吉利德科學 (GILD) 2018 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Gilead Sciences First Quarter 2018 Earnings Conference Call. My name is Candace, and I will be your conference operator today. (Operator Instructions)

女士們、先生們，感謝各位的耐心等待，歡迎參加吉利德科學公司2018年第一季財報電話會議。我叫坎迪斯，今天我將擔任你們的會議接線生。（操作說明）

And as a reminder, this conference call is being recorded.

再次提醒大家，本次電話會議正在錄音。

I would now like to turn the call over to Sung Lee, Vice President of Investor Relations. Please go ahead.

現在我將把電話交給投資人關係副總裁李成先生。請繼續。

Thank you, Candace, and good afternoon, everyone. Just after market closed today, we issued a press release with earnings results for the first quarter 2018. The press release and detailed slides are available on the Investor Relations section of the Gilead website.

謝謝你，坎迪斯，大家下午好。今天股市收盤後不久，我們發布了 2018 年第一季獲利結果的新聞稿。新聞稿和詳細幻燈片可在吉利德公司網站的投資者關係部分查看。

The speakers on today's call will be John Milligan, President and Chief Executive Officer; John McHutchison, Chief Scientific Officer and Head of Research and Development; and Robin Washington, Executive Vice President and Chief Financial Officer. Also in the room with us for the Q&A session is Andrew Cheng, Chief Medical Officer and Executive Vice President.

今天電話會議的發言人有：總裁兼執行長約翰·米利根；首席科學官兼研發主管約翰·麥克哈奇森；以及執行副總裁兼財務長羅賓·華盛頓。與我們一同參加問答環節的還有首席醫療官兼執行副總裁 Andrew Cheng。

Before we begin with our prepared comments, let me remind you that we will be making forward-looking statements, including plans and expectations with respect to products, product candidates, financial projections and the use of capital, all of which involve certain assumptions, risks and uncertainties that are beyond our control and could cause actual results to differ materially from these statements.

在我們開始發表準備好的評論之前，請允許我提醒各位，我們將發表一些前瞻性聲明，包括有關產品、候選產品、財務預測和資本使用的計劃和預期，所有這些都涉及某些我們無法控制的假設、風險和不確定性，這些因素可能導致實際結果與這些聲明存在重大差異。

A description of these risks can be found in the latest SEC disclosure documents and recent press releases. In addition, Gilead does not undertake any obligation to update any forward-looking statements made during this call.

有關這些風險的描述可以在最新的美國證券交易委員會披露文件和最近的新聞稿中找到。此外，吉利德不承擔更新本次電話會議中任何前瞻性聲明的義務。

Non-GAAP financial measures will be used to help you understand the company's underlying business performance. The GAAP to non-GAAP reconciliations are provided in the earnings press release as well as on the Gilead website.

我們將使用非公認會計準則財務指標來幫助您了解公司的基本業務表現。GAAP 與非 GAAP 的調整表已在盈利新聞稿以及吉利德網站上提供。

I will now turn the call over to John Milligan.

現在我將把電話交給約翰·米利根。

Thank you, Sung, and thank you, everyone, for joining us today. I would like to start by introducing John McHutchison and Andrew Cheng in their new roles. As you know, Norbert made the decision earlier this year to step down from his position as Chief Scientific Officer. I've worked along Norbert for 27 years, and on behalf of the entire Gilead organization, I would like to express my profound thanks to him for his many, many contributions.

謝謝宋，也謝謝各位今天蒞臨。首先，我想介紹一下約翰·麥克哈奇森和安德魯·程的新職位。如你所知，諾伯特在今年稍早決定辭去首席科學官一職。我與諾伯特共事了 27 年，我謹代表整個吉利德公司，對他所做的許多貢獻表示由衷的感謝。

In terms of succession, Gilead is fortunate to have strong leaders across our R&D organization who will build on the tremendous success that we have had for over 3 decades. I look forward to the leadership of John in his new role as Chief Scientific Officer and Head of R&D and Andrew in his new role as Chief Medical Officer as we continue our work to invent and develop new products for patients in need.

在繼任方面，吉利德很幸運，我們的研發部門擁有眾多優秀的領導者，他們將在我們過去三十多年來取得的巨大成功的基礎上繼續前進。我期待約翰擔任首席科學官兼研發主管，安德魯擔任首席醫療官，在他的領導下，我們將繼續致力於為有需要的患者發明和開發新產品。

Turning to the business and results for the quarter. We continue to see strong growth in our HIV business, driven by broad acceptance and uptake of our Descovy-based regimens. We are confident that this franchise will remain a key growth driver for the company moving forward.

接下來談談本季的業務和業績。我們的 HIV 業務持續強勁成長，這得益於我們基於 Descovy 的治療方案的廣泛接受和採用。我們相信，該特許經營權將繼續成為公司未來發展的重要驅動力。

One of the products contributing to the growth is our latest Descovy-based single-tablet regimen, Biktarvy, formerly referred to as BIC/F/TAF, which was approved in February by the U.S. Food and Drug Administration for the treatment of HIV. In March, Biktarvy was added to the U.S. DHHS guidelines for the use of antiretroviral agents in adults and adolescents living with HIV as one of the recommended initial regimens.

推動成長的產品之一是我們最新的基於 Descovy 的單片療法 Biktarvy，以前稱為 BIC/F/TAF，該療法於 2 月獲得美國食品藥物管理局批准用於治療 HIV。今年 3 月，Biktarvy 被美國衛生與公共服務部 (DHHS) 列入成人和青少年 HIV 感染者抗逆轉錄病毒藥物使用指南，作為推薦的初始治療方案之一。

Last week, we announced that the CHMP has adopted a positive opinion on the Marketing Authorization Application for Biktarvy in the EU. We expect approval in the third quarter of this year. Biktarvy represents Gilead's sixth single-tablet regimen, and with the approval of SYMTUZA in the EU by our partner, Janssen, the fourth containing Descovy backbone.

上週，我們宣佈人用藥品委員會 (CHMP) 對 Biktarvy 在歐盟的上市許可申請給予了積極意見。我們預計將於今年第三季獲得批准。Biktarvy 是吉利德的第六款單晶片療法，而隨著我們的合作夥伴 Janssen 在歐盟批准 SYMTUZA，第四款含有 Descovy 骨架的療法也獲得了批准。

SYMTUZA is currently under FDA review in the U.S. Biktarvy is a combination of an unboosted integrase inhibitor and a well-established backbone Descovy. Its small-size, mineral drug interactions and established renal and bone safety profile make Biktarvy an important treatment option for most HIV patients. This is particularly true for an aging HIV population, which is at increased risk for age-related morbidities.

SYMTUZA 目前正在接受美國 FDA 的審查。 Biktarvy 是一種未增強的整合酶抑制劑與成熟的骨架藥物 Descovy 的組合。由於其體積小、藥物交互作用少，且腎臟和骨骼安全性良好，Biktarvy 成為大多數 HIV 患者的重要治療選擇。對於老化的愛滋病毒感染人群來說，這一點尤其如此，因為他們患上與年齡相關的疾病的風險更高。

In February, at CROI, the conference on retroviruses and opportunistic infections, one of the most important meetings for HIV research, we had the opportunity to share our progress on the work we are doing to bring innovative therapies to people living with HIV. Gilead's compounds were featured in 21 abstracts and data presentations, including promising preclinical results from our HIV cure research program. These data show that the combination of 2 investigational agents, GS-9620, a toll-like receptor 7 agonist; and PGT121, a broadly neutralizing antibody that binds to the HIV envelope, induce viral remission in the absence of antiviral therapy in SIV-infected monkeys and support clinical investigation of such combination strategies.

今年二月，在逆轉錄病毒和機會性感染會議（CROI）上，這是愛滋病毒研究領域最重要的會議之一，我們有機會分享了我們在為愛滋病毒感染者帶來創新療法方面所取得的進展。吉利德的化合物在 21 篇摘要和數據報告中有所提及，其中包括我們 HIV 治癒研究計畫取得的令人鼓舞的臨床前結果。這些數據表明，兩種研究藥物 GS-9620（一種 Toll 樣受體 7 激動劑）和 PGT121（一種與 HIV 包膜結合的廣譜中和抗體）的組合，可以在未接受抗病毒治療的情況下誘導 SIV 感染猴子的病毒緩解，並支持對這種組合策略進行臨床研究。

Investigators also presented Phase III data in patients switching from a regimen containing abacavir, dolutegravir and lamivudine to Biktarvy and data from a multinational Phase III study of Biktarvy in women, a group that is often underrepresented in clinical trials. Data for these studies further demonstrate that Biktarvy may be appropriate for a wide range of people living with HIV.

研究人員也發表了從含有阿巴卡韋、多替拉韋和拉米夫定的方案轉用 Biktarvy 的患者的 III 期數據，以及一項針對女性的 Biktarvy 多國 III 期研究的數據，女性群體在臨床試驗中往往代表性不足。這些研究的數據進一步表明，Biktarvy 可能適用於廣泛的 HIV 感染者。

The data presented at CROI represented encouraging progress and demonstrates our continued leadership in driving innovation in HIV therapy.

在 CROI 大會上公佈的數據代表了令人鼓舞的進展，並表明我們在推動 HIV 治療創新方面持續處於領先地位。

Moving to liver disease. Our team recently attended the International Liver Congress in Paris, where there's a lot of emerging data around NASH and hepatitis B. The particular focus on NASH was very much like what we saw with the early breakthroughs in hepatitis C before the disease took center stage at the conference. John will share more specifics about EASL and the data presented there in a few minutes.

轉而討論肝病。我們的團隊最近參加了在巴黎舉行的國際肝病大會，會上公佈了許多關於非酒精性脂肪性肝炎（NASH）和乙型肝炎的新數據。大會對NASH的關注程度，與我們之前在C型肝炎成為大會焦點之前所看到的早期突破非常相似。約翰將在幾分鐘後分享更多關於EASL及其所展示數據的具體細節。

In oncology, we're encouraged by the response from the health care provider and patient communities to the lifesaving potential for Yescarta in people with aggressive large B cell lymphoma who have run out of options. We're seeing an increase in patient enrollment as clinical experience with Yescarta steadily grows and additional authorized cancer centers with expanded geographic reach come online.

在腫瘤學領域，我們很欣慰地看到，醫療保健提供者和患者群體對 Yescarta 的救命潛力給予了高度評價，尤其對於那些已經沒有其他治療選擇的侵襲性大 B 細胞淋巴瘤患者而言。隨著 Yescarta 的臨床經驗不斷積累，以及更多授權、覆蓋範圍更廣的癌症中心上線，我們看到患者註冊人數不斷增加。

We have now completed the authorization of 40 cancer centers and are on track to have enough centers certified to treat 80% of Yescarta-eligible patients in the United States by the middle of the year.

