福泰製藥 (VRTX) 2011 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Vertex Pharmaceutical Incorporated third 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, and instructions will follow at that time. (Operator Instructions). As a reminder, this conference is being recorded. I would now like to introduce your host for today's conference. Michael Partridge, you may begin.

各位女士、先生，大家好，歡迎參加 Vertex Pharmaceutical Incorporated 2011 年第三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，屆時將提供相關指示。(接線員指示)。提醒各位，本次會議將被錄音。現在我想介紹今天會議的主持人。Michael Partridge，您可以開始了。

Thank you. Good evening, and welcome to Vertex's third quarter 2011 conference call. Our commercial team has had great success with the launch of INCIVEK combination treatment for people with genotype 1 chronic hepatitis C. After only five months into the launch, we have seen rapid adoption of INCIVEK, and increasing penetration into the prescriber base. Matt Emmens will kick things off for us here today, with comments on the importance of the reintroduction of INCIVEK, what it means for the future of the Company, and how we are positioned to just maybe, develop and commercialize more new medicines like INCIVEK, that can cure or significantly improve the treatment of other serious diseases.

謝謝。各位晚安，歡迎參加 Vertex 2011 年第三季電話會議。我們的商業團隊在為基因型 1 慢性 C 型肝炎患者推出 INCIVEK 聯合治療方面取得了巨大成功。在上市僅五個月後，我們已看到 INCIVEK 的快速採用，以及在處方醫師基礎中的滲透率持續提升。Matt Emmens 將先為我們開場，說明重新推出 INCIVEK 的重要性、其對公司未來的意義，以及我們如何定位自己，或許能夠開發並商業化更多像 INCIVEK 這樣的新藥，得以治癒或顯著改善其他嚴重疾病的治療。

Ian will review the financial statement, with a particular focus on the revenue stream being generated by INCIVEK which allows for reinvestment into the business, and also creates the potential for significant earnings and cash flows. Nancy will discussed how she and her team are progressing in the early launch, and particularly, how the increasing penetration of the prescriber base is important to the adoption of INCIVEK. Nancy will also comment on how we are positioning ourselves, to continue to play major role in the hepatitis C market as it evolves. Dr. Peter Mueller will end the call with a review of the significant progress, with the development of our other hepatitis C regimens including the INCIVEK VX-222 combination regimen, and the pipeline of other medicines including the recent NDA and MAA submissions of KALYDECO, also known as the VX-770. KALYDECO is Vertex's second breakthrough oral medicine, and is for cystic fibrosis, a genetic disease that affects children and adults. He will also review the recent progression of the VX-509 in rheumatoid arthritis.

Ian 將回顧財務報表，特別聚焦於 INCIVEK 所帶來的營收來源，這使我們得以再投資於業務，同時也創造顯著獲利與現金流的潛力。Nancy 將說明她與團隊在早期上市推進上的進展，尤其是處方醫師基礎滲透率提升對 INCIVEK 採用的重要性。Nancy 也將談到，隨著 C 型肝炎市場演進，我們如何定位自己以持續扮演重要角色。Dr.Peter Mueller 將在電話會議最後回顧我們其他 C 型肝炎療法方案的重大進展，包括 INCIVEK 與 VX-222 的聯合療法方案，以及其他藥物的研發管線，其中包含近期已提交 NDA 與 MAA 的 KALYDECO（亦稱 VX-770）。KALYDECO 是 Vertex 的第二款突破性口服藥物，用於囊性纖維化（cystic fibrosis），這是一種影響兒童與成人的遺傳性疾病。他也將回顧 VX-509 在類風濕性關節炎方面的近期進展。

I will comment, that in the weeks ahead, we have data from three disease franchises being presented at major medical meetings. First, the North American Cystic Fibrosis Conference in Anaheim on November 3 through 5, where we will have Phase III data presented for KALYDECO in the G551D population. We will also have there, Phase II data for the KALYDECO VX-809 combination in F508del patients. Then, ASLD the major liver meeting, taking place in San Francisco from November 5 through 8. We will have data there for INCIVEK in patients who are co-infected with HCV and HIV. And also data for our short duration Quad regimen for INCIVEK VX-222, pegylated interferon and ribavirin. Finally in Chicago, the American College of Rheumatology Conference or ACR, taking place from November 5 to 9, we'll feature the first presentation of data for our selective JAK3 compound, VX-509. We are looking forward to highlighting our robust and diverse pipeline of medicines at these prominent conferences.

我也想補充，在接下來幾週，我們將在多個重要醫學會議上發表來自三個疾病領域的數據。首先是 11 月 3 日至 5 日在阿納海姆舉行的北美囊性纖維化會議（North American Cystic Fibrosis Conference），我們將發表 KALYDECO 在 G551D 族群的第三期數據。同時也將發表 KALYDECO 與 VX-809 聯合治療在 F508del 患者的第二期數據。接著是主要肝病會議 ASLD，將於 11 月 5 日至 8 日在舊金山舉行。我們將在會中發表 INCIVEK 用於 HCV 與 HIV 共感染患者的數據。也將發表我們短療程四聯方案（Quad regimen）的數據，該方案包含 INCIVEK、VX-222、聚乙二醇化干擾素與利巴韋林。最後是在芝加哥舉行的美國風濕病學會年會（American College of Rheumatology Conference，ACR），時間為 11 月 5 日至 9 日，將首次發表我們選擇性 JAK3 化合物 VX-509 的數據。我們期待在這些重要會議上重點展示我們強健且多元的藥物研發管線。

After our prepared remarks today, we will be joined by Dr. Bob Kauffman, and we will be happy to take your questions. We expect today's call to conclude at 6 PM. Finally, let me note that information discussed on this conference call includes forward-looking statements, which are subject to the risks and uncertainties discussed in detail in our reports filed with the Securities and Exchange Commission, including our 10-K. These statements, including those regarding the market launch of INCIVEK, are based on management's current assumptions, and are subject to risk and uncertainties that could cause actual outcomes and events to differ materially.

在我們今天的預備發言之後，Dr.Bob Kauffman 也將加入，我們很樂意回答各位的問題。我們預期今天的電話會議將於下午 6 點結束。最後提醒，本次電話會議所討論的資訊包含前瞻性陳述，並受我們向美國證券交易委員會（SEC）提交之報告（包括 10-K）中詳述的風險與不確定性影響。這些陳述（包括關於 INCIVEK 市場上市的相關陳述）係基於管理層目前的假設，並可能受到風險與不確定性影響，導致實際結果與事件與所述內容出現重大差異。

GAAP and non-GAAP financial measures will be discussed on this call. Information regarding our use of non-GAAP financial measures, and the reconciliation of those measures to GAAP is available in our third quarter 2011 financial press release, which is on our website. Thank you. I will now turn the call over to Matt Emmens.

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 之間的調節表，已載於我們 2011 年第三季財務新聞稿，並可於公司網站查閱。謝謝。現在我把電話交給 Matt Emmens。

Thank you, Michael, and good evening, everyone. There are three key themes that we want to convey in today's call, that we believe are defining our Company. First, early INCIVEK revenues are impressive, and we have only just begun to treat the many people living with hepatitis C. Second, Vertex is more than just INCIVEK. We have a diverse and robust pipeline of eight different medicines in development. And third, we are well along in establishing Vertex, as a global health sciences Company. Vertex is fulfilling it's mission of bringing transformative medicines to people with serious diseases world-wide. And INCIVEK combination therapy for hepatitis C is now available for patients in multiple countries, including the US and Canada, where we are commercializing the medicine ourselves, four countries in Europe where it is marketed as INCIVO by Janssen, and Japan where it will be sold by Mitsubishi Tanabe, under the brand name, Telavic.

謝謝你，Michael，各位晚安。今天的電話會議我們想傳達三個關鍵主題，我們相信這些主題正在定義我們的公司。第一，INCIVEK 的早期營收表現令人印象深刻，而我們才剛開始治療眾多 C 型肝炎患者。第二，Vertex 不僅僅只有 INCIVEK。我們擁有多元且強健的研發管線，共有八項不同藥物正在開發中。第三，我們在建立 Vertex 成為全球健康科學公司方面已取得長足進展。Vertex 正在實現其使命：為全球嚴重疾病患者帶來具變革性的藥物。目前，INCIVEK 的 C 型肝炎聯合療法已在多個國家提供給患者使用，包括美國與加拿大（由我們自行商業化），歐洲四個國家（由 Janssen 以 INCIVO 之名行銷），以及日本（將由 Mitsubishi Tanabe 以 Telavic 品牌銷售）。

INCIVEK has a compelling profile, and many groups across our Company have done an outstanding job of understanding the needs of patients and physicians in this market. We believe that we are delivering real solutions for the hepatitis C community. With INCIVEK, we believe we have set a high bar in the treatment of hepatitis C. Our goal is to sustain leadership in this disease. That means continuing the very successful launch of INCIVEK, continuing our efforts to explore new ways of achieving high viral cure rates, and furthering shortening treatment duration, and continuing to improve treatment options and outcomes for people living with hepatitis C.

INCIVEK 具備極具吸引力的產品特性，而公司內多個團隊在理解此市場中患者與醫師需求方面表現出色。我們相信，我們正在為 C 型肝炎社群提供真正的解決方案。透過 INCIVEK，我們相信已為 C 型肝炎治療樹立了很高的標準。我們的目標是在此疾病領域維持領導地位。這意味著持續推進 INCIVEK 極為成功的上市表現，持續探索達成高病毒治癒率的新方法，進一步縮短治療療程，並持續改善 C 型肝炎患者的治療選項與治療結果。

We are expanding our commercial portfolio rapidly. Just five months after the approval of INCIVEK, we have a new drug applications under review by global regulatory agency for KALYDECO, our second potential breakthrough medicine. If approved, KALYDECO would be the first medicine to address the underlying cause of cystic fibrosis or CF, a major step for Vertex and the cystic fibrosis community. I want to recognize the many people at Vertex who have been dedicated to this program for so many years. I also want to thank the CF Foundation who provided us with early financial support to help advance our research programs. We were able to move forward quickly, thanks to the efforts of many doctors and nurses at CF centers in the US, Europe, Canada, and Australia. The families who are touched by this disease every day, and most importantly, the children and the adults living with cystic fibrosis who remain ever hopeful that new medicines are just around the corner. The CF program sets the stage for Vertex to become a global Company. We are focused on ensuring a successful global launch of KALYDECO

我們正在快速擴大我們的商業化產品組合。在 INCIVEK 獲准僅五個月後，我們的第二款潛在突破性藥物 KALYDECO 已有新藥申請正在接受全球監管機構審查。若獲核准，KALYDECO 將成為首款針對囊性纖維化（cystic fibrosis，CF）根本病因的藥物，這對 Vertex 與囊性纖維化社群而言都是重大一步。我想表彰 Vertex 許多多年來投入此計畫的同仁。我也要感謝 CF Foundation 在早期提供財務支持，協助推進我們的研究計畫。在美國、歐洲、加拿大與澳洲的 CF 中心，許多醫師與護理人員的努力讓我們得以快速推進。也感謝每天都受到此疾病影響的家庭；最重要的是，感謝仍始終抱持希望、相信新藥即將到來的囊性纖維化兒童與成人患者。CF 計畫為 Vertex 成為全球性公司奠定了基礎。我們專注於確保 KALYDECO 的全球上市取得成功

We are putting significant effort into hiring exceptional commercial leaders, and therapeutic specialists with experience in CF or other orphan disorders. The CF program is at the sweet spot of Vertex's mission and vision, and exemplifies who we are, that is a Company committed to taking on the biggest challenges, in areas with the greatest need for new, more efficient medicines. Data from our pivotal studies for KALYDECO validated the scientific hypothesis, that the CFTR protein is the right target. This validation makes us optimistic, that with continued investment we will have a good chance of improving the lives of many more people living with this very difficult disease. Breakthrough science is the common thread that leads us to innovative, transformative medicines that can have significant impact on patient lives. Our broad and diverse pipeline also includes mid-stage opportunities in rheumatoid arthritis, epilepsy, and flu. These are areas where we hope to repeat our successes in Hepatitis C and CF.

我們正投入大量心力，延攬傑出的商業領導人才，以及具備囊性纖維化（CF）或其他罕見疾病經驗的治療領域專家。CF 計畫正處於 Vertex 使命與願景的最佳契合點，並體現了我們的本質：一家致力於迎戰最重大挑戰、在最迫切需要更有效新藥的領域投入的公司。我們針對 KALYDECO 的關鍵性研究數據驗證了科學假說，即 CFTR 蛋白是正確的標的。這項驗證使我們樂觀地相信，若持續投資，我們將有很大機會改善更多罹患這種極其棘手疾病患者的生活。突破性科學是引領我們走向創新、具變革性的藥物之共同主軸，這些藥物能對病患生活產生重大影響。我們廣泛且多元的產品線亦包含類風濕性關節炎、癲癇與流感等中期機會。這些領域是我們希望複製在 C 型肝炎與 CF 所取得成功的地方。

Heading into 2012, we have significant momentum in our business and commercial development and research, and we will keep investing in areas where we believe we can make important advances in treatment. Thank you for your time. And I would now like to turn the call over to Ian, who will review our third quarter financial results.

展望 2012 年，我們在業務與商業發展以及研發方面都具備強勁動能，並將持續投資於我們相信能在治療上取得重要進展的領域。感謝各位撥冗。接下來我想把電話交給 Ian，由他回顧我們第三季的財務結果。

Thanks, Matt, and good evening to everyone. Our financial performance in the third quarter was principally driven by the successful introduction and launch of INCIVEK. We had significant revenues from the sale of INCIVEK, and it enabled us to record profitability and cash flow, in just our first full quarter since the INCIVEK launch. With the continued, strong INCIVEK revenues, we can create a financial platform of value creation by reinvesting in our pipeline, as well as generate significant earnings and cash flows.

謝謝你，Matt，各位晚安。我們第三季的財務表現主要由 INCIVEK 成功導入與上市所帶動。我們自 INCIVEK 銷售取得可觀營收，並使我們在 INCIVEK 上市後的第一個完整季度就能記錄獲利與現金流。在 INCIVEK 營收持續強勁的情況下，我們可以透過再投資於產品線來建立價值創造的財務平台，同時也能產生可觀的獲利與現金流。

Let's now turn to third quarter results. First, total revenues for our third quarter of 2011 were approximately $659 million, compared to approximately $24 million in the same quarter last year. The higher revenue in the third quarter of this year was primarily due to approximately $420 million of net product revenues from INCIVEK. And $200 million of revenues for the achievement of approval and launch milestones for INCIVO in European geographies. Our third quarter net product revenues of approximately $420 million were derived from gross product revenues of approximately $466 million. In the third quarter, our gross to net adjustment was approximately 10%, similar to what we saw in the second quarter earlier this year. And we expect that the gross to net will widen further, as our contracts are signed, and our payer mix continues to evolve. The INCIVEK net revenues of $420 million for this quarter includes 2.5 weeks of INCIVEK in the distribution channel at September 30, 2011. As of today's call, this product in the channel has already been sold through. We continue to see, and expect to see, an average of two to three weeks of INCIVEK in the distribution channel going forward.

