福泰製藥 (VRTX) 2011 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Vertex Pharmaceuticals, Incorporated first-quarter 2011 financial results conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Instructions on how to participate will be given at that time. (Operator Instructions) As a reminder, today's conference call is being recorded.

各位女士、各位先生，大家好，歡迎參加 Vertex Pharmaceuticals, Incorporated 2011 年第一季財務業績電話會議。目前所有與會者皆處於僅收聽模式。稍後我們將進行問答環節，屆時將提供參與方式說明。（接線員指示）提醒各位，今天的電話會議正在錄音。

Now, I would like to turn the conference over to your host, Michael Partridge.

現在，我想把會議交給主持人 Michael Partridge。

Thank you. Good evening, and welcome to Vertex's first quarter 2011 conference call. We are pleased to be able to review with you Vertex's achievements to date in 2011 and also highlight the further progress we anticipate in the months ahead. Since the start of this year, we have advanced our business significantly in the disease areas of hepatitis C and cystic fibrosis. Starting with hepatitis C, we intend to use the name INCIVEK as the trade name for telaprevir in the US. Last week, the advisory committee completed its review of INCIVEK and we now look forward to potential approval within weeks. We are ready for approval and believe that INCIVEK will be important for people seeking an improved treatment option for this disease.

謝謝。各位晚安，歡迎參加 Vertex 2011 年第一季電話會議。我們很高興能與各位回顧 Vertex 在 2011 年迄今的各項成果，並重點說明我們預期在未來幾個月將取得的進一步進展。自今年年初以來，我們在丙型肝炎與囊性纖維化等疾病領域大幅推進了業務。先談丙型肝炎，我們擬在美國以 INCIVEK 作為 telaprevir 的商品名。上週，諮詢委員會已完成對 INCIVEK 的審查，我們現在期待在數週內可能獲得核准。我們已為核准做好準備，並相信 INCIVEK 將為尋求更佳治療選項的患者帶來重要意義。

In cystic fibrosis, we are concluding our Phase 3 program and have seen results that suggest we have the potential to provide a substantial benefit for certain people with this disease. We anticipate global regulatory submissions in US, Europe, and Canada, including an NDA and an MAA in the second half of this year.

在囊性纖維化方面，我們正完成第三期計畫，並已看到結果顯示，我們有潛力為部分患者帶來顯著效益。我們預期今年下半年在美國、歐洲與加拿大進行全球法規申請，包括提交 NDA 與 MAA。

We remain financially strong, with a cash position of more than $820 million at the end of the first quarter, sufficient to support the anticipated launch of INCIVEK and the advancement of our pipeline.

我們的財務狀況依然穩健，第一季末現金部位超過 8.2 億美元，足以支應 INCIVEK 的預期上市以及我們研發管線的推進。

With me on the call today are Dr. Peter Mueller, who will provide a comment on the advisory committee for INCIVEK and also briefly review our pipeline progress; Nancy Wysenski, who will summarize our launch readiness for INCIVEK; Ian Smith, who will comment on our first-quarter financial results; and Matt Emmens, who will comment on our business for 2011 and beyond.

今天與我一同參與電話會議的有：Peter Mueller 醫師，他將就 INCIVEK 的諮詢委員會提供評論，並簡要回顧我們的研發管線進展；Nancy Wysenski，她將總結我們對 INCIVEK 上市準備的情況；Ian Smith，他將評論第一季財務結果；以及 Matt Emmens，他將評論我們 2011 年及未來的業務。

After the prepared remarks, we will be joined by Dr. Bob Kauffman and will be happy to take your questions. I will remind you that we are between our advisory committee meeting and our PDUFA date for INCIVEK. This means that we cannot provide any comment on INCIVEK labeling discussions. We look forward to updating you on that in the very near future. Once the call concludes, our IR team, joined by Ian, will be in the office to answer any additional questions that you have.

在預先準備的發言之後，我們將邀請 Bob Kauffman 醫師加入，並很樂意回答各位的問題。我提醒各位，我們目前正處於 INCIVEK 諮詢委員會會議與其 PDUFA 日期之間。因此，我們無法就 INCIVEK 標示（labeling）討論提供任何評論。我們期待在不久的將來向各位更新相關資訊。電話會議結束後，我們的投資人關係（IR）團隊將與 Ian 一同在辦公室，回答各位可能有的其他問題。

Finally, let me note that information discussed on this conference call includes forward-looking statements which are subject to the risks and uncertainties discussed in detail in our reports filed with the SEC, including our 10-K. GAAP and non-GAAP financial measures will be discussed on this call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available on our first-quarter 2011 financial results press release, which is now on our website. All 2010 and 2011 expenses discussed in this call exclude stock-based compensation.

最後請注意，本次電話會議所討論的資訊包含前瞻性陳述，可能受到我們向 SEC 提交之報告（包括 10-K）中詳述的風險與不確定性影響。本次電話會議將討論 GAAP 與非 GAAP 財務衡量指標。關於我們使用非 GAAP 財務衡量指標的資訊，以及這些指標與 GAAP 的調節表，已載於我們 2011 年第一季財務業績新聞稿，現已公布於我們網站。本次電話會議所討論之 2010 年與 2011 年費用均不包含以股票為基礎之薪酬。

Thank you, and I will now turn the call over to Peter.

謝謝，現在我把電話會議交給 Peter。

Thank you, Michael, and good evening, everyone. It is a real pleasure to start today's call. As Michael noted, we are coming just off a positive FDA advisory committee meeting. And we prepared for this meeting for several months and I think I speak for everyone at Vertex when I say that we are excited to finally be within a few steps of the finish line. The PDUFA date, which is the target date for the FDA to make a decision regarding approval, is May 23. We are now working closely with the FDA on the potential label for INCIVEK.

謝謝你，Michael，各位晚安。很高興能開始今天的電話會議。如 Michael 所提，我們剛結束一場正面的 FDA 諮詢委員會會議。我們為這次會議準備了好幾個月，我想我代表 Vertex 的每一位同仁表示，我們很興奮終於只差幾步就能抵達終點線。PDUFA 日期，也就是 FDA 針對是否核准作出決定的目標日期，是 5 月 23 日。我們目前正與 FDA 密切合作，討論 INCIVEK 的潛在標示內容。

As we progress in 2011, we continue to be focused on advancing the significant opportunities in our pipeline. In the coming months, we expect to report 48-week results from our Phase 3 ENVISION trial for VX-770 in children with cystic fibrosis. We also expect to announce data from our Phase 2 combination study of VX-809 and VX-770 in cystic fibrosis. In the second half of the year, we plan to submit the NDA and MAA for VX-770. We expect to report the first data from VX- 509, our JAK3 inhibitor in rheumatoid arthritis. And we also expect to initiate additional trials in hepatitis C, cystic fibrosis, and epilepsy. So as you can see, 2011 is a very busy year for us, from a developmental and regulatory standpoint, and a number of important events are approaching.

隨著 2011 年的推進，我們仍專注於推動研發管線中的重大機會。在未來幾個月，我們預期將公布 VX-770 於囊性纖維化兒童族群之第三期 ENVISION 試驗的 48 週結果。我們也預期將公布 VX-809 與 VX-770 在囊性纖維化的第二期合併用藥研究數據。今年下半年，我們計畫提交 VX-770 的 NDA 與 MAA。我們預期將公布 VX-509（我們用於類風濕性關節炎的 JAK3 抑制劑）的首批數據。我們也預期將在丙型肝炎、囊性纖維化與癲癇領域啟動更多試驗。因此各位可以看到，從研發與法規角度而言，2011 年對我們來說非常忙碌，且多項重要事件即將到來。

Let me focus now on hepatitis C first. With completion of the advisory committee meeting last week, we are in position for an FDA decision within the next few weeks. At the meeting, the committee members voted unanimously that clinical benefits of INCIVEK outweigh the risk in a broad group of people with genotype 1 hepatitis C. An important aspect of the discussion with the FDA regarding our NDA submission in the meeting was updated SVR rates of 79% in treatment naive patients upon which we and the FDA agreed. We believe that this high viral cure rate is both an important treatment modulator for patients and a high bar for future regimens.

我先聚焦於丙型肝炎。隨著上週諮詢委員會會議的完成，我們已具備在未來幾週內獲得 FDA 決定的條件。在會議中，委員一致投票認為，對於廣泛的第 1 型基因型丙型肝炎患者，INCIVEK 的臨床效益大於風險。會議中與 FDA 就我們 NDA 申請所討論的一個重要面向，是更新後的 SVR（持續病毒學反應）比率：在初治患者中為 79%，此數據已獲我們與 FDA 共同同意。我們相信，這樣的高病毒治癒率對患者而言是重要的治療變革，也為未來療法樹立了很高的門檻。

Also, at the meeting the panel recommended that an educational program be put in place to manage the risks associated with regimens containing INCIVEK primarily focused on rash and anemia. We agree this will be important and I am pleased to say that our team has been working the past several months to develop educational tools. Also, I would like to note that toward the end of the outcome session, the panel strongly suggested that the therapy, including direct-acting antivirals, should be considered the new standard of care. We appreciate that the FDA seeks advice from the outcome, but it is not required to follow its recommendation.

此外，在會議中，專家小組建議建立一項教育計畫，以管理含 INCIVEK 療程相關的風險，主要聚焦於皮疹與貧血。我們同意這點很重要，也很高興地表示，我們的團隊在過去幾個月一直在開發教育工具。另外我也想指出，在結果討論環節接近尾聲時，專家小組強烈建議，包含直接作用型抗病毒藥物在內的治療應被視為新的照護標準。我們理解 FDA 會向該小組徵詢建議，但 FDA 並不必須遵循其建議。

With respect to education and competition, we believe that the introduction of more than one new hepatitis C regimen will be a positive for patients and healthcare providers, as this increases the amount of disease awareness and educational information available. As for the process we have ongoing with the FDA, I will not make any further comments about the outcome or regulatory path for INCIVEK.

就教育與競爭而言，我們相信，推出不只一種新的丙型肝炎療程將對患者與醫療照護提供者帶來正面影響，因為這會提高疾病認知並增加可取得的教育資訊。至於我們目前與 FDA 進行中的流程，我將不再就 INCIVEK 的結果或法規路徑作進一步評論。

In the meantime, we continue to receive positive feedback regarding INCIVEK's clinical data. We look forward to the Digestive Disease Week Conference in Chicago, which kicks off at the end of this week. DDW is the largest meeting in the world for GI professionals, and we have 10 abstracts related to INCIVEK scheduled for presentation. In addition to finalizing the regulatory process for INCIVEK, we are focused on the next evolution of hepatitis C treatment, including the potential to further shorten treatment duration for the entire regimen to 12 weeks, with similar high viral cure rates.

同時，我們持續收到對 INCIVEK 臨床數據的正面回饋。我們期待本週末在芝加哥登場的消化疾病週（Digestive Disease Week）會議。DDW 是全球規模最大的胃腸（GI）專業人士會議，我們安排了 10 篇與 INCIVEK 相關的摘要將進行發表。除了完成 INCIVEK 的法規流程外，我們也專注於丙型肝炎治療的下一階段演進，包括有機會將整體療程的治療時間進一步縮短至 12 週，同時維持類似的高病毒治癒率。

One area we are exploring in a trial we expect to start in the third quarter is 12 weeks of INCIVEK in combination with pegylated-interferon ribavirin for people who have a specific polymorphism known as CC near the IL28B gene. We presented data recently at the EASL conference that showed patients with that polymorphism were highly responsive to a triple regimen containing INCIVEK, suggesting that 12 weeks of total treatment may be possible. We estimate that close to one-third of people who have not been treated for the hepatitis C have this marker.

