英賽德 (INCY) 2017 Q3 法說會逐字稿

Greetings, and welcome to the Incyte Corporation Third Quarter 2017 Earnings Call. (Operator Instructions) As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Mike Booth, Vice President of Investor Relations. Please go ahead.

您好，歡迎參加 Incyte Corporation 2017 年第三季度收益電話會議。（操作員指示）謹此提醒，本次會議正在錄製中。現在我想將會議交給東道主投資者關係副總裁邁克·布斯 (Mike Booth)。請繼續。

Thank you, Diego. Good morning, and welcome to Incyte's Third Quarter 2017 Earnings Conference Call and Webcast. The slides used today are available for download on the Investor section of incyte.com. And I'm joined on the call today by Hervé, Barry, Steven and Dave and Reid.

謝謝你，迭戈。早上好，歡迎來到 Incyte 2017 年第三季度收益電話會議和網絡廣播。今天使用的幻燈片可在 incyte.com 的投資者部分下載。今天，埃爾韋、巴里、史蒂文、戴夫和里德也加入了我的電話會議。

We would like to remind you that some of the statements made during the call today are forward-looking statements, including statements regarding our expectations for 2017 guidance, the commercialization of our products and our development plans for the compounds in our pipeline as well as the development plans for our collaboration partners. These forward-looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our 10-Q for the quarter ended June 30, 2017, and from time to time in our other SEC documents.

我們想提醒您，今天電話會議中所做的一些陳述屬於前瞻性陳述，包括有關我們對 2017 年指導的預期、我們產品的商業化、我們管道中化合物的開發計劃以及我們的合作夥伴的發展計劃。這些前瞻性陳述受到許多風險和不確定性的影響，可能導致我們的實際結果出現重大差異，包括我們截至 2017 年 6 月 30 日的季度 10-Q 中描述的風險和不確定性，以及我們不時在其他 SEC 中描述的風險和不確定性。文件。

I'd now like to pass the call to Hervé for his introductory remarks.

現在我想將電話轉接給 Hervé，請他作介紹性發言。

Thank you, Mike, and good morning, everyone. So I'm very pleased to report another very successful quarter at Incyte with dynamic revenue growth driven by sales of both Jakafi and Iclusig and with significant progress in multiple places in our clinical development portfolio.

謝謝你，邁克，大家早上好。因此，我很高興地向大家報告 Incyte 又一個非常成功的季度，在 Jakafi 和 Iclusig 的銷售推動下實現了動態收入增長，並且我們的臨床開發組合中的多個方面都取得了重大進展。

So let's begin with Q3 revenues. So you can see on Slide 5 remarkable growth in product-related revenue over the past 5 years, so that's revenue without the milestones, which has seen a compounded annual growth rate of more than 50%. 5 years ago, Incyte's product-related revenue was made of Jakafi sales and Jakavi royalties in myelofibrosis, and we have come a long way since then. Jakafi sales and royalties remain a key component of our revenue growth, and Iclusig sales and Olumiant royalties are now adding to it. We believe Incyte is in a unique position, combining strong revenue growth with a cutting-edge portfolio of projects at every stage of development.

讓我們從第三季度的收入開始。所以你可以在幻燈片 5 上看到過去 5 年產品相關收入的顯著增長，所以這是沒有里程碑的收入，年復合增長率超過 50%。5 年前，Incyte 的產品相關收入來自 Jakafi 銷售額和 Jakavi 骨髓纖維化領域的特許權使用費，從那時起我們已經取得了長足的進步。Jakafi 銷售和特許權使用費仍然是我們收入增長的關鍵組成部分，Iclusig 銷售和 Olumiant 特許權使用費現在也加入其中。我們相信 Incyte 處於獨特的地位，將強勁的收入增長與每個發展階段的尖端項目組合相結合。

And I will now spend a few minutes in our late-stage development portfolio.

我現在將花幾分鐘時間介紹我們的後期開發組合。

So Slide 6 summarizes late-stage projects and the indications being pursued. Pivotal program for ruxolitinib is open in both steroid-refractory GVHD and essential thrombocythemia, and itacitinib is also in a pivotal program for GVHD. Recruitment is proceeding well in our 2 key FGFR trials, and our PI3 kinase-delta program is also moving forward where we are opening trials in 4 different non-Hodgkin lymphomas. And of course, the ECHO program for epacadostat continues to progress, and we are looking forward to the results of the pivotal ECHO-301 trial in melanoma expected in the first half of 2018.

因此，幻燈片 6 總結了後期項目和正在尋求的跡象。ruxolitinib 的關鍵計劃在類固醇難治性 GVHD 和原發性血小板增多症中均已開放，itacitinib 也在 GVHD 的關鍵計劃中。我們的 2 個關鍵 FGFR 試驗的招募工作進展順利，我們的 PI3 激酶 δ 項目也在取得進展，我們將在 4 種不同的非霍奇金淋巴瘤中開展試驗。當然，epacadostat 的 ECHO 項目仍在繼續取得進展，我們期待預計於 2018 年上半年進行的針對黑色素瘤的關鍵 ECHO-301 試驗的結果。

I believe that over the next 5 years, these 5 late-stage product candidates have the potential to further accelerate our revenue growth, and we look forward to reporting on future developments.

我相信，在未來 5 年裡，這 5 個後期候選產品有潛力進一步加速我們的收入增長，我們期待報告未來的發展。

So on Slide 7, you see our leadership position in immuno-oncology is driven by our roots in immunology research, and we consider our ongoing epacadostat plus PD-1 collaboration to be only the beginning for us in this field. Our discovery and development teams now have many candidates in the clinic to explore the I/O space, such as IDO1, obviously, arginase, JAK1, bromodomain and PI3 kinase delta inhibitors as well as our GITR and OX40 agonist.

因此，在幻燈片 7 中，您可以看到我們在免疫腫瘤學領域的領導地位是由我們在免疫學研究方面的根基推動的，我們認為我們正在進行的 epacadostat 與 PD-1 合作只是我們在該領域的開始。我們的發現和開發團隊現在在臨床上有許多候選藥物來探索 I/O 空間，例如 IDO1，顯然還有精氨酸酶、JAK1、溴結構域和 PI3 激酶 δ 抑製劑，以及我們的 GITR 和 OX40 激動劑。

We have recently announced 2 new collaborations that we believe will serve to further enhance our immuno-oncology portfolio, and I'll touch on this on Slide 8 and 9.

我們最近宣布了兩項新的合作，我們相信這將有助於進一步增強我們的免疫腫瘤學產品組合，我將在幻燈片 8 和 9 中談到這一點。

On Slide 8, you can see that we have agreed with AstraZeneca to expand our existing clinical collaboration and move into Phase III development in a trial which will study epacadostat plus durvalumab in patients with non-small cell lung cancer. This study builds on AstraZeneca's recent success in the PACIFIC study, and the objective of the study is to establish a new standard of care in the same patient population as was studied in PACIFIC. We will share the cost of the trial with AstraZeneca, and the trial is expected to begin in the first half of next year.

在幻燈片 8 上，您可以看到我們已與阿斯利康達成一致，擴大我們現有的臨床合作，並進入一項試驗的 III 期開發，該試驗將研究 epacadostat 聯合 durvalumab 治療非小細胞肺癌患者。這項研究建立在阿斯利康最近在 PACIFIC 研究中取得成功的基礎上，該研究的目標是在與 PACIFIC 研究相同的患者群體中建立新的護理標準。我們將與阿斯利康分擔試驗費用，預計明年上半年開始試驗。

We are also excited to announce last week that we have entered into a global collaboration and license agreement with MacroGenics for its PD-1 antagonist MGA012, which is already in the clinic. Under the agreement, Incyte will hold exclusive worldwide development and commercialization rights in all indications, and Incyte will record all global sales for the compound. As you can see here on Slide 9, we have a total of 7 in-house assets today that have the potential to be combined with the PD-1 antagonist and are currently in a Phase I PD-1 combination trial, and we intend to proceed into combination trials with 012 as soon as possible. Yet, what is different about this collaboration is that the agreement also grants MacroGenics the right to develop 012 in combination with its own pipeline, and we believe that this innovative collaboration structure with MacroGenics provides us with significant optionality and may increase the compound's commercial potential.

我們還很高興地宣布，上週我們已與 MacroGenics 就其 PD-1 拮抗劑 MGA012 達成全球合作和許可協議，該藥物已進入臨床。根據協議，Incyte 將擁有所有適應症的全球獨家開發和商業化權利，並且 Incyte 將記錄該化合物的所有全球銷售額。正如您在幻燈片 9 中看到的，我們目前共有 7 個內部資產，有可能與 PD-1 拮抗劑聯合使用，目前正在進行 I 期 PD-1 聯合試驗，我們打算盡快與012進行聯合試驗。然而，這次合作的不同之處在於，該協議還授予 MacroGenics 結合其自己的管道開發 012 的權利，我們相信與 MacroGenics 的這種創新合作結構為我們提供了重要的選擇性，並可能增加該化合物的商業潛力。

Now on Slide 10. Drug discovery remains central at Incyte, and we have successfully added 2 large molecule discovery alliances to our small molecule expertise, one for monoclonals and one for a bispecific antibodies. These 3 platforms are expected to enable us to go after a multitude of future targets. We have 5 late-stage programs within our development portfolio. And in readiness for what could potentially be a good number of new product and new indication approvals, we'll now have an operation in the U.S., Europe and Japan as we continue to build Incyte into a world-class biopharmaceutical company.

現在在幻燈片 10 上。藥物發現仍然是 Incyte 的核心，我們已經成功地將 2 個大分子發現聯盟添加到我們的小分子專業知識中，一個用於單克隆抗體，一個用於雙特異性抗體。這三個平台預計將使我們能夠實現眾多未來目標。我們的開發組合中有 5 個後期項目。為了做好可能獲得大量新產品和新適應症批准的準備，我們現在將在美國、歐洲和日本開展業務，繼續將 Incyte 打造成世界一流的生物製藥公司。

As part of this process, we're also very pleased to have Jackie Fouse join our Board of Directors. Jackie has extensive experience in oncology and in the biopharma field, and she will be a wonderful addition to our team.

作為此過程的一部分，我們也很高興 Jackie Fouse 加入我們的董事會。Jackie 在腫瘤學和生物製藥領域擁有豐富的經驗，她將成為我們團隊的絕佳補充。

With that, I'll pass the call to Barry for an update on Jakafi.