我們目前已完成 40 家癌症中心的授權，並預計在今年年中之前獲得足夠的認證中心，為美國 80% 符合 Yescarta 治療條件的患者提供治療。

The future is incredibly bright for cellular therapy, and we're excited to be at the forefront of the field pursuing a variety of approaches to develop the next-generation of cellular therapies in blood cancers and solid tumors. As I look ahead to the remainder of 2018, we will continue to advance scientific innovation, including progressing a robust pipeline, which has the potential to transform the treatment of NASH, inflammatory diseases and certain cancers. In addition, we will look for business development opportunities that add to our pipeline and capabilities across our therapeutic areas, diversify our portfolio and increase future opportunities for growth.

細胞療法的未來無比光明，我們很高興能夠站在該領域的前沿，探索各種方法來開發下一代血液癌症和實體瘤的細胞療法。展望 2018 年剩餘時間，我們將繼續推動科學創新，包括推動強大的研發管線，有可能改變 NASH、發炎性疾病和某些癌症的治療方式。此外，我們將尋找能夠豐富我們在各個治療領域的產品線和能力、使我們的產品組合多元化並增加未來成長機會的業務發展機會。

For example, earlier in the quarter, we announced an agreement with Sangamo on gene editing to create next-generation cellular therapies. And just yesterday, we announced another with Verily to better understand the immune system of patients in our clinical studies with filgotinib. John McHutchison will provide more details on these collaborations.

例如，在本季度早些時候，我們宣布與 Sangamo 達成基因編輯協議，以開發下一代細胞療法。就在昨天，我們宣布與 Verily 合作，以更好地了解我們在 filgotinib 臨床研究中患者的免疫系統。約翰·麥克哈奇森將提供有關這些合作的更多細節。

I'm confident that our innovation and hard work will deliver on our goal, developing new treatment for people living with some of the world's most serious diseases.

我相信，我們的創新和努力將實現我們的目標，為患有世界上一些最嚴重疾病的人開發出新的治療方法。

And finally, tomorrow, we will publish our 2017 year in review that highlights our scientific advancements, sustainability initiatives, community support programs and our continued efforts to improve public health globally. I'm proud of the work that's being led by our employees and extend my many thanks to them for all the ways they are making a difference around the world.

最後，明天我們將發布 2017 年度回顧，重點介紹我們的科學進步、永續發展舉措、社區支持計畫以及我們為改善全球公共衛生所做的持續努力。我為我們員工所做的工作感到自豪，並衷心感謝他們以各種方式在世界各地做出貢獻。

I will now turn the call over to John, who will provide additional updates on our R&D efforts. John?

現在我將把電話交給約翰，他將介紹我們研發工作的更多最新進展。約翰？

Thank you, John. I'm honored to have the opportunity to lead our R&D organization, which has been at the forefront of scientific innovations for more than 30 years. Under Norbert's leadership, Gilead has brought forward 25 innovative treatments that have improved the lives of millions of people with serious diseases around the world. I'm confident that our team will build on these remarkable accomplishments.

謝謝你，約翰。我很榮幸有機會領導我們的研發部門，該部門在科學創業領域一直處於領先地位超過 30 年。在諾伯特的領導下，吉利德推出了 25 種創新療法，改善了全球數百萬重症患者的生活。我相信我們的團隊會在這些卓越成就的基礎上再創佳績。

I'd like to spend the next few minutes detailing our recent progress in liver diseases, inflammation and cell therapy.

接下來幾分鐘，我想詳細介紹我們在肝臟疾病、發炎和細胞療法方面取得的最新進展。

Beginning with liver disease. We continue to make excellent progress in NASH, where our efforts are focused on treating patients with the most serious forms of the disease, those with advanced fibrosis who are at the highest risk to progress to end-stage liver disease, liver cancer and ultimately the need for liver transplantation.

從肝病開始。我們在 NASH 的治療方面繼續取得優異的進展，我們的努力集中在治療患有最嚴重疾病的患者，即那些患有晚期纖維化、最有可能發展為終末期肝病、肝癌並最終需要肝移植的患者。

As we recently announced, STELLAR 3 and STELLAR 4, our 2 ongoing Phase III trials, completed enrollment ahead of schedule. Both studies are evaluating selonsertib, our ASK1 inhibitor, in patients with F3 and F4 stages of fibrosis. We now expect data from both Phase III studies in the first half of 2019. If the data support the safety and have a statistically significant and clinically meaningful effect on fibrosis, we could file for regulatory approval towards the end of 2019.

正如我們最近宣布的那樣，我們正在進行的 2 項 III 期試驗 STELLAR 3 和 STELLAR 4 已提前完成入組。這兩項研究都在評估我們的 ASK1 抑制劑 selonsertib 對 F3 和 F4 期纖維化患者的療效。我們現在預計將在 2019 年上半年獲得兩項 III 期研究的數據。如果數據支持其安全性，並且對纖維化有統計意義和臨床意義，我們可能會在 2019 年底申請監管部門批准。

In addition, we are exploring combination therapy approaches with compounds with distinctly different mechanisms of action. In animal models of NASH, combination approaches have proven safe and have led to greater anti-fibrotic responses compared to monotherapy.

此外，我們正在探索將作用機制截然不同的化合物進行聯合治療的方法。在 NASH 動物模型中，聯合療法已被證明是安全的，並且與單一療法相比，聯合療法產生更大的抗纖維化反應。

As John mentioned, at the International Liver Congress in Paris last month, there was a growing interest and focus on NASH. We had the opportunity to present promising early results from a proof-of-concept study exploring both single agent and combinations of selonsertib with Gilead's ACC inhibitor, GS-0976; or our FXR agonists, GS-9674, in patients with NASH. Now the primary objective of this study was to determine the safety of the combination therapy. Based on the 12-week study, our combination therapies were well-tolerated, and they offered additional benefits for improving NASH by reducing liver fat content, liver cell injury and other markers of fibrosis. This is also the first study to show that GS-9674 alone had activity in patients with NASH.

正如約翰在上個月於巴黎舉行的國際肝臟大會上所提到的那樣，人們對 NASH 的興趣和關注度越來越高。我們有機會展示一項概念驗證研究的早期結果，該研究探索了 selonsertib 與 Gilead 的 ACC 抑制劑 GS-0976 或我們的 FXR 激動劑 GS-9674 的單藥和聯合用藥在 NASH 患者中的療效。本研究的主要目的是確定聯合療法的安全性。根據為期 12 週的研究，我們的聯合療法耐受性良好，並且透過減少肝臟脂肪含量、肝細胞損傷和其他纖維化標記物，為改善 NASH 提供了額外的益處。這也是第一項研究表明，GS-9674 單獨使用對 NASH 患者俱有活性。

Based on these encouraging data and supported by the preclinical results, Gilead has initiated a larger 350-patient Phase IIb study of combinations of selonsertib, GS-0976 and GS-9674 in patients with advanced fibrosis due to NASH. The treatment duration will be 48 weeks, with liver biopsies before and at the end of the treatment period.

基於這些令人鼓舞的數據，並得到臨床前結果的支持，吉利德公司啟動了一項更大規模的 IIb 期研究，該研究納入了 350 名患者，研究 selonsertib、GS-0976 和 GS-9674 聯合用藥治療 NASH 引起的晚期纖維化患者的療效。治療週期為 48 週，治療開始前和治療結束時將進行肝臟切片檢查。

Another goal of our NASH program is to identify accurate noninvasive tests that will hopefully allow health care providers to identify those in need of treatment. At the recent Liver Congress, we presented data using 2 different machine-learning methods on our earlier NASH study. The results indicate that noninvasive tests can predict with a high degree of specificity and sensitivity the risk of clinical disease progression and, separately, improvement in liver histology. We will continue to investigate noninvasive tests with the goal of replacing liver biopsies for the diagnosis of NASH and for patient management.

我們 NASH 計畫的另一個目標是找到準確的非侵入性檢測方法，希望能夠幫助醫療保健提供者識別出需要治療的患者。在最近的肝臟大會上，我們展示了使用兩種不同的機器學習方法對我們早期 NASH 研究的數據。結果表明，非侵入性檢測可以高度特異性和敏感性地預測臨床疾病進展的風險，並分別預測肝臟組織學的改善。我們將繼續研究非侵入性檢測方法，目標是用這些方法取代肝臟活檢，用於診斷 NASH 和進行患者管理。

Moving to inflammation. I'm pleased to share that our 3 Phase III studies of filgotinib, a JAK1 specific inhibitor in patients with rheumatoid arthritis, FINCH 1, FINCH 2 and FINCH 3, are now fully enrolled. These studies are evaluating the efficacy and safety of filgotinib in biologics-inadequate responder patients, methotrexate-inadequate responder patients and treatment-naïve patients, respectively. We expect the FINCH 2 data will be available in the second half of this year, and FINCH 1 and FINCH 3 data will be available in the first half of 2019.

轉向炎症。我很高興地宣布，我們針對類風濕性關節炎患者進行的 3 項 III 期研究（FINCH 1、FINCH 2 和 FINCH 3）已全部完成入組，這些研究針對的是 JAK1 特異性抑製劑 filgotinib。這些研究分別評估了filgotinib對生物製劑反應不足的患者、甲胺蝶呤反應不足的患者和初治患者的療效和安全性。我們預計 FINCH 2 數據將於今年下半年發布，FINCH 1 和 FINCH 3 數據將於 2019 年上半年發布。

Filgotinib is also being investigated in 2 other Phase III studies in Crohn's disease and ulcerative colitis that will enroll more than 2,500 patients and also in a number of smaller Phase II studies in psoriatic arthritis, ankylosing spondylitis, cutaneous lupus, Sjogren's syndrome and uveitis. We expect to have data available from some of those Phase II studies during this year.

Filgotinib 目前還在另外兩項針對克羅恩病和潰瘍性結腸炎的 III 期研究中進行研究，這兩項研究將招募超過 2500 名患者；此外，它還在一些規模較小的 II 期研究中用於治療銀屑病關節炎、強直性脊柱炎、皮膚狼瘡、乾燥綜合徵和葡萄膜炎。我們預計今年內將獲得部分二期臨床試驗的數據。

Also yesterday, as John said, we announced an important scientific collaboration with Verily, the life sciences unit owned by Google's parent company, Alphabet, to accelerate our understanding of 3 common and serious inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and lupus-related diseases. Most patients with these immunologically-driven diseases don't experience deep or long-lasting remissions with currently available therapies. There's clearly a need. Through this partnership, we will use Verily's Immunoscape platform to interrogate the molecular characteristics of these immune-related diseases. By segmenting each patient's individual leukocytes into more than 2-dozen [compound,] immune cell subsets and utilizing epigenetic and transcriptomic assays, we believe this technology could allow us to identify particular groups of patients that respond to specific therapies and also to potentially identify new drug discovery targets.