我們正在探索的一個方向，是在預期第三季啟動的試驗中，針對在 IL28B 基因附近具有特定多型性（polymorphism），即所謂 CC 型的患者，評估 12 週 INCIVEK 合併聚乙二醇化干擾素與利巴韋林（pegylated-interferon ribavirin）的療程。我們近期在 EASL 會議上發表的數據顯示，具有該多型性的患者對包含 INCIVEK 的三合一療程反應非常良好，顯示總治療 12 週可能可行。我們估計，約有接近三分之一未曾接受丙型肝炎治療的人具有此標記。

As you all know, another area where we are exploring 12 weeks of treatment is the combination of VX-222, our polymerase inhibitor, with INCIVEK pegylated-interferon ribavirin. This Phase 2 combination trial includes 2-drug regiments that are response-guided towards 12- or 24-week duration. As part of this Phase 2 combination study, enrollment is underway for a triple interferon sparing regimen with INCIVEK, VX-222 and ribavirin. We look forward to the first post-treatment data from the quarter arms of this study and on-treatment data from the triple therapy arm in the second half of this year. These data will inform us of our next steps in advancing this potential hepatitis C treatment regimen.

各位都知道，我們探索 12 週治療的另一個領域，是將 VX-222（我們的聚合酶抑制劑）與 INCIVEK、聚乙二醇化干擾素及利巴韋林合併使用。這項第二期合併試驗包含 2 藥物方案，並依反應導向（response-guided）設定為 12 或 24 週療程。作為此第二期合併研究的一部分，一項以 INCIVEK、VX-222 與利巴韋林組成、可免用干擾素（interferon sparing）的三合一療程正在進行收案。我們期待在今年下半年取得本研究各組別於治療後的首批數據，以及三合一治療組於治療期間的數據。這些數據將協助我們決定推進此潛在丙型肝炎治療方案的下一步。

So let me now turn to 3 key highlights from our cystic fibrosis program. First, I want to highlight 770. In the first quarter, we announced that VX-770 showed profound improvement in lung function and other measures of disease across several age groups, including children as young as 6, in 2 separate pivotal trials.

接下來我將談我們囊性纖維化計畫的 3 項關鍵重點。第一，我想強調 770。在第一季，我們宣布 VX-770 在兩項獨立的關鍵性試驗中，於多個年齡層（包括年僅 6 歲的兒童）展現了肺功能及其他疾病衡量指標的顯著改善。

We are also very pleased with the safety profile shaping up for VX-770, specifically VX-770 was generally well tolerated with a lower rate of adverse events in the VX-770 treatment groups compared to control. We think our pivotal data support a clear regulatory pathway for people with the G551DCFTR mutation, which represents approximately 4% of people with cystic fibrosis. We hope that with VX-770, we can provide the first treatment option that targets the underlying disease and not just the symptoms.

我們也對 VX-770 逐步成形的安全性概況感到非常滿意；具體而言，VX-770 整體耐受性良好，且 VX-770 治療組的不良事件發生率低於對照組。我們認為，我們的關鍵性數據支持針對帶有 G551D CFTR 突變患者的明確法規審查路徑，該族群約占囊性纖維化患者的 4%。我們希望透過 VX-770，能提供第一個針對疾病根本原因、而不僅僅是症狀的治療選項。

VX-770 remains on track for an NDA submission in the US and an MMA submission in Europe in the second half of the year, in people with G551D mutations. Our submissions will be focused on this specific mutation first and will include 48-week data from both the STRIVE trial in people aged 12 and older and the ENVISION trial in people aged 6 to 11. We are also planning to include data from the Phase 2 DISCOVER trial evaluating the safety of VX-770 in people with the F508del mutation, the most common CFTR mutation. Our submission will also include 2-year carcinogenesis studies.

VX-770 仍按計畫於今年下半年在美國提交 NDA、並在歐洲提交 MMA，適用於具有 G551D 突變的患者。我們的申請將先聚焦於此一特定突變，並將納入 STRIVE 試驗（12 歲及以上）與 ENVISION 試驗（6 至 11 歲）兩項研究的 48 週數據。我們也計畫納入第 2 期 DISCOVER 試驗的數據，該試驗評估 VX-770 在帶有 F508del 突變（最常見的 CFTR 突變）患者中的安全性。我們的申請也將包含為期 2 年的致癌性研究。

I want to take this time to be clear on our plans for use of VX-770 monotherapy in non-G551D mutations. We continue to conduct in vitro studies, evaluating the potential of VX-770 monotherapy to address people with other CFTR mutations that may have a similar modality to the G511D mutation. We expect to use this information to initiate either new clinical trials in people with non-G551D mutation, as well as further our discussions with regulatory agencies.

我想藉此時間清楚說明我們對於在非 G551D 突變中使用 VX-770 單藥治療的計畫。我們持續進行體外研究，評估 VX-770 單藥治療是否有潛力幫助具有其他 CFTR 突變、且其作用機制可能與 G511D 突變相似的患者。我們預期將運用這些資訊，啟動針對非 G551D 突變患者的新臨床試驗，並推進我們與監管機構的進一步討論。

Second, I will highlight an upcoming CF medical conference. Four abstracts have been accepted for presentation at the European Cystic Fibrosis Conference, June 8 to 11, including Phase 3 data from STRIVE and Phase 2 data from DISCOVER, as well as data related to in vitro studies of VX-770. We have additional plans to present data for VX-770 in other medical venues this year.

第二，我要提及即將舉行的一場囊性纖維化（CF）醫學會議。共有四篇摘要獲選於 6 月 8 日至 11 日的歐洲囊性纖維化會議發表，其中包括 STRIVE 的第 3 期數據與 DISCOVER 的第 2 期數據，以及與 VX-770 體外研究相關的數據。我們今年也規劃在其他醫學場合發表 VX-770 的更多數據。

Third, I will highlight our combination therapy work. The Phase 3 data from VX-770 in G551D patients validated our approach of targeting CFTR, enabling us to initiate trials in other mutations. Specifically, with regard to efforts to expand the treatment of CF in people with the F508del mutation, we are conducting part 1 of a Phase 2 combination study with VX-809 and VX-770.

第三，我要強調我們的聯合療法工作。VX-770 在 G551D 患者中的第 3 期數據驗證了我們以 CFTR 為標的的策略，使我們得以在其他突變中啟動試驗。具體而言，為了將 CF 的治療擴展至帶有 F508del 突變的患者，我們正在進行 VX-809 與 VX-770 的第 2 期聯合研究第 1 部分。

This combination study has an adaptive design and the decision to move forward into part 2 will be driven by data. The primary end points of that study are safety and change in sweat chloride when VX-770 is combined with VX-809. Based on the design of the study with 14 days of VX-809 [monitor people] followed by 7 days of combination with VX-770, we will be looking to see whether VX-770 provides an additional response in sweat chloride compared to VX-809 alone, which would be consistent with what we observed in our in vitro studies. We are on track to announce interim data this quarter. Depending on results from this study, we plan to start part 2 in the second half of this year that may involve investigation of other doses and longer durations of VX-770 and VX-809 combinations, as well as a larger number of patients with the F508del mutation.

這項聯合研究採用適應性設計，是否推進至第 2 部分將由數據驅動。該研究的主要終點為安全性，以及當 VX-770 與 VX-809 併用時汗氯的變化。根據研究設計，先給予 VX-809 14 天[監測受試者]，再與 VX-770 併用 7 天；我們將觀察相較於單用 VX-809，VX-770 是否能在汗氯方面帶來額外反應，這將與我們在體外研究中的觀察一致。我們按計畫將於本季公布期中數據。視研究結果而定，我們計畫於今年下半年啟動第 2 部分，可能會探討 VX-770 與 VX-809 聯合用藥的其他劑量與更長療程，並納入更多帶有 F508del 突變的患者。

Another development for our CF program in the first quarter was the expansion of our existing collaboration with the Cystic Fibrosis Foundation to support development of a second corrector VX-661 and for accelerated discovery and development of next generation correctors. We believe it is very prudent to investigate multiple opportunities to treat a broad set of people with cystic fibrosis. By working with the CF Foundation, we not only have additional financial support, but also benefit from a network of caregivers, clinical sites, and patients. We expect to start a Phase 2 study with VX-661 in people with the F508del mutation by the end of this year.

我們 CF 計畫在第一季的另一項進展，是擴大與囊性纖維化基金會（Cystic Fibrosis Foundation）的既有合作，以支持第二種校正劑 VX-661 的開發，並加速新一代校正劑的發現與開發。我們認為，審慎地探索多種機會以治療更廣泛的囊性纖維化患者族群非常重要。透過與 CF 基金會合作，我們不僅獲得額外的財務支持，也能受益於照護者、臨床試驗中心與患者的網絡。我們預期將於今年年底前在帶有 F508del 突變的患者中啟動 VX-661 的第 2 期研究。

I have just highlighted our lead programs in hepatitis C and cystic fibrosis. Behind these programs is a robust pipeline. The first reported data from our Phase 2 trial of VX-765 in epilepsy, 60 patients who had a history of being resistant to current therapy were enrolled in the trial. People who do not respond to standard medicines for epilepsy are often severely debilitated by frequent seizures that limit daily activities and independence. Results from the study were an important step forward towards understanding the potential role of VX-765 in helping people with severe epilepsy, and we expect to start a larger and longer-duration study in epilepsy as early as the fourth quarter of 2011.

我剛才重點介紹了我們在 C 型肝炎與囊性纖維化方面的領先計畫。在這些計畫背後，是一條強健的研發管線。我們在癲癇適應症中對 VX-765 的第 2 期試驗首次公布的數據顯示，該試驗納入了 60 名對現有治療具有抗藥史的患者。對標準癲癇藥物無反應的患者，往往因頻繁癲癇發作而嚴重失能，限制日常活動與獨立性。該研究結果是理解 VX-765 在協助重度癲癇患者方面潛在角色的重要一步；我們預期最早於 2011 年第四季在癲癇領域啟動一項規模更大、療程更長的研究。

For VX-509, our JAK3 inhibitor, we have completed enrollment of approximately 200 patients in an ongoing Phase 2 trial in rheumatoid arthritis. We expect to announce clinical data from this study, including safety, tolerability, and clinical efficacy in the third quarter of this year.

就 VX-509（我們的 JAK3 抑制劑）而言，我們已完成一項正在進行的類風濕性關節炎第 2 期試驗之約 200 名患者的入組。我們預期將於今年第三季公布該研究的臨床數據，包括安全性、耐受性與臨床療效。

With that, I would like to end my remarks, but let me summarize. Following our advisory committee meeting, we are now working closely with the FDA on the potential label for INCIVEK. We are excited about our lead medicine VX-770 in cystic fibrosis. And operationally, we are preparing for the submission of the NDA and MMA in the second half of this year. We are evaluating opportunities to further advance treatment regimens of hepatitis C and cystic fibrosis, and are conducting or plan to conduct several trials in these disease areas as we go forward. At the same time, we remain committed to our strong research engine and expect additional candidates to emerge in 1 or more disease area later this year.

說到這裡，我想結束我的發言，但先做個總結。在諮詢委員會會議之後，我們目前正與 FDA 密切合作，討論 INCIVEK 的潛在標籤。我們對囊性纖維化領域的主力藥物 VX-770 感到振奮。在營運層面，我們正為今年下半年提交 NDA 與 MMA 做準備。我們正在評估進一步推進 C 型肝炎與囊性纖維化治療方案的機會，並且在這些疾病領域進行或計畫進行多項試驗。同時，我們仍致力於強大的研發引擎，並預期今年稍晚在一個或多個疾病領域會有更多候選藥物浮現。

Thank you very much, and I will now turn the call over to Nancy.