這樣，我會將電話轉給巴里，了解有關賈卡菲的最新情況。

Thank you, Hervé, and good morning, everyone. Jakafi net sales were strong in Q3 of 2017 at $304 million, a 36% increase over Q3 2016 and a 10% increase over the second quarter of this year. Jakafi's performance in the quarter was driven by strong patient demand for both indications. We believe this demonstrates that our approach of educating physicians on the benefits of intervening early with Jakafi therapy and supporting patients through our educational and awareness initiatives continues to be very effective.

謝謝你，Hervé，大家早上好。Jakafi 2017 年第三季度的淨銷售額強勁，達到 3.04 億美元，比 2016 年第三季度增長 36%，比今年第二季度增長 10%。Jakafi 本季度的業績得益於患者對這兩種適應症的強勁需求。我們相信，這表明我們教育醫生早期干預 Jakafi 療法的好處以及通過我們的教育和宣傳活動支持患者的方法仍然非常有效。

We did see that -- we did see some inventory build in Q3, which is now slightly above the high end of our typical range of 2.5 to 3 weeks. In dollar amounts, this inventory represents approximately $5 million of net sales.

我們確實看到了——我們確實在第三季度看到了一些庫存增加，目前略高於我們 2.5 至 3 週的典型範圍的上限。以美元計算，該庫存相當於淨銷售額約 500 萬美元。

As a result of our strong sales growth, we are revising our full year 2017 net product revenue guidance for Jakafi from a range of $1.090 billion to $1.120 billion to a new range of $1.125 billion to $1.135 billion.

由於銷售增長強勁，我們正在將 Jakafi 2017 年全年產品淨收入指引從 10.90 億美元至 11.20 億美元調整為 11.25 億美元至 11.35 億美元的新範圍。

I'd like to take a moment to remind everyone of the long-term revenue potential of Jakafi beyond MF and PV. Jakafi also has the potential to benefit patients with graft-versus-host disease, an underserved community of patients who may have been cured of their cancer by a stem cell transplant only to suffer a side effect of that treatment resulting in GVHD. Data from REACH1 in steroid-refractory acute GVHD are expected in the first half of next year. And if the results are positive, we expect to be able to file a sNDA for Jakafi in this indication in 2018.

我想花點時間提醒大家 Jakafi 除了 MF 和 PV 之外的長期收入潛力。Jakafi 還具有使移植物抗宿主病患者受益的潛力，這是一個服務不足的患者群體，這些患者可能通過乾細胞移植治癒了癌症，但卻遭受了導致 GVHD 的治療副作用。類固醇難治性急性 GVHD 的 REACH1 數據預計將於明年上半年獲得。如果結果是積極的，我們預計能夠在 2018 年為 Jakafi 提交該適應症的 sNDA。

We have also opened a pivotal study in patients with essential thrombocythemia. Jakafi has already transformed the lives of thousands of patients with MPNs, and we continue to work with doctors, patients, patient advocacy groups and the FDA to further expand access to those who may be able to benefit from this treatment.

我們還針對原發性血小板增多症患者開展了一項關鍵研究。Jakafi 已經改變了數千名 MPN 患者的生活，我們將繼續與醫生、患者、患者權益團體和 FDA 合作，進一步擴大那些可能從這種治療中受益的人的使用範圍。

With that, I'll pass along the call to Steven for a clinical update.

這樣，我會將電話轉給史蒂文，以獲取臨床最新情況。

Thanks, Barry, and good morning, everyone. On Slide 15, I'd like to start by reminding you of the scope of our current pivotal program with epacadostat. As you are all aware, ECHO-301 is ongoing in patients with unresectable or metastatic melanoma. The trial has completed enrollment, and we are now waiting for events to accrue. We remain on track to announce results in the first half of 2018.

謝謝巴里，大家早上好。在幻燈片 15 上，我想首先提醒您我們當前 epacadostat 關鍵計劃的範圍。眾所周知，ECHO-301 正在針對不可切除或轉移性黑色素瘤患者進行治療。試驗已完成註冊，我們現在正在等待事件的發生。我們仍有望在 2018 年上半年公佈業績。

Earlier this year, we announced that we would be expanding the epacadostat program to include pivotal trials in 4 additional tumor types in combination with either Merck's pembro or Bristol's nivo. These studies are all on track to begin enrollment by the end of 2017.

今年早些時候，我們宣布將擴大 epacadostat 項目，將與默克公司的 pembro 或布里斯托爾公司的 nivo 聯合進行 4 種其他腫瘤類型的關鍵試驗。這些研究均有望於 2017 年底開始招募。

As Hervé mentioned, we were pleased to announce that we are expanding further with a pivotal study in combination with AstraZeneca's durva in patients with stage 3 non-small cell lung cancer.

正如 Hervé 提到的，我們很高興地宣布，我們正在進一步擴大一項與阿斯利康 durva 聯合治療 3 期非小細胞肺癌患者的關鍵研究。

Our clinical development team, along with our partners at Merck and Bristol, are working hard to initiate the additional trials of epacadostat in combination with either pembro or nivo. The details of the renal and both lung studies with pembro are now available on ct.gov (clinicaltrials.gov), and we've summarized the trial schema for these studies on this slide, Slide 16. All 3 trials will be conducted in patients that are treatment naïve for their advanced disease.

我們的臨床開發團隊與默克和布里斯托爾的合作夥伴正在努力啟動 epacadostat 與 pembro 或 nivo 聯合的額外試驗。使用 pembro 進行腎臟和雙肺研究的詳細信息現已在 ct.gov (clinicaltrials.gov) 上提供，我們在這張幻燈片（幻燈片 16）上總結了這些研究的試驗方案。所有 3 項試驗都將在未接受過治療的晚期疾病患者中進行。

ECHO-302 will study the combination of epacadostat in pembro in patients with renal cell carcinoma versus standard of care, in this case, either Sutent or Votrient in a simple 2-arm design.

ECHO-302 將研究腎細胞癌患者中 epacadostat 與 pembro 的組合與標準護理（在本例中為簡單 2 臂設計中的 Sutent 或 Votrient）的組合。

ECHO-305 will study the combination of epacadostat and pembro in patients with PD-L1 high-expression lung cancer versus pembro monotherapy. Pembro monotherapy is the care standard in this population.

ECHO-305 將研究 epacadostat 和 pembro 聯合治療 PD-L1 高表達肺癌患者與 pembro 單一療法的對比。Pembro 單一療法是該人群的護理標準。

ECHO-306 will evaluate patients with lung cancer, irrespective of their PD-L1 status. The evolving care standard in this population is pembro plus platinum doublet chemotherapy. And therefore, this is used as the comparator arm.

ECHO-306 將評估肺癌患者，無論其 PD-L1 狀態如何。該人群不斷發展的護理標準是 pembro 加鉑類雙重化療。因此，將其用作比較器臂。

We are also taking the opportunity in this study to investigate the possibility of a chemotherapy-free combination. And so we are not only including a triplet arm of epacadostat plus pembro plus chemotherapy, but also a third arm of epacadostat plus pembro. The co-primary endpoints for all 3 trials will be progression-free survival and overall survival.

我們還利用這項研究的機會來研究無化療組合的可能性。因此，我們不僅包括 epacadostat 加 pembro 加化療的三聯組，而且還包括 epacadostat 加 pembro 的第三組。所有 3 項試驗的共同主要終點是無進展生存期和總生存期。

Next, I'd like to spend a few minutes speaking about our other immuno-oncology assets and the significant progress we are making here. Our GITR agonist, '1876, and our OX40 agonist, '1949, have both completed dose escalation. Each of these candidates is now moving ahead in multiple combination cohorts.

接下來，我想花幾分鐘談談我們的其他免疫腫瘤學資產以及我們在這裡取得的重大進展。我們的 GITR 激動劑（'1876）和我們的 OX40 激動劑（'1949）均已完成劑量遞增。這些候選人中的每一位現在都在多個組合隊列中取得進展。

'1876 is in combination with epacadostat and pembro and separately in combinations with nivo monotherapy or nivo plus ipi.

'1876 與 epacadostat 和 pembro 聯合使用，並單獨與 nivo 單藥療法或 nivo 加 IPI 聯合使用。

'1949 is currently progressing into combinations with either nivo monotherapy or nivo plus ipi.

'1949 目前正在開發與 nivo 單一療法或 nivo 加 IPI 的組合療法。

Our first-in-class arginase inhibitor, '1158, is continuing with dose escalation and has recently moved into combination studies with pembro. We also plan to evaluate '1158 in both epacadostat and chemotherapy-based combinations.

我們的一流精氨酸酶抑製劑 '1158 正在繼續增加劑量，最近已進入與 pembro 的聯合研究。我們還計劃評估 epacadostat 和基於化療的組合中的 '1158。

On Slide 18, outside of immuno-oncology, we have what we believe is an exciting portfolio of targeted therapies. Over the last year, we have put together a broad program to study the effects of JAK inhibition for patients suffering from graft-versus-host disease. The program spans both acute and chronic graft-versus-host disease and will also evaluate various other treatment settings, such as prophylaxis for the condition, patients that are treatment-naïve and patients that are steroid-refractory.

在幻燈片 18 上，除了免疫腫瘤學之外，我們還擁有令人興奮的靶向治療組合。去年，我們制定了一項廣泛的計劃來研究 JAK 抑制對移植物抗宿主病患者的影響。該計劃涵蓋急性和慢性移植物抗宿主病，還將評估各種其他治療方案，例如對該病的預防、未接受治療的患者以及類固醇難治性的患者。

The first pivotal trial of ruxolitinib in graft-versus-host disease, REACH1, is evaluating ruxolitinib in patients with steroid-refractory acute graft-versus-host disease and is expected to read out next year.

魯索替尼治療移植物抗宿主病的第一個關鍵試驗 REACH1 正在評估魯索替尼在類固醇難治性急性移植物抗宿主病患者中的作用，預計將於明年公佈。

The GRAVITAS-301 study was recently initiated and will evaluate itacitinib in patients with treatment-naïve acute graft-versus-host disease.

GRAVITAS-301 研究最近啟動，將評估伊塔替尼治療初治急性移植物抗宿主病患者的效果。

On Slide 19, I'd like to cover our other 2 late-stage assets. Our selective FGFR1/2/3 inhibitor, '54828, is being evaluated in 2 key programs, one in metastatic bladder cancer and the other in cholangiocarcinoma. These studies are recruiting well.

