吉利德科學 (GILD) 2018 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to Gilead Sciences' Fourth Quarter 2018 Earnings Conference Call. My name is Jonathan, and I will be your conference operator today. (Operator Instructions) And as a reminder, this conference call is being recorded.

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年第四季財報電話會議。我叫喬納森，今天我將擔任你們的會議接線生。（操作員說明）再次提醒，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, Jonathan, and good afternoon, everyone. Just after market close today, we issued a press release with earnings results for the fourth quarter 2018. The press release and detailed slides are available on the Investor Relations section of the Gilead website.

謝謝你，喬納森，大家下午好。今天股市收盤後不久，我們發布了 2018 年第四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: Robin Washington, Executive Vice President and Chief Financial Officer; Laura Hamill, Executive Vice President, Worldwide Commercial Operations; and John McHutchison, Chief Scientific Officer and Head of Research and Development. Also in the room is Gregg Alton, Interim CEO and Chief Patient Officer.

今天電話會議的發言人有：執行副總裁兼財務長 Robin Washington；執行副總裁兼全球商業營運負責人 Laura Hamill；以及首席科學官兼研發主管 John McHutchison。房間裡還有臨時執行長兼首席患者長格雷格·奧爾頓。

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. A description of these risks can be found in our 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.

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。有關這些風險的描述，請參閱我們最新的美國證券交易委員會披露文件和近期發布的新聞稿。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 Robin.

現在我會把通話轉給羅賓。

Thank you, Sung, and good afternoon, everyone. We are pleased to share our financial results for the fourth quarter and full year 2018 and provide 2019 guidance. I will first review financials followed by comments from Laura and John.

謝謝宋，大家午安。我們很高興與大家分享 2018 年第四季和全年的財務業績，並提供 2019 年的業績指引。我將首先回顧財務數據，然後是勞拉和約翰的評論。

2018 was a year filled with accomplishments where we met our financial and operational goals. Beginning with our HIV franchise, we extended our leadership position and grew the business to an all-time high in product revenue. We continue to execute and maximize our opportunity in HCV and initiated a plan to launch authorized generics this year, which should keep us very competitive in a durable long-term market. In cell therapy, we made tremendous progress in the number of centers authorized and saw the steady and measured adoption of Yescarta in the U.S. and the approval of Yescarta in Europe. We advanced our pipeline and finished the year with a strong balance sheet that will enable us to continue to execute on M&A and partnerships to drive future growth.

2018 年是碩果累累的一年，我們實現了財務和營運目標。從我們的 HIV 產品線開始，我們鞏固了領先地位，並將業務發展到產品收入的歷史新高。我們將繼續掌握並最大限度地利用我們在丙型肝炎領域的機遇，並啟動了今年推出授權仿製藥的計劃，這將使我們在持久的長期市場中保持很強的競爭力。在細胞療法領域，我們獲得了大量授權中心，並在美國穩步推進了 Yescarta 的推廣應用，同時 Yescarta 也在歐洲獲得了批准。我們推進了專案儲備，並以強勁的資產負債表結束了這一年，這將使我們能夠繼續執行併購和合作，以推動未來的成長。

Turning to the financials. Total revenues for the fourth quarter were $5.8 billion, with non-GAAP earnings of $1.44 per share. This compares to revenue of $5.9 billion, with non-GAAP earnings of $1.78 per share for the same period last year.

接下來來看財務數據。第四季總營收為 58 億美元，非 GAAP 每股收益為 1.44 美元。相比之下，去年同期營收為 59 億美元，非 GAAP 每股收益為 1.78 美元。

For the full year 2018, total revenues were $22.1 billion, down 15% year-over-year. Non-GAAP diluted earnings were $6.67 per share for the year, down from $8.84 per share for the full year 2017. The full year 2018 GAAP diluted earnings of $4.17 per share included an unfavorable impact of $0.98 (sic) [$0.99] per share due to an impairment charge for in-processed research and development for the KITE-585 anti-BCMA program for the treatment of multiple myeloma and a noncash tax charge related to intangible assets acquired from Kite.

2018 年全年總營收為 221 億美元，年減 15%。本年度非GAAP稀釋後每股收益為6.67美元，低於2017年全年的每股8.84美元。2018 年全年 GAAP 稀釋後每股收益為 4.17 美元，其中包括每股 0.98 美元（原文如此）[0.99 美元] 的不利影響，原因是 KITE-585 抗 BCMA 治療多發性骨髓瘤項目的在研發減值支出，以及與從 Kite 收購的無形資產相關的非現金稅額支出。

Now turning to our product sales. Product sales for the fourth quarter were $5.7 billion, up 4% sequentially and down 3% year-over-year. For the full year, product sales were $21.7 billion, down 16% year-over-year driven by lower HCV sales.

現在來說說我們的產品銷售狀況。第四季產品銷售額為 57 億美元，季增 4%，年減 3%。全年產品銷售額為 217 億美元，年減 16%，主要原因是C肝病毒 (HCV) 銷售額下降。

In the U.S., product sales for the quarter were $4.5 billion, up 8% sequentially and 8% year-over-year. This marks the first quarter in several years where U.S. product sales grew year-over-year as the revenue growth of our HIV franchise more than offset the market dynamics of our HCV franchise. While demand, particularly for Biktarvy and Truvada for PrEP, was a driver of sequential growth, the quarter also benefited from seasonal inventory purchases and a favorable payer mix. These 2 factors contributed an estimated incremental $250 million to the sequential performance.

在美國，該季度產品銷售額為 45 億美元，季增 8%，年增 8%。這是美國產品銷售額幾年來首次實現同比成長的季度，因為我們 HIV 產品線的收入成長超過了 HCV 產品線的市場波動。雖然對 Biktarvy 和 Truvada（用於 PrEP）的需求是環比增長的驅動力，但本季也受益於季節性庫存採購和有利的支付方組合。這兩個因素預計為業績環比成長貢獻了 2.5 億美元。

In Europe, product sales for the quarter were $813 million, down 7% sequentially and 29% year-over-year. The sequential and year-over-year declines were anticipated and included the full quarter impact and launch of generic HIV products in certain markets as well as an accounting adjustment related to statutory revenue clawback reserves.

在歐洲，該季度產品銷售額為 8.13 億美元，季減 7%，年減 29%。環比和年減均在預期之內，其中包括整個季度的影響以及某些市場推出仿製 HIV 產品的影響，以及與法定收入追回準備金相關的會計調整。

Now turning to the expenses for the full year 2018. Non-GAAP cost of goods sold were $300.6 billion (sic) [$3.6 billion], up 5% compared to $3.4 billion in 2017. The increase was caused by a $410 million reserve on unfavorable $0.31 EPS impact, primarily for excess Harvoni inventory due to a shift in demand to Epclusa.

現在來看2018年全年的各項支出。非GAAP銷售成本為3006億美元（原文如此）[36億美元]，比2017年的34億美元成長了5%。此次成長是由於每股盈餘不利影響0.31美元而提列了4.1億美元的準備金，主要原因是由於需求轉向Epclusa，導致Harvoni庫存過剩。

Non-GAAP R&D expenses were $3.5 billion, and non-GAAP SG&A expenses were $3.6 billion. Both expense categories increased by 7% compared to the same period last year, primarily due to a full year of investments to support the growth of our business following the acquisition of Kite.

非GAAP研發費用為35億美元，非GAAP銷售、管理及行政費用為36億美元。與去年同期相比，兩項支出類別均成長了 7%，這主要是由於收購 Kite 後，我們投入了一整年資金來支持業務成長。

Our non-GAAP effective tax rate for the full year 2018 decreased to 19.8% compared to 24.5% in the same period last year, primarily due to a reduction of the U.S. corporate tax rate as a result of tax reform and the favorable impact of a tax settlement.

2018 年全年，我們的非 GAAP 實際稅率降至 19.8%，而去年同期為 24.5%，主要是由於稅收改革導緻美國企業稅率降低以及稅收和解的有利影響。

Turning to the balance sheet. We generated $8.4 billion in cash from operations for the full year 2018 and $2.3 billion for the quarter. We ended the year with $31.5 billion in cash and cash equivalents.

接下來看一下資產負債表。2018 年全年，我們的經營活動產生了 84 億美元的現金，而該季度則產生了 23 億美元的現金。截至年底，我們持有現金及現金等價物315億美元。

During 2018, we repaid $6.3 billion of debt, the majority of which was related to our acquisition of Kite, and paid cash dividends of $3 billion. In 2018, we repurchased 40 million shares for $2.9 billion. In Q4, we made opportunistically purchases of approximately 14 million shares for $962 million, resulting in a reduction of diluted shares outstanding at year-end.

2018 年，我們償還了 63 億美元的債務，其中大部分與我們收購 Kite 有關，並支付了 30 億美元的現金股利。2018 年，我們以 29 億美元的價格回購了 4,000 萬股股票。第四季度，我們抓住機會，以 9.62 億美元的價格購買了約 1400 萬股股票，導致年底稀釋後流通股數量減少。

Earlier today, we announced an 11% increase in our quarterly dividend from $0.57 to $0.63 per share, which will become effective in the first quarter of 2019. This represents the fourth consecutive year of double-digit increases to the dividend and underscores our confidence in the strength of the business and future cash flows.

今天早些時候，我們宣布將季度股息提高 11%，從每股 0.57 美元增至 0.63 美元，該調整將於 2019 年第一季生效。這標誌著股息連續第四年實現兩位數成長，凸顯了我們對公司業務實力和未來現金流的信心。

In 2019, our capital allocation priorities will remain the same with a focus on M&A and partnerships to augment our pipeline followed by dividends and share repurchases.

2019 年，我們的資本配置重點將保持不變，重點是併購和合作，以增強我們的產品線，其次是股利和股票回購。

Before I provide details for our full year 2019 guidance, I would like to highlight aspects of 2018 performance, as illustrated on Slide 20, which will impact the anticipated level of product revenue growth in 2019 relative to 2018.

在詳細介紹我們 2019 年全年業績指引之前，我想重點介紹 2018 年業績的幾個方面，如投影片 20 所示，這些方面將影響 2019 年產品收入成長相對於 2018 年的預期水準。

In October, during our Q3 earnings announcement, we increased our 2018 full year product revenue guidance due to 2 unanticipated events: our second half 2018 revenues did not reflect the entry of a generic version of Letairis in the U.S. as expected when we issued our original guidance at the beginning of 2018; secondly, we saw the entry of generic versions of our HIV products occurred later in certain ex U.S. countries than we had originally expected. It is important to keep these events in mind as our 2019 revenue performance unfold as they will have an impact on the level of product revenue growth in the year.