現在我們來看第三季業績。首先，2011 年第三季總營收約為 6.59 億美元，相較去年同季約 2,400 萬美元。今年第三季較高的營收主要來自 INCIVEK 約 4.20 億美元的產品淨營收。以及在歐洲地區達成 INCIVO 核准與上市里程碑所帶來的 2.00 億美元營收。我們第三季約 4.20 億美元的產品淨營收，係由約 4.66 億美元的產品毛營收所推導而來。第三季毛轉淨（gross to net）調整約為 10%，與今年稍早第二季所見相近。我們預期毛轉淨差異將進一步擴大，因為合約陸續簽署，且付款方組合（payer mix）持續演變。本季 INCIVEK 4.20 億美元的淨營收包含截至 2011 年 9 月 30 日在通路中約 2.5 週的 INCIVEK 庫存。截至今天的電話會議，通路中的該產品已經售罄（sold through）。我們持續看到並預期未來通路中平均將維持約兩到三週的 INCIVEK 庫存。

Now to the GAAP and the non-GAAP net income. In the third quarter, due to significant INCIVEK revenues, we achieved profitability on both a GAAP and non-GAAP basis. Specifically, the GAAP net income attributable to Vertex for the third quarter was approximately $221 million or $1.02 per diluted share, compared to a GAAP net loss of approximately $209 million or $1.04 per share for the third quarter 2010. The GAAP net income includes an intangible asset impairment charge, stock compensation charges, and revenues related to INCIVO European milestones. Although we saw future rights to these milestones in 2009, according to GAAP reporting, these payments pass through our income statement, and appear as revenues on the collaborative revenues line. In connection with realization of these milestones, we have to record a non-cash expense of approximately $11 million, and we expect record an expense in the fourth quarter of approximately $7 million with the closure of this transaction. We recorded all other expenses related to this transaction in prior periods.

接著談 GAAP 與非 GAAP 淨利。第三季由於 INCIVEK 營收顯著，我們在 GAAP 與非 GAAP 基礎上皆達成獲利。具體而言，第三季歸屬於 Vertex 的 GAAP 淨利約為 2.21 億美元，或稀釋後每股 1.02 美元；相較之下，2010 年第三季 GAAP 淨損約為 2.09 億美元，或每股 1.04 美元。GAAP 淨利包含無形資產減損費用、股票酬勞費用，以及與 INCIVO 歐洲里程碑相關的營收。雖然我們在 2009 年已出售這些里程碑的未來權利，但依 GAAP 報導規定，這些款項仍會經由損益表流入，並在合作收入（collaborative revenues）項下列示為營收。在實現這些里程碑的同時，我們必須認列約 1,100 萬美元的非現金費用，且預期在第四季隨著此交易結束再認列約 700 萬美元費用。與此交易相關的其他費用我們已於先前期間全數認列。

Our non-GAAP income attributable to Vertex for third quarter of 2011 was approximately $151 million or $0.70 per diluted share, compared to a non-GAAP loss of approximately $175 million or $0.87 per share for the third quarter of 2010. The non-GAAP financials exclude stock compensation and intangible asset impairment charge, and the revenue from INCIVO European milestones. With respect to detail of our operating expenses, the increase compared to 2010 was principally driven by the support to launch INCIVEK, EU commercial build for CF, and the expansion of the development portfolio. For more information, please refer to our income statement, which can be found in our third quarter press release.

2011 年第三季歸屬於 Vertex 的非 GAAP 淨利約為 1.51 億美元，或稀釋後每股 0.70 美元；相較之下，2010 年第三季非 GAAP 淨損約為 1.75 億美元，或每股 0.87 美元。非 GAAP 財務數字排除股票酬勞與無形資產減損費用，以及 INCIVO 歐洲里程碑的營收。就營業費用細項而言，相較 2010 年的增加主要由支援 INCIVEK 上市、CF 在歐盟的商業化建置，以及開發組合的擴張所驅動。更多資訊請參閱我們的損益表，可於第三季新聞稿中查閱。

The successful launch of INCIVEK has made us cash flow positive for the third quarter, and we ended the quarter with approximately $660 million of cash, cash equivalents and marketable securities. Looking now to the remainder of 2011 and 2012, we expect to benefit from the significant INCIVEK revenues, and manage total operating expenses for the Company, with a view to a financial profile to support the planned launch of KALYDECO in 2012, and maintain reinvestments into R&D, while creating future significant earnings. Thank you. And over to you Nancy.

INCIVEK 的成功上市使我們第三季轉為正向現金流，我們在季末持有約 6.60 億美元的現金、約當現金與有價證券。展望 2011 年剩餘期間與 2012 年，我們預期將受惠於可觀的 INCIVEK 營收，並管理公司總營業費用，以形成可支援 2012 年 KALYDECO 規劃上市的財務輪廓，同時維持對研發的再投資，並創造未來可觀的獲利。謝謝。接下來交給你，Nancy。

Thanks, Ian, and good evening, everyone. For the next few minutes, I would like to review with you certain aspects about the launch of INCIVEK, as well as provide some insight into our thoughts on the evolution of Hepatitis C treatment. Let's start first with the launch. I'd like to thank the hundreds of people at Vertex who contributed to the development, distribution and launch of INCIVEK. It is amazing that a group could produce such a phenomenal launch, having never worked together in this capacity before. Physicians have been able to prescribe INCIVEK combination therapy to more than 17,000 patients during the first five months following approval. The rapid acceptance by physicians and patients, is evidenced in the high market share of INCIVEK.

謝謝你，Ian，各位晚安。接下來幾分鐘，我想與各位回顧 INCIVEK 上市的若干面向，並就我們對 C 型肝炎治療演進的看法提供一些洞見。我們先從上市談起。我要感謝 Vertex 數百位同仁對 INCIVEK 的開發、配送與上市所做出的貢獻。令人驚嘆的是，一個團隊在此前從未以這種方式合作過，卻能完成如此卓越的上市表現。在核准後的前五個月內，醫師已能為超過 17,000 名病患開立 INCIVEK 聯合療法。醫師與病患的快速採用，反映在 INCIVEK 的高市占率上。

INCIVEK's profile is compelling, for both people with hepatitis C and their doctors. People initiating treatment with INCIVEK include those new to treatment, as well as those previously treated with pegylated interferon and ribavirin. Our research indicates that 60% to 70% of INCIVEK prescriptions written today represent patients who are new to treatment, and many are also fairly early in the course of their disease. Consistent with the specialist-driven nature of the Hepatitis C market, adoption of INCIVEK is highest among gastroenterologists, hepatologists, and infectious disease specialists, and the nurse practitioners and physician assistants who work within these practices. However, I would point out that we are also seeing a number of additional prescribers, who had not recently been prescribing pegylated interferon and ribavirin. This is another encouraging sign of acceptance and broadening of the prescriber base.

INCIVEK 的產品特性對 C 型肝炎患者及其醫師都極具吸引力。開始使用 INCIVEK 治療的人群包含初次治療者，以及先前曾接受聚乙二醇化干擾素與利巴韋林治療者。我們的研究顯示，目前所開立的 INCIVEK 處方中有 60% 至 70% 代表初次治療的病患，且許多人也仍處於疾病進程的相對早期。與 C 型肝炎市場由專科醫師主導的特性一致，INCIVEK 的採用率在腸胃科醫師、肝臟科醫師、感染科專科醫師，以及在這些診所中工作的專科護理師與醫師助理之間最高。不過我要指出的是，我們也看到一些額外的開立者，他們近期並未開立聚乙二醇化干擾素與利巴韋林。這是另一個令人鼓舞的訊號，顯示接受度提升且開立者基礎正在擴大。

In terms of payers, we are in the process of contracting with various commercial and government plans, and we are pleased with the progress so far. Through recent favorable formulary decisions, our co-pay assistance and free drug programs, we continue to ensure broad patient access to INCIVEK. To date, INCIVEK is available on formulary in healthcare plans that represent more than 180 million covered lives in the US, following formal drug utilization reviews. That means that more than half of the population of the US, now has approved access to INCIVEK post-formulary review. Most other patients also have access to INCIVEK, but their plans have not yet reviewed the protease inhibitor class of medicines.

就付款方而言，我們正與各類商業與政府保險計畫洽談簽約中，且對目前的進展感到滿意。透過近期有利的處方集（formulary）決策、我們的自付額（co-pay）補助與免費用藥計畫，我們持續確保病患能廣泛取得 INCIVEK。截至目前，在完成正式的藥物使用審查後，INCIVEK 已納入美國代表超過 1.8 億受保人數的醫療保險計畫之處方集中。這表示，美國人口中已有超過一半，在處方集審查後獲得對 INCIVEK 的核准使用權。多數其他病患也能取得 INCIVEK，但其保險計畫尚未審查蛋白酶抑制劑（protease inhibitor）這一類藥物。

Now, allow me to dig into some of the specifics of the launch. First, I would like to briefly describe for you, our way of thinking about the hepatitis C market. A common way of understanding treatment behavior is by grouping physicians into deciles or 10 groups, based upon how many prescriptions they write. Since the highest prescribers write many more prescriptions, there are far fewer of them in these top deciles. For example, historically, there were less than 100 physicians in the top decile who were producing 10% of all Hepatitis C prescriptions. On the other hand, in the lowest decile, there were more than 2,500 physicians who wrote the same number of Hepatitis C related prescriptions, as those 100 prescribers at the top. Key opinion leaders, many of whom are also involved in clinical trials, typically see the greatest number of people with Hepatitis C, and are well-represented within the top few deciles. Naturally, these physicians possess high awareness of medicines before they launch, and this was no different with INCIVEK.

現在，請容我深入說明上市的一些細節。首先，我想先簡要向各位說明我們對 C 型肝炎市場的思考方式。理解治療行為的一種常見方法，是依醫師開立處方的數量，將醫師分成十分位（deciles）或 10 個群組。由於最高處方量的醫師開立的處方遠多於其他人，因此位於前幾個十分位的醫師人數要少得多。例如，過去在最高十分位中，歷史上不到 100 位醫師就產生了所有 C 型肝炎處方的 10%。另一方面，在最低十分位中，則有超過 2,500 位醫師所開立的 C 型肝炎相關處方總量，與上述最高十分位那 100 位醫師相同。關鍵意見領袖（KOL），其中許多人也參與臨床試驗，通常會看診最多的 C 型肝炎患者，並且在前幾個十分位中占有相當比例。自然地，這些醫師在藥品上市前就具有高度認知，INCIVEK 也不例外。

Through their understanding of INCIVEK, bolstered by our commercial support after launch, this group of physicians rapidly accepted therapy, at a level that has been unprecedented in the treatment of Hepatitis C. INCIVEK, therefore, achieved significant penetration in this segment, and has built a strong base of prescriptions moving forward. Based on our research, we believe the high adoption rates and market share in this segment could result in greater acceptance by the other prescribers, as physician behavior in the top deciles tend to influence the broader prescribing base. At this time, there are thousands of doctors in the mid to lower deciles, who have not yet prescribed any direct acting anti-viral and represent future opportunity. Our goal is to continue to educate and engage healthcare providers who are already prescribing INCIVEK, as well as those in deeper deciles. We are ready have a solid base, as INCIVEK performs more strongly than any other PI in each of the 10 deciles. In fact, based on the most recent data, INCIVEK commands more than 70% market share in any decile of prescribers.

在他們對 INCIVEK 的理解之上，加上我們上市後的商業支持，這群醫師迅速接受該療法，其程度在 C 型肝炎治療領域前所未見。因此，INCIVEK 在此族群中達到顯著滲透率，並建立了未來持續成長的強勁處方基礎。根據我們的研究，我們相信此族群的高採用率與市占率，可能促使其他開方醫師更廣泛接受，因為前幾個十分位的醫師行為往往會影響更廣泛的處方群體。目前，在中低十分位仍有數千名醫師尚未開立任何直接作用抗病毒藥（direct acting anti-viral），這代表未來的機會。我們的目標是持續教育並與已在開立 INCIVEK 的醫療照護提供者互動，同時也涵蓋更深層的十分位醫師。我們已準備就緒並擁有穩固基礎，因為 INCIVEK 在 10 個十分位中的每一個十分位表現都比任何其他 PI 更強。事實上，根據最新數據，INCIVEK 在任何一個十分位的開方醫師中，市占率都超過 70%。

Now I'd like to make a comment on how we have seen the launch of INCIVEK progress from a sales perspective over the past few months, using some of our internally drive data and metrics. I'll refer you to the graph on slide number 24 in our webcast slide deck, which plots our monthly ex-Factory sales of INCIVEK through September, together with data that describes wholesale inventory levels. I'll make that comment, that we have seen continued strong demand, so far in October. Following our launch, we saw an extremely rapid take of uptake -- I'm sorry, a rapid uptake of INCIVEK. In fact, for the first few months, it is not only faster than any other medicine launched within the Hepatitis C market, it may be one of the strongest launches within Pharma in this timeframe. In addition, wholesale inventory levels have remained fairly constant at 2.5 weeks, since the start of the third quarter. This slide is not intended as a forecast or guidance, and we won't necessarily be providing this level of detail in future quarterly calls. But we thought it was important for you to appreciate some of the key metrics we see, at this early stage in the launch.