在幻燈片 19 上，我想介紹一下我們的另外 2 個後期資產。我們的選擇性 FGFR1/2/3 抑製劑“54828”正在兩個關鍵項目中進行評估，一個用於轉移性膀胱癌，另一個用於膽管癌。這些研究招募情況良好。

Our highly selective PI3 kinase delta inhibitor, '50465, is being studied in a broad program which includes trials for a number of non-Hodgkin lymphomas. Our program is additionally investigating dose and scheduling to maintain efficacy while hopefully ameliorating toxicity.

我們的高選擇性 PI3 激酶 δ 抑製劑“50465”正在一項廣泛的計劃中進行研究，其中包括針對多種非霍奇金淋巴瘤的試驗。我們的計劃還在研究劑量和時間安排，以保持療效，同時希望改善毒性。

On Slide 20, I'll discuss some highlights from our upcoming news flow. As I've already mentioned, the additional Phase III studies with pembro and nivo are on track to begin by the end of this year. Also expected by the end of this year will be the first-in-man data from our lead BRD inhibitor, which will highlight the data we used to determine to prioritize development of '57643 over '54329. First-in-man data from our PIM inhibitor, '53914, is also expected later this year.

在幻燈片 20 上，我將討論即將發布的新聞流中的一些要點。正如我已經提到的，有關 pembro 和 nivo 的額外 III 期研究有望在今年年底開始。預計到今年年底，我們的主要 BRD 抑製劑將獲得首次人體數據，這將突出顯示我們用來確定優先開發“57643”而不是“54329”的數據。我們的 PIM 抑製劑“53914”的首次人體數據預計也將於今年晚些時候獲得。

Heading into the first half of 2018, we are looking forward to the results of the ECHO-301 study as well as the results from REACH1, our pivotal study of rux in patients with steroid-refractory acute graft-versus-host disease.

進入2018年上半年，我們期待ECHO-301研究的結果以及REACH1的結果，REACH1是我們對類固醇難治性急性移植物抗宿主病患者進行rux的關鍵研究。

Lastly and following the new go-forward decision with AstraZeneca, we expect to initiate a Phase III study of epacadostat in combination with durva for the treatment of lung cancer patients in the first half of 2018.

最後，在與阿斯利康做出新的推進決定後，我們預計將在 2018 年上半年啟動 epacadostat 聯合 durva 治療肺癌患者的 III 期研究。

We've made significant advances in the clinic so far in 2017, and we have ambitious goals as we head into next year. We look forward to keeping you updated on our progress.

2017 年迄今為止，我們在臨床方面取得了重大進展，並且在進入明年時我們制定了雄心勃勃的目標。我們期待向您通報我們的最新進展。

With that, I'll pass the call to Dave for the financial update.

這樣，我會將電話轉給戴夫，了解最新的財務情況。

Thanks, Steven, and good morning, everyone. Our financial performance for the third quarter was very strong. We recorded $382 million of total revenue. This was comprised of $304 million in Jakafi net product revenue, $18 million in Iclusig net product revenue, $41 million in Jakavi royalties from Novartis and $3 million of Olumiant royalties from Lilly. In addition, we recorded a $15 million milestone related to the approval of Olumiant in Japan as contract revenue.

謝謝史蒂文，大家早上好。我們第三季度的財務業績非常強勁。我們的總收入為 3.82 億美元。其中包括 3.04 億美元的 Jakafi 產品淨收入、1800 萬美元的 Iclusig 產品淨收入、諾華公司的 4100 萬美元 Jakavi 特許權使用費和禮來公司的 300 萬美元 Olumiant 特許權使用費。此外，我們還創下了與日本批准 Olumiant 相關的 1500 萬美元合同收入里程碑。

Jakafi's net product revenue of $304 million represents 36% growth over the same period last year. Based on Jakafi's performance for the first 9 months of the year, we are increasing our full year Jakafi net product revenue guidance to a range of $1.125 billion to $1.135 billion.

Jakafi 的產品淨收入為 3.04 億美元，比去年同期增長 36%。根據 Jakafi 今年前 9 個月的業績，我們將 Jakafi 全年淨產品收入指導提高至 11.25 億美元至 11.35 億美元。

Our gross to net adjustment for the third quarter was approximately 12%. We expect that the total gross to net adjustment for the full year to be approximately 13%.

我們第三季度的毛淨調整約為 12%。我們預計全年毛淨調整總額約為 13%。

Our cost of product revenue for the quarter was $22 million. This includes the cost of goods sold for Jakafi and Iclusig, the payment of royalties to Novartis on U.S. Jakafi net sales and the amortization of acquired product rights related to the Iclusig product acquisition in Europe.

本季度我們的產品收入成本為 2200 萬美元。這包括 Jakafi 和 Iclusig 的銷售成本、根據美國 Jakafi 淨銷售額向諾華支付的特許權使用費以及與在歐洲收購 Iclusig 產品相關的產品權利的攤銷。

Our R&D expense for the quarter was $270 million, including $23 million in noncash stock compensation and a $12 million in-process research and development asset impairment charge due to the discontinuation of Iclusig second-line CML trial that began prior to the acquisition of the European ARIAD operations in 2016. The remaining increase in R&D expense over the previous quarter was driven by continued progress on epacadostat Phase III studies, the advancement of ruxolitinib GVHD studies and the expansion of studies in our large molecule programs. For the full year, we expect R&D expense to be in the range of $1.250 billion to $1.3 billion, of which approximately $360 million is related to the amended Agenus collaboration and the Merus, Calithera and MacroGenics collaborations. The increase in R&D expense guidance over the prior quarter is primarily related to the $150 million upfront payment under the recently announced license agreement with MacroGenics.

我們本季度的研發費用為 2.7 億美元，其中包括 2300 萬美元的非現金股票補償以及由於在收購歐洲公司之前開始的 Iclusig 二線 CML 試驗中止而產生的 1200 萬美元的正在進行的研發資產減值費用。 2016 年 ARIAD 運營情況。與上一季度相比，研發費用的剩餘增長是由 epacadostat III 期研究的持續進展、魯索替尼 GVHD 研究的進展以及我們的大分子項目研究的擴展所推動的。我們預計全年研發費用將在 12.5 億美元至 13 億美元之間，其中約 3.6 億美元與修訂後的 Agenus 合作以及 Merus、Calithera 和 MacroGenics 合作有關。研發費用指導較上一季度增加主要與根據最近宣布的與 MacroGenics 的許可協議支付的 1.5 億美元預付款有關。

Our SG&A expense for the quarter was $91 million, including $12 million in nonstock cash compensation.

本季度我們的 SG&A 費用為 9100 萬美元，其中包括 1200 萬美元的非股票現金補償。

We recorded a $16 million net benefit related to the change in the fair market value of the contingent consideration for the Iclusig royalty liability. This net benefit included $8 million of recurring expense related to the change in the fair market value of the contingent consideration for the Iclusig royalty liability and a $24 million benefit related to the discontinued Iclusig second-line CML trial, as previously mentioned. As a result, we expect full year expense related to the change in fair market value contingent consideration for the Iclusig royalty liability to be in the range of $5 million to $7 million. This is a decrease in expense from the previous guidance last quarter.

我們記錄了與 Iclusig 特許權使用費負債的或有對價的公平市場價值變化相關的 1600 萬美元淨收益。如前所述，該淨收益包括與 Iclusig 特許權使用費負債或有對價的公平市場價值變化相關的 800 萬美元經常性費用，以及與已終止的 Iclusig 二線 CML 試驗相關的 2400 萬美元收益。因此，我們預計全年與 Iclusig 特許權使用費負債的公平市場價值或有對價變化相關的費用將在 500 萬美元至 700 萬美元之間。與上季度之前的指導相比，費用有所減少。

Moving on to nonoperating expenses. We recorded a $23 million unrealized gain on our long-term investments in Merus and Agenus during the quarter.

繼續討論非營業費用。本季度我們對 Merus 和 Agenus 的長期投資獲得了 2300 萬美元的未實現收益。

Looking at the balance sheet. We ended the third quarter with $1.3 billion in cash and marketable securities and expect to end the year with over $1.1 billion. The increase in cash and marketable securities compared to the prior quarter is primarily related to the recent public offering of approximately 5 million shares of our common stock, resulting in net proceeds for the company of approximately $650 million.

看資產負債表。第三季度末，我們擁有 13 億美元的現金和有價證券，預計年底將超過 11 億美元。與上一季度相比，現金和有價證券的增加主要與最近公開發行約 500 萬股普通股有關，這為公司帶來了約 6.5 億美元的淨收益。

On the final slide, you'll see our full-year guidance. Incorporating all the previously discussed changes, we now expect a net loss between $290 million and $300 million for the year. Subtracting the upfront and milestone expenses of approximately $360 million related to the amended Agenus collaboration and the Merus, Calithera and MacroGenics collaborations, our forecasted results for the full year 2017 would be net income of $60 million to $70 million.

在最後一張幻燈片上，您將看到我們的全年指導。考慮到之前討論的所有變化，我們現在預計今年的淨虧損在 2.9 億美元至 3 億美元之間。扣除與修訂後的 Agenus 合作以及 Merus、Calithera 和 MacroGenics 合作相關的約 3.6 億美元的前期和里程碑費用，我們預測 2017 年全年淨利潤將為 6,000 萬至 7,000 萬美元。

To summarize, we are very pleased with our third quarter performance. We exceeded $1 billion in total revenue year-to-date. Our clinical development programs are advancing as planned. We continue to add to our development pipeline, and we have a strong balance sheet to support our continued growth for the long term.

總而言之，我們對第三季度的業績非常滿意。今年迄今為止，我們的總收入已超過 10 億美元。我們的臨床開發項目正在按計劃推進。我們不斷增加我們的開發渠道，我們擁有強大的資產負債表來支持我們的長期持續增長。

Operator, that concludes our prepared remarks. Please give your instructions and open up the call for Q&A.

接線員，我們準備好的發言到此結束。請給出您的指示並撥打電話進行問答。

(Operator Instructions) Our first question comes from Cory Kasimov with JPMorgan Chase & Co.

（操作員指令）我們的第一個問題來自摩根大通公司的 Cory Kasimov。

So I have 2 for you. I guess the first is probably for Steven, and it's on the overall strategy for epacadostat in lung cancer now that you've added durvalumab to pembro and nivo in terms of advancing to Phase III, and each seemed to be going after different segments or combinations in the market. And maybe specifically on this front, as it relates to ECHO-306, do you have evidence of additive effects for IDO when added to a PD-1 chemo combo? And then I have one follow-up.