正如約翰昨天所說，我們也宣布與Google母公司Alphabet旗下的生命科學部門Verily開展一項重要的科學合作，以加速我們對三種常見且嚴重的發炎性疾病的了解：類風濕性關節炎、發炎性腸道疾病和狼瘡相關疾病。大多數患有這些免疫驅動疾病的患者，使用目前可用的療法都無法獲得深度或持久的緩解。顯然存在這種需求。透過此次合作，我們將利用 Verily 的 Immunoscape 平台來探討這些免疫相關疾病的分子特徵。透過將每位患者的單一白血球分割成 24 種以上的[複合]免疫細胞亞群，並利用表觀遺傳學和轉錄組學分析，我們相信這項技術可以讓我們識別出對特定療法有反應的特定患者群體，並有可能識別出新的藥物發現標靶。

Moving to cell therapy. We anticipate that the CHMP will adopt an opinion for Yescarta in the second quarter, and if positive, approval would follow likely in the third quarter of this year. Given the innovative nature of CAR T therapies, the European Medicines Agency is evaluating the application under standard review to allow them sufficient time to review that data that we submitted with the application.

轉向細胞療法。我們預計 CHMP 將在第二季對 Yescarta 發表意見，如果意見積極，則很可能在今年第三季獲得批准。鑑於 CAR-T 療法的創新性，歐洲藥品管理局正在按照標準審查程序評估該申請，以便有足夠的時間審查我們隨申請提交的數據。

Also in cell therapy, we continue to enroll patients in ZUMA-7, a Phase III randomized study comparing Yescarta to the standard of care, which is salvage chemotherapy followed by autologous stem cell transplantation in the second line treatment of patients with diffused large B-cell lymphoma. ZUMA-7 is also the first global randomized Phase III study of a CAR T therapy and will enroll 350 patients across 50 sites in North America and Europe. There remains a significant unmet medical need for patients with relapsed or refractory DLBCL after first-line therapy. Salvage chemotherapy, followed by transplantation, cures only approximately 10% to 20% of these patients. If the ZUMA-7 trial provides positive data in this setting, Yescarta has the potential to become an alternative option earlier in the course of the disease, thereby expanding the therapeutic potential of cell therapy for patients living with diffuse large B-cell lymphoma.

此外，在細胞治療方面，我們繼續招募患者參與 ZUMA-7，這是一項 III 期隨機研究，旨在比較 Yescarta 與標準療法（即挽救性化療，然後進行自體幹細胞移植，作為瀰漫性大 B 細胞淋巴瘤患者的二線治療）的療效。ZUMA-7 也是第一個 CAR T 療法的全球隨機 III 期研究，將在北美和歐洲的 50 個地點招募 350 名患者。對於第一線治療後復發或難治性瀰漫性大B細胞淋巴瘤患者而言，仍存在巨大的未滿足醫療需求。挽救性化療後進行移植，只能治癒約 10% 到 20% 的這類患者。如果 ZUMA-7 試驗在此方面提供積極數據，Yescarta 有可能成為疾病早期階段的替代選擇，從而擴大細胞療法對瀰漫性大 B 細胞淋巴瘤患者的治療潛力。

We are also excited about our partnership with Sangamo Therapeutics, which was announced in February. This agreement will allow our researchers access to Sangamo's zinc finger nuclease gene-editing technology, which we believe will lead to the development of allogeneic T-cell therapies that can be manufactured using the cells of healthy donors. The gene-editing approach would reduce or eliminate some of the complications currently seen in allogeneic stem cell transplants such as rejection and graft-versus-host disease. Allogeneic therapies would also enable us to manufacture CAR T therapies that could be used universally, providing people, particularly those who are very, very ill, to access treatment much more quickly.

我們也對2月宣布與Sangamo Therapeutics建立的合作關係感到興奮。該協議將使我們的研究人員能夠使用 Sangamo 的鋅指核酸酶基因編輯技術，我們相信這將有助於開發利用健康供體細胞製造的同種異體 T 細胞療法。基因編輯方法可以減少或消除目前在同種異體幹細胞移植中出現的一些併發症，如排斥反應和移植物抗宿主疾病。同種異體療法還可以讓我們生產出可普遍使用的 CAR-T 療法，使人們，特別是那些重症患者，能夠更快地獲得治療。

Combining gene editing with the synthetic biology tools we acquired with Cell Design Laboratories last year will also help us to develop treatment that can more precisely target hematological malignancies and solid tumors and make it safer more effective and easier to manufacture.

將基因編輯與我們去年從 Cell Design Laboratories 獲得的合成生物學工具相結合，也將有助於我們開發能夠更精確地靶向血液惡性腫瘤和實體瘤的治療方法，使其更安全、更有效、更容易生產。

We have achieved a great deal across our R&D organization this quarter, and I am confident we will continue to make significant progress throughout the remainder of the year.

本季度，我們的研發部門取得了巨大成就，我相信在今年餘下的時間裡，我們將繼續取得重大進展。

In closing, I am excited to lead the talented Gilead R&D team going forward. I am also looking forward to partnering with Andrew Cheng in his new role and, of course, with all my R&D colleagues.

最後，我很高興能夠帶領吉利德才華洋溢的研發團隊繼續前進。我也期待與 Andrew Cheng 在新職位上合作，當然，還有與我所有的研發同事們合作。

There has never been a more interesting time in science and medicine with extraordinary new discoveries on an almost weekly basis. It will be our job here to leverage those advances and develop more effective and targeted therapies for patients with serious medical needs.

科學和醫學領域從未像現在這樣充滿變革，幾乎每週都有非凡的新發現。我們在這裡的任務是利用這些進展，為有嚴重醫療需求的患者開發更有效、更有針對性的療法。

I'll now turn the call over to Robin.

現在我將把電話交給羅賓。

Thank you, John, and good afternoon, everyone. We are pleased to share our financial results for the first quarter of 2018.

謝謝你，約翰，大家下午好。我們很高興與大家分享2018年第一季的財務表現。

Total revenues for the first quarter were $5.1 billion with non-GAAP diluted earnings per share of $1.48. This compares to revenues of $6.5 billion and non-GAAP earnings per share of $2.23 for the same period last year.

第一季總收入為 51 億美元，非 GAAP 稀釋後每股收益為 1.48 美元。相比之下，去年同期營收為 65 億美元，非 GAAP 每股收益為 2.23 美元。

Starting with HIV and HBV. Product sales for the first quarter were $3.3 billion, up 2% year-over-year and down 10% sequentially. The year-over-year increase was driven by the continued uptake of our Descovy-based regimens, partially offset by the entry of generics and greater U.S. inventory draw-down than in the prior year period. Sequentially, the decline was due to U.S. sub-wholesaler inventory, reflective of the seasonal pattern from the fourth quarter to the first quarter and the availability of generic versions of TDF in the U.S., which impacted our HBV revenue.

從愛滋病毒和B型肝炎病毒開始。第一季產品銷售額為 33 億美元，年增 2%，季減 10%。同比成長主要得益於我們基於 Descovy 的治療方案的持續推廣，但部分被仿製藥的進入以及美國庫存比上年同期下降更多所抵消。從季度來看，下降是由於美國二級批發商庫存，反映了從第四季度到第一季的季節性模式，以及美國TDF仿製藥的供應，這影響了我們的乙肝收入。

Our U.S. HIV business remains robust, led by the continued uptake of Descovy-based regimens. On a year-over-year basis, U.S. HIV product sales grew 8%, and total prescriptions for Descovy-based and Truvada-containing regimens grew 12%, consistent with growth seen in each of the preceding 4 quarters.

在以 Descovy 為基礎的治療方案持續被採用的推動下，我們在美國的 HIV 業務依然強勁。與去年同期相比，美國 HIV 產品銷售額增長了 8%，以 Descovy 為基礎和含有 Truvada 的治療方案的總處方量增長了 12%，與前 4 個季度的增長情況一致。

As John mentioned, Biktarvy, our newest single-tablet regimen for HIV, was approved in the U.S. in February, and we are encouraged by the initial uptake among prescribers. It's very early days, but launch to date, Biktarvy is tracking very well against our expectations. With this trajectory, we anticipate, over time, Biktarvy will become the #1 single-tablet regimen for treatment-naïve and switch patients, a distinction currently held by Genvoya.

正如約翰所提到的，我們最新的單片HIV治療藥物Biktarvy於2月在美國獲得批准，我們對處方醫生最初的接受度感到鼓舞。現在還處於早期階段，但就目前的發布情況來看，Biktarvy 的表現遠遠超出我們的預期。按照這種發展軌跡，我們預計，隨著時間的推移，Biktarvy 將成為初治患者和轉診患者的首選單片治療方案，而目前這項殊榮由 Genvoya 維持。

Approximately 80% of Biktarvy's prescription came from switches of which approximately 1/3 came from Genvoya and 2/3 from other regimens, including approximately 20% from regimens that contain dolutegravir, confirming Biktarvy's broad utility across patient types.

Biktarvy 約 80% 的處方來自治療方案轉換，其中約 1/3 來自 Genvoya，2/3 來自其他治療方案，包括約 20% 來自含有多替拉韋的治療方案，這證實了 Biktarvy 對各類患者的廣泛適用性。

Similar to the launch of Genvoya, access to Biktarvy has been strong, with the vast majority of state ADAPs and Medicaid programs now covering Biktarvy with coverage in additional state program expected this quarter.

與 Genvoya 的推出類似，Biktarvy 的普及程度很高，目前絕大多數州 ADAP 和 Medicaid 計劃都涵蓋了 Biktarvy，預計本季度還將有更多州計劃涵蓋該藥物。

Truvada for PrEP continued to grow with approximately 167,000 individuals taking Truvada for this indication in Q1.

Truvada 用於 PrEP 的人數持續成長，第一季約有 167,000 人服用 Truvada 用於此適應症。

In Europe, sales of Descovy-based regimens comprise more than half of our HIV product revenues and continue to grow, primarily driven by strong uptake in important markets such as France and Italy. Genvoya remained the #1 regimen for naïve and switch patients across the EU 5 collectively for the fourth consecutive quarter, reflective of the strong physician and patient preference for Descovy-based regimens.

在歐洲，基於 Descovy 的治療方案的銷售額占我們 HIV 產品收入的一半以上，並且持續成長，這主要得益於法國和義大利等重要市場的強勁需求。Genvoya 連續第四個季度在歐盟 5 國所有初治患者和轉診患者中保持排名第一的地位，這反映出醫生和患者對基於 Descovy 的治療方案的強烈偏好。

Turning to HCV. Product sales for the first quarter were $1 billion, down 59% year-over-year and down 30% sequentially. Consistent with our expectations, in Q1, we observed a downward pricing and market share trend across the major geographies as a result of a more competitive environment. Price has now largely stabilized, and we expect market share to stabilize by mid-year. In addition, patient starts have become more predictable, and we expect a slow and steady decline moving forward.

