potential for new, more convenient regimens that may treat hepatitis C. This led to a reduced number of HCV patients initiating treatment, beginning in the second quarter and continuing through the rest of 2012. As a result of these dynamics, INCIVEK revenues in 2012 were $1.16 billion, with $223 million of revenues in the fourth quarter.

在丙型肝炎方面，我們仍是市場領導者，美國約四分之三的新病患以INCIVEK開始治療——此一指標自上市以來未曾改變。如同我們先前所述，2012年我們看到治療率因市場預期可能出現新的、更便利、可治療丙型肝炎的療法而改變。這導致自第二季開始、並延續至2012年其餘期間，啟動治療的HCV病患數量下降。在這些動態影響下，INCIVEK於2012年的營收為11.6億美元，其中第四季營收為2.23億美元。

In 2013, we anticipate maintaining our market-leading position. However, we do expect a further decline in patients initiating treatment. We expect continued demand for INCIVEK from motivated patients who don't want to wait for treatment as well as patients who are too advanced with their disease and can't wait for treatment. Therefore, we expect INCIVEK will continue to be an important revenue contributor to our total revenues in 2013.

在2013年，我們預期將維持市場領先地位。然而，我們確實預期啟動治療的病患數將進一步下降。我們預期INCIVEK仍將持續受到有強烈治療意願、且不想等待新療法的病患需求，以及病情已較為進展、無法等待治療的病患需求所支撐。因此，我們預期INCIVEK在2013年仍將是公司總營收的重要貢獻來源。

In the EU and in other areas outside the US, the use of INCIVO to treat hepatitis C patients increased in the fourth quarter compared to the third quarter of 2012, resulting in an increased royalty to Vertex. INCIVO is now available in 40 countries, and we expect modest growth in the INCIVO royalty in 2013, resulting from the expansion of INCIVO into new geographies and a slower anticipated rate of patient warehousing in advance of potential new therapies compared to that in the US.

在歐盟及美國以外的其他地區，第四季使用INCIVO治療丙型肝炎病患的情況較2012年第三季增加，因而帶動Vertex取得較高的權利金。INCIVO目前已在40個國家上市，我們預期2013年INCIVO權利金將呈現溫和成長，成長動能來自INCIVO拓展至新地理市場，以及相較於美國，因預期新療法而進行病患「囤積/延後治療」（patient warehousing）的速度較慢。

Now, turning to KALYDECO. We achieved $172 million in revenues for KALYDECO in 2012, following the US launch in February. Specifically, in Q4, total revenues were $58.6 million, with the majority of those revenues derived from the US. We are treating the vast majority of G551D patients, age 6 and older, in the US, and we expect to maintain the level of our current US quarterly revenues.

接著談KALYDECO。在2月於美國上市後，KALYDECO於2012年達成1.72億美元營收。具體而言，第四季總營收為5,860萬美元，其中大部分營收來自美國。在美國，我們已治療絕大多數年齡6歲以上的G551D病患，並預期可維持目前美國單季營收水準。

We anticipate growth for KALYDECO in 2013 will come from Europe, beginning in the second quarter as a result of the previously announced access and reimbursement decisions from Scotland and England. Reimbursement discussions are progressing well in the other markets, and we expect to have completed them across the major EU markets, that is the UK, Ireland, Germany, and France, in 2013. Combined, these markets represent approximately 80% of the G551D population in Europe.

我們預期KALYDECO在2013年的成長將來自歐洲，並將自第二季開始，原因是先前已公布的蘇格蘭與英格蘭之用藥可近性與給付決策。在其他市場的給付協商進展良好，我們預期在2013年完成主要歐盟市場——亦即英國、愛爾蘭、德國與法國——的協商。合計而言，這些市場約占歐洲G551D族群的80%。

In summary, I am pleased with the performance of the commercial organization in 2012. And, as we begin 2013, we have two important medicines for patients that contribute significant revenues for our Company.

總結而言，我對商業團隊在2012年的表現感到滿意。而在我們邁入2013年之際，我們有兩項對病患重要的藥物，為公司帶來可觀營收貢獻。

With that, I will turn it over to Ian.

接下來，我把時間交給Ian。

Thanks, Stuart; and good evening to everyone.

謝謝你，Stuart；也向各位道晚安。

Tonight I'd like to discuss our financial position and the strategies that support plans for 2013. Specifically, I will focus on our 2013 financial guidance and the basis for such guidance. A detailed discussion of our 2012 financial results was provided in the press release we issued earlier today, and I'm happy to address any aspect of those results during Q&A.

今晚我想討論我們的財務狀況，以及支撐2013年計畫的策略。具體而言，我將聚焦於我們2013年的財務指引，以及該指引的依據。我們已在今天稍早發布的新聞稿中，提供對2012年財務結果的詳細討論，我也很樂意在問答環節回應這些結果的任何面向。

Firstly, to our financial position and how we may expect to progress through 2013. As Jeff mentioned, INCIVEK has been incredibly successful for Vertex, generating more than $2 billion of revenue since launch, and we expect it to continue to contribute significant revenues in 2013.

首先談我們的財務狀況，以及我們預期在2013年的推進情形。如Jeff所提，INCIVEK對Vertex而言極為成功，自上市以來已創造超過20億美元營收，我們預期其在2013年仍將持續貢獻可觀營收。

We expect INCIVEK revenues, combined with the expected growth in KALYDECO revenues and other revenue sources, will enable us to complete 2013 in a strong financial position, while also supporting investment into the Company. This investment will provide important data throughout 2013 to guide our future business opportunities. We are in an investment period for our Business, and we expect to return to revenue and earnings growth based on the successful advancement of our late-stage medicines.

我們預期 INCIVEK 的營收，加上預期 KALYDECO 營收成長及其他營收來源，將使我們能以強勁的財務狀況完成 2013 年，同時也支持對公司的投資。這項投資將在 2013 年期間提供重要數據，以引導我們未來的業務機會。我們正處於業務投資期，並預期隨著我們後期藥物的成功推進，將回到營收與獲利成長的軌道。

Now to the 2013 financial guidance and the basis for such guidance. We expect 2013 total revenues to be in the range of $1.1 billion to $1.25 billion. These revenues will enable investment into our Business, while maintaining our strong financial position. Our 2013 non-GAAP operating expenses will be in the range of $1.09 to $1.15 billion and principally consist of our R&D and SG&A expenses. Our non-GAAP OpEx guidance excludes cost of revenues, charges for stock-based compensation, and expenses related to the accounting for our Alios collaboration.

接下來談 2013 年財務指引以及該指引的依據。我們預期 2013 年總營收將介於 11 億美元至 12.5 億美元。這些營收將使我們得以投資於業務，同時維持我們強勁的財務狀況。我們 2013 年非 GAAP 營業費用將介於 10.9 億至 11.5 億美元，主要由研發費用與銷售、一般及行政（SG&A）費用構成。我們的非 GAAP 營業費用指引不包含營收成本、以股份為基礎之薪酬費用，以及與 Alios 合作之會計處理相關費用。

Now to the components of our total revenue guidance. We expect worldwide KALYDECO revenues to be in the range of $280 million to $320 million. These projected revenues are based on maintaining our currently quarterly rough revenue rates of approximately $50 million in the US and EU revenues that will grow in 2013.

接下來說明我們總營收指引的組成。我們預期全球 KALYDECO 營收將介於 2.8 億至 3.2 億美元。這些預估營收係基於維持我們目前每季約 5,000 萬美元的美國粗略營收水準，以及歐盟營收在 2013 年將成長。

The two main factors that will impact growth are one, the time to complete reimbursement negotiation processes with each of the remaining major European countries, Germany, Ireland, France, and the rest of the UK; and two, the rate of adoption by G551D patients outside of the US. Because of this, the growth will likely not be linear. We anticipate that the first quarter 2013 KALYDECO revenues will be similar to that of the fourth quarter 2012 and that growth in revenues should commence in the second quarter of 2013.