10 月份，在第三季度收益公佈期間，我們提高了 2018 年全年產品收入預期，原因是兩個意料之外的事件：首先，我們 2018 年下半年的收入沒有反映出 Letairis 的仿製藥在美國的上市，這與我們在 2018 年初發布最初預期時的情況有所不同；其次，我們發現，在某些美國以外的國家發布，仿製藥時間比我們預期的公司有所不同；其次，我們發現，在某些美國以外的國家。在展望 2019 年營收表現時，請務必牢記這些事件，因為它們將對當年的產品營收成長水準產生影響。

Turning to guidance. Our 2019 non-GAAP financial guidance is summarized on Slides 19 through 23 in the earnings presentation available on our corporate website. Product sales are expected to be in the range of $21.3 billion to $21.8 billion. This guidance is subject to a number of uncertainties, including slower-than-anticipated growth in our HIV franchise; a larger-than-anticipated shift in payer mix to more highly discounted payer segment such as PHS, FSS, Medicaid and the VA; lower-than-expected market share and greater price erosion resulting from the sale of generic versions of TDF, the fixed dose combination of FTC/TDF and the fixed dose combination of FTC/TDF efavirenz; the accuracy of our assumptions about HCV market share; the accuracy of our estimates for HCV patient starts in 2019; unanticipated pricing pressures from payers and competitors; as well as volatility in foreign currency exchange rates, which could be plus or minus $300 million for each 10% change relative to our assumptions.

尋求指導。我們的 2019 年非 GAAP 財務指引總結在公司網站上提供的獲利簡報的第 19 至 23 頁。預計產品銷售額將在 213 億美元至 218 億美元之間。此指導意見受多種不確定因素的影響，包括：HIV業務成長速度低於預期；支付方結構向折扣力度更大的支付方（如PHS、FSS、Medicaid和VA）的轉變幅度超出預期；TDF仿製藥、FTC/TDF固定劑量複方製劑和FTC/TDF依非韋倫固定劑量複方製劑的銷釘售導致市場佔有率低於預期，價格侵蝕幅度更大；我們對HCV市場佔有率的假設是否準確；我們對2019年HCV患者起始治療人數的估計是否準確；來自支付方和競爭對手的意外定價壓力；以及外匯匯率的波動，相對於我們的假設，匯率每變動10%，就可能產生正負3億美元的損失。

Non-GAAP product gross margins are expected to be in the range of 85% to 87%. We expect our non-GAAP R&D expenses to be in the range of $3.6 billion to $3.8 billion. Non-GAAP SG&A expenses are expected to be in the range of $3.9 billion to $4.1 billion and include investments to prepare for commercial launches in NASH and inflammation. For the full year, our non-GAAP effective tax rate is expected to be in the range of 20% to 21%. We anticipate the full-year diluted EPS impact of acquisition-related stock-based compensation and other expenses to be in the range of $1.40 to $1.50 per share.

非GAAP產品毛利率預計在85%至87%之間。我們預計非GAAP研發費用將在36億美元至38億美元之間。非GAAP SG&A費用預計在39億美元至41億美元之間，其中包括為NASH和發炎領域的商業化推出做準備的投資。預計全年非GAAP有效稅率將在20%至21%之間。我們預計與收購相關的股票選擇權費用和其他費用對全年稀釋後每股盈餘的影響將在每股 1.40 美元至 1.50 美元之間。

As we look towards Q1 2019, we anticipate total Gilead product sales will decline sequentially by a percentage similar to what we've seen over the past 2 years, which was in the range of 12% to 14%, primarily driven by the U.S. seasonal inventory patterns and buying patterns of public payers that negatively impact payer mix. Also factored into the Q1 sequential decline is a step-down in price for our HCV drugs sold into U.S. Medicare. Despite this anticipated sequential decline in total product sales in Q1, I want to underscore our confidence in the health of our worldwide HIV business from which we expect double-digit year-on-year growth again in 2019.

展望 2019 年第一季度，我們預計吉利德產品總銷售額將環比下降，降幅與過去兩年類似，在 12% 到 14% 之間，這主要是由於美國季節性庫存模式和公共支付方的購買模式對支付方組合產生負面影響所致。第一季環比下降的另一個原因是，我們向美國聯邦醫療保險銷售的丙型肝炎藥物價格有所下降。儘管預計第一季產品總銷售額將環比下降，但我仍要強調我們對全球 HIV 業務的健康狀況充滿信心，我們預計 2019 年該業務將再次實現兩位數的同比增長。

I will now turn the call over to Laura.

現在我將把通話轉給勞拉。

Thank you, Robin. Good afternoon, everyone. I will provide an update on our commercial performance during the fourth quarter and share some highlights from markets around the world.

謝謝你，羅賓。大家下午好。我將介紹我們第四季的商業業績，並分享來自世界各地市場的亮點。

Beginning with HIV. We achieved an all-time high in quarterly revenues. This speaks to the appeal of our Descovy-based regimen led by Biktarvy, the growing use of Truvada for PrEP and our ability to execute commercially. In the U.S., total HIV revenue was $3.4 billion in the fourth quarter, up 30% year-over-year and 13% quarter-over-quarter. Year-over-year growth was driven by a 13% increase of prescription and also benefited from inventory purchases and favorable payer mix mentioned earlier by Robin. We continue to see strong adoption of Descovy-based regimens, which accounted for 77% of Gilead's total U.S. HIV prescription volume as we ended the fourth quarter. This is a remarkable achievement considering the first Descovy-based regimen was introduced just 3 years ago.

從愛滋病毒開始。我們的季度營收創歷史新高。這說明了我們以 Descovy 為基礎、以 Biktarvy 為主導的治療方案的吸引力，Truvada 在 PrEP 中的應用日益廣泛，以及我們在商業執行方面的能力。在美國，第四季 HIV 相關收入總額為 34 億美元，較去年同期成長 30%，較上季成長 13%。年成長主要得益於處方量成長 13%，同時也受益於庫存採購和 Robin 前面提到的有利的支付方組合。我們繼續看到基於 Descovy 的治療方案被廣泛採用，截至第四季度末，該方案佔吉利德在美國 HIV 處方總量的 77%。考慮到第一個基於 Descovy 的治療方案僅在 3 年前才推出，這真是一項了不起的成就。

Through its first 11 months, Biktarvy remains the best HIV launch of all time in the U.S. as measured by total prescriptions on a launch-aligned basis. During the fourth quarter, Biktarvy generated $551 million in revenue in the U.S. and is the #1 prescribed regimen for both treatment naïve and switch patients. Approximately 80% of Biktarvy's U.S. prescriptions came from switches, 25% of these switches from dolutegravir and another 25% coming from Genvoya. This is a testament to the profile of Biktarvy, its strong efficacy and no identified cases of treatment emergent resistance at week 96 in our Phase III studies. Biktarvy provides the renal and bone safety advantages offered by Descovy backbone with minimal drug-to-drug interactions. These are important considerations for an aging HIV population and for younger patients on lifelong treatment.

從上市後的前 11 個月來看，以上市前後的處方總量計算，Biktarvy 仍然是美國有史以來表現最好的 HIV 藥物上市產品。第四季度，Biktarvy 在美國創造了 5.51 億美元的收入，是初治患者和轉診患者的首選處方方案。Biktarvy 在美國的處方中約有 80% 來自藥物轉換，其中 25% 來自 dolutegravir，另有 25% 來自 Genvoya。這證明了 Biktarvy 的良好特性、強大的療效，並且在我們的 III 期研究中，第 96 週未發現任何治療抗藥性病例。Biktarvy 具有 Descovy 骨架的腎臟和骨骼安全優勢，同時藥物交互作用極小。對於老化的愛滋病患者群體和需要終身治療的年輕患者來說，這些都是重要的考慮因素。

Moving to prevention. Truvada for PrEP continues to grow as we invest in the U.S. to raise awareness among at-risk individuals and treating physicians. We estimate that approximately 202,000 people were taking Truvada for PrEP at the end of the fourth quarter in 2008. We initiated 2 direct consumer campaigns in mid-2008 and have a dedicated team of therapeutic specialists focused on Truvada for PrEP. Additionally, we have a number of commercial programs aimed at helping populations disproportionately impacted by HIV where utilization of Truvada for PrEP is low. While these investments have helped increase awareness, there is still so much more we can do. The CDC estimates that 1.1 million people in the U.S. could benefit from PrEP.

轉向預防。Truvada 用於 PrEP 的銷售持續成長，我們加大了在美國的投資，以提高高風險族群和治療醫生的認識。我們估計，2008 年第四季末，約有 202,000 人服用 Truvada 進行 PrEP。我們在 2008 年中發起了 2 項直接面向消費者的活動，並擁有一支專門的治療專家團隊，致力於 Truvada 在 PrEP 中的應用。此外，我們還有一些商業計畫旨在幫助受 HIV 影響較大的人群，這些人群使用 Truvada 進行 PrEP 的比例較低。雖然這些投入有助於提高公眾意識，但我們仍有許多工作要做。美國疾病管制與預防中心估計，美國有 110 萬人可以從 PrEP 中受益。

Now turning to Europe. Total HIV revenue was $511 million in the fourth quarter, down 21% year-over-year and down 13% quarter-over-quarter. This decline was driven by the expected availability of generics across all major EU countries. During 2018, we experienced slower erosion of the HIV franchise due to later generic entry in a few countries, while at the same time, we saw rapid uptake of our Descovy-based products, which accounted for more than 80% of our total HIV revenue in Europe for the fourth quarter.

現在轉向歐洲。第四季 HIV 相關營收總計 5.11 億美元，年減 21%，季減 13%。這一下降是由於歐盟所有主要國家預期仿製藥的供應充足所致。2018 年，由於一些國家仿製藥上市較晚，我們的 HIV 產品線流失速度有所放緩；與此同時，我們基於 Descovy 的產品迅速普及，在第四季度占我們在歐洲 HIV 總收入的 80% 以上。

We are encouraged by the strong uptake of Biktarvy in Germany and in France. In Germany, Biktarvy was #1 prescribed regimen for both treatment naïve and switch patients during the fourth quarter. And in France, just 6 weeks after launch, Biktarvy was among the top 5 regiments for switch patients.

Biktarvy 在德國和法國的強勁反響令我們倍感鼓舞。在德國，Biktarvy 在第四季是初治患者和轉診患者處方量排名第一的治療方案。在法國，Biktarvy上市僅6週後就躋身於轉診患者最常用的5種療法之列。

We anticipate by mid-year, Biktarvy will also launch in Spain, Italy and the U.K. Once Biktarvy is broadly reimbursed and entrenched in the market, we believe our European HIV business will stabilize and return to growth.

我們預計到年中，Biktarvy 也將在西班牙、義大利和英國上市。一旦 Biktarvy 獲得廣泛報銷並在市場上站穩腳跟，我們相信我們的歐洲 HIV 業務將會穩定下來並恢復成長。

Now turning to HCV. Product sales for the fourth quarter were $738 million, down 51% year-over-year and 18% quarter-over-quarter, in line with the guidance we provided in 2018. As previously announced, our authorized generic version of Epclusa and Harvoni have become available in the U.S. this quarter through Asegua Therapeutics LLC, a separate subsidiary. We expect to see a positive impact on sharing Medicaid markets during the second half of 2019. Over the long term, we anticipate the adoption of these authorized generics will allow us to be more competitive in a rapidly growing Medicaid segment.

