福泰製藥 (VRTX) 2012 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to Vertex Pharmaceuticals, Incorporated, first-quarter 2012 financial results conference call. At this time all participants are in a listen-only mode. Later we will conduct a question-and-answer session with instructions following at that time. (Operator Instructions) As a reminder, this conference call is being recorded. Now I'll turn it over to your host, Michael Partridge, Vice President of Investor Relations. Please begin.

各位女士、各位先生，大家好，歡迎參加 Vertex Pharmaceuticals, Incorporated 2012 年第一季財務業績電話會議。此刻所有與會者皆處於僅收聽模式。稍後我們將進行問答環節，屆時會提供相關指示。(接線員指示) 提醒各位，本次電話會議將被錄音。現在我將把電話交給本次會議主持人——投資人關係副總裁 Michael Partridge。請開始。

Thank you. Good evening and welcome to Vertex's first-quarter 2012 conference call.

謝謝。各位晚安，歡迎參加 Vertex 2012 年第一季電話會議。

We're off to a great start for 2012. INCIVEK for the treatment of hepatitis C continues to lead the market in the US. And our collaborator, J&J has now also achieved the leading share in major European countries with INCIVO.

我們在 2012 年有一個非常好的開端。用於治療 C 型肝炎的 INCIVEK 在美國持續領先市場。而我們的合作夥伴 J&J 也已在主要歐洲國家以 INCIVO 取得領先市占。

In the area of cystic fibrosis, we are making strong progress early in the launch of KALYDECO. The launches of INCIVEK in North America, INCIVO in Europe and KALYDECO in the US are driving strong financial performance while we also continue to advance our broad pipeline of medicines for serious diseases. Vertex is now a multi-product, profitable, global business generating significant revenues that enable investment for future medicines while delivering significant earnings in cash flow for our shareholders.

在囊性纖維化領域，我們在 KALYDECO 的上市初期取得了強勁進展。INCIVEK 在北美的上市、INCIVO 在歐洲的上市，以及 KALYDECO 在美國的上市，正推動亮眼的財務表現；同時我們也持續推進針對嚴重疾病的廣泛藥物研發管線。Vertex 現已成為一家多產品、獲利、全球化的企業，創造可觀營收，使我們得以投資未來藥物，同時也為股東帶來顯著的獲利與現金流。

With me on the call tonight are Dr. Jeff Leiden, who will provide a perspective on Vertex's recent progress; and Ian Smith, who will review our first-quarter financial results. After the brief prepared remarks, Nancy Wysenski, Bob Kauffman and Peter Mueller will join us to take your questions. We would ask that you please limit your questions to one with a related follow-up. We expect to conclude the call at 6.00 pm. Once the call concludes, we will be in the office to answer any additional questions.

今晚與我一同參與電話會議的有 Jeff Leiden 博士，他將就 Vertex 近期進展提供觀點；以及 Ian Smith，他將回顧我們第一季的財務結果。在簡短的事先準備發言後，Nancy Wysenski、Bob Kauffman 與 Peter Mueller 將加入我們回答各位提問。我們請各位將問題限制為一題，並可附帶一個相關追問。我們預計在晚上 6 點結束本次電話會議。電話會議結束後，我們將在辦公室回覆任何額外問題。

I'll 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, which has been filed with the Securities and Exchange Commission. These statements, including those regarding the market launch of INCIVEK and KALYDECO, 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。這些陳述（包括關於 INCIVEK 與 KALYDECO 的市場上市）係基於管理層目前的假設，並受可能導致實際結果與事件出現重大差異之風險與不確定性影響。

GAAP and non-GAAP financial measures will be discussed on this call. Information regarding our use of these measures and a reconciliation of non-GAAP to GAAP is available in our first-quarter 2012 financial press release which is on our website.

本次電話會議將討論 GAAP 與非 GAAP 財務衡量指標。關於我們使用這些指標的資訊，以及非 GAAP 與 GAAP 的調節表，已載於我們網站上的 2012 年第一季財務新聞稿。

Thank you. I'll now turn the call over to Jeff.

謝謝。我現在把電話交給 Jeff。

Thanks, Michael. Good evening, everyone.

謝謝你，Michael。各位晚安。

The approval of our second medicine, KALYDECO, in January of this year, the continued strength in the global launch of INCIVEK and INCIVO, the financial performance we've achieved while advancing our pipeline of medicines, are all important measures of the success of our business model. We're particularly pleased that Vertex has grown rapidly into a global business with multiple approved medicines that are changing the lives of thousands of patients.

我們第二款藥物 KALYDECO 於今年 1 月獲批、INCIVEK 與 INCIVO 的全球上市持續強勁，以及我們在推進藥物研發管線的同時所達成的財務表現，都是衡量我們商業模式成功的重要指標。我們尤其欣慰的是，Vertex 已快速成長為一家全球化企業，擁有多款已核准藥物，正在改變數千名病患的生活。

My remarks today will cover three main areas. First, product revenues and earnings. Second, our pipeline of additional medicines and development; and third, our business model.

我今天的發言將涵蓋三個主要面向。第一，產品營收與獲利。第二，我們其他藥物的研發管線與開發進展；

Starting with our approved medicines, the strength of the global launch for INCIVEK in North America and INCIVO in Europe and other countries. We launched INCIVEK in the US in May 2011, and our partner Janssen began launching INCIVO in the second half of 2011 in its own territories. INCIVEK and INCIVO are now generating a very significant revenue stream for us, approximately $390 million in the first quarter, including $357 million from INCIVEK and $33 million in royalty revenues from INCIVO.

先從我們已核准的藥物談起：INCIVEK 在北美、以及 INCIVO 在歐洲與其他國家的全球上市表現強勁。我們於 2011 年 5 月在美國推出 INCIVEK，而我們的合作夥伴 Janssen 於 2011 年下半年在其自有市場開始推出 INCIVO。INCIVEK 與 INCIVO 現在正為我們帶來非常可觀的營收來源，第一季約為 3.90 億美元，其中 INCIVEK 貢獻 3.57 億美元，INCIVO 的權利金收入為 3,300 萬美元。

In the most recent months, we've observed a steady flow of people beginning treatment with INCIVEK, which to date commands a greater than 70% share in the US. INCIVO has also achieved a majority share in the major European countries where the medicine is available. And as INCIVO becomes available in more countries throughout the upcoming months, we expect to see continued significant growth in our royalty revenues.

在最近幾個月，我們觀察到開始使用 INCIVEK 治療的人數穩定流入；截至目前，INCIVEK 在美國的市占率超過 70%。INCIVO 也在該藥物已上市的主要歐洲國家取得過半市占。隨著 INCIVO 在未來幾個月於更多國家上市，我們預期權利金收入將持續顯著成長。

Let me move to KALYDECO for cystic fibrosis. We obtained FDA approval for KALYDECO and launched this breakthrough medicine just over two months ago for people with cystic fibrosis who have the G551D mutation. Reimbursement has gone smoothly and the launch is going very well. Approximately 600 people have started treatment with KALYDECO since approval, and we recorded approximately $18 million of net revenues in the first quarter. Again, we expect these revenues to grow as more patients begin and maintain treatment with KALYDECO.

接著談囊性纖維化的 KALYDECO。我們已取得 FDA 對 KALYDECO 的核准，並在兩個多月前為帶有 G551D 突變的囊性纖維化患者推出這款突破性藥物。給付報銷進行順利，上市進展非常良好。自核准以來，約有 600 人已開始接受 KALYDECO 治療，我們在第一季認列約 1,800 萬美元的淨營收。同樣地，隨著更多患者開始並持續接受 KALYDECO 治療，我們預期這些營收將成長。

In the last few months, we've heard from many patients and their families, and this is one of the most gratifying aspects of bringing a medicine like KALYDECO to patients. Specifically we've heard how much this medicine has impacted their lives, how they feel better, are healthier, and are for the first time optimistic about their futures.

在過去幾個月，我們聽到許多患者及其家屬的回饋；能將像 KALYDECO 這樣的藥物帶給患者，是最令人欣慰的事情之一。具體而言，我們聽到這款藥物對他們生活造成多大的影響——他們感覺更好、更健康，並且首次對未來抱持樂觀。

A young man with CF and his mom recently visited Vertex to share with us their experiences with KALYDECO, an experience that was truly life-changing for their family in many ways. This young man told us that thanks to KALYDECO, CF no longer defines him, but is just a part of him. He's looking forward to applying to colleges, and we are happy to hear that he visited one of our neighbors, MIT, during his trip to Vertex. It's these kinds of real-life experiences that inspire us and motivate our team to continue in our efforts to help others with this disease.