影響成長的兩個主要因素是：第一，與其餘主要歐洲國家（德國、愛爾蘭、法國及英國其他地區）完成給付/報銷談判流程所需的時間；第二，美國以外 G551D 病患的採用速度。因此，成長很可能不會呈線性。我們預期 2013 年第一季 KALYDECO 營收將與 2012 年第四季相近，而營收成長應會在 2013 年第二季開始。

For the combination of INCIVEK revenues, INCIVO royalties, and collaborative and other royalty revenues, we expect a range of revenues of $820 million to $930 million. We anticipate significant revenues from INCIVEK, although we do expect a continuing decline in the HCV patient treatment rates and reduced quarterly revenues compared to $223 million in Q4 2012.

就 INCIVEK 營收、INCIVO 權利金，以及合作與其他權利金營收的合計而言，我們預期營收區間為 8.2 億至 9.3 億美元。我們預期 INCIVEK 將帶來可觀營收，但也確實預期 HCV 病患治療率將持續下降，且每季營收將低於 2012 年第四季的 2.23 億美元。

With respect to INCIVO royalties, in Q4 2012 we realized $36.8 million of royalties, compared to a third quarter of $20 million of royalties, and we expect INCIVO royalty to show modest growth in 2013, compared to $118 million in 2012, consistent with the reasons Stuart mentioned earlier.

就 INCIVO 權利金而言，2012 年第四季我們認列 3,680 萬美元權利金，相較之下第三季為 2,000 萬美元；我們預期 2013 年 INCIVO 權利金將呈現溫和成長，相較 2012 年的 1.18 億美元，原因與 Stuart 先前提到的一致。

Finally, we have collaborative and other royalty revenues in 2012 of $76 million, and we anticipate a similar level in 2013. These revenue assumptions are based on existing relationships and do not include any potential collaborative and other royalty revenues. To reiterate, we are providing 2013 total revenue guidance of $1.1 billion to $1.25 billion.

最後，2012 年我們的合作與其他權利金營收為 7,600 萬美元，我們預期 2013 年將維持相近水準。這些營收假設係基於既有合作關係，且不包含任何潛在的合作與其他權利金營收。再次重申，我們提供的 2013 年總營收指引為 11 億至 12.5 億美元。

Now to the operating expenses. We are providing 2013 non-GAAP operating expenses guidance of $1.09 billion to $1.15 billion. The operating expense will vary quarter to quarter. However, we anticipate that the first quarter 2013 will be similar to that of the fourth quarter 2012, given the timing and the initiation of planned clinical trials and certain marketing expenses, as well as the realization of identified cost reductions. The main components of our operating expense are R&D and SG&A expenses, and our 2013 guidance for these expenses is $750 million to $790 million and $340 million to $360 million, respectively.

接下來談營業費用。我們提供的 2013 年非 GAAP 營業費用指引為 10.9 億至 11.5 億美元。營業費用將隨季度而變動。然而，考量已規劃臨床試驗的時程與啟動、部分行銷費用，以及已辨識的成本降低逐步反映，我們預期 2013 年第一季將與 2012 年第四季相近。我們營業費用的主要組成為研發與 SG&A 費用；我們對 2013 年這兩項費用的指引分別為 7.5 億至 7.9 億美元，以及 3.4 億至 3.6 億美元。

I'd now like to take a few moments to provide a better understanding of this R&D investment. Essentially, you can think of it in three categories. First, we plan to invest approximately $200 million in basic research to support the creation of future medicines. This is consistent with our 2012 levels.

我現在想花幾分鐘更清楚說明這項研發投資。基本上可分為三大類。第一，我們計畫在基礎研究上投資約 2 億美元，以支持未來藥物的創製。這與我們 2012 年的水準一致。

Second, we expect to spend between $400 million and $440 million on late-stage development programs. Over 80% of this development amount is in to support cystic fibrosis and hepatitis C and also includes significant supply-chain investments to prepare commercial supply for the potential clinical success of VX-809.

第二，我們預期在後期開發計畫上支出 4 億至 4.4 億美元。其中超過 80% 的開發金額用於支持囊性纖維化與 C 型肝炎，並且也包含重大供應鏈投資，以為 VX-809 可能在臨床上成功後的商業供應做準備。

And finally, we expect to spend approximately $150 million on a variety of essential activities and obligations relating to our commercial products. These include safety, pharmacovigilance, medical affairs, quality, and post-marketing commitments for INCIVEK and KALYDECO.

最後，我們預期在與商業化產品相關的各項關鍵活動與義務上支出約 1.5 億美元。這些包括 INCIVEK 與 KALYDECO 的安全性、藥物安全監測、醫學事務、品質，以及上市後承諾。

Turning, now, to the 2013 SG&A guidance of $340 million to $360 million. We are anticipating a reduction in SG&A, compared with the $390 million in 2012. This is a result of reduced US marketing expenses for INCIVEK and KALYDECO and a broad review of our Business where we made cost reductions for which we expect to see the full effect in 2013.

接著談 2013 年 SG&A 指引：3.4 億至 3.6 億美元。相較 2012 年的 3.9 億美元，我們預期 SG&A 將下降。這是因為 INCIVEK 與 KALYDECO 在美國的行銷費用降低，以及我們對業務進行全面檢視後所做的成本削減；我們預期 2013 年將看到其完整效果。

In summary, we are committed to managing our operating expense at a level to 2012 while increasing our R&D investment to support our late-stage medicines and reducing our SG&A expenses. We believe our 2013 guidance reflects our ability to maintain financial strength while we continue to invest in our pipeline of medicines to drive future growth. We are carefully balancing these priorities.

總結而言，我們致力於將營業費用管理在接近 2012 年的水準，同時提高研發投資以支持我們的後期藥物，並降低 SG&A 費用。我們相信 2013 年指引反映了我們在持續投資藥物研發管線以推動未來成長的同時，仍能維持財務實力的能力。我們正謹慎地在這些優先事項之間取得平衡。

With that, I will ask the Operator to please open the line for questions.

接下來，我將請接線員開放提問。

(Operator Instructions)

(接線員指示)

Geoffrey Porges, Bernstein.

Geoffrey Porges，Bernstein。

Just a follow up on Peter's comments about the CF combination programs -- could you confirm that the 400-milligram BID information has been provided to the FDA and that you're just waiting for them to come back before starting that Phase 3 -- and by implication that you've applied to add that arm to the study?

針對 Peter 關於囊性纖維化（CF）聯合療法計畫的評論再追問一下——你能否確認 400 毫克、每日兩次（BID）的資訊已提供給 FDA，而你們只是等待他們回覆後才會啟動該第 3 期試驗——並且也意味著你們已申請將該組別加入研究？

Secondly, on 661, you mentioned the cohorts, Peter. Could you give us a little bit more color on where you are in the recruitment of the cohorts? Specifically, is the first 120 patients being recruited and being studied out to the, I think, it's 28 days, or the end of treatment, so that you're starting to get that PK/PD data in now? Thanks.

第二，關於 661，你提到了各個隊列（cohorts），Peter。你能否再多提供一些目前隊列招募進度的細節？具體來說，第一批 120 名病患是否正在招募中，並且已被追蹤研究至我想是 28 天或治療結束，以便你們現在開始取得 PK/PD 數據？謝謝。

Geoff, this is Bob. I'll take the first part of the question. If you remember, the Cohort 3 was designed really to provide PK/PD data to fit into our PK/PD model as well as safety data at the dose level of 400-milligrams BID. Data have been provided to the FDA, along with our plan for the Phase 3 program; and yes, we're in active discussions with them, at this point, to finalize that program. And obviously, we'll provide further feedback once we get that information.

Geoff，我是 Bob。我先回答問題的第一部分。如果你記得，第 3 隊列的設計主要是為了在 400 毫克、每日兩次（BID）的劑量水準下，提供可納入我們 PK/PD 模型的 PK/PD 數據以及安全性數據。相關數據已提供給 FDA，並附上我們第 3 期計畫的方案；是的，我們目前正與他們積極討論，以定案該計畫。當然，一旦我們取得相關資訊，我們會再提供進一步回饋。

Great, thanks. And 661?

很好，謝謝。那 661 呢？

With respect to 661, yes, the study is well along and recruited, and we're waiting for the data to come in. As we said before, we'll be providing that for that study in the first half of the year.