現在來說說丙型肝炎。第四季產品銷售額為 7.38 億美元，年減 51%，季減 18%，與我們 2018 年提供的預期一致。正如先前宣布的那樣，我們授權的 Epclusa 和 Harvoni 仿製藥版本已於本季度透過我們的獨立子公司 Asegua Therapeutics LLC 在美國上市。我們預計在 2019 年下半年，醫療補助市場共享將受到正面影響。從長遠來看，我們預計這些授權仿製藥的採用將使我們在快速成長的醫療補助領域更具競爭力。

In 2018, we launched a new direct-to-consumer campaign highlighting Epclusa as a pan-genotypic, pan-fibrotic, single-tablet regimen. Epclusa has the right profile to address the broadest population in HCV. As a leading liver company, we remain fully committed to serving patients with HCV, contributing to the elimination of this disease and competing with a great deal of confidence based on the profiles of our HCV products.

2018 年，我們發起了一項新的直接面向消費者的活動，重點介紹 Epclusa 是一種泛基因型、泛纖維化單片療法。Epclusa 具有適合最廣泛 HCV 患者族群的特性。作為一家領先的肝臟疾病治療公司，我們始終致力於服務丙型肝炎患者，為消除這種疾病做出貢獻，並憑藉我們丙型肝炎產品的卓越性能，充滿信心地參與競爭。

Turning to Yescarta. We are building on the momentum generated by the 2-year real-world data prevented at the American Society of Hematology annual meeting. This year, we expect to steadily and measurably progress in the U.S. and in Europe and potentially see a doubling of our revenue for Yescarta as centers gain experience and community oncologists become increasingly aware of this lifesaving therapy. We now have 68 centers in the U.S. certified to provide treatment with Yescarta. In Europe, we are encouraged by the early stages of our launch. We have treated commercial patients in the U.K. and in Germany, and we have activated sites in France. In total, we have authorized 12 centers and look forward to additional centers coming online this quarter. We are pleased with the engagement of countries across EU markets wanting to rapidly offer Yescarta.

轉向 Yescarta。我們正在利用美國血液學會年會上公佈的兩年真實世界數據所產生的勢頭繼續前進。今年，我們預計在美國和歐洲將穩步取得顯著進展，隨著各中心積累經驗，社區腫瘤學家對這種救命療法的認識不斷提高，Yescarta 的收入可能會翻倍。目前，我們在美國有 68 個中心獲得認證，可以提供 Yescarta 治療。在歐洲，我們對產品上市初期的進展感到鼓舞。我們已在英國和德國為商業患者提供治療，並在法國啟動了治療點。我們目前已批准設立 12 個中心，並期待本季有更多中心上線。我們很高興看到歐盟各國積極參與，希望盡快提供 Yescarta 服務。

Finally, our U.S. cardiopulmonary team continues to deliver impressive results. Letairis and Ranexa revenue totaled $431 million for the quarter. We did not see any generic competition for Letairis in the fourth quarter. We currently anticipate the entry of generics in the second quarter of 2009 (sic) [2019].

最後，我們的美國心肺團隊持續取得令人矚目的成果。Letairis 和 Ranexa 本季總營收為 4.31 億美元。第四季我們沒有看到 Letairis 出現任何仿製藥競爭對手。我們目前預計仿製藥將於 2009 年第二季（原文如此）[2019 年]進入市場。

We begin the year from a position of strength. I would like to thank the teams around the world for their incredible efforts. With a continued focus on our outstanding portfolio of products and operational excellence, we are confident in our ability to deliver on our 2019 goals.

我們以強大的實力開啟了新的一年。我要感謝世界各地的團隊所付出的巨大努力。我們將繼續專注於我們卓越的產品組合和卓越的運營，我們有信心實現2019年的目標。

Now I will turn the call over to John.

現在我將把電話交給約翰。

Thank you, Laura, and thank you, everyone, for joining us today. As you know, this is a very exciting time for Gilead's R&D organization. We anticipate readouts from 5 Phase III clinical trials in the first half of this year. I will talk briefly about those studies, provide an update on our cell therapy and oncology programs and then close with some thoughts on 2019.

謝謝勞拉，也謝謝各位今天光臨。如您所知，對於吉利德的研發部門來說，這是一個非常令人興奮的時刻。我們預計將在今年上半年公佈 5 項 III 期臨床試驗的結果。我將簡要介紹這些研究，報告我們的細胞療法和腫瘤學計畫的最新進展，最後對 2019 年發表一些看法。

We expect upcoming readouts of STELLAR 3 and STELLAR 4, our ongoing Phase III trials evaluating selonsertib an ASK1 inhibitor in patients with advanced fibrosis due to NASH. If supported by the data, we expect to file for regulatory approvals in the second half of this year.

我們期待即將公佈的 STELLAR 3 和 STELLAR 4 的結果，這是我們正在進行的 III 期試驗，旨在評估 ASK1 抑制劑 selonsertib 對 NASH 引起的晚期纖維化患者的療效。如果數據支持，我們預計今年下半年提交監管部門的批准申請。

In addition, we continue to advance multiple other investigational compounds in NASH as both single agents and as combination therapies. We anticipate ATLAS, our Phase IIb study of various 2-drug combinations or regimens in patients with NASH and advanced fibrosis, to read out in the fourth quarter.

此外，我們也持續推動其他多種用於 NASH 的研究性化合物，包括單藥治療和聯合治療。我們預計針對 NASH 和晚期纖維化患者進行的 IIb 期研究 ATLAS（針對各種 2 藥組合或方案）將於第四季度公佈結​​果。

As we continue to build our pipeline in NASH, I would like to highlight 2 other recent preclinical agreements. Last month, we announced a collaboration and license agreement with Yuhan to codevelop novel treatments for patients with advanced fibrosis due to NASH that will complement our other internal programs. In December, we also entered into another collaboration with Scholar Rock to discover and develop highly specific inhibitors of TGF-beta activation. We will work with Scholar Rock to investigate this novel approach directed towards one of the core pathways driving fibrotic diseases, including NASH and diabetic kidney disease.

隨著我們不斷拓展 NASH 領域的研發管線，我想重點介紹另外兩項近期達成的臨床前協議。上個月，我們宣布與 Yuhan 達成合作與許可協議，共同開發針對 NASH 引起的晚期纖維化患者的新型療法，這將補充我們其他的內部項目。12 月，我們還與 Scholar Rock 進行了另一項合作，旨在發現和開發 TGF-β 活化的高特異性抑制劑。我們將與 Scholar Rock 合作，研究這種針對驅動纖維化疾病（包括 NASH 和糖尿病腎病變）的核心路徑之一的新方法。

Now turning to inflammation. This quarter, we expect results from FINCH 1 and FINCH 3, 2 Phase III studies of our selective JAK1 inhibitor filgotinib in rheumatoid arthritis. As you may recall, last year, we announced positive results from FINCH 2, the first of our Phase III studies to read out. Those results demonstrated that filgotinib met all primary and secondary efficacy endpoints in a difficult-to-treat group of patients. Now if supported by the data, we expect to be able to then progress the filgotinib rheumatoid arthritis indication filings for regulatory approvals globally. In the U.S., our ability to file the NDA is dependent on data from the MANTA study, a safety study in men with ulcerative colitis. This was requested by the FDA and is designed to address nonclinical findings observed in preclinical animal studies. The FDA recently allowed us to expand the inclusion criteria, which has enabled us to enhance enrollment. We will continue to evaluate our progress and options to advance time lines. Once we have the Phase III data from 3 FINCH studies in hand, we will initiate and request further interactions with the FDA and other regulatory groups worldwide. We will then be able to provide greater clarity as to filing timeline in the U.S.

現在來說說炎症。本季度，我們將公佈 FINCH 1 和 FINCH 3、2 兩項 III 期研究的結果，這兩項研究旨在評估我們選擇性 JAK1 抑制劑 filgotinib 在類風濕性關節炎中的療效。您可能還記得，去年我們公佈了 FINCH 2 的正面結果，這是我們第一個公佈結果的 III 期研究。這些結果表明，filgotinib 在難治性患者群體中達到了所有主要和次要療效終點。如果數據支持，我們預計能夠推進 filgotinib 治療類風濕性關節炎的適應症申請，以獲得全球監管部門的批准。在美國，我們能否提交新藥申請取決於 MANTA 研究的數據，這是一項針對潰瘍性結腸炎男性患者的安全研究。這是 FDA 提出的要求，旨在解決臨床前動物研究中觀察到的非臨床發現。FDA 最近允許我們擴大納入標準，這使我們能夠增加招募人數。我們將繼續評估進展和推進時間表的各種方案。一旦我們掌握了 3 項 FINCH 研究的 III 期數據，我們將啟動並要求與 FDA 和世界各地的其他監管機構進行進一步的互動。屆時我們將能夠更清楚地說明在美國提交申請的時間表。

Moving to HIV. In the coming months, we anticipate the results from the DISCOVER trial, a Phase III randomized, double-blind study of more than 5,000 people, evaluating whether Descovy is as safe and as effective as Truvada at reducing the risk of HIV infection when used as PrEP or pre-exposure prophylaxis. The trial speaks to our ongoing commitment to people at risk of HIV infection and those living with HIV, where our goal is to continue to lead and drive innovation across the spectrum of care from prevention to treatment to, hopefully, one day, a cure.

轉向愛滋病毒。在接下來的幾個月裡，我們期待 DISCOVER 試驗的結果。這是一項 III 期隨機雙盲研究，納入了 5000 多人，旨在評估 Descovy 作為 PrEP 或暴露前預防藥物使用時，在降低 HIV 感染風險方面是否與 Truvada 一樣安全有效。這項試驗體現了我們對面臨 HIV 感染風險的人群和 HIV 感染者的持續承諾，我們的目標是繼續引領和推動從預防到治療，甚至最終治愈整個護理領域的創新。

And finally, I'd like to make a few comments on cell therapy. Our investment in cell therapy is and always has been an investment in the future. Similar to what we've done in other areas historically, we are committed to leading with cutting-edge science that one day creates a path to a cure. Last December, the American Society of Hematology annual meeting, we presented a number of significant updates. The 2-year safety and efficacy ZUMA-1 data presented at the meeting and simultaneously published in Lancet Oncology showed an unprecedented plateau in duration of response and overall survival in patients with refractory large B-cell lymphoma. After a single infusion of Yescarta with a minimum follow-up of 2 years, more than half of the patients were still alive, and nearly 40% of patients had an ongoing response. The 2-year point is a major milestone for Yescarta. This is the longest duration of follow-up of any registrational, clinical cell therapy study, and the results set the bar, reinforcing our leadership in cell therapy.