所以我有 2 個給你。我想第一個可能是針對 Steven 的，這是 epacadostat 治療肺癌的總體策略，現在你已經將 durvalumab 添加到 pembro 和 nivo 中，進入 III 期，並且每個似乎都在追求不同的部分或組合在市場上。也許特別是在這方面，因為它與 ECHO-306 相關，您是否有證據表明 IDO 添加到 PD-1 化療組合中時會產生附加效應？然後我有一個後續行動。

Cory, hi it's Steven. Thank you for your question. So obviously, as you well know and others, too, lung cancer incorporates many different settings and different histologies as well. The whole premise behind immunotherapy has always pointed to the fact that its maximum benefit may be in areas of low disease burden or even in the adjuvant setting where you have maybe potentially micrometastatic disease to beat. So our studies encompass the high-expressing PD-L1 population in combination with pembro monotherapy, which is the care standard there. In the low-expressing settings, the chemotherapy combination with pembro is felt to be the care standard. Despite what happened last week with Merck withdrawing the application in Europe based on KEYNOTE-021G subgroup, we've always felt that the KEYNOTE-189 data was going to be the gating event. That data will report out way before our study finishes. And so we obviously incorporate in a Phase III study in combination there but also exploring a chemotherapy-free option as well. So there're 3 arms in that particular study. If you're asking me, do we have efficacy data in combination with chemotherapy that has enabled us, we have ongoing work looking primarily at the safety with chemotherapy combinations. And no -- and we have not presented efficacy data with that particular combination yet. In the adjuvant to early setting, the stage 3 non-small cell lung cancer setting building on PACIFIC data, which is post-chemotherapy radiation combination therapy for patients who are either in a complete remission, partial remission or stable disease, obviously, the durva data in PACIFIC was highly encouraging for a progression-free survival/ disease-free survival benefit. And this is again where immunotherapy, as I said upfront, is felt to potentially work best. And that is what we exploring there - the combination versus durva alone. Overarching everything that I'm saying is that our tolerability profile, as you know - we've presented now on a number of occasions with exposure data that now exceeds a year- we're very comfortable in our tolerability profile. And again, should there be the efficacy we want then the adjuvant setting would be a real win to have that sort of tolerability profile. That's our current strategy across lung cancer. We have not yet announced our BMS plans publicly.

科里，嗨，我是史蒂文。謝謝你的問題。顯然，正如您和其他人所知，肺癌也包含許多不同的環境和不同的組織學。免疫療法背後的整個前提始終指出這樣一個事實，即其最大益處可能是在疾病負擔低的領域，甚至是在可能需要戰勝潛在微轉移性疾病的輔助環境中。因此，我們的研究涵蓋了高表達 PD-L1 群體與 pembro 單一療法的結合，這是那裡的護理標準。在低表達環境中，化療與 pembro 組合被認為是護理標準。儘管上週默克公司撤回了基於 KEYNOTE-021G 亞組的歐洲申請，但我們始終認為 KEYNOTE-189 數據將成為門控事件。這些數據將在我們的研究結束之前報告出來。因此，我們顯然將聯合進行 III 期研究，同時也在探索免化療的選擇。因此，該特定研究有 3 個組。如果您問我，我們是否有與化療相結合的療效數據，使我們能夠繼續開展工作，主要關注化療組合的安全性。不，我們還沒有提供該特定組合的功效數據。在早期輔助治療中，基於 PACIFIC 數據的 3 期非小細胞肺癌治療，是針對完全緩解、部分緩解或疾病穩定的患者的化療後放射聯合治療，顯然，durva PACIFIC 的數據對於無進展生存/無病生存獲益非常令人鼓舞。正如我之前所說，這又是免疫療法被認為可能發揮最佳作用的地方。這就是我們在那裡探索的——組合與單獨的 durva。我所說的最重要的是，我們的耐受性概況，如您所知 - 我們現在已經在多個場合提供了超過一年的暴露數據 - 我們對我們的耐受性概況感到非常滿意。再說一次，如果有我們想要的功效，那麼佐劑設置將是真正的勝利，具有這種耐受性。這是我們目前針對肺癌的策略。我們尚未公開宣布我們的 BMS 計劃。

Okay. And then the second question is for probably Hervé or maybe Steven as well. Can you just discuss the strategic thinking behind the MacroGenics collaboration for their PD-1 inhibitor? What was the primary driving force behind doing this deal?

好的。第二個問題可能是針對 Hervé 或 Steven 的。您能否簡單討論一下 MacroGenics 合作開發 PD-1 抑製劑背後的戰略思維？完成這筆交易的主要推動力是什麼？

Okay. So maybe a step back on the immuno-oncology. What we have seen over the past few years is really the establishment of single-agent PD-1 in multiple indications across multiple tumor types across many different companies, in fact. And that has been very steady. It has been making progress over more or less the past 5 years. If you remember, CTLA-4 was the first mechanism and then PD-1 more or less took the position of being the single-agent leader in multiple indications. What we believe, and that's shared by many, many people, is that the next wave, the next frontier for everybody is how do we establish IO/IO combinations either with or without chemotherapy, by the way. But how do we find a good combination that will improve the profile of PD-1 alone? We know in that field, the only existing combination is CTLA-4 and PD-1. And obviously, with our epacadostat PD-1, we are also trying to establish that across a number of indications. So what we see in front of us is a new effort, a new wave of clinical tests that will be trying to establish combinations of PD-1 plus other product. And as you saw on the slide we showed a little bit earlier, we have 7 of them already in the clinic. It includes very different hypotheses from the scientific standpoint. So some of them are large molecules, like GITR and OX40. Some of them are small molecules like arginase, JAK, PI3 kinase delta, epacadostat. And what we were looking at is saying as we are backing into this new wave of studies, what we would like is to be able to do it with our own PD-1. We have ongoing studies with pembro and nivo with all of these products. And with this deal, what we will be able to do is initiate in 2018 combination study with each of these 7 mechanisms. And then based on what we learn from the biology and the existing data, we'll be able to move this program to the next step of pivotal study after we have established that. So what it gives us is flexibility. It gives us speed. In fact, there's an economic benefit of doing it with your own PD-1 and it could potentially also be beneficial -- in fact, it certainly will be beneficial to the top line by having an additional product to our portfolio and amortizing the cost of development across 2 products instead of 1. So that was what was driving us. It's not very different from what we discussed over the past 2 years. But this opportunity came up, and we think it's a good product and we will be able to move quickly to combination trial in '18.

好的。因此，免疫腫瘤學或許可以退一步。事實上，過去幾年我們所看到的實際上是許多不同公司在多種腫瘤類型的多種適應症中建立了單藥 PD-1。而且這種情況一直非常穩定。在過去的五年裡，它或多或少地取得了進展。如果您還記得的話，CTLA-4 是第一個機制，然後 PD-1 或​​多或少地佔據了多種適應症中單藥領導者的地位。我們相信，並且得到許多人的認同，下一波浪潮，每個人的下一個前沿是我們如何建立 IO/IO 組合，無論有或沒有化療，順便說一下。但我們如何找到一個好的組合來單獨改善 PD-1 的特性呢？我們知道，在該領域，唯一現有的組合是 CTLA-4 和 PD-1。顯然，通過我們的 epacadostat PD-1，我們也在嘗試在多種適應症中建立這一點。因此，我們面前看到的是一項新的努力，一波新的臨床測試浪潮，將試圖建立 PD-1 與其他產品的組合。正如您在我們之前展示的幻燈片中看到的那樣，我們已經在診所中有 7 個這樣的患者。它包括從科學角度來看非常不同的假設。所以其中一些是大分子，例如 GITR 和 OX40。其中一些是小分子，如精氨酸酶、JAK、PI3 激酶 δ、epacadostat。我們正在關注的是，當我們支持這一新的研究浪潮時，我們希望能夠用我們自己的 PD-1 來做到這一點。我們正在對 pembro 和 nivo 的所有這些產品進行研究。通過這筆交易，我們將能夠在 2018 年啟動這 7 種機制的組合研究。然後，根據我們從生物學和現有數據中學到的知識，在我們確定這一點後，我們將能夠將該計劃轉移到關鍵研究的下一步。所以它給我們帶來的是靈活性。它給了我們速度。事實上，用您自己的 PD-1 來做這件事會帶來經濟利益，而且也可能是有益的——事實上，通過在我們的產品組合中添加額外的產品並攤銷成本，它肯定會對營收有利。跨 2 個產品而不是 1 個產品進行開發。這就是我們的動力。這與我們過去兩年討論的內容沒有太大不同。但這個機會來了，我們認為這是一個很好的產品，我們將能夠在 18 年迅速進入組合試驗。

Our next question comes from Geoff Meacham with Barclays.

我們的下一個問題來自巴克萊銀行的傑夫·米查姆。

I have a couple, I think, for either Steve or Reid. So the first one is on epacadostat. I know small numbers based on your Phase II, but I want to get your perspective on the opportunity in PD-L1 negative patients or minimal expressors, especially as you ramp up Phase III combo studies outside of melanoma. And then on rux in GVHD, I know data coming up next year for REACH1, but maybe what would you point to in doing this indication as a clinically meaningful result, either response rate or duration of response? And how is this different between the chronic and the acute setting?