關於 661，是的，研究進展順利且已完成招募，我們正在等待資料回收。如同先前所說，我們會在上半年提供該研究的資料。

Okay, I'll get back in the queue. Thanks.

好的，我會回到等候隊列。謝謝。

Geoff Meacham, JPMorgan.

Geoff Meacham，摩根大通。

For the KALYDECO, the ongoing monotherapy trial, can you give us any updates you have on the enrollment status for the different studies? And then, maybe speak to the review timeline, given your interpretation of the breakthrough designation? I have one follow up.

關於 KALYDECO 目前進行中的單藥試驗，能否提供各項研究的招募狀態更新？另外，基於你們對「突破性療法」認定的解讀，能否談談審查時程？我還有一個追問。

This is Bob. I'll take the last part first. Yes, obviously, we have breakthrough designation, although we're working with the FDA now to determine exactly what impact that will have on those programs. With respect to the review time, I can't really give you any further update at this point. Those discussions are ongoing.

我是 Bob。我先回答最後一部分。是的，我們顯然已獲得突破性療法認定，但我們目前正與 FDA 合作，以釐清這將對這些計畫帶來何種具體影響。至於審查時間點，我目前無法提供進一步更新。相關討論仍在進行中。

The studies are moving along very well, particularly the mutations -- other gating mutations, aside from G551D, is fully enrolled and moving along. R117H doing very well, as well, and the NF1 study, again, also doing well. So, no issues with recruitment.

各項研究進展都非常順利，特別是突變類型——除 G551D 之外的其他閘門突變（gating mutations）研究已完全招募並持續推進。R117H 也進展良好，而 NF1 研究同樣表現不錯。因此，招募沒有任何問題。

Then, for KALYDECO commercially in Europe, I don't know if it's possible to get a little bit more granular with what you think the pace of reimbursement discussion will be? That will be helpful, but maybe if you could also address other regions, such as Australia that may be also similar to the [ninth] review cycle? And, maybe any other gating factors that you feel like when it comes to your European reimbursement that we could get some clarity on in the next quarter or so?

另外，就 KALYDECO 在歐洲的商業化而言，不知道是否可以更細緻地說明你們認為給付（reimbursement）談判的推進速度？這會很有幫助；也請你們談談其他地區，例如澳洲，可能也類似於第[九]次審查週期？以及，當涉及歐洲給付時，你們認為有哪些其他關鍵因素，讓我們在接下來一季左右能更清楚？

Sure, Geoff, it's Stuart. I have to say, we are pleased with the speed with which the discussions have gone; and frankly, I'm delighted that we've already been able to come to a satisfactory and positive conclusion with England. And as we said, we're expecting that to really pick up from Q2.

當然，Geoff，我是 Stuart。我必須說，我們對討論推進的速度感到滿意；坦白說，我很高興我們已經能與英格蘭達成令人滿意且正面的結論。而且如我們所說，我們預期從第二季開始會明顯加速。

As you'll know in Scotland, they created a special orphan drug fund and have said that all patients with G551D mutations in Scotland will be eligible for that fund which begins in March. All I can really tell you about the other discussions is that they're very active; they're ongoing; they're very productive. Nobody has any doubts about the clinical benefit that KALYDECO brings, and we're working as quickly as we can the to bring them to a successful conclusion across the major markets in Europe.

如你所知，蘇格蘭設立了特殊的罕見疾病藥物基金，並表示蘇格蘭所有帶有 G551D 突變的病患都將符合該基金資格，基金將於三月開始。至於其他談判，我能說的是它們非常活躍、仍在進行中，而且非常有成效。沒有人懷疑 KALYDECO 帶來的臨床效益，我們正以最快速度推動，力求在歐洲主要市場都能成功定案。

In terms of Australia, we've filed and we're hopeful that we'll see an approval for the product this year. As you know, the process for reimbursement in Australia is as rigorous and lengthy as anywhere else in the rest of the world, and I wouldn't necessarily be optimistic that we'll be able to conclude that within 2013.

就澳洲而言，我們已提交申請，並希望今年能看到產品獲准。如你所知，澳洲的給付流程與世界其他地方一樣嚴謹且耗時，我不一定樂觀能在 2013 年內完成。

Geoff, let me just add to Stuart's comments. In my prepared remarks, how this translates to revenue expectations in 2013, I do want to reiterate that we anticipate in Q1 the KALYDECO revenues to be similar to that of Q4 2012. And, based on Stuart's outlining of the timing of approval for reimbursements in these markets, and specifically, those four major markets in Europe, we would anticipate growth starting to be seen in the second quarter of 2013.

Geoff，我補充一下 Stuart 的評論。在我事先準備的發言中，談到這如何轉化為 2013 年的營收預期時，我想再次強調：我們預期第一季的 KALYDECO 營收將與 2012 年第四季相近。並且，根據 Stuart 對這些市場給付核准時點的說明，特別是歐洲四大主要市場，我們預期 2013 年第二季開始會看到成長。

Okay. Thanks.

好的。謝謝。

Mark Schoenebaum, ISI Group.

Mark Schoenebaum，ISI Group。

First one is why would the FDA not allow you to include a 400-milligram BID dose in a pivotal trial, hypothetically? And number two, what should our and investor expectations be for the 661 trial? Small number of patients, no run-in, should we be expecting a FEV change or not, in your opinion? Thank you, very much.

第一個問題是：假設性地說，FDA 為什麼可能不允許你們在關鍵性試驗中納入 400 毫克、每日兩次（BID）的劑量？第二，你們認為我們以及投資人對 661 試驗應該抱持什麼樣的預期？病患數量少、沒有導入期（run-in），你們認為我們是否應該預期 FEV 會有變化？非常感謝。

Thanks, Mark, I'll have Bob answer the first question, and when we talk about investor expectations -- always an awkward one to set expectations. I'll take the second question.

謝謝，Mark。我先請 Bob 回答第一個問題；至於投資人預期——設定預期總是有點尷尬——我來回答第二個問題。

For the first one, we've submitted data to them, and we're in discussions. I can't comment on the nature of those discussions; but obviously, in every case they'll be looking at the data we send in to verify for themselves that they believe the risk/benefit is favorable for the inclusion of that dose, and I think we'll see how that goes.

就第一點，我們已向他們提交資料，並正在討論中。我無法評論這些討論的性質；但顯然，在每個案例中，他們都會檢視我們送交的資料，自行確認他們認為納入該劑量的風險/效益是否有利，我想我們就拭目以待。

Mark, to your second question, thank you. The VX-661 study in combination with KALYDECO, or ivacaftor -- it is a different study design than the VX-809 and ivacaftor study. You've given me an opportunity just to describe the study design, but then, in terms of what that means of readouts. It is a dose escalation study, so low-dose monotherapy, moves into that low-dose combination therapy; and then, as you move through that, you move into higher doses monotherapy, and then, move in combination therapy. It is sequential dose escalating study.

Mark，關於你的第二個問題，謝謝。VX-661 與 KALYDECO（或 ivacaftor）的合併研究，其研究設計不同於 VX-809 與 ivacaftor 的研究。你給了我一個機會先描述研究設計，再談這對讀出結果意味著什麼。這是一項劑量遞增研究：先從低劑量單藥開始，接著進入低劑量合併治療；然後隨著進程，進入較高劑量單藥，再進入合併治療。這是一項序列式的劑量遞增研究。

We're moving nicely through it, as Bob mentioned earlier, and we would anticipate in the first half of this year providing you a top-line result of that of FEV, sweat chloride, and safety. So, we look forward to providing that data at a later point in time.

我們進展順利，如 Bob 先前提到的，我們預期在今年上半年提供主要結果，包括 FEV、汗氯（sweat chloride）以及安全性。因此，我們期待在稍後時間點提供這些資料。

The only comment I want to make on top of that is it is a different set of patients in the monotherapy versus in the combo. It's not like what it was in 809, so there is no lead-in phase or any of those things going on.

我唯一想補充的是：單藥組與合併組是不同的一批病患。不像 809 的情況，因此沒有導入期或任何類似安排。

Is that a risk, Peter -- and then I'll drop off -- that there is no lead-in phase, or am I over thinking it? Thanks.