最後，我想就細胞療法談幾點看法。我們對細胞療法的投資過去是、現在仍是對未來的投資。就像我們過去在其他領域所做的一樣，我們致力於引領尖端科學，希望有朝一日能找到治癒方法。去年 12 月，在美國血液學會年會上，我們提出了一些重要的最新進展。在會議上公佈並同時發表在《柳葉刀腫瘤學》上的 ZUMA-1 2 年安全性和有效性數據顯示，在難治性大 B 細胞淋巴瘤患者中，緩解持續時間和總生存期達到了前所未有的平台期。在接受單次 Yescarta 輸注治療後，經過至少 2 年的隨訪，超過一半的患者仍然存活，近 40% 的患者仍有持續療效。兩週年是 Yescarta 的一個重要里程碑。這是迄今為止所有註冊臨床細胞治療研究中追蹤時間最長的，研究結果樹立了標桿，鞏固了我們在細胞治療領域的領先地位。

Also at the ASH meeting, there were numerous presentations highlighting real-world Yescarta data from centers outside of the clinical trial setting. It was encouraging to see similar 30-day efficacy and safety data in this setting, despite sicker patients compared with ZUMA-1 as well as a consistent manufacturing performance and product turnaround time.

在 ASH 會議上，還有許多報告重點介紹了來自臨床試驗環境之外的中心的 Yescarta 真實世界數據。儘管與 ZUMA-1 相比，患者病情更重，但在此情況下，30 天的療效和安全性數據仍然令人鼓舞，而且生產性能和產品週轉時間也保持一致。

Finally, for Yescarta, we are moving forward in earlier lines of therapy in large B-cell lymphoma and several new indications for other B-cell malignancies as part of our broader registrational plan. This year, we will also continue several studies aimed at investigating strategies to further improve the safety and the efficacy of Yescarta.

最後，對於 Yescarta，作為我們更廣泛的註冊計劃的一部分，我們正在推進其在大 B 細胞淋巴瘤早期治療以及其他 B 細胞惡性腫瘤的幾個新適應症方面的應用。今年，我們也將繼續進行幾項研究，旨在探索進一步提高 Yescarta 安全性和有效性的策略。

More broadly now in cell therapy, we are advancing an allogeneic platform to IND this year, progressing different cell therapy approaches in multiple solid tumors with next-generation technologies and leveraging our best-in-class cell therapy manufacturing. We will also continue to pursue scientific collaborations that will help us achieve these goals when they make sense.

現在，在細胞治療領域，我們正在推進同種異體平台在今年提交IND申請，利用下一代技術推進多種實體瘤的不同細胞治療方法，並充分利用我們一流的細胞治療生產能力。我們將繼續尋求科學合作，以幫助我們實現這些目標（如果這些合作是合理的）。

With regard to our other oncology programs. During the fourth quarter, we announced a global collaboration with Tango Therapeutics to discover, develop and commercialize a pipeline of innovative, targeted immuno-oncology treatments to patients with cancer. Our collaboration will combine Tango's CRISPR-based discovery technology, alongside Gilead's drug discovery and development capabilities. We also recently entered into a partnership with Agenus focused on the development and commercialization of up to 5 novel immuno-oncology therapies, 3 of which are expected to be in the clinic in 2019. We believe these double approaches can augment the impressive benefits that have been seen with checkpoint inhibition in a variety of cancers. Last quarter, we disclosed an initial patent outlining some of our exciting preclinical work related to our small molecule PD-L1 program. To that end, we have now initiated a Phase I study of GS-4224 in healthy volunteers.

關於我們的其他腫瘤治療項目。第四季度，我們宣布與 Tango Therapeutics 進行全球合作，共同發現、開發和商業化一系列創新的標靶免疫腫瘤療法，以造福癌症患者。我們的合作將結合 Tango 基於 CRISPR 的發現技術與 Gilead 的藥物發現和開發能力。我們最近也與 Agenus 建立了合作關係，專注於開發和商業化多達 5 種新型免疫腫瘤療法，其中 3 種預計將於 2019 年進入臨床試驗階段。我們相信，這些雙重方法可以增強檢查點抑制劑在多種癌症中取得的顯著療效。上個季度，我們公開了一項初步專利，概述了我們與小分子 PD-L1 項目相關的一些令人興奮的臨床前工作。為此，我們現在已經啟動了 GS-4224 在健康志願者中的 I 期研究。

I am confident we will continue to make significant progress in 2019. I want to close by highlighting several key areas for Gilead this year. We are focused on returning to growth in terms of product sales and are confident this can be achieved with our operational excellence, a strong and growing HIV franchise and a stabilizing hepatitis C market. As I have just shared on the R&D side, we continue to make excellent progress with our pipeline, and we are looking forward to the readout of the 5 Phase III studies, as I described today.

我相信我們在2019年將繼續取得重大進展。最後，我想重點介紹吉利德今年的幾個關鍵領域。我們專注於恢復產品銷售成長，並相信憑藉我們卓越的營運、強大且不斷增長的 HIV 產品線以及趨於穩定的丙型肝炎市場，我們可以實現這一目標。正如我剛才在研發方面分享的那樣，我們的研發管線繼續取得優異的進展，我們期待著今天我所描述的 5 項 III 期研究的結果公佈。

With regard to cell therapy, we will maintain our position of leadership as we continue to reach more patients with Yescarta and advance the next generations of cell therapy.

在細胞療法方面，我們將繼續保持領先地位，透過 Yescarta 為更多患者提供服務，並推動下一代細胞療法的發展。

And finally, we are in a position of financial strength, which gives us the flexibility to execute on M&A and partnerships to augment our pipeline.

最後，我們擁有雄厚的財務實力，這使我們能夠靈活地進行併購和合作，以擴充我們的業務線。

On behalf of the entire organization, we look forward to welcoming Dan O'Day to Gilead next month as our new Chairman and CEO.

我們代表整個公司，期待下個月歡迎 Dan O'Day 加入吉利德，擔任新的董事長兼執行長。

In closing, I would like to thank our 11,000 employees around the world. It's your commitment and dedication that have made us successful and will continue to make us successful in 2019 and into the future.

最後，我要感謝我們遍佈全球的11,000名員工。正是你們的投入和奉獻使我們取得了成功，也必將使我們在 2019 年及未來繼續取得成功。

So let's now open the call for questions. Operator?

現在開始接受提問。操作員？

(Operator Instructions) And our first question comes from the line of Geoff Meacham from Barclays.

（操作員說明）我們的第一個問題來自巴克萊銀行的傑夫·米查姆。

John, I want to continue the thought on BD. I'm looking at the step-up in 2018 that you guys had. It's mostly on early to mid-stage assets. So the question is, one, does this change Gilead's appetite for later-stage deals? And two, what's the appetite for an expansion beyond your core therapeutic areas? And I realize the answer is likely to change after Dan gives a more detailed review of the business.

約翰，我想繼續討論BD。我正在關注你們在 2018 年的進步。主要集中在早期到中期階段的資產。所以問題是，第一，這是否會改變吉利德對後期交易的興趣？第二，貴公司是否有意願將業務拓展到核心治療領域之外？我知道，在丹對公司進行更詳細的審查之後，答案很可能會改變。

Geoff, it's Robin. Why don't I start? I'd say, again, the high bar and criteria for us when it comes to M&A is scientific differentiation. I think you're right to state that we are primarily focused on our existing therapeutic areas. While these have been small deals, I think we've continued to look for deals with commercial assets as well as later-stage pipeline deals as well, but they happen when they happen. So as you can see, we've been very active. We've been even more active the second half of the year, and we'll continue to focus in this area as Dan joins us.

傑夫，我是羅賓。我為什麼不開始呢？我想再次強調，我們在併購方面設定的高標準和準則是科學差異化。我認為您說得對，我們主要專注於現有的治療領域。雖然這些都是小額交易，但我認為我們一直在尋找擁有商業資產的交易以及後期管道交易，但這些交易何時發生就什麼時候發生。如你所見，我們一直非常活躍。今年下半年我們更加活躍，隨著丹的加入，我們將繼續專注於此領域。

Geoff, it's John, and I'll just add on to what Robin has said also. We have looked at many other things as well over the last year, and we'll continue to do so. And it is driven by the science, and it is driven by the opportunity and the importance and impact it will have on certain diseases. So we will look at late- and earlier-stage opportunities as they come forward. But as Robin said, the late-stage opportunities are few and far between.

傑夫，我是約翰，我再補充一下羅賓剛才說的話。在過去一年裡，我們也研究了許多其他方面，並將繼續這樣做。這是由科學驅動的，也是由機會、重要性以及它將對某些疾病產生的影響所驅動的。因此，我們會密切關注後期和早期階段出現的各種機會。但正如羅賓所說，後期機會寥寥無幾。

Our next question comes from the line of Michael Yee from Jefferies.

我們的下一個問題來自傑富瑞集團的邁克爾葉。

I guess my question is -- although Dan hasn't come onboard yet, I mean, what do you think investors should anticipate or should expect through the course of the year? Is that him just trying to get onboard familiar with everything and that could take a year? Do you think that he would -- or management and the board anticipate urgency to put the balance sheet to work? I mean, I guess, what should investors expect through 2019 as it relates to Dan coming onboard?

我想問的是──雖然丹還沒有加入公司，我的意思是，您認為投資人應該對今年的情況抱持什麼樣的預期？他是不是只是想盡快熟悉所有事情，這可能需要一年？你認為他會這樣做嗎？或者說，管理階層和董事會預計會很緊急地利用資產負債表來解決問題？我的意思是，我想，隨著丹的加入，投資人在 2019 年應該抱持什麼樣的預期？

Sure. This is Gregg Alton. I'll take this question. I think it's neither of the scenarios that you laid out there. I think that Dan will come onboard March 1, as you know. I think he will be patient. He's going to take his time to get to know the company, spend more time with the management team. Get to know our strategy. Certainly, he will then -- I think he'll put his own mark on where he wants to take the company. I wouldn't expect it to take up a year, but I think he will be patient, and I think he's going to be thoughtful and make sure that he's really understanding what we're doing.

當然。這是格雷格·奧爾頓。我來回答這個問題。我認為都不是你們列出的這兩種情況。如你所知，我認為丹將於3月1日加入團隊。我認為他會很有耐心。他會花時間了解公司，多花時間與管理團隊交流。了解我們的策略。當然，我認為他會——他會按照自己的想法來決定公司未來的發展方向。我並不認為這會耗費一年時間，但我認為他會很有耐心，而且我認為他會深思熟慮，確保他真正理解我們正在做的事情。

Our next question comes from the line of Brian Abrahams from 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。

How should we be thinking about your 2019 guidance for HIV with respect to contribution from volume versus price? And then along those lines, for the longer term, there's been some discussion around CMS practices shifting for protected classes. Can you talk a little bit about the impact that you foresee, elements like formulary management or prior authorization potentially having on clinical practice and HIV and on potential future revenues for the franchise?