我想，我有兩個適合史蒂夫或里德的。所以第一個是 epacadostat。我知道基於您的 II 期研究的少量數據，但我想了解您對 PD-L1 陰性患者或最小表達者的機會的看法，特別是當您在黑色素瘤之外加強 III 期組合研究時。然後關於 GVHD 中的 rux，我知道明年將有 REACH1 的數據，但也許您會指出將這一適應症作為具有臨床意義的結果，是反應率還是反應持續時間？慢性和急性環境有何不同？

Geoff, it's Steven, thanks for your question. In terms of your question related to epacadostat and our Phase II data in both PD-L1 positive patients and PD-L1 negative -- and again, we need to be careful in general in terms of which test we're using, whether it's Merck or BMS, and what cutoffs we're using. So that's just as a general caveat. Obviously, to date, we have presented data in both those populations across multiple tumors. We have some intriguing albeit low numbers to date responses in PD-L1 negatives. And we have PD-L1 unknown data, which may include both. And so I think the jury is still out on whether we'll be able to further enhance the effect in low expressors in PD-L1 negatives and get T cells to do what they need to do there. But that's being tested across the programs, including, as you said, in melanoma where there's no selection upfront. There's merely stratification after the fact. And we expect the vast majority of patients with melanoma to be PD-L1 high or positive. In lung cancer, as we've outlined in the things we put out publicly to date, there's selection upfront in both those populations. And the question being answered at least in the ECHO-306 is also in combination with chemotherapy. But all we can point to, to date is the data we've shown publicly with some intriguing responses in the negatives. In terms of rux in graft-versus-host disease and across the populations, it's a little bit different for acute versus chronic in terms of what's considered clinically meaningful benefit as well as regulatory benefit. But for REACH1, there's an established primary endpoint of a day 28 response rate, which is defined by -- internationally defined bone marrow criteria, which will look at that response data. But it has to be coupled with durability of response as well. So in the shorter settings, in the acute setting, you look, for example, at 3-month durability of response data coupled with the primary day 28 response rates. In the chronic setting, you look a little bit further out upwards of 6 months. And it's really the combination of both response as well as the duration of response for both those settings.

傑夫，我是史蒂文，謝謝你的提問。就您與 epacadostat 相關的問題以及我們在 PD-L1 陽性和 PD-L1 陰性患者中的 II 期數據而言，我們需要謹慎對待我們使用的測試，無論是默克公司的測試或 BMS，以及我們使用的截止值。所以這只是一般性的警告。顯然，迄今為止，我們已經提供了這兩個人群在多個腫瘤中的數據。迄今為止，我們有一些有趣的 PD-L1 陰性反應，儘管數量很少。我們有 PD-L1 未知數據，可能包括兩者。因此，我認為我們是否能夠進一步增強 PD-L1 陰性低表達細胞的效果並讓 T 細胞做它們需要做的事情，目前還沒有定論。但這正在跨項目進行測試，包括，正如你所說，在黑色素瘤中沒有預先選擇。事後僅存在分層。我們預計絕大多數黑色素瘤患者的 PD-L1 水平較高或呈陽性。在肺癌方面，正如我們在迄今為止公開發布的內容中概述的那樣，這兩個人群都存在預先選擇。至少在 ECHO-306 中回答的問題也是與化療相結合。但迄今為止，我們所能指出的只是我們公開展示的數據，以及一些有趣的負面回應。就移植物抗宿主病和整個人群的 rux 而言，急性與慢性疾病在臨床上有意義的益處以及監管益處方面略有不同。但對於 REACH1，有一個既定的主要終點，即第 28 天的反應率，該終點由國際定義的骨髓標准定義，該標準將查看該反應數據。但它還必須與響應的持久性相結合。因此，在較短的設置中，在緊急設置中，您會查看響應數據的 3 個月持久性以及主要第 28 天的響應率。在慢性環境中，您需要考慮 6 個月以上的時間。它實際上是這兩種設置的響應以及響應持續時間的組合。

Our next question comes from Eric Schmidt with Cowen and Company.

我們的下一個問題來自 Cowen and Company 的 Eric Sc​​hmidt。

Maybe another one for Steven. It seems like there's increased interest in moving I/O into the adjuvant setting, and I'm wondering if it's too early to talk about epacadostat in such a role and whether you're planning such trials.

也許史蒂文還有另一件事。似乎人們對將 I/O 轉移到佐劑環境中的興趣越來越大，我想知道現在談論 epacadostat 的這種作用是否還為時過早，以及您是否正在計劃此類試驗。

Yes. Eric, it's Steven. As I said upfront, in the adjuvant setting, what you're doing in those patients in that population is treating potential disease that you can't see, so micrometastatic disease, to try and increase cure rates. In those settings, it's where, in general, immunotherapy-based approaches are felt to be potentially most beneficial. So you see now reported out adjuvant melanoma studies with different checkpoint and checkpoint plus CTLA-4 combinations showing benefit already. So the next thing to do is in melanoma, if the ECHO-301 data points to it, is to test epacadostat in combination with checkpoint in adjuvant melanoma. And what you're seeing us doing in the lung cancer setting is trying to build on the durva data in a stage 3 non-small cell lung cancer setting, which is a much higher risk for relapse. So many of those patients untreated unfortunately will relapse. And you saw the very impressive progression-free and disease-free survival data with durva and now looking at the combination with epacadostat to see if we can further enhance that. And then I'll end by the comment I made earlier. Tolerability is key in an adjuvant population. These patients who are otherwise well, want to get on with their lives and don't, for the most part, want to suffer if they can avoid it any debilitating side effects. So our tolerability profile here is encouraging. Obviously, it has to be coupled with an efficacy win as well.

是的。埃里克，這是史蒂文。正如我之前所說，在輔助治療中，您對該人群中的患者所做的就是治療您看不到的潛在疾病，例如微轉移性疾病，以嘗試提高治愈率。在這些情況下，一般來說，基於免疫療法的方法被認為可能是最有益的。因此，您現在看到報導的不同檢查點和檢查點加 CTLA-4 組合的輔助黑色素瘤研究已經顯示出益處。因此，接下來要做的是在黑色素瘤中，如果 ECHO-301 數據表明這一點，那就是在輔助性黑色素瘤中測試 epacadostat 與檢查點的結合。您看到我們在肺癌治療中所做的就是嘗試在 3 期非小細胞肺癌治療中建立 durva 數據，該癌症的複發風險要高得多。不幸的是，許多未經治療的患者將會復發。您看到了 durva 令人印象深刻的無進展和無疾病生存數據，現在正在研究與 epacadostat 的組合，看看我們是否可以進一步增強這一點。然後我將以我之前發表的評論結束。耐受性是佐劑群體的關鍵。這些患者在其他方面都很好，希望繼續生活，並且在大多數情況下，如果可以避免任何使人衰弱的副作用，他們就不想遭受痛苦。因此，我們的耐受性狀況令人鼓舞。顯然，它還必須與效率的勝利相結合。

Our next question comes from Salveen Richter with Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

With regard to the pipeline, can you provide us with the clinical rationale here for this JAK1 plus osimertinib combination study? And then when should we expect the pivotal FIGHT and CITADEL programs to read out?

關於管道，您能否向我們提供這項 JAK1 加奧希替尼聯合研究的臨床原理？那麼我們應該什麼時候才能看到關鍵的《FIGHT》和《CITADEL》節目呢？

So It's Steven. I'll start. If you look at EGFR inhibitor therapy in lung cancer in general and now this -- the newer generation EGFR inhibitors like osimertinib with their enhanced efficacy post-upfront EGFR therapy and potentially in earlier line setting, one of the potential mechanisms of resistance is up-regulation of the JAK-STAT pathway during therapy with those EGFR inhibitors. So it's looking at the addition of JAK to osimertinib in that setting to see if we can avert the development of resistance and thus improve clinical outcomes, namely time to event outcomes. I think your second question was related to timelines to pivotal data from the CITADEL and the FIGHT programs, is that correct? I'll address that and then you can correct me afterwards. So those are underway at the moment. The FIGHT program is our FGFR 1/2/3 inhibitor looking at 3 different settings, metastatic bladder cancer, cholangiocarcinoma and a rare myeloproliferative neoplasm. All of those entities are driven by genetic mutations involving the FGFR pathway that are oncogenic and felt to drive those diseases. In the bladder setting, it's FGFR3. In cholangio, it's FGFR1. And then the myeloproliferative neoplasm, it's an 8p11 translocation. Those studies are ongoing. They're enrolling really, really well. Despite needing genetic selection, we've been really encouraged by the enrollment. And we should be getting data over the ensuing 24 months. For the CITADEL program in general, that's our PI3 kinase delta inhibitor across different non-Hodgkin lymphomas, diffuse large B-cell, mantle, marginal and follicular lymphomas. That program is looking at trying to avert toxicity by changing dosing schedule over time. And that is also -- we'll be enrolling patients over the ensuing 24 months. So it's a little early to speak about when we will be seeing pivotal data on those.

所以是史蒂文.我開始吧。如果您總體上觀察肺癌中的 EGFR 抑製劑治療，那麼新一代 EGFR 抑製劑（例如奧西替尼）在前期 EGFR 治療後以及可能在早期治療中的療效增強，並且可能在早期治療中發揮作用，潛在的耐藥機制之一是： EGFR 抑製劑治療期間 JAK-STAT 通路的調節。因此，我們正在研究在這種情況下將 JAK 添加到奧西替尼中，看看我們是否可以避免耐藥性的發展，從而改善臨床結果，即事件發生時間結果。我認為你的第二個問題與 CITADEL 和 FIGHT 計劃的關鍵數據的時間表有關，對嗎？我會解決這個問題，然後你可以糾正我。所以這些目前正在進行中。FIGHT 項目是我們的 FGFR 1/2/3 抑製劑，針對 3 種不同的情況：轉移性膀胱癌、膽管癌和罕見的骨髓增生性腫瘤。所有這些實體都是由涉及 FGFR 通路的基因突變驅動的，這些突變具有致癌性，並且被認為會導致這些疾病。在膀胱環境中，它是 FGFR3。在膽管中，它是 FGFR1。然後是骨髓增生性腫瘤，它是 8p11 易位。這些研究正在進行中。他們的報名情況非常非常好。儘管需要基因選擇，但我們對入學感到非常鼓舞。我們應該會獲得接下來 24 個月的數據。對於一般的 CITADEL 項目，這是我們針對不同非霍奇金淋巴瘤、瀰漫性大 B 細胞、套膜、邊緣和濾泡性淋巴瘤的 PI3 激酶 δ 抑製劑。該計劃正在考慮通過隨著時間的推移改變給藥方案來避免毒性。我們還將在接下來的 24 個月內招募患者。因此，現在談論我們何時會看到這些方面的關鍵數據還為時過早。

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

我們的下一個問題來自美銀美林的黃英。

Specifically, I want to ask about the Phase III ECHO-301 primary analysis. Is it going to be done in all-comers or PD-L1 positive melanoma patients only? And then maybe another one for Steve. Have you guys enrolled any patients with stage 3 non-small cell lung cancer in the ECHO-203 trial in combination with durvalumab?