轉向丙型肝炎。第一季產品銷售額為 10 億美元，年減 59%，季減 30%。與我們的預期一致，由於競爭環境加劇，我們在第一季觀察到主要地區的定價和市場份額呈下降趨勢。目前價格已基本穩定，我們預期市佔率將在年中趨於穩定。此外，患者發病率已變得更加可預測，我們預計未來將緩慢且穩定地下降。

We continue to see the HCV market as durable, and albeit a smaller component of our revenues going forward, there are still many patients that remain to be treated.

我們仍然認為丙型肝炎市場具有持久性，儘管未來其在我們收入中所佔的比例會較小，但仍有許多患者需要治療。

Our cardiovascular products, Ranexa and Letairis, generated $399 million in the first quarter. As a reminder, the patent for ambrisentan in the U.S. will expire in July this year.

我們的心血管產品 Ranexa 和 Letairis 在第一季創造了 3.99 億美元的收入。提醒大家，安立生坦在美國的專利將於今年7月到期。

And finally, sales of Yescarta were $40 million in the first full quarter since approval in October. As John mentioned earlier, we are making great progress in training and certifying additional centers.

最後，Yescarta 自 10 月獲得批准以來的第一個完整季度銷售額為 4000 萬美元。正如約翰之前提到的，我們在培訓和認證更多中心方面取得了巨大進展。

In terms of access in the U.S., we are seeing the payer mix play out as expected, with approximately 2/3 of Yescarta patients covered by commercial and fee-for-service plan and approximately 1/4 of patients covered by Medicare. There is broad coverage of Yescarta-eligible patients with commercial insurance.

就美國的醫療服務取得而言，我們看到支付方構成符合預期，約 2/3 的 Yescarta 患者由商業保險和按服務收費計劃承保，約 1/4 的患者由聯邦醫療保險承保。Yescarta 為符合資格且擁有商業保險的患者提供了廣泛的覆蓋範圍。

It's encouraging to see the strong execution by our commercial, medical affairs and manufacturing teams, the positive feedback from centers and the growing awareness of Yescarta in the hematology and patient community.

令人鼓舞的是，我們的商業、醫學事務和生產團隊都展現出了強大的執行力，各中心也給予了積極的回饋，血液病學界和患者群體對 Yescarta 的認知度也日益提高。

Now turning to expenses. Non-GAAP R&D expenses were $814 million for the first quarter, down 8% compared to the same period last year, primarily due to our purchase of a priority review voucher in the prior year. Non-GAAP SG&A expenses were $884 million for the first full quarter, up 10% compared to the same period last year, primarily due to costs associated with our newest product launches, including Biktarvy and Yescarta, geographic expansion and increased expenses to support the growth of our business following the acquisition of Kite.

現在來說說費用。第一季非GAAP研發費用為8.14億美元，比去年同期下降8%，主要原因是我們在上一年購買了優先審查券。第一季非GAAP SG&A費用為8.84億美元，比去年同期增長10%，主要原因是與我們最新產品發布相關的成本，包括Biktarvy和Yescarta，地理擴張以及收購Kite後為支持業務增長而增加的費用。

Moving to the balance sheet. During the first quarter, we generated cash flow from operations of $2.3 billion and ended the quarter with $32.1 billion in cash and investments. We repaid $4.5 billion of term loan filed in connection with our acquisition of Kite, paid cash dividends of $753 million and repurchased 13 million shares of stock for $1 billion. The amount of shares repurchased was aligned to our stock compensation awards, which are largely granted in the first quarter and reflects a onetime impact to repurchases related to unvested equity assumed from the Kite transaction.

接下來查看資產負債表。第一季度，我們的經營活動產生的現金流為 23 億美元，季末現金和投資總額為 321 億美元。我們償還了與收購 Kite 相關的 45 億美元定期貸款，支付了 7.53 億美元的現金股息，並以 10 億美元的價格回購了 1,300 萬股股票。回購的股份數量與我們的股票補償獎勵相符，這些獎勵大多在第一季授予，並反映了從 Kite 交易中獲得的未歸屬股權對回購的一次性影響。

While our cash flows will remain strong for the remainder of the year, we anticipate a sequential decrease in Q2 2018 due to anticipated tax-related payments.

雖然今年剩餘時間我們的現金流量將保持強勁，但由於預計的稅款相關支出，我們預計 2018 年第二季現金流將較上季下降。

The year is progressing consistent with our expectations, and we are reiterating our full year guidance, which can be found on Slide 47 in the earnings results presentation.

今年的進展與我們的預期一致，我們重申全年業績指引，詳情請見收益報告簡報第 47 頁。

Our confidence in the future is supported by a strong and growing HIV business, led by the launch of Biktarvy in the U.S., increasing momentum in our cell therapy business and potential opportunities in emerging R&D areas of NASH and inflammation.

我們對未來的信心源於我們強勁且不斷增長的 HIV 業務，這主要得益於 Biktarvy 在美國的推出；此外，我們的細胞療法業務也取得了持續增長的勢頭，並且在 NASH 和炎症等新興研發領域也存在著潛在的機遇。

I would like to conclude by thanking our nearly 10,000 employees for their commitment to excellence and hard work that is well represented in the results this quarter.

最後，我要感謝我們近 10,000 名員工，感謝他們對卓越的追求和辛勤工作，這在本季度的業績中得到了充分體現。

Let's now open the call for questions. Operator?

現在開始接受提問。操作員？

(Operator Instructions)

（操作說明）

And our first question comes from Geoffrey Porges of Leerink.

我們的第一個問題來自 Leerink 公司的 Geoffrey Porges。

John McHutchison, congratulations on all the responsibilities. Maybe we can start off with a commercial question but more seriously on the R&D side, could you give us the latest disclosure on the PE and DVT events you've seen so far in the RA program for filgotinib? And then perhaps, you could talk a little bit more generally about what areas you're particularly excited about in your new position that you think the company has the opportunity to invest in more aggressively.

約翰·麥克哈奇森，恭喜你承擔了所有重任。或許我們可以先從一個商業問題開始，但更嚴肅地說，在研發方面，您能否向我們提供一下您在 filgotinib 的 RA 項目中迄今為止所觀察到的 PE 和 DVT 事件的最新披露信息？然後，或許您可以更廣泛地談談您對新職位中哪些領域特別感興趣，以及您認為公司有機會在這些領域加強投資。

Thank you, Geoff, for the kind words and for the question. So regarding the first part of your question, the thromboembolic event rates with baricitinib, the most recent data that we have shown was a presentation at ACR late last year by Mark Genovese, which was an oral presentation. Now this is just from the DARWIN 1, 2 and 3 extension studies. We have about 700, 800 patient years of exposure but that rate was very low. Only 1 patient in that presentation who had both a DVT and a PE. So the rate actually in that presentation was 0.06 per 100 patient years. But Geoff, so far, we've got thousands of patients in Phase III. We've got a relatively small data set in terms of exposure but that's what we have said so far. We continue to collect all of that information. The other point to raise about this was the discussion recently at the Advisory Committee and whether this is slightly or partly related to JAK2. As you know, filgotinib is very selective for JAK1. And in terms of JAK2 specificity, we don't have that at all. So we don't see any changes in hemoglobin. We see positive changes in hemoglobin. We don't see any increase in platelets. In fact, we see a small decrease in platelets. Whether or not that's related to thromboembolic phenomena, we don't know. In terms of what we're excited about or excited about in R&D, well, I mean, Geoff, I'm always excited about everything. But I mean, the opportunity to make a huge progress in cell therapy, not just with Yescarta, which has enormous potential, but the future of cell therapy going forward, investing in researchers we have to come forward with next-generation products is really exciting for the organization to lead that entire field, and we will continue to lead that and I will ensure that, as will Andrew and others in the organization as well. Additionally, I think we have a lot of opportunities in NASH. The ability to have a drug approved for an anti-fibrotic endpoint in liver disease is -- it's never been done before, and we clearly want to do that and there's a lot of patients out there with NASH. And then I believe, our fledgling programs that are now developing in full force in inflammation with filgotinib in multiple diseases are becoming differentiated, exciting and heading in the right direction, particularly with things such as the Verily collaboration. So that's a long answer. I'm sorry, Geoff.

謝謝你，傑夫，謝謝你的讚揚和提問。關於您問題的第一部分，即巴瑞替尼的血栓栓塞事件發生率，我們最近公佈的數據是 Mark Genovese 去年底在 ACR 會議上發表的口頭報告。以上數據僅來自 DARWIN 1、2 和 3 擴展研究。我們大約有 700 到 800 患者年的暴露量，但這個比率非常低。那次就診中只有 1 例患者同時患有深部靜脈栓塞和肺栓塞。所以，那次報告中實際的發生率為每 100 患者年 0.06。但傑夫，到目前為止，我們已經有數千名患者進入了 III 期臨床試驗。就暴露情況而言，我們的資料集相對較小，但這就是我們目前所說的。我們將繼續收集所有這些資訊。關於這一點，還有一點需要提出，那就是最近諮詢委員會的討論，以及這是否與 JAK2 有些或部分相關。如您所知，filgotinib 對 JAK1 具有很高的選擇性。就 JAK2 特異性而言，我們完全沒有這方面的證據。因此，我們沒有看到血紅蛋白有任何變化。我們看到血紅蛋白含量出現正面變化。我們沒有看到血小板數量增加。事實上，我們發現血小板數量略有下降。我們尚不清楚這是否與血栓栓塞現像有關。至於我們在研發方面感到興奮的事情，嗯，我的意思是，傑夫，我對所有事情都感到興奮。但我的意思是，細胞療法領域取得巨大進展的機會，不僅是Yescarta，它具有巨大的潛力，而且是細胞療法的未來發展，投資於研究人員以開發下一代產品，這對於我們組織來說真的令人興奮，能夠引領整個領域，我們將繼續引領這一領域，我將確保這一點，Andrew和組織中的其他人也將如此。此外，我認為我們在 NASH 領域有很多機會。能夠批准一種藥物用於治療肝病中的抗纖維化終點——這在以前從未發生過，我們顯然想做到這一點，而且有很多患有 NASH 的患者。而且我相信，我們目前正在全力發展的、利用 filgotinib 治療多種疾病發炎的新興項目，正在變得與眾不同、令人興奮，並朝著正確的方向發展，尤其是在與 Verily 等機構的合作方面。答案很長。對不起，傑夫。

And our next question comes from Geoff Meacham of Barclays.

下一個問題來自巴克萊銀行的傑夫·米查姆。

So HIV franchise is really key to Gilead getting back to a growth company. So I was hoping you guys could give a bit more detail on the underlying demand trends in the U.S. and Europe, just independent of inventory fluctuations. I'm just -- I guess I'm trying to reconcile the 2% growth with maintaining guidance and the positive commentary.

因此，愛滋病業務對於吉利德重返成長型公司行列至關重要。所以我希望你們能更詳細地介紹美國和歐洲的潛在需求趨勢，而不考慮庫存波動。我只是——我想我是在努力調和2%的成長率與維持業績預期和正面的評論之間的矛盾。

So I'm going to let Andrew start with just giving you really underlying details around the Biktarvy launch, and then I'll kind of jump in with some of the revenue areas.