我們該如何看待您在 2019 年針對 HIV 的指導方針中關於銷售與價格貢獻的部分？此外，從長遠來看，也有人討論過 CMS 對受保護群體的做法是否需要轉變。您能否談談您預見的因素，例如處方集管理或事先授權等，可能對臨床實踐、愛滋病以及特許經營的未來潛在收入產生的影響？

Brian, it's Robin. Maybe I'll take the first part of your question and then turn it over to Gregg. So thank you for calling out both those parameters. I mean, keep in mind that volume is the major driver growth for our business, and that will be the case in 2019. For our HIV business, we have taken price increases in the U.S. in the past, but keep in mind that the net effect of them has been limited because the majority of our volume goes through public channels. For instance, ADAP has not had a price increase in -- since 2008, and that's part of our U.S. business. In Europe, as you know, we actually take price decreases. So the net result on a worldwide basis is really a low single-digit price benefit when we think about any price increases. For this year, you can appreciate. Due to competitive reasons, we're not going to mention if we are or aren't taking price increases at this point in time. Recall that mid-year, we announced no price increases for 6 months. But any thinking that we do have around price increases is currently reflected in our guidance, and I'd say that we are aware and continue to be aware of the climate out there, and we've always had a very sensible approach to how we think about pricing.

布萊恩，我是羅賓。或許我會先回答你問題的第一部分，然後再交給格雷格。感謝您指出這兩個參數。我的意思是，請記住，銷售量是我們業務成長的主要驅動力，2019 年也將如此。對於我們的 HIV 業務，我們過去曾在美國提價，但請記住，由於我們的大部分銷售都是透過公共管道銷售的，因此漲價的淨影響是有限的。例如，ADAP 自 2008 年以來就沒有漲價，這是我們美國業務的一部分。如您所知，在歐洲，我們實際上是會降價的。因此，從全球範圍來看，考慮到任何價格上漲，最終結果實際上是個位數的價格優勢。今年，你可以好好珍惜。基於競爭原因，我們目前不會透露是否會漲價。請記住，年中我們曾宣布6個月內不漲價。但我們目前對價格上漲的任何想法都已反映在我們的指導方針中，而且我認為我們了解並將繼續了解當前的市場環境，我們一直以非常理智的方式考慮定價問題。

And so if I can just jump in on the second part of the question relating to the proposal by CMS on the protected classes. As you're all aware, Gilead has been on the forefront of innovation in HIV for 30 years now, bringing out products for treatment and prevention that improve potency, safety, tolerability, simplicity. And the protected classes has been a very important component to ensure that patients have access to that and physicians are free to prescribe what's best for their patients. And the reason for the protected classes, as many of you know, is these are disease areas -- there's 6 disease areas where the products really are not interchangeable, and they really need to be the right -- right for the patients. This has allowed patients -- individuals to do very well with HIV but also allows us to have a very good public health response to HIV and reducing new infections. We believe that any challenges to the protected class, particularly the prior authorization or step therapy, would be a significant step backwards in these efforts. We also share this with a lot of the other therapeutic areas that are impacted by the protected classes, so we are in constant discussions with them. This is the #1 public policy initiated by Gilead, is ensuring that people understand the importance of protected classes. We're very engaged with the administration at CMS, HHS as well as the Senate and Congress. So we are ensuring that we're very vocal there. We're also very closely tied with the patient groups and the physician groups who care very much about this issue. So this isn't the first time this has come up, but we take this very seriously. And we are making sure that the message is very strong that this would be a step backwards, and we also don't see significant cost savings to our health system from doing this and potentially a long-term step back in terms of what we've accomplished.

那麼，如果我可以插一句關於CMS關於受保護類別的提案的第二部分問題的話。眾所周知，吉利德公司 30 年來一直處於 HIV 創新領域的前沿，不斷推出治療和預防產品，以提高療效、安全性、耐受性和簡便性。受保護群體一直是確保患者能夠獲得這些服務，以及醫生能夠自由地為患者開出最佳處方的重要組成部分。正如你們許多人所知，受保護類別的原因是這些是疾病領域——有 6 個疾病領域的產品確實不能互換，它們確實需要是正確的——對患者來說是正確的。這不僅使愛滋病患者能夠很好地康復，也使我們能夠對愛滋病做出非常有效的公共衛生應對，並減少新的感染病例。我們認為，任何對受保護群體的挑戰，特別是對事先授權或階梯療法的挑戰，都將是這些努力的重大倒退。我們也與其他許多受保護類別影響的治療領域分享了這一訊息，因此我們與他們保持持續的討論。這是吉利德公司推行的首要公共政策，即確保人們了解受保護群體的重要性。我們與美國醫療保險和醫療補助服務中心 (CMS)、美國衛生與公眾服務部 (HHS) 以及參議院和眾議院的行政部門保持密切聯繫。所以我們確保在那裡發出我們非常積極的聲音。我們也與非常關心這個問題的患者團體和醫生團體保持著非常密切的聯繫。這並非第一次出現這種情況，但我們非常重視此事。我們正在確保傳達的訊息非常明確：這將是一個倒退，而且我們認為這樣做不會為我們的醫療系統節省大量成本，並且從長遠來看，這可能會使我們所取得的成就倒退。

Our next question comes from the line of Geoffrey Porges from Leerink.

我們的下一個問題來自 Leerink 的 Geoffrey Porges。

Robin, could you talk us through the increase in SG&A, specifically? It's about a 10% increase compared to where you are this year. It's about $500 million above what The Street was expecting. Can you talk it through where the incremental $500 million is going? And was it at all possible -- I presume you went through everything else you were spending on previously and couldn't find any way to reduce in other areas?

羅賓，你能具體解釋一下銷售、一般及行政費用（SG&A）的成長情況嗎？與今年相比，大約成長了10%。這比華爾街的預期高出約5億美元。能詳細說明一下新增的5億美元將用於哪些方面嗎？而且，這是否完全有可能？我猜你已經仔細審查了之前所有的開支，但找不到其他方面可以削減開支的方法了？

Yes, thanks for the question, Geoff. Let me first talk about the sequential increase. That was driven by a onetime grant, so I wouldn't take Q4 and assume that's the run rate, right? I mean, during the second half of the year, to your specific question, we have included incremental expenses focused on our new emerging therapeutic area launches, in particular NASH and inflammation. We've also included some incremental expense for our cell therapy ramp. As you know, we're continuing to build outside of the U.S. in that area as well. So those are some of the primary drivers. The kind of the smaller drivers include just some geographic expansion. If you saw from our guidance, we're expected to have HIV revenue in Japan next year, so there's some investment that we're [waking] there. We also continue to get products approved in China, so that's an area of focus. So yes, there is a second half ramp in our expenses to support those very new launches. I would say, Geoff, to your point have we thought about trade-offs, yes, we have. I would say, particularly for NASH, we have -- and maybe Laura can comment on this as well. We do believe continuing to stay focused on our hep C franchise in a much more competitive environment is the way to go so there are some incremental expenses that we hadn't initially thought about associated with NASH, but we've appropriately included them in our guidance.

是的，謝謝你的提問，傑夫。首先讓我談談順序成長。這是由一次性撥款推動的，所以我不會把第四季度的數據當作正常水平，對吧？我的意思是，針對您提出的具體問題，在下半年，我們增加了專注於新興治療領域（特別是 NASH 和發炎）的增量支出。我們也計入了一些用於細胞療法推廣的額外費用。如您所知，我們也在繼續在美國以外的地區進行該地區的建設。以上是一些主要驅動因素。規模較小的驅動因素僅包括一些地域擴張。從我們的指導方針可以看出，我們預計明年在日本將獲得 HIV 相關收入，所以我們正在那裡進行一些投資。我們的產品也持續獲得中國市場的批准，所以這也是我們關注的重點領域。是的，為了支持這些全新產品的推出，我們的下半年支出將會增加。傑夫，關於你提出的問題，我們是否考慮過權衡取捨？是的，我們考慮過。我想說，特別是對於 NASH 而言，我們有——也許勞拉也可以就此發表一些看法。我們相信，在競爭日益激烈的環境中，繼續專注於我們的C型肝炎業務才是正確的方向。因此，與 NASH 相關的一些額外支出是我們最初沒有考慮到的，但我們已將其適當地納入了我們的預期中。

Yes, I think Robin did a perfect job covering it. For HCV, we believe not only from a field force prospective that we want to be fully focused around the world but also in terms of reaching consumers in the United States -- that's a very strong focus. And external and outside of the United States, there is a number of initiatives to really help with elimination in conjunction with the government, and we're committed to that. So I think that's really what we were contemplating with selonsertib would we have an opportunity to join forces. We believe that we should keep those separate and continue to focus on them as individual, very important products uniquely.

是的，我認為羅賓報道得非常完美。對於C型肝炎，我們不僅從現場服務團隊的角度來看，希望在全球範圍內全力投入，而且在接觸美國消費者方面——這也是我們非常重視的重點。在美國以外，有許多措施旨在與政府合作，真正幫助消除毒品，我們也致力於此。所以我覺得，這正是我們和 selonsertib 一直在考慮的問題，我們是否有機會攜手合作。我們認為應該將它們分開，並繼續將它們作為獨立的、非常重要的產品進行重點發展。

Our next question comes from the line of Matthew Harrison from Morgan Stanley.

我們的下一個問題來自摩根士丹利的馬修·哈里森。

John, I have one for you, specifically on the NASH study. Can you talk a little bit about how you powered those studies? I know you've talked in the past about the 20% delta is clinically meaningful. I wonder if you can comment if you achieved the delta below that, if those studies could still be statistically successful and how you might look at a result like that.

約翰，我有一個問題想問你，是關於 NASH 研究的。您能談談您是如何進行這些研究的嗎？我知道你之前說過 20% 的變化在臨床上是有意義的。我想知道，如果您達到了低於該值的增量，這些研究是否仍然具有統計意義，以及您將如何看待這樣的結果。

Thank you, Matthew. We're excited about the NASH readouts from STELLAR 3 and STELLAR 4. We have 1,600 patients with bridging fibrosis or cirrhosis. So those results are due to imminently read out this quarter, so we are looking forward to them. To answer your question, we are looking for a significant increase over placebo response rate, which we believe we can calculate accurately from our previous trials. And we believe that we would like to show a 10% to 15% increase or a doubling of response rates over placebo to have a meaningful effect in a group of people that have a high likelihood of disease progressing to transplant, et cetera. So without getting into all the details about the numbers, this would be our first step forward for patients with advanced fibrosis due to NASH and a meaningful improvement if we could allow 1 in 5 of them to prevent progression of the disease to transplant decompensation, et cetera. We believe that would be meaningful clinically, statistically and otherwise.

謝謝你，馬修。我們對 STELLAR 3 和 STELLAR 4 的 NASH 檢測結果感到興奮。我們有 1600 名患有橋接纖維化或肝硬化的患者。因此，這些結果預計將在本季很快公佈，我們非常期待。為了回答您的問題，我們正在尋找比安慰劑反應率顯著提高的指標，我們相信可以根據我們先前的試驗準確計算出這一指標。我們相信，如果能比安慰劑提高 10% 到 15% 的反應率，或使反應率翻倍，就能對那些很可能發展到需要移植等疾病的人產生有意義的影響。因此，在不深入探討所有數字細節的情況下，這將是我們為患有 NASH 晚期纖維化的患者邁出的第一步，如果我們能夠讓其中 5 人中的 1 人阻止疾病發展到移植失代償等情況，這將是一個有意義的進步。我們認為這在臨床、統計學和其他方面都具有重要意義。

Our next question comes from the line of Robyn Karnauskas from Citi.