Peter，這會是個風險嗎——我問完就下線——因為沒有導入期，還是我想太多了？謝謝。

No, there is no risk, as much as we can see it.

不，就我們所能判斷，沒有風險。

Thank you.

謝謝。

Rachel McMinn, Bank of America Merrill Lynch.

Rachel McMinn，美國銀行美林。

Just, I guess, to go back to the question that's been asked a couple of times on the high dose of VX-809 inclusion in the Phase 3 -- do you view that as a potential sticking point in the conversations, or is it really focused on the actual end point? Because, I think you guys have talked about the potential to have a 6-month efficacy end point, as opposed to 12 months.

我想回到那個已被問過幾次的問題：在第三期試驗中納入高劑量 VX-809——你們是否認為這可能會成為對話中的潛在卡點，還是其實重點在於實際的終點指標？因為我想你們曾談到，療效終點可能是 6 個月，而不是 12 個月。

Then, separately on KALYDECO 4Q sales, was all of the growth in the fourth quarter Europe, so US was flat? I just want to make sure I understand that.

另外，關於 KALYDECO 第四季銷售額，第四季的成長是否全部來自歐洲，因此美國是持平？我只是想確認我理解正確。

Then finally, can you give us a little bit more color on your 135-ribavirin study? It says in clinical trials that you're enrolling 150 patients as a target, but I think you've talked about, initially, being a much smaller cohort. I wanted to get a sense of how many patients are really being enrolled, initially, in that study? Thanks.

最後，能否再多提供一些關於你們 135-利巴韋林（ribavirin）研究的細節？臨床試驗網站上寫你們目標招募 150 名病患，但我記得你們曾提到一開始會是小得多的隊列。我想了解這項研究初期實際會招募多少病患？謝謝。

This is Bob. I'll take the first and the third, and I'll leave the middle for Ian. In terms of the 809-770 combo trial, no we don't see any sticking points here. I think the only thing I'll say about some of the other points you mentioned is that, obviously, we have breakthrough status for this program as well; and clearly, the discussions we're having with the FDA may be colored by the discussions regarding breakthrough status and what impact that might have on the study. Right now, I just don't have anything to report about that, so I think I'll have to leave it that way.

我是 Bob。我先回答第一點和第三點，中間那點留給 Ian。就 809-770 聯合試驗而言，不，我們沒有看到任何卡關點。我想我唯一要補充的是，關於你提到的其他一些點，顯然這個計畫也具有突破性療法資格；而且很明顯，我們與 FDA 的討論可能會受到突破性療法資格相關討論的影響，以及這可能對研究造成的影響。目前我沒有任何可報告的內容，所以我想就先說到這裡。

For the third point about the 135 and ribavirin, yes, the study is -- we have a clear way forward to begin that trial. We have been asked to go slowly with some exploratory number of patients, initially, with very careful monitoring. We have included the monitoring in the protocol, and we're about to get that under way.

關於第三點，也就是 135 與 ribavirin（利巴韋林），是的，該研究——我們有一條明確的前進路徑來啟動那項試驗。我們被要求一開始先慢慢來，先納入一些探索性數量的病人，並進行非常謹慎的監測。我們已將監測納入試驗方案中，並且即將開始推動。

The exact patient numbers, yes, I know what's listed there. We'll be going a little bit slowly to begin with, and then we expect that that will accelerate once we have some initial data. We are quite cognizant of the need for safety data in that program to progress into Phase 3. So, we'll be looking at that very carefully as we go along.

至於確切的病人數，是的，我知道那裡列的是什麼。我們一開始會稍微放慢步調，之後一旦有一些初步數據，我們預期會加速。我們非常清楚，該計畫要推進到第三期需要安全性數據。因此，我們會在進行過程中非常仔細地評估。

On KALYDECO, Rachel, yes, the majority of the growth between Q4 and Q3 was as a result of Europe, as we said on the Q3 call. Back then, we had already had the vast majority of G551D patients in the US were already being treated. We added a few through Q4, as they rolled off some of the long-term extension studies and things like that, but the vast majority of the growth in Q4 was due to Europe.

關於 KALYDECO，Rachel，是的，第四季相較第三季的成長大多來自歐洲，正如我們在第三季電話會議中所說。當時，美國的 G551D 病患絕大多數已經在接受治療。我們在第四季又增加了一些，因為他們從一些長期延伸研究等結束轉出，但第四季成長的絕大部分仍是來自歐洲。

Great. Thank you.

很好。謝謝。

Michael Yee, RBC Capital Markets.

RBC Capital Markets 的 Michael Yee。

On the Cohort 3 of the combo study, can you perhaps describe qualitatively what you were looking for in your PK/PD analysis, and whether the data you saw there generally supported what you were looking for?

關於聯合研究的第 3 組（Cohort 3），你能否從質性角度描述一下你們在 PK/PD 分析中想要看到什麼，以及你們看到的數據是否大致支持你們原本的預期？

Then, on 661, I know you described the design of the study, but what is your stopping criteria -- how do you define when you would actually stop and report results?

另外，關於 661，我知道你描述了研究設計，但你們的停止標準是什麼——你們如何界定何時會真正停止並公布結果？

In terms of Cohort 3, we have a PK/PD model for the combination. Really, what we're looking for is consistency with the model, and we always look for whether we're getting more bang for the buck with higher doses, and that's really part of the assessment.

就第 3 組而言，我們有一個針對該組合的 PK/PD 模型。我們真正要看的，是與模型的一致性；而且我們一向會看更高劑量是否能帶來更高的「效益/投入比」，這也是評估的一部分。

Actually, I would say that that is the same philosophy regarding the stopping criteria in the 661 trial; again, we always look for a PK/PD relationship, whether we're getting plateauing of the PK and PD responses. And obviously, safety factors into the decision about whether to continue to dose escalate or not. So, it's just a combination of things. It's pretty hard to give a hard-and-fast rule.

其實我會說，這也同樣是 661 試驗停止標準背後的理念；同樣地，我們總是尋找 PK/PD 關係，觀察 PK 與 PD 反應是否出現平台期。而且很明顯，安全性也會納入是否繼續加量的決策。所以，這是多項因素的綜合。要給出一條硬性規則其實很難。

Okay.

好的。

Liisa Bayko, JMP Securities.

JMP Securities 的 Liisa Bayko。

Hello, Lisa. We can't hear you if you're asking.

你好，Lisa。如果你在提問，我們聽不到。

Sorry. Can you give us a little more color -- maybe this has been asked already, but just on the discussions, let's say, in the key European countries, France, Spain, Italy -- it's really important for timing and modeling, where we might expect those to roll out? Thanks.

抱歉。你能否再多提供一些背景——也許之前已經有人問過，但就討論進展而言，假設在歐洲幾個主要國家，法國、西班牙、義大利——這對時程與模型推估非常重要，我們大概何時可以預期這些市場開始推進/落地？謝謝。

With France, I'll say the discussions are ongoing and our next important time point with them is likely to be around February is when they've said that they would get back to us, and they've been public about that being the date, when they would next have reached a decision. In Italy -- Italy really isn't a major market for patients with G551D, so I won't comment more on that.

就法國而言，我會說討論仍在進行中，而我們下一個重要時間點很可能在二月左右，因為他們表示會在那時回覆我們，而且他們也公開表示那會是他們下一次做出決定的日期。至於義大利——義大利其實不是 G551D 病患的重要市場，所以我就不多評論。

Then in Germany, the product is available, currently, and is reimbursed. And, we're in discussions, as is the normal course of things in Germany, to establish the ongoing price that the product will be reimbursed at. Those discussions are ongoing. Again, tough to predict exactly when they'll come to a conclusion.

接著在德國，該產品目前已可取得，且已獲給付。而且我們正如在德國的正常流程一樣，正在討論以確立該產品後續可獲給付的持續價格。這些討論仍在進行中。同樣地，很難精準預測他們何時會得出結論。

I wish I could be more precise, but just the nature of these things is that they are difficult to predict in any event. I think they're particularly difficult when you're dealing with such a breakthrough medicine, where they have a real desire to try and get them available for their patients. So, it's tough to be more specific, I'm afraid.