最近，一位罹患囊性纖維化（CF）的年輕人與他的母親到 Vertex 拜訪，與我們分享他們使用 KALYDECO 的經驗；這段經歷在許多方面確實為他們的家庭帶來翻天覆地的改變。這位年輕人告訴我們，多虧了 KALYDECO，CF 不再定義他，而只是他的一部分。他期待申請大學，我們也很高興聽到他在造訪 Vertex 期間參觀了我們的鄰居之一——麻省理工學院（MIT）。正是這些真實生活中的經驗啟發我們、激勵我們的團隊持續努力，幫助更多受此疾病影響的人。

I particularly want to give credit for the remarkable efforts of the CF community who have made it possible for so many people with CF to get KALYDECO so quickly following approval. This includes the CF Foundation, treatment centers, advocates in the CF community, the families and friends of people with CF, as well as our own internal and field teams, whose performance and commitment to this disease have been absolutely exemplary.

我特別要肯定囊性纖維化社群所付出的卓越努力，正因如此，才讓許多 CF 患者能在核准後如此迅速地取得 KALYDECO。這包括囊性纖維化基金會（CF Foundation）、治療中心、CF 社群中的倡議者、CF 患者的家人與朋友，以及我們內部與外勤團隊；他們在此疾病上的表現與投入都堪稱典範。

We're also preparing for the potential approval of KALYDECO in Europe later this year. In addition we're planning to initiate three pivotal studies of KALYDECO in 2012, that will enroll people with CF who have certain CFTR mutations not evaluated in the previous Phase III studies, as well as children with CF as young as two years of age.

我們也正為今年稍晚 KALYDECO 可能在歐洲獲批做準備。此外，我們計畫於 2012 年啟動三項 KALYDECO 的關鍵性試驗（pivotal studies），將納入先前第三期研究未評估之特定 CFTR 突變的 CF 患者，以及年齡低至 2 歲的 CF 兒童。

A study in people with the R117 H mutation and a study in people with other gating mutations are both expected to begin in the middle of this year. And a third study in children with CF as young as two years of age who have gating mutations is planned for later this year, pending final feedback from regulatory agencies. If successful, these studies could expand the number of people with CF who could benefit from KALYDECO monotherapy to approximately 8% to 10% of the estimated 70,000 people with CF worldwide.

針對帶有 R117 H 突變者的研究，以及針對其他閘控（gating）突變者的研究，預期都將於今年年中開始。第三項研究則計畫於今年稍晚展開，對象為年齡低至 2 歲且具有閘控突變的 CF 兒童；該研究將視監管機關的最終回饋而定。若研究成功，這些試驗可望將可從 KALYDECO 單藥治療受益的 CF 患者比例，擴大至全球估計 7 萬名 CF 患者中的約 8% 至 10%。

Now I'd like to turn to the progress of our pipeline of developing medicines. Our next wave of potential new medicines could expand and extend our opportunities in CF and hepatitis C, and we're making very nice progress with potential treatments for diseases like rheumatoid arthritis and flu. In addition to the three pivotal studies of KALYDECO monotherapy that I just mentioned, we are also conducting two Phase II exploratory studies, that combine KALYDECO with a CFTR corrector, either VX-809 or VX-661, and people with CF who have the most common CFTR mutation called Delta 508.

現在我想轉到我們藥物研發管線的進展。我們下一波潛在新藥可望擴大並延伸我們在囊性纖維化（CF）與丙型肝炎方面的機會，而我們在類風濕性關節炎與流感等疾病的潛在治療上也取得非常良好的進展。除了我剛提到的三項 KALYDECO 單藥關鍵性研究之外，我們也正在進行兩項第二期探索性研究，將 KALYDECO 與 CFTR 校正劑（VX-809 或 VX-661）合併使用，研究對象為帶有最常見 CFTR 突變、稱為 Delta 508 的 CF 患者。

The goal of combining KALYDECO with a corrector is to provide the majority of the CF population with a new treatment option. We expect to get the final results from the study of KALYDECO and VX-809 in mid-2012, followed by data from the KALYDECO on VX-661 study in the second half of this year. Because we have a deep knowledge and understanding of this disease, we have high hopes for what we may be able to do for the many children and adults living with cystic fibrosis.

將 KALYDECO 與校正劑合併的目標，是為大多數 CF 人口提供新的治療選項。我們預期在 2012 年年中取得 KALYDECO 與 VX-809 研究的最終結果，接著在今年下半年取得 KALYDECO 與 VX-661 研究的數據。由於我們對此疾病具備深厚的知識與理解，我們對於能為許多罹患囊性纖維化的兒童與成人帶來的改善抱持高度期待。

Now moving to hepatitis C, where the future goal in the treatment of this disease is to create well-tolerated, short duration, high viral cure regimens and specifically interferon-free, all-oral regimens. Toward this goal, we're in the process of initiating an interferon-free combination study with INCIVEK plus the VX-222 and ribavirin. We will also have the first seven-day viral kinetic data from Alios nucs in the next couple of months. Pending these viral kinetic data, we're focused on starting additional combination studies with the nucs later this year. Now this area is moving very fast; however, based on the most recent data in the field, we believe we have several excellent opportunities to play a leading role in the future evolution of new, all-oral treatments for patients with hepatitis C.

接著談丙型肝炎；此疾病治療的未來目標，是建立耐受性佳、療程短、病毒治癒率高的治療方案，特別是無干擾素、全口服的療法。為了達成此目標，我們正著手啟動一項無干擾素的合併研究，使用 INCIVEK 加上 VX-222 與利巴韋林（ribavirin）。我們也將在接下來幾個月取得 Alios 核苷類（nucs）首個為期七天的病毒動力學數據。視這些病毒動力學數據而定，我們將聚焦於在今年稍晚啟動更多與核苷類的合併研究。此領域進展非常迅速；然而，根據該領域最新數據，我們相信在未來新型全口服丙肝治療的演進中，我們有數個極佳機會扮演領導角色。

We also continue to make progress in other areas of the pipeline with our medicines and development and for rheumatoid arthritis and flu. In RA, we're in the process of starting a six-month, Phase II B study with VX-509, our selective JAK3 inhibitor, on a background of methotrexate. And in flu, we have now begun a proof-of-concept study for VX-787 where we will have data in the second half of the year.

我們在其他研發管線領域也持續取得進展，包括類風濕性關節炎與流感的藥物研發。在類風濕性關節炎（RA）方面，我們正準備啟動一項為期六個月的第二期 B 試驗，評估 VX-509（我們的選擇性 JAK3 抑制劑）在以甲氨蝶呤（methotrexate）為背景治療下的效果。在流感方面，我們已開始 VX-787 的概念驗證研究，並將在今年下半年取得數據。

Let me close by stating that our Business is strong and growing with revenues from two, marketed products and a significant royalty income that together allow for reinvestment to create future medicines, earnings and cash flows. What I highlighted for you this evening are the key ways to understand the positive trajectory of our Business, and the markers on the horizon for how we will drive growth in the future. I look forward to updating you as we go.

最後我想總結：我們的業務強勁且持續成長，來自兩項已上市產品的營收以及可觀的權利金收入，使我們得以再投資以創造未來的藥物、獲利與現金流。我今晚為各位重點說明的是理解我們業務正向軌跡的關鍵方式，以及展望未來我們將如何推動成長的里程碑。我期待在後續進展中持續向各位更新。

Thanks, and over to you, Ian.

謝謝，接下來交給你，Ian。

Thanks, Jeff, and good evening to everyone.

謝謝你，Jeff，也向各位道晚安。

Financially, 2012 is proceeding as we expected. And we have demonstrated that we now have a significant revenue base, one that is both diverse and has multiple sources. These revenues enable investments in our pipeline while also generating significant earnings.

在財務方面，2012 年的進展符合我們的預期。我們也證明目前已擁有可觀的營收基礎，且該基礎具備多元性並有多個來源。這些營收使我們得以投資研發管線，同時也產生顯著的獲利。

Now to the financials. In the first quarter of 2012, total revenues were approximately $439 million, compared to approximately $74 million in the same quarter of last year. The key components of these revenues are as follows; firstly, we reported approximately $357 million from INCIVEK net product revenues, which were affected by a reduction of approximately $22 million in inventory levels by wholesalers between December 31, 2011 and March 31, 2012. The current wholesaler, inventory level for INCIVEK at the end of the quarter is now approximately 2.5 weeks. In recent months, and early April, we observed a steady flow of patients beginning treatment with INCIVEK.