我們的下一個問題來自花旗銀行的 Robyn Karnauskas。

My question is on PrEP. So you talked about over 200,000 on PrEP. And by our math, that could be around $2 billion worth of sales coming from PrEP. I don't know if that's right. But my question is more about -- there's data out there saying that this could be a 1 million to 2 million, 3 million people that ideally could benefit from PrEP. How are you thinking about getting that -- getting Descovy in the hands of those people? What is the argument you would make to make sure those patients go on PrEP? And do you think -- my question is more about a lot of these patients are young. So how are you going to make that argument? And where do you think PrEP could go? And what kind of benefits from DTC? Very long question. I'm sorry.

我的問題是關於暴露前預防（PrEP）的。所以你提到了超過 20 萬人正在服用 PrEP。據我們計算，PrEP 的銷售額可能達到 20 億美元左右。我不知道這樣是否正確。但我的問題更多的是關於——有數據顯示，可能有 100 萬到 200 萬，甚至 300 萬人可以從 PrEP 中受益。你打算如何實現——如何讓這些人使用 Descovy？您會提出什麼理由來確保這些患者接受PrEP治療？你認為——我的問題更多的是關於這些患者中有很多都很年輕。那你打算如何提出這個論點呢？你認為PrEP的發展方向是什麼？DTC模式能帶來哪些好處？問題很長。對不起。

Yes. So how about if I take the conversion question, and on the clinical study, I'm going to leave that up to John. So this is Laura. Thank you, Robyn, for the question. So as it relates to PrEP, as I mentioned earlier, in the United States has 1.1 million people that the CDC estimates that could benefit from PrEP. And we really believe there's a lot more to do. There's a lot of populations that are affected that just don't have the awareness that they really need to protect themselves. So not only do we have a dedicated field force, but we have a lot of community individuals that have come from nonprofits that are very much committed to helping these communities, and we are leaning into these communities to try to raise awareness. In addition, we've actually put a significant amount of additional funding behind both Biktarvy and Truvada for PrEP in 2019 because we believe that's very important thing to do. Now to answer your question about the conversion from a TDF-based regimen to a TAP-based regimen or Descovy-based regimen. Obviously, the clinical trial results, I'll let John talk to. But what I would say is when we look at the treatment market, as I mentioned, in the U.S., we're at 77% of prescription -- total prescriptions now in Descovy-based backbone. And in Europe, we're at 80%. Now we believe that the benefits that accrue to a patient for HIV are the same benefits that we need to have for a patient at risk that is being treated for PrEP. Some of the duration of therapy is longer than we would -- you may anticipate. So these otherwise healthy individuals want to have a normal, healthy life, and the Descovy-based regimen really blends for that to be a great treatment option. I'll then turn it over to John on this study.

是的。那麼，關於轉換率的問題，我來說說臨床研究，至於這部分，我打算交給約翰來處理。這位是勞拉。謝謝Robyn的提問。所以，就 PrEP 而言，正如我之前提到的，根據 CDC 估計，美國有 110 萬人可以從 PrEP 中受益。我們堅信還有很多工作要做。很多受影響的人群缺乏保護自己所需的意識。因此，我們不僅有一支專門的現場隊伍，還有很多來自非營利組織的社區人士，他們非常致力於幫助這些社區，我們正在深入這些社區，努力提高人們的意識。此外，我們實際上在 2019 年為 Biktarvy 和 Truvada 這兩種 PrEP 產品投入了大量額外資金，因為我們認為這樣做非常重要。現在來回答您關於從基於 TDF 的治療方案轉換為基於 TAP 的治療方案或基於 Descovy 的治療方案的問題。臨床試驗結果方面，我當然會讓約翰來談。但我想說的是，當我們審視治療市場時，正如我所提到的，在美國，目前 77% 的處方藥——總處方藥——都是以 Descovy 為基礎。在歐洲，我們已經達到 80%了。現在我們認為，愛滋病患者所獲得的益處，與接受 PrEP 治療的高風險患者所需要獲得的益處是一樣的。部分治療療程的持續時間可能比您預期的要長。因此，這些原本健康的人想要過正常、健康的生活，而以 Descovy 為基礎的治療方案恰好滿足了這一需求，因此是一個很好的治療選擇。接下來我會把這項研究交給約翰。

So Robyn, the safety advantages of taking a [TAF-based] backbone as has been the case and seen in the conversion rates for the HIV-infected individual will apply equally to the at-risk individual who's taking medication for PrEP. So we'll be able to show in the study with over 5,000 patients that there are differences, I presume, in terms of safety, kidney and bone. And because of their young age and their longevity in terms of taking medicines to prevent HIV infection, the same principles apply as it does to somebody who is infected already. So another way of saying what Laura has already said. And hopefully, the study will lead us down the answers to that question. We -- it's reading out in the coming months.

所以 Robyn，對於 HIV 感染者而言，服用 [TAF 基] 骨架藥物的安全優勢（正如之前所觀察到的，並且在轉化率方面也得到了證實）同樣適用於服用 PrEP 藥物的高危險群。因此，我們將能夠在對超過 5000 名患者的研究中證明，在安全性、腎臟和骨骼方面存在差異，我推測。由於他們年紀小，而且服用預防 HIV 感染藥物的時間長，因此，同樣的原則也適用於已經感染 HIV 的人。換句話說，就是勞拉之前說的那句話的意思。希望這項研究能幫助我們找到這個問題的答案。我們——它將在未來幾個月內公佈。

Our next question comes from the line of Alethia Young from Cantor Fitzgerald.

我們的下一個問題來自坎托·菲茨杰拉德的阿萊西亞·楊的詩句。

I'm just asking about the MANTA study. I just wanted to clarify maybe one thing. Is that study needed for like a label? Or is it really needed actually for the filing package? And then just can you update us with a little bit more precision on how those initiatives have played out with the enrollment timelines?

我只是想問關於 MANTA 研究的事。我只是想澄清一件事。這項研究是給唱片公司貼標籤之類的嗎？或者說，它真的是歸檔材料中必需的嗎？那麼，您能否更具體地向我們介紹一下這些措施在招生時間表上的進展？

Thanks, Alethia, and thank you for your question on MANTA. Before I go into it and answer that, first, let me say that I really do appreciate everybody's interest in the program. It's a somewhat different situation than we've found ourselves in before. And the data that we're generating in the Phase III trials will provide me with a lot more -- and our team with a lot more details that will allow us to be able to answer your questions with greater clarity regarding the timelines. So we have had a pickup in enrollment, Alethia, since we've made the modifications to the programs. And as I said today, really, I think we don't need it for labeling necessary, but it would give clarity as to whether there's any risk associated with male infertility and so forth because it is a male safety study. So it's not required, but it's obviously advantageous for us to have it in all of those respects. As I said to you, this is an issue that we -- we are really addressing an FDA issue of the nonclinical filing that we observed in the preclinical animal studies. We've seen a pickup in enrollment. I don't want to get into specifics about the numbers, but there has been a significant pickup in enrollment. And I'll keep watching, and we will keep watching that process very carefully to advance our timeline. So once we have the data from the 3 Phase III FINCH trials, we will be able to initiate further interactions, discuss the MANTA study and its progress more and then be able to provide you with greater clarity.

謝謝 Alethia，也謝謝你對 MANTA 的提問。在我深入回答這個問題之前，首先，我想說我非常感謝大家對這個專案的關注。這種情況與我們之前遇到的情況有所不同。我們在 III 期試驗中產生的數據將為我提供更多信息，也將為我們的團隊提供更多細節，使我們能夠更清晰地回答您關於時間表的問題。阿萊西亞，自從我們對課程進行調整以來，入學人數有所增加。正如我今天所說，實際上，我認為我們不需要它來進行必要的標籤標註，但它可以明確是否存在與男性不孕等相關的風險，因為它是一項男性安全研究。所以這不是必須的，但顯然在所有這些方面，擁有它對我們都是有利的。正如我之前對你說的，這是一個我們——我們實際上是在解決FDA關於非臨床申報的問題，這個問題我們在臨床前動物研究中觀察到了。我們看到入學人數增加。我不想透露具體數字，但入學人數確實大幅增加。我會繼續關注，我們也會密切關注這個過程，以推進我們的時間表。一旦我們獲得了 3 項 III 期 FINCH 試驗的數據，我們將能夠展開進一步的互動，更深入地討論 MANTA 研究及其進展，並能夠為您提供更清晰的資訊。

Our next question comes from the line of Umer Raffat from Evercore ISI.

我們的下一個問題來自 Evercore ISI 的 Umer Raffat。

I have one for Robin and one quick clarification on something John said. So Robin, there was an expectation among investors based on a lot of the comments you shared and the rest of the management shared at the January conference that 2018 was a trough and 2019 should be a growth year in product sales. But judging by guidance, at least, it doesn't quite look like that. So can you please go over that? And also particularly curious about hep C because it looks like versus 4Q run rate, there isn't a whole lot of erosion modeled into it? And John, just to clarify something you mentioned on NASH earlier, is there a hierarchal analysis for the low dose versus high dose in the readout? Or is the p-value being split?

我有個問題想問羅賓，還有一個問題想就約翰說的話做個簡單的澄清。所以羅賓，根據你和其他管理階層在1月會議上分享的許多評論，投資人普遍預期2018年是低谷期，2019年應該是產品銷售成長的一年。但至少從指導意見來看，情況似乎並非如此。所以，您能詳細解釋一下嗎？另外，我對C型肝炎也特別感興趣，因為與第四季的運作率相比，C型肝炎的模型中似乎並沒有體現出太多的侵蝕？約翰，為了澄清你之前提到的 NASH 問題，讀數中是否有低劑量與高劑量的分層分析？還是 p 值被拆分了？

So Umer, let me start with your question on guidance. And so I just want to reiterate, as I've said, at your conference -- I mean, we are very focused on returning the growth in 2019 and really believe that's achievable if you look at the strength of our HIV franchise. As I said, we expect double-digit year-on-year growth, stabilizing trends in our HCV business as well as the momentum of our cell therapy franchise, where as you saw we expected to practically double this year. I think the other thing we tried to do is to be very transparent in our 2019 guidance of outlining those unplanned factors in 2018 that definitely will impact growth or the level of growth that we expect in 2019. The other thing I want to point is just our philosophy around setting guidance at the beginning of the year. It remains pretty consistent with how we've done it prior years, and it includes all the uncertainties that you could expect that could impact our franchises. I mentioned several on the call. And just take FX, that alone, volatility could have a, plus or minus, $300 million impact. So yes, the guidance, particularly our first guidance of the year, does include downside risk, and we're going to monitor those and manage them throughout the year. But our conviction as well as our confidence around returning a net product revenue growth is very, very strong, and we're going to look forward to updating you throughout the year as activities progress across our franchises.