具體來說，我想詢問 III 期 ECHO-301 初步分析。是否會針對所有患者或僅針對 PD-L1 陽性黑色素瘤患者進行？也許還有史蒂夫的另一份。你們是否在 ECHO-203 試驗中招募了任何 3 期非小細胞肺癌患者與 durvalumab 聯合治療？

Ying, it's Steven. The Phase III ECHO-301 melanoma study is in all-comers. There is stratification for PD-L1 status. So PD-L1 positive and negative is captured upfront, and they'll be balanced between the treatment arms for each of those groups. So both the standard of care arm of pembro and the experimental arm of pembro plus epacadostat will have the same representation proportionally of PD-L1 positives and negatives. So again, just to be clear, it's a stratification factor, but the primary analysis is in everybody. In terms of stage 3 non-small cell lung cancer patients in the program to date, no, we have not enrolled those sorts of patients because of their potential curative nature to date. So our program is focused to date on latter stage patients.

英，是史蒂文。III 期 ECHO-301 黑色素瘤研究已全面展開。PD-L1 狀態存在分層。因此，PD-L1 陽性和陰性數據會被預先捕獲，並且它們將在每個組的治療組之間進行平衡。因此，pembro 的標準護理組和 pembro 加 epacadostat 的實驗組將具有相同比例的 PD-L1 陽性和陰性表示。再次強調，這是一個分層因素，但主要分析是針對每個人的。就迄今為止該計劃中的 3 期非小細胞肺癌患者而言，我們尚未招募此類患者，因為迄今為止它們具有潛在的治愈性質。因此，迄今為止，我們的計劃主要針對晚期患者。

Our next question comes from Brian Abrahams with RBC Capital markets.

我們的下一個問題來自加拿大皇家銀行資本市場的布萊恩·亞伯拉罕斯 (Brian Abrahams)。

A couple of questions on the epacadostat-pembro lung cancer Phase III designs. I guess, I'm just wondering if you could talk about any potential dose ranging you might need to do for the chemo study for the epacadostat PD-1 chemo arm whether you're looking for superiority or non-inferiority for the chemo-free checkpoint IDO arm versus the checkpoint chemo arm. Which epacadostat arm would need to hit to constitute success of that study? And then if you might be able to give us any sense of timelines for potential interim or full data from those recently announced non-small cell lung cancer programs.

關於 epacadostat-pembro 肺癌 III 期設計的幾個問題。我想，我只是想知道您是否可以談談您可能需要為 epacadostat PD-1 化療組進行化療研究的任何潛在劑量範圍，無論您是在尋找免化療藥物的優越性還是非劣效性檢查點 IDO 組與檢查點化療組。需要使用哪一個 epacadostat 臂才能使該研究取得成功？然後，您能否向我們提供有關最近宣布的非小細胞肺癌項目的潛在中期或完整數據的時間表。

So Brian, it's Steven. I'll try and answer all 4 of your questions. So the enabling safety work for the chemotherapy combinations has been going on in the background for months now. The intent is not to have to change dosing at all and use our Phase III doses that we have been using across the program and the ones we have announced to date, all at 100 milligrams b.i.d. So as long as safety stands up to what it's been to date, that's the dose we'll be using in the announced programs, for which we have greater than 80% to 90% inhibition of the enzyme, which we've shown in our Phase I data. Your question 2, all the analyses are superiority in the announced programs to date. All the comparisons are superiority comparisons. There is no non-inferiority comparison in anything we've announced to date. In terms of success, the study is all undertaken with equipoise upfront, looking at a standard of care and then comparator, either one or in the other announced study, ECHO-306, 2 different comparator arms, both looking at superiority. Success will be hitting the endpoint in terms of efficacy that is clinically meaningful and statistically significant for any of those arms, either the chemo-containing or the chemo-free one. And I think in terms of timelines down the pike, it's really too early given that the studies haven't initiated. The aims on the publicly announced ones in terms of the enrollment numbers are there for you on ct.gov (clinicaltrials.gov). And we hope we have the success we had with the melanoma study already in terms of enrollment. And then we'll be waiting for the endpoints. And then -- so you can do your own calculations there in terms of when we may see it, and I think those were all 4 of your questions.

布萊恩，是史蒂文。我會盡力回答您的所有 4 個問題。因此，化療組合的安全工作已經在後台進行了幾個月。目的是完全不必改變劑量，而是使用我們在整個項目中一直使用的 III 期劑量以及我們迄今為止已宣布的劑量，均為 100 毫克，每日兩次。因此，只要安全性符合迄今為止的水平，這就是我們將在已宣布的計劃中使用的劑量，對此我們對酶的抑制率超過 80% 至 90%，我們在我們的研究中已經證明了這一點。第一階段數據。你的問題2，所有的分析都是迄今為止公佈的計劃的優勢。所有的比較都是優勢比較。迄今為止，我們宣布的任何產品都沒有非劣效性比較。就成功而言，這項研究都是在預先平衡的情況下進行的，著眼於護理標準，然後是比較器，無論是一項研究還是另一項已宣布的研究，ECHO-306，2個不同的比較組，都著眼於優越性。對於任何一組（無論是含化療組還是不含化療組）而言，成功將達到具有臨床意義和統計顯著性的療效終點。我認為就時間表而言，考慮到研究尚未啟動，現在還為時過早。您可以在 ct.gov (clinicaltrials.gov) 上找到公開宣布的註冊人數目標。我們希望我們在黑色素瘤研究方面已經在入組方面取得了成功。然後我們將等待端點。然後，你可以自己計算一下我們什麼時候可以看到它，我認為這些都是你的 4 個問題。

Our next question comes from Alethia Young with Credit Suisse.

我們的下一個問題來自瑞士信貸銀行的 Alethia Young。

One, just around the trends you're seeing now that the NCCN Guidelines have changed for PV and just kind of wanted to see kind of how -- do you feel like you're kind of in the midpoint of the education process? Or is there still sufficiently more wood to chop? And the last one is just philosophically on CTLA-4. Do you think there's a need for better CTLA-4? Or is that something you're interested in, in future I/O combinations?

一，圍繞您現在看到的趨勢，NCCN 指南針對 PV 發生了變化，只是想看看如何 - 您是否覺得自己正處於教育過程的中間？或者還有足夠多的木頭可以砍伐嗎？最後一個只是從哲學角度探討 CTLA-4。您認為需要更好的 CTLA-4 嗎？或者這是您對未來 I/O 組合感興趣的東西？

Okay. Alethia, this is Barry. I'll take the first part of your question about the NCCN Guidelines in PV. We continue to grow very nicely in PV. The NCCN Guidelines obviously helped, as we said before, that PV total patients continue to grow faster than MF total patient growth, but both MF and PV total patients continue to grow. The education process continues for PV, but we think it's going very well, and we continue to penetrate the available patient population.

好的。阿萊西亞，這是巴里。我將回答您關於 PV NCCN 指南的問題的第一部分。我們在光伏領域繼續保持良好增長。正如我們之前所說，NCCN 指南顯然有幫助，PV 患者總數的增長速度繼續快於 MF 患者總數的增長，但 MF 和 PV 患者總數都在繼續增長。PV 的教育過程仍在繼續，但我們認為進展非常順利，我們將繼續滲透到可用的患者群體中。

Alethia, this is Reid. I'll take your question on CTLA-4. I think, obviously, with the first-in-class mechanism really that established immune therapy and serves as the foundation for the wave that we're in right now, it's fundamentally limited by its systemic tolerability profile. But clearly, it's an efficacious agent. And when added to backbone checkpoint inhibitor therapy like PD-1, access blockade can be highly active and unfortunately also highly toxic, at least for some patients with irreversible inflammatory conditions. So it's important, I think, for the field that we try to learn from that experience with CTLA-4, and that can come from a few different directions. One is understanding the importance of selecting targets that have a mechanism of action that's constrained to the tumor microenvironment and not necessarily systemically acting drugs. And I think we've seen now a wave of new mechanisms coming into the clinic, which are designed to do just that. Certainly, epacadostat and IDO1 inhibition is one of those mechanisms, but there's many others in our pipeline and in others. I think there's another question as to whether or not we can be better at constraining CTLA-4 activity to the tumor microenvironment through other approaches. Bristol is taking a few different approaches, such as enhancing effector function of the antibody, trying to mask activity and release it only in the tumor microenvironment through another technology within CytomX. There may be bispecific approaches to CTLA-4 that could be interesting as well. There's still a lot we don't know about the basics of why CTLA-4 is active in one cell type it's active in and why its systemic toxicities are the way they are. But I think a lot of these approaches are going to design to determine whether there could be a better CTLA-4 antibody and one that still contains its tumor-directed efficacy but avoids the systemic toxicity. So it's a work in progress, but it's absolutely an important one for the field to continue to study.

阿蕾西亞，這是里德。我將回答你關於 CTLA-4 的問題。我認為，顯然，隨著確實建立了免疫療法並成為我們現在所處的浪潮的基礎的一流機制，它從根本上受到其係統耐受性的限制。但顯然，它是一種有效的藥劑。當添加到像 PD-1 這樣的骨幹檢查點抑製劑療法中時，通路阻斷可能具有高度活性，但不幸的是也具有劇毒，至少對於一些患有不可逆炎症的患者來說是這樣。因此，我認為，對於該領域來說，我們嘗試從 CTLA-4 的經驗中學習非常重要，這可以來自幾個不同的方向。一是了解選擇具有受腫瘤微環境限制的作用機制且不一定具有全身作用的藥物的靶點的重要性。我認為我們現在已經看到一波新機制進入臨床，其目的就是為了做到這一點。當然，epacadostat 和 IDO1 抑制是其中一種機制，但我們的管道和其他管道中還有許多其他機制。我認為還有一個問題是我們是否可以通過其他方法更好地將 CTLA-4 活性限制在腫瘤微環境中。Bristol 正在採取幾種不同的方法，例如增強抗體的效應器功能，嘗試通過 CytomX 內的另一項技術掩蓋活性並僅在腫瘤微環境中釋放抗體。CTLA-4 的雙特異性方法可能也很有趣。關於為什麼 CTLA-4 在它所活躍的一種細胞類型中具有活性以及為什麼它的全身毒性是這樣的，我們還有很多不了解的基礎知識。但我認為，這些方法中的許多方法將被設計來確定是否存在一種更好的 CTLA-4 抗體，並且一種仍然具有腫瘤導向功效但避免全身毒性的抗體。所以這是一項正在進行的工作，但對於該領域繼續研究來說絕對是一項重要的工作。

Our next question comes from Ian Somaiya with BMO Capital Markets.