接下來談財務數字。2012 年第一季總營收約為 4.39 億美元，相較去年同期約 7,400 萬美元。這些營收的主要組成如下：首先，我們認列 INCIVEK 淨產品營收約 3.57 億美元；該數字受到批發商庫存水位在 2011 年 12 月 31 日至 2012 年 3 月 31 日期間下降約 2,200 萬美元的影響。本季末 INCIVEK 的批發商庫存水位目前約為 2.5 週。近幾個月以及 4 月初，我們觀察到開始使用 INCIVEK 治療的患者人數呈現穩定流入。

Secondly, we recorded $18 million of net product revenues for KALYDECO, which reflected the first two months of sales. As Jeff mentioned, approximately 600 people with CF have now started treatment with KALYDECO since the approval in late January. This reflects the strong patient demand, the connectivity of the CF community and broad awareness of the importance of KALYDECO for these patients. We expect this revenue stream to grow as more people start to maintain treatment with KALYDECO. Later this year, we expect approval in Europe, and this will add to this revenue growth. The strength of the launch in the US and potential future European approval puts us in a position to quickly build a significant and sustainable, long-term revenue base from KALYDECO.

第二，我們認列 KALYDECO 淨產品營收 1,800 萬美元，反映前兩個月的銷售。如 Jeff 所提，自 1 月下旬獲准以來，約有 600 位 CF 患者已開始使用 KALYDECO 治療。這反映出患者需求強勁、CF 社群的緊密連結，以及對 KALYDECO 對這些患者重要性的廣泛認知。隨著更多人開始並持續接受 KALYDECO 治療，我們預期此營收來源將成長。今年稍晚我們預期可在歐洲獲准，這將進一步帶動營收成長。美國上市初期的強勁表現以及未來可能在歐洲獲准，使我們得以迅速建立來自 KALYDECO 的可觀且可持續的長期營收基礎。

Thirdly, $39 million of royalty revenues, including $33 million of INCIVO royalty from J&J. This is a very important and growing revenue stream for the Company and contributes significantly to the bottom line. It reflects the fact that our hepatitis C leadership extends beyond the US and into Europe and other countries. INCIVO is now available in more than 15 countries worldwide, and more launches are planned this year by our collaborator. We expect our INCIVO royalties will grow significantly in 2012, given the early stage of launch in these European countries and other markets.

第三，權利金營收 3,900 萬美元，其中包括來自 J&J 的 INCIVO 權利金 3,300 萬美元。這對公司而言是一項非常重要且持續成長的營收來源，並對淨利貢獻顯著。這也反映我們在丙型肝炎領域的領導地位不僅在美國，也延伸至歐洲及其他國家。INCIVO 目前已在全球超過 15 個國家上市，我們的合作夥伴今年也規劃更多上市推進。鑑於這些歐洲國家及其他市場仍處於上市初期階段，我們預期 2012 年 INCIVO 權利金將大幅成長。

And finally, collaborative revenues of $24 million. A portion of these revenues provide funding for R&D activities, where we have relationships in the areas of hepatitis C and cystic fibrosis. This total revenue resulted in a GAAP net income attributable to Vertex of approximately $92 million in the first quarter of 2012, or approximately $0.43 per diluted share, which includes stock compensation charge of $28 million.

最後，合作收入為 2,400 萬美元。其中一部分收入用於資助研發活動，我們在丙型肝炎與囊性纖維化領域皆有合作關係。上述總營收使我們在 2012 年第一季依 GAAP 計算、歸屬於 Vertex 的淨利約為 9,200 萬美元，或每股稀釋後約 0.43 美元，其中包含 2,800 萬美元的股票酬勞費用。

For the first quarter of 2012, our non-GAAP net income attributable to Vertex was approximately $119 million, or $0.55 per diluted share. On the basis of $439 million of total revenues this quarter, our non-GAAP income from operations represents an operating margin of approximately 28%. And we expect this operating margin to grow significantly during the rest of 2012. We anticipate the growth of our operating margin to be driven by increases in total revenues and continued cost control over the top total, operating expenses. The operating margin is an important financial measure that is consistent with our business model.

2012 年第一季，我們依非 GAAP 計算、歸屬於 Vertex 的淨利約為 1.19 億美元，或每股稀釋後約 0.55 美元。以本季總營收 4.39 億美元為基礎，我們的非 GAAP 營業利益對應的營業利益率約為 28%。我們預期在 2012 年剩餘期間，該營業利益率將顯著提升。我們預期營業利益率的成長將由總營收增加，以及對總營業費用持續的成本控管所驅動。營業利益率是一項重要的財務衡量指標，且與我們的商業模式一致。

In summary, we continue to see steady demand for INCIVEK. We are seeing significant and growing revenues from INCIVO royalties, and we now have the first revenues from KALYDECO. Taken together, we are well-positioned to advance our pipeline while generating significant earnings and adding to our current cash position of approximately $1 billion.

總結而言，我們持續看到對 INCIVEK 的需求穩定。我們看到來自 INCIVO 權利金的營收顯著且持續成長，而我們也已取得 KALYDECO 的首批營收。綜合來看，我們具備良好條件在推進研發管線的同時，創造可觀獲利，並增加目前約 10 億美元的現金部位。

Thank you. Michael, back to you.

謝謝。Michael，交回給你。

Thank you, Ian. That concludes our prepared remarks. And we'd now like to open the call to Q&A.

謝謝你，Ian。以上為我們事先準備的發言。接下來我們想開放電話會議進入問答環節。

Thank you. (Operator Instructions) Geoffrey Porges of Bernstein.

謝謝。(接線員指示) Bernstein 的 Geoffrey Porges。

This is Alex here for Jeff. Congratulations on a great start with KALYDECO. Could you please clarify to us what was the channel inventory for KALYDECO? And I understand that all 600 patients are on the commercial drug, but then how many patients do you still expect to roll off the trial to commercial drug? And then I have a quick follow-up question.

我是 Alex，代替 Jeff 發言。恭喜 KALYDECO 有個很好的開局。能否請你們釐清一下 KALYDECO 的通路庫存是多少？我了解 600 位病患都在使用商業用藥，但那麼你們預期還有多少病患會從試驗用藥轉換到商業用藥？另外我還有一個簡短的追問。

Okay. Thanks for the question, Alex. It's Ian. Just to confirm that the net sales recorded for KALYDECO for the first quarter are actually there representative of the sales to the patient. There is no significant inventory stocking that occurs with KALYDECO.

好的。謝謝你的問題，Alex。我是 Ian。先確認一下，第一季 KALYDECO 所記錄的淨銷售額，實際上代表的是對病患端的銷售。KALYDECO 並沒有發生任何顯著的庫存囤積。

And, Alex, to the second half of your question, as you noted, we're very pleased that we have approximately 600 patients who are taking KALYDECO right now. We expect that there are approximately 100 patients in the US on the PERSIST trial and sometime between late second, early third quarter and the beginning of next year, those patients will be completing that trial and rolling over onto commercial supply.

另外，Alex，針對你問題的後半段，如你所提，我們很高興目前約有 600 位病患正在使用 KALYDECO。我們預期在美國約有 100 位病患參與 PERSIST 試驗，並且在第二季末、第三季初到明年年初之間的某個時間點，這些病患將完成該試驗並轉換為商業供藥。

Got it. And the quick follow-up question, just thinking about the combination file, and we're getting a lot of questions on that, what percentage of patients do you need to see to have a response above a certain sweat, chloride threshold level to decide to proceed to a Phase III trial?

了解。那個簡短的追問：就組合療法的申報檔案來看，我們收到很多相關問題；你們需要看到多少比例的病患，其反應高於某個汗液氯離子門檻值，才會決定推進到第三期試驗？

So, Alex, the ongoing trial is sort of a second cohort out of a longer existing, exploratory Phase II setting. And basically, what we are looking in to is predominantly safety and tolerability; that's number 1. And then we look at a bunch of parameters, like sweat chloride and FEV and everything else. And then out of the combination of all of those, we will make a decision how we move forward.

所以，Alex，目前進行中的試驗，算是既有較長期、探索性第二期研究架構下的第二個隊列。基本上，我們主要觀察的是安全性與耐受性；這是第一優先。接著我們會看一系列參數，例如汗液氯離子、FEV 以及其他指標。然後綜合所有這些結果，我們會做出後續如何推進的決策。

Thank you.