非常感謝，接下來我把電話會議交給 Nancy。

Thanks, Peter. I would like to echo Peter's comments regarding the advisory committee meeting. I am equally as pleased with the unanimous vote supporting the safety and efficacy profile of INCIVEK. Our studies, we believe, showed a compelling profile for a regimen containing INCIVEK. Based on our market research, we believe the simplicity of this regimen, the high SVR rates regardless of race or ethnicity, stage of disease, and prior treatments, coupled with shorter duration for the majority of treatment-naive patients, and a manageable safety profile will be appreciated by both patients and healthcare providers.

謝謝你，Peter。我想呼應 Peter 對諮詢委員會會議的評論。我同樣對一致投票支持 INCIVEK 的安全性與有效性概況感到非常滿意。我們相信，我們的研究顯示出包含 INCIVEK 的治療方案具有令人信服的概況。根據我們的市場調查，我們認為，該方案的簡便性、在不論種族或族裔、疾病分期與既往治療情況下皆具高 SVR 比例，再加上對多數初治患者而言療程更短，以及可管理的安全性概況，將會受到患者與醫療照護提供者的肯定。

We're looking forward to the planned launch of INCIVEK and executing on the marketing and commercial plans we have in place. Following approval, a major focus of our efforts will be on offering information to patients and healthcare providers to educate them on the potential benefits and risks of INCIVEK, in combination with pegylated-interferon and ribavirin, to ensure people with hepatitis C have the best possible chance for a viral cure.

我們期待 INCIVEK 的計畫上市，並落實我們既定的行銷與商業化計畫。獲批後，我們工作的重點之一將是向患者與醫療照護提供者提供資訊，教育他們在與聚乙二醇化干擾素（pegylated-interferon）及利巴韋林（ribavirin）聯合使用時，INCIVEK 的潛在效益與風險，以確保 C 型肝炎患者擁有最佳機會達成病毒治癒。

On the commercial front, we've been executing on 4 key priorities this year. Number 1, hiring an experienced and talented group of people across the commercial organization who are focused on ensuring a robust launch. To date, we've hired approximately 200 field-based employees, which include about 115 in field sales. Number 2, training our field force, who will be key in educating providers and unlocking the substantial potential of INCIVEK in the hepatitis C community. 3, initiating and expanding our hepatitis C disease awareness campaigns to provide information to the general public.

在商業化方面，我們今年一直在推進四項關鍵優先事項。第一，於整個商業組織中招募一支經驗豐富且才華出眾的團隊，專注於確保成功上市。迄今為止，我們已聘用約 200 名外勤員工，其中包括約 115 名外勤銷售人員。第二，訓練我們的外勤團隊，他們將在教育醫療提供者並釋放 INCIVEK 在 C 型肝炎社群中的巨大潛力方面扮演關鍵角色。第三，啟動並擴大我們的 C 型肝炎疾病認知宣導活動，向一般大眾提供資訊。

And, 4, importantly, creating Vertex's first patient-assistance program to help people with hepatitis C who might otherwise have a hard time getting INCIVEK because of financial constraints. I'm happy to tell you that this comprehensive program will enable us to help people in a number of ways, including providing reimbursement support and free medicine for qualified patients. I'll talk more about this program after approval.

第四，也是非常重要的一點，建立 Vertex 的第一個患者援助計畫，協助那些因財務限制而可能難以取得 INCIVEK 的 C 型肝炎患者。我很高興告訴各位，這項全面性的計畫將使我們能以多種方式提供協助，包括提供給付/報銷支援，以及為符合資格的患者提供免費藥物。我會在獲批後再更詳細介紹這個計畫。

We've recently gone live with a disease awareness campaign, which includes a nurse hotline, radio ads, media and print placements, as well as the website, www.BetterToKnowC.com. Through this venue, we intend to increase awareness of hepatitis C and Vertex. And the community is responding. Since kicking off the campaign in March, we've already had more than 61,000 unique visits to our website, more than 2,200 calls into the nurse support line, and approximately 1,600 views of our educational video on hepatitis C on YouTube. We're learning there is a real demand for information and further resources for people suffering from hepatitis C.

我們最近已正式推出一項疾病認知宣導活動，內容包括護理師專線、廣播廣告、媒體與平面投放，以及網站 www.BetterToKnowC.com。透過這個平台，我們希望提升對 C 型肝炎以及 Vertex 的認知，而社群也正在回應。自 3 月啟動活動以來，我們的網站已累計超過 61,000 次不重複造訪、護理師支援專線接獲超過 2,200 通來電，且我們在 YouTube 上的 C 型肝炎衛教影片觀看次數約 1,600 次。我們了解到，C 型肝炎患者對資訊與更多資源確實有強烈需求。

Our ultimate goal is to provide specific resources to help diagnose and treat people with hepatitis C and help to bring them to the successful outcome that patients and their families, providers, and payers all want. We have an outstanding team in place and we're excited about INCIVEK and we look forward with great anticipation to the potential launch in the US.

我們的最終目標是提供具體資源，協助 C 型肝炎患者的診斷與治療，並幫助他們達成患者及其家屬、醫療提供者與支付方都希望看到的成功結果。我們已建立一支出色的團隊，對 INCIVEK 感到振奮，並非常期待其在美國潛在上市。

Now, turning to cystic fibrosis. We have begun the hiring of key commercial staff for VX-770, including a general manager for Europe. If approved, we're committed to launching VX-770 and potentially other medicines for cystic fibrosis on a worldwide basis. And we're establishing a global commercial infrastructure to support that approach. Cystic fibrosis is an orphan disorder, with approximately 70,000 patients in the US and Europe; there are more than 2,000 people with the G551D mutation alone. This is a unique, highly concentrated commercial model that will enable us to meet the needs of providers and patients by building a focused marketing operation, with a sales team of approximately 40 people supporting the global use of VX-770. Thank you for your time, and I'll now turn the call over to Ian.

現在，轉到囊性纖維化。我們已開始為 VX-770 招募關鍵商業人員，包括歐洲的總經理。若獲核准，我們承諾在全球範圍內推出 VX-770，並可能推出其他囊性纖維化藥物。我們也正在建立全球商業基礎設施以支持這一策略。囊性纖維化屬於罕見疾病，在美國與歐洲約有 70,000 名患者；僅 G551D 突變就有超過 2,000 人。這是一種獨特且高度集中的商業模式，將使我們能透過建立聚焦的行銷運作來滿足醫療提供者與患者的需求，並由約 40 人的銷售團隊支援 VX-770 的全球使用。感謝各位撥冗，我現在把電話交給 Ian。

Thanks, Nancy, and good evening to everyone. Once again, we ended the quarter in a strong financial position, with more than $820 million in cash, cash equivalents, and marketable securities. The solid financial footing is where we had hoped to be and support the planned launch of INCIVEK in the coming weeks, while maintaining our investment in other disease areas.

謝謝你，Nancy，各位晚安。本季我們再次以強勁的財務狀況作結，現金、約當現金與有價證券合計超過 8.2 億美元。這樣穩健的財務基礎符合我們的期待，並可支援未來幾週內計畫推出 INCIVEK，同時維持我們在其他疾病領域的投資。

It's a challenge to launch 1 new major medicine and we have the potential to launch 2 and advance the pipeline. This requires investment, and we're in good financial position to support this required investment as we transition to a cash flow positive Company. The business model we aspire to is tried and true, although somewhat rarely achieved. We focus on important drugs for serious diseases in specialty-driven markets. These drugs require significant investment, but they also offer the potential for high returns. The bottom line, we are committed to being a financial performer.

推出 1 款新的重大藥物本身就是一項挑戰，而我們有機會推出 2 款並推進研發管線。這需要投資，而在我們轉型為現金流轉正的公司之際，我們具備良好的財務狀況來支援所需投資。我們所追求的商業模式已被反覆驗證、行之有效，雖然相對少見。我們聚焦於專科驅動市場中、用於嚴重疾病的重要藥物。這些藥物需要大量投資，但也提供高報酬的潛力。總而言之，我們承諾成為財務表現優異的公司。

With that backdrop, let me turn to the first-quarter results. I'm going to cover the loss components of our financials on today's call. You may refer to our press release for the further details about our financial results.

在此背景下，讓我轉到第一季的結果。今天的電話會議中，我將說明我們財務報表中的虧損構成。關於財務結果的更多細節，請參閱我們的新聞稿。

Specifically, our GAAP net loss in the first quarter of 2011 was approximately $176 million. This compares to the first quarter of 2010 loss of approximately $165 million. When comparing the first-quarter 2011 non-GAAP loss to the first quarter of 2010, our increased loss was approximately $184 million from approximately $140 million. The change was principally attributable to costs to support the planned launch of INCIVEK, including SG&A costs. The mainline actions within our income statements can be found in our first-quarter press release.

具體而言，我們 2011 年第一季的 GAAP 淨損約為 1.76 億美元；相較之下，2010 年第一季的虧損約為 1.65 億美元。比較 2011 年第一季的非 GAAP 虧損與 2010 年第一季，我們的虧損由約 1.40 億美元增加至約 1.84 億美元。此變動主要歸因於支援 INCIVEK 計畫上市的成本，包括銷售、一般及行政（SG&A）費用。損益表中的主要項目可在我們第一季新聞稿中查閱。

Before I conclude, we are reiterating our operating expense guidance we provided earlier this year. Specifically, we guided to 2011 total operating expenses, principally those of R&D and SG&A expense, but excluding cost of revenues and stock compensation, and we reiterate our guidance in the range of $890 million to $930 million.

在我結束之前，我們重申今年稍早提供的營運費用指引。具體而言，我們對 2011 年總營運費用（主要為研發與 SG&A 費用，但不含營收成本與股票薪酬）之指引維持不變，區間為 8.9 億至 9.3 億美元。

In summary, we are committed to leveraging our business model to achieve positive operating cash flow and earnings with INCIVEK, while making the investments necessary for potential future successes in our current and future disease areas. Thank you, and Matt, over to you.

總結來說，我們承諾運用我們的商業模式，透過 INCIVEK 實現正向的營運現金流與獲利，同時進行必要投資，以支持我們在現有與未來疾病領域中潛在的後續成功。謝謝，Matt，交給你。

Thanks, Ian, and good evening, everyone. You have just heard from the team about our accomplishments since the beginning of the year, as well as our milestones for the remainder of this year. I hope you took away from their remarks a true understanding of the breadth of Vertex and the transformational potential our clinical programs may create for patients, the Company, and our shareholders.

謝謝你，Ian，各位晚安。各位剛剛聽到團隊分享我們自年初以來的成果，以及今年剩餘時間的里程碑。我希望各位從他們的發言中，能真正理解 Vertex 的廣度，以及我們的臨床計畫可能為患者、公司與股東帶來的轉型性潛力。

Looking at the big picture, we are proud of the Company that we are building and we believe we are positioned for long-term growth. We have spent more than $4 billion over the past 22 years to discover and test new medicines with the goal of developing breakthroughs that make a real difference for people with serious diseases. As a result of the hard work of Vertex's scientists and clinicians, we now have 2 lead medicines, 1 in hepatitis C, and 1 in cystic fibrosis, that have the potential to change the way these diseases are treated. We believe we have established the foundation for a sustainable business that will continue to grow and enable us to discover and develop more breakthroughs.