我們的下一個問題來自 BMO 資本市場的 Ian Somaiya。

Two questions. First on just the MacroGenics PD-1. I'm just trying to understand what the larger goal is. Just given the ongoing studies with PD-1s, whether it's pembro, OPDIVO or now with durva with epacadostat, your goal is obviously to establish a new standard of care, which would also make it more challenging for you to be able to succeed in those settings with the MacroGenics PD-1. And I guess, what I'm trying to understand is, is the goal of the MacroGenics deal to establish simply new triplets? Is that where we should -- how we should be thinking about the future development? And then I have a question on Jakafi.

兩個問題。首先是 MacroGenics PD-1。我只是想了解更大的目標是什麼。鑑於正在進行的 PD-1 研究，無論是 pembro、OPDIVO 還是現在的 durva 和 epacadostat，您的目標顯然是建立新的護理標準，這也將使您在這些方面取得成功更具挑戰性使用 MacroGenics PD-1 進行設置。我想，我想了解的是，MacroGenics 交易的目標只是建立新的三胞胎嗎？這是我們應該如何思考未來的發展嗎？然後我有一個關於賈卡菲的問題。

Okay, let me try to answer the question about PD-1. Epacadostat is not the key driver of the PD-1 agreement. I know it sounds a little bizarre because, obviously, epacadostat will be a potential beneficiary of this, having our own PD-1 in the long run. But the way we were thinking was more the other 6 products we have currently in Phase I combination trial with pembro and nivo and how to make that clinical development faster, economically easier and potentially giving us the economic benefit of having our own PD-1. So that was really -- the key driver was not to have some sort of short-term epacadostat impact but to have an impact on the other 6 products we are now moving through the process. And that could be done by starting the safety studies in 2018. And then where we feel we have information to move forward, we will be able then to get each of these projects moving forward. Concerning epacadostat, obviously, someday there could be a benefit of having our own PD-1. There are 2 scenarios. One of them is that pembro and nivo and durva plus epacadostat are established standard of care in multiple indications. So that would be one where the question is can we do it with our own PD-1 also. But there is something that probably has a far higher probability of success is that we will be also moving through triplets as you were describing, where as we are identifying other combinations that include epacadostat and potentially some of our other products, we will be able to do it with our own PD-1. So there is a strategic aspect, there is a tactical, clinical development aspect, and there is a commercial aspect. And that's why I think it's very important for us to have this product in our own portfolio.

好吧，讓我嘗試回答一下關於PD-1的問題。Epacadostat 不是 PD-1 協議的關鍵驅動因素。我知道這聽起來有點奇怪，因為從長遠來看，epacadostat 將成為我們自己的 PD-1 的潛在受益者。但我們更多的是考慮目前與 pembro 和 nivo 進行 I 期聯合試驗的其他 6 個產品，以及如何使臨床開發更快、經濟上更容易，並有可能為我們帶來擁有自己的 PD-1 的經濟效益。所以這確實是——關鍵驅動因素不是產生某種短期 epacadostat 影響，而是對我們現在正在進行的其他 6 種產品產生影響。這可以通過 2018 年開始安全研究來實現。然後，當我們認為我們有信息可以推進時，我們將能夠推動每個項目的進展。顯然，關於 epacadostat，有一天我們自己的 PD-1 可能會帶來好處。有兩種情況。其中之一是 pembro 和 nivo 以及 durva 加 epacadostat 已成為多種適應症的護理標準。所以問題是我們是否也可以用我們自己的 PD-1 來做到這一點。但有一點成功的可能性可能要高得多，那就是我們也將像您所描述的那樣進行三聯體，當我們正在確定包括 epacadostat 和可能的一些其他產品在內的其他組合時，我們將能夠用我們自己的 PD-1 來做。因此，有戰略方面，有戰術、臨床開發方面，還有商業方面。這就是為什麼我認為將這個產品納入我們自己的產品組合中對我們來說非常重要。

Okay. That's very helpful. And the other question I had on Jakafi and maybe one I've asked before, can you just speak to the line expansion? The investor base -- investors generally are obviously focused -- more focused on company's lead assets and the sustainability of that revenue stream. We appreciate, obviously, lack of near-term competition or any sort of visible competition. But just if you could speak to how you can maintain this revenue stream, what line extension opportunities you're working on and is there any timeline which you could share.

好的。這非常有幫助。我對 Jakafi 的另一個問題也許是我之前問過的，你能談談產品線的擴展嗎？投資者基礎——投資者通常顯然更關注——更關注公司的主導資產和收入流的可持續性。顯然，我們讚賞缺乏近期競爭或任何形式的可見競爭。但如果您能談談如何維持這種收入來源、您正在從事哪些產品線延伸機會以及您是否可以分享任何時間表。

Ian, it's Barry. So I'll just try to expand. So I think we've said before -- we certainly said before that we'll exceed $2 billion in total revenue for Jakafi mostly just with MF and PV and adding in GVHD. When we talk about GVHD as a line extension, we're really talking about acute and chronic GVHD together, right? And then obviously, we have essential thrombocythemia. But we really think the drivers continue to be myelofibrosis and polycythemia vera patients and then add-ons are acute and chronic GVHD and essential thrombocythemia.

伊恩，是巴里。所以我會嘗試擴展。所以我想我們之前說過——我們之前確實說過我們 Jakafi 的總收入將超過 20 億美元，其中大部分只是 MF 和 PV，再加上 GVHD。當我們談論 GVHD 作為產品線延伸時，我們實際上是在一起談論急性和慢性 GVHD，對吧？顯然，我們患有原發性血小板增多症。但我們確實認為驅動因素仍然是骨髓纖維化和真性紅細胞增多症患者，此外還有急性和慢性 GVHD 以及原發性血小板增多症。

Well, Barry, I guess, how do you replace Jakafi when...

好吧，巴里，我想，當……時你如何取代賈卡菲？

Yes, so let me -- and maybe you can -- Reid can help on the mechanism, but we have like basically 2 phases of development where we are trying to improve over Jakafi for both MF and PV and maybe potentially some of the other indications. One of them is working on a combination of mechanisms, and this is already in the clinic where we are testing combination with delta. We are testing some alternative schedule of JAK. A lot of that is already ongoing. On top of that, we are also looking at new mechanisms that could be helping patients with MF and PV, and maybe Reid can speak about some of these collaborations.

是的，所以讓我——也許你可以——Reid 可以在機制上提供幫助，但我們基本上有兩個開發階段，我們正在努力改進 Jakafi 的 MF 和 PV，也許還有其他一些跡象。其中之一正在研究機制的組合，這已經在臨床中進行，我們正在測試與 Delta 的組合。我們正在測試 JAK 的一些替代時間表。其中很多工作已經在進行中。最重要的是，我們還在尋找可以幫助 MF 和 PV 患者的新機制，也許 Reid 可以談論其中一些合作。

Yes. Ian, this is Reid. I think it's an important area for us to continue to innovate in. We're very proud of the efforts that we've done in the MPN space and I think have brought a very important therapy now to patients. But there still are patients that unfortunately don't receive an optimized benefit from the available therapies. And there's still other aspects of benefit that we may be able to achieve with new approaches, new combinations, new therapies. So this is an active subject of research here. Hervé mentioned the doublet studies in myelofibrosis. I'll remind you that really the selection of targets like PIM, delta, BRD and even LSD1 were in part because of their potential activity downstream of the JAK-STAT pathway. And in fact, for every one of those mechanisms I just mentioned, there exists preclinical or translational correlative data that support their potential utility in combination with ruxolitinib. So that will be something that Steven's group will be executing on over the coming months and several years. The delta study is already ongoing. Beyond that, it's an active area of research within Incyte as to how we think differently about myelofibrosis, what do we think about new targets, how do we think about achieving different types of benefit in patients. And that's a very early stage research effort, but it's one that's very important for us to maintain if we're going to continue to have a leadership position in MPNs and continue to drive patient benefits forward. So that's a longer-term endeavor, but it's absolutely one that we, as a company, are very committed to.

是的。伊恩，這是里德。我認為這是我們繼續創新的一個重要領域。我們對在 MPN 領域所做的努力感到非常自豪，我認為現在已經為患者帶來了非常重要的治療方法。但不幸的是，仍然有一些患者沒有從現有療法中獲得最佳益處。通過新方法、新組合、新療法，我們還可以實現其他方面的益處。所以這是這裡的一個活躍的研究課題。Hervé 提到了骨髓纖維化的雙重研究。我要提醒您的是，像 PIM、delta、BRD 甚至 LSD1 這樣的靶點的選擇實際上部分是因為它們在 JAK-STAT 通路下游的潛在活性。事實上，對於我剛才提到的每一種機制，都存在臨床前或轉化相關數據，支持它們與魯索替尼聯合使用的潛在效用。因此，這將是史蒂文團隊將在未來幾個月和幾年內執行的事情。三角洲研究已經在進行中。除此之外，這是 Incyte 內部的一個活躍研究領域，涉及我們如何以不同的方式看待骨髓纖維化，我們如何看待新的目標，我們如何看待為患者實現不同類型的益處。這是一項非常早期的研究工作，但如果我們要繼續在 MPN 領域保持領導地位並繼續推動患者福利向前發展，那麼維持這一研究工作對於我們來說非常重要。因此，這是一項長期的努力，但這絕對是我們作為一家公司非常致力於的目標。

Our next question comes from Katherine Xu with William Blair & Company.

我們的下一個問題來自 William Blair & Company 的 Katherine Xu。

If you could indulge me with three questions. Number one is on the Flexus feud. I'm just wondering whether you could give us an overview and your strategy there and potential scenarios that we could expect. Number two is on the ECHO-302, -305 and -306 studies. I'm just curious about your rationale and basis for designing those studies in terms of powering and others, in particular just based on the evidence that we have so far and then just what gives you the confidence about those designs. And number three, assuming -301 is positive, epacadostat and pembro become the standard of care, what is the next step that you are thinking about taking to take the frontline melanoma cure to a higher level?

如果你能問我三個問題。第一個是 Flexus 之間的不和。我只是想知道您能否向我們介紹一下您的概述、您的策略以及我們可以預期的潛在場景。第二個是 ECHO-302、-305 和 -306 研究。我只是好奇你在供電和其他方面設計這些研究的基本原理和基礎，特別是基於我們迄今為止所掌握的證據，以及是什麼讓你對這些設計充滿信心。第三，假設 -301 呈陽性，epacadostat 和 pembro 成為護理標準，您考慮採取的下一步是什麼，將一線黑色素瘤治療提升到更高水平？

So let me start with Flexus, it will be short, but there are obviously public documents that are available. We had press coverage, which was surprising, coming last -- in the last days or last week we were -- I'm not sure exactly why it came at that point, but we cannot comment further. So I think the best is to refer to the existing publicly available documents.