謝謝。

Terence Flynn, Goldman Sachs.

Goldman Sachs 的 Terence Flynn。

Thanks for taking the question. Congratulations on another strong launch. Was wondering if you can just tell us, remind us, how many centers you're targeting with KALYDECO and how many of those centers have already initiated a patient on drug? And then on the European front, I was wondering if you guys have gotten the Day 120 questions yet for KALYDECO, and if there was anything new in there that you can tell us about? Thanks.

謝謝讓我提問。恭喜再次有強勁的上市表現。想請教並請你們提醒一下：KALYDECO 你們目標覆蓋多少個中心？其中有多少中心已經讓病患開始用藥？另外在歐洲方面，我想問你們是否已收到 KALYDECO 的 Day 120 問題清單？其中是否有任何新的內容可以跟我們分享？謝謝。

To start with the question on KALYDECO, it all depends on -- the answer is really -- it all depends on how you count a center. So, there are adult centers, there are pediatric centers and if you want to literally go through and accumulate a total count, you're looking at over 250 centers. But of those, there are probably 120 or so that are really critically important. And we have penetrated and have prescriptions coming out of the vast majority of those critical centers across the US. Peter?

先從 KALYDECO 的問題開始，這其實取決於——答案真的——取決於你如何定義一個中心。因為有成人中心，也有兒科中心；如果你逐一累計總數，會超過 250 個中心。但其中大概有 120 個左右是非常關鍵的重要中心。而在美國各地這些關鍵中心中，我們已經在絕大多數取得滲透，並且有處方從這些中心開出。Peter？

So Terry, with respect to the regulatory path, we have submitted in time the MIA, and the process is well on track. And as we said earlier, we will not comment on particulars on the regulatory path. And we still are believing, and optimistically believing, that we will be approved in third quarter this year.

Terry，關於法規審查路徑，我們已按時提交 MIA，流程進展順利。如同我們先前所說，我們不會就法規審查路徑的細節發表評論。我們仍然相信，而且樂觀地相信，我們將在今年第三季獲得核准。

Okay. Thanks a lot.

好的。非常感謝。

Mark Schoenebaum, ISI Group.

ISI Group 的 Mark Schoenebaum。

This is Omar filling in for Mark. Just a couple questions on KALYDECO, number 1, are there any patients among these 600 that are currently on drugs that have some gating mutation other than G551D? And a quick follow-up to that, in Europe, how does payer confirmation of G551D status differ just in terms of mechanics versus how that plays out in the US? Thank you very much.

我是 Omar，代替 Mark。關於 KALYDECO 有兩個問題：第一，在這 600 位病患中，是否有人帶有 G551D 以外的其他 gating mutation（閘控突變）但目前仍在用藥？另外快速追問：在歐洲，付款方確認 G551D 狀態的方式，在流程機制上與美國相比有何不同？非常感謝。

Omar, let me answer the first half, and then I didn't quite literally understand the second half of your question in Europe. But in the US, we are very, very firm about the fact that we are promoting KALYDECO totally and only on label, which is only for the G551D mutation in patients who are six years old and over. Because of that, we have no real way to understand all the different genotyping mutations that would account for patients being put on the drug, but that's where we focus our promotion. And what was the second half of your question relative to Europe?

Omar，我先回答你問題的前半段；至於你在歐洲那部分的後半段，我沒有完全理解你的意思。但在美國，我們非常、非常堅持只依照核准標籤推廣 KALYDECO，也就是僅適用於 6 歲以上、帶有 G551D 突變的病患。因此，我們沒有真正的方法去了解所有不同的基因分型突變，哪些會導致病患被開立此藥；但我們的推廣重點就是在標籤適應症上。那你關於歐洲的後半段問題是什麼？

Sure. So just trying to understand the mechanics, in the market, how do payers verify that the patient that just initiated the drug had G551D? How does the process, just the mechanics of the process, differ in Europe versus how they are in the US?

好的。我想了解的是市場上的實務流程：付款方如何核實剛開始用藥的病患確實具有 G551D？也就是這個流程的運作機制，在歐洲相較於美國有何不同？

I think the general mechanics of reimbursement in Europe differ significantly from the US, and that you essentially have government-sponsored systems, so it's pretty much a one-payer system in the major countries, particularly the four driving countries that will be launching into for the G551D mutation. We really don't have insight into, in the US or in Europe, how many plans will be asking to validate or if those that are, how they're going about that. I'm sorry.

我認為歐洲的給付機制與美國有顯著差異；歐洲基本上是政府主導的體系，因此在主要國家幾乎是單一付款方制度，特別是我們將針對 G551D 突變上市的四個主要驅動國家。不論在美國或歐洲，我們其實都無法掌握有多少保險計畫會要求驗證；即便有要求驗證的，也不清楚他們會如何進行。很抱歉。

Okay. Great. Very helpful. Thank you.

好的。很好。非常有幫助。謝謝。

Yaron Werber, Citi.

Citi 的 Yaron Werber。

This is Gloria Woo in for Yaron. I just had a question about INCIVEK, actually. I was wondering if you guys are going to update your guidance on INCIVEK based on your current run rate?

我是 Gloria Woo，代替 Yaron。我其實有一個關於 INCIVEK 的問題。我想請問你們是否會根據目前的實際銷售運行速度（run rate）更新 INCIVEK 的財測指引？

Thanks for the question, Gloria. We actually reiterated our guidance in our press release this evening. The guidance for the full year that we provided, February 2. That reiteration of guidance is a reflection of our experience this year with INCIVEK. January sales, as I mentioned in my prepared remarks, were affected by a drawdown of inventory of around $22 million. But for February, March and April, we saw a steady trend of scripts and billing, based on all of this, plus we did provide a 7% price increase effective April 1. We remain comfortable with our guidance for the remainder of the year.

謝謝你的問題，Gloria。我們其實已在今晚的新聞稿中重申了我們的指引。我們在 2 月 2 日提供的全年指引；這次重申反映了我們今年在 INCIVEK 上的經驗。1 月的銷售，如我在事先準備的發言中提到，受到約 2,200 萬美元庫存去化的影響。但在 2 月、3 月與 4 月，我們看到處方量與請款呈現穩定趨勢；基於這些因素，再加上我們於 4 月 1 日起實施 7% 的價格調升，我們仍對今年剩餘期間的指引感到有信心。

Maybe to add to that, Gloria, this is Nancy. On the demand side, we've had a real steady stream of new RXs since the beginning of this year. If you look at your IMS data, you'll see that there have been between 850 and 1000 prescriptions generated weekly, and that's been in a pretty tight range there.

也許補充一下，Gloria，我是 Nancy。在需求端，自今年年初以來，我們一直有相當穩定的新處方（RX）流入。如果你看 IMS 數據，你會看到每週產生的處方量介於 850 到 1000 之間，而且一直維持在相當緊密的區間內。

Just to add confidence to the information that we have related to sales to date, in visiting with several thought leaders, well, more than several, last week at EASL, it's clear that there continue to be a good number of patients who are coming into practices who are requesting and need treatment for their hepatitis C. And based upon the information we have at this point in time, we continue to be confident that patients will be seeking treatment.

再補充一點，以強化我們目前掌握的截至目前銷售相關資訊的信心：上週在 EASL 與幾位意見領袖交流——其實不只幾位——很清楚地看到，仍有相當多病患走進診所，主動要求且需要接受丙型肝炎治療。根據我們目前掌握的資訊，我們仍然有信心病患會持續尋求治療。

And, Gloria, just to the other piece of our operating guidance, which is the operating expenses, we have an understanding and a controllable aspect to those operating expenses. And based on that and the trajectory we see for the rest of this year, we remain comfortable with the guidance we set earlier this year.

另外，Gloria，關於我們營運指引的另一部分，也就是營運費用，我們對這些營運費用有一定的掌握，且其中有可控的面向。基於這點以及我們對今年剩餘期間所看到的走勢，我們仍然對今年稍早所提出的指引感到安心。

Thanks so much.

非常感謝。

Rachel McMinn, Bank of America, Merrill Lynch.

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

Rachel?

Rachel？

Can you hear me?

你聽得到我嗎？

Yes, we can.

是的，我們聽得到。

Sorry about that. I have a couple of questions. When you talked about the Alios nucs, I might have missed this, but you said the next couple of months of data would be available. Does that mean we shouldn't be expecting it for sure in Q2? And then on KALYDECO, can you talk about where you think penetration is? Is the 600 patients, does that include any off-label use? And then you might have just answered this, but I might have missed it. On the price increase, how much of the 7% price increase is actually effective? Thanks.