接下來我想就過去幾個月我們從銷售角度所觀察到的 INCIVEK 上市進展做些評論，並使用部分我們內部驅動的數據與指標。請參考我們網路直播簡報第 24 頁的圖表，該圖呈現截至 9 月的 INCIVEK 每月出廠價（ex-Factory）銷售額，並同時提供描述批發端庫存水位的數據。我也要補充，我們在 10 月迄今仍看到持續強勁的需求。在上市後，我們看到 INCIVEK 的採用速度極為迅速——抱歉，是非常快速的採用。事實上，在最初幾個月，它不僅比 C 型肝炎市場中任何其他上市藥物都更快，甚至可能是此期間整體製藥業最強勁的上市表現之一。此外，自第三季開始以來，批發端庫存水位一直相對穩定，約為 2.5 週。本頁並非預測或指引，我們未必會在未來的季度電話會議中提供如此細節的資訊。但我們認為，在上市初期讓各位了解我們所看到的一些關鍵指標很重要。

Now, some thoughts on how we believe Hepatitis C treatment will evolve with different combinations of medicines, and new regimens. We believe the advancement of Hepatitis C treatment will occur in waves, and we intend to continue to provide new options for patients and physicians as treatment evolves. This will be visible in a number of clinical studies, that you will hear more about at this year's AASLD. The initial wave will be built on expanded indications for interferon-based regimens. A second wave will likely feature more powerful direct-acting antiviral combination regimens, that still include interferon. And the third wave, will hopefully offer all oral or interferon-free regimen. We're excited to be developing medicines that may contribute to these future waves of treatment.

接著談談我們認為 C 型肝炎治療將如何隨著不同藥物組合與新療程而演進。我們相信 C 型肝炎治療的進步將以「波段」方式發生，而我們也打算在治療演進的過程中，持續為病患與醫師提供新的選擇。這將在多項臨床研究中有所呈現，您將在今年的 AASLD 聽到更多相關內容。第一波將建立在干擾素（interferon）為基礎療程的適應症擴大之上。第二波可能會以更強效的直接作用抗病毒藥（direct-acting antiviral）聯合療程為特色，但仍包含干擾素。第三波則希望能提供全口服或無干擾素（interferon-free）的療程。我們很興奮能開發可能對這些未來治療波段有所貢獻的藥物。

Each year during AASLD and other scientific conferences, we get a glimpse into investigational approaches that may benefit patients in the future, and this year is no different. Building upon the strong foundation that the label for INCIVEK already offers, you will begin to see our plans in the first wave to address patient groups that are considered the most difficult to treat, through large well-controlled randomized trials. One such potential group, includes people co-infected with HCV and HIV. Another group is those with recurring hepatitis C, following liver transplantation. Peter will tell you more about these in just a few moments.

每年在 AASLD 與其他科學會議期間，我們都能一窺可能在未來造福病患的研究性方法，今年也不例外。在 INCIVEK 現有標籤（label）所提供的堅實基礎之上，您將開始看到我們在第一波中的計畫：透過大型、良好控制的隨機試驗，針對被認為最難治療的病患族群。其中一個潛在族群包括 HCV 與 HIV 共感染者。另一個族群則是肝臟移植後 C 型肝炎復發的患者。Peter 將在稍後幾分鐘內向各位說明更多。

Relevant to the second wave of this year's AASLD, we will show [FVR] data from the Zenith trial investigating our Quad regimen. Zenith explores the use of INCIVEK, the VX-222 and pegylated interferon with ribavirin, to shorten the duration of therapy for patients even further. In addition to helping people who are new to treatment, this Quad regimen could also help patients whose Hepatitis C is considered difficult to treat, including nulls and cirrhotics.

與今年 AASLD 的第二波相關，我們將展示 Zenith 試驗中研究我們 Quad 療程的 [FVR] 數據。Zenith 探討使用 INCIVEK、VX-222，以及聚乙二醇化干擾素（pegylated interferon）合併利巴韋林（ribavirin），以進一步縮短患者的治療時間。除了幫助初治（new to treatment）患者之外，這個 Quad 療程也可能幫助被認為難治的 C 型肝炎患者，包括無反應者（nulls）與肝硬化患者（cirrhotics）。

You'll also hear about our trial looking at INCIVEK, pegylated interferon and ribavirin in patients with the CC genotype known as IL28B, who may have the potential for total treatment duration of 12 weeks. These individuals represent approximately one-third of the treatment naive group. But we are not stopping there. As we look further into the future, our strategy is to develop all oral interferon-free regimens for the third wave in the second half of this decade. Soon we will see results from an all oral regimen of INCIVEK with VX-222 and ribavirin, as well as steps we are making to add our allele [nucs] into the mix. And again Peter will address this in a moment.

您也將聽到我們的一項試驗，研究在具有 IL28B 的 CC 基因型患者中使用 INCIVEK、聚乙二醇化干擾素與利巴韋林，這些患者可能有機會將總治療療程縮短至 12 週。這些個體約占初治族群的三分之一。但我們不會止步於此。展望更長遠的未來，我們的策略是在本十年後半段為第三波開發全口服、無干擾素的療程。我們很快將看到 INCIVEK 合併 VX-222 與利巴韋林的全口服療程結果，同時也會看到我們將 allele [nucs] 納入組合所採取的步驟。同樣地，Peter 也會在稍後說明。

Now like to turn your attention to our next commercial program, which is in cystic fibrosis. This is an orphan disease affecting approximately 70,000 children and adults in North America and Europe. Earlier this year, we began building the global infrastructure to prepare for the launch of KALYDECO, previously known as VX-770, including the establishment of our European headquarters in Geneva, Switzerland. We carefully built the commercial team when we launched INCIVEK, focusing on the needs of healthcare providers and people with Hepatitis C. Now, we're refining this model to support the launch of KALYDECO, taking into account the unique needs of people with cystic fibrosis. This model will focus on building a long-term relationship with the cystic fibrosis community.

現在我想把各位的注意力轉向我們下一個商業化計畫，也就是囊性纖維化領域。這是一種罕見疾病，在北美與歐洲約影響 70,000 名兒童與成人。今年稍早，我們開始建置全球基礎設施，以為 KALYDECO（先前稱為 VX-770）的上市做準備，包括在瑞士日內瓦設立我們的歐洲總部。在推出 INCIVEK 時，我們審慎地建立商業團隊，聚焦於醫療照護提供者與 C 型肝炎患者的需求。現在，我們正精進這個模式以支援 KALYDECO 的上市，同時考量囊性纖維化患者的獨特需求。此模式將著重於與囊性纖維化社群建立長期關係。

In phase III registration studies, KALYDECO showed rapid significant and sustained improvements across a variety of disease measures, including lung functions in people aged 6 and older with the G551D mutation. KALYDECO is intended to provide patients with a twice-daily oral medicine, to be used with their current medications. It's the first medicine of its kind, to target the underlying cause of CF. Physicians have made great strides over the years in treating CF with the current medicines, and have improved treatment and care for people living with cystic fibrosis. However, these therapies treat only the symptoms of the disease, and it's complication. We're hopeful that KALYDECO, if approved, will build upon the treatment regimen that physicians are already using to offer a significant benefit for the people with cystic fibrosis.

在第三期註冊研究中，KALYDECO 在多項疾病指標上展現快速、顯著且可持續的改善，包括在帶有 G551D 突變且年滿 6 歲的患者之肺功能。KALYDECO 旨在為患者提供每日兩次的口服藥物，並與其現有用藥併用。這是同類首創藥物，能針對囊性纖維化（CF）的根本原因。多年來，醫師在使用現有藥物治療 CF 方面已取得重大進展，並改善了囊性纖維化患者的治療與照護。然而，這些療法僅能治療疾病症狀及其併發症。我們期盼 KALYDECO 若獲核准，能在醫師目前已採用的治療方案基礎上再加強，為囊性纖維化患者帶來顯著效益。

So let's look for a moment at the CF market that we hope to address with KALYDECO There are approximately 1,000 people in the US and Canada who have the G551D mutation on at least one allele, and who are also six years old or older. In Europe, we estimate approximately 1,000 people with the G551D or other gating mutations who are six years old or older consistent with our MAA submissions. Assuming KALYDECO is approved, we will be providing financial and other support services, in order to help patients and their caregivers before and during treatment. The Vertex teams who will lead these efforts will make information about CF as a disease, KALYDECO, reimbursement and support services available to the CF community. I will share more about these programs following approval. We are in a unique position, and feel a great sense of responsibility in launching KALYDECO There are several areas where we are focusing our attention today, to ensure that we get it right. This includes understanding and establishing the value of KALYDECO, as well as focusing on educating the community on the importance of each person knowing their genotype. In this way, we can be sure that KALYDECO can be prescribed for the right patients. We have a lot to do, and we will be ready.

接下來我們花點時間看看我們希望以 KALYDECO 服務的囊性纖維化市場：在美國與加拿大，約有 1,000 人在至少一個等位基因上帶有 G551D 突變，且年滿 6 歲。在歐洲，依據我們的 MAA 送件內容，我們估計約有 1,000 名年滿 6 歲、帶有 G551D 或其他閘控（gating）突變的患者。假設 KALYDECO 獲核准，我們將提供財務及其他支援服務，以協助患者及其照護者在治療前與治療期間獲得支持。將主導這些工作的 Vertex 團隊，會向囊性纖維化社群提供關於 CF 疾病、KALYDECO、給付/報銷以及支援服務的資訊。在獲核准後，我會分享更多關於這些計畫的內容。我們處於一個獨特的位置，並在推出 KALYDECO 時深感責任重大；為確保一切到位，我們今天將注意力聚焦在幾個面向。其中包括理解並建立 KALYDECO 的價值，以及著重教育社群了解每個人知悉自身基因型的重要性。如此一來，我們就能確保 KALYDECO 能被開立給合適的患者。我們還有很多工作要做，而我們會準備就緒。

Thank you. And I would now like to turn the call over to Peter.

謝謝。接下來我想把電話會議交給 Peter。

Thank you, Nancy, and hello to everyone listening to today's call. Vertex's approach to serious diseases has yielded two transformative medicines in two distinct disease areas, Hepatitis C and cystic fibrosis, and a pipeline of opportunities. Our pipeline is the direct consequence of the innovative approach we take in R&D. Mainly, we have the willingness and passion to tackle the toughest diseases. And we don't, and we won't develop (inaudible) medicines. We seek to understand the complexity of the disease pathologies first, and then let the signs lead the away. I think that it is pretty unique, and it makes me optimistic about what we can do beyond INCIVEK and KALYDECO, to transform the treatment of serious diseases.

謝謝你，Nancy，也向所有收聽今天電話會議的各位問好。Vertex 對嚴重疾病的策略已在兩個不同疾病領域——C 型肝炎與囊性纖維化——帶來兩項具變革性的藥物，並建立了一系列研發機會的產品線。我們的產品線是我們在研發上採取創新方法的直接成果。主要在於，我們有意願與熱情去挑戰最棘手的疾病。而且我們不會、也不將開發（聽不清）藥物。我們會先致力於理解疾病病理的複雜性，然後讓線索引導我們前進。我認為這相當獨特，也讓我對我們在 INCIVEK 與 KALYDECO 之外，仍能做些什麼來改變嚴重疾病的治療感到樂觀。

I'll start the day with a review of our Hepatitis C program. INCIVEK combination therapy as Matt noted, is now available in multiple countries. With INCIVEK entering the market so successfully, it obvious that we are now looking to expand the label (inaudible), the combination therapy, and therefore broaden the patient population that may have the opportunity for INCIVEK. We have several drugs underway and planned. These drugs include first, the CONCISE trial which is a Phase IIIb study that will evaluate the potential of INCIVEK combination therapy be to shortened to a total of 12 weeks in some patients. The CONCISE trial will enroll approximately 350 genotype 1 hepatitis C patients, who have the CC variation near the IL28B gene. This study began this week, and is evaluating twice-daily dosing of INCIVEK.

我將以回顧我們的 C 型肝炎計畫作為今天的開場。如 Matt 所提到的，INCIVEK 聯合療法目前已在多個國家上市。隨著 INCIVEK 成功進入市場，很明顯我們現在正著眼於擴大適應症標籤（聽不清）、聯合療法，從而擴大可能有機會使用 INCIVEK 的患者族群。我們有數項藥物正在進行中並已規劃推進。這些項目首先包括 CONCISE 試驗，這是一項第三期 b 研究，將評估在部分患者中，INCIVEK 聯合療法是否有可能縮短至總療程 12 週。CONCISE 試驗將納入約 350 名基因型 1 的 C 型肝炎患者，這些患者在 IL28B 基因附近具有 CC 變異。本研究於本週開始，並評估 INCIVEK 的每日兩次給藥。

Second, a Phase 2 HCV HIV co-infection study. Data from this study will be presented at ASOD next week. We will use what we learned from this study to inform the design of a pivotal co-infection study planned for later this year in approximately 150 people with HCV HIV co-infection. And thirdly, a Phase IIb study evaluating approximately 80 genotype 1 patients, with recurring hepatitis C following a liver transplant. We expect to begin this study also by the end of 2011.

第二，是一項第二期的 HCV/HIV 共感染研究。該研究數據將於下週在 ASOD 發表。我們將運用從此研究中獲得的經驗，來完善今年稍晚規劃進行的一項關鍵性共感染研究設計，該研究預計納入約 150 名 HCV/HIV 共感染者。第三，是一項第二期 b 研究，評估約 80 名基因型 1 患者在肝臟移植後出現 C 型肝炎復發的情況。我們預期也將在 2011 年底前啟動此研究。

As you might expect, to sustain our leadership role in Hepatitis C, beyond our INCIVEK combination medicine, we diligently continue to explore additional, new and improved treatment regimens, allowing potentially for higher cure rates, shorter treatment duration, improved tolerability, higher compliance, increased convenience, and eventually being all oral. In this context, I want to focus your attention to the ZENITH study. This study is investigating the potential of two 4 drug or Quad arms of VX-222 and INCIVEK with pegylated interferon and ribavirin to raise [SVR] rates, and shorten treatment durations to as few as 12 and no more than 24 weeks for people with genotype 1 hepatitis C. This study also includes two arms evaluating on all oral, 3 drug regimen of VX-222 and INCIVEK and ribavirin.

如各位所預期，為了在 C 型肝炎領域維持我們的領導地位，除了 INCIVEK 聯合用藥之外，我們也持續積極探索更多新的、改良的治療方案，期望能帶來更高治癒率、更短療程、更佳耐受性、更高依從性、更高便利性，並最終達成全口服治療。在此背景下，我想請各位特別關注 ZENITH 研究。該研究正在探討兩個四藥（Quad）治療組合的潛力：VX-222 與 INCIVEK 搭配聚乙二醇化干擾素與利巴韋林，以提高 [SVR] 率，並將基因型 1 C 型肝炎患者的治療時間縮短至最少 12 週、最多不超過 24 週。本研究也包含兩個治療組合，評估全口服的三藥方案：VX-222、INCIVEK 與利巴韋林。

During the third quarter, I'm pleased to announce that we completed enrollment of the two all oral arms. And we are nearing the point where all patients will reach the week 12 all oral treatment end point of the study. The study is progressing well, and to date, neither arm has met stopping criteria, with respect to safety or viral breakthrough. We expect to have end of treatment data from these arms early next year. Beyond the ZENITH trial, we are planning additional studies aimed at creating an all oral short duration regimen with high viral cure rate. As part of this strategy earlier this year, we licensed two nucleotide compounds, ALS-2200 and ALS-2158 from Alios Biopharma. Based on impressive in vitro data, we have an opportunity here with this medicine, in combination with INCIVEK and/or VX -222 to explore and develop, several highly potent oral/oral combination regimens for hepatitis C. We continued to work with Alios to initiate first-in-human trials later this year with ALS-2200, followed by a study of ALS-2151 in early 2012.