從大局來看，我們為正在打造的公司感到自豪，並相信我們已具備長期成長的定位。過去 22 年來，我們投入超過 40 億美元用於發現與測試新藥，目標是開發能為嚴重疾病患者帶來真正改變的突破性療法。由於 Vertex 科學家與臨床人員的努力，我們目前有 2 款領先藥物：1 款用於 C 型肝炎，1 款用於囊性纖維化，皆有潛力改變這些疾病的治療方式。我們相信已建立可持續的業務基礎，將持續成長並使我們能發現與開發更多突破。

If I may, I would like to repeat a couple of statements from the panel members during the vote at the INCIVEK advisory committee meeting held last week. One member said that INCIVEK was a huge advancement. And another said -- I would like to congratulate the sponsor on a very well-done and thoughtful presentation. Thank you as a hepatologist for the elegant simplicity of the regimen and making the telaprevir dosage so short that if there are any adverse events they can be well managed.

如果可以的話，我想重述上週舉行的 INCIVEK 諮詢委員會會議投票期間，委員們的幾句話。有一位委員表示 INCIVEK 是一項巨大的進步。另一位則表示——我想祝賀申辦方做了一場非常出色且深思熟慮的簡報。作為一名肝病專科醫師，感謝你們在療程設計上的優雅簡潔，並將 telaprevir 的給藥時間縮短到如此程度，以致即使出現任何不良事件也能妥善管理。

So, even as we anticipate the launch of INCIVEK in the coming weeks, we are committed to helping people with hepatitis C and their healthcare providers over the long term, and see opportunities to future advance our leadership. We are evaluating ways to expand INCIVEK's profile and broaden the potential benefits of this medicine with the study of BID dosing, exploring additional subsets of patients, such as HIV and hepatitis C co-infection, pre- and post-liver transplants, and perhaps shortening treatment duration even further, while maintaining high viral cure rates.

因此，即使我們預期在未來幾週推出 INCIVEK，我們仍承諾長期協助 C 型肝炎患者及其醫療照護提供者，並看到未來進一步鞏固領導地位的機會。我們正在評估擴大 INCIVEK 產品定位並拓展其潛在效益的方法，包括研究每日兩次（BID）給藥、探索更多患者亞群（例如 HIV 與 C 型肝炎共感染者、肝臟移植前後患者），以及在維持高病毒治癒率的同時，或許進一步縮短治療時間。

Before I move on to CF, I would like to recognize and express my thanks to our entire R&D group who participated in or helped the team prepare for INCIVEK's advisory committee meeting. I would also like to thank all of the investigators and clinical staff and patients who participated in INCIVEK trials over the last 7 years. Folks, we are almost there.

在我轉到囊性纖維化之前，我想先表達對整個研發團隊的肯定與感謝，他們參與了 INCIVEK 諮詢委員會會議，或協助團隊進行準備。我也要感謝過去 7 年參與 INCIVEK 試驗的所有研究者、臨床人員與患者。各位，我們就快到了。

I would like now to take a moment to comment on our cystic fibrosis program. The results of the Phase 3 registration program for VX-770 exceeded our expectations for people with CF and the G551D mutation. Cystic fibrosis can be devastating for people and their families, particularly when current therapies don't address the underlying causes of this disease. We believe the profile we showed for VX-770 in Phase 3 for people with the G551D mutation has the potential, if approved, to make a profound impact in the care of patients living with this disease. We know we have more to do to further exploit our scientific leadership in investigating the underlying causes of this disease for the benefit of those with CF who do not have the G551D mutation.

我現在想花一點時間評論我們的囊性纖維化計畫。VX-770 的第三期註冊試驗結果，對於帶有 G551D 突變的囊性纖維化患者而言，超出我們的預期。囊性纖維化對患者及其家庭可能是毀滅性的，尤其是在現有療法無法處理此疾病根本原因時。我們相信，VX-770 在第三期針對 G551D 突變患者所展現的特性，若獲核准，將有潛力對此疾病患者的照護帶來深遠影響。我們也知道，為了讓不具 G551D 突變的囊性纖維化患者受益，我們仍需做更多工作，以進一步發揮我們在探究此疾病根本原因方面的科學領導力。

Important to that effort are trials that are underway or planned in the F508del mutation using a combination of our CFTR modulators. Almost 90% of children and adults have at least 1 copy of the F508del mutation. The recent signing of our new collaboration with the CF Foundation underscores our commitment to this orphan disease, and we and the CF Foundation are more focused than ever on determining how we can help improve the lives of a greater number of people living with cystic fibrosis.

對此努力而言，關鍵在於目前進行中或規劃中的 F508del 突變試驗，將使用我們的 CFTR 調節劑組合療法。近 90% 的兒童與成人至少帶有 1 份 F508del 突變拷貝。近期我們與囊性纖維化基金會（CF Foundation）簽署新的合作協議，凸顯我們對這項罕見疾病的承諾；我們與基金會比以往更專注於釐清如何協助更多囊性纖維化患者改善生活。

Finally, we have other opportunities behind hepatitis C and cystic fibrosis to make a difference for patients and grow our Company. Specifically, we have robust clinical programs ongoing for VX-765 in epilepsy and VX-509 in rheumatoid arthritis, and we anticipate adding new medicines in new disease areas to our clinical pipeline later this year.

最後，在 C 型肝炎與囊性纖維化之外，我們還有其他機會為患者帶來改變並推動公司成長。具體而言，我們針對癲癇的 VX-765 與針對類風濕性關節炎的 VX-509 皆有強健的臨床計畫正在進行中，並預期在今年稍晚將新藥納入新的疾病領域，擴充我們的臨床研發管線。

I would also like to make one comment. I spent last night and several times over the last several weeks with our new field force, and I can't tell you how excited and competent these people are. They are literally biting at the bit to get out there once our drug is approved. We have a clear goal of discovering, developing and launching breakthrough medicines. I continue to believe this is the best way to enhance and grow our business. Thank you, and I will now turn the call back to Michael.

我也想補充一點。昨晚以及過去幾週的數次，我都與我們新的外勤團隊共度時間；我無法充分形容這些人有多興奮且能力出眾。一旦藥物獲核准，他們真的迫不及待要走出去。我們有明確目標：發現、開發並推出突破性藥物。我仍然相信，這是強化並擴大我們業務的最佳方式。謝謝，我現在把電話交回 Michael。

Thank you, Matt. For anyone who joined the call late, I'll just reiterate, we won't be able to comment on the label discussions we are having with the FDA. We are nevertheless happy to take your questions related to other aspects of the business. Thank you, and we will now open up the call to Q&A.

謝謝你，Matt。對於較晚加入電話會議的各位，我再重申一次：我們無法評論目前與 FDA 進行的標籤（label）討論。不過，我們很樂意回答各位關於業務其他面向的問題。謝謝，現在我們開放問答（Q&A）。

(Operator Instructions) Geoffrey Porges of Bernstein.

（接線員指示）Bernstein 的 Geoffrey Porges。

Thanks very much for taking the question. Focus on CF a little bit, Peter, first, could you comment on whether your further analysis of STRIVE, DISCOVER, and what you have for ENVISION, in that analysis, how strong is the correlation between sweat chloride change FEV-1. And specifically have you been able to establish a threshold as a percentage of millimole change in sweat chloride associated with or predictive of lung function change? And then maybe if I could just ask a question on CF after that. Could you start off with that?

非常感謝讓我提問。先把焦點放在囊性纖維化（CF）上，Peter，首先你能否評論一下，你們對 STRIVE、DISCOVER，以及你們在 ENVISION 中所掌握資料所做的進一步分析中，汗氯（sweat chloride）變化與 FEV-1 之間的相關性有多強？更具體地說，你們是否已能建立一個門檻值——以汗氯變化的毫摩爾（millimole）百分比來表示——其與肺功能變化相關或具有預測性？然後如果可以的話，我之後還想再問一個關於 CF 的問題。你能先從這個開始嗎？

Hi, Geoff, it's Peter speaking now. Thanks for the question. So there were a whole bunch of questions in this entire thing. So first, I think what we can say is, at this given point in time, we have at least a first insight that sweat chloride might be correlated with FEV. I think that was the first trials ever that showed the potential correlation. Statistically significant, obviously you cannot easily do this at this point in time and you have to have a deeper insight. I think we will evaluate as we go forward how we basically built a correlation between sweat chloride and other parameters to describe basically a functional benefit, whether it's lung functions or other functions that are impacted in that disease. I think it's a more complicated picture. So that's that point.

嗨，Geoff，我是 Peter。謝謝你的問題。這裡面其實有一大堆問題。首先，我想我們可以說的是，在目前這個時間點，我們至少得到第一個初步洞見：汗氯（sweat chloride）可能與 FEV 相關。我想這是首次試驗顯示出這種潛在相關性。當然在統計上是顯著的，但你在目前這個時間點不可能很容易就把這件事做得很完整，還需要更深入的理解。我想我們會在往前推進的過程中評估，如何在汗氯與其他參數之間建立相關性，以描述功能性獲益——不論是肺功能或是此疾病影響到的其他功能。我認為這是一個更複雜的圖像。這就是那一點。

But I think there is a trend that if sweat chloride goes down, you might have a possibility to see a therapeutic benefit. But I cannot give, because at this given point in time those are not basically existing, and I think you can speculate on whatever you want, because there's historical data that show that if you get, and you can look into those, the published, you get to about a 10% lowering in sweat chloride you might see a therapeutic benefit in different strengths, depending where you are with your disease.

但我認為有一個趨勢是，如果汗氯下降，你可能有機會看到治療獲益。不過我無法給出（更明確的說法），因為在目前這個時間點，這些（對應關係）基本上還不存在；而且我想你可以就任何你想的去推測，因為有一些歷史數據顯示，如果你達到——你也可以去看那些已發表的資料——大約 10% 的汗氯降低，你可能會看到不同強度的治療獲益，取決於你的疾病處於什麼階段。

Okay. And could I just follow up. It sounds as though there's a change in your tone on G551D and the likely label, the application in the label for VX-770. It sounds as though the discussions with the Agency have moved towards it being a G551D only application. Is that a reasonable interpretation? And if so, what's your strategy for the other 48% who don't have G551D and don't have delta F508? Thanks.

好的。我可以追問一下嗎？聽起來你對於 G551D 以及 VX-770 可能的標籤、標籤申請的語氣有所改變。聽起來與主管機關的討論已經朝向只針對 G551D 的申請。這樣理解合理嗎？如果是的話，那對於另外 48% 沒有 G551D、也沒有 delta F508 的患者，你們的策略是什麼？謝謝。

So to that question, our number one comment is there was no change in strategy or tone. I think it was always predominantly first 551 and that's what we have done. We are currently in negotiations with regulatory agencies in Europe as well as in the US how we can basically move forward and extend the label into other populations that might benefit form a monotherapy of 770. But I think the safe bet is 551 is a good first chart.

針對這個問題，我們第一個要說的是：策略或語氣沒有改變。我想一直以來主要都是先做 551，這也是我們一直在做的。我們目前正在與歐洲以及美國的監管機構協商，看看我們如何能夠往前推進，並把標籤延伸到其他可能從 770 單藥治療中受益的人群。不過我想比較保險的做法是，551 是一個很好的第一步。

Jeff, I'll just jump in on Peter's answer, as well. One of the things that you may be hearing in the prepared remarks was us being clear on the day that we expect to support the filing, which is the 48-week data from both STRIVE and ENVISION. I think that was something we haven't been as clear on in the past, but we do anticipate 48-week study data will be required to support the filing. And then also carcinogenistic studies, which we want to be clear on.