抱歉。我有幾個問題。你們提到 Alios 的 nucs（核苷類），我可能漏聽了，但你說接下來幾個月的數據會出來。這是否表示我們不應該預期一定會在第二季（Q2）看到？另外關於 KALYDECO，你能談談你們認為目前滲透率到哪裡了嗎？這 600 位病患是否包含任何適應症外（off-label）使用？還有你可能剛剛已經回答了，但我可能漏掉了。關於漲價，7% 的漲幅有多少已經實際生效？謝謝。

So, Rachel, I'll take the first piece with the disclosure question. As we said in our proposed remarks, we expect the first data from the Alios nucs to be available in the second quarter of this year. And I'll refer to Nancy for the remainder of your question.

Rachel，我先回答第一部分關於揭露的問題。如同我們在事先準備的發言中所說，我們預期 Alios nucs 的第一批數據會在今年第二季取得。其餘問題我請 Nancy 來回答。

Sure. On the KALYDECO question, we're really pleased with the fact that we've got approximately 600 patients on drug. Because we're only promoting KALYDECO in the G551D patients who are over six years of age, and those are the only patients that we interact with in the support of our patient's support system and helping them with reimbursement, we can't really speculate about any off-label usage. We don't have insight into that.

好的。關於 KALYDECO 的問題，我們對目前約有 600 位病患用藥感到非常高興。因為我們只在年滿六歲的 G551D 病患族群中推廣 KALYDECO，而我們在病患支持系統、協助報銷（reimbursement）時也只會與這些病患互動，所以我們無法對任何適應症外使用做推測。我們沒有這方面的洞察。

Moving along to the price increases, I'm sure you're aware, Rachel, we can't give you a specific number, but at any point in manufacturers -- or in a product's life, when we take a price increase, not all of that drops to the bottom line, because of agreements that you have with both some commercial, as well as government payers.

再談到漲價，Rachel，我相信你也知道，我們無法提供你一個具體數字；但在任何製造商——或任何產品的生命週期中——當我們調漲價格時，並不是全部都會直接反映到最終獲利（bottom line），因為你與部分商業保險以及政府支付方之間都有協議。

Okay. So maybe half of the price increase, somewhere around there?

了解。所以也許大約一半的漲幅，差不多是那樣？

The majority of the price increase drops to the bottom line, Rachel.

大部分的漲幅會反映到最終獲利，Rachel。

The majority, okay. Thanks very much.

大部分，了解。非常感謝。

John [Vishnar] of JPMorgan.

摩根大通（JPMorgan）的 John [Vishnar]。

This is John in for Geoff Meacham. I had a question more about the correctors, 809 and 661. Since they're coming in so close to the each other at the end of this year and very soon with 809, what's the plan of attack going forward since they are too similar mechanisms? If you could just elaborate on that?

我是 John，代 Geoff Meacham 提問。我有個問題比較是關於 corrector（校正劑）809 和 661。由於它們在今年底的時間點非常接近，而且 809 很快就會有進展，既然機制很相似，接下來的推進策略是什麼？能否請你多說明一下？

So, John, that's actually a very good question. Here's Peter. So the answer to that is, there is a differentiation between the two molecules. And so 661, yes, has the same mechanism of action. It acts as the same type of corrector, but it has a different distribution profile as we have stated in earlier days. And what that could do is, it could give you an opportunity, because of higher exposure potentially in the lung to go with the lower dose regimen and a smaller pill burden and all those type of things in patient populations.

John，這其實是個非常好的問題。我是 Peter。答案是，這兩個分子之間是有差異化的。所以 661，沒錯，具有相同的作用機制。它作為同一類型的 corrector 發揮作用，但如同我們先前所說，它有不同的分布特性（distribution profile）。這可能帶來的機會是：由於在肺部可能有更高的暴露量，因此可以採用較低劑量的療程、較小的服藥負擔（pill burden），以及在病患族群中帶來這類好處。

If it materializes, based on data, we will make a decision how we compare the two molecules to each other and then go forward. I think it's too early to say something, because both studies are ongoing, and we have no data to make a decision at that point in time.

如果根據數據顯示確實如此，我們會決定如何比較這兩個分子，然後再往前推進。我認為現在說還太早，因為兩項研究都仍在進行中，我們目前沒有數據可以在此時做出決策。

John, this is Jeff. I think you're probably asking the question, do we plan on waiting till we have all of the data before we choose between the two? And the answer is no, not necessarily. We're going to evaluate them independently. As we've said, we'll have the 809 data first. We'll look at all that data and make a decision on how to proceed with 809. We'll then have the 661 data. We'll look at all that data and make a decision independently. Is that your question?

John，我是 Jeff。我想你問的可能是：我們是否打算等到所有數據都出來後，才在兩者之間做選擇？答案是不一定。我們會分別獨立評估。如同我們所說，我們會先拿到 809 的數據。我們會檢視所有數據，並決定 809 接下來如何推進。之後我們會拿到 661 的數據。我們會檢視所有數據，並獨立做出決策。你問的是這個嗎？

Yes, it does. And since they're so similar, I don't assume that you would use them in combination with KALYDECO. Both of them?

是的，沒錯。既然它們很相似，我不認為你們會把它們兩個都和 KALYDECO 併用。兩個都用？

You mean three drugs at a time?

你的意思是同時用三種藥？

Yes, exactly.

對，正是。

No, there's no intention to have a three-drug regimen. So, given the similarity from the mechanisms point of view, they bind basically at the same binding site, in a way. There's no additivity expected.

不會，我們沒有要做三藥併用療程的意圖。因此，從機制相似性的角度來看，它們基本上會結合在同一個結合位點（binding site）上，某種程度上是這樣。預期不會有加成效果（additivity）。

Great. Thank you so much.

很好。非常感謝。

Howard Liang, Leerink Swann.

Leerink Swann 的 Howard Liang。

Congratulations on a nice launch. Can you just -- do you have an estimate of how many G551D patients there are in the US? I know you talk about 600 patients. I think normally we think about 4% of the population is G551D, but that would seem to mean that you already half the patients on the drug within two months?

恭喜上市表現不錯。你們能否——你們是否估計美國有多少 G551D 病患？我知道你們提到 600 位病患。我想一般我們會認為約 4% 的族群是 G551D，但那似乎表示你們在兩個月內就已經讓一半病患用上藥了？

Howard, this is Nancy. Great to talk to you, and thank you for the compliment. You're right, we think about 1000, G551D patients in the US. But we have to keep in mind that as we don't yet have any indication for those who are under six years of age, that does remove a small subset. So, we're pleased and we believe that we have already reached a majority point of the appropriate, potential patients.

Howard，我是 Nancy。很高興和你交流，也謝謝你的稱讚。你說得對，我們認為美國大約有 1000 位 G551D 病患。但我們必須記得，由於我們目前尚未取得六歲以下的適應症核准，這會排除掉一小部分族群。因此，我們很高興，也相信我們已經觸及到符合條件之潛在病患中的多數。

Great. Thanks. And which countries has INCIVO been launched in?

很好。謝謝。那麼，INCIVO 已在哪些國家上市？

INCIVO has been launched in more than a dozen countries in Europe. Additionally, in Canada. I don't know if you're looking for a list of those. The major countries in Europe, and they have already achieved a dominant market share.

INCIVO 已在歐洲十多個國家上市。另外，在加拿大也已上市。我不確定你是否想要一份清單。在歐洲的主要國家，而且他們已經取得主導性的市占率。

Okay. So, the royalty from this quarter is already from those countries, or is it only a subset of those countries?

好的。所以，本季的權利金已經來自那些國家了，還是只來自其中一部分國家？

It is from the countries that Nancy is referring to the launch, Howard. However, as you can imagine, it's really the first stages of the launch. I made the comments in my prepared remarks that we do anticipate a growth from the royalty stream, and that's because as they gain critical mass in each of the countries, it should drive an increased royalty to us on a quarterly basis.

權利金來自 Nancy 所提到已上市的那些國家，Howard。不過，如你所想，這確實還在上市初期階段。我在事先準備的發言中提到，我們確實預期權利金收入會成長；原因是當他們在各國達到臨界規模時，應會推動我們每季收到的權利金增加。

Thanks very much.

非常感謝。

Jason Kantor, RBC Capital Markets.