在第三季期間，我很高興宣布我們已完成兩個全口服治療組合的受試者招募。我們也即將到達所有患者完成本研究第 12 週全口服治療終點的時間點。研究進展良好，截至目前，兩個治療組合在安全性或病毒突破方面都未達到停止標準。我們預期將在明年初取得這些治療組合的治療結束（EOT）數據。除了 ZENITH 試驗之外，我們也規劃進一步研究，目標是建立一個全口服、短療程且具高病毒治癒率的治療方案。作為此策略的一部分，今年稍早我們自 Alios Biopharma 授權引進兩個核苷酸化合物 ALS-2200 與 ALS-2158。基於令人印象深刻的體外數據，我們有機會將此藥物與 INCIVEK 和/或 VX -222 併用，探索並開發多種高效力的口服/口服聯合治療方案，用於 C 型肝炎。我們持續與 Alios 合作，計畫於今年稍晚啟動 ALS-2200 的首次人體試驗，並於 2012 年初接續進行 ALS-2151 的研究。

Turning now to our second disease area, our CF program. We are fully committed to driving forward this program with the goal of treating many patients with this life-threatening disease. As you know, we submitted the NDA for KALYDECO last week, seeking approval for this medicine in the US for a subset of people age six and older with the G551D mutation. The MAA has also been submitted in Europe. The MAA was submitted for approval of people with the G551D mutation, as well as those with other gating mutation. Data from our Phase III program that supported our global regulatory submission, will be presented by leading CF physicians at the North American CF conference next week.

現在轉到我們第二個疾病領域：我們的囊性纖維化（CF）計畫。我們全力致力於推進此計畫，目標是治療許多罹患這種危及生命疾病的患者。如各位所知，我們上週已提交 KALYDECO 的 NDA，尋求在美國核准用於一部分年滿六歲且帶有 G551D 突變的人群。在歐洲也已提交 MAA。該 MAA 申請核准的對象包括帶有 G551D 突變者，以及帶有其他閘門型（gating）突變者。支持我們全球法規申請的第三期計畫數據，將於下週北美 CF 會議上由領先的 CF 醫師發表。

Early treatment of people with cystic fibrosis is of utmost importance, and we have defined a Phase II study to evaluate KALYDECO dose as monotherapy in young children with the G551D mutation, ages two to five years old. We have developed a pediatric formulation for this age group, and are looking forward to initiating this study in 2012. The next stage of development for KALYDECO monotherapy is to initiate studies in people with the CFTR mutations other than G551D for which literature or our own research showed the potential to significantly increase the CFTR function with KALYDECO. We are in discussions with global regulatory agencies about innovative medical strategies to move forward. We anticipate that these studies will also explore biomarkers that correlate with clinical benefits. We will have more to say about this studies, as our discussions evolve with regulators, and the studies get underway which is expected in 2012.

對囊性纖維化患者而言，及早治療至關重要；我們已規劃一項第二期研究，評估 KALYDECO 作為單一療法在帶有 G551D 突變、年齡二至五歲幼兒中的劑量。我們已為此年齡層開發兒科劑型，並期待於 2012 年啟動該研究。KALYDECO 單一療法的下一階段開發，是在除 G551D 之外的其他 CFTR 突變人群中啟動研究；文獻或我們自身研究顯示，KALYDECO 可能顯著提升這些突變的 CFTR 功能。我們正與全球監管機構就創新的醫療策略進行討論，以推動後續進展。我們預期這些研究也將探索與臨床效益相關的生物標記。隨著我們與監管機構的討論持續演進、研究於預計 2012 年展開，我們將就這些研究提供更多說明。

Everyone working on the CF at Vertex has a share vision in what we are trying to do here. For us, it is not about simply making another medicine. It is something we feel deeply committed to, personally and professionally. We see the same passion in the healthcare providers in the areas where we specialize. As such, KALYDECO is just the start, and we feel a real sense of responsibility to develop medicine that can treat many more patients with cystic fibrosis. From the beginning of our cystic fibrosis program, we have focused on ways to improve the lives of people with the most common CFTR mutation, the F508del mutation. These patients have minimal CFTR function, and we believe the best approach is based on therapy called the corrector. We have two correctors in the development, VX-809 and VX-661. Today, we announced that we have initiated part two of our Phase II study of VX-809 in combination with KALYDECO.

Vertex 內所有投入 CF 的同仁，對我們在此要達成的目標有共同願景。對我們而言，這不只是單純再做出一款藥。這是我們在個人與專業層面都深切投入並承諾的事。我們也在我們所專注領域的醫療照護提供者身上，看見同樣的熱情。因此，KALYDECO 只是起點；我們深感責任重大，必須開發能治療更多囊性纖維化患者的藥物。自囊性纖維化計畫一開始，我們就聚焦於改善帶有最常見 CFTR 突變——F508del 突變——患者的生活。這些患者的 CFTR 功能極低，我們相信最佳方法是以稱為「校正劑（corrector）」的療法為基礎。我們有兩個校正劑正在開發中：VX-809 與 VX-661。今天，我們宣布已啟動 VX-809 與 KALYDECO 併用之第二期研究的第二部分。

Part 2 will be geared toward identifying the right dose range for the corrector (inaudible) combination, and we'll evaluate higher doses of VX-809 monotherapy for four weeks, followed by KALYDECO dosing combination with VX-809 for another four weeks. This study will measure sweat chloride, [FVB1] and safety, as well as other markers of clinical activity in about 100 patients with cystic fibrosis, with either one or two copies of the F508del mutation. For VX-661, we are currently working with regulators on the design of our Phase II study to evaluate monotherapy, followed by dosing of VX-661 in combination. Our goal of the Phase II study of VX-809 combination therapy, and the Phase II study with VX-661 is to generate sufficient data by the second half of 2012, to better inform us how to best to move forward in later stage clinical trials.

第二部分將著重於找出校正劑（聽不清）併用療法的適當劑量範圍；我們將先評估較高劑量的 VX-809 單藥治療四週，接著再以 KALYDECO 與 VX-809 併用給藥四週。本研究將在約 100 名囊性纖維化患者中測量汗氯、[FVB1] 與安全性，以及其他臨床活性指標；受試者帶有一份或兩份 F508del 突變拷貝。至於 VX-661，我們目前正與監管機構就第二期研究設計進行合作，先評估單藥治療，之後再進行 VX-661 併用給藥。VX-809 併用療法第二期研究與 VX-661 第二期研究的目標，是在 2012 年下半年之前產出足夠數據，以更好地指引我們在後期臨床試驗中應如何推進。

Turning now to our third and emerging disease area of inflammatory disorders. Specifically, our selective oral JAK3 for the VX-509. In September, we announced top line clinical data from our Phase II proof of concept study in rheumatoid arthritis, in which VX-509 showed significant clinical benefit to people with rheumatoid arthritis, as measured by the ACR-20, ACR-50, and ACR 70 scores. We are also encouraged by the data which showed that 35% of people in the 100 milligram treatment arm, and 37% of people in the 150 milligram treatment arm, experienced a clinical remission. These data has been accepted as a late breaker poster at the upcoming ACR conference in Chicago next week. Based on this data, in the first quarter of 2012 we expect to begin a six month Phase IIb study of VX-509, in combination with methrodrexate that will enroll about 350 people with moderate to severe rheumatoid arthritis, despite stable methodrexate therapy.

現在轉到我們第三個、正在興起的疾病領域：發炎性疾病。具體而言，是我們的選擇性口服 JAK3 抑制劑 VX-509。9 月，我們公布了 VX-509 在類風濕性關節炎第二期概念驗證研究中的主要臨床數據；以 ACR-20、ACR-50 與 ACR 70 分數衡量，VX-509 為類風濕性關節炎患者帶來顯著臨床效益。我們也受到數據鼓舞：在 100 毫克治療組有 35% 的受試者、在 150 毫克治療組有 37% 的受試者達到臨床緩解。這些數據已被接受，將於下週在芝加哥舉行的 ACR 會議上以 late breaker 海報形式發表。基於這些數據，我們預期在 2012 年第一季啟動一項為期六個月的 VX-509 第二期 b 期研究，與甲氨蝶呤（methrodrexate）併用，預計納入約 350 名中度至重度類風濕性關節炎患者，儘管其甲氨蝶呤（methodrexate）治療已維持穩定。

Altogether, we have eight medicines in development, including those that I have already covered. And I would close therefore, on a brief update on VX-765 for epilepsy and VX-797 for flu. VX-765 is on track to begin a Phase IIb study in approximately 400 patients with treatment-resistant epilepsy by the end of this year. VX-765 is an anti-inflammatory medicine that works by modifying (inaudible) immune responses, and is designed to treat people who did not respond to standard treatment for epilepsy, and who are often severely debilitated by frequent seizures daily. We are looking forward to getting the Phase IIb study underway, and learning more about the potential of this medicine in the course of the next year. For VX-797, in the third quarter, we initiated a Phase I trial in healthy volunteers, and we plan to start a proof-of-concept Phase II trial by mid 2012.

總體而言，我們有八項藥物正在開發中，包括我先前已提到的項目。最後我將簡要更新 VX-765（癲癇）與 VX-797（流感）。VX-765 進展順利，預計在今年底前啟動一項第二期 b 期研究，納入約 400 名治療抗性癲癇患者。VX-765 是一種抗發炎藥物，透過調節（聽不清）免疫反應發揮作用，旨在治療對癲癇標準療法無反應、且常因每日頻繁發作而嚴重失能的患者。我們期待推進第二期 b 期研究，並在未來一年中更深入了解此藥物的潛力。至於 VX-797，我們已於第三季在健康志願者中啟動第一期試驗，並計畫於 2012 年年中前啟動概念驗證的第二期試驗。

As you have just heard, we have a lot going on in R&D. We are confident in our approach to tackling diseases that have historically been considered among the most difficult to treat. And we look forward to keeping you updated on the progress in our pipeline. We hope to bring more medicines like INCIVEK to people living with serious diseases. And I want to thank you now, and back to Michael.

如各位剛才所聽到的，我們在研發方面有許多工作同時進行。我們對於攻克那些歷來被認為最難治療的疾病之策略充滿信心。我們也期待持續向各位更新我們產品線的進展。我們希望能將更多像 INCIVEK 這樣的藥物帶給罹患嚴重疾病的人們。現在先謝謝各位，接下來交回給 Michael。

Thank you, Peter. This now concludes our prepared remarks. And we would now like to open the call to Q&A.

謝謝你，Peter。以上為我們事先準備的發言內容。接下來我們將開放電話會議進入問答。

(Operator Instructions)

（接線員指示）

And our first question comes from Geoff Porges from Bernstein

我們的第一個問題來自 Bernstein 的 Geoff Porges

Thank you very much for taking the question. And congratulations, really on a spectacular launch. Great start, and nice to see profitability finally. It has been a long time. And hopefully, you can move beyond the controversial phase of the Company's development. I just wanted to ask a couple questions. First, on gross margin, you've got just the royalty showing in the gross margin now. How long before that goes up to a more normalized level, and what might it look like? And then your patient number looked as though it was flat, in total versus September. Can you tell us what you are seeing, as the month has progressed? Is there genuine (inaudible) in patients? And then lastly, for Nancy. Are there a lot of patients still on the sidelines here, or are we seeing some sort of slowing down of the accumulation of patients? I mean, what proportion do you think we are really tackling, in terms of the addressable market right now?

非常感謝讓我提問。也恭喜你們，這次上市表現確實非常亮眼。開局很棒，也很高興終於看到獲利。這等了很久。也希望你們能走出公司發展中具爭議的階段。我想問幾個問題。第一個關於毛利率：目前毛利率裡看起來只反映了權利金。要多久毛利率才會回升到較正常的水準？大概會是什麼樣子？另外，你們的患者人數看起來與 9 月相比總體持平。能否談談隨著本月進行，你們觀察到什麼情況？患者數是否真的出現（聽不清）？最後一個問題給 Nancy。目前是否仍有很多患者在觀望，還是我們看到患者累積速度有些放緩？我的意思是，就目前可觸及市場而言，你們認為我們實際上正在覆蓋的比例大概是多少？

Jeff, I'll take the first one, which is your asking about the gross to net adjustment, which this quarter was approximately 10%, and that is consistent with the second quarter. As we start to put our contracts and then formulary decisions are made, and that channel comes online, we do expect that gross to net adjustment to start widen. We don't anticipate a significant change in the fourth quarter, although if it should start to widen, but as we get into 2012 and probably and mid 2012, we expect it to be starting to get towards a more normal state.

Jeff，我先回答第一個，也就是你問到的總額到淨額（gross to net）調整；本季約為10%，與第二季一致。隨著我們開始簽訂合約、並做出處方集（formulary）決策，且該通路上線後，我們確實預期總額到淨額調整會開始擴大。我們不預期第四季會有顯著變化；不過若開始擴大，隨著進入2012年、可能到2012年年中，我們預期會逐步走向較正常的狀態。

Ian, I'm sorry, I don't know whether that was my accent or your accent, but I meant gross margin not gross to net?

Ian，不好意思，我不確定是我的口音還是你的口音，但我指的是毛利率（gross margin），不是總額到淨額？

Oh, you mean as far as -- well, let's just be careful on the definition. Gross margin, in terms of revenues, cost of products, and that?

喔，你是指就——嗯，我們先小心定義。毛利率是指營收、產品成本（cost of products）以及那些嗎？

Yes, the cost of products. You are right now, only reflecting royalties. But presumably at some point, you are actually going to reflect true manufacturing costs, and when might that be and what would it look like?

對，產品成本。你們目前只反映權利金（royalties）。但推測在某個時間點，你們會實際反映真正的製造成本；那會在什麼時候、會呈現什麼樣子？

Yes, so we expect to get to a more normal gross margin, probably about 18 months following launch, given the amount of inventory we built, to be ready for launch. More normal gross margin, would be close to normal pharmaceutical margins of around 90%. You would then have to add on to the product royalties.