我希望我能更精確，但這類事情的本質就是很難預測。我認為，當你面對的是如此具突破性的藥物時，情況尤其難以預測，因為他們非常希望能讓藥物提供給病患使用。所以很抱歉，確實很難再更具體。

Liisa, something that sometimes happens in these -- let's say the discussions with -- if investors are asking about this expectation, it helps to frame the market for people. It's not always clearly understood. Approximately 80% of the G551D patients in Europe are actually in France, Germany, UK and Ireland, and then 80% of that 80% is actually in UK and Ireland. So, as you try and triangulate the timing, and let's say, the revenues -- that might give you a little more understanding of Stuart's point that we're engaged in discussions with all those countries.

Liisa，這類討論中有時會發生一件事——比方說，若投資人問到這方面的預期，從市場結構的角度來框定會有幫助。這並不總是被清楚理解。歐洲約 80% 的 G551D 病患其實在法國、德國、英國與愛爾蘭，而那個 80% 裡又有 80% 實際上在英國與愛爾蘭。因此，當你試著推算時程以及例如營收時——這或許能讓你更理解 Stuart 所說的：我們正與所有這些國家進行討論。

Okay. Any more granularity on -- I know you had some pushback with pricing, but there's been some funds set aside with some of the other countries -- sorry, the other regions within the UK. When might we expect to start seeing revenue there?

好的。再更細一點的資訊呢——我知道你們在定價上遇到一些阻力，但英國內其他國家/地區似乎已預留了一些資金——抱歉，是英國內的其他區域。我們大概何時可以開始看到那邊的營收？

Well, in terms of --

嗯，就——

Ireland, Scotland --

愛爾蘭、蘇格蘭——

Revenue from England and Scotland -- so Scotland, they've set aside a separate fund. In England, they've agreed to reimburse it. We expect to see commercial sales in England from Q2, and the Scottish fund is supposedly open from March 1. So really, as Ian said, we're expecting Q1 to be similar to Q4, and then Q2 is when we would expect the growth really to pick up as patients get broader access and reimbursement in those major markets like England and Scotland.

來自英格蘭與蘇格蘭的營收——就蘇格蘭而言，他們設立了一個獨立基金。在英格蘭，他們已同意給付。我們預期從第二季開始在英格蘭看到商業銷售，而蘇格蘭的基金據說會在 3 月 1 日開放。因此，正如 Ian 所說，我們預期第一季會與第四季相近；而第二季則是我們預期成長會真正開始加速的時點，因為病患在英格蘭與蘇格蘭等主要市場將獲得更廣泛的可近性與給付。

Thank you, very much.

非常感謝。

Yaron Werber, Citi.

Citi 的 Yaron Werber。

Just a couple questions. One, just to follow-up on Liisa. Stuart, just to clarify, in Germany sounds like you're still negotiating the price to a certain degree. As you said, the product is available, and it is being used, so I'm trying to get a sense -- are you recording most of the revenues in Germany, with a potential contingent reserve against potential discounts in the future or how do we think about that?

我有幾個問題。第一個，延續 Liisa 的問題。Stuart，想確認一下，在德國聽起來你們仍在某種程度上協商價格。如你所說，產品已可取得且正在使用中，所以我想了解——你們是否已在德國認列大部分營收，同時針對未來可能的折扣提列或有準備金，或我們應該如何看待這件事？

Second, and I hate to bring this up, I just want to be clear -- in terms of your communication and the combination data this quarter on the combo of the KALYDECO and 809 -- the high dose, the 400-milligram BID, are you going to show us the full efficacy data once you communicate whether you're taking that into Phase 3? Or, is that something that will be communicated in the future, after Q1?

第二個問題，我不太想提但想確認清楚——就你們本季對 KALYDECO 與 809 聯合用藥數據的溝通而言——高劑量、400 毫克 BID（每日兩次），你們在溝通是否要推進到第三期之後，會把完整的療效數據提供給我們嗎？還是那會在未來、第一季之後才會再對外溝通？

On the question on Germany -- so, Germany has, essentially, a two-step process. Products are reimbursed, almost immediately following their approval; and yes, we are recording commercial sales in Germany already. And then, in parallel to the product being available, as is a standard part of the process in Germany, you then negotiate the price that the product will be reimbursed at on an ongoing basis. We're in that part of that second part of the process, currently.

關於德國的問題——基本上，德國有一個兩步驟的流程。產品在獲准後幾乎立即就會獲得給付；是的，我們已經在德國記錄到商業銷售。同時，在產品可取得之後，作為德國流程的標準部分，接著會就該產品在持續性給付下的給付價格進行談判。我們目前正處於流程的第二步，也就是第二部分。

And then, on the combo data, I'll pass that off to Ian to answer.

接著，關於聯合用藥數據，我把這題交給 Ian 來回答。

Yaron, thanks for the question. Again, it gives us a chance to continue to clarify how to expect this data disclosure. As we've said in the past, we're currently in discussions with the FDA regarding the protocol design for our Phase 3 with ivacaftor combination with 809, and that discussion is now under the umbrella of breakthrough designation. So, we're still engaged in those discussions.

Yaron，謝謝你的提問。同樣地，這也讓我們有機會持續釐清應如何期待這次的數據揭露。如同我們過去所說，我們目前正與 FDA 討論我們以 ivacaftor 與 809 聯合用藥之第三期試驗的方案設計，而這項討論現在是在突破性療法認定的框架之下進行。因此，我們仍在進行這些討論。

Once those conclude and we have a clear line of sight for that Phase 3 protocol, we will find out whether the BID -- 400-BID dosing of 809 is included as a dose arm in that Phase 3. Consistent with that disclosure, we'll provide the basis for that inclusion in the Phase 3 protocol or its non-inclusion. So, that's the point we would expect.

一旦討論結束，且我們對該第三期方案有清楚的方向後，我們就會知道 809 的 BID——400 BID 劑量是否會被納入第三期的一個劑量組。與該揭露一致，我們將提供其被納入第三期方案或未被納入的依據。因此，我們預期會在那個時間點說明。

Now, the basis for that disclosure would be based on the basis that we find it is included or not included within our protocol. So, we look forward to clarifying all of that in the first quarter. As we've announced, we expect to initiate this Phase 3 study in the first quarter of this year.

而這項揭露的依據，將取決於我們最終在方案中是否納入。所以，我們期待在第一季把這些都釐清。如同我們已公告的，我們預期在今年第一季啟動這項第三期研究。

Yaron, this is Jeff. Maybe one comment on Germany just to make sure that you're thinking of it the way we are. As Stuart said, we are reimbursed at this point and in the pricing -- final pricing discussions.

Yaron，我是 Jeff。也許補充一句關於德國的情況，確保你對它的理解與我們一致。如 Stuart 所說，我們目前已獲得給付，並且正在進行最終定價討論。

During that first year when those negotiations are going on, there is not full uptake, nor do we expect full and rampant uptake in Germany. There tends to be a much slower uptake until formal reimbursement is attained. Just want to make that sure you're thinking of Germany as something that, clearly, is not fully penetrated, at this point, and will continue to grow when and if we get reimbursement.

在第一年、也就是談判進行期間，市場不會完全採用，我們也不預期德國會出現全面且快速的採用。通常在正式取得給付之前，採用速度會慢得多。只是想確認你把德國視為目前顯然尚未完全滲透的市場；而且當我們取得（或如果我們取得）給付後，仍會持續成長。

Got it, thank you.

了解，謝謝。

Robyn Karnauskas, Deutsche Bank.

Robyn Karnauskas，德意志銀行。

I guess two -- for 661, so will the Part-A data that you're going to release the first half of this year give you enough information to have a sense of whether or not you're going to take that product forward, or do you really need to see the Part B and C to give you greater comfort?

我想有兩個問題——關於 661，你們將在今年上半年公布的 A 部分數據，是否足以讓你們判斷要不要推進該產品，還是你們真的需要看到 B 與 C 部分，才能更有把握？

Then, regarding Ireland, what gives you confidence that you can get reimbursement? Is it just the pharmacoeconomic question, or do you -- is it really a price negotiation at this point?