Jeff，我也補充一下 Peter 的回答。你可能在事先準備的發言中聽到的一點，是我們更清楚地說明：我們預期用來支持申報的時間點，是 STRIVE 與 ENVISION 兩個試驗的 48 週數據。我想過去我們沒有把這點講得那麼清楚，但我們確實預期需要 48 週的研究數據來支持申報。另外還有致癌性研究（carcinogenicity studies），我們也希望把這點講清楚。

Brian Abrahams of Wells Fargo Securities.

Wells Fargo Securities 的 Brian Abrahams。

Hi, thanks very much for taking my question, and congratulations to the team on a great job with the panel. Question for Nancy on pricing. Recognize that you're not in a position to talk specifically about telaprevir pricing now, but I was wondering if you could maybe give us any general sense, perhaps drawing off of the reimbursement dynamics that's been seen for peg interferon and ribavirin, as to how you expect the actual realized price per patient to be, net of discounts, patient assistant programs, et cetera, relative to what you set as the list price?

嗨，非常感謝讓我提問，也恭喜團隊在座談會上做得很出色。我有一個關於定價的問題想問 Nancy。我知道你現在不方便具體談 telaprevir 的定價，但我想請你從一般角度、也許參考 peg 干擾素與 ribavirin 的給付動態，談談你預期每位患者的實際實現價格（扣除折扣、病患協助計畫等等之後）相對於你們設定的牌價（list price）大概會是什麼關係？

Sure, Brian. Let me take a shot at that. As you know, depending upon the different channel that one is dealing with, be that commercial or different government payers, we'll be apt to provide obvious statutory reimbursement rates for the governments and other additional reimbursement or discounts to other channels. I think you can probably get a sense for what those tend to look like by looking at the way the market has performed historically. Beyond that, we really haven't set our price for INCIVEK. I'm pleased to tell you that we have planned a very aggressive patient assistance program that will be rolled out at the point of launch to ensure that any patients who really need INCIVEK can gain access to it, even if they can't afford it. Beyond that, we're considering a number of other factors that will eventually take us to a final price. And that, of course, will be the final label as that comes in from the FDA over the coming weeks. How well INCIVEK worked in the clinical trials, as measured by our SVR cure rates. The cost of other medicines and procedures that have been used for the treatment of hepatitis C up to this point in time. And of course the amount of money we need to generate to enable our scientists and our labs here at Vertex to continue to discover and test new medicines for other serious diseases in the future.

當然可以，Brian。我試著回答。如你所知，取決於所面對的不同通路——不論是商業保險或不同的政府給付方——我們會依規定提供政府端明確的法定給付/報銷比率，並對其他通路提供額外的給付安排或折扣。我想你大概可以透過回顧市場過往的表現，來了解這些通常會長什麼樣子。除此之外，我們其實還沒有為 INCIVEK 訂出價格。我很高興告訴你，我們規劃了一個非常積極的病患協助計畫，會在上市時推出，以確保任何真正需要 INCIVEK 的病患，即使負擔不起也能取得用藥。除此之外，我們也在考量多項因素，最終才會形成定價。當然其中包括：未來幾週 FDA 核發的最終標籤內容；INCIVEK 在臨床試驗中的療效表現（以 SVR 治癒率衡量）；截至目前用於治療 C 型肝炎的其他藥物與處置的成本；以及我們需要產生的資金規模，以便 Vertex 的科學家與實驗室能在未來持續發現並測試用於其他嚴重疾病的新藥。

Rachel McMinn of Bank of America.

美國銀行（Bank of America）的 Rachel McMinn。

Hi, this is Marcia for Rachel. I was wondering if you have already had your pre-NDA meeting for CF? And given your guidance for second half submissions, were there other gating factors for the regulatory filings here aside from the 48-week data?

嗨，我是 Marcia，代替 Rachel 提問。我想請問你們是否已經針對 CF 進行過 pre-NDA 會議？另外，基於你們對下半年提交申請的指引，除了 48 週數據之外，這裡在監管申報上是否還有其他關鍵門檻因素（gating factors）？

Bob will answer that.

Bob 會回答。

This is Bob. In terms of the pre-NDA meeting, it is upcoming shortly. We've not yet had the pre-NDA meeting, but it's scheduled.

我是 Bob。就 pre-NDA 會議而言，它很快就會進行。我們還沒有開 pre-NDA 會議，但已經排定了。

That's for the clinical side. And on the CMC side, where you have also pre-NDA meetings, I think we had our pre-NDA meeting on CMC in the US. We are going to have a pre MAA meeting in Europe next week.

那是臨床端的部分。而在 CMC 端，你們也會有 pre-NDA 會議；我想我們在美國已經就 CMC 開過 pre-NDA 會議。我們下週會在歐洲開 pre-MAA 會議。

Terence Flynn of Goldman Sachs.

Goldman Sachs 的 Terence Flynn。

Hi, thanks for taking the question. Just wondering in terms of the combo study, I know that that trial's enrolling patients that are homozygous for 508del. Was wondering, first, if you could maybe outline your thoughts on any potential differences in efficacy between a patient that's homozygous for that mutation versus heterozygouos. And then what percent of the market does each of those represent?

嗨，謝謝讓我提問。我想就聯合用藥（combo）研究請教一下。我知道那個試驗正在招募 508del 純合子（homozygous）的患者。我想先請你們概述一下：對於該突變的純合子患者與雜合子（heterozygous）患者之間，療效可能會有哪些差異？另外，這兩類各自大概占市場的百分比是多少？

This is Bob. Yes, you're right. The study is enrolling homozygous patients. We're trying to keep as homogeneous a population for this initial study as possible. We do plan, as we go through this trial and as you had heard, it's an adaptive trial, it gives us some freedom to look at different patient groups, and we probably will be looking at heterozygous patients as part of that evaluation as the trial goes forward. I can't comment on any differences in efficacy because we haven't seen any results yet.

我是 Bob。是的，你說得對。這項研究正在招募純合子患者。我們希望在這個初始研究中，讓受試族群盡可能同質。隨著試驗進行——你也聽到這是一個適應性試驗（adaptive trial）——它讓我們有一些彈性去看不同的病患族群；因此在試驗往前推進時，我們很可能也會把雜合子患者納入評估的一部分。我無法評論療效差異，因為我們還沒有看到任何結果。

In terms of population, the 508 is the biggest portion, and I think that covers about 80% or more.

就族群而言，508 是占比最大的部分，我想它涵蓋大約 80% 或更多。

That's absolutely right.

完全正確。

So the homozygous are about 40% overall and heterozygous make up the other 40%.

所以純合子整體大約占 40%，雜合子則構成另外 40%。

Okay, and then just a quick follow-up question, if I might. Can you give us any benchmark in terms of what you want to see on sweat chloride to consider making that decision to go forward to part 2 of the study?

好的，那我再快速追問一個問題。如果可以的話，你們能否提供一個基準：在汗氯方面，你們希望看到什麼樣的結果，才會考慮做出決定、進入研究的第 2 部分？

Yes. I get asked the question often, and all I will say is that our hope is to see some additive activity above and beyond each individual alone, each individual agent. We don't really have a target in mind. It really depends a little bit on what we see. There's also dose ranging going on and other aspects that will help us to analyze that. But at this point there's no definitive target.

可以。這個問題我常被問到；我只能說，我們的希望是看到某種加成活性（additive activity），也就是超越每一個單一藥物各自單獨使用時的效果。我們其實沒有預設一個目標值。這在某種程度上取決於我們看到的結果。研究中也在做劑量探索（dose ranging）以及其他面向，這些都會幫助我們分析。但在目前這個時間點，沒有明確的目標。

And the reason for that is because it is not understood yet what PKBD is in vivo in human beings. And we first have to figure out what the right dose regimens are before we can make any statement what direction we have to look. I think the excitement will come if see additive effect in whatever form, because that will prove the concept.

原因是，我們目前還不理解 PKBD 在人體體內（in vivo）是什麼。我們必須先弄清楚正確的給藥劑量方案，才能對我們應該朝哪個方向觀察做出任何陳述。我想如果我們以任何形式看到加成效果，令人興奮之處就在於那將證明這個概念（prove the concept）。

Yaron Werber of CitiGroup.

CitiGroup 的 Yaron Werber。

Hi. Thanks for taking my question, and congrats on really a wonderful panel. Maybe the first question, can you help us understand how fast can you launch once you get approved? And second, you've mentioned how many incoming calls you've had and so a point of contact into your hot line, and that was really an impressive number. I'm just trying to get a sense. Is there any way you're able to maybe ascertain how many of those are actually patient calls or unique patient calls? Maybe it gives us a very early gauge as to how many people are already contacting you. And then I had a follow-up on CF as well.

嗨，謝謝讓我提問，也恭喜你們，這真的是一場很精彩的座談。第一個問題是，你們能否幫我們理解：一旦獲批，你們最快能多快完成上市推廣（launch）？第二，你們提到接到多少來電、以及打進你們熱線的聯絡數量，那個數字非常令人印象深刻。我想了解的是：你們是否有任何方式可以判斷其中有多少其實是病患來電，或是獨立/唯一的病患來電？也許這能讓我們非常早期地衡量，已經有多少人正在主動聯絡你們。然後我也還有一個關於 CF 的追問。

Okay. Those are two good questions. I think the rapidity of launch is limited only by how fast you can get drug supply out through the channels and to the actual retail outlet. And we think we'll be able to do that within a matter of several weeks at the outside. Beyond that, I am fully confident that we will have every piece of infrastructure in place, each person trained, and waiting to make the calls on physicians and managed care organizations as soon as we get that drug out to the outlets. The second piece was a question -- can you remind me?

好的。這是兩個很好的問題。我認為上市啟動的速度，唯一的限制在於你能多快把藥品供應透過通路送出並送達實際的零售端。我們認為最慢在幾週之內就能做到。除此之外，我完全有信心我們會把所有基礎設施都就位、每個人都完成訓練，並且一旦藥品送到各零售據點，就能立刻開始拜訪醫師與受管理式照護組織（managed care organizations）。第二個部分是個問題——你可以提醒我一下嗎？

Yes, you've mentioned an impressive number of hits already or contacts into your hotline and website. Is there any way you're able to ascertain how many of them were patients and maybe even unique contacts into your hotline and website?

是的，你已經提到有相當驚人的來電數或對你們客服專線與網站的聯繫量。你們是否有任何方法可以判斷其中有多少是病患，甚至能否辨識出有多少是對你們專線與網站的「唯一」聯繫者？

No, I'm sorry. I can't tell you how many of those are actually patients, due to privacy laws that prohibit that sort of thing.

不，抱歉。由於隱私法規禁止那類資訊的揭露，我無法告訴你其中有多少實際上是病患。

Okay, but presumably at this point, do you have that information? I'm just trying to understand if maybe that can help you actually also reaching out to patients also?

好的，但推測在這個時間點，你們應該有那個資訊吧？我只是想了解，這是否也能幫助你們實際上去觸及病患？

No, we know that a good number of the patients who do come into the website end up opting into our relationship management program, so we will be able to stay in touch with them. But that is a voluntary decision made on their part, and we have no insight into why others don't make that decision.