是的，所以我們預期在上市後大約18個月，毛利率會回到較正常的水準，考量到我們為了上市準備而建立了相當數量的庫存。較正常的毛利率會接近一般藥品的毛利水準，大約90%。之後你還需要再把產品權利金加上去。

Great, thanks.

很好，謝謝。

So, Geoff, to your question, I wasn't exactly crisp on what the first piece of it was? I think talking about patients, we continue to see new patients coming into therapy every week. As we stated, we are above 17,000 now. And in terms of prescribers, at this point, we're seeing between 100 and 150 new physicians prescribing INCIVEK for the first time each week. And that is more than double the rate for any of the other compounds that are competing out there. So, I think you'll agree that, that uptake rate is ahead of any of the other launches in this market. And the only thing I would say is, you look at that, and you add in a constant wholesale inventory, fairly constant between 2 and 2.5 weeks for the last 6 or 7 weeks. And you can come to your own conclusion.

所以，Geoff，針對你的問題，我對第一部分到底是什麼不太確定？我想談到病患方面，我們持續看到每週都有新病患開始接受治療。如我們所說，目前已超過17,000人。至於開立處方的醫師，目前我們每週看到約有100到150位新醫師首次開立INCIVEK。而這個速度是其他任何競爭化合物的兩倍以上。所以我想你會同意，這個採用（uptake）速度領先於此市場上其他任何上市案。我唯一要補充的是，你看這些數據，再加上批發端庫存維持相對穩定，過去6到7週大致維持在2到2.5週。你可以自行得出結論。

Great. Thank you very much.

很好。非常感謝。

Thank you. And our next question comes from Rachel McMinn from Bank of America.

謝謝。下一個問題來自美國銀行（Bank of America）的Rachel McMinn。

Hi, Matt. And I'll add my congratulations as well, on a -- an amazing first start here. I guess I wanted to ask a little bit more about that one slide that I think is going to be the focus of everyone's attention, the $40 million to $45 million, in weekly sales? Is that -- I guess, how are we supposed to look at that? I guess, first question is, is that a gross sales or a net sales number? And then I guess, as we think about that for 4Q, I mean are we talking about $560 million in revenue, if we just kind of use that as a 13 week number? Should we be thinking about $2.3 billion in 2012 sales? I'm just trying to understand what -- I guess those questions. And then -- the next to last question on this is, it was pretty flat between September and October, so what do you think the barriers are, to increased growth beyond what you're seeing in October? Thanks.

嗨，Matt。我也要補上我的恭喜——這裡的第一個開局真的很驚人。我想再多問一點關於那張我認為會成為大家關注焦點的投影片：每週銷售額4,000萬到4,500萬美元？那——我想，我們應該怎麼看待那個數字？第一個問題是，那是總銷售（gross sales）還是淨銷售（net sales）的數字？然後，當我們思考第四季時，我是說，如果我們把它當作13週的數字來用，是不是就代表5.6億美元的營收？我們是否應該把2012年的銷售想成23億美元？我只是想理解——我想就是這些問題。另外——倒數第二個問題是，9月到10月之間相當平坦，所以你認為在10月所看到的水準之外，進一步成長的障礙是什麼？謝謝。

Rachel, thanks for the question, a lot of questions in there. First of all, let me give you the basis of the data in the chart. And then you can use the data as you wish. It is actually net revenues that we record. And to validate that, what you'll actually be able to do, is take the quarters with the revenues. And you will be able to actually calculate back, and you will get approximately $420 million of net revenues. It is calculated as taking the months worth of net revenues, and then averaging out a weekly net revenue for that month. So you will find that it does equate back to our net revenue line, in our income statement, appropriately so. Now as far as -- should you then take the number that is between $40 million and $45 million in September and October, and translate that through to both November and December, I'll leave that for you to do a forecast. It is not intended as a forecast.

Rachel，謝謝你的提問，裡面有很多問題。首先，我先說明圖表中數據的基礎。接著你可以依你的需要使用這些數據。那其實是我們入帳的淨營收（net revenues）。為了驗證這點，你實際上可以用各季的營收數字。你可以回推計算，會得到約4.2億美元的淨營收。其計算方式是取該月份的淨營收，然後換算成該月的每週平均淨營收。所以你會發現，它確實能適當地回推到我們損益表上的淨營收項目。至於——你是否要把9月與10月介於4,000萬到4,500萬美元之間的數字，延伸推算到11月與12月，我把這留給你做預測。這並非用來作為預測。

The reason we put this slide up, was to get people -- to get a -- help people get an understanding of the high volume of patients that are actually being treated, and the high volume of scripts that are being written by prescribers. Our feeling has been that this has not always been tracked the way, that we are tracking it internally. And we believe that we have the most accurate internal metrics of how this launch is going. And we believe hat that's revenues, and looking at the inventory in the channel, because we monitor that on a daily basis. And so, we wanted to give people an idea, of where this launch currently stands. And I think the best way to do that is on the revenues. And Nancy will make a comment -- assume about how we look at the future from there.

我們放這張投影片的原因，是希望讓大家——幫助大家理解實際接受治療的病患量很高，以及處方醫師開立的處方量也很高。我們的感覺是，外界並不總是以我們內部追蹤的方式來追蹤這些數據。而我們相信，我們擁有最準確的內部指標來衡量這次上市進展。我們認為那就是營收，以及通路中的庫存水位，因為我們每天都在監控。因此，我們想讓大家對這次上市目前所處的位置有個概念。我認為最好的方式就是用營收來呈現。Nancy會補充評論——假設——我們如何從這裡看待未來。

Yes, in response to the chart, Rachel, I think -- you are noticing that the rate of growth has changed. But I think that is more a reflection of the exceptionally quick ramp early in the launch. There are further opportunities for penetration into this market. There are many more patients to treat. And we are going to continue to do everything we are doing, with a highly effective sales team to target those prescribers and that patient base.

是的，針對這張圖表，Rachel，我想——你注意到成長率已經改變。但我認為那更多反映的是上市初期異常快速的拉升（ramp）。在這個市場仍有進一步滲透的機會。還有更多病患需要治療。我們將持續做我們正在做的一切，透過一支高效的銷售團隊，鎖定那些處方醫師與病患族群。

Great, thanks very much.

很好，非常感謝。

Thank you. And our next question comes from Terence Flynn, Goldman Sachs.

謝謝。下一個問題來自高盛（Goldman Sachs）的Terence Flynn。

Congrats as well from me. I was just wondering if you guys think you have the appropriate sized sales force to maybe target the rest of the prescriber base. Has it kind of broadened your reach? And then, just had one question on the cystic fibrosis program as well. I was wondering -- I know in the first part of the combo trial of 508, and going after 508 patients, you were looking at homozygous patients. But I noticed in Part two, you're going after, both homozygous and heterozygous patients. And just wondering, for the reason in the change there?

我也表示恭喜。我只是想知道，你們是否認為目前的銷售團隊規模足以去觸及其餘的處方醫師基礎。你們的覆蓋範圍是否已經擴大？另外，還有一個關於囊性纖維化（cystic fibrosis）計畫的問題。我想問——我知道在508聯合試驗的第一部分、針對508病患時，你們看的是同型合子（homozygous）病患。但我注意到在第二部分，你們同時針對同型合子與異型合子（heterozygous）病患。想請問，這樣改變的原因是什麼？

So, Terence, maybe I'll go first. This is Nancy, in the question about the sales force. I think our commercial strategy right out of the gate was absolutely the right one. And that was that we had an appropriately sized sales force. And let's remind everyone, we were up against two companies, not one. We focused on the KOLs and the top prescribers. And we know that those behaviors that they generate, influence people who are prescribing in the deeper deciles.

所以，Terence，也許我先說。我是 Nancy，針對銷售團隊的問題。我認為我們一開始的商業策略絕對是正確的。也就是我們配置了規模適當的銷售團隊。也提醒大家，我們面對的是兩家公司，不是一家。我們聚焦在 KOL 與最主要的開立處方醫師。而且我們知道，他們所帶動的行為會影響到更深層十分位（deciles）中也在開立處方的人。

We also know that the top half of physicians generate 90% of the prescriptions. And those are the physicians we are targeting on, so the very top of that list, on down. Now, in response to what we saw as additional prescribers, who I mentioned that hadn't been in the market in the recent past, in the last year or two. And in response to the fact that, now we are starting to really into some pull through, that we have got half of those covered lives, past a formulary decision. We are likely to make a minor adjustment, and add a few people here and there, as we find where we could use a little more backup.

我們也知道，前一半的醫師產生了 90% 的處方量。而這些就是我們鎖定的醫師，也就是名單最頂端一路往下。現在，針對我們看到的新增開立處方者——我提到過，這些人在最近一段時間、過去一兩年並未在市場上活躍——以及針對我們現在開始真正看到一些「拉動效應（pull through）」的事實：我們已經讓一半的承保人數在處方集（formulary）決策後獲得涵蓋。我們很可能會做一些小幅調整，視需要在某些地方增補幾位人員，作為額外支援。

This is Bob, I'll take the second part of your question about CF. So yes, you are right. We studied homozygous patients first in the 509 -- in the 809 study -- I'm sorry. Because it was a homogeneous population, and because all of the CFTR in that case is of the same type, carries all the same mutant protein. Obviously, that is 40% of the population. However, there is a large group of patients out there who are heterozygotes. They are a little bit more heterogeneous, because they have another gene on the other allele. And it is important as we think about Phase 3, and what populations we would want to study, to get an understanding of what the effect of the combination of treatment in heterozygotes is. And that's why it was added into the second cohort, kind of looking ahead to where we will ultimately want to be, obviously in the market, and also for the studies, of course.

我是 Bob，我來回答你關於 CF 的第二部分問題。所以是的，你說得對。我們先在 509——呃，在 809 研究中——抱歉——先研究同型合子（homozygous）患者。因為那是一個同質性族群，而且在那種情況下所有 CFTR 都是同一種類型，攜帶相同的突變蛋白。很明顯，那占了族群的 40%。不過，外面還有一大群患者是異型合子（heterozygotes）。他們更具異質性，因為在另一個等位基因上有另一個基因。因此，當我們思考第三期（Phase 3）以及想研究哪些族群時，理解在異型合子中合併治療的效果就很重要。這也是為什麼把它加入第二個隊列（cohort），算是提前布局我們最終想達到的位置——顯然包括市場端，也包括研究端。

And will 551D patients be excluded, patients who have 551D on the other allele?

那麼會排除 551D 患者嗎？也就是在另一個等位基因上帶有 551D 的患者？

Yes, of course, they would, because they would obviously respond to 770. And of course, many of those patients already in our trial. The addressable populations are already our trials, so there aren't too many of those out there.

是的，當然會，因為他們顯然會對 770 有反應。而且當然，這些患者中有很多已經在我們的試驗裡。可納入的族群其實已經在我們的試驗中，所以外面剩下的不會太多。

Okay, thanks a lot.

好的，非常感謝。

Thank you. Our next question comes from Geoff Meacham from JPMorgan.

謝謝。下一個問題來自摩根大通（JPMorgan）的 Geoff Meacham。

Wow, I'm moving up in the queue. So congrats on the launch, first of all. I have a couple of questions for you guys on CF. So you are studying in Delta F different doses and durations for the combo, but how do you think a larger study will be designed? And is a response guided, is something that you think is really feasible for registration type of study? And I have one follow-up.

哇，我在隊列裡往前了。首先恭喜上市。我有幾個關於 CF 的問題。你們在 Delta F 族群中針對聯合療法研究不同劑量與療程長度，但你們認為更大型的研究會如何設計？另外，以反應來引導（response guided）的方式，你們覺得在註冊型研究（registration type of study）中真的可行嗎？我還有一個追問。

In terms of how we go forward, we obviously have to see the result of the current trial, before we can design the next one. And that is obviously, what we are trying to do. I think the issue of a response guided therapy, will depend on our analysis of the data that we are getting. Part of our goal is to collect information to allow us to decide whether there are response markers, that we can use to identify responsive patients. And that is the goal of this next trial. I would not speculate as to whether it would -- what its regulatory utility would be, until we actually see the strength of the data, and make a determination of that.

至於我們接下來如何推進，我們顯然必須先看到目前試驗的結果，才能設計下一個。而這也正是我們正在做的事。我認為「反應引導治療」這個議題，將取決於我們對所取得資料的分析。我們的部分目標是蒐集資訊，讓我們能判斷是否存在反應標記（response markers），可用來辨識有反應的患者。而這就是下一個試驗的目標。在我們真正看到資料力道並做出判斷之前，我不會推測它在法規上的效用會是什麼。

Got you. And just from a reimbursement perspective, is -- what have your initial discussions revealed, for the core G551D patients? And do you get the sense, there is a worry from insurance companies about off label use, in Delta F for getting these patients or is there more flexibility given the orphan disease?

了解。那從給付（reimbursement）的角度來看，你們與核心 G551D 患者相關的初步討論揭示了什麼？你們是否感覺保險公司會擔心在 Delta F 上的適應症外使用（off label use）來取得這些患者？還是因為是罕見疾病，所以彈性更大？

Orphan diseases and ultra orphan diseases, particularly as we will initially be entering command prices in the range of rare diseases. And I would think because of that, the managed care community is going to be a little bit careful about what they will reimburse for. But you have to balance that with the fact that these are kids who are really, really suffering from a debilitating disease. And we've got really profound data to show what it can do to change their lives.

罕見疾病與超罕見疾病，特別是我們一開始將以罕見疾病的價格區間進入市場。我認為因此，商業保險／管理式醫療（managed care）社群在核付哪些項目時會比較謹慎。但你也必須平衡一個事實：這些孩子正因為一種使人衰弱的疾病而非常、非常痛苦。而我們有非常有力的數據顯示，這項治療能如何改變他們的生活。

Okay, thanks a lot.

好的，非常感謝。

Okay. Our next question comes from Mark Schoenebaum, ISI Group

好的。下一個問題來自 ISI Group 的 Mark Schoenebaum。

Hi, guys. Add my congratulations. I had a couple of questions maybe for Nancy. Number one, are you surprised that -- unless I think -- please correct me if I miss -- if I heard incorrectly on any of these things, but are you surprised that the majority of patients coming on to INCIVEK are naives? And then related to that, if we could drill on to the refractory population. I remember pre-launch for many years, there was a lot of discussion around the size of the, quote, Refractory warehouse of patients. I always heard figures between 100,000 and 300,000 patients that were out there that had been treated before, and it failed.