讓我從 Flexus 開始，它會很短，但顯然有可用的公共文檔。我們有新聞報導，這令人驚訝，是最後發生的——在最後幾天或上週——我不確定為什麼會在那時發生，但我們不能進一步發表評論。所以我認為最好是參考現有的公開文件。

And then Katherine, in terms of your second and third question. Your second one mentions ECHO-302, -305 and -306. The renal cell study is looking at a combination of PD-1 plus IDO, beating the current care standard of a VEGF inhibitor based, tyrosine kinase inhibitor, so either Sutent or Votrient. We needed to execute that study briskly because it's an evolving care standard there. We have data from our own program in combination with Merck in ECHO-202 that's already been presented that enabled that decision to be made. In terms of ECHO-305 and ECHO-306, the lung cancer studies, again, the enabling data comes from ECHO-202's lung program in general. It's the PD-L1 high. And again, looking at the combo versus PD-1 alone in the high expressors and then in the all-comers are looking at the care standard of triplet-based therapy -- excuse me, PD-1 plus chemotherapy and then comparing the triplet, PD-1 plus IDO plus chemo, versus PD-1 plus IDO alone. The somewhat controversial area there is the withdrawal in Europe of that application, but that has not impacted our design, and their KEYNOTE-189 study will report out before the study finishes. So we remain confident. We do not address powering of our program at all or those design characteristics publicly. We view that as proprietary information between us and Merck, which we use to design the program, but we don't put that out publicly. If ECHO-301 is positive in melanoma, that would be the care standard there. As I mentioned earlier, the natural next place to go, to address your question, to enhance cure rates is the adjuvant setting to look at the combination in an adjuvant population to increase disease-free survival and overall survival. And that would be the intent after that study.

然後是凱瑟琳，關於你的第二個問題和第三個問題。您的第二個提到了 ECHO-302、-305 和 -306。腎細胞研究正在研究 PD-1 與 IDO 的組合，超越目前基於 VEGF 抑製劑的酪氨酸激酶抑製劑（即 Sutent 或 Votrient）的治療標準。我們需要迅速執行這項研究，因為這是一個不斷發展的護理標準。我們從我們自己的項目以及默克在 ECHO-202 中獲得的數據已經提供，使得我們能夠做出這個決定。就肺癌研究 ECHO-305 和 ECHO-306 而言，支持數據總體上來自 ECHO-202 的肺部項目。這是 PD-L1 高值。再說一次，在高表達者中觀察組合療法與單獨的 PD-1 的比較，然後在所有參與者中觀察基於三聯療法的護理標準——對不起，PD-1 加化療，然後比較三聯療法， PD-1 加 IDO 加化療，與單獨 PD-1 加 IDO 比較。存在爭議的領域是歐洲撤回了該申請，但這並沒有影響我們的設計，他們的 KEYNOTE-189 研究將在研究結束之前報告。所以我們依然充滿信心。我們根本不公開討論我們程序的供電或這些設計特徵。我們認為這是我們和默克之間的專有信息，我們用它來設計該程序，但我們不會公開發布。如果 ECHO-301 在黑色素瘤中呈陽性，這將是那裡的護理標準。正如我之前提到的，為了解決您的問題，為了提高治愈率，下一個自然要去的地方是佐劑設置，以觀察佐劑群體中的組合以增加無病生存率和總體生存率。這就是該研究之後的意圖。

Our next question comes from Carter Gould with UBS.

我們的下一個問題來自瑞銀集團的卡特·古爾德。

I guess one for Hervé and maybe Steven. On the strategy for OX40, GITR and, I guess, with the next wave of I/O assets, is the message really that we should only expect pivotals with your own PD-1? Could we still see pivotals with other approved PD-1s? Just want to be -- I guess, it's a clarifying question there. And then also when you just think about the MacroGenics PD-1, any reason to think that you might still move that forward as a monotherapy either for regulatory or strategic purposes as you broaden out the indications you might go after?

我猜想埃爾維也可能是史蒂文。關於 OX40、GITR 以及我猜的下一波 I/O 資產的策略，信息真的是我們應該只期待您自己的 PD-1 的關鍵嗎？我們還能看到其他已批准的 PD-1 的關鍵作用嗎？只是想——我想，這是一個需要澄清的問題。然後，當您考慮 MacroGenics PD-1 時，當您擴大您可能追求的適應症時，有什麼理由認為您仍然可能出於監管或戰略目的將其作為單一療法推進？

Yes, maybe I'll start on the -- I think -- obviously, as I said, I mean, the goal is to get this combination done with products from our own portfolio. So you should expect if we go in pivotal study with a PD-1 with OX40 or GITR or any other products in the I/O portfolio to see that include an '012 plus that product in the pivotal studies. Would it be only with our own PD-1? It will depend highly on the indication we will be pursuing because, as I said, in some of these indication, pembro or nivo or durva PDL-1 inhibitors could be the standard of care. But obviously, at the end of the day, we want that pivotal program to include '012 plus GITR or '012 plus OX40 or plus arginase, et cetera, et cetera. So that would be the way to think about it. In terms of monotherapy, obviously, you know there are indications where there is the option to receive an indication in monotherapy for PD-1. It could be either of the so-called niche approach, which we have heard a lot from many different companies. So that could -- that is an option so we are looking at that as a possibility or it could be frankly in a less niche indication where we would be trying to establish it as a single agent across a larger indication. We don't know that yet. So what we are doing in the short term are 2 things. It's the so-called niche approach with a single agent, '012. And as I described, we will be initiating a number of combination studies in 2018 so that we can be prepared for the next step in combination with our portfolio.

是的，也許我會開始——我想——顯然，正如我所說，我的意思是，目標是用我們自己的產品組合中的產品來完成這種組合。因此，如果我們對帶有 OX40 或 GITR 的 PD-1 或​​ I/O 產品組合中的任何其他產品進行關鍵研究，您應該會看到在關鍵研究中包括 '012 加上該產品。難道只能用我們自己的PD-1嗎？這將在很大程度上取決於我們將尋求的適應症，因為正如我所說，在其中一些適應症中，pembro 或 nivo 或 durva PDL-1 抑製劑可能是標準治療。但顯然，歸根結底，我們希望該關鍵計劃包括“012 加 GITR”或“012 加 OX40 或加精氨酸酶”，等等。所以這就是思考這個問題的方式。就單一療法而言，顯然，您知道有跡象表明可以選擇接受 PD-1 單一療法的適應症。這可能是所謂的利基方法中的一種，我們從許多不同的公司那裡聽到過很多這種方法。因此，這是一個選擇，因此我們正在將其視為一種可能性，或者坦率地說，它可能是在一個不太利基的適應症中，我們將嘗試將其建立為跨更大適應症的單一藥物。我們還不知道這一點。所以我們短期內要做的有兩件事。這就是所謂的單一代理“012”的利基方法。正如我所描述的，我們將在 2018 年啟動多項組合研究，以便我們能夠結合我們的產品組合為下一步做好準備。

And our final question comes from Michael Schmidt with Leerink.

我們的最後一個問題來自 Leerink 的 Michael Schmidt。

A couple of quick ones. Number one on ECHO-301. What is the number of events needed to trigger unblinding of the study? And number two, maybe for Reid, can you comment on how important potential differences are among the various IDO inhibitors in development in terms of the PK, PD profile and whether -- or how that might translate into differentiated clinical profiles?

幾個快速的。ECHO-301 上排名第一。觸發研究揭盲所需的事件數量是多少？第二，也許對 Reid 來說，您能否評論一下正在開發的各種 IDO 抑製劑在 PK、PD 方面的潛在差異有多麼重要，以及是否或如何轉化為差異化的臨床特徵？

Michael, it's Steven. Just quickly upfront, we do not disclose the event number that would be -- would trigger the ultimate unblinding. So that's not public information.

邁克爾，是史蒂文。只是很快，我們不會透露將觸發最終揭盲的事件編號。所以這不是公開信息。

Yes. Michael, this is Reid. On the IDO inhibitor question, the key thing for this target, as we know, is near complete or complete inhibition. We can do that safely with this mechanism, and that's going to be the bar by which we judge compounds. And I think if any compound can safely, with appropriate drug-like properties, achieve those levels of inhibition, then that should drive the pharmacology irrespective of any biochemical nuances. At the end of the day, it's about inhibiting the enzyme to a maximum degree. Differentiation between agents will come from their ability or inability to do that as well as any other off-target liabilities they may have.

是的。邁克爾，這是里德。關於IDO抑製劑問題，據我們所知，該靶點的關鍵是接近完全或完全抑制。我們可以通過這種機制安全地做到這一點，這將成為我們判斷化合物的標準。我認為，如果任何化合物能夠安全地具有適當的類似藥物的特性，達到這些抑制水平，那麼無論生化的細微差別如何，這都應該推動藥理學的發展。歸根結底，這是為了最大程度地抑制酶。代理人之間的區別將取決於他們是否有能力做到這一點，以及他們可能承擔的任何其他偏離目標的責任。

I'll now turn the conference back over to Hervé Hoppenot for closing remarks.

現在我將把會議轉回埃爾韋·霍佩諾 (Hervé Hoppenot) 致閉幕詞。

Okay, thank you. Thank you for attending this meeting today and your time. A great quarter, progress on the pipeline, some new entries into our portfolio with the deal with MacroGenics and also a new board member. So a lot of good progress from the Incyte side, and we look forward to seeing you -- some of you at the upcoming investor medical conferences including at ASH. But for now, thank you again for your participation in the call today. Bye-bye.

好的謝謝。感謝您參加今天的會議並抽出時間。這是一個偉大的季度，管道方面取得了進展，我們的投資組合中出現了一些新的條目，包括與 MacroGenics 的交易以及新的董事會成員。因此，Incyte 方面取得了很多良好進展，我們期待在即將舉行的投資者醫療會議（包括 ASH 會議）上見到你們。但現在，再次感謝您參加今天的電話會議。再見。

This concludes today's webcast. All parties may disconnect. Have a great day. Thank you.

今天的網絡廣播到此結束。所有各方都可以斷開連接。祝你有美好的一天。謝謝。