那麼，烏默爾，讓我先回答你關於指導的問題。所以，我只想重申一下，就像我在你們的會議上說的那樣——我的意思是，我們非常專注於在 2019 年恢復增長，而且如果你看看我們 HIV 業務的實力，我們真的相信這是可以實現的。正如我所說，我們預計年增長率將達到兩位數，HCV 業務的趨勢將趨於穩定，細胞療法業務也將保持增長勢頭，正如你所看到的，我們預計今年的增長將幾乎翻一番。我認為我們努力做的另一件事是，在 2019 年的業績指引中，盡可能透明地概述 2018 年那些肯定會影響成長或我們預期 2019 年成長水準的計畫外因素。我想指出的另一點是我們在年初制定指導方針的理念。它與我們往年的做法基本一致，並且包含了所有可能影響我們特許經營權的不確定因素。我在電話中提到了好幾個。僅以外匯為例，單是外匯波動就可能造成正負 3 億美元的影響。所以，是的，我們的業績指引，特別是今年的第一份業績指引，確實包含了下行風險，我們將全年監控並管理這些風險。但是，我們對實現淨產品收入成長的信念和信心非常非常強烈，我們將在今年隨著我們各個特許經營業務的進展情況，及時向您報告最新進展。

Umer, in regard to your second question, it's John, we took 2 doses into the Phase III trials, a, because we had target engagement of both doses in terms of immunohistochemistry; we also allowed ourselves to have another chance in terms of the safety profile that might be potentially differentiated at lower or higher doses. Those were the 2 reasons for taking 2 doses forward into Phase III. And without getting into all the details of the statistical analysis plan, we will be able to compare both doses to placebo in terms of the primary endpoint.

Umer，關於你的第二個問題，我是John，我們在III期試驗中使用了2劑，a，因為在免疫組織化學方面，兩種劑量都達到了靶點結合；我們也給自己一次機會，看看在較低或較高劑量下安全性是否會有差異。這就是將兩劑藥物推進到 III 期臨床試驗的兩個原因。無需贅述統計分析計劃的所有細節，我們將能夠根據主要終點對兩種劑量與安慰劑進行比較。

Our next question comes from the line of Cory Kasimov from JPMorgan.

我們的下一個問題來自摩根大通的科里·卡西莫夫。

Wanted to ask on the cell therapy side of things. Can you talk about the source of your confidence in the projected growth for Yescarta in 2019? I believe you said it's up $200 million, given there's only $6 million of sequential growth from 3Q to 4Q. And along these lines, I think you previously guided to having more centers online for the product in Europe by the end of '18 and where you ended up. So how should we be thinking about kind of the cadence of opening centers into 2019? And how that plays into your guidance?

想問一下細胞療法方面的問題。您能否談談您對 Yescarta 在 2019 年預期成長的信心來源？我相信你說過成長了 2 億美元，但考慮到第三季到第四季僅環比成長了 600 萬美元。沿著這個思路，我認為你之前曾表示要在 2018 年底前在歐洲建立更多線上產品銷售中心，而最終你也做到了。那麼，我們該如何考慮2019年各中心開放的節奏呢？這又將如何影響你的指導呢？

This is Laura. Thanks for the question. I will say that our launches of Yescarta have really made excellent progress both in U.S. and in EU. As part of our guidance, we do expect Yescarta revenue to nearly double, as you had mentioned. So we feel like we have very, very strong momentum. We are seeing greater depth and breadth of treatment with Yescarta across the 68 certified sites in the U.S. So when we started off, there is a process of the institution really figuring out how to operationalize treatment, and we had a very high amount in the -- for top 20 academic institutions. We're starting to see that spread further across the 68 institutions and also, like I said, depth of patients going through. In addition, at ASH, as we've mentioned, the data that was presented for the follow-up to the real-world evidence, I think, really is providing that extra energy in the community about the importance of treating, not only at obviously the 68 sites. But what's more important is that the community oncologists are referring these patients into the sites for treatment, and we do have a field force focused on helping with that referral process. And you did ask us specifically about Europe. So we do have 12 sites in Europe that are actively engaged. And we will tell you that in terms of what we're seeing in Germany, we're very, very impressed with the results. And we continue to have additional -- Germany actually and the U.K. And we also have provided product and open up sites in France, and we will continue to expand throughout 2019 in the European markets.

這是勞拉。謝謝你的提問。我想說，Yescarta 在美國和歐盟的推廣都取得了非常好的進展。正如您所提到的，根據我們的預期，我們預計 Yescarta 的收入將幾乎翻倍。所以我們感覺我們勢頭非常強勁。我們看到 Yescarta 在美國 68 個認證機構的治療深度和廣度都在不斷提高。所以當我們開始的時候，機構確實需要弄清楚如何實施治療，而且我們在排名前 20 名的學術機構中獲得了非常高的比例。我們開始看到這種情況在 68 個機構中進一步蔓延，而且，就像我說的，接受治療的患者人數也在增加。此外，正如我們之前提到的，在 ASH 會議上，針對真實世界證據提出的後續數據，我認為，確實為社區提供了額外的動力，讓人們認識到治療的重要性，而不僅僅是在 68 個地點。但更重要的是，社區腫瘤醫師正在將這些患者轉診到治療中心接受治療，我們也有一支專門負責協助轉診流程的現場團隊。而且您確實專門問了我們關於歐洲的問題。因此，我們在歐洲有 12 個活躍的站點。我們可以告訴大家，就我們在德國看到的情況而言，我們對結果非常非常滿意。我們繼續拓展業務——實際上，我們在德國和英國也有業務。我們也在法國提供了產品並開設了站點，我們將繼續在 2019 年全年拓展歐洲市場。

Our next question comes from the line of Phil Nadeau from Cowen and Company.

我們的下一個問題來自 Cowen and Company 的 Phil Nadeau。

Question on the HIV franchise. I think in your prepared remarks, you mentioned that the use of TDF generic regimens is a risk to HIV pricing this year. And in fact, we have seen some payer programs to incentivize the use of those generic regimens. So just curious if you could maybe talk in a little bit more detail what you are seeing from payers, any impact on pricing of those generic regimens, how it's being used by physicians. And should payers get more aggressive about recommending their use? How would Gilead account for that?

關於愛滋病特許經營權的問題。我認為您在事先準備好的演講稿中提到，使用 TDF 仿製藥療法會對今年的 HIV 藥物定價構成風險。事實上，我們已經看到一些支付方推出了激勵使用這些通用療法的計劃。所以我很好奇，您能否更詳細地談談您從支付方那裡了解到的情況，這些情況對這些仿製藥的價格有何影響，以及醫生是如何使用它們的。那麼，支付方是否應該更積極地推薦使用這些技術呢？吉利德公司會如何解釋這種情況？

So this is Laura. Thank you for taking the question. Yes, that was a pretty consistent question that we had at the JPMorgan conference, too. And when we look at specifically one, particular payer that was emphasized, we really have not seen any major impact at all. As a matter of fact, when we look at the program, which was specifically supporting Cimduo, we saw no more than 100 prescriptions generated during the 10-month period of time. And in addition to that, in December, United basically sent a letter out to physicians saying they were no longer going to run the My Scripts program. So that's -- I think that, that was an effort that was tried to see if patients would choose to switch back, but we really did not see any impact.

這位是勞拉。感謝您回答這個問題。是的，這也是我們在摩根大通會議上常被問到的問題。當我們具體觀察某個被重點關注的特定付款方時，我們實際上並沒有看到任何重大影響。事實上，當我們查看專門支持 Cimduo 的計劃時，我們發現，在 10 個月的時間裡，產生的處方不超過 100 張。除此之外，去年 12 月，聯合航空也向醫生們發出了一封信，表示他們將不再經營 My Scripts 計畫。所以，我認為，我們嘗試這樣做是為了看看患者是否會選擇換回原來的治療方案，但我們並沒有看到任何影響。

Our next question comes from the line of Salim Syed from Mizuho Securities.

我們的下一個問題來自瑞穗證券的 Salim Syed。

I actually have 2 quick ones, if you don't mind. The first is on HIV Japan. So if I recall at the end of last year, towards the end of last year, you guys bought back the HIV rights from Japan Tobacco. I was wondering if you could just give us some color. How should we be modeling that opportunity coming out of Japan now that you are marketing that solo? And what should we be taking out of the royalty line, where, I believe, you previously booked the economics? And then on the second question, just on your allo CD19 CAR, wondering if you guys view CD19 CAR NK cells therapy as complementary or competition to your allo T-cell therapy?

如果你不介意的話，我其實還有兩個簡短的問題。第一篇是關於日本愛滋病防治的。如果我沒記錯的話，去年年底，你們從日本菸草公司買回了愛滋病防治權益。我想問您能否為我們增添一些色彩。既然你現在要獨自負責日本市場的推廣，我們該如何借鏡這個市場機會呢？那我們該從版稅收入中扣除多少呢？我相信，您之前已經確定了這部分的經濟效益。第二個問題，關於你們的同種異體 CD19 CAR，我想知道你們認為 CD19 CAR NK 細胞療法是同種異體 T 細胞療法的補充療法還是競爭療法？

So maybe I'll start with the HIV question, Salim. Thanks for asking that. Yes, we're really excited about the opportunity in Japan. It is included in our guidance. And to your point, in the past, we got between about $50 million and $60 million a year in Japan Tobacco royalties, and that was in total revenue, not for the product revenue. So net-net, this is a positive for us, and that we'll now see those revenues flow through net product revenue, but we'll lose that royalty contract in Other going forward. So again, I think very excited about gaining the commercial rights to the HIV products. And Laura, I don't know if you want to expand a bit on the commercialization of that relationship at all.

那我或許就先從愛滋病的問題開始吧，薩利姆。謝謝你的提問。是的，我們對在日本的機會感到非常興奮。它包含在我們的指導方針中。正如您所說，過去我們每年從日本菸草公司獲得的特許權使用費大約在 5000 萬美元到 6000 萬美元之間，而且這指的是總收入，而不是產品收入。總而言之，這對我們來說是件好事，我們現在將看到這些收入透過淨產品收入流入市場，但我們將失去「其他」類別的特許權使用費合約。所以，我再次感到非常興奮，因為我獲得了愛滋病產品的商業權利。蘿拉，我不知道你是否想就這段關係的商業化問題再深入探討。

Yes. So the teams have been actively working in this move for a smooth transition for the HIV franchise. I think it's not only the HIV franchise that exists currently, but it's really the opportunity this year, 2019, to launch Biktarvy. So we're really, really excited about that opportunity. And the teams, like I said, are working hard, and we appreciate the great partnership with Japan Tobacco on kind of helping us with the conversion and building this franchise for us and helping us with a successful launch.

是的。因此，各團隊一直在積極努力，以確保 HIV 特許經營權的平穩過渡。我認為不僅是目前存在的 HIV 專案業務，而且今年（2019 年）也是推出 Biktarvy 的真正機會。所以我們對這個機會真的非常興奮。正如我所說，各個團隊都在努力工作，我們非常感謝與日本菸草公司的良好合作，他們幫助我們進行轉型，為我們建立這個特許經營權，並幫助我們成功推出產品。

In terms of the question, Salim, related to the allogeneic program, what -- as I said on the call, we are very pleased to announce that we hope to have our IND for allogeneic CD19 program this year. And we will engineer certain factors into that program, one of which we've already announced it will be HLA-I related that will have an effect on NK cells that will allow, we hope, an advantage in terms of persistence of those cells -- persistence of the manipulated or engineered CAR T-cells. So it's an early field. More to be seen. Lots of different approaches. We are pleased with our progress so far.