嗨，各位。也讓我表達恭喜。我有幾個問題，可能是問 Nancy。第一，你是否驚訝——除非我理解有誤——如果我漏聽或聽錯任何部分請糾正我——你是否驚訝於開始使用 INCIVEK 的患者大多是未治療過（naive）的？接著相關地，我們能否深入談談難治（refractory）族群。我記得在上市前很多年，大家一直在討論所謂「難治患者倉庫（Refractory warehouse）」的規模。我一直聽到的數字是在 10 萬到 30 萬之間，指的是曾接受治療但失敗的患者。

And you're telling us that only 17,000 patients so far have been treated with INCIVEK. So, A, why wouldn't there just be a massive acceleration into that warehouse? And, B, the deciles that you talked about, are they the same, when you look at the naive population versus that warehoused population? Are the doctors the same? Or would those deciles look different? Thanks a lot.

而你們告訴我們，到目前為止只有 17,000 名患者接受了 INCIVEK 治療。所以，A，為什麼不會出現大量加速進入那個「倉庫」的情況？B，你提到的十分位（deciles），在看未治療（naive）族群與那個被「倉庫化」的族群時，是否相同？醫師是一樣的嗎？還是那些十分位會看起來不同？非常感謝。

Okay, well, first of all thank you, Mark, and everyone who has already said, congratulations. We really appreciate that. It feels good. Let me see if I can get all of those questions you had. I'll start with the last one first. And that is, although perhaps the top decile physicians might be likely to see a group of patients who are a little more skewed toward the difficult to treat. And therefore they may be seeing more of the re-treat patients, or I think where you are going with the warehousing, the more difficult to treat patients. You might make that assumption, but it is really a guess. Because to my knowledge, we have never measured that, and there are no data sources for that. That would require a proprietary one-off study.

好的，首先謝謝你，Mark，也謝謝所有已經說恭喜的人。我們真的很感謝。感覺很好。我看看能不能把你那些問題都回答到。我先從最後一個開始。也就是說，雖然也許最高十分位的醫師更可能看到一群患者，其組成會更偏向較難治療者。因此他們可能會看到更多再治療（re-treat）患者，或我想你所指的「倉庫化」——也就是更難治療的患者。你可以做這樣的假設，但那其實只是推測。因為就我所知，我們從未衡量過這件事，而且也沒有可用的資料來源。那需要一個專有的一次性研究（proprietary one-off study）。

Onto the naives, I think the rate of patient uptake is reflective of a balance that, yes, goes a little bit more toward naives than we had originally thought. And so it isn't that the re-treated or more serious patients aren't there in the mix. It is just that, this is such great news, that not only patients, but physicians who hadn't been treating are rejoining. And we hear physicians telling us that patients are just showing up. So, what that means, in terms of your other questions about a massive acceleration into that warehouse, it is not quite that planful a process.

關於初治（naive）患者，我認為患者採用率反映了一種平衡：是的，確實比我們原先想的更偏向初治患者一些。因此，並不是再治療或病情更嚴重的患者沒有在組合中。只是，這是個非常好的消息：不僅是患者，連先前未治療的醫師也正在回流加入。而且我們聽到醫師告訴我們，患者就是自己上門。所以，就你其他關於是否會大幅加速導入那個「倉庫」的問題而言，這並不是一個那麼有計畫、按部就班的流程。

Each office comes up with their own approach. And I have really only heard of one yet, one academic practice in the entire United States, that went through a very formal thought-provoking process to call patients back. Otherwise, it is sort of a mix of, who happens to be on recall, which patients are aggressive about calling in. And I think the patients who know they've got a great shot at being cured with the new therapy, are likely to put more pressure, and come in early, and that's likely what we are seeing.

每個診所都會提出自己的做法。而我目前真的只聽說過一個——全美只有一家學術型醫療機構——採取非常正式、深思熟慮的流程去把患者召回。除此之外，基本上就是各種混合：哪些人剛好在回診名單上、哪些患者會積極打電話進來。我認為那些知道自己用新療法有很大機會治癒的患者，可能會施加更大壓力、更早來就診，而這很可能就是我們正在看到的情況。

May I ask one follow-up?

我可以再追問一個問題嗎？

Sure.

當然。

Do you have an updated estimate as to the size of that refractory warehouse? And within that group, how many are addressable, meaning accessible? Thank you very much.

你們對那個難治（refractory）「倉庫」的規模是否有更新的估計？另外在那個族群中，有多少是可處理的，也就是說可接觸、可觸及的？非常感謝。

I do not have an updated size of the warehouse. But I can tell you that the patients are coming in fast and furious. And they're -- more and more physicians are stepping up to treat them. And we can't keep up with new patients kits.

我沒有更新的「倉庫」規模數字。但我可以告訴你，患者來得又快又猛。而且——越來越多醫師正在站出來治療他們。我們甚至跟不上新患者套件（kits）的供應。

Thanks.

謝謝。

You're welcome.

不客氣。

Your next question comes from Yaron Werber from Citigroup

下一個問題來自花旗集團（Citigroup）的 Yaron Werber。

Thanks for taking my question. So congrats as well. And I have a couple of questions sort of follow on Mark's questions. So help us understand maybe just a little bit, what you seeing in terms of, we've been hearing a lot on whether practices actually have enough capacity to treat these patients? And what are you seeing maybe in your top deciles, versus sort of the lower deciles, in terms of their capacity? And then I have a follow-up, also.

謝謝讓我提問。也恭喜你們。我有幾個問題，算是延續 Mark 的問題。請幫我們更了解一下：我們聽到很多關於各診所是否真的有足夠的量能來治療這些患者？你們看到的情況是什麼——例如在你們最高十分位（top deciles）與較低十分位（lower deciles）的診所之間，在量能方面有何差異？我也還有一個追問。

Yes, thanks. That's a great question, and we actually have done a little mini survey to look at that. And as you might imagine, the people who are most known for being the really experienced treaters, where we went first, to get their support, their practices in some cases are filling up. Now it is less than half. But I would think that it is skewed a little bit toward the highest prescribers, because they are known hepatology centers. There is still capacity. I would remind you again in the other offices, and in deeper deciles, and in those new physician offices who are coming back to prescribe again, or deciding to prescribe for the first time. And a lot of offices who are feeling the crush of that demand from the patient side, are adding new staff, et cetera. So each practice addresses it a little differently. And I would say, that is a great challenge to have.

好的，謝謝。這是個很好的問題，我們其實做了一個小型調查來看這件事。如你所想，那些最有名、最有經驗的治療者——我們一開始先去爭取他們支持的那些人——他們的診所在某些情況下確實快滿了。不過不到一半。但我認為這會稍微偏向最高開立處方者，因為他們是知名的肝病學中心。仍然有量能。我也再次提醒你，在其他診所、在更深的十分位，以及那些重新回來開立處方、或第一次決定開立處方的新醫師診所，仍有空間。而且很多診所感受到患者端需求的擠壓，正在增聘新員工等等。所以每個診所的因應方式都不太一樣。我會說，這是一個很好的「甜蜜的負擔」。

And then let me ask you, in terms of net, and that is very useful. About eight years ago, it was thought that about 100,000 patients or 120,000 patients came on therapy. And let's say about 75% of those with genotype 1, I mean do you think that this time around, we're going to get to the same patient number? Or it is going to be higher, or maybe perhaps it's going to be lower this time, since these drugs are a little bit more difficult to use? And it's going to take longer to treat them? Do you have any thoughts about that?

接著我想問，從整體（net）的角度來看，這也很有幫助。大約八年前，大家認為大概有 100,000 或 120,000 名患者開始接受治療。假設其中約 75% 是基因型 1；你覺得這一次我們會達到相同的患者數量嗎？還是會更高，或也許會更低，因為這些藥物使用上稍微更困難？而且治療時間會更長？你有什麼想法嗎？

Yaron, I think that with, if you laid out either the number of prescribers and how fast they are coming online to use INCIVEK -- and by the way, there is another drug, so they are adding some more effort here, right? But just INCIVEK alone, and/or you look at the rate of uptake of INCIVEK, it far outpaces what we saw when the pegylated interferon's were launched. So, I have no reason to be concerned about that.

Yaron，我認為如果你把開立處方的醫師數量，以及他們開始上線使用 INCIVEK 的速度攤開來看——順帶一提，市場上還有另一個藥，所以他們也在投入更多力氣，對吧？但就 INCIVEK 單獨來看，或你看 INCIVEK 的採用速度，它遠遠快過我們在聚乙二醇化干擾素（pegylated interferon）上市時看到的情況。所以我沒有理由對此感到擔心。

As far as the difficulties to use this regimen, that has not been an issue, whatsoever, in physician selection at the rates that you're seeing. I don't understand the question.

至於使用這個療程的困難度，在你看到的這種醫師選擇速度下，完全不是問題。我不太理解這個問題。

The question really has to do with -- it is not just the ramp, but sort of the amplitude of how many patients are going to come on therapy, and are going to be treated at any one-time.

我的問題其實是——不只是爬坡（ramp），而是整體幅度（amplitude）：會有多少患者開始接受治療，以及在任何一個時間點會有多少人正在被治療。

There is no survey of patients, you really don't -- we know how many patients are infected. And we took a guess at how many patients are out there. And you can see by the sales, that are a heck of a lot of patients are showing up. And some of the top prescribers, they are at a flow rate that they want to be at, but we have a whole bunch of physicians to go. So were going to go after that business.

沒有針對患者的調查，你其實不會——我們知道有多少人感染。而我們也猜測外面大概有多少患者。你從銷售數字就看得出來，有非常非常多的患者正在出現。而一些最高開立處方者，他們的流量已經達到他們希望的水平，但我們還有一大批醫師尚未啟動。所以我們會去爭取那部分業務。

Yaron, I would just add to your point about the usage of the drug in the physician's office. One thing that comes back constantly from the field is viral cure. It came back through our clinical trials, of the importance of maintaining a high viral cure. And so when you comment on the use of the drug, viral cure and potentially 80% of patients that go on therapy have a chance of a cure. That drives the rapid uptake of INCIVEK.

Yaron，我想就你提到藥物在醫師診所端的使用情況再補充一點。從第一線不斷回傳的一件事就是病毒治癒（viral cure）。這也在我們的臨床試驗中反覆顯示：維持高病毒治癒率的重要性。因此，當你談到藥物的使用時，病毒治癒，以及可能有 80% 的接受治療患者有機會治癒，這正是推動 INCIVEK 快速採用的動力。

And Nancy, you mentioned there is another drug out there? (Laughter). I didn't hear about it.

Nancy，你提到外面還有另一個藥？（笑聲）。我沒聽說過。

Okay. Nevermind.

好吧。算了。

Thank you.

謝謝。

Thank you. Our next question comes from Philip Nadeau from Cowen and Company.

謝謝。下一個問題來自 Cowen and Company 的 Philip Nadeau。

Good evening and thanks for taking my question. Actually just a follow-up to Yaron's question. Nancy, when you were answering his question, you mentioned that some of the high prescribers are undertaking efforts to hire new staff. Could you talk a little bit about what you guys do to facilitate that process? And is there a pharmacological economic case that can be made? Or maybe more specifically an economic case that could be made for physicians, where adding that staff, is actually profitable for their practices?

晚安，謝謝讓我提問。其實是延續 Yaron 的問題。Nancy，你在回答他的問題時提到，一些高處方量的醫師正在努力增聘新員工。你能談談你們會做些什麼來促進這個流程嗎？是否能提出一個藥物經濟學（pharmacological economic）的論點？或更具體地說，是否能為醫師提出一個經濟面的論點：增加這些人力實際上能讓他們的診所獲利？

I think that is an economic situation, that each physician has to look at. It probably becomes more relevant, when you look at all of the specialties a center offers, and they want to be seen as a liver center, and they therefore want to be able to really give great effective treatment for the HCV patients, along with other issues. Your other question was about bringing staff on. They used to do things like that years ago. It is really not allowed anymore. It is no longer considered a compliant practice, and that is not a strategy that we are pursuing.

我認為那是一種經濟層面的情況，需要每位醫師自行評估。當你檢視一個中心所提供的所有專科、而他們希望被視為肝臟中心，因此也希望能夠在處理其他議題的同時，為 HCV 病患提供真正優質且有效的治療時，這點可能就更為相關。你另一個問題是關於引進人員。他們多年前確實曾做過那類事情。但現在其實已不再被允許。那不再被視為合規的作法，而這也不是我們正在採取的策略。

Okay. And just one clarification. When you were answering Yaron's question you said about half of physicians are seeing a capacity issue. And I wasn't clear if that was half of the top decile physicians or half the physicians overall?

好的。再請教一點釐清。你在回答 Yaron 的問題時提到，大約有一半的醫師正面臨產能問題。我不太確定那是指前十分位（top decile）的醫師中有一半，還是指整體醫師中有一半？

No, no, what I said was, it is less than half of the physicians that have any kind of complaint or issue about capacity constraints. But that one might logically go to the next step, where the largest practices that are best known, had an aggressive flow of patients. And I think those are oftentimes the physicians we all go to for opinions. So there is plenty of capacity left. There are plenty of patients lining up. And as I said, I think this is a great challenge for us to continue to face, with our sales force who has done a great job to this point.

不，不，我的意思是：有任何抱怨或對產能限制有任何問題的醫師，不到一半。但從邏輯上，這可能會延伸到下一步：那些最大型、最知名的診所，病患流入量很積極。而我認為，那些往往也是我們大家會去徵詢意見的醫師。所以仍然有充足的產能。也有很多病患在排隊等候。而如我所說，我認為這對我們而言是一項很大的挑戰，需要持續面對；我們的銷售團隊到目前為止做得非常出色。

Great, thanks for taking my questions.

很好，謝謝你回答我的問題。

Thank you.

謝謝。

Thank you. Our next question comes from Howard Liang with Leerink Swann.

謝謝。下一個問題來自 Leerink Swann 的 Howard Liang。

Congrats. Two questions, first, make sure I heard it correctly, did Peter say that in Europe, KALYDECO was filed for G551D and other activating mutations?

恭喜。兩個問題，第一個，確認我是否聽對了：Peter 是否說在歐洲，KALYDECO 已針對 G551D 以及其他活化突變（activating mutations）提出申請？

Yes, for -- so that, Howard, that is true. The submission in Europe based on discussions we had over there with several regulatory agencies and registers was basically sent in, by covering 551D and the obligating mutations.

是的——所以，Howard，這是真的。歐洲的送件是基於我們在那邊與數個監管機構及登錄系統（registers）的討論，基本上是以涵蓋 551D 以及其他符合條件的突變（qualifying mutations）為範圍送交。

Okay, great. And then I think it was Nancy, who mentioned wave two. Can you talk about when you might be able to start Phase 3 for your Quad, and what data you need to make that decision? Thanks.