那麼，我將讓 Andrew 先為大家介紹 Biktarvy 的發布細節，然後我將從收入方面切入正題。

Yes. Geoff, it's Andrew. So I just want to touch on and reiterate some of the things that Robin's mentioned during the call in her prepared remarks, primarily that when we look up Biktarvy, we see 80% of Biktarvy comes -- scripts comes from switches. Those switches, 1/3 from Genvoya and about 20% come from dolutegravir-based regimens, both Tivicay and Triumeq. When we see the switches and as well as naïve patients trajectory overall, they're right on target for what we predicted prior to the launch. And really are in line for where we think Biktarvy will ultimately end up as the top switch as well as naïve drug in HIV and a position that's currently occupied by Genvoya.

是的。傑夫，我是安德魯。所以我想談談並重申 Robin 在電話會議中準備好的演講稿中提到的一些事情，主要是當我們查找 Biktarvy 時，我們發現 80% 的 Biktarvy 腳本來自交換機。這些轉換中，1/3 來自 Genvoya，約 20% 來自基於多替拉韋的療法，包括 Tivicay 和 Triumeq。當我們觀察轉換情況以及未接受過治療的患者的整體軌跡時，發現它們與我們在產品上市前預測的結果完全一致。我們認為 Biktarvy 最終將成為 HIV 治療領域首屈一指的替代療法和新藥，取代 Genvoya 目前的地位。

Right. And Geoff, I'd add to that, but keep in mind that the launch for Biktarvy, we basically got 6 weeks of revenue currently in the quarter. So while a partial quarter, we also had about half of it was related to inventory. But underlying to your point, we're really excited with the overall launch of Biktarvy and the success to date. The launch trajectory is looking very close to Genvoya. And over time, we expect it to overtake Genvoya, as I mentioned, as the #1 STR for naïve and switch patients over time. I think if you've been trying to think about just Europe beyond Biktarvy, we're also seeing, as I mentioned, over 50% of our HIV sales came from Descovy-based products in Europe, and that's exceeding in advance of the fact that generics are widely available. So to the point I made on the call and John made, we're really excited with the opportunity for HIV to be a growth business. That's inclusive of PrEP as well, but we're excited where we are for the year and for the opportunity to have this business be a growth trajectory for us beyond 2018.

正確的。傑夫，我還要補充一點，請記住，Biktarvy 的推出，我們基本上在本季度獲得了 6 週的收入。所以，雖然只佔了部分季度，但其中大約一半與庫存有關。但從你的觀點來看，我們對 Biktarvy 的整體發布以及迄今為止的成功感到非常興奮。發射軌跡看起來非常接近 Genvoya。正如我之前提到的，我們預計隨著時間的推移，它將超越 Genvoya，成為初治患者和轉診患者的首選 STR。我認為，如果你一直試圖只考慮 Biktarvy 以外的歐洲市場，那麼正如我所提到的，我們也看到，我們超過 50% 的 HIV 銷售額來自歐洲的 Descovy 產品，而且這還是在仿製藥廣泛上市之前就已經超過了這一比例。所以，正如我在電話會議中和約翰所說的那樣，我們對愛滋病防治領域有機會成為一個成長型業務感到非常興奮。這其中也包括 PrEP，但我們對今年的進展感到興奮，並期待這項業務在 2018 年以後成為我們的成長軌跡。

And our next question comes from Michael Yee of Jefferies.

下一個問題來自傑富瑞集團的麥可葉。

Two-part question. On HIV, can you just, perhaps, quantify how much inventory impacted the results? I think people are quite concerned on the HIV numbers. So maybe just help us out there relative to consensus, 100 million, 200 million more of inventory. And on hep C, there was a miss there, and I guess, concerned about that relative to competition. So maybe just talk to that because you're reiterating the guidance.

問題分為兩部分。關於愛滋病毒，您能否量化一下庫存對結果的影響程度？我認為人們非常關注愛滋病毒感染人數。所以，或許可以幫我們估算一下，相對於市場共識，庫存應該再增加 1 億到 2 億。在C肝方面，我們有所疏漏，我想，這可能與競爭有關。所以或許就跟他們談談吧，因為你是在重申指導。

Sure. So Michael, let me start with HIV inventory. The draw-down in inventory was primarily from our HIV products. But as I mentioned, if you look at underlying U.S. prescription growth overall, it was 12% year-over-year, and as I mentioned, 50% of our HIV revenues in Europe were comprised of Descovy-containing regimens. So while we haven't quantified the dollar magnitude, the draw-down was larger than what we have seen in past quarters. Typically, if you go back the last 8 quarters, we've had that Q4 to Q1 dynamic relative to inventory, so it is seasonal. There were 2 key events this quarter that made that inventory decline greater than expected. One was availability of generic versions of TDF. So therefore, wholesales weren't carrying Viread anymore. And then two, the anticipation of Biktarvy approval from lower stocking of both TAF and TDF-containing regimens. Keep in mind, if you look at year-on-year and quarter-on-quarter growth, the availability of generic versus the TDF in the U.S. impacted our HBV business. Overall, if we think about our big 3 wholesalers, we were in line relative to our inventory agreement. I'll remind you that we don't have agreements in place for the sub-wholesalers. But again, just emphasizing that overall, our underlying HIV growth remains strong but we have the typical seasonal inventory, driven by the 2 events that I just mentioned. Yes, so return to your second question on HCV, which the question...

當然。那麼邁克爾，讓我先從愛滋病毒感染情況說起。庫存減少主要來自我們的愛滋病產品。但正如我之前提到的，如果你看美國整體處方藥的潛在增長，它同比增長了 12%；而且正如我之前提到的，我們在歐洲的 HIV 收入中有 50% 來自含有 Descovy 的治療方案。雖然我們還沒有量化美元的跌幅，但此次跌幅比過去幾季我們看到的要大。通常情況下，回顧過去 8 個季度，庫存都會呈現第四季度到第一季的這種動態變化，所以這是季節性的。本季發生了兩件大事，導致庫存下降幅度超出預期。一是TDF通用版本的可取得性。因此，批發商不再銷售Viread了。其次，由於 TAF 和 TDF 療法的庫存減少，預計 Biktarvy 將獲得批准。請記住，如果您查看同比和環比增長，美國仿製藥與 TDF 的供應情況會影響我們的 HBV 業務。總的來說，如果我們考慮我們的三大批發商，我們的庫存狀況與我們的庫存協議相符。我提醒各位，我們目前還沒有與二級批發商簽訂協議。但再次強調，總體而言，我們的 HIV 感染率成長依然強勁，但我們出現了典型的季節性庫存，這是由我剛才提到的兩個事件造成的。是的，那麼請回到你關於C型肝炎的第二個問題，這個問題是…

Competitive environment?

競爭環境？

Yes, the competitive environment. I mean, I would say, if you step back and think about where we are relative to our guidance and our expectations, we reiterated guidance, it is pretty much paying out -- playing out in line with our expectations. We talked about the fact that my comments that the U.S. pricing has largely stabilized, and we expect market share to stabilize by mid-year. I would say, Michael, that the ex U.S. competition has intensified, but I'd also say that the competition was more intense environment prior to the launch of a competitor and remains [to be.] So we do believe that overall, hep C is a long and durable market. We'll continue to compete very aggressively with our competitor. But in summary, our expectations for 2018 are intact, and we believe our revenue reflects the guidance that we provided at the beginning of the year.

是的，競爭環境。我的意思是，如果你退後一步，想想我們目前與我們的指導和預期之間的關係（我們重申了指導方針），它基本上正在奏效——一切都在按照我們的預期發展。我們討論了我之前關於美國定價已基本穩定的觀點，我們預計市場份額將在年中趨於穩定。邁克爾，我認為美國以外的競爭加劇了，但我也認為，在競爭對手推出產品之前，競爭環境就已經非常激烈，而且現在仍然如此。因此，我們相信，總體而言，C型肝炎市場是一個長期且可持續的市場。我們將繼續與競爭對手展開激烈的競爭。但總而言之，我們對 2018 年的預期保持不變，我們相信我們的收入反映了我們在年初提供的指導。

And our next question comes from Brian Abrahams of RBC Capital Markets.

下一個問題來自加拿大皇家銀行資本市場的布萊恩亞伯拉罕。

My congrats to Norbert about your accomplishments and to Andrew and John around your new roles and responsibilities. A question on Yescarta. As we try to gauge avenues of continued growth there this year and beyond, it would be helpful to understand the proportion of centers that are operating at high throughput and perhaps how far along in infrastructure establishment those additional centers that you expect will be authorized are going to be relative to those already online. And then I guess, I'm also just curious on revenue recognition there related to -- relative to reimbursement, how we should be thinking about that.

恭喜諾伯特的成就，也祝賀安德魯和約翰承擔新的角色和責任。Yescarta 上的一個問題。當我們試圖評估今年及以後該地區持續增長的途徑時，了解高吞吐量運營中心的比例，以及預計獲準建設的新增中心的基礎設施建設進度與已上線中心的進度相比如何，將會很有幫助。然後，我想問的是，關於收入確認，特別是與報銷相關的收入確認，我們應該如何考慮這個問題。

So I'll start, Brian. I would say, you're right. It's early days, so we're not going to get into throughput discussions or specifically what we're seeing at every center. We're really pleased with our full first quarter revenue. We talked about this being a very measured at launch with our focus being this year on getting centers authorized and being sure that their experience with Yescarta meets the expectation of the centers and the patients. So I mentioned we have 40 centers authorized, and we expect by mid-year that we'll have coverage for 80% of the eligible Yescarta patients as we continue to ramp up centers. Relative to revenue recognition, no overall concerns there. We're seeing good reimbursement overall from -- for both commercial as well as Medicare patients. So we're really comfortable where we are with the launch to date.

那我先來，布萊恩。我覺得你說得對。現在還處於早期階段，所以我們不會深入討論吞吐量，也不會具體討論我們在每個中心看到的情況。我們對第一季的總營收非常滿意。我們討論過，在推出時要非常謹慎，今年的重點是獲得中心的授權，並確保他們在使用 Yescarta 時的體驗符合中心和患者的期望。正如我之前提到的，我們已經有 40 個獲準的中心，我們預計到年中，隨著我們繼續擴大中心規模，我們將為 80% 符合 Yescarta 條件的患者提供醫療服務。就收入確認而言，整體上沒有需要擔心的問題。我們看到整體報銷情況良好——無論是商業保險患者還是聯邦醫療保險患者。所以，我們對目前的發布情況非常滿意。

And our next question comes from Matthew Harrison of Morgan Stanley.