另外，關於愛爾蘭，是什麼讓你們有信心能取得給付？只是藥物經濟學的問題，還是——目前其實是價格談判的問題？

Peter will take the first question, Robyn, and then Stuart will follow up.

Robyn，第一個問題由 Peter 回答，接著 Stuart 再補充。

Yes, in terms of the value of 661 and our decision to move it forward, the study as is Part A would basically give us enough confidence to make a decision whether we move forward or not. I want to just reiterate at one point in time, it is not a discussion any longer whether we exchange 809 with 661. 661 is a separate molecule, and if [we decide so] has a different base for future regimens, like combination regimens with other correctors. And, 809 is basically on its own and on a fast-track moving forward.

是的，就 661 的價值以及我們是否推進的決策而言，A 部分的研究基本上就能給我們足夠的信心來決定是否繼續推進。我想再次強調一點：現在已不再討論是否用 661 取代 809。661 是一個獨立分子，若我們決定推進，它將成為未來療法組合（例如與其他校正劑的聯合療法）的不同基礎。而 809 基本上會以自身路徑、並以快速通道持續推進。

On Ireland, I guess the first thing I would say is while the past is not necessarily a perfect predictor of the future, I would say the success we've already had with gaining access and reimbursement for KALYDECO gives me a lot of confidence that we'll reach a successful conclusion in Ireland. In addition to that, as I said, the discussions are ongoing. They're going well. There's clearly a high level of unmet need in Ireland. It has the highest incidence of G551D mutation in the world, and so there's a desire on both sides to reach an amicable solution, and I'm optimistic that we'll do so.

關於愛爾蘭，我想先說，雖然過去不一定能完美預測未來，但我們先前已成功讓 KALYDECO 取得可近性與給付，這讓我對我們在愛爾蘭能達成成功結論很有信心。此外，如我所說，討論仍在進行中。進展良好。愛爾蘭顯然存在高度未被滿足的醫療需求。它是全球 G551D 突變發生率最高的國家，因此雙方都有意願達成友善的解決方案；我對此抱持樂觀。

Terence Flynn, Goldman Sachs.

Terence Flynn，高盛。

Was just wondering, in terms of, I guess -- first on the CF combo program, if you can provide us with any insight on how you're thinking about a 6-month versus 12-month end point, with respect to, I guess, exacerbations? Because, it seems to me like there's a focus on 12 month for the exacerbation data. So, I was wondering if that's in line with your thinking?

我想問的是，就 CF 聯合用藥計畫而言，你們能否提供一些想法：在惡化（exacerbations）方面，你們如何看待 6 個月相對於 12 個月的終點？因為在我看來，惡化數據似乎更聚焦在 12 個月。所以我想知道這是否符合你們的思考？

Then, on 661, was wondering in terms of the dose escalation if you could provide us with some additional details on how, and I guess, who made the decision to stop at the dose you decide to stop on? And, if you think that's enough, or if you think there's a possibility that maybe you have to go back and do some further dose exploration work, how you did with 809? Thanks.

另外，關於 661，我想就劑量遞增請你們提供更多細節：你們是如何、以及由誰做出在某個劑量停止的決定？你們是否認為這樣就足夠，或是否可能需要回頭再做更多劑量探索工作，就像你們對 809 所做的那樣？謝謝。

This is Bob, maybe I'll do the second one first. The team has made a decision about the dose escalation all the way through the trial and that's who's empowered to do that. That's all I can really say about that one.

我是 Bob，也許我先回答第二個問題。團隊已就整個試驗中的劑量遞增做出決定，而也正是該團隊被授權做出這樣的決策。關於這點，我大概只能說到這裡。

In terms of the 809-770 combo trial, I really can't comment on durations at this point. I think that's still a topic of discussion. Again, largely a part of our breakthrough designation discussion with FDA. All of the end points, if you measured, are certainly ones that are of interest to us. They are all very important ones, and they're all going to be included in the trial, but the durations, I think, are not at all settled at this point.

至於 809-770 聯合試驗，我目前真的無法評論試驗期間長短。我認為這仍是討論中的議題。同樣地，這在很大程度上是我們與 FDA 就突破性療法認定所進行討論的一部分。所有你提到的終點指標，若進行量測，當然都是我們關注的。它們都非常重要，而且都會納入試驗中，但我認為試驗期間長短目前完全尚未定案。

Matt Roden, UBS.

Matt Roden，瑞銀。

Going back to the 400-milligram BID dose, Bob, you mentioned PK/PD models that you'll be comparing the data against. Can you help us with what your bar is for inclusion in the Phase 3? In other words, does it have to be better than the 600-milligram QD dose, or could it be similar and justify inclusion in Phase 3. What I'm trying to get to is would you caution us against drawing conclusions about what the data implies simply by its inclusion or exclusion from Phase 3.

回到 400 毫克 BID 劑量，Bob，你提到你們會把數據與 PK/PD 模型做比較。你能否說明你們納入第三期的門檻是什麼？換句話說，它必須優於 600 毫克 QD 劑量嗎？還是只要相近也能合理納入第三期？我想問的是：你是否會提醒我們，不要僅憑其是否被納入第三期，就對數據意涵下結論？

Then secondly, just real quick, can you update us on how you plan to address the Delta 508 heterozygous patient population? Haven't heard about that in a while.

第二個問題很快問一下：你能否更新你們打算如何處理 Delta 508 雜合子患者族群？好一陣子沒聽到相關消息了。

To answer the first part of your question -- it is just a complicated equation about how one factors in all the pieces here. Remember that the cohort is relatively small. The PK/PD data tend to be more powerful than just estimates of the effects that are seen in a small study. And, we are really looking for consistency with our model, and that will determine whether we go forward or not. Clearly, the safety piece of it was also a factor, and all of that was provided to FDA, and we're looking forward to completing those discussions.

回答你問題的第一部分——這其實是一個相當複雜的方程式，要把所有因素都納入考量。請記得，該隊列的樣本數相對較小。PK/PD 數據往往比在小型研究中觀察到的效果估計更具說服力。而我們真正要找的是與我們模型的一致性，這將決定我們是否繼續推進。顯然，安全性也是一個因素；我們已將所有資料提供給 FDA，並期待完成這些討論。

Matt, as we've said before, this isn't only about an increased overall dose -- this is Jeff. Importantly, the BID dose potentially changes both Cmin and Cmax, and we're learning a lot about what the effects of Cmin and Cmax may be on efficacy as well. As Bob said, it's more complicated than simply a higher dose. It's really how that dose is distributed and what exposures are, both at Cmin and Cmax, and that's why it was so important to confirm the PK/PD model.

Matt，如同我們先前所說，這不僅僅是整體劑量提高——這是 Jeff 的問題。重要的是，BID（每日兩次）劑量可能同時改變 Cmin 與 Cmax，而我們也正在深入了解 Cmin 與 Cmax 對療效可能造成的影響。如 Bob 所說，這比單純提高劑量更複雜。真正關鍵在於劑量如何分配、以及在 Cmin 與 Cmax 時的暴露量，因此確認 PK/PD 模型才會如此重要。

In terms of the heterozygous -- I think there's no comments to be made, number one. I think we anticipate that we have basically include some heterozygous in our Phase 3 program, from a safety point of view. So, we will explore, basically, the combination there. The other thing is as we go forward with the dual corrector and other programs, that's basically the main route that we try to explore value for patients of that category.

就異型合子而言——我認為第一點是沒有什麼可評論的。我想從安全性的角度，我們預期在第三期計畫中基本上會納入一些異型合子受試者。因此，我們將會探索那裡的組合方案。另外，隨著我們推進雙校正劑（dual corrector）及其他計畫，這基本上是我們嘗試為該類別患者探索價值的主要途徑。

Thank you.

謝謝。

Ying Huang, Barclays.

Barclays 的 Ying Huang。

This is Christina Zhang on behalf of Ying Huang. First, I had a question around whether the decision has been made to include a VX-809 monotherapy arm in the Phase 3 trial?