好的，很好。接著我想是 Nancy 提到第二波（wave two）。你能談談你們的 Quad 可能何時能啟動第三期（Phase 3），以及你們需要哪些數據來做出該決策嗎？謝謝。

So -- want to take it?

那——要不要你來回答？

Obviously, we are going to be looking at the results of the current study, the results of which are going to be presented at the ASLD meeting next week. We are really considering that, and will be formulating a plan, and going to the regulatory agencies, likely within the next couple of months. And hope to have a registration strategy within that time frame.

很明顯地，我們會先看目前研究的結果；該結果將在下週的 ASLD 會議上發表。我們正在認真評估，並將擬定計畫，可能在接下來幾個月內與監管機構溝通。並希望在那段時間內確立註冊（registration）策略。

On top of that, Howard, there is also something we have to consider the, the triple oral -- that is currently in the makes and then we have beginning of next year data, that might actually also influence, how we develop the entire going forward. We really want to keep your attention on this triple oral too, because so far as I said, it's going nicely, and well. And we will have patients at the 12 week treatment point in a couple weeks from now. And this is something you should not forget.

此外，Howard，我們也必須考量目前正在進行中的三合一口服（triple oral）方案；而明年年初會有數據出來，可能也會影響我們整體後續的開發方向。我們也希望你把注意力放在這個三合一口服上，因為到目前為止，如我所說，進展順利、表現良好。再過幾週，我們就會有病患達到 12 週治療節點。這是你不應該忽略的。

Thanks very much.

非常感謝。

Thank you. And our next question comes from Ted Tenthoff from Piper Jaffray

謝謝。下一個問題來自 Piper Jaffray 的 Ted Tenthoff。

Thank you very much. Let me add my congratulations too. And I'm really excited about all the moving parts of the story right now. And I think there is a lot of growth drivers that we're looking at. Just one quick question if I may. Have you heard of cases, of either death from anemia in cirrhotic patients, or any cases of Steven Johnson syndrome that have popped up?

非常感謝。也讓我加入恭喜。我對目前這個故事的所有動態部分都感到非常振奮。我認為我們正在看到很多成長驅動因素。如果可以的話，我只有一個簡短問題。你們是否聽過有肝硬化病患因貧血死亡的案例，或是有任何史蒂文斯－強森症候群（Stevens-Johnson syndrome）的案例出現？

So, this is Bob, I'll take that one. We obviously can't -- we can't really comment on specific cases. I'll just say that, obviously we appreciated our responsibilities for monitoring safety, very aggressively during the launch. And we have a very intensive post-marketing surveillance system. We are looking at that very carefully. At this point, all I can say is that the safety profile we're seeing post launch, is consistent with the profile that is in our label. And beyond that, I'm just not able to comment on any specific cases.

我是 Bob，我來回答。我們當然不能——我們確實無法對特定個案發表評論。我只能說，很明顯地，我們在上市初期非常積極地履行監測安全性的責任。我們也有非常密集的上市後監測系統。我們正在非常仔細地檢視。截至目前，我能說的是：我們在上市後看到的安全性概況，與標籤（label）中所載的概況一致。除此之外，我無法對任何特定個案進一步評論。

Okay, Great. I appreciate that. And I have heard feedback that the training programs are going well, so I do appreciate the efforts that you are making there. Thanks so much.

好的，很好。我理解並感謝。而且我也聽到回饋說訓練計畫進行得很順利，所以我也很感謝你們在那方面所做的努力。非常謝謝。

Yes.

是的。

Thank you. Our next question comes from David Friedman with Morgan Stanley

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

Thanks for taking the question. The is questions about the average weekly INCIVEK revenue chart. And the first question is, it seems like that chart includes stocking revenue. Are there figures on an average weekly, that you could give ex -- inventory? And then the other question is as you look week to week with your data, that you guys have access to that we don't, how does that compare to what you see in IMS? Is there a consistent delta between the two, or is it more variable?

謝謝讓我提問。這個問題是關於 INCIVEK 平均每週營收圖表。第一個問題是：看起來該圖表包含了鋪貨（stocking）營收。你們是否能提供一個扣除——庫存（inventory）後的平均每週數字？第二個問題是：當你們逐週查看你們掌握、而我們無法取得的數據時，與你們在 IMS 看到的相比如何？兩者之間是否存在一致的差異（delta），還是差異較為波動？

So, let me -- a number of questions there, Dave. And maybe Nancy will help me out as well, with the final piece of IMS as well. But as far as the chart is concerned, the key numbers that I think you're focusing on, is both Q3 and then October. Through that period, the inventory in the channel stayed at 2.5 weeks. So it's not really affecting our net revenues that we are reporting. There is some slight growth, but it is really not having that significant of an effect, given that the inventory in the channel is spinning very quickly -- 2.5 weeks it sits there. And then it gets out to the pharmacists and to the patients. So the inventory holding period, because of the brevity of the holding period, really isn't having an effect. So what we tried to show in this chart, was a couple of things. And this may be where -- this is where Nancy will take up for me as well. But it is that the inventory holding period is flat through the Q3, where we have recorded the significant revenues. And it remained flat into October as well, the inventory holding period.

Dave，你這裡有好幾個問題。也許 Nancy 也會協助我回答最後一段關於 IMS 的部分。就圖表而言，我想你關注的關鍵數字是第三季（Q3）以及 10 月。在那段期間，通路庫存維持在 2.5 週。因此它其實並未影響我們所報告的淨營收。雖然有些微成長，但由於通路庫存周轉非常快——庫存只停留 2.5 週——因此影響並不顯著。接著就會流向藥師與病患。所以庫存持有期間，因為持有期很短，實際上並沒有造成影響。因此我們在這張圖表中想呈現幾件事。而這可能也是——Nancy 會接著補充的部分。也就是：在第三季期間，庫存持有期間是持平的，而我們在該季記錄了顯著營收。而進入 10 月後，庫存持有期間也同樣維持持平。

And then we are still recording the significant level of revenues, on an average weekly basis, which for September and October was between $40 million and $45 million. So it helps you understand the -- to use a financial term, run rate of the revenues, that we are recording at this point, and -- which is the measure of the number of patients we are treating. The reason we did put this chart up, is that all of our internal metrics of measuring this launch, including our financial statements, suggest that we are treating many more patients than might be tracked on some other sources. And we felt it was appropriate to address that. I don't know whether Nancy has a--?

然後我們仍在以平均每週為基礎記錄相當可觀的營收水準，9 月與 10 月介於 4,000 萬至 4,500 萬美元之間。因此，這有助於你理解——用一個財務術語來說——我們目前所記錄的營收「運行率」（run rate），而——這也是我們正在治療的病患人數的衡量指標。我們之所以放上這張圖表，是因為我們用來衡量此次上市的所有內部指標（包括我們的財務報表）都顯示，我們治療的病患數遠多於某些其他來源可能追蹤到的數字。我們覺得有必要對此作出說明。我不知道 Nancy 是否有——？

Yes, so, David, I really don't want to talk specifically to IMS, I mean that's not what I'm here for. I think you should refer to the three product bulletins that they have issued within the last three weeks. And I would also remind you that most of the data, that many of you are using are the NPA data, and they only represent retail sales.

是的，所以，David，我其實不想特別談 IMS，我的意思是那不是我來這裡的目的。我認為你應該參考他們在過去三週內發布的三份產品公告。我也要提醒你們，你們許多人使用的大多數資料是 NPA 資料，而那只代表零售銷售。

Okay, I guess just back sort of to Ian, your comments, if I could quickly. If you look from 1Q -- or sorry, sorry -- the first Q of sales or 2Q, the inventory build was $37.5 million. And you say, that is sort of two to three weeks, and so that was about $15 million a week implied. So it would seem like there would be sort of a one-time build up to get to a higher run rate, that would have been captured in 3Q? Is that not correct, or?

好的，我想如果可以的話，回到 Ian 的評論，我快速問一下。如果你看 1Q——或抱歉，抱歉——第一季的銷售或 2Q，庫存建立是 3,750 萬美元。而你說那大概是兩到三週，所以隱含約每週 1,500 萬美元。所以看起來似乎會有一次性的建立，以達到更高的運行率，而那應該會在 3Q 被反映出來？這不正確嗎，還是？

We can talk about this off line, David,.

David，我們可以私下再談這個。

Okay.

好的。

The second quarter inventory build is all about filling the channel, so you can get the product to the patient as quickly as possible. And that is all about launch, and that is very typical as I'm sure you're aware. The key part of this graph is more about the third quarter. And then into current data, as recently as the end of last week, where we have seen inventory levels start to stabilize is our wholesalers get a very good understanding of how to send that product to the pharmacy. The fact that the wholesalers are understanding now -- that how to stock inventory. And their maintaining two to three weeks of inventory is the key part of this chart. It's less about that initial piece at the beginning, which is atypical for stocking.

第二季的庫存建立完全是為了把通路補滿，讓產品能盡快到達病患手上。這完全是上市（launch）所需，而且如你所知，這非常典型。這張圖的關鍵其實更在第三季。以及到目前的數據，甚至到上週末為止，我們看到隨著批發商對如何把產品配送到藥局有了非常清楚的理解，庫存水位開始趨於穩定。事實上，批發商現在已經理解——如何備貨。而他們維持兩到三週的庫存，是這張圖表的重點。重點較不在一開始那段初期的部分，那段對備貨而言是非典型的。

Okay.

好的。

Thank you. Our next question come from Brian Abrahams from Wells Fargo Securities

謝謝。我們的下一個問題來自 Wells Fargo Securities 的 Brian Abrahams。

Good evening. This is Matthew Andrews calling in for Brian. Thanks for taking the questions. Can you give us any sort of sense on what you're seeing, in terms of the first and second refills for INCIVEK? Is it consistent with the compliance rate you have seen in the Phase 3 studies?

晚安。我是 Matthew Andrews，代替 Brian 來電。謝謝讓我提問。你們能否提供一些你們所看到的情況，關於 INCIVEK 的第一次與第二次續配（refill）？是否與你們在第三期研究中看到的依從性（compliance）比率一致？

That's a great question, Matthew, and it is a little early. We are just starting to get early samplings of those data. It is small, but what we have seen, suggests that it is consistent with what's occurred in our clinical trials.

這是個很好的問題，Matthew，不過現在還稍早。我們才剛開始取得那些數據的早期抽樣。樣本量不大，但我們目前看到的情況顯示，與我們臨床試驗中的結果一致。

Great, thank you.

很好，謝謝。

Thank you.

謝謝。

Thank you. Our next question is from Jason Kantor from RBC Capital Markets.

謝謝。我們的下一個問題來自 RBC Capital Markets 的 Jason Kantor。

Thanks, and let me also add my congratulations. I'm a little confused by these lower decile prescribers. Are they in fact, still prescribing two drug regimens, or are they just not treating anyone at this point? And I think you said, you were adding 100 to 152 -- to 100 to 150 new docs per week? Where do you think that trajectory maxes out? And over what period of time, do you think you're going to be penetrating some of the lower decile prescribers?

謝謝，也讓我補上一句恭喜。我對這些較低十分位（lower decile）的開立處方醫師有點困惑。他們實際上仍在開立雙藥療法（two drug regimens）嗎？還是他們目前根本沒有在治療任何人？另外我想你說你們每週新增 100 到 152——也就是 100 到 150 位新醫師？你認為那個軌跡最高會到哪裡？以及在多長的時間內，你們認為會滲透到一些較低十分位的開立處方醫師？

Yes, so. Let me see if again, I can be more clear about that. There are about -- and every Company cuts this a little differently. But we believe there are about 8,000 prescribers out there, who historically looking, at pegylated interferon and ribavirin were using some amount. If you took those 8,000 prescribers, and cut it in half, the top 4,000 wrote 80%-some of the prescriptions. 85% approximately. Okay? So I guess the point I am trying to make on that one, Jason, is just that people say, well, some people here -- well, you haven't called on this doctor, or that doctor.

是的。我再試著把這點說得更清楚。大約有——而且每家公司切分方式會有些不同。但我們相信大約有 8,000 位開立處方醫師，從歷史上看，在聚乙二醇化干擾素（pegylated interferon）與利巴韋林（ribavirin）方面都有一定用量。如果把這 8,000 位醫師對半切，前 4,000 位開了 80% 多的處方。大約 85%。好嗎？所以我想表達的重點是，Jason，有人會說，嗯，有些人這裡——嗯，你們還沒拜訪這位醫師或那位醫師。

Well, that is a good thing because you want to start with the most prolific writers up in that top decile, where you can get a huge stream of prescriptions going. And they will also influence the people deeper in those deciles. So, I'm just trying to encourage people to think about that it is not a straight run rate. This is not a doctor for a doctor. Sometimes we're comparing your kitchen faucet and the stream of water that comes out of that, at the bottom, with what you see when a fire hydrant is flushed in the top decile.

嗯，那其實是好事，因為你會想先從最常開立處方的那群人開始，也就是在最高十分位（top decile）裡，你可以讓處方量形成很大的流量。而且他們也會影響在更低十分位的那些人。所以我只是想鼓勵大家用這種方式思考：它不是一條筆直的運行率曲線。這不是一位醫師對一位醫師的線性對比。有時候我們是在比較你家廚房水龍頭底部流出的水流，與在最高十分位把消防栓打開沖水時你看到的水流。

Right. But you're suggesting that these top decile, at least not the top 4,000, but something about that are -- have a lot of built-up demand, we're expecting it. And in some cases, are running at full capacity, whereas perhaps some of these others haven't come online yet. So in terms of the incremental growth, it seems that a lot of that is in these new docs that you are targeting.

了解。但你的意思是，這些最高十分位——至少不是指前 4,000 位全部，但其中某些——有很多累積的需求，我們原本就預期會出現。而且在某些情況下，他們已經滿載運作；相較之下，其他一些人可能還沒開始加入。所以就增量成長而言，看起來很大一部分來自你們正在鎖定的這些新醫師。

Okay. Let me give you a couple more numbers that should help with that. Of those 4,000 prescriptions -- I'm sorry -- 4,000 physicians who write 85% of the prescriptions, right? At least -- or we are approaching, just about half of them, have now written at least one prescription for INCIVEK. That is the hardest thing, is getting someone to try the drug the first time, right? So that is pretty aggressive penetration -- 4 or 4.5 months into a launch. The other way that we look at this -- so, is there more opportunity? Yes. But the other way we look at this is, we look at how many physicians in each of those deciles, have written for your drug, at least one prescription.