下一個問題來自摩根士丹利的馬修·哈里森。

I guess, one, with HCV price stabilizing, I wonder if you'd just give us some idea of where that's stabilized relative to some of the prior comments you've made around what the average price was across the regimens. And then if I can ask a separate question for John McHutchison related to the UC program for filgotinib, I believe there's a -- you had a futility analysis to move from Phase II to Phase III. Could you just talk a little bit about what the bar is and what the hurdle is to move into the Phase III program and how you're thinking about that?

我想，第一，隨著C型肝炎藥物價格趨於穩定，我想知道您能否告訴我們，相對於您之前對各種治療方案平均價格的一些評論，目前的穩定價格是多少。然後，如果我可以單獨問 John McHutchison 一個與 filgotinib 的 UC 專案有關的問題，我相信你們曾進行過一項無效性分析，以從 II 期推進到 III 期。您能否簡單談談進入第三階段計畫的標準和障礙是什麼，以及您對此有何看法？

So I'll start, Matthew. I think the main change that you saw in Q1 in that step-down, was we talked about on our February call, was related to Medicare in the U.S. So as I -- as we mentioned this call and the prior, we expected that step-down with a price adjustment as we move to the new contractual arrangements at the beginning of the year.

那我先來，馬修。我認為您在第一季看到的主要變化，也就是我們在二月電話會議上討論過的降級，與美國的醫療保險有關。正如我在這次電話會議和之前的電話會議上提到的，我們預計隨著年初新合約安排的實施，價格會進行調整，從而導致降級。

And Matthew, the second part of the -- it's John McHutchison. The second part of the question was about the futility interim analysis for the selection of filgotinib ulcerative colitis Phase III study. Just to remind you, the reason we did this futility analysis is we hadn't studied filgotinib in ulcerative colitis in Phase II. We had in Crohn's disease in the FITZROY study. And we have obviously had data in rheumatoid arthritis but we had to have an interim analysis in the ulcerative colitis study to make sure that we were on track. And that analysis is planned, without getting into all the details, coming up this -- shortly this year. It's based on the week 10 induction time point and the endoscopic response and improvement in endoscopic response in the 2 groups of patients that are enrolled in the trial, those that are naïve and those that are biologic nonresponders. So I'll leave it at that, I think, to answer the question, and we'll see how it goes.

還有馬修，第二部分──是約翰‧麥克哈奇森。問題的第二部分是關於選擇 filgotinib 治療潰瘍性結腸炎 III 期研究的無效性中期分析。提醒一下，我們進行這項無效性分析的原因是，我們還沒有在 II 期臨床試驗中研究過 filgotinib 治療潰瘍性結腸炎的療效。我們在 FITZROY 研究中發現了克羅恩病患者。我們顯然已經有了類風濕性關節炎的數據，但我們必須對潰瘍性結腸炎研究進行中期分析，以確保我們走在正確的軌道上。這項分析計畫於今年內進行，具體細節暫且不談。這是根據第 10 週的誘導時間點以及試驗中入組的兩組患者的內視鏡反應和內視鏡反應改善情況得出的，這兩組患者分別是初治患者和生物製劑無反應者。所以，我想我就此打住，不再贅述這個問題了，我們看看事情會如何發展。

And our next question comes from Robyn Karnauskas with Citi.

下一個問題來自花旗銀行的 Robyn Karnauskas。

So just one quick question on HCV. You did not reiterate HCV guidance, so I was just curious whether or not that's reiterated as well. And then on Yescarta, just trying to understand a little bit about what you're seeing in the real world on safety, given that it will be -- you'll be facing some competition. Are you seeing safety in line with your clinical trial work or side effects that are not as common?

關於C型肝炎，我還有一個問題。您沒有重申丙型肝炎的指導意見，所以我很好奇這方面是否也有重申。然後，在 Yescarta 上，我只是想稍微了解你在現實世界中看到的安全問題，因為你們將面臨一些競爭。您在臨床試驗中觀察到的安全性是否與預期相符，還是出現了一些不常見的副作用？

So Robyn, I'll take the first question regarding guidance. We didn't give specific HCV guidance but again, if you take a look at our revenues and you look at the components that we provided in our guidance overview last quarter, we're pretty much in line, and it's the high end of that guidance overall with $1 billion-plus in global HCV revenues. And we did reiterate our total guidance, which is how we guided this year on total net product revenue. Relative to safety on Yescarta?

羅賓，我先來回答第一個關於指導的問題。我們沒有給出具體的 HCV 業績指引，但是，如果你看一下我們的收入，再看一下我們上個季度在業績指引概述中提供的各項指標，就會發現我們基本上符合預期，而且整體而言，我們的全球 HCV 收入達到了指引的高端，超過 10 億美元。我們重申了我們的整體業績預期，即我們今年對產品淨收入總額的預期。與Yescarta的安全性相比如何？

Robyn, it's John McHutchison. So yes, I've been talking to some of the team in Santa Monica over the last couple of days, and in general, there's nothing untoward that's been observed to my knowledge as well outside of the clinical trial.

羅賓，我是約翰‧麥克哈奇森。是的，過去幾天我一直在和聖莫尼卡團隊的一些成員交談，據我所知，除了臨床試驗之外，總體上沒有觀察到任何不尋常的情況。

And our next question comes from Umer Raffat of Evercore.

我們的下一個問題來自 Evercore 公司的 Umer Raffat。

This is Regina Grebla on for Umer. So first, many investors think that you're in an earnings trough this year. Do you think that you're in an earnings trough? And NASH is emerging as an important catalyst in your pipeline. We saw some data from Allergan at EASL where patients in their placebo arm seesawed between fibrosis stages. We do recognize that the Allergan study enrolled earlier fibrosis stage patients in F3s. But how much of a risk do you think this could be in your Phase III program?

這裡是 Regina Grebla 為 Umer 做客。首先，許多投資者認為你今年的獲利正處於低谷期。你認為你正處於收入低谷期嗎？NASH 正成為您研發管線中的重要催化劑。我們在 EASL 會議上看到了 Allergan 的一些數據，其中安慰劑組的患者在纖維化階段之間搖擺不定。我們確實注意到，艾爾建的研究納入了處於纖維化早期階段（F3）的患者。但您認為這在您的三期臨床試驗計畫中會有多大的風險？

Regina, so I'll start off. As I mentioned on the call, I think we're off to a great start. We've reiterated guidance in mid-year is progressing in line with our expectations. We do believe that 2018 is a trough year for us on which we can grow. We'll have seasonality fluctuations from quarter-to-quarter, but we're very confident since we reiterated our overall guidance for the year and expect to be able to grow off of our 2018 base going forward.

雷吉娜，那我就先來吧。正如我在電話會議中提到的，我認為我們開局很好。我們重申，年中業績指引正如預期推進。我們相信2018年對我們來說是低谷之年，我們可以藉此機會實現成長。雖然每季都會有季節性波動，但我們非常有信心，因為我們重申了全年的整體預期，並期望能夠在 2018 年的基礎上繼續成長。

Regina, it's John McHutchison. In terms of the second part of your question relating to variability in placebo response rates, it is an issue with liver biopsy where we know there's a 30% variability if you have 2 pathologists read the same liver biopsy. And I think some of the presentations you referred to at AASLD may be partly reflecting that. So it's an imperfect tool at best that -- what we have in terms of drug approvals for NASH patients. We have had the fortunate opportunity of being able to address this. Our previous simtuzumab trial enrolled many hundreds of patients. Now the drug didn't work, unfortunately but we have a lot of patients with 2 liver biopsies a long time apart. So we are very, very confident of what we expect to see in F3 and F4 patients in terms of the placebo response rate in terms of a fibrosis improvement score of 1 point with no worsening of NASH. So we have that number, and that is what we've used to calculate our power and our sample size in our STELLAR 3 and STELLAR 4 programs.

里賈納，我是約翰‧麥克哈奇森。關於你問題的第二部分，即安慰劑反應率的變異性，這是肝臟活檢的一個問題，我們知道，如果讓兩位病理學家解讀同一份肝臟活檢樣本，結果會有 30% 的差異。我認為您在 AASLD 會議上提到的一些報告可能在一定程度上反映了這一點。所以，就 NASH 患者的藥物批准而言，它充其量只是一個不完美的工具。我們有幸能夠解決這個問題。我們先前的simtuzumab試驗招募了數百名患者。很遺憾，這種藥物沒有起作用，但我們有很多患者接受了兩次間隔很長時間的肝臟活檢。因此，我們對 F3 和 F4 患者的安慰劑反應率非常有信心，即纖維化改善評分達到 1 分，且 NASH 沒有惡化。所以我們有了這個數字，並且我們在 STELLAR 3 和 STELLAR 4 專案中就是用這個數字來計算我們的功效和樣本量。

And our next question comes from Phil Nadeau of Cowen.

下一個問題來自 Cowen 公司的 Phil Nadeau。

Two follow-up questions in -- on the commercial side. So first, on HCV. Just to maybe ask Robyn's question in a different way. On Slide 35 of the slide deck you handed out on the last call, you did give a range for 2018 expected HCV sales of $3.5 billion to $4 billion even if it was informal guidance. And you said that the decrease versus the $9.1 billion from 2017 would be due to about $1 billion hit from total market patient starts and 43 to -- $4.3 billion to $4.6 billion hit from the competitive environment. So if you're going to redo that slide today, given what you've seen in Q1, would those numbers still hold? Would you still expect the same hit from market starts, competitive environment leading to the same 2018 range? And then just briefly on Biktarvy. I know you said that the access was good. We've heard from physician consultants that insurers are requiring prior auths and other methods early in the launch of HIV products. What are you seeing in terms of prior auths from insurance plans for Biktarvy?

接下來還有兩個問題──關於商業方面。首先，我們來談談丙型肝炎。或許可以換個方式問Robyn的問題。在您上次電話會議上分發的幻燈片第 35 頁中，您確實給出了 2018 年預期 HCV 銷售額範圍為 35 億美元至 40 億美元，即使這只是非正式的指導。您曾表示，與 2017 年的 91 億美元相比，下降的原因是市場患者總數減少約 10 億美元，以及競爭環境造成的 43 億至 46 億美元的損失。所以，如果今天你會根據第一季的情況重新製作那張投影片，這些數字還能成立嗎？您是否仍預期市場開盤和競爭環境會帶來與 2018 年相同的衝擊，並導致相同的價格區間？然後簡單介紹一下Biktarvy。我知道你說過交通便利。我們從醫生顧問那裡了解到，保險公司要求在 HIV 產品上市初期就進行事先授權和其他審批程序。您觀察到 Biktarvy 的保險計劃事先授權情況如何？

Phil, I'll think the first part and then turn it over to Andrew for Biktarvy. We are looking at page -- at the slide that you referred to, and again, I'll reiterate our HCV revenues for the quarter were $1 billion. So if I think about what we talked about, the reason for the step-down, one being price, right, because we did the new contracting in Q1. That would fall under competitive environment as well as thinking about share. I mean, the combination of those 2 make our competitive environment. Starts, we've talked about them being a slow and steady decline. So yes, I believe this slide is intact, and it's included in our overall reiteration of our guidance for the full year of $20 billion to $21 billion.