關於 Salim 提出的問題，與同種異體計畫有關，正如我在電話會議上所說，我們非常高興地宣布，我們希望今年能獲得同種異體 CD19 計畫的 IND 申請。我們將把某些因素融入到該計劃中，其中一個我們已經宣布與 HLA-I 相關，它將對 NK 細胞產生影響，我們希望這將使這些細胞——經過改造或工程化的 CAR T 細胞——的持久性獲得優勢。所以這是早期階段。還有更多精彩內容，敬請期待。有很多不同的方法。我們對目前的進展感到滿意。

Our next question comes from the line of Terence Flynn from Goldman Sachs.

我們的下一個問題來自高盛的 Terence Flynn。

Maybe just on selonsertib. Was just wondering if you can confirm if you'd be able to file on only one positive Phase III trial or if you need both of those trials to file. And then would love your thoughts on how you see this market playing out over the near and longer term under a positive outcome for the STELLAR studies. And importantly, what are the key inputs on pricing? Do you need the event-free survival beta to really drive the value proposition? Or do you think just the histology data is enough?

或許只服用塞隆塞替布。我想確認一下，是否只需要一項積極的 III 期臨床試驗結果就可以提交申請，還是需要兩項試驗結果都呈陽性才能提交申請。然後，我很想聽聽您對STELLAR研究取得正面結果後，該市場在短期和長期內的發展趨勢有何看法。更重要的是，定價的關鍵因素是什麼？您是否需要無事件生存測試版來真正提升其價值主張？或者您認為僅憑組織學數據就足夠了？

Thanks, Terence. Look, we would like both studies to be positive. They are imminently going to be available in the next quarter or a few months as well. If one was positive and one was negative, as you outlined, we'd have to have a discussion with the regulators. And that would be something that we would discuss, analyzing data in that situation. Look, in terms of pricing and moving forward, I'll hand those aspects on to Laura. But...

謝謝你，特倫斯。我們當然希望這兩項研究的結果都是正面的。它們很快就會在下一季或幾個月內上市。如果一個結果呈陽性，一個結果呈陰性，正如你所描述的那樣，我們就需要和監管機構進行討論。而這正是我們需要討論的內容，我們需要分析這種情況下的數據。至於定價和未來發展方面，我會把這些方面交給勞拉負責。但...

Yes. Thank you, John. Thank you. So obviously, it's too early to really comment on our pricing strategy. But of course, we model scenarios. I will say that the medical affairs team has done a lot of work from a health economics perspective. We're quite familiar with the overall cost of an F3, F4 patient. These patients are extremely expensive to the system. So having that real-world data, which shows us how expensive and unfortunately how many patients when they get to that level really are in pretty dire need, we can take that information, coupled with what John produces from a clinical perspective, and be able to utilize that for our discussions.

是的。謝謝你，約翰。謝謝。所以很顯然，現在評論我們的定價策略還為時過早。當然，我們會模擬各種場景。我想說，醫療事務團隊從衛生經濟學的角度做了很多工作。我們非常清楚F3、F4級患者的總費用。這些病人為醫療系統帶來了極大的經濟負擔。因此，有了這些真實世界的數據，我們就能了解治療費用有多高，而且不幸的是，許多患者到了那個階段確實非常需要幫助。我們可以將這些信息，結合約翰從臨床角度提供的信息，用於我們的討論。

Terence, just to add, it is subpar H approval. So once we have the histological endpoint at week 48, that would then allow approval of the drug that would be linked to the 5-year follow-up to show the improvement in clinical benefit as well as the time.

Terence，補充一點，這是次級H級認證。因此，一旦我們在第 48 週獲得組織學終點，就可以批准該藥物，並將其與 5 年的追蹤聯繫起來，以顯示臨床效益的改善以及時間。

Our next question comes from the line of Ying Huang from Bank of America Merrill Lynch.

我們的下一個問題來自美國銀行美林證券的黃穎。

So maybe first for Robin. In your assumptions for the incremental SG&A for 2019 and perhaps for the launch for filgotinib and NASH, I assume that will probably mostly occur in the second half. And if NASH unfortunately fails, does that mean SG&A would actually be lower than they were expected? And then secondly, on the assumption for the HIV launch in your guidance, does that assume incremental more switches from dolutegravir-containing regimens are not in 2019?

所以，或許羅賓是第一個。在您關於 2019 年新增銷售、一般及行政費用以及 filgotinib 和 NASH 上市的假設中，我認為這些費用很可能主要發生在下半年。如果 NASH 不幸失敗，這是否意味著銷售、管理及行政費用實際上會低於預期？其次，根據您指引中關於 HIV 啟動的假設，是否假設 2019 年不會有更多人從含多替拉韋的方案轉向其他方案？

Sure, Ying. So first to talk about SG&A. As I mentioned earlier, yes, it is -- the ramp in SG&A is more second half 2019. Don't use Q4 2018 as your baseline. Yes, it's an unfortunate yes, if for some reason we would not launch, our SG&A expenses would go down, and that is hopefully not what happens. This is one place where as a CFO, I hope we spend every single dollar that we've allocated. I'll also add that again because of the health of our HIV franchise, I didn't mention earlier, but there is a component of incremental investment we're making there as well. But to your question, if NASH did not launch, it would have lower expenses. If you think about $100 million for us in terms of SG&A spend or expenses in general, it's about $0.06 a share.

當然可以，瑩。首先來談談銷售、一般及行政費用。正如我之前提到的，是的——SG&A 的上漲主要發生在 2019 年下半年。不要以 2018 年第四季作為基準。是的，這確實令人遺憾。如果我們因為某些原因無法推出產品，我們的銷售、一般及行政費用就會下降，但希望這種情況不會發生。身為財務官，我希望我們把撥出的每一分錢都花在這個領域。我還要補充一點，由於我們愛滋病防治業務的健康狀況，我之前沒有提到，我們也在加大對該業務的投資。但回到你的問題，如果NASH沒有成立，它的成本就會降低。如果把我們1億美元的銷售、一般及行政費用或一般支出看作是每股0.06美元，那也差不多是每股0.06美元。

And then there was a question on the HIV launch assumptions in terms of a competitor. I think Ying it's safe to say we're not going to get into our detailed assumptions of our guidance, but we fully anticipate Biktarvy will go on to be the best-selling single-tablet regimen.

然後還有一個關於 HIV 疫苗上市假設（考慮到競爭對手）的問題。我認為 Ying，我們可以肯定地說，我們不會詳細討論我們的指導意見，但我們完全預期 Biktarvy 將成為最暢銷的單片療法。

Our next question comes from the line of Carter Gould from UBS.

我們的下一個問題來自瑞銀集團的卡特古爾德。

Just wanted to dig in a little bit deeper to the EU dynamics in HIV. You obviously highlighted a couple of countries still to launch with Biktarvy. But you were a little more, I guess, opaque on around if that business will sort of stabilize this year and/or return to growth. Or is that really something we should be looking to 2024? Any color there'd be appreciated.

我想更深入地了解歐盟在愛滋病方面的動態。您顯然重點提到了幾個尚未與 Biktarvy 合作推出的國家。但我覺得你對這家企業今年能否穩定下來和/或恢復成長這個問題，態度有點含糊其辭。或者，這真的是我們應該展望2024年的事嗎？任何顏色都可以。

Yes. This is Carter?

是的。這是卡特嗎？

Yes.

是的。

Okay, hi Carter, this is Robin. Maybe I'll start, and if Laura has any color. Yes, I would say, in 2019, we actually don't expect U.S. HIV revenues to grow, but we'll have the full year impact of genericization. And as Laura talked about, we'll continue to see that ramp of our Descovy-based product. So keep in mind, over the next 2 years, we'll be launching Biktarvy throughout Europe. The one component of that quarter sequential decline that we saw was a onetime adjustment we had to make relative to prior periods, where certain southern European countries reach a cap in terms of spending on pharmaceutical products. And then they do what's called clawback, where we get kind of an additional tax. There's been a lot of changes in government [spend], and we did make an additional adjustment. If you take that out, I'd say the sequential declines are more consistent of what we've seen in the past. But beyond 2019, again, Laura talked about the great uptake of Descovy with Biktarvy, we do expect over time in '20 or '21 to return to growth for EU HIV.

好的，你好卡特，我是羅賓。也許我會先開始，如果勞拉有顏色的話。是的，我認為，2019 年我們實際上並不預期美國 HIV 收入會成長，但我們將面臨全年仿製藥上市帶來的影響。正如勞拉所說，我們將繼續看到基於 Descovy 的產品銷售成長。所以請記住，在接下來的兩年裡，我們將在整個歐洲推出 Biktarvy。我們看到的該季度環比下降的一個組成部分是，相對於以前的時期，我們必須進行一次性調整，因為某些南歐國家在藥品支出方面達到了上限。然後他們會進行所謂的追回，也就是要額外徵收一筆稅。政府支出方面發生了許多變化，我們也做出了額外的調整。如果排除這個因素，我認為連續下跌的趨勢與我們過去看到的情況更一致。但勞拉再次談到 2019 年後 Descovy 與 Biktarvy 的廣泛應用，我們預計在 2020 年或 2021 年，歐盟 HIV 感染率將恢復成長。

Yes. So I'll just add a little bit. I think Robin covered it very well. In terms of launches, we've definitely been able to with Biktarvy launch. Like I said, just some at the very end of the year, some of the big countries, we have launches going on all through '19 for Biktarvy. There will still be erosion [of the] generics to spring through '19. So we had it in '18. We'll see it happen through '19. But we believe we're going to have some erosion, but the conversion of the -- to the Descovy-based regimen being at 80%, those 3 variables, we believe, that we will be able to move through '19 and then continue to grow from that base.

是的。所以我再補充一點。我覺得羅賓解釋得很好。就產品發布而言，我們確實透過 Biktarvy 的發布取得了成功。就像我說的，只是在年底的一些時候，一些大國家，我們在整個 2019 年都會推出 Biktarvy 產品。仿製藥的市場份額在 2019 年春季仍將受到侵蝕。所以我們在 2018 年就有了。我們將在 2019 年看到這種情況發生。但我們相信會有一些下滑，但向 Descovy 療法的轉化率達到 80%，這三個變量，我們相信，我們將能夠度過 2019 年，並在此基礎上繼續增長。

This does conclude the question-and-answer session of today's program. I'd like to hand the program back to management for any further remarks.

今天的問答環節到此結束。我想把這個程序交還給管理階層，讓他們再做進一步說明。

Thank you, Jonathan, 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.

謝謝你，喬納森，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。

Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.

感謝各位女士、先生參加今天的會議。節目到此結束。您現在可以斷開連線了。再會。