不。我們知道有相當一部分造訪網站的病患最後會選擇加入我們的關係管理計畫，因此我們能夠與他們保持聯繫。但那是他們自願做出的決定，而我們也無從得知為什麼其他人不做這個決定。

Okay, great. And then just a question, the CF data was very impressive. When you look at the magnitude of the improvement in lung function, inevitably that should translate into survival benefit over time. That can really help you really drive home a great price for VX-770. And when we look at the orphan indications, pricing could be all over the map, from $200,000 on the low end. And if you look at myozyme for adult patients, as we even remember, that drug actually did not even hit the primary end point in the studies, they're charging about $1 million for an adult patient. So it gives you huge flexibility. Help us understand a little bit how do you think what's a good benchmark to think about pricing for 770, if you can.

好的，很棒。接著一個問題，CF 的數據非常令人印象深刻。當你看到肺功能改善的幅度時，這終究應該會隨時間轉化為存活效益。這確實能幫助你們為 VX-770 訂出很好的價格。再看孤兒適應症，定價可能差異很大，低端可能從 20 萬美元起。如果看 myozyme 用於成人病患，我們甚至記得那個藥在研究中其實連主要終點都沒有達成，他們對成人病患的收費大約是 100 萬美元。所以你們有很大的彈性。能否請你們協助我們理解一下，你們認為 770 定價時，一個好的參考基準應該怎麼看？如果你能分享的話。

It looks like everyone is doing their homework, just as quickly as we are. And you're right, the ranges are quite considerable, from an actual orphan indication to what we might term treatment of a rare disease, which is even beyond ultra orphan status. But it's too early for us to really have any sense at this point where a specific price will come in.

看起來大家做功課的速度跟我們一樣快。你說得對，區間確實非常大，從真正的孤兒適應症，到我們可能稱之為罕見疾病治療、甚至超越超孤兒（ultra orphan）狀態的情況。不過現在對我們來說還太早，還無法判斷具體價格最後會落在哪裡。

Howard Liang of Leerink Swann.

Leerink Swann 的 Howard Liang。

Can you comment on whether it's possible the FDA decision can come before the PDUFA data? In other words, could the two drugs be approved at the same time?

你能否評論一下，FDA 的決定是否可能在 PDUFA 日期之前出來？換句話說，兩個藥是否可能同時獲批？

It is possible both drugs can be approved at the same time. That's also possible.

兩個藥同時獲批是有可能的。這也是可能的。

Great. And if I could ask another question. How is 651, the second corrector different from 809?

很好。如果我可以再問一個問題。651，作為第二個校正劑（corrector），與 809 有何不同？

661 is the number. So it has a different metabolic profile, and also a different tissue penetration profile, which gives you a possibility to basically have different outcomes in different organs that might be beneficial.

編號是 661。它有不同的代謝特性（metabolic profile），也有不同的組織穿透特性（tissue penetration profile），這讓你有可能在不同器官上得到不同的結果，而這可能是有益的。

Ted Tenthoff of Piper Jaffray.

Piper Jaffray 的 Ted Tenthoff。

Great. And let me share my congrats on a hard-fought and well-won panel. My question goes, what have you done for me lately. And now that telaprevir is on the track to approval, I think a lot of people are really looking at future combination therapy. And I wanted to get a sense based on your data with 222 at EASL, as well as some of the competitive data out there. How is your view of combination therapy evolving? And specifically, what other HCV drug classes interest you to look at with telaprevir and how can you explore that?

很好。先讓我表達祝賀，你們在一場艱苦的戰役中奮戰並贏得了小組會議。我的問題是：你們最近又為我做了什麼？現在 telaprevir 正走在獲批的軌道上，我想很多人都在看未來的聯合療法。我想根據你們在 EASL 上的 222 數據，以及外界一些競品數據，了解你們對聯合療法的看法如何演進？具體來說，還有哪些 HCV 藥物類別是你們有興趣與 telaprevir 一起研究的？你們打算如何探索？

This is Bob. I'll take that. I guess my take-away from EASL was, for one, dual drug combinations appear not to be sufficiently robust in terms of resistance to be able to really make it in a significant way. That was a piece of learning that we've gotten pretty clearly. Otherwise, I would say that there are many, many different combinations being evaluated, and I think the field is moving along very quickly in that regard. And obviously we are looking to be competitive with all of those other regimens, as well. And I other take-away was that there's at least a hint that interferon may not be necessary as part of the regimen. There was a very small amount of information from the VMS trial, and I think that was pretty exciting to people, although, again, it was a very small experience. I think our view hasn't really changed all that much. Obviously we want to maintain our leadership position in this field. The 222 telaprevir data, particularly the quad regimens, are very encouraging. We're still pursuing non-interferon-based regimens with ribavirin. And as we've said before, we are continuing to look always for new mechanisms to potentially combine with the agents that we currently have to basically, produce a portfolio of agents that can be mixed and matched in appropriate ways, and that position hasn't changed at all. I think in fact the data suggests that that's the right approach and we're continuing to do that.

我是 Bob。我來回答。我想我從 EASL 得到的主要結論是：第一，雙藥組合在抗藥性（resistance）方面似乎不夠強韌，難以真正以顯著方式成功。這點我們學得很清楚。除此之外，我會說目前正在評估的組合非常非常多，而且我認為這個領域在這方面進展很快。顯然，我們也希望在所有其他療程方案中保持競爭力。另一個結論是，至少有一些跡象顯示干擾素（interferon）可能不是療程的一部分所必需。VMS 試驗提供的資訊非常少，但我認為這讓大家相當興奮，儘管再次強調，樣本經驗非常有限。我們的觀點其實沒有太大改變。我們顯然希望維持在這個領域的領先地位。222 的 telaprevir 數據，特別是四聯療法（quad regimens），非常令人鼓舞。我們仍在推進以利巴韋林（ribavirin）為基礎的非干擾素療程。我們也如先前所說，會持續尋找可與現有藥物結合的新作用機轉，以建立一個可依需要混搭的藥物組合（portfolio），而這個立場完全沒有改變。我認為數據其實顯示這是正確的做法，我們也會持續這麼做。

Mark Schoenebaum of ISI Group.

ISI Group 的 Mark Schoenebaum。

Hi, yes. It's actually [Nevine Jek] for Mark. Michael, I think you said we can't, ask comments about the label, but perhaps we could ask about the AdCom, is that fair?

嗨，是的。其實我是代替 Mark 的 [Nevine Jek]。Michael，我想你說我們不能評論標籤（label），但或許我們可以問一下 AdCom（諮詢委員會），這樣可以嗎？

Yes, I think our comments on the AdCom have to be very limited. Feel free to ask any question, we'll tell you if we can answer it.

是的，我想我們對 AdCom 的評論必須非常有限。你儘管提問，我們會告訴你能不能回答。

Just wondering, obviously you guys have tremendous data. And again, congrats on a successful panel. But with regards to the null patients, the panel seemed a little hesitant about treatment in nulls because of resistance. The members of the panel that were bullish on telaprevir for nulls spoke about use specifically in cirrhotic patients. But they also referred to the significant benefit that telaprevir provides. And they talked about 30% in nulls. But when you look at cirrhotic patients that are null, the treatment benefit there is only about 10%, so I was just wondering whether that's a concern for you with regards to resistance. And I'm aware of the extend data, as well.

只是想問，顯然你們的數據非常強，再次恭喜小組會議成功。不過就無反應（null）病患而言，小組似乎對在 null 病患中治療有點猶豫，因為擔心抗藥性。對於看好 telaprevir 用於 null 病患的委員，特別提到在肝硬化病患中的使用。但他們也提到 telaprevir 帶來的顯著效益，並談到 null 病患有 30% 的效果。但如果看肝硬化且為 null 的病患，治療效益只有大約 10%，所以我想知道，這是否會讓你們在抗藥性方面感到擔憂？我也知道有 extend 的數據。

Yes. Ultimately we're pretty happy with the discussion that occurred at the advisory committee. I think they looked at it in the appropriate way. At this point, really it's up to the FDA and the labeling and that's something we really just can't really get into. And don't really know how that's all going to come out at this point.

是的。總體而言，我們對諮詢委員會上的討論相當滿意。我認為他們以適當的方式看待這件事。此刻真正取決於 FDA 與標籤內容，而這是我們確實無法深入討論的。我們也不清楚最後會如何定案。

You have to understand, the advisory committee is just a supportive instrument. It's not a binding instrument.

你必須了解，諮詢委員會只是支持性的工具，並不是具有約束力的工具。

Sure. Fair enough. And then maybe one question for Ian, if I may. Ian, you've previously given us good guidance on telaprevir inventory that you've built up, saying that we have to be careful in how we model COGS. Wondering if you have any update there. Have you been continuing to build up telaprevir inventory?

當然，可以理解。那如果可以的話，我再問 Ian 一個問題。Ian，你之前對我們提供過關於你們建立的 telaprevir 庫存的良好指引，並說我們在建模 COGS（銷貨成本）時要小心。想請問你是否有更新？你們是否仍在持續建立 telaprevir 庫存？

Yes, we do continue to build it up, with our expectation. We have multiple scenarios that we planned out for launch possibilities and uptake, and we try to cover all of them, including the most optimistic, as well. So yes, we've continued to build inventory significantly. And I'll just point that on our balance sheet, you'll notice we started to capitalize the inventory as well. That came after the acceptance of our filing and also the positive outcome which gives us a confidence of potential approval and launch this inventory into the market, and then create a more normal cost of goods. But initially we do anticipate that there will be minimal cost of goods relating to telaprevir INCIVEK.

是的，我們確實持續在建立庫存，符合我們的預期。我們針對可能的上市情境與採用速度規劃了多種情境，並嘗試涵蓋所有情境，包括最樂觀的情境。所以是的，我們持續大幅增加庫存。我也補充一下，在資產負債表上你會注意到我們也開始將庫存資本化。那是在我們的申請案被受理之後，以及正面結果出來之後，這讓我們對可能獲批並將這些庫存投放市場更有信心，進而形成較正常的銷貨成本。不過一開始，我們預期與 telaprevir（INCIVEK）相關的銷貨成本會非常低。

Phil Nadeau of Cowen and Company.

Cowen and Company 的 Phil Nadeau。

Yes, good afternoon, thanks for taking my questions. Peter, first a follow-up question for you. In your prepared remarks, you mentioned the educational program on rash and anemia and that your teams have been working on it. But what was unclear to me was whether you feel that that educational program has been completed. So have you actually finished that educational program, and is that even possible to do before you have a final label?

是的，下午好，謝謝讓我提問。Peter，先問你一個追問。在你準備好的發言中，你提到關於皮疹與貧血的教育計畫，以及你們團隊一直在推動。但我不太清楚的是，你是否認為那個教育計畫已經完成了。所以你們是否已經完成那個教育計畫？而且在還沒有最終標籤之前，這真的有可能完成嗎？

This is Bob. I'll take that. No, we're obviously still working on that. Yes, we obviously need to see the final labeling in order to be sure we're in tune with what all the final numbers are and comments that are made in the label. So it's an ongoing, evolving process, but it's well underway.

我是 Bob。我來回答。不是，我們顯然還在處理那件事。是的，我們顯然需要看到最終的標示內容，才能確定我們與所有最終數據以及標籤中所做的評論一致。因此這是一個持續、逐步演進的流程，但已經進展得很順利。

This is Nancy. I just want to point out that it's standard practice with the approval of any new drug to have a solid educational program that is shared between medical affairs and commercial, utilizing, again, both your medical affairs staff, as well as your commercial team. And in our case, even our website and educators who will reach out to patients to be sure that treaters have the possibility to get the best outcome from a drug by fully understanding all of the adverse events that can occur and how to handle them. So we will be prepared at the point of launch with an aggressive support program educationally related to the benefits of the drug, as well as the adverse events.