菲爾，我來想第一部分，然後交給安德魯去處理 Biktarvy 的問題。我們正在查看您提到的那張投影片，我再次重申，我們本季的 HCV 收入為 10 億美元。所以，如果我回顧一下我們討論的內容，降級的原因之一就是價格，對吧，因為我們在第一季度簽訂了新的合約。這既屬於競爭環境的範疇，也屬於考慮市場佔有率的範疇。我的意思是，這兩者的結合造就了我們如今的競爭環境。我們已經討論過，它們的下降趨勢是緩慢而穩定的。所以，是的，我相信這張投影片是完整的，並且包含在我們對全年200億至210億美元業績指引的總體重申中。

So Phil, it's Andrew. So we'll switch gears, and you were asking about prior authorizations with Biktarvy. I think as you're well aware of that within any new product launches that there's some degree of prior authorization as they start to review the product. However, as John mentioned on his initial remarks on the call, March 27, the DHHS guidelines place the Biktarvy top-tier of its recommended initial regimens list. Since that time, we've had -- received some feedback that amount of prior authorizations has really decreased and become less of an impediment. Not -- taken together, that helps put us to, and reiterate what Robin said earlier on the call, that we have every expectation that Biktarvy will match and then exceed Genvoya when it comes to #1 position for both naïve and switch patients.

菲爾，我是安德魯。所以我們換個話題，你剛剛問到了關於 Biktarvy 的事先授權問題。我想您應該很清楚，在任何新產品發布過程中，都會有一定的事先授權，因為他們會開始審查產品。然而，正如約翰在 3 月 27 日的電話會議上首次發言時所提到的那樣，美國衛生與公眾服務部 (DHHS) 的指導方針將 Biktarvy 列為推薦初始治療方案清單中的頂級藥物。自那時以來，我們收到了一些回饋，表示事先授權的數量確實減少了，不再構成太大障礙。不——總而言之，這有助於我們重申 Robin 早些時候在電話會議上所說的，我們完全有理由相信 Biktarvy 在初治患者和轉診患者中都能達到甚至超越 Genvoya 的排名第一地位。

And our next question comes from Terence Flynn of Goldman Sachs.

下一個問題來自高盛的特倫斯·弗林。

I was just wondering, maybe, John McHutchison, if you can discuss the importance of first mover advantage for Yescarta and DLBCL versus any potential modest benefit that a future competitor might have on CRS. Just wondering how you think about that. And then maybe one for Robin. Just HIV pricing in Europe. Have you guys seen any change in the pricing dynamics from the branded side, given the entry of generics?

約翰·麥克哈奇森，我只是想問問，您能否談談 Yescarta 和 DLBCL 的先發優勢的重要性，以及未來競爭對手在 CRS 方面可能獲得的任何潛在的微小優勢。想知道你對此有何看法。然後也許還要給羅賓一個。歐洲愛滋病毒定價情況。鑑於仿製藥的進入，你們是否觀察到品牌藥價格走勢有任何變化？

Terence, it's John McHutchison. Thank you for the question. I think the first mover advantage is important. We have the relationships. We have the experience now in the community, particularly in the U.S., which will obviously extend elsewhere. I think it's an important advantage as it has been for us in other diseases, including HIV and hepatitis C, where we were fortunate to be first as well. So that's a brief and general answer but I think it is important.

特倫斯，我是約翰‧麥克哈奇森。謝謝你的提問。我認為先發優勢非常重要。我們有人脈關係。我們現在在社區，尤其是在美國，累積了經驗，這顯然會推廣到其他地方。我認為這是一個重要的優勢，就像它在其他疾病領域（包括愛滋病和C型肝炎）對我們一樣，我們很幸運地也成為了第一個突破的領域。以上是一個簡短而概括的回答，但我認為這很重要。

Terence, it's Andrew. So I'll touch on the impact in Europe and what we've seen. Generics for Viread TDF are available in Europe, and we have seen some impact on certain prices in certain countries. However, I think it's important to recognize that over 50% of our European revenues come from TAF-based products, and you can see, as we mentioned on our last call that in certain countries, the conversion rate from TDF to TAF products like Germany exceeds 70%. So I think when one thinks about the impact, we've already made that switchover for a large -- for a number of countries, and that impact is somewhat muted.

特倫斯，我是安德魯。接下來我將談談它在歐洲的影響以及我們所看到的情況。Viread TDF 的仿製藥已在歐洲上市，我們看到某些國家的價格受到了一定影響。不過，我認為重要的是要認識到，我們超過 50% 的歐洲收入來自基於 TAF 的產品，而且正如我們在上次電話會議中提到的，在某些國家，例如德國，從 TDF 到 TAF 產品的轉換率超過 70%。所以我覺得，從影響的角度來看，我們已經對許多國家進行了大規模的轉變，而這種影響在某種程度上是微不足道的。

And Terence, to follow on to that. We priced Genvoya at parity with STRIBILD. So our ability to get early access in those markets where we've launched, it helps, and it helps that overall transition that Andrew just referred to as greater than 50% being Descovy regimens overall.

接下來是特倫斯。我們將 Genvoya 的定價與 STRIBILD 持平。因此，我們能夠在已推出產品的市場中儘早獲得准入資格，這很有幫助，也有助於安德魯剛才提到的整體轉型，即超過 50% 的產品都採用了 Descovy 療法。

And our next question comes from Cory Kasimov with JPMorgan.

下一個問題來自摩根大通的科里·卡西莫夫。

Thanks for taking my question. It's on Yescarta, and I'm wondering, is the $40 million in sales in Q1 pretty evenly distributed across your 40 authorized centers? Or is it more concentrated in a handful of them? And then just in general terms, should we be thinking about patient capacity per center as something that also gradually evolves over time?

謝謝您回答我的問題。它已在 Yescarta 上發布，我想知道，第一季 4000 萬美元的銷售額是否在你們的 40 個授權中心之間分配得相當均勻？或者說，它更集中在少數幾個人身上？那麼，從總體上看，我們是否應該將每個中心的患者容量視為隨著時間而逐漸變化的因素呢？

Cory, it's Robin. I'd say, again, it's early days relative to our centers being certified and getting launched to get really get at a throughput per center, any of those type of metrics. And I'll also say that because this is such a specialized treatment, we've selected centers that we think can be successful, we're helping them through that. Yes, some of the earlier centers we're seeing higher volumes as you would anticipate but I think the volume is not just determined by saying, "You're now certified." It's just determined by the hospital and their resources and looking at the other various treatments, et cetera, and other capacity [centers] that any hospital has to manage. So it's going to be harder, particularly in this therapeutic area, to provide the level of detail and granularity or, at this stage, details by center. The $40 million was very robust growth. We're happy with the results today. And as I mentioned, it's going to be a controlled, measured launch for us, and we're going to continue in that process and provide you updates on that as much as we can.

科里，我是羅賓。我想再次強調，就我們的中心獲得認證和正式啟動而言，現在還處於早期階段，要真正獲得每個中心的吞吐量或任何此類指標還為時過早。我還要說，因為這是一種非常專業的治療，我們已經選擇了我們認為能夠成功實施治療的中心，我們正在幫助他們完成治療。是的，正如你所預料的，一些較早獲得認證的中心確實出現了較高的就診量，但我認為就診量並非僅僅取決於“你現在獲得認證了”這句話本身，而是取決於醫院及其資源，以及醫院必須管理的其他各種治療方案、其他醫療中心等因素。因此，尤其是在治療領域，要提供足夠詳細的信息，或者在這個階段按中心提供詳細信息，將會更加困難。這4000萬美元的成長非常強勁。我們對今天的結果很滿意。正如我之前提到的，我們將採取可控、有條不紊的發布方式，我們將繼續推進這一過程，並盡可能地向您提供最新資訊。

And our next question comes from Alethia Young of Credit Suisse.

下一個問題來自瑞士信貸的阿萊西亞·楊。

Congrats to John and Andrews. This is more on the commercial standpoint, just kind of big picture. So Biktarvy has taken like roughly 80% switch from Genvoya. I just kind of wanted to think about broadly. Should we think Genvoya kind of continues to grow or does it kind of inflect and then Biktarvy kind of picks up where Genvoya lets -- left off? Or is it just the case that the 80% Biktarvy switch most likely may moderate a little bit, so that trend may not be as pronounced?

恭喜約翰和安德魯斯。這比較是從商業角度出發，從宏觀角度來看。所以 Biktarvy 大約有 80% 的用戶從 Genvoya 轉投 Biktarvy。我只是想從更廣泛的角度思考。我們應該認為 Genvoya 會繼續發展壯大，還是會發生一些轉變，然後 Biktarvy 會接手 Genvoya 未完成的工作？或者，80% Biktarvy 的轉變可能會有所緩和，因此這種趨勢可能不會那麼明顯？

So Alethia, let me just clarify something in your call just to recognize that. When we think about Biktarvy scripts, 80% come from switches. About 1/3 of those come from Genvoya. So I think when we think about 1/3 from Genvoya, that about 20% for dolutegravir-based regimen either Tivicay or Triumeq, and then the remainder of the switches come from a mix of different regimens. So when we think about it overall, I think we're very happy with the mix. And given our robust development plan where 2 of the 4 studies were based on the switch, one from Triumeq and one from protease inhibitor regimen, we expect that, that mix to actually to be the same going forward, about an 80-20 switch given the overall dynamics. Now there's certainly going to be some degree of variability from quarter-to-quarter to the proportion of Genvoya versus dolutegravir-based regimens. But certainly, we're very comfortable where we are and expect that the overall growth in Biktarvy to continue, as we mentioned earlier.

所以阿萊西亞，我只想澄清一下你通話中的一些事情，以示確認。當我們想到 Biktarvy 腳本時，80% 都來自 switch 語句。其中約有三分之一來自 Genvoya。所以我認為，當我們考慮 Genvoya 時，大約有 1/3 的患者轉用了基於多替拉韋的治療方案（Tivicay 或 Triumeq），大約有 20% 的患者轉用了其他治療方案，其餘的患者則轉用了其他治療方案。所以總的來說，我們對這個組合非常滿意。鑑於我們強大的研發計劃，其中 4 項研究中有 2 項是基於轉換的，一項是從 Triumeq 轉換，一項是從蛋白酶抑製劑方案轉換，我們預計，考慮到整體動態，這種組合實際上將保持不變，大約是 80-20 的轉換。現在，Genvoya 與基於多替拉韋的治療方案的比例肯定會因季度而異。但當然，我們對目前的狀況非常滿意，並預計 Biktarvy 的整體成長將會繼續，正如我們之前提到的。

And our next question comes from Salim Syed of Mizuho.

下一個問題來自瑞穗銀行的Salim Syed。

Just one on Yescarta. Could you just maybe comment on what sort of education you guys are doing with the medical community for the non-CAR T oncology docs? And if these docs are actually referring patient to the CAR T centers, after which line of therapy in general?