我是 Christina Zhang，代表 Ying Huang 提問。首先，我想問一下，是否已經決定在第三期試驗中納入 VX-809 單藥治療組？

Secondly, on VX-661, also wanted to drill a bit further on the stopping criteria. Did you see any dose-limiting toxicity, or have you seen satisfactory lung function improvement to stop the dose escalation?

第二，關於 VX-661，也想再深入追問一下停止標準。你們是否看到任何劑量限制性毒性（DLT），或是已看到令人滿意的肺功能改善而停止劑量遞增？

Lastly on VX-135, have you conducted any pre-clinical tests to rule out cardiovascular [tox]?

最後，關於 VX-135，你們是否進行任何臨床前測試以排除心血管[毒性]？

Okay. Let's see, I'll take the last one first. And yes, as part of our standard battery of testing, we always do cardiovascular evaluations, and they were satisfactory to move the molecule forward. For 661, it's an ongoing study and I just can't really comment on the findings or -- the criteria for stopping or not stopping in that trial. When we report the results, you'll really see how we came out. In terms of an 809 monotherapy arm, again, I'm not able to comment on that until we complete our discussions with the FDA.

好的。我先回答最後一題。是的，作為我們標準測試組合的一部分，我們一向會做心血管評估，而結果令人滿意，足以推進該分子。至於 661，這是一項進行中的研究，我確實無法評論其發現，或——該試驗停止或不停的標準。等我們公布結果時，你們就會看到我們的結論。至於 809 單藥治療組，同樣地，在我們完成與 FDA 的討論之前，我無法評論。

David Friedman, Morgan Stanley.

Morgan Stanley 的 David Friedman。

This is Sarah calling for Dave. On a slightly different topic, just had a quick question about the upcoming flu data. Can you give us a sense of what information we could expect in the press release, and I think the initial guidance we've got is actually 4Q, so if you could talk about what's causing the delay? Thanks.

我是 Sarah，代 Dave 提問。換個稍微不同的主題，我想快速問一下即將公布的流感數據。你們能否讓我們了解新聞稿中可能會有哪些資訊？另外，我想我們先前得到的初步指引其實是在第四季（4Q），所以也請談談造成延後的原因？謝謝。

In terms of the delay, really, the recruitment went on a little longer than we thought. There was also a little bit of a delay in some of the bioanalytic work that supports that trial, particularly, some of the viral-titer work, which is very extensive, and it just took a little longer than we thought.

關於延後，主要是招募時間比我們預期稍長。此外，支援該試驗的一些生物分析工作也有些延遲，特別是某些病毒滴度（viral-titer）相關工作，這部分非常繁重，因此比我們原先想的多花了一點時間。

Can you repeat the first part of the question?

你可以重複一下問題的第一部分嗎？

Yes, what you should expect in the press release.

可以，新聞稿中你們會公布哪些內容。

I think we talked about this once before, but clearly, the primary end points that we're interested in are the anti-viral effect measured by virus excretion, and also clinical symptomatology, as well as the safety of the molecules. I think those are the three key pieces that you'll be looking for.

我想我們之前談過一次，但很明確地，我們關注的主要終點包括：以病毒排出（virus excretion）衡量的抗病毒效果，以及臨床症狀表現，還有分子的安全性。我想這三點是你們會重點關注的關鍵內容。

Great. Thanks.

很好。謝謝。

Brian Abrahams, Wells Fargo.

Wells Fargo 的 Brian Abrahams。

Thanks for taking my question, and congrats on the progress. A question on 135, obviously, one of the last [nucs] standing, I'm just wondering if there are any external assets or classes that you are still considering for potential combinations to leverage its scarcity value and ensure that it's a backbone in future combinations -- wondering if getting through that initial highly monitored cohort is gaining factor?

謝謝讓我提問，也恭喜進展。關於 135 的問題，顯然它是少數仍在的 [nucs] 之一；我想了解是否仍在考慮任何外部資產或類別，用於潛在的組合，以利用其稀缺價值並確保它成為未來組合的骨幹——我想問的是，通過最初那個高度監測的隊列是否是一個加分因素？

Then, just a quick follow up on the KALYDECO commercial dynamics in the US -- just wondering if there's any opportunity for additional use in the label indication, perhaps with slight increases, improvements in compliance, and why are those few patients who are not on it still on the sidelines?

另外，關於 KALYDECO 在美國的商業動態再追問一下——想了解在標籤適應症內是否還有額外使用的機會，例如小幅增加、提升用藥依從性等；以及為什麼仍有少數患者尚未使用、仍在觀望？

Brian, this is Jeff. I'll take the VX-135 question. I think you remember that we said, probably five, six months ago now, that our strategy is to find the best combination of all-oral medicines for patients with HCV, both by combining VX-135 as a backbone with our own medicines, but also potentially with those of others. Of course, that led to the collaborations with JNJ and GSK, which we're very pleased with.

Brian，我是 Jeff。我來回答 VX-135 的問題。我想你記得我們大概在五、六個月前說過，我們的策略是為 HCV 患者找到最佳的全口服藥物組合，一方面以 VX-135 作為骨幹與我們自家的藥物組合，另一方面也可能與其他公司的藥物組合。當然，這也促成了與 JNJ 和 GSK 的合作，我們對此非常滿意。

With respect to additional assets, if we found an asset that we thought added significant value to VX-135, we would be open to combining with that as well.

至於其他額外資產，如果我們找到一個我們認為能為 VX-135 帶來顯著價值的資產，我們也會願意與其進行組合。

Just on the KALYDECO in the US, frankly, there's very few patients on the sidelines. The vast majority have been exposed to KALYDECO at some point in time.

至於 KALYDECO 在美國的情況，坦白說，仍在觀望的患者非常少。絕大多數患者在某個時間點都曾使用過 KALYDECO。

In terms of compliance, is there an opportunity to increase that? Possibly, but actually, the compliance rates are remarkably high -- much higher than we would see with virtually any product I've come across in 26 years doing this. So, there may be some marginal increases we can get, but they really are on the margin, which is why we say that kind of net-net we're expecting to maintain the quarterly revenues we're seeing here in the US in Q4 as we move into 2013.

就依從性而言，有機會再提高嗎？可能有，但實際上依從性比率高得驚人——遠高於我在 26 年從業經驗中幾乎任何我見過的產品。因此，我們或許能取得一些邊際性的提升，但真的只是邊際，這也是為什麼我們說，整體而言，我們預期在進入 2013 年時，能維持我們在美國於第四季所看到的季度營收水準。

Thanks very much for the color.

非常感謝這些補充說明。

Howard Liang, Leerink Swann.

Leerink Swann 的 Howard Liang。

Does the breakthrough designation cover all of additional indications for monotherapy KALYDECO, including patients with residual CFTR function? When should we expect to see the Phase 3 data? Could it be this year?

突破性療法認定是否涵蓋 KALYDECO 單藥治療所有額外適應症，包括具有殘餘 CFTR 功能的患者？我們何時應該期待看到第三期數據？有可能在今年嗎？

The breakthrough designation has the two components. One is for KALYDECO and the label expansion intent that we have, which covers basically those populations that you have mentioned. We will know when we know what we discussed with the agency in terms of breakthrough, at what point in time we have a submission criteria, and then we will also see what data we will release at that point in time. It's still ongoing discussions, and therefore, it's hard to predict.

突破性療法認定包含兩個部分。其一是針對 KALYDECO 以及我們意圖進行的標籤擴增，基本上涵蓋你提到的那些族群。至於我們與主管機關就突破性療法所討論的內容、在何時達到提交（submission）標準，我們會在確定後才知道；屆時我們也會看到在那個時間點會公布哪些數據。目前仍在持續討論中，因此很難預測。

Howard, to the second part of your question of when you could see KALYDECO monotherapy data in the other mutations, we've guided to the second half of this year, we anticipate to start seeing data from those studies.

Howard，關於你第二部分的問題，也就是何時能看到 KALYDECO 單藥治療在其他突變上的數據，我們的指引是今年下半年，我們預期將開始看到那些研究的數據。

Thank you.

謝謝。

Katherine Xu, William Blair.

William Blair 的 Katherine Xu。

With regard to VX-135, I'm wondering in the initial [crossover] study, how many patients do you need to get to? I might have missed this because I couldn't hear very well. How many patients do you have to get to to get a sense of safety that could be satisfactory to go on?