Jason Kantor，RBC Capital Markets。

Thank you and another congratulations on KALYDECO. Just wondering, you got 600 patients really fast; and you said you have another 100 patients in clinical trials that could roll off later this year, early next year. But is that gap, the remaining market share, is that something we should expect to also come on to therapy in sort of the same rapid trajectory? Or is there some portion of this population that's hard to get to for whatever reason?

謝謝，也再次恭喜 KALYDECO。我想請教，你們很快就有 600 名病患；而且你們說還有另外 100 名在臨床試驗中的病患，可能會在今年稍晚或明年初結束試驗轉出。但那個缺口、也就是剩餘的市場份額，我們是否也應該預期會以類似的快速軌跡開始接受治療？或者這個族群中是否有一部分病患因某些原因而比較難觸及？

Jason, as you might expect, every launch is unique. You typically start out with a really strong show when you've got a great product like KALYDECO, and we're delighted that that is exactly what is happening here. I can't really tell you, we'd all be speculating about where we'll be by a certain point in time, or how many patients we'll have under treatment, but we're delighted with the fact that we've already gotten the majority of patients, only three months into the launch, and we know that there are another 100 imminent.

Jason，如你所料，每一次上市都各有不同。通常當你有像 KALYDECO 這樣優秀的產品時，一開始會有非常強勁的表現；我們很高興這裡正是如此。我無法真正告訴你——如果要說某個時間點我們會到哪裡、或會有多少病患接受治療，那都只是推測——但我們很高興在上市僅三個月內就已經涵蓋了大多數病患，而且我們知道還有另外 100 名即將加入。

Now this 600 patients, that was as of the end of the quarter or that's as of today? And if you're giving us INCIVEK kind of April trends, can we get the same for KALYDECO?

那這 600 名病患是截至季末的數字，還是截至今天？另外，如果你們能提供 INCIVEK 類似四月的趨勢數據，我們也能拿到 KALYDECO 的同類資訊嗎？

The 600 patients are as of last week. So, in the through the majority of April. And no, I think the last number we've used is more than 35,000 patients on INCIVEK, but we don't have plans to update that number.

600 名病患是截至上週的數字。也就是涵蓋了四月的大部分時間。至於後者，不行；我想我們最後一次使用的數字是 INCIVEK 用藥病患超過 35,000 人，但我們沒有計畫更新那個數字。

Thank you.

謝謝。

Matthew Roeder, UBS.

Matthew Roeder，UBS。

This is actually Andrew in for Matt. And let me add my congratulations on the good KALYDECO number. I guess my question is a bit of an extension from the one just asked. You mentioned earlier the 120 or so critical centers. Of the 600 patients that are on drug right now, how many of those are coming from the critical centers? And I guess I have a short follow-up.

其實我是 Andrew，代替 Matt。也讓我恭喜你們 KALYDECO 的數字表現不錯。我想我的問題是延伸剛才那個問題。你們先前提到大約 120 個關鍵中心。目前用藥的 600 名病患中，有多少是來自這些關鍵中心？我還有一個簡短的追問。

I actually don't have those data. You may also recall that this launch came three months earlier than anticipated. And everyone's moving at a pretty rapid clip here, so I can tell you that we have gotten prescriptions from all the major centers, and in fact from the majority of centers, generally.

我手上其實沒有那些數據。你也許還記得，這次上市比預期早了三個月。而且大家都在很快的節奏下推進，所以我可以告訴你，我們已經從所有主要中心拿到處方，事實上也從大多數中心普遍拿到處方。

Okay. And I guess the follow-up would be, are the scripts coming one or two at a time? Or are docs putting the majority of their patients on drug?

好的。那追問是，處方是一次開一兩張嗎？還是醫師把他們大多數病患都用上這個藥？

I don't have insight into that.

我沒有這方面的洞見。

All right. Thank you.

好。謝謝。

Brian Abrams, Wells Fargo Securities.

Brian Abrams，Wells Fargo Securities。

This is Matthew calling in for Brian, thank you for the question. In light of the macroeconomic situation in Europe and some of the recent technology assessments by European countries for some recently-approved pharmaceuticals, can you discuss your general thoughts about what clinical data from the KALYDECO studies do you believe will provide compelling evidence for the drug's benefit in these G551D patients that will help enable strong reimbursement? Thank you.

我是 Matthew，代替 Brian 來電，謝謝讓我提問。鑑於歐洲的總體經濟情勢，以及部分歐洲國家近期對一些新近核准藥品所做的技術評估，你能否談談你們的整體看法：你們認為 KALYDECO 研究中的哪些臨床數據，能為這些 G551D 病患提供具說服力的藥物效益證據，以協助促成強勁的給付／報銷？謝謝。

That's a great question, Matthew. And of course, speaking for Peter and Bob we never know exactly what a label will read like until it's granted. But clearly, with the data that were involved in the US label and how things are progressing in Europe, we feel confident that there will be significant information and that that will enable us to approach the appropriate authorities in the four major countries where 80% of the patients exist.

這是個很好的問題，Matthew。當然，代表 Peter 和 Bob 來說，在核准之前我們永遠無法確切知道標籤內容會怎麼寫。但很明顯，基於美國標籤所採用的數據，以及目前在歐洲的進展，我們有信心會有相當多的重要資訊，而這將使我們能夠與四個主要國家的相關主管機關接洽，因為 80% 的病患都在那四個國家。

Okay. Thank you.

好的。謝謝。

Ravi Mehrotra, Credit Suisse.

Ravi Mehrotra，Credit Suisse。

This is [Kuhn] actually calling on behalf of Ravi. I had two quick questions here. First of all, how quickly could you move into a Phase III trial, depending on how the Alios nucs data looks? How quickly could you move into a Phase III interferon 3 combo trial? And the question on INCIVEK, have you seen any indications of doctors warehousing patients in light of the recent developments in HDV? Thanks.

其實我是 [Kuhn]，代表 Ravi 來電。我有兩個簡短問題。第一，取決於 Alios 核苷（nucs）數據的表現，你們最快能多快推進到第三期試驗？你們最快能多快推進到第三期的干擾素三合一（3 combo）聯合試驗？另外關於 INCIVEK，鑑於近期 HDV 的發展，你們是否看到醫師有把病患「囤著不治療」（warehousing）的任何跡象？謝謝。

The first question was how fast can you move on the Alios. I think the first thing is we have to go in Phase II. We are currently in viral kinetic studies which is a 1B, and this will happen in the second half of this year. Shortly after, we have data available. So I think we are preparing for that and moving, hopefully, one or several, dependent on data outcome, regimens into our Phase II setting, and then basically from there, it's not a question of Phase III, it's a question of pivotal drugs in general, and you have to develop a development strategy basically that takes care of it.

第一個問題是 Alios 那邊你們能推進多快。我想第一點是我們必須先進入第二期。我們目前在做病毒動力學研究，這是 1B，將在今年下半年進行。之後不久，我們就會有可用數據。所以我認為我們正在為此做準備，並希望依據數據結果，把一個或數個療程方案推進到第二期；接下來基本上就不只是第三期的問題，而是整體關鍵性（pivotal）藥物開發的問題，你必須制定一個能夠涵蓋這些需求的開發策略。

The only thing we have said is, which I want to reiterate, is we have a chance with our regimens to basically come, by the end of 2014, to the first submission for regulatory approval in all-oral setting, whatever that setting might be.

我們唯一說過、我也想重申的是：透過我們的療程方案，我們有機會在 2014 年底前，針對全口服（all-oral）治療的某種設定（不論最終是哪一種設定）提出第一份監管核准申請。

This is Jeff. I guess the one other thing I would add is obviously we are, as are others, aiming for shorter and shorter trials with these all-oral regimens and hopefully getting down to as short as 12 weeks. And that does have a major impact on the timing and the speed at which one can move in these trials, which is quite different from the previous trials containing peg-riba.

我是 Jeff。我想我另外要補充的是，很明顯我們和其他公司一樣，都在追求全口服療程更短、更短的試驗期，希望能縮短到最短 12 週。而這會對時程與推進試驗的速度產生重大影響，這與過去包含 peg-riba 的試驗非常不同。

And on the question related to warehousing, this is something we talked quite a bit about during our fourth-quarter call, and we had done some fairly extensive research looking into this. So, although we're delighted in that we are also participating in the development of potential, all-oral therapies, at this point, we don't have any data to suggest that there is additional secondary warehousing beyond what goes on all the time as physicians triage patients into appropriate therapies.