我是 Nancy。我只想指出，任何新藥獲批時的標準作法，是建立一個扎實的教育計畫，由醫藥事務與商業團隊共同推動，再次強調，會同時運用你們的醫藥事務人員以及商業團隊。而在我們的情況下，甚至包括我們的網站與教育人員，他們會主動接觸病患，以確保治療者有機會在充分了解所有可能發生的不良事件以及如何處置的前提下，讓藥物達到最佳療效。因此在上市時點，我們會準備好一套積極的支援計畫，在教育層面同時涵蓋藥物的效益以及不良事件。

Okay. And you may have just answered this, but I'll ask it anyway. Does this need to be completed per FDA statute on the day of approval? Is this like a REMS where it has to be in place, or is there some leeway where it's more up to the Company as to exactly when the educational program's ready?

好的。你可能剛剛已經回答了，但我還是問一下。依 FDA 法規，這是否必須在核准當天就完成？這是否像 REMS 一樣必須先到位，還是有一些彈性，更多取決於公司教育計畫究竟何時準備就緒？

There are two different approaches. Obviously if the FDA requires a REMS you would negotiate that with them. But traditionally what you think about is many methods to educate physicians, including patient treatment brochures, nurse hot lines, patient starter kits with patient-specific information, et cetera, et cetera. That's all part of the standard approach.

有兩種不同的作法。顯然，如果 FDA 要求 REMS，你會與他們協商。但傳統上你會考量許多教育醫師的方法，包括病患治療手冊、護理師諮詢專線、含有病患專屬資訊的病患入門套組，等等等等。這些都是標準作法的一部分。

Okay. So it's fair to think that the educational program doesn't need to be totally finalized at the time of approval. That could be something that actually evolves with time.

好的。所以可以合理地認為，教育計畫不需要在核准時就完全定稿。它可能會隨時間而持續演進。

There is a REMS piece, which you have to get agreement on. This will be finalized at the given PDUFA time line. And then there's all the other activities, the non-REMS educational activities that Nancy mentioned, that you basically do as fast as you can. And basically we add to them anyhow, as you go forward. It's not a one type of thing.

其中有一個 REMS 的部分，你必須取得一致同意。這會在既定的 PDUFA 時程內定稿。然後還有其他活動，也就是 Nancy 提到的非 REMS 教育活動，你基本上就是能多快就多快去做。而且基本上，隨著後續推進我們也會持續加上去。它不是一次性的事情。

And Bob, just to reiterate, as we said before, we certainly expect the approval to be on or before the PDUFA data. We see nothing that would interfere with that at this point.

另外 Bob，重申一下，正如我們先前所說，我們確實預期核准會在 PDUFA 日期當天或之前。我們目前看不到任何會干擾這件事的因素。

Okay, and then one last question for Nancy. Nancy, I'm sure your sales and marketing folks are out there talking to physicians even though not strictly marketing for telaprevir. Do you have a sense of what proportion of physicians have already begun to schedule patients to come in over the summer, into the fall, once telaprevir and boceprevir are available?

好的，最後一個問題問 Nancy。Nancy，我確定你們的銷售與行銷人員即使不是嚴格在推廣 telaprevir，也已經在外面與醫師交流。你是否掌握大概有多少比例的醫師，已經開始安排病患在夏季到秋季期間回診，一旦 telaprevir 和 boceprevir 可用就開始治療？

I think we're all aware that physicians have been holding patients back from treatment. I hate to use the term warehousing when talking about human beings, but we're all aware of that. And I think it's pretty easy to estimate what that is by looking at the decline in the usage rates of the current standard of therapy. And to your earlier point, yes, we are actively out there. We have visited with about 65% or 70% of all physicians already, doing our unbranded campaign which helps physicians understand some of the key dynamics related to the treatment of HCV, most notably that a rapid decline in viral rates is typically associated with a very productive clinical outcome.

我想大家都知道，醫師一直在延後讓病患接受治療。我不太想在談人類時用「囤病患（warehousing）」這個詞，但大家都知道確實有這種情況。而且我認為，透過觀察目前標準治療的使用率下滑，就很容易估算其規模。回到你先前的觀點，是的，我們確實積極在外面推動。我們已經拜訪了約 65% 到 70% 的所有醫師，進行我們的非品牌宣導活動，協助醫師理解與 HCV 治療相關的一些關鍵動態，最重要的是，病毒量快速下降通常與非常良好的臨床結果相關。

Tom Russo of Baird.

我是 Baird 的 Tom Russo。

Good afternoon. Thanks for taking the question. Following what seemed like an endorsement from the panel and seemingly even FDA itself, is there any reason we should not now expect response-guided treatment for prior relapsers in some way at this go-round? And could you at least give us a flavor for how your market research says that might impact uptake or market share in that subset?

下午好。謝謝讓我提問。延續剛才看起來像是委員會、甚至 FDA 本身的背書，在這一輪審查中，是否有任何理由讓我們不再期待針對既往復發者（prior relapsers）以某種方式採用反應導向治療（response-guided treatment）？另外，你們至少能否分享一下，你們的市場研究認為這可能會如何影響該子族群的使用採納或市占？

Bob, I'll just answer the question in that I can't really answer the question. Obviously it will depend on how things go with the discussions with the FDA and we're in the midst of that now.

我是 Bob。我只能回答說，我其實無法回答這個問題。顯然這將取決於與 FDA 討論的進展，而我們目前正在進行當中。

And you don't typically do research on a point that is that fine. We're pleased generally with the very high marks that we're getting right now on the research we've done that generally describes the current view of telaprevir in the marketplace.

而且你通常不會針對如此細微的點去做研究。我們整體上對目前研究結果給我們的高分感到滿意；這些研究大致描述了市場上對 telaprevir 的當前看法。

Okay. And maybe, Nancy, just continuing on that theme, pricing came up earlier, but now that we've seen how the FDA looks at your data, do some of the things moving in a positive direction, like 79% SCR, a 10X improvement over standard of care in nulls, and maybe even more response-guided therapy, does that influent on the margin what you think you can charge?

好的。也許 Nancy，延續這個主題，先前提到定價，但現在我們看到 FDA 如何看待你們的數據後，一些正向的變化，例如 79% 的 SCR、在無反應者（nulls）相較標準治療提升 10 倍，甚至可能更多的反應導向治療，這些是否會在邊際上影響你們認為可收取的價格？

I wish I could comment more specifically. I just have to say again, we're very pleased with the way that the advisory committee went and we will be getting to you with our pricing decision as soon as it is finalized at the point of approval.

我希望我能更具體地評論。我只能再說一次，我們對諮詢委員會的進展方式感到非常滿意；而一旦在核准時點最終定案，我們會盡快向各位公布我們的定價決策。

Geoff Meacham of JPMorgan.

我是 JPMorgan 的 Geoff Meacham。

Hello, guys. Thanks for taking the question. A couple of questions about CF and the regulatory path and other gating mutations for 770. I know you guys are still in discussions, but how short do you think the treatment may have to be to see a potentiation effect and what types of measures of efficacy do you guys think that you may have to show here?

各位好，謝謝讓我提問。我有幾個關於 CF、法規路徑，以及 770 其他關鍵突變（gating mutations） 的問題。我知道你們仍在討論中，但你們認為治療需要多短才能看到增效（potentiation）效果？以及你們認為在這裡可能需要展示哪些療效衡量指標？

At this given point in time -- I started the second one first, I think. Currently approved and validated in regulatory agencies across the world from a CF readout point of view, is only FEV-1. That's the only basically validated end point and you have to assume that in all those studies that you do, that you have to show a benefit in that parameter. Other parameters are to be considered as we go forward. None of them are validated at this given point in time in the regulated environment, and therefore we have to do work in order to basically bring some of them forward. And there are several ones that go with lung functions, but also other organ functions. So that's what the situation is. In terms of treatment duration, I think we cannot take out their genes out of bodies so therefore it's a chronic treatment, life-long.

就目前這個時間點——我想我先回答了第二個問題。就 CF 的讀出（readout）而言，目前在全球各地監管機構中已核准且被驗證的，只有 FEV-1。這基本上是唯一被驗證的終點，你必須假設在你做的所有研究中，都必須在該參數上顯示出效益。其他參數會在我們後續推進時納入考量。但在目前的受監管環境下，沒有任何其他參數在此時點被驗證，因此我們必須做工作，才能把其中一些推進到可用的程度。這裡有幾個與肺功能相關的指標，也有其他器官功能的指標。這就是現況。至於治療期間，我認為我們不可能把他們的基因從身體裡拿掉，因此這是一種慢性治療、終身治療。

Peter, this is Bob. I'll just add on to that. We're not certain at this point what would be required in terms of these other mutations to demonstrate. As you know from the Phase 2a study of 770, both hose sweat chloride changes and FEV-1 changes we're really seeing quite soon after the initiation of treatment. And perhaps even two weeks or a month might be sufficient to show that. That's not to say that we have any agreements. We're just discussing that with the agencies. But it doesn't take very much time in order to see both of those changes.

Peter，我是 Bob。我補充一下。我們目前不確定，針對這些其他突變，需要展示哪些內容才算足夠。正如你從 770 的第 2a 期研究所知，無論是汗液氯離子（sweat chloride）的變化，或是 FEV-1 的變化，我們在開始治療後很快就看到了。也許兩週或一個月就足以顯示出來。這並不是說我們已經有任何共識；我們只是正在與主管機關討論。但要看到這兩項變化，其實不需要太長時間。

But I think what is really true for that length of the clinical trials, was the length of treatment duration afterwards. So those are two different things. And I think what will happen, what has to happen, and we will take the lead on that obviously, that you have to validate more markers so that agencies can feel comfortable in basically going forward. And we have heard those requests already in different settings.

但我認為，對於臨床試驗長度真正重要的是，之後的治療持續時間。所以這是兩件不同的事。我想接下來會發生、也必須發生的事情——而我們當然會主導——是你必須驗證更多標記（markers），讓主管機關在推進時能感到安心。我們也已經在不同場合聽到這些要求。

Could I just clarify your question, because maybe you were talking about the 809, 770 study and just the 7 days of combination therapy. Were you pointing to that?

我可以澄清一下你的問題嗎？因為也許你是在談 809、770 的研究，以及僅 7 天的合併治療。你指的是那個嗎？

No, sorry. Just 770 in and of itself.

不，抱歉。只是 770 本身。

So I think clinical studies in general to see an effect can be relatively short. Treatment duration is to be anticipated for long. And then the question you have to answer and discuss with agencies is how much safety data over what period of time do they want to see, to basically grant you an addition to your label.

所以我認為，一般而言，為了看到效果，臨床研究可以相對較短。治療持續時間則預期會很長。接著你必須回答並與主管機關討論的問題是：他們希望看到在多長期間內累積多少安全性數據，才能基本上同意在你的標籤上新增內容。

Is there any reason for you to think that Europe would be any different in terms of regulatory path end points or duration?

你是否有任何理由認為，歐洲在法規路徑的終點或治療期間方面會有所不同？

They are. They are. The regulatory path is anyhow different. And it takes normally longer and you have less intervention possibilities. And then I think what accelerated approval in the US is a priority review, six months, and other factors that can get in Europe behind, assuming that you answer the 120-day questions, which you get all at once, within four weeks. If you're not, then you go back to the normal phase, which is a 12-months type of approval regimen. So there is differences. And there's also a difference in how they look at drug regimens with respect to efficacy and also safety.