關於 VX-135，我想問在最初的 [交叉] 研究中，你們需要做到多少名患者？我可能漏聽了，因為我聽得不是很清楚。你們需要做到多少名患者，才能對安全性有一個足以令人滿意、可以繼續往下推進的判斷？

Then, on the pricing of KALYDECO in Europe, just curious, can you give us some kind of guidance on the pricing relative to the US -- in Germany, in UK, Ireland, and France, relative to the US, how should we think about pricing?

那麼，關於 KALYDECO 在歐洲的定價，我只是好奇，您能否就相對於美國的定價給我們一些指引——在德國、英國、愛爾蘭與法國，相對於美國，我們應該如何看待定價？

For VX-135, we are looking at a relatively small number of patients in that initial cohort, and then an expansion once we receive those data, and we expect that will occur relatively quickly to allow us to expand. That is in the first of the trials, the ribavirin 135 trial. As you know, we are also initiating trials with the GSK and the TMC molecules, and those will be following the initiation of the ribavirin trial.

就 VX-135 而言，我們在最初的隊列中會觀察相對少量的病患，待我們取得那些數據後再進行擴增；我們預期這將會相對快速地發生，以便我們擴大規模。這是在第一個試驗，也就是利巴韋林（ribavirin）135 試驗中。如各位所知，我們也正在啟動與 GSK 以及 TMC 分子相關的試驗，而那些將會在利巴韋林試驗啟動之後陸續展開。

Small number would be 20 or 100 --?

少量是指 20 還是 100——？

Yes, in the order of 20 or so.

是的，大約是 20 位左右。

Okay.

好的。

And then Katherine, on price, I'm obviously not going to talk to the specifics of the pricing discussions that we are having in Europe. What I will say is that, obviously, we view KALYDECO as a breakthrough medicine and we priced it as such for the value it brings to patients, and we believe we know from clinical trials it brings the same value to patients in the EU as it does in the US. And we're going to be, and are, defending that value in our ongoing discussions with reimbursement authorities.

然後，Katherine，關於價格，我顯然不會談我們在歐洲所進行的定價討論細節。我能說的是，很明顯地，我們將 KALYDECO 視為一項突破性藥物，並依其為病患帶來的價值來定價；而且我們相信，從臨床試驗得知，它在歐盟為病患帶來的價值與在美國相同。在與給付／償付主管機關持續進行的討論中，我們將會、也正在捍衛這個價值。

Jason Kolbert, Maxim Group.

Jason Kolbert，Maxim Group。

I'd like to explore a little bit about what's really next with flu? What kind of expenses you're prepared to spend in order to support that program, or whether you're going to be looking for other sources of funding outside of the Company?

我想稍微探討一下流感項目接下來真正會怎麼走？為了支持該計畫，你們準備投入多少費用，或者你們是否會尋求公司以外的其他資金來源？

If we -- thanks, Jason, for the question. If we progress forward, I think we've been very clear about our priorities for investment in 2013; and if we haven't, I'll take the opportunity to say cystic fibrosis, hepatitis C, all-oral therapies, and autoimmune diseases; therefore, that does exclude investment towards flu. We're still waiting on the data. If the data's good and signals for a progression forward, then we would use, maybe, collaborations or external monies to fund the next steps of development for the flu molecule.

如果我們——謝謝你，Jason，這個問題。如果我們要往前推進，我想我們對 2013 年的投資優先順序已經說得很清楚；如果還不夠清楚，我就藉此機會再說一次：囊性纖維化、C 型肝炎、全口服療法，以及自體免疫疾病；因此，這確實排除了對流感的投資。我們仍在等待數據。如果數據良好並顯示可以往前推進，那麼我們可能會透過合作或外部資金來資助流感分子後續的開發步驟。

Thank you, very clear.

謝謝，很清楚。

Our next question is --

我們的下一個問題是——

Operator, I was going to say, I think we have time for about one more question. We're right up on call time.

接線員，我想說，我們大概還有時間再回答一個問題。我們已經快到電話會議結束時間了。

Phil Nadeau, Cowen and Company.

Phil Nadeau，Cowen and Company。

Stuart, I wanted to follow up on some of the comments you made about Ireland. I think you said that negotiation's going well there and proceeding, but the dossier from the National Center for Pharmacoeconomics is actually available online, and in that, it says that, basically, it can't recommend reimbursement at the submitted price, and you need to either fortify the clinical data -- the long-term clinical data, suggest a mechanism, such as performance-based risk sharing or significantly cut the price. So, can you talk a little bit more about why Ireland is going well, and what the next steps are there, and when we might get clarity on when or if they're going to reimburse?

Stuart，我想跟進你對愛爾蘭的一些評論。我記得你說那邊的談判進展順利、正在推進，但國家藥物經濟學中心（National Center for Pharmacoeconomics）的檔案其實在網路上可取得，而其中指出，基本上它無法在所提交的價格下建議給付，並且你們需要要麼強化臨床數據——長期臨床數據——、提出某種機制，例如以成效為基礎的風險分攤，或是大幅降價。所以，你能否再多談一點為什麼愛爾蘭進展順利、接下來的步驟是什麼，以及我們何時可能更清楚他們何時或是否會給付？

Sure, just to set expectations, these reimbursement-type discussions have a number of phases. There's usually an evaluation of the clinical benefit. That's always been unanimously positive for KALYDECO. Then, there is often an assessment, from a cost-effectiveness point of view, and then you get into a more substantive discussion about the data and the discussions on price.

當然。先設定一下預期，這類給付／償付的討論通常有多個階段。一般會先評估臨床效益。對 KALYDECO 而言，這一點一直都是一致正面的。接著，往往會從成本效益的角度進行評估，然後才會進入對數據與價格更實質的討論。

And, all I'll say is that those discussions continue; they're ongoing. This is all part of the process. These things aren't linear. You get these kind of tos and fros; and as I say, I remain optimistic that we will reach a successful conclusion in Ireland. Exactly when that is, I can't say, but I remain optimistic.

我只能說，這些討論仍在持續；目前仍在進行中。這都是流程的一部分。這些事情不是線性推進的。你會遇到這種來來回回；而且如我所說，我仍然樂觀地認為我們會在愛爾蘭達成成功的結論。確切何時我無法說，但我仍然樂觀。

Okay, and could you give us some sense of what additional data you have to submit to them, either on the long-term clinical benefit or a performance-based risk sharing?

好的，那你能否讓我們了解一下，你們還需要向他們提交哪些額外數據，無論是關於長期臨床效益，或是以成效為基礎的風險分攤？

I really can't go into the details of the data that we're submitting.

我真的無法深入說明我們正在提交的數據細節。

Okay, thank you.

好的，謝謝。

Thanks, very much, everyone, for listening tonight and for your questions. We will be in our offices tonight, following the call, for any follow up. Jeff will provide the final word.

非常感謝各位今晚收聽並提出問題。電話會議結束後，我們今晚會在辦公室，若有任何後續問題都可以再跟進。Jeff 會做最後總結。

Yes, thanks, Michael.

是的，謝謝你，Michael。

I think, as you heard tonight, we feel that we're very well positioned as we go into 2013. We have a strong financial position, we have two products that are performing well and we expect to continue to perform well, and we have a late-stage pipeline that's advancing very nicely with a number of milestones coming up through the year that will allow us and you to judge our progress. We look forward to updating you as we get those milestones, and we're looking forward to 2013. Thanks.

我想，正如各位今晚所聽到的，我們認為在邁入 2013 年之際，我們的定位非常有利。我們有強勁的財務狀況，有兩項產品表現良好且我們預期將持續表現良好，並且我們有一個後期研發管線正在非常順利地推進，全年將有多個里程碑，讓我們以及各位能夠評估我們的進展。我們期待在達成這些里程碑時向各位更新，也期待 2013 年。謝謝。

Ladies and gentlemen, thank you for participating in today's conference. This concludes today's program. You may all disconnect. Everyone, have a great day.

各位女士先生，感謝您參與今天的會議。今天的議程到此結束。各位可以掛線。祝各位有美好的一天。