好的。我再給你幾個數字，應該能幫助釐清。在那 4,000 位——抱歉——開出 85% 處方的 4,000 位醫師之中，對吧？至少——或者說我們正接近——其中大約一半的人，現在已經至少開過一張 INCIVEK 的處方。最難的是讓某個人第一次嘗試這個藥，對吧？所以在上市 4 或 4.5 個月的時間點，這是相當積極的滲透率。我們看待這件事的另一種方式——所以，還有更多機會嗎？有。但我們另一種看法是，我們會看在每個十分位中，有多少位醫師至少為你的藥開過一次處方。

And I can tell you, that when we do that, the number for the top decile is the highest percentage. And literally, it goes down like you couldn't have planned it more beautifully to -- in the 20% range at the bottom. And it is up, in the mid-to high 80%s at the top. That is exactly the way you want to do it. So we've gotten the biggest bang for the buck out of the gate. But there is more usage out there yet, that we will be continuing to pursue throughout the coming months.

我可以告訴各位，當我們這麼做時，最高十分位的數字是最高的百分比。而且確實如同你不可能規劃得更漂亮一樣——一路往下遞減到最底部約 20% 的區間。而在頂端則上升到 80% 中段到高段。這正是你希望看到的方式。所以我們一開始就以最少的投入獲得了最大的效益。但外面仍然還有更多使用量，我們會在接下來幾個月持續推進。

Okay. One last question, so the people that are not prescribing, either your drug or Merck's drug, are people actually starting patients without protease inhibitors at this point? I mean, that seems almost crazy but.

好的。最後一個問題，所以那些沒有開立處方、無論是你們的藥或默克的藥的人，現在是否真的有人在沒有蛋白酶抑制劑的情況下開始讓病人用藥？我的意思是，那看起來幾乎很瘋狂，但……

Yes, that's a great question, Jason. Yes, there are, because we don't have indications for the co-infected patients yet, for liver transplants. So there are always going to be -- I mean until we get additional expanded labels, there are always going to be some physicians who are prescribing that. And it is also hard to tell, how much of the total prescription usage that is still in that -- the old standard of care, is just the patients who started earlier, and they are just still finishing out, because it takes them a year to through the therapy.

是的，這是個很好的問題，Jason。是的，確實有，因為我們目前還沒有針對共感染病人、以及肝臟移植的適應症。所以總是會有——我的意思是，在我們取得更多擴大標籤之前，總是會有一些醫師會那樣開立處方。而且也很難判斷，在總處方使用量中，有多少仍屬於——舊的標準治療——其實只是較早開始治療的病人，他們只是還在把療程完成，因為整個治療要花一年才能走完。

There is also phenomena that is kind of interesting, in that when you -- even if you are a teaching physician or an influencer, or one of these top prescribers is many of them will try a drug for a while, and see how their response is, until they put more patients on it. That phenomena, is probably has not happened yet. That is generally six month to a year out, when you see that happen. That is in most markets, I'm not predicting this one -- but most -- if you talk to physicians, they will often say, I want to give it a try, in so many patients, so you can see how -- in clinical trials, so to speak.

另外還有一種現象也挺有意思：當你——即使你是教學醫師或意見領袖，或是這些頂尖開立處方者之一，很多人會先試用某個藥一段時間，看看反應如何，之後才會讓更多病人使用。這種現象可能還沒有發生。一般要到六個月到一年後，你才會看到這種情況出現。這在大多數市場都是如此，我不是在預測這個市場——但大多數情況下——如果你跟醫師聊，他們常會說，我想先在一定數量的病人身上試試看，好讓你看看——某種程度上就像臨床試驗一樣。

Thank you very much.

非常感謝。

Operator, we are at 6.15 PM. We will just have time for two more questions.

接線員，我們現在是晚上 6 點 15 分。我們只剩下時間再回答兩個問題。

Thank you. And our next question comes from Matt Roden with UBS

謝謝。下一個問題來自 UBS 的 Matt Roden。

Thanks for having me on the call, and extending the time of the call. It's very generous of your time, and we appreciate it. Also, just wanted to congratulate the entire organization on the launch. Really very impressive. So, Nancy, you mentioned that you are seeing prescribers new to Hepatitis C. And can you say what proportion of INCIVEK volumes are being written by those physicians new to hep C? And then, Bob, when you think about this 770 809 trial, the Part 2 of this trial, are you confident that the treatment duration is sufficient enough to see a difference in lung function, secondary endpoint. The feedback we've heard from docs, is that maybe two months treatment might give a better shot of seeing an FEV-1, but is that -- do you think that that is right? Is that something you take issue with?

謝謝讓我加入這通電話，也謝謝延長會議時間。你們撥冗非常慷慨，我們很感激。另外，也想恭喜整個組織這次上市。真的非常令人印象深刻。所以，Nancy，你提到你們看到一些以前沒有開立 C 型肝炎處方的醫師。你能否說明 INCIVEK 的用量中，有多少比例是由那些對 C 肝而言屬於新開立者的醫師所開出的？然後，Bob，當你看這個 770 809 試驗、也就是第二部分時，你是否有信心治療期間足以在肺功能這個次要終點上看到差異？我們從醫師那邊聽到的回饋是，也許兩個月的治療更有機會看到 FEV-1 的變化，但那——你覺得這說法對嗎？你是否不同意這點？

Let me get the easy question out of the way. When I talk about prescribers who haven't been historically prescribing, they are not necessarily new to this. They might just not have written for the last couple of years. Sometimes that is because they know there are new therapies coming. So, they are not brand-new to HCV. They just haven't written in the last year or two. And they are, I can tell you there are about 500 of them. And they write a low volume of prescriptions. So there are people who are just sort of dabbling and coming back in, because they -- I'm assuming because they see advances, and a new opportunity. And now I will turn it over to Peter.

我先把比較簡單的問題回答掉。當我談到那些過去沒有一貫開立處方的醫師時，他們不一定是新手。他們可能只是過去幾年沒有開立處方。有時候那是因為他們知道有新療法即將到來。所以，他們並不是對 HCV 完全陌生。他們只是過去一兩年沒有開立而已。而且我可以告訴你，大約有 500 位這樣的醫師。他們開立的處方量不高。所以有些人只是稍微試水溫、重新回來，因為他們——我推測是因為看到了進展與新的機會。接下來我把問題交給 Peter。

So, the question about response and length of treatment in combinations. I would say, when you go back, I think what you normally see, is for single regimens, correct, or, I think we have data for 809, that shows that in the course of four weeks, you basically can see a statistically significant difference in FEV, but also in some of those, let's say, response, markers that we basically have investigate, as sweat chloride is one of them, and maybe LCI is another one, and so on. So I think this is basically being driven by our earlier 809 studies, where we can see that. In terms of the potentiation, when you go into the combination mix, I think potentiation is a shorter-term type of response, because you basically potentiate what is already out there on the surface. And I think we believe that you are also there, in a four week period we'll see a substantial difference, if it is really working out. It is all driven by the right exposure levels that you have to have for those compounds, and the right target organs. And I think that is the reason why we do dose range findings, to figure out how that all works.

關於反應與合併療法治療長度的問題。我會說，回頭看，你通常會看到的是，對於單一療法，對吧？或者，我想我們有 809 的數據顯示，在四週的過程中，你基本上就能看到 FEV 出現具統計顯著性的差異；同時也能在一些——比如說——我們正在研究的反應指標上看到差異，例如汗氯（sweat chloride）是其中之一，可能 LCI 也是，等等。所以我認為這主要是由我們先前的 809 研究所驅動，因為我們能看到那樣的結果。至於增效（potentiation），當你進入合併用藥的組合時，我認為增效屬於較短期的反應，因為你基本上是在增強表面上既有的作用。而且我們相信，在四週期間，如果它真的有效，我們也會看到相當顯著的差異。這一切都取決於你必須讓這些化合物達到正確的暴露濃度，以及到達正確的標的器官。我想這就是我們做劑量範圍探索的原因，用來釐清這些如何運作。

Do you expect the results of these studies to, essentially give you proof of concept, because it sounds like it is a relatively short duration without necessarily having optimized dose?

你是否預期這些研究的結果，基本上能給你概念驗證（proof of concept），因為聽起來療程相對較短，而且未必已經把劑量最佳化？

I can (inaudible) at least, I would say that. Proof of concept is more linked to therapeutic long-term value. It could come out that way, but I think that needs to be seen.

我至少可以（聽不清）我會這麼說。概念驗證更偏向與治療的長期價值連結。結果可能會呈現那樣，但我認為還需要再觀察。

Okay, thanks very much.

好的，非常感謝。

Okay. And our last question comes from Katherine Xu from William Blair.

好的。我們最後一個問題來自 William Blair 的 Katherine Xu。

Hi, thank you for taking my questions. I'm just curious, Peter or Bob, can you describe the profile differences between 809 and 661?

嗨，謝謝讓我提問。我只是好奇，Peter 或 Bob，你們能否描述 809 與 661 之間的特性差異？

Yes, I can. So that's -- so both of them are basically molecules, number one, that are in the same class of correctors, and they bind basically to the same site of CFTR. So I think from that point of view, they are identical. The difference is tissue penetration. On the one hand so 661 has a higher tissue penetration in animals, into tissues of relevance like lung. And you have -- potentially if, that holds true in patients, which we don't know yet, a 4 point higher chance of penetration, which could impact the therapeutic benefit, if it ever comes to that point.

是的，我可以。所以——兩者基本上都是分子，第一，它們屬於同一類的校正劑（correctors），而且基本上都會結合到 CFTR 的同一個位點。所以從這個角度來看，它們是相同的。差異在於組織滲透性。一方面，661 在動物體內對相關組織（例如肺）的組織滲透性更高。而且如果——這在病人身上是否成立我們還不知道——若確實如此，可能有高出 4 個百分點的滲透機會，這可能會影響治療效益，如果未來真的走到那一步的話。

That is one of the things -- and we could also go on the other side, with a lower dose regimen, which will basically make the pills more -- and the compliance and convenience of the entire thing better. That is the one thing. The other thing is half-life of 661 is substantially different from 809. It has a longer half-life, and that gives you at least an option for once a day, if you ever want to go for that. That is probably the two biggest distinctions. And then there are some smaller ones, in terms of how to take the compound and manufacture it, and all those type of things, which are less relevant, because they are sort of in the same price class.

那是其中一點——我們也可以從另一個方向著手，採用較低劑量的給藥方案，基本上會讓藥丸更——並且讓整體的依從性與便利性更好。這是一點。另一點是 661 的半衰期與 809 有顯著差異。它的半衰期更長，這至少讓你有一個選項：如果你日後想要那樣做，可以改為每日一次。這大概是兩個最大的差異。然後還有一些較小的差異，例如如何服用該化合物以及如何製造它等等，這些相對不那麼相關，因為它們大致屬於相同的價格區間。

Great. And then finally, what do you know so far about the pricing of the INCIVO in East European countries? So far I think we know, in the UK it is 35,000. There is a negotiated pricing with the French government, but it is being launched right now, country by country, any information there?

很好。最後，你目前對 INCIVO 在東歐國家的定價了解多少？到目前為止，我想我們知道在英國是 35,000。與法國政府有協商定價，但目前正按國家逐一上市，那邊有任何資訊嗎？

Well, we can tell you that it is available in the UK and Germany and Sweden and France. The only price that we know of that is available publicly is in the UK. There will be a range of prices in Europe, depending on local factors.

嗯，我們可以告訴你，它在英國、德國、瑞典和法國都有供應。我們所知道、且可公開取得的唯一價格是在英國。歐洲各地的價格會有一個區間，取決於當地因素。

All right. Sorry, one last question, if you don't mind. Just wondering about your RA program strategy going forward? Phase 3 will be very large, and involves a lot of investment. Just curious what are the thoughts there, in terms of partnering, or take it all the way yourself?

好的。抱歉，如果你不介意，最後再問一個問題。只是想了解你們未來的 RA 計畫策略？第三期將會非常龐大，且需要大量投資。只是好奇你們的想法是什麼：在合作夥伴方面，或是自己一路做到最後？

Well, Katherine, the first step for that program, as Peter said in his comments, is that we plan to do a six month study, in which we have Phase 2b study, that we expect to start at the end of this year. That's the next step. So when you talk about Phase 3, progress to Phase 3, we would like to see good data from that Phase 2b, before we commit to the breadth of the Phase 3 program, which as you know in this disease, would be thousands of patients. But that would be -- much further out, that would be 2014, or 2013 around there.

嗯，Katherine，正如 Peter 在他的評論中所說，該計畫的第一步是我們計畫做一項為期六個月的研究，也就是第二期 b（Phase 2b）研究，我們預期在今年年底開始。那是下一步。所以當你談到第三期、推進到第三期時，我們希望在承諾第三期計畫的規模之前，先看到第二期 b 的良好數據；如你所知，在這個疾病領域，第三期將會是數千名病患。但那會是——更往後的事，大概是 2014 年，或 2013 年左右。

We will make that judgment at that time. But I would stay consistent to comments financially, which is if we continue to perform well, with INCIVEK. And following along with the launch of our CF opportunity, I think we're going to have plenty of financial capacity to still reinvest in the Company, and still have significant earnings. And I think the JAK3 compound gives the Company a significant growth opportunity for the 2015 plus period, which I think is very important when you look at the Company long-term.

我們會在那個時點做出判斷。但我會在財務方面維持與先前評論一致，也就是如果我們持續在 INCIVEK 上表現良好，並且配合我們 CF 機會的上市進展，我認為我們將有充足的財務能力持續再投資公司，同時仍能維持可觀的獲利。而且我認為 JAK3 化合物為公司在 2015 年以後的期間帶來顯著的成長機會；從公司長期來看，這點非常重要。

Thank you.

謝謝。

You're welcome.

不客氣。

At this time, I would like to turn the call back over to Michael Partridge for any closing remarks.

此時，我想把電話交回給 Michael Partridge，請他做任何結語。

Thank you. We will now conclude the call. We certainly appreciate you taking the time to turn in. Tonight, the IR team, joined by Ian, Nancy, Bob, and Peter will be available in the office to answer any additional questions you have. Thank you.

謝謝。我們現在將結束本次電話會議。我們非常感謝你撥冗收聽。今晚，投資人關係（IR）團隊將與 Ian、Nancy、Bob 和 Peter 一起在辦公室待命，回答你可能有的任何其他問題。謝謝。

Ladies and gentlemen, this does conclude your conference. You may all disconnect, and have a wonderful day.

各位女士、先生，本次電話會議到此結束。各位可以掛線，祝各位有美好的一天。