會的。會的。法規路徑本來就不同。而且通常需要更長時間，且你可介入的空間較少。另外我認為，美國的加速核准是優先審查，六個月，還有其他因素；在歐洲則可能落後，前提是你能在四週內回答一次性收到的 120 天問題。如果不能，那就回到一般流程，也就是約 12 個月的核准機制。因此確實存在差異。而且他們在看待藥物療程時，對療效以及安全性的評估方式也有所不同。

And final question here on 661. And thanks, Peter, for your earlier comment on the differences here. But when you guys look at some in vitro work with Delta S, does 661 exhibit any greater synergy with 770 than 809 did?

最後一個關於 661 的問題。也謝謝 Peter 先前對這裡差異的評論。不過當你們看一些與 Delta S 相關的體外研究時，661 與 770 的協同作用是否比 809 與 770 的協同作用更強？

It's comparable, but I think that's in vitro and as you know the truth in the pudding is in vivo. We have to see what that means.

差不多，但我認為那是體外結果，而如你所知，真正的關鍵在於體內。我們得看看那代表什麼。

Lisa Bayko of JMP Securities.

JMP Securities 的 Lisa Bayko。

Hi, there. Thanks for taking my questions. I just wanted to drill down on Brian's question that he asked earlier. Could you maybe just give us a flavor or a breakdown of the hep C landscape in terms of reimbursement. What relative fraction of people are Medicare versus Medicaid versus private or who have no insurance whatsoever?

嗨，謝謝讓我提問。我想再深入追問一下 Brian 先前問的問題。你們能否大致說明或拆解一下丙肝在給付（reimbursement）方面的現況？大概有多少比例是 Medicare、Medicaid、商業保險，或是完全沒有保險？

Let me see if I can help out a little bit, Lisa. Generally speaking, about 60% of the audience is covered through commercial insurance plans. The other 40% breaks down, as you might imagine, between all the different government plans, Medicare, which is outsourced these days through commercial plans, and a little bit of cash. I think probably what you're trying to get at is, maybe related to some issues that other companies have had, with increasing reimbursement rates within Medicaid. And I think most of that has been an issue with other companies because they were looking at chronic therapies for patients. For instance, when you're treating hepatitis B or HIV. Those patients are going on those therapies ad infinitum. The advantage we have is that it's a 12-week cure market. And in my mind, I'm very confident that monies will be made available through the off-patent products that are going to really be bringing big injections of cash back into all of these different types of funding.

Lisa，我看看能不能稍微幫忙說明一下。一般來說，大約 60% 的族群是由商業保險計畫承保。其餘 40% 如你所想，會分散在各種政府計畫之間，包括 Medicare（如今多由商業計畫外包承作）、以及少量自費。我想你可能想問的是，或許與其他公司遇到的一些問題有關，例如 Medicaid 給付比例提高的議題。我認為那多半是其他公司之所以有問題，是因為他們面對的是慢性治療。比方說治療 B 型肝炎或 HIV，那些病人會無限期地使用那些療法。我們的優勢在於這是一個 12 週即可治癒的市場。在我看來，我非常有信心，資金將會透過那些已過專利期的產品釋出，並為各類資金來源帶來大量現金挹注。

David Friedman of Morgan Stanley.

Morgan Stanley 的 David Friedman。

Hi. Thanks for taking our question. Just wondering if you have a sense as to whether telaprevir, or INCIVEK, would primarily be distributed through specialty pharmacies or just your regular pharmacies? And just as a corollary to that, is there any reason why you think this drug would not be accurately tracked by IMS?

嗨，謝謝讓我們提問。我想知道你們是否認為 telaprevir（INCIVEK）主要會透過專科藥局（specialty pharmacies）配銷，還是一般藥局？另外延伸問一下，你們認為有任何原因會導致這個藥無法被 IMS 準確追蹤嗎？

The first question's really easy to answer. The second one is much more complex, and I probably won't be able to give you a full and compelling answer today. Our general attitude about the way that we would like to see INCIVEK go out to the market is an open distribution model. And we think that will enable the greatest number of patients in need to be able to gain access to the drug. That means that we'll be using major wholesalers, regional wholesalers, as well as specialty pharmacies. And as I'm sure you're aware, David, from your experience, that may leave some minor gaps in the data that will be available through the common sources such as IMS.

第一個問題很容易回答。第二個就複雜得多，我今天可能無法給你完整且有說服力的答案。我們對於希望 INCIVEK 進入市場的方式，整體態度是採取開放式配銷模式。我們認為這能讓最多有需求的病人取得藥物。這表示我們會使用大型批發商、區域批發商，以及專科藥局。正如你憑經驗也很清楚的，David，這可能會讓像 IMS 這類常見資料來源所能取得的數據出現一些小缺口。

Alan Carr of Needham & Company.

Needham & Company 的 Alan Carr。

Hi, thanks for taking my questions. And congratulations on the advisory committee. To follow up real quick on 661, to make sure I understand that, is the difference here mainly that you're getting greater distribution in the lung, Peter?

嗨，謝謝讓我提問，也恭喜諮詢委員會（advisory committee）的結果。快速追問一下 661，確認我理解正確：這裡的差異主要是你們在肺部的分布更高，是嗎，Peter？

Could you repeat that?

你可以再重複一次嗎？

The difference between 661 and 809, it sounds like there's a lot of similarity in vitro, but you mentioned that there was a different tissue penetration. Is it better penetration into the lung? Is that the difference?

661 和 809 的差異，聽起來在體外有很多相似之處，但你提到組織穿透性不同。是對肺部的穿透更好嗎？這就是差異嗎？

There is a higher penetration towards the lung, but we don't know whether it really translates into a therapeutic benefit.

確實對肺部的穿透更高，但我們不知道這是否真的能轉化為治療效益。

Okay. And, Nancy, about the prescriber rates, I'm curious whether, do you expect the prescriber base to grow, or stay the same, or become more concentrated or specialized as you layer on protease inhibitors

了解。那 Nancy，關於處方醫師比例（prescriber rates），我想知道你們預期處方醫師基礎會擴大、維持不變，還是隨著蛋白酶抑制劑（protease inhibitors）加入而變得更集中或更專科化？

I think the net-net as the drugs are released and as practitioners gain experience will be pretty even keel. It may take a little longer for people who don't see as many patients to find the courage. They are often not on that cutting edge of innovation. They may want to wait for some of your higher treatment prescribers and key thought lead to gain that experience and help advise them. But we don't expect it to change in a very dramatic way.

我認為整體而言，隨著藥物上市、臨床醫師累積經驗，會相當平穩。對於看診病人數較少的醫師，可能需要更久才會有信心；他們通常不在創新最前沿。他們可能會先等一些治療量較高的處方醫師與關鍵意見領袖累積經驗並提供建議。但我們不預期會有非常戲劇性的改變。

Ying Lang from Gleecher & Company.

Gleecher & Company 的 Ying Lang。

This is Ryan for Ying, thanks for taking my questions. Just two questions. First for the phase 3 telaprevir BID study, could you give us some more details regarding where you are with enrollment. From the ClinicalTrials.gov site it looks like the study was initiated last year. And then second, this is for Ian, given the number of studies you're conducting, could you comment generally on how you're thinking about R&D expense, maybe longer term? Thanks.

我是代 Ying 提問的 Ryan，謝謝讓我提問。兩個問題。第一個是關於第 3 期 telaprevir BID（每日兩次）研究，你們能否提供更多關於收案進度的細節？從 ClinicalTrials.gov 看起來，該研究是去年啟動的。第二個問題給 Ian：鑑於你們正在進行的研究數量，你能否概括評論一下你們對研發費用（R&D expense）較長期的思考？謝謝。

This is Bob. I'll answer the first one. It's going along as we planned. The sites are active and patients are actively enrolling, so we expect things to be basically on track.

我是 Bob。我先回答第一個。進度如我們規劃進行。各研究中心都已啟動，病人也在持續收案，因此我們預期整體會基本按計畫推進。

And then to the guidance for R&D, I can't provide you guidance looking at the 2012 or '13. What we tried to do this year, though, is we gave you guidance for 2011 to help you understand our total operating expenses. Clearly you have your own models in terms of revenues, and that will help you navigate the waters, let's say. As we go into '12 and '13, with how our total operating expense are trending, taking last year, looking at this year, and how we might go into 2012. And then you can apply that to your revenue models and that should give you a good understanding that we're looking at 2012 to be a year where we are continuing reimbursement in R&D because of the pipeline that we've been building. But we still have great potential given the scale of the top line to create significant earnings. So that's how we model the business. That's what we're planning for for '12 and '13, and it's how we're going to take our budgets into 2012.

至於研發指引（guidance），我無法提供你們對 2012 或 2013 年的指引。不過我們今年嘗試做的是，提供 2011 年的指引，幫助你們理解我們的總營運費用。很明顯你們各自都有收入模型，這會幫助你們「掌舵」前行。當我們進入 2012 與 2013 年，從總營運費用的趨勢來看，對照去年、今年，以及我們可能如何進入 2012 年，你們就可以把這些套用到你們的收入模型，並應該能很好地理解：我們認為 2012 年會是持續加大研發投入的一年，因為我們一直在建立的產品線（pipeline）。但考量營收規模（top line）的量體，我們仍有很大潛力創造顯著獲利。因此我們就是這樣建模這個業務、也是我們對 2012 與 2013 年的規劃，並且會以此來制定 2012 年的預算。

So it's now past 6.00 PM I think in the interest of everybody's time, we will take just one more question and be available in our offices after that, if you have additional inquiries.

現在我想已經超過晚上 6 點了。為了大家的時間，我們只再接受最後一個問題；之後如果你們還有其他詢問，我們會在辦公室待命。

Vernon Bernardino from Dawson James.

Dawson James 的 Vernon Bernardino。

Congratulations, as well, for a great panel. One panelist was persistent on the issue of rash anemia and how pyrazinoic acid, metabolite telaprevir plays a role in the risk of gout and tuberculosis. You didn't really get a good chance to reply during the meeting, or at least in detail. Could you comment on what studies are planned to address the panelist's issue?

也恭喜你們有一個很棒的委員會。會中有一位委員一直關注皮疹、貧血，以及吡嗪酸（pyrazinoic acid）這個 telaprevir 代謝物在痛風與結核病風險中所扮演的角色。你們在會議中沒有太多機會回應，或至少沒有詳細回應。你們能否說明為了回應該委員的疑慮，規劃進行哪些研究？

So, yes, it's true that pyrazinoic acid is a metabolizer telaprevir. It's present in relatively low concentrations in plasma compared to the parent molecule. The safety profile of telaprevir has obviously been developed with pyrazinoic acid as it has been, but we don't anticipate any additional studies being necessary at this point.

是的，吡嗪酸確實是 telaprevir 的一個代謝物。與母體分子相比，它在血漿中的濃度相對較低。telaprevir 的安全性特徵顯然是在吡嗪酸存在的情況下建立起來的，但我們目前不預期需要進行任何額外研究。

Okay. Thank you very much, everyone, for joining us tonight. Thank you very much for your kind words and your questions. We certainly look forward to updating you further on INCIVEK in the coming weeks. And, again, we are in our offices tonight if you have any additional questions. Thank you.

好的。非常感謝各位今晚加入我們。也非常感謝你們的鼓勵與提問。我們期待在接下來幾週進一步向各位更新 INCIVEK 的進展。再次提醒，如果你們還有其他問題，我們今晚會在辦公室。謝謝。

Ladies and gentlemen, thank you for your participation on today's conference. This does conclude the program and you may now disconnect.

各位女士先生，感謝您參與今天的電話會議。本次活動到此結束，您現在可以掛線。