至於與「囤病患」相關的問題，這是我們在第四季電話會議中談了很多的議題，而且我們也做了相當廣泛的研究來檢視這件事。因此，雖然我們很高興也參與潛在全口服療法的開發，但就目前而言，我們沒有任何數據顯示存在額外的次級囤病患情況；除了醫師一向會做的事情——也就是將病患分流（triage）到適當的治療方案。

We are ready for the next question.

我們準備好進行下一個問題。

Ying Huang, Barclays.

黃穎，巴克萊。

I want to also echo my congratulations on the KALYDECO launch. First question, can you give us the gross and net adjustment for both INCIVEK and KALYDECO last quarter? And then, Ian, you mentioned that inventory drawdown for about $22 million for INCIVEK. Do you expect that to bounce back in the future quarters? Thank you.

我也想再次表達我對 KALYDECO 上市的祝賀。第一個問題，您能否提供上一季 INCIVEK 與 KALYDECO 的毛額與淨額調整（gross-to-net adjustment）各是多少？另外，Ian，你提到 INCIVEK 約有 2,200 萬美元的庫存去化（inventory drawdown）。你預期未來幾季會回補（bounce back）嗎？謝謝。

Thanks, Ying, thanks for the questions. So, just as a statement, the gross to net, first on INCIVEK, it actually did move up slightly in the first quarter, so the net revenues were affected by that. It moved from approximately 13% in our fourth-quarter to 16% in this first quarter. We would anticipate that that 16%, around there, will be maintained for the rest of the year. We've now completed the majority of our contracting process.

謝謝你，Ying，謝謝你的問題。先說明一下 gross-to-net，先談 INCIVEK：第一季其實略有上升，因此淨營收受到影響。它從我們第四季約 13% 上升到本季的 16%。我們預期今年剩餘期間將維持在約 16% 左右。我們現在已完成大部分的合約簽訂流程。

On KALYDECO, we're still getting a better understanding of that margin or the net that the discount -- it's early on in the launch, so we're still setting up our contracting. For this quarter, though, it was mid-single digits, maybe slightly above there. And we do expect that to increase slightly. And the -- sorry, the inventory question. Yes, so the inventory did reduce from December 31 to March 31 for INCIVEK inventory holding by approximately $22 million, so of course that affects the revenues that we would accrue in the first quarter.

至於 KALYDECO，我們仍在更深入了解該毛利／淨額，也就是折扣的影響——因為上市初期，我們仍在建立合約安排。不過就本季而言，大約是中個位數百分比，可能略高一些。我們也預期它會小幅上升。然後——抱歉，關於庫存的問題。是的，INCIVEK 的庫存持有量從 12 月 31 日到 3 月 31 日約減少 2,200 萬美元，因此當然會影響我們第一季可認列的營收。

As it affects going forward, we ended the first quarter with approximately 2.5 weeks of inventory, so that's a pretty low level of inventory, so as we go forward, we're not sure where it will go, but it shouldn't have a significant impact as we move forward, given that the drawdown has pushed the inventory levels to a low of 2.5 weeks.

至於對未來的影響，我們在第一季末的庫存約為 2.5 週，這是相當低的庫存水位；因此往後會如何我們不確定，但由於這次去化已把庫存水位推到 2.5 週的低點，未來應不致造成重大影響。

Great. That was helpful. Thank you.

很好。這很有幫助。謝謝。

Liisa Bayko, JMP Securities.

Liisa Bayko，JMP 證券。

Congratulations on the good launch of KALYDECO. As we think about the combination moving forward, what's really going to drive your decision about this particular combination? Is it really the FEV data or are you going to be thinking more about the sweat chloride? I'm just trying to anticipate the data as it comes out.

恭喜 KALYDECO 上市表現良好。在我們思考未來的聯合療法（combination）時，究竟是什麼會真正驅動你們對這個特定組合的決策？主要會看 FEV 的數據，還是你們會更著重汗氯（sweat chloride）？我只是想預先理解接下來數據公布時該如何解讀。

Liisa, that's Peter again. I think it's not the one or the other. You have to look at the overall pattern that you're basically get in those exploratory drugs, which is a smaller number of patients to make a decision. Obviously, from a therapeutic point of view, FEV is the one that is accepted by regulatory agencies, and that has the major impact, and so if you don't see anything in FEV, that's never a good thing.

Liisa，我是 Peter。我認為不是二選一。你必須看整體的趨勢樣貌，因為這些探索性藥物的受試者人數較少，需要綜合判斷來做決策。顯然，從治療角度來看，FEV 是監管機構接受的指標，影響最大；因此如果在 FEV 上看不到任何效果，那絕不是好事。

That's helpful. Thanks. And then maybe just an additional question, but on a different topic, related to R&D. The Alios nucs, I'm just curious, obviously you have two and that presents some unique opportunities for development. But as you think about interferon-free regimens and the Alios nucs, what's really your strategy to develop these? Are you thinking nuc, new combinations or combinations of other classes? And might you consider looking outside of your own pipeline there? Thank you very much.

這很有幫助。謝謝。另外也許再問一個不同主題、與研發（R&D）相關的問題。關於 Alios 的核苷類（nucs），我很好奇，顯然你們有兩個，這帶來一些獨特的開發機會。但當你們思考無干擾素（interferon-free）療法與 Alios nucs 時，你們真正的開發策略是什麼？你們是考慮 nuc 與新的組合，或是與其他類別的藥物組合？你們是否也會考慮在自家產品線之外尋找資產？非常感謝。

Liisa, that's a good question. I think there is many different aspects that you have to consider in FEV strategy, given the fact that we believe and I think data more and more show that different patient population might benefit from different regimens, and that there's not a one-size-fits-all regimen. And that will drive sort of how we basically go forward.

Liisa，這是個好問題。我認為在 FEV 策略上有許多不同面向需要考量，因為我們相信、而且越來越多數據顯示，不同病人族群可能會從不同療程中受益，並不存在一套適用所有人的療程。而這將驅動我們接下來基本上要如何推進。

The nice thing in the Vertex world, outside of having INCIVEK being the leading drug, is that we basically have a plethora of molecules that we can combine in many different forms and fashions, and there's not just the one regimen that we are looking into. And that's driven by patient populations that we selected that we go forward. So, I think we have here a very good opportunity. And so this is what is. And then obviously, we will not stop here. We constantly also are looking for other opportunities; and as you have seen, companies partner and do things, and we are completely open to consider those type in our strategy too.

在 Vertex 的世界裡，除了 INCIVEK 是領先藥物之外，另一個優勢是我們基本上擁有大量分子，可用各種不同方式進行組合；我們並不是只在研究單一療程。而這會由我們選定、要往前推進的病人族群所驅動。所以我認為我們在這裡有非常好的機會。事情就是如此。當然，我們不會止步於此。我們也持續尋找其他機會；而且如你所見，各家公司會合作、做各種安排，我們也完全願意在策略中考慮這類型的作法。

Liisa, this is Jeff. I totally agree with what Peter said. And just to perhaps add a couple of things. I think we are in a uniquely advantageous situation, because we have multiple swings at the ball inside, as Peter said, and we know they are combinable; and that's very important, I think. The combinability is in some cases, I think, been lost in the discussion. We've done a lot of work on that.

Liisa，我是 Jeff。我完全同意 Peter 所說的。我再補充幾點。我認為我們處於一個獨特且有利的位置，因為如 Peter 所說，我們內部有多次「揮棒」的機會，而且我們知道它們可以彼此組合；我認為這點非常重要。我覺得在討論中，有時候「可組合性」這件事被忽略了。我們在這方面做了很多工作。

The second thing is, I think, because we have some unique asset and particularly the nucs, that also would place us in a more powerful position with respect to partnering with other outside assets. And so our plan is to fully explore our internal pipeline as well as, once we begin to understand that, to explore partnering possibilities that might work for both parties.

第二點是，我認為因為我們擁有一些獨特資產，特別是這些 nucs，也會讓我們在與外部資產合作（partnering）方面處於更有力的位置。因此，我們的計畫是充分探索內部產品線；同時，一旦我們開始更清楚了解之後，也會探索可能對雙方都有利的合作可能性。

Great. Thank you very much for answering my questions.

很好。非常感謝你們回答我的問題。

David Friedman, Morgan Stanley.

David Friedman，摩根士丹利。

Thanks for taking the question. In regards to, I think, something that was mentioned earlier around off-label use of 770, and you said that because you don't have -- you're not promoting off label, obviously, and therefore you don't have interactions with people, does that mean that there is no co-pay support or any other services that you are allowed to provide for patients who do not have G551D until they're labeled? Or is there some amount of interaction that you're allowed to have just to facilitate what was the physician's decision to put the patient on drug or not?

謝謝讓我提問。關於先前提到的 770 適應症外使用（off-label use），你們說因為你們不推廣適應症外使用，顯然也因此不會與相關人士互動；這是否表示，對於尚未有 G551D、在標籤核准前的病人，你們不能提供任何自付額（co-pay）補助或其他服務？或者你們是否仍被允許有某種程度的互動，只是為了協助醫師已做出的決定——也就是讓病人使用或不使用該藥？

So, David, that's a great question. And, no, we have no -- we don't have any of our support programs extended to patients beyond the G551D, six and over, indication in our label.

David，這是個很好的問題。答案是否定的；我們沒有——我們不會把任何支援計畫延伸到標籤適應症之外的病人；我們標籤上的適應症是 G551D、6 歲以上。

Okay. And then just as a quick follow-up, do you have an estimate, or have you gotten any sense of what an average co-pay is for a patient with this, and what percent you've needed to provide some support to?

好的。再快速追問一下，你們是否有估計，或是否已大致了解，這類病人的平均自付額（co-pay）大約是多少？以及你們需要提供某種支援的比例大概是多少？

As you can imagine, the majority of patients do look for co-pay support, but those are usually in a very reasonable range. I know that some questions have come up about free drug, and the provision of free drug occurs at an extremely low level. And so far, the data we have on co-pays is not at a very high rate. Ian, would you like to expound?

如您所能想像，大多數病患確實會尋求自付額（co-pay）補助，但通常都在相當合理的範圍內。我知道有些問題提到免費用藥，而提供免費用藥的情況發生在極低的水準。截至目前，我們掌握的自付額數據並未顯示比例很高。Ian，你願意再補充說明嗎？

Yes. David, just -- I mentioned a gross-to-net adjustment for KALYDECO earlier on this call. It's approximately 6%. That includes a lot of the patient's support. So as you can see, there's not a significant discount on the gross to net due to patient support programs.

是的。David，剛才在這通電話中我先前提到 KALYDECO 的毛額到淨額（gross-to-net）調整。大約是 6%。其中包含了大量的病患支持。所以如你所見，因病患支持計畫而造成的毛額到淨額折讓並不顯著。

Got it. Great. Thanks very much.

了解了。很好。非常感謝。

Marko Kozul, ThinkEquity.

Marko Kozul，ThinkEquity。

This is Irene in for Marko. Thanks for taking the question and congratulations on the progress. When you present the first cystic fibrosis combination trial for KALYDECO and VX-809, what kind of data do you plan to report? In other words, do you plan to only provide mean FEV1 and sweat chloride data? Or might you consider also providing sub group analysis and potential correlation data between FEV1 and sweat chloride?

我是代替 Marko 的 Irene。謝謝讓我提問，也恭喜你們的進展。當你們公布 KALYDECO 與 VX-809 的首個囊性纖維化聯合試驗時，計畫報告哪一類數據？換句話說，你們是否只會提供平均 FEV1 與汗氯（sweat chloride）數據？或者也會考慮提供亞組分析，以及 FEV1 與汗氯之間可能的相關性數據？

Thanks for the question. At this time we can't really prescribe the press release that we'll be putting out. What I could say is that when we have the data and we're in a position to release it, we'll provide you with the top line data from that study, but I can't go beyond that at this point in time, because we don't know how we'll be providing it.

謝謝你的提問。目前我們無法確切說明將發布的新聞稿內容。我能說的是，當我們拿到數據並且具備發布條件時，我們會提供該研究的重點（top line）數據，但此刻我無法再進一步，因為我們還不確定會以何種方式提供。

Thank you.

謝謝。

We have time I believe for two more questions.

我想我們還有時間再回答兩個問題。

Thank you. Next is from Katherine Xu, William Blair.

謝謝。下一位是 William Blair 的 Katherine Xu。

Good afternoon. I was just curious, for the INCIVEK launch, what is the ratio between naive and experienced patients? Do you have a sense of that? And the other one is, do you have any pricing information on the ex-US countries that you have launched to date?

午安。我只是好奇，關於 INCIVEK 的上市推廣，新治療（naive）與既往治療（experienced）病患的比例是多少？你們有概念嗎？另外，你們是否有截至目前已在美國以外（ex-US）上市國家的任何定價資訊？

The INCIVEK split, Katherine, we continue to see a majority of the patients coming into the naive descriptor, about 70%. And, Ian, do you want to comment on pricing in Europe? That's totally out of our control, as you know, and it's decided by Johnson & Johnson.

Katherine，關於 INCIVEK 的分布，我們持續看到多數病患屬於新治療（naive）類別，大約 70%。另外，Ian，你要不要評論一下歐洲的定價？如你所知，那完全不在我們控制之內，是由 Johnson & Johnson 決定的。

Yes. My comment is towards the INCIVO royalty. We don't comment on J&J's pricing decisions. But the royalties, there's a significant royalty stream as you can see in the first quarter; and that's just at the first part of this launch. So we anticipate that that will grow. And the majority of that royalty goes straight to our bottom line, so it's a very healthy cash flow for us, given the scale of the European market and also the lead position that INCIVO seems to be in early on in the launch.

是的。我的評論會聚焦在 INCIVO 的權利金。我們不評論 J&J 的定價決策。但就權利金而言，如你在第一季所見，有一筆可觀的權利金收入流；而這還只是這次上市初期。因此我們預期它會成長。而且其中大部分權利金會直接反映到我們的最終盈餘，因此在歐洲市場規模以及 INCIVO 在上市初期似乎處於領先地位的情況下，對我們而言是非常健康的現金流。

Great. And for KALYDECO so far, what is the percentage of successful reimbursement decisions?

很好。另外，就目前 KALYDECO 而言，成功獲得給付核准的比例是多少？

I guess, Katherine, that's a really hard question to answer, because the launch is so young, and in an orphaned disease state, one typically expects that it might take as long as two to three months to receive reimbursement once the paperwork is put into place. So, we're delighted that it's going as fast as it is, and that the majority of patients have already received reimbursement, but of course there are others who are still waiting, and we believe that's probably part of why we're seeing a high ratio of commercial pays, because typically the commercial plans make quicker reimbursement decisions.

Katherine，我想這個問題很難回答，因為上市時間還很短，而且在罕見疾病領域，一般而言從文件備齊送出到取得給付，通常可能需要兩到三個月。所以我們很高興進展比預期快，而且多數病患已經獲得給付，但當然也有一些仍在等待；我們認為這可能也是為什麼我們看到商業保險給付（commercial pays）比例偏高，因為商業保險方案通常做出給付決策更快。

Thank you and congratulations, as well.

謝謝，也恭喜你們。

Thank you.

謝謝。

Thanks, Katherine.

謝謝你，Katherine。

Alan Carr, Needham & Co.

Alan Carr，Needham & Co.。

This is Mark [Venuella] on for Alan. Thanks for taking my question. I was wondering if you guys could talk a little bit about the royalty expenses, and what portion of that might be due to KALYDECO?

我是代替 Alan 的 Mark [Venuella]。謝謝讓我提問。我想請教你們能否談談權利金費用，以及其中有多少部分可能是由 KALYDECO 所致？

So, we do have a royalty payment to the Cystic Fibrosis Foundation on the KALYDECO revenue stream. It's an escalating royalty that starts in mid to high-single digits and goes into pre-teens royalty once the product gets significant scale.

我們確實需要就 KALYDECO 的營收流向囊性纖維化基金會（Cystic Fibrosis Foundation）支付權利金。這是一種遞增式權利金，起始約在中到高個位數百分比，當產品達到相當規模後，會提高到約十幾個百分點（pre-teens）的權利金水準。

And it actually appears in the cost-of-product revenue's line, the KALYDECO royalty that we pay out. It does not appear in the royalty payout revenue line.

而且我們支付的 KALYDECO 權利金實際上列在產品成本（cost-of-product revenue）那一行。它不會列在權利金支出（royalty payout）那一行。

Okay. Thanks very much, very helpful.

好的。非常感謝，很有幫助。

Sure. Are there any additional questions?

當然。還有其他問題嗎？

No further questions in the queue. I'd like to turn the call over to Management for any closing remarks.

佇列中沒有其他問題。我想把電話交回管理層做結語。

Thank you very much for joining us tonight. We will be in the office to take any additional questions that you have. Have a pleasant evening.

非常感謝各位今晚加入我們。我們會在辦公室，隨時回覆你們的其他問題。祝各位夜晚愉快。

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。