Yescarta 上只有一個。能否請您談談貴公司正在為非CAR-T腫瘤科醫師進行哪些方面的醫學教育？如果這些醫生真的將患者轉診到 CAR-T 治療中心，那麼通常是在患者接受哪一線治療之後呢？

Salim, it's John Milligan. I just wanted to -- it's actually a very timely question. So as you know, we've been out in the community detailing Zydelig, and we've just recently taken those representatives, our therapeutic specialists and put them through a specific CAR T training so that they can start to have a conversation with doctors in the communities about what CAR T is, what kinds of patients are eligible for CAR T and can help them with referral. [I don't know about the procedurals] but I think certainly, encouraging doctors to refer those patients who would be eligible to specialists who then can handle those cases. So we are starting an educational campaign in the community that really kicked off this week.

薩利姆，我是約翰‧米利根。我只是想說——這其實是一個非常及時的問題。如你所知，我們一直在社區中詳細介紹 Zydelig，最近我們也對這些代表和治療專家進行了專門的 CAR-T 培訓，以便他們能夠開始與社區中的醫生討論 CAR-T 是什麼，哪些類型的患者符合 CAR-T 的條件，並幫助他們進行轉診。[我不了解具體程序]，但我認為，鼓勵醫生將符合條件的患者轉診給能夠處理這些病例的專家，這當然是值得的。因此，我們在社區發起了一項教育宣傳活動，這項活動本周正式啟動。

And our next question comes from Ying Huang of Bank of America Merrill Lynch.

下一個問題來自美國銀行美林證券的黃穎。

First one I have related to the data you presented at EASL. So if you look at the MRI PDFF data, it seems that the ASK1 inhibitor does not appear to be very potent compared to the ACC inhibitor or even FXR. So I was wondering, based on that, how much confidence do you have on the ultimate success of the Phase III trial for ASK1 in STELLAR 3 and 4 trials? And then maybe, Robin, can you elaborate a little bit on the ex U.S. dynamics for HCV? Because it appears that AbbVie has enjoyed very much success in launching Mavyret in ex U.S. based on the numbers reported. I was wondering if you see that evolving in the next few quarters, whether you can gain back shares from AbbVie or not.

我的第一個問題與您在 EASL 上展示的數據有關。因此，如果你查看 MRI PDFF 數據，你會發現 ASK1 抑制劑與 ACC 抑制劑甚至 FXR 相比，似乎效力並不強。所以我想知道，基於以上情況，您對 ASK1 在 STELLAR 3 和 4 試驗中的 III 期試驗最終取得成功有多大信心？那麼，羅賓，你能否詳細談談美國以外地區的C型肝炎疫情動態？根據已公佈的數據來看，艾伯維在美國以外地區推出 Mavyret 似乎取得了非常大的成功。我想知道您認為未來幾季情況會如何發展，您是否能夠從艾伯維手中奪回股份。

Ying, it's John McHutchison to answer the first part of your question. The observation you made and noted in our EASL presentation that selonsertib has less of an effect on steatosis in the liver than our ACC inhibitor that inhibits de novo lipogenesis is exactly what we wanted to see and expected to see because of the mechanism of action. Selonsertib doesn't have a primary anti lipotoxicity effect. It's an [anti-ASK] and it works on hepatic steatosis as well. So that's what we expected to see. In terms of the second part of your question, does it give us more or less confidence in terms of our Phase III STELLAR programs. I think you need to take the context of what we presented at EASL in a 12-week study and think about it in the overall context. What we did in all of these programs is we did single-agent small studies for us to show that each drug was effective, which was done for all of our 3 drugs. Then we did a small combination study to see if there was combination safety. That's what we presented at EASL. We did, however, also present some of the parameters that you've been talking about. But our goal was always, once we had combination safety, to then be able to kick off a definitive, larger study for the longer duration of therapy to determine which of those drugs is safer, which is what we're doing. To get back to the selonsertib question. We decided to do a Phase III STELLAR selonsertib study based on a previous study that we presented last year that was 24 weeks in duration, that had 2 liver biopsies. It showed a dose-dependent effect on the regression of fibrosis, and an inverse relationship to the development of cirrhosis. We also showed that the target (inaudible) P38 is up regulated in NASH those patients, and it's also blocked or inhibited or down regulated the drug. So everything is heading in the right direction. And I think what's happening here is people are taking this small 12-week experiment that was due and looking at combination safety out of context. When we started our STELLAR 3 Phase III program, it was based on a larger Phase II study, 2 biopsies 6 months apart that showed a definitive effect on fibrosis. So we are in good shape. I'm excited about the results. We have enrolled them ahead of schedule, and we look forward to getting the results early next year.

瑩，我是約翰‧麥克哈奇森，來回答你問題的第一部分。您在 EASL 會議上提出的觀察結果，即 selonsertib 對肝臟脂肪變性的影響小於我們抑制從頭脂肪生成的 ACC 抑制劑，正是我們想要看到和預期會看到的，因為其作用機制與 ACC 抑制劑的作用機制相符。Selonsertib 不具有主要的抗脂毒性作用。它是一種[抗ASK]藥物，對肝脂肪變性也有效。所以，這和我們預想的一樣。關於您問題的第二部分，這是否讓我們對我們的第三階段 STELLAR 計劃更有信心或更缺乏信心？我認為你需要結合我們在 EASL 上提出的為期 12 週的研究背景來思考這個問題。我們在所有這些項目中所做的，就是進行單藥小規模研究，以證明每種藥物的有效性，我們所有的 3 種藥物都進行了這樣的研究。然後我們進行了一項小規模的組合研究，以檢驗組合用藥的安全性。這就是我們在EASL會議上展示的內容。不過，我們也確實提出了一些您一直在談論的參數。但我們的目標始終是，一旦確定了聯合用藥的安全性，就可以啟動一項更大規模的、更長期的治療研究，以確定哪種藥物更安全，而這正是我們正在做的。回到 selonsertib 的問題。我們決定進行一項 III 期 STELLAR selonsertib 研究，該研究基​​於我們去年發表的一項為期 24 週、進行了 2 次肝臟活檢的先前研究。它顯示出對纖維化消退的劑量依賴性效應，以及與肝硬化發展呈反比關係。我們也發現，在 NASH 患者中，標靶（聽不清楚）P38 表達上調，且該藥物也會阻斷、抑製或下調 P38。所以一切都在朝著正確的方向發展。我認為這裡發生的情況是，人們把這項原本應該進行的為期 12 週的小型實驗脫離了實際情況，去看待組合安全性。當我們啟動 STELLAR 3 III 期計畫時，它是基於一項更大規模的 II 期研究，該研究間隔 6 個月進行了兩次活檢，結果顯示對纖維化有明確的療效。所以我們情況良好。我對結果感到很興奮。我們已經提前完成了他們的入學手續，期待明年年初就能得到結果。

Thanks, John. And I think, Ying, your other question related to ex U.S. HCV sales. So let me start by saying I think that's always been a much more competitive environment compared to the U.S. The OUS sales, as we compare what we did relative to our competitor, includes a wide variety of geographies, including Europe, Japan and Asia. And I would say the market share is very -- they're very different from country to country. I think it is fair to say that we've seen our competitors do very well in Japan, for example, with some of the prior [CAA] failures and some warehousing there. But there are other countries where we're doing well. And we're going to pick our opportunities to focus on. While we know this is a competitive market, we feel we have the sales force and necessary folks in place to be competitive. And as mentioned, I think we're on track. And relative to where we expected to be, we see things playing out very close to that. So as I also said, we expect our share to stabilize by mid-year. So I think we'll be able to provide more insight around share going forward during the next call.

謝謝你，約翰。英，我認為你的另一個問題與美國以外的HCV銷售有關。首先我想說的是，我認為與美國相比，海外市場一直是個競爭更激烈的環境。當我們把我們的業績與競爭對手進行比較時，海外市場的銷售額涵蓋了包括歐洲、日本和亞洲在內的廣泛地區。而且我認為市佔率非常——各國之間的差異非常大。我認為可以公平地說，我們已經看到我們的競爭對手在日本做得非常好，例如，利用之前一些[CAA]的失敗案例以及在日本的一些倉儲業務。但在其他國家，我們做得很好。我們將挑選出需要重點關注的機會。雖然我們知道這是一個競爭激烈的市場，但我們相信我們有足夠的銷售團隊和必要的人員，能夠保持競爭力。正如前面提到的，我認為我們正按計劃進行。與我們預期的情況相比，目前的情況非常接近預期。正如我之前所說，我們預計到年中我們的市佔率將趨於穩定。所以我認為，在下次電話會議上，我們將能夠就未來的市場份額提供更多見解。

And our final question comes from the line of Carter Gould of UBS.

最後一個問題來自瑞銀集團的卡特古爾德。

I was looking to get some clarity on the regulatory strategy for filgotinib and if investors should expect you to file, I guess, following that the FINCH 1 and FINCH 3 data become available. Or will you look to wait for maybe one of the GI-focused indications to have Phase III data in hand as well?

我想了解一下filgotinib的監管策略，以及投資者是否應該期待你們在FINCH 1和FINCH 3數據公佈後提交申請。或者您會考慮等待某個以胃腸道為重點的適應症獲得 III 期臨床試驗數據嗎？

Yes. So Carter, it's John McHutchison. Thank you for the question. So as I said today in my prepared notes that we now are in the fortunate position to have all FINCH 3 trials enrolled of both methotrexate naïve and inadequate responders and our virologic [non-] responders. So we can file if the data supports that of course, we can file for RA with all of those 3 studies. And they are in a different timeline from the inflammatory bowel disease studies. So we would not wait for the inflammatory bowel disease studies.

是的。所以卡特，我是約翰‧麥克哈奇森。謝謝你的提問。正如我今天在準備好的筆記中所說，我們現在很幸運地已經招募了所有 FINCH 3 試驗的受試者，包括未接受過甲氨蝶呤治療的患者、療效不佳的患者以及病毒學（無）應答者。所以，如果數據支持，我們當然可以提交申請；當然，我們可以用這 3 項研究結果申請 RA。而且它們與發炎性腸道疾病研究處於不同的時間線。所以，我們不會等待發炎性腸道疾病的研究結果。

And that concludes our question-and-answer session for today. I'd like to turn the conference back over to Sung Lee for any closing remarks.

今天的問答環節到此結束。我謹將會議交還給李成先生，請他作總結發言。

Thank you, Candace, and thank you all for joining us today. We appreciate your continued interest in Gilead, and the team here looks forward to providing you with updates on our future progress.

謝謝坎迪斯，也謝謝各位今天蒞臨現場。我們感謝您一直以來對吉利德的關注，我們的團隊期待向您報告我們未來的進展。

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

女士們、先生們，感謝各位參加今天的會議。程式到此結束，各位可以斷開連接了。祝大家今天